The Neurology and Neuropsychiatry of COVID-19

Evidence on the neurological and neuropsychiatric manifestations and complications of COVID-19 infections is emerging and this is likely to accelerate as the pandemic develops and clinical syndromes are detected, characterized and their mechanisms investigated. This published research database is listed by topic in order of date of publication. 

To date and of interest to the AE community, conditions COVID-19 has triggered are Guillain-Barré Syndrome (GBS), Encephalopathy, Encephalitis, Meningoencephalitis, Psychiatric, Epilepsy, ADEM,  anti-NMDAr encephalitis, Limbic encephalitis, and acute myelitis. 

COVID-19 NEUROLOGY RESOURCE CENTER

Neurology Colleagues:  You can count on the American Acadamy of Neurology (AAN) to provide you with expert guidance on the care of neurology patients affected by COVID-19, as well as timely news on how this pandemic is affecting the field of neurology overall. Please visit this page often for continuous updates.

LATEST COVID-19 ARTICLES, VIDEOS, AND PODCASTS

The Lancet COVID-19 RESOURCE CENTER

To assist health workers and researchers working under challenging conditions to bring this outbreak to a close, The Lancet has created a Coronavirus Resource Centre. This resource brings together new 2019 novel coronavirus disease (COVID-19) content from across The Lancet journals as it is published. All of our COVID-19 content is free to access.

critical care COVID-19 Management Protocol
Kawasaki Disease and Covid-19

Facial Masking for Covid-19 — Potential for “Variolation” as We Await a Vaccine

As SARS-CoV-2 continues its global spread, it’s possible that one of the pillars of Covid-19 pandemic control — universal facial masking — might help reduce the severity of disease and ensure that a greater proportion of new infections are asymptomatic. If this hypothesis is borne out, universal masking could become a form of “variolation” that would generate immunity and thereby slow the spread of the virus in the United States and elsewhere, as we await a vaccine.

Facial Masking for Covid-19 — Potential for “Variolation” as We Await a Vaccine. Ultimately, combating the pandemic will involve driving down both transmission rates and severity of disease. Increasing evidence suggests that population-wide facial masking might benefit both components of the response.

Postpartum consciousness disturbance: can covid-19 cause posterior reversible encephalopathy syndrome?

We describe the case of a 24-year-old pregnant woman with no history of note who was admitted with a diagnosis of bilateral pneumonia caused by the new coronavirus. Due to clinical worsening, she required urgent cesarean section with general anaesthesia and intubation for decubitus intolerance. After extubation, she presented altered mental state that required a differential diagnosis of encephalitis/meningitis secondary to SARS-CoV-2.

Genomic evidence for reinfection with SARS-CoV-2: a case study

Genetic discordance of the two SARS-CoV-2 specimens was greater than could be accounted for by short-term in vivo evolution. These findings suggest that the patient was infected by SARS-CoV-2 on two separate occasions by a genetically distinct virus. Thus, previous exposure to SARS-CoV-2 might not guarantee total immunity in all cases. All individuals, whether previously diagnosed with COVID-19 or not, should take identical precautions to avoid infection with SARS-CoV-2. The implications of reinfections could be relevant for vaccine development and application.

Remdesivir Effective, Well-Tolerated in Final Trial Report

Other data have demonstrated that remdesivir shortens recovery in patients with lower acuity. In our study, evidence of pneumonia was an enrollment requirement. “We saw bigger benefits in patients with more severe infections. The benefits are not as large in patients with mild disease, but I think remdesivir should be considered in any hospitalized patient,” Dr. Beigel said.

WHO reveals corticosteroids are effective in reducing the fatality rate of COVID-19

Easy read: 

  • When severely ill COVID-19 patients are treated with corticosteroids such as dexamethasone, their survival rates increase, according to the WHO.
  • Mimicking the action of cortisol in the body, these drugs can help avoid ‘cytokine storms’ which cause deadly levels of inflammation.
  • Those treated with corticosteroids had a risk of death after 28 days of 32%. For those receiving usual care or a placebo, the risk was 40%.

Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients

These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.

Stroke May Be First Symptom of COVID-19 in Younger Patients

Investigators carried out a meta-analysis of data, including 160 patients with COVID-19 and stroke, and found that nearly half of patients under the age of 50 were asymptomatic at the time of stroke onset.

Stroke May Be First Symptom of COVID-19 in Younger Patients

Investigators carried out a meta-analysis of data, including 160 patients with COVID-19 and stroke, and found that nearly half of patients under the age of 50 were asymptomatic at the time of stroke onset.

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection.

We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

Age groups that sustain resurging COVID-19 epidemics in the United States

Conclusions: 1. “We estimate by November 24 2020 a 253.7% increase in infections among children aged 0-11, and 24 excess COVID-19 attributable deaths among children aged 0-11, resulting in pediatric COVID-19 attributable mortality figures that are similar to pediatric influenza-like mortality. The forecasts further estimate 6,181 excess COVID-19 attributable deaths in the total population, which is a 12.6% increase compared to the continued school closure scenario, by November 24, 2020.” 2. “Adults aged 20-49 are a main driver of the COVID-19 epidemic in the United States; yet, in areas with resurging epidemics, opening schools will lead to more COVID-19-aƩributable deaths, so more targeted interventions in the20-49 age group could bring epidemics under control, avert deaths, and facilitate the safe reopening of schools.”

Novel use of home pulse oximetry monitoring in COVID-19 patients discharged from the emergency department identifies need for hospitalization

This study found that home pulse oximetry monitoring identifies the need for hospitalization in initially non-severe COVID-19 patients when a cut off of SpO2 92% is used. Half of the patients who ended up hospitalized had SpO2 <92% without worsening symptoms. Home SpO2 monitoring also reduces unnecessary ED revisits.

Cytokine Storm

This study compared the cytokine levels in patients with COVID-19 to levels in patients with spetic shock and ARDS.

Infectious COVID-19 Can Persist in Gut for Weeks

For the first time, researchers detected active and prolonged infection of SARS-CoV-2 virus in the gastrointestinal (GI) tracts of people with confirmed COVID-19. Stool tests were positive among people with no GI symptoms, and in some cases up to 6 days after nasopharyngeal swabs yielded negative results. This occurred even after recovery, suggesting that coronavirus could remain in the gut of asymptomatic carriers.

How the Coronavirus Attacks the Brain

Easy read article:

The coronavirus targets the lungs foremost, but also the kidneys, liver, and blood vessels. Still, about half of patients report neurological symptoms, including headaches, confusion, and delirium, suggesting the virus may also attack the brain.

A new study offers the first clear evidence that, in some people, the coronavirus invades brain cells, hijacking them to make copies of itself. The virus also seems to suck up all of the oxygen nearby, starving neighboring cells to death.

It’s unclear how the virus gets to the brain or how often it sets off this trail of destruction. Infection of the brain is likely to be rare, but some people may be susceptible because of their genetic backgrounds, a high viral load or other reasons.

“If the brain does become infected, it could have a lethal consequence,” said Akiko Iwasaki, an immunologist at Yale University who led the work.

The coronavirus seems to rapidly decrease the number of synapses, the connections between neurons. “Days after infection, and we already see a dramatic reduction in the amount of synapses,” Dr. Muotri said. “We don’t know yet if that is reversible or not.”

ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection

May-2020 Not certified by peer review

Risk Score Predicts COVID-19 Mortality, Outperforms Others

Clinical observations, patient demographics, and blood measurements at hospital admission combined in a brief score predicted the likelihood of in-hospital mortality in a prospective, observational cohort of more than 57,000 individuals with COVID-19.

Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19

Question  Is administration of systemic corticosteroids associated with reduced 28-day mortality in critically ill patients with coronavirus disease 2019 (COVID-19)?

Findings  In this prospective meta-analysis of 7 randomized trials that included 1703 patients of whom 647 died, 28-day all-cause mortality was lower among patients who received corticosteroids compared with those who received usual care or placebo (summary odds ratio, 0.66).

Meaning  Administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality in critically ill patients with COVID-19.

AI Can Pinpoint COVID-19 From Chest X-Rays

Conventional chest x-rays combined with artificial intelligence (AI) can identify lung damage from COVID-19 and differentiate coronavirus patients from other patients, improving triage efforts, new research suggests.

Unexpected Results in New COVID-19 'Cytokine Storm' Data

The immune system overactivation known as a “cytokine storm” does not play a major role in more severe COVID-19 outcomes, according to unexpected findings in new research. The findings stand in direct contrast to many previous reports.

Temporal profile and determinants of viral shedding and of viral clearance confirmation on nasopharyngeal swabs from SARS-CoV-2-positive subjects: a population-based prospective cohort study in Reggio Emilia, Italy

Objectives To determine the timing of viral clearance (first negative RT-PCR on nasopharyngeal swab) and the probability of viral clearance confirmation (two consecutive negative swabs) in COVID-19 patients and to identify related determinants.

Conclusions Postponing follow-up testing of clinically recovered COVID-19 patients could increase the efficiency and performance of testing protocols. Understanding viral shedding duration also has implications for containment measures of paucisymptomatic subjects.

SARS-CoV-2 infects human neural progenitor cells and brain organoids

In summary, our results demonstrated that iPSC-derived hNPCs were permissive to SARS-CoV-2, but not SARS-CoV infection. Extensive viral protein expression and infectious viral particles were detected in neurospheres and brain organoids infected with SARS-CoV-2, which suggest SARS-CoV-2 can productively infect the human brain.

The finding that SARS-CoV-2 can productively infect human brain organoids highlights the potential of direct viral involvement in neurological symptoms in COVID-19 patients. These results provided insight on the pathognomonic symptoms of anosmia (loss of smell) and ageusia (loss of taste) as well as other neurological manifestations of COVID-19 including seizure, encephalopathy, encephalitis, Guillain-Barre syndrome, and Miller Fisher syndrome.

Neurologic complications of COVID-19

Highly Recommended

August 14-2020

Common neurologic complications in patients with coronavirus disease 2019 (COVID-19), resulting from SARS-CoV-2 infection, are presented. ACUTE ENCEPHALOPATHY, ACUTE CEREBROVASCULAR DISEASES, Acute ischemic stroke, Encephalitis, meningitis, Acute necrotizing hemorrhagic encephalopathy, Acute disseminated encephalomyelitis, Acute disseminated encephalomyelitis (ADEM),  SEIZURES, Critical illness polyneuropathy, and myopathy, Acute inflammatory demyelinating polyneuropathy, and Olfactory neuropathy

CONCLUSIONS
Human coronaviruses, including SARS-CoV-2, have the ability for neurotropism. Commonly reported neurologic complications in patients infected with
SARS-CoV-2 include encephalopathy, neuromuscular disorders, and acute cerebrovascular disorders.
Other complications, such as postinfectious demyelination, encephalitis, and seizures are likely underreported given the inability to obtain further diagnostic information, such as CSF sampling and EEG
monitoring. Clinicians should have a high clinical suspicion for associated neurologic complications in a COVID-19–infected patient.

Guillain-Barré syndrome: The first documented COVID-19–triggered autoimmune neurologic disease More to come with myositis in the offing

Objective To present the COVID-19–associated GBS, the prototypic viral-triggered autoimmune disease, in the context of other emerging COVID-19–triggered autoimmunities, and discuss potential concerns with ongoing neuroimmunotherapies.

Conclusions Emerging data indicate that COVID-19 can trigger not only GBS but other autoimmune neurological diseases necessitating vigilance for early diagnosis and therapy initiation. Although COVID-19 infection, like most other viruses, can potentially worsen patients with pre-existing autoimmunity, there is no evidence that patients with autoimmune neurological diseases stable on common immunotherapies are facing increased risks of infection.

Obesity Boosts Risks in COVID-19 From Diagnosis to Death

Easy Read:

A new analysis of existing research confirms a stark link between excess weight and COVID-19: People with obesity are much more likely to be diagnosed with the novel coronavirus, undergo hospitalization and ICU admission, and die.

On the biological front, it appears that the immune system is much weaker if you’re obese, and excess weight may worsen the course of a respiratory disease such as COVID-19 because of lung disorders such as sleep apnea.

In addition to highlighting inflammation and a weakened immune system, the review offers multiple explanations for why patients with obesity face worse outcomes in COVID-19. It may be more difficult for medical professionals to care for them in the hospital because of their weight, the authors wrote, and “obesity may also impair therapeutic treatments during COVID-19 infections.” The authors noted that ACE inhibitors may worsen COVID-19 in patients with type 2 diabetes.

The researchers noted that “potentially the vaccines developed to address COVID-19 will be less effective for individuals with obesity due to a weakened immune response.” They pointed to research that suggests T-cell responses are weaker and antibody titers wane at a faster rate in people with obesity who are vaccinated against influenza.

International experience of mechanical thrombectomy during the COVID-19 pandemic: insights from STAR and ENRG

Conclusion We observed a low rate of COVID-19 infection among stroke patients undergoing mechanical thrombectomy (MT) in low-COVID burden counties (LCC). Overall, more than half of the patients underwent intubation prior to MT, leading to prolonged door to reperfusion time, higher in-hospital mortality, and a lower likelihood of functional independence at discharge.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the COVID-19 pandemic or until otherwise determined by BMJ. You may use, download, and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trademarks are retained.

Clinical Characteristics and Viral RNA Detection in Children With Coronavirus Disease 2019 in the Republic of Korea

Key Points

Question  How long is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detected in children, and are children with coronavirus disease 2019 (COVID-19) identifiable by symptoms?

Findings  In this case series of 91 children with COVID-19 in Korea, 22.0% were asymptomatic. Only 8.5% of symptomatic cases were diagnosed at the time of symptom onset, while 66.2% had unrecognized symptoms before diagnosis and 25.4% developed symptoms after diagnosis; SARS-CoV-2 RNA was detected for a mean of 17.6 days overall and 14.1 days in asymptomatic cases.

Meaning  Symptom screening fails to identify most COVID-19 cases in children, and SARS-CoV-2 RNA in children is detected for an unexpectedly long time.

Convalescent Plasma Therapy for COVID-19: State of the Art

Convalescent plasma (CP) therapy has been used since the early 1900s to treat emerging infectious diseases; its efficacy was later associated with the evidence that polyclonal neutralizing antibodies can reduce the duration of viremia. Recent large outbreaks of viral diseases for which effective antivirals or vaccines are still lacking has renewed the interest in CP as a life-saving treatment. The ongoing COVID-19 pandemic has led to the scaling up of CP therapy to unprecedented levels. Compared with historical usage, pathogen reduction technologies have now added an extra layer of safety to the use of CP, and new manufacturing approaches are being explored. This review summarizes historical settings of application, with a focus on betacoronaviruses, and surveys current approaches for donor selection and CP collection, pooling technologies, pathogen inactivation systems, and banking of CP. We additionally list the ongoing registered clinical trials for CP throughout the world and discuss the trial results published thus far.

Evaluating the evidence for direct central nervous system invasion in patients infected with the nCOVID-19 virus

The current nCOVID-19 pandemic is raising several questions in the approximately 25% of patients who present with neurological symptoms. While secondary brain injury from the systemic manifestations of the disease account for the majority of non-specific neurological symptoms that include headache, nausea, and progressive confusion, the question that remains unanswered is does the nCOVID-19 virus use the olfactory mucosa as a portal to directly invade the brain?

We performed a PubMed review of the literature to specifically assess the evidence for the direct CNS invasion by the nCOVID-19 virus. This phenomenon would explain the cerebral oedema and encephalitis, that does occur, and bring Neurosurgeons into the management of these patients by for example directed intra-cranial pressure management post insertion of an intra-cranial pressure monitor. Unfortunately, the answers to these questions were not definitively answered by the research reviewed.

Immunology of COVID-19: Current State of the Science

Here, we reviewed the recent literature and highlighted hypotheses that interrogate mechanisms for viral escape from innate sensing, for hyperinflammation associated with CRS and inflammatory myeloid subpopulations, for lymphopenia marked by T cell and NK cell dysfunction, and for correlates of protection and their duration, among others. Still, additional studies are needed to address how these immune differences across patients or between different types of coronavirus infections dictate who succumbs to disease and who remains asymptomatic. Existing studies of SARS-CoV-1 and MERS-CoV and ongoing studies of SARS-CoV-2 will likely provide a robust framework to fulfill that unmet need.

55% of coronavirus patients still have neurological problems three months later: study

Could the coronavirus lead to chronic illness?

While lung scarring, heart, and kidney damage may result from COVID-19, doctors and researchers are starting to clock the potential long-term impact of the virus on the brain also.

Younger COVID-19 patients who were otherwise healthy are suffering blood clots and strokes.

And many “long-haulers,” or COVID-19 patients who have continued showing symptoms for months after the initial infection passed, report neurological problems such as confusion and difficulty concentrating (or brain fog), as well as headaches, extreme fatigue, mood changes, insomnia and loss of taste and/or smell.

Now a study of 60 COVID-19 patients published in Lancet this week finds that 55% of them were still displaying such neurological symptoms during follow-up visits three months later. And when doctors compared brain scans of these 60 COVID patients with those of a control group who had not been infected, they found that the brains of the COVID patients showed structural changes that correlated with memory loss and smell loss.

And that’s not exclusive to adults. A U.K. study of 4 cases showed children developed neurological manifestations such as headaches, muscle weakness, confusion, and disorientation. While two of the kids recovered, the other two continued to show symptoms, including muscle weakness so severe that they needed a wheelchair. The University College of London warned about a potential brain damage “epidemic” caused by COVID-19 in the journal Brain last month.

While it’s too soon to say whether such post-COVID conditions will be chronic, there is worry about recovered patients being able to return to work and school. “Patients are going to be somewhat debilitated, so their ability to work, their contribution to the workforce, to the domestic product, is going to be reduced,” he said. “It will affect society on many levels if the rates [of infection and long-term illness] persist to be this great.”

 

Research shows the most and least effective materials for face masks

In a study in the Journal of Hospital Infection, researchers assessed the ability of a variety of nontraditional mask materials to protect a person from infection after 30 seconds and after 20 minutes of exposure in a highly contaminated environment.

When the researchers compared wearing masks to wearing no protection during 20-minute and 30-second exposures to the virus, they found that infection risks were reduced by 24-94% or by 44-99% depending on the mask and exposure duration. Risk reduction decreased as exposure duration increased, they found.

This article lists masks from best to worse.

Surprisingly, vacuum cleaner filters, which can be inserted into filter pockets in cloth masks are highly effective. The vacuum filters reduced infection risk by 83% for a 30-second exposure and 58% for a 20-minute exposure. Of the other nontraditional materials evaluated by the researchers, tea towels, cotton-blend fabrics, and antimicrobial pillowcases were the next best for protection.

Scarves, which reduced infection risk by 44% after 30 seconds and 24% after 20 minutes, and similarly effective cotton t-shirts are only slightly better than wearing no mask at all, they found.

“We knew that masks work, but we wanted to know how well and compare different materials’

 

Cleaner Data Confirm COVID-19 Link to Diabetes, Hypertension

The connections identified between COVID-19, diabetes, and hypertension mean that patients with these chronic diseases should receive education about their COVID-19 risks and should have adequate access to the drugs and supplies they need to control blood pressure and hyperglycemia.

Patients with diabetes also need to be current on vaccinations to reduce their risk for pneumonia. And recognition of the heightened COVID-19 risk for people with these comorbidities is important among people who work in relevant government agencies, health care workers, and patient advocacy groups

 

“This is the first opportunity for the neuroscience community to understand the virus”

Easy Read ~ Senior clinician Benedict Michael started leading groundbreaking research into the neurological complications caused by Covid-19.

“When it became apparent the virus had taken hold in Italy, I said to the guys, ‘We’ve got to get something up and running’,” Michael wanted to find out: what is Covid-19 doing to the brain, how is it doing it, what makes a person more at risk of these complications, and how do these patients recover?

Michael and his team developed a way for doctors to record the symptoms of patients experiencing neurological and psychiatric complications.  Michael’s work is ongoing. Alongside his team, he plans to focus on looking at patients’ immune response and carrying out geometric testing to try to understand genetic differences in patients who experience more severe symptoms.

Hyperglycemia Predicts COVID-19 Death Even Without Diabetes

Nearly half of hospitalized COVID-19 patients without a prior diabetes diagnosis have hyperglycemia, and the latter is an independent predictor of mortality at 28 days, new research indicates.. The findings, from a retrospective analysis of 605 patients with COVID-19 seen at two hospitals in Wuhan, China, were published online July 10. Compared to patients with normal glucose (< 6.1 mmol/L), 28-day mortality was twice as high (HR, 2.06) for those with a fasting blood glucose of 6.1-6.9 mmol/L and more than threefold higher for ≥ 7.0 mmol/L (HR, 3.54).

Conjunctivitis Can Be Sole Covid-19 Symptom

(Reuters Health) — Acute, non-remitting conjunctivitis may be the only presenting symptom of Covid-19 infections in some instances, according to case reports on five patients in Italy.

“Conjunctivitis per se is not a very common finding among positive subjects, but when it occurs, it generally presents with or anticipates other symptoms, such as fever, general malaise, cough,” said Dr. Edoardo Trovato Battagliola.

“We don’t know in what percentage of patients, conjunctivitis will be the sole or the starting symptom of SARS-COV-2,” said Dr. Saeed Shoar,”But as (these case reports) revealed, it can start days before the typical symptoms of COVID-19 begin,”

Spectrum of Neurological Manifestations in Covid-19: A Review

In COVID-19, both central and peripheral nervous systems can be affected. The SARS-CoV-2 virus causes the disease COVID-19 and has the potential to invade the brain. The most severe neurological manifestations, altered sensorium (agitation, delirium, and coma), are because of hypoxic and metabolic abnormalities. Characteristic cytokine storm incites severe metabolic changes and multiple organ failure. Profound coagulopathies may manifest with ischemic or hemorrhagic stroke. Rarely, SARS-CoV-2 virus encephalitis or pictures like acute disseminated encephalomyelitis or acute necrotizing encephalopathy have been reported. Recently, many cases of Guillain-Barré syndrome in COVID-19 patients have been observed, and a postinfectious immune-mediated inflammatory process was held responsible for this. The spectrum of neurological complications is likely to widen further.

Postinfectious brainstem encephalitis associated with SARS-CoV-2

We report a postinfectious brainstem syndrome in a patient with COVID-19 who presented with generalized myoclonus, ocular flutter with convergence spasm, and acquired hyperekplexia. Clinical improvement was seen following corticosteroids, highlighting this as a possible treatment in patients where a post-COVID-19 autoimmune encephalitis is suspected.

Continuous EEG Monitoring Reveals Seizures, Other Abnormalities in COVID-19 Patients

Easy Read. Acute symptomatic seizures detected in five of 22 patients monitored. Patients with severe COVID-19 disease are at increased risk for acute symptomatic seizures and a variety of electroencephalographic (EEG) abnormalities. The largest study to date of continuous EEG (cEEG) monitoring of patients with COVID-19 concludes.

“Knowing that COVID-19 may increase the risk of seizures is important, especially since signs often cannot be detected while patients are heavily sedated on a ventilator,” says neurologist Christopher Newey, DO, MS. “For COVID-19 patients with neurologic changes, continuous EEG monitoring may inform evaluation and management. Seizures could indicate that COVID-19 is neurotropic or may possibly lead to microthrombi in the brain secondary to hypoxia or inflammation,” he conjectures. “It’s also possible that excessive cytokine activity disrupts the blood-brain barrier.”

Scientists warn of potential wave of COVID-linked brain damage

Easy Read Article: Scientists warn of a potential wave of coronavirus-related brain damage as new evidence suggested COVID-19 can lead to severe neurological complications, including inflammation, psychosis and delirium. Neuroscientists and specialist brain doctors say emerging evidence of its impact on the brain is concerning.

“My worry is that we have millions of people with COVID-19 now. And if in a year’s time we have 10 million recovered people, and those people have cognitive deficits … then that’s going to affect their ability to work and their ability to go about activities of daily living,” Adrian Owen, a neuroscientist at Western University in Canada, told Reuters in an interview.

In the UCL study, published in the journal Brain, nine patients who had brain inflammation were diagnosed with a rare condition called acute disseminated encephalomyelitis (ADEM) which is more usually seen in children and can be triggered by viral infections.

The team said it would normally see about one adult patient with ADEM per month at their specialist London clinic, but this had risen to at least one a week during the study period, something they described as “a concerning increase”.

Identifying airborne transmission as the dominant route for the spread of COVID-19

Our analysis reveals that the difference with and without mandated face-covering represents the determinant in shaping the pandemic trends in the three epicenters. This protective measure alone significantly reduced the number of infections, that is, by over 78,000 in Italy from April 6 to May 9 and over 66,000 in New York City from April 17 to May 9.

Other mitigation measures, such as social distancing implemented in the United States, are insufficient by themselves in protecting the public.

We conclude that wearing of face masks in public corresponds to the most effective means to prevent interhuman transmission, and this inexpensive practice, in conjunction with simultaneous social distancing, quarantine, and contact tracing, represents the most likely fighting opportunity to stop the COVID-19 pandemic. Our work also highlights the fact that sound science is essential in decision-making for the current and future public health pandemics.

Headache May Predict Clinical Evolution of COVID-19

Headache may be a key symptom of COVID-19 that predicts the disease’s clinical evolution in individual patients, new research suggests.

An observational study of more than 100 patients showed that headache onset could occur during the presymptomatic or symptomatic phase of COVID-19 and could resemble tension-type or migraine headache.

In a subgroup of participants, headache persisted even after the symptoms of COVID-19 had been resolved.

Comorbidities Increase COVID-19 Deaths by Factor of 12

The most frequently reported underlying conditions were cardiovascular disease (32%), diabetes (30%), chronic lung disease (18%), and renal disease (7.6%), and there were no significant differences between males and females.

The pandemic “is an ongoing public health crisis in the United States that continues to affect all populations and result in severe outcomes including death,” they said, emphasizing “the continued need for community mitigation strategies, especially for vulnerable populations, to slow COVID-19 transmission.”

WHO Halts Trial of Hydroxychloroquine in COVID-19 Patients

The World Health Organization has announced that testing of the malaria drug hydroxychloroquine in its large multi-country trial of treatments for COVID-19 patients had been halted after new data and studies showed no benefit.

Data from those studies “showed that hydroxychloroquine does not result in the reduction of mortality of hospitalized COVID-19 patients,” the WHO statement said.

The U.S. Food and Drug Administration on Monday, June 15th, revoked its emergency use authorization for hydroxychloroquine to treat COVID-19, saying it was no longer reasonable to believe that hydroxychloroquine and the related drug chloroquine would be effective in treating the disease.

Dexamethasone Hailed as 'Breakthrough' in COVID-19 Trial, Reduced Deaths

LONDON (Reuters) – A cheap and widely-used steroid called dexamethasone has become the first drug shown to be able to save lives among COVID-19 patients in what scientists said is a “major breakthrough” in the coronavirus pandemic.

Trial results announced on Tuesday showed dexamethasone, which is used to reduce inflammation in other diseases such as arthritis, reduced death rates by around a third among the most severely ill of COVID-19 patients admitted to hospital.

The preliminary results suggest the drug should immediately become standard care in patients with severe cases of the pandemic disease, said the researchers who led the trials.

“This is a (trial) result that shows that if patients who have COVID-19 and are on ventilators or are on oxygen are given dexamethasone, it will save lives, and it will do so at a remarkably low cost,” said Martin Landray, an Oxford University professor co-leading the trial, known as the RECOVERY trial.

Save Lives Around the World

England’s chief medical officer, Chris Whitty, said Tuesday’s announcement was “the most important trial result for COVID-19 so far”, adding: “It will save lives around the world

New Study Reveals COVID-19 Causes Serious Neurological Symptoms Shockingly Often

This easy to read article discusses how about half of hospitalized coronavirus patients experience neurological symptoms including dizziness, difficulty concentrating, a loss of smell and taste, seizures, strokes, and weakness.

The findings illustrate that COVID-19, the disease the coronavirus causes, is far more than a respiratory infection and rather one that  poses “a global threat” to the whole nervous system, including the brain, spinal cord, and nerves, the study authors say.

“It’s important for the general public and physicians to be aware of this, because a SARS-CoV-2 infection may present with neurological symptoms initially, before any fever, cough or respiratory problems occur,” lead study author Igor Koralnik, professor of neurology at Northwestern University Feinberg School of Medicine, said in a press release.

Some of the other neurological symptoms patients experienced included headache, decreased alertness, and muscle pain.

COVID-19-associated acute necrotizing myelitis

Case Study: In our patient, the presence of a longitudinal extensive transverse myelitis with subsequent worsening along with development of a necrotic area, associated with focal swelling, peripheral enhancement, and hypointense foci on T2 images, led us to the diagnosis of ANM in a patient COVID-19 positive. Immunomodulatory treatment such as steroids or plasmapheresis can result in neurologic improvement as the patient reported here.

Mutation of Coronavirus Is Significantly Increasing Its Ability To Infect

A tiny genetic mutation in the SARS coronavirus 2 variant circulating throughout Europe and the United States significantly increases the virus’ ability to infect cells, lab experiments performed at Scripps Research show.

“Viruses with this mutation were much more infectious than those without the mutation in the cell culture system we used,” says Scripps Research virologist Hyeryun Choe, PhD, senior author of the study.

It is still unknown whether the new D614G variant affects the severity of symptoms of infected people, or increases mortality, the scientists say.

 

COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome?

The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term “hyperferritinemic syndrome” and including macrophage activation syndrome (MAS), adult-onset Still’s disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic inflammatory reaction and “hyperferritinemic syndromes” are all characterized by high serum ferritin and a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. In this review, we analyze the possible epidemiological and molecular mechanisms responsible for hyper-inflammation in patients with severe COVID-19 and we underline the similarities between this condition and “hyperferritinemic syndromes” which would allow considering this entity as the fifth member of the spectrum of inflammatory conditions

 

SARS-CoV-2 Infection Rate 16% in Asymptomatic Pregnant Women at Delivery

In all, researchers screened 158 patients with a planned delivery, and 155 agreed to undergo COVID-19 testing. Of the 155 women tested, 24 (16%) tested positive for SARS CoV-2 infection. Among 146 support persons who had a negative interview screen and underwent SARS-CoV-2 testing, 14 (10%) tested positive for SARS-CoV-2 infection.

Test results were substantially concordant among patient and support person pairs. “Among patients who tested positive for COVID-19 infection and had a support person present, 11 of 19 (58%) support persons also tested positive for COVID-19 infection,” the authors reported. “Among patients who tested negative for COVID-19 infection and had a support person present, only 3 of 127 (2.4%) support persons tested positive for COVID-19 infection.”

 

Anti-NMDA receptor encephalitis in a psychiatric Covid-19 patient: A case report

Anti N-Methyl-D aspartate (NMDA) receptor (anti-NMDAR) encephalitis is one of the most common types of autoimmune encephalitis with its clinical presentation characterized by simultaneous presentation of neurological and psychiatric symptoms, the latter miming schizophrenia and psychotic spectrum disorders or substance induced psychosis. The importance of this case study is due to the probability that COVID-19 leads to neurological damage, an indirect pathway involving the immune system. Interleukin (IL)-6, an important member of the cytokine storm, is positively correlated with the severity of Coronavirus symptoms. Additional experiments have confirmed that primary glial cells cultured in vitro secrete a large amount of inflammatory factors including IL-6, IL-12, IL-15 and TNF-alpha after being infected with SARS-CoV-2. This data suggests that the activation of immune cells in the brain may cause inflammation and brain damage.

 

COVID-19 patients having known psychiatric disorders should be monitored closely for neurologic manifestations including headache, dizziness, and symptoms, changes in mental status, meningeal signs, dyskinesias. Patients with severe infection may be at greater risk for developing neurological sequelae and increased mortality. Furthermore, SARS-CoV-2 infection should be considered as a differential diagnosis in psychiatric patients with presentation of sudden onset symptoms including respiratory distress and other Covid-19 related symptoms to avoid wrong or delayed diagnosis

Psychosis spike linked to effect of coronavirus

Dozens of patients across Scotland have been treated for psychosis in recent weeks, as evidence mounts that the coronavirus pandemic can trigger mental illness.

A UK-wide surveillance programme suggests that some patients infected with Covid-19 suffer “altered mental states” such as psychosis and encephalitis, an inflammation of the brain that can cause seizures and hallucinations.

About 400 cases have been flagged to the project, known as CoroNerve, in the past month. Behind a stroke, psychosis has emerged as the second most common condition linked to the virus, affecting about one in three patients.

COVID-19 Data Dives: Airborne Transmission Increases With Crowding

Reviews two studies and illustrates the value of distancing (ie, avoiding crowding).

Even if the airborne transmission can happen, it doesn’t mean that it is the dominant mode of transmission or the major contributor to dynamics. The evidence we have now is still that close contacts are the most important. I will revisit this as the evidence evolves.

Respiratory virus shedding in exhaled breath and efficacy of face masks

We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.

Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for the treatment of COVID-19.

Neurological Manifestations of COVID-19 and Other Coronavirus Infections: A Systematic Review

Highlights

Neurological manifestations has been reported in SARS-CoV2 infection recently.

SARS-CoV2 could spread to the brain hematogenously or through the cribriform plate.

Neurological symptoms can be due to systemic illness or viral invasion of the CNS.

UK-wide surveillance of neurological and neuropsychiatric complications of COVID-19: The first 153 patients

This is the first nationwide, cross-specialty surveillance study of acute complications of COVID-19 in the nervous system. Alteration in mental status was common, reflecting encephalopathy/encephalitis and primary psychiatric diagnoses, often in young patients.

These data provide valuable and timely information urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy throughout the areas of neurology and neuropsychiatry

Convalescent plasma in Covid-19: Possible mechanisms of action

Highlights:  Coronavirus disease 19 (COVID-19) is an emerging viral threat with major repercussions for public health.

There is not specific treatment for COVID-19.

Convalescent plasma (CP) emerges as the first option of management for hospitalized patients with COVID-19.

Transference of neutralizing antibodies helps to control COVID-19 infection and modulates inflammatory response.

Other plasma components may enhance the antiviral and anti-inflammatory properties of CP.

Children are falling sick with a rare mystery inflammatory syndrome linked to Coronavirus

The new condition that’s being linked to COVID-19 got an official name this week: pediatric multisystem inflammatory syndrome.

Children and teens with the rare but potentially dangerous complication have been identified in at least seven states and the Washington, D.C., area as well as some parts of Europe. The condition can resemble features of other inflammatory illnesses like the Kawasaki Disease and toxic shock-like syndrome.

Physicians and scientists are working hard to understanding the mechanisms at play, and why only some children are so severely affected,” she said. Dr. John revealed that “the feature that’s been most concerning is that they have problems with their heart function.”

Dr. John added: “In general, families do not need to worry about this. I doubt that this is really new. I think it’s just really newly recognized. I hope what comes of this is that, because we’re seeing more cases, it will not take long before we will be better at recognizing this and treating it.”

Immunomodulation in COVID-19

Here, we expand on the theoretical basis of IL-6 inhibition and propose potential benefits from other immunomodulators that could, in theory, prove more efficacious.

 

As insight is gained into the clinical phenotypes associated with COVID-19, we propose JAK and IL-1 inhibitors as therapeutic targets warranting rapid investigation. Multidisciplinary collaboration with experts in haematology, inflammation, tissue damage, and repair and resolution is paramount.

Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children.

Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged.

Rapid development of an inactivated vaccine candidate for SARS-CoV-2

We developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.

FDA Authorizes Emergency Use of Remdesivir for COVID-19

The FDA writes, “Based on evaluation of the emergency use authorization criteria and the scientific evidence available, it was determined that it is reasonable to believe that remdesivir may be effective in treating COVID-19, and that, given there are no adequate, approved, or available alternative treatments, the known and potential benefits to treat this serious or life-threatening virus currently outweigh the known and potential risks of the drug’s use.”

Neurons promote encephalitogenic CD4 + lymphocyte infiltration in experimental autoimmune encephalomyelitis

To our knowledge, we for the first time adopted inhibitory DREADD and a migration assay using embryonic cerebral cortex neurons with CD4+ T cells. This methodology will pave a new way to investigate the pathophysiological role of excitatory neurons in EAE.

'Hypercoagulation,' Antiphospholipid Antibodies Seen in COVID-19

Researchers from China describe three patients admitted to the intensive care unit (ICU) with confirmed SARS-CoV-2 infection, severe COVID-19, and clinically significant coagulopathy, antiphospholipid antibodies, and multiple cerebral infarcts.

“Antiphospholipid antibodies abnormally target phospholipid proteins, and the presence of these antibodies is central to the diagnosis of the antiphospholipid syndrome.

Why Some People Get Sicker Than Others

Personal storytelling of COVID-19 cases. Includes a podcast and overview of clinical trials for therapies. An easy and worthwhile read for the layperson.

Sudden Loss of Taste and Smell Should Be Part of COVID-19 Screen

In her survey of patients who presented to UC San Diego Health for SARS-CoV-2 testing, Yan and colleagues reported that 68% (40 of 59) of COVID-19-positive patients reported olfactory impairment and 71% (42 of 59) reported taste impairment.

“Based on our study, if you have smell and taste loss, you are more than 10 times more likely to have COVID-19 infection than other causes of infection. The most common first sign of a COVID-19 infection remains fever, but fatigue and loss of smell and taste follow as other very common initial symptoms,” said Yan.

Hydroxychloroquine for COVID-19: What's the Evidence?

The bottom line is that we don’t need to abandon evidence-based medicine in the face of the pandemic. We need to embrace it more than ever. But in that embrace, we need to realize what we’ve known all along: Evidence-based medicine is not just about randomized trials; it’s about appreciating the strengths and weaknesses of all data, and allowing the data to inch us closer and closer toward truth.

Remdesivir Prevents Disease Progression in Monkeys With COVID-19

Early treatment with the experimental antiviral drug remdesivir significantly reduced clinical disease and damage to the lungs of rhesus macaques infected with SARS-CoV-2, the coronavirus that causes COVID-19, according to National Institutes of Health scientists.

Twelve hours after the initial treatment, the scientists examined all animals and found the six treated animals in significantly better health than the untreated group, a trend that continued during the seven-day study.

The investigators note that the data supports initiating remdesivir treatment in COVID-19 patients as early as possible to achieve maximum treatment effect. “This finding is of great significance for patient management, where a clinical improvement should not be interpreted as a lack of infectiousness,” they write.

Imaging Recommendations Issued for COVID-19 Patients

  • Recommendations: Imaging is indicated for patients with features of moderate to severe COVID-19 regardless of COVID-19 test results.
  • Imaging is indicated for patients with COVID-19 and evidence of worsening respiratory status.
  • When access to CT is limited, chest radiography may be preferred for COVID-19 patients unless features of respiratory worsening warrant using CT.
  • Additional recommendations: Daily chest radiographs are not indicated in stable, intubated patients with COVID-19.
  • CT is indicated in patients with functional impairment, hypoxemia, or both, after COVID-19 recovery.
  • COVID-19 testing is warranted in patients incidentally found to have findings suggestive of COVID-19 on a CT scan.

COVID-19: First Data Confirm Neurologic Symptoms Common

Investigators based in Wuhan, China, analyzed data from more than 200 adult patients with COVID-19 and found that 36.4% had neurologic manifestations. In addition, close to half of those with severe disease had neurologic symptoms, compared to roughly one-third of those with less severe disease.

Nervous system manifestations of COVID-19 were “significantly more common” in severe versus nonsevere infection.

The public and medical personnel alike need to be aware that there may be neurological manifestations of COVID-19 and such symptoms indicate a need for prompt medical attention.

COVID-19: Exercise may protect against deadly complication

Regular exercise may reduce the risk of acute respiratory distress syndrome, a major cause of death in patients with the COVID-19 virus, a top exercise researcher reports. He is urging people to exercise based on his findings, which also suggest a potential treatment approach.

Hydroxychloroquine for COVID-19 Study Did Not Meet 'Expected Standard'

The paper that appears to have triggered the Trump administration’s obsession with hydroxychloroquine as a treatment for infection with the novel coronavirus has received a statement of concern from the society that publishes the journal in which the work appeared.

Elisabeth Bik took a close look at the IJAA article and detailed a long list of serious problems with the study, including questions about its ethical underpinnings, messy confounding variables, missing patients, rushed and conflicted peer review, and confusing data.

COVID-19:Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism

This paper  explains the action of the virus from a hematological point of view, meaning that the severe hypoxia is because of the desaturation in oxygen of the red blood cells being attacked by the virus and not because of pulmonary inflammation.

A first Case of Meningitis/Encephalitis associated with SARS-Coronavirus-2

Highlights

Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly.
This is the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance.
The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF.
This case warns the physicians of patients who have CNS symptoms.

Responding to stress experienced by hospital staff working with Covid-19

Drawing on research, best practice guidelines and expert clinical opinions, the COVID Trauma Response Working Group has created rapid guidance for planners putting in place psychological support for staff in the early stages of dealing with the Covid-19 outbreak.

Download Graphic here https://www.kingsfund.org.uk/sites/default/files/2020-04/rapid-guidance-stress-diagram.pdf

The Spectrum of Neurologic Disease in the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic Infection

April 10-2020  In these 214 patients, they report 36.4% had some nervous system-related clinical finding.1 These neurologic manifestations ranged from fairly specific symptoms (eg, loss of sense of smell or taste, myopathy, and stroke) to more nonspecific symptoms (eg, headache, depressed level of consciousness, dizziness, or seizure).1 Whether these more nonspecific symptoms are manifestations of the disease itself or consistent with a systemic inflammatory response in patients who were quite ill will need to be defined in future studies. Importantly, the authors found that patients in their series with some of the more common specific symptoms, including smell or taste impairment and myopathy, tended to have these symptoms early in their clinical course; this appears to be quite distinct from SARS, where manifestations appeared quite late in established disease.

Coronavirus disease 2019 has now reached pandemic status and is common all over the world; thus, with so many affected patients, we can expect as neurologists to be confronted with these patients commonly in coming months and years.

Many Children With COVID-19 Don't Have Cough or Fever

The characteristic COVID-19 symptoms of cough, fever, and shortness of breath are less common in children than adults, according to the Centers for Disease and Prevention Control.

Among pediatric patients younger than 18 years in the United States, 73% had at least one of the trio of symptoms, compared with 93% of adults aged 18-64, noted Lucy A. McNamara, PhD, and the CDC’s COVID-19 response team, based on a preliminary analysis of the 149,082 cases reported as of April 2.

Neurologic Symptoms and COVID-19: What's Known, What Isn't

Since the Centers for Disease Control and Prevention (CDC) confirmed the first US case of novel coronavirus infection on January 20, much of the clinical focus has naturally centered on the virus’ prodromal symptoms and severe respiratory effects.

However, US neurologists are now reporting that COVID-19 symptoms may also could include encephalopathy, ataxia, and other neurologic signs.

Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know

The looming public health crisis for people with rheumatic diseases who will be unable to obtain HCQ is the result of a perfect storm of fear and dissemination of overpromised data. However, there is still time to mitigate the damage. Physicians should educate themselves about the strength of available data regarding HCQ and CQ in treating COVID-19. They should avoid misuse of HCQ and CQ for the prophylaxis of COVID-19, because there are absolutely no data to support this. Public figures should refrain from promoting unproven therapies to the public, and instead provide clear messages around the uncertainties we face in testing and using experimental treatments during the current pandemic, including the risk for serious adverse events. Well-done, randomized clinical trials should be performed urgently to test potential therapies, including HCQ. In the meantime, physicians should remember that first, we must do no harm to the patients with rheumatic disease for whom high-quality evidence shows that HCQ improves health.

Risk Factors for Death From COVID-19 Identified in Wuhan Patients

Nonsurvivors compared with survivors had higher frequencies of respiratory failure (98% vs 36%), sepsis (100%, vs 42%), and secondary infections (50% vs 1%).

The average age of survivors was 52 years compared to 69 for those who died. Liu cited weakening of the immune system and increased inflammation, which damages organs and also promotes viral replication, as explanations for the age effect.

From the time of initial symptoms, median time to discharge from the hospital was 22 days. Average time to death was 18.5 days.

The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro

Highlights:

Ivermectin is an inhibitor of the COVID-19 causative virus (SARS-CoV-2) in vitro.

A single treatment able to effect ∼5000-fold reduction in virus at 48h in cell culture.

Ivermectin is FDA-approved for parasitic infections, and therefore has a potential for repurposing.

Ivermectin is widely available, due to its inclusion on the WHO model list of essential medicines.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.

Coronavirus survivors' plasma could save lives

This paper: The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study

Two independent research studies have shown the benefit of receiving infusions of blood from COVID-19 survivors.

The teams – both based in China – extracted blood plasma from patients who had recovered from COVID-19, which contained antibodies against the disease. The first study from the National Engineering Technology Research Center for Combined Vaccines in Wuhan   gave plasma to 10 patients who were severely ill with COVID-19. Six days after receiving the infusion, the COVID-19 virus was undetectable in seven of the 10 patients.

Hydroxychloroquine: Possible COVID Drug Can Be Toxic to Retinas

Comorbidities Increase Likelihood of Retinal Toxicity

While a detailed patient history may be impossible to obtain if HCQ is used in the treatment of COVID-19, certain comorbidities do place patients at an increased risk for retinal toxicity. HCQ is excreted through renal clearance, so the dosage should be reduced in those with compromised kidney function to minimize the risk for toxicity. The presence of macular disease, such as age-related macular degeneration, has also been demonstrated to be a risk factor for the development of toxic maculopathy. The concurrent use of tamoxifen also increases the risk for retinal toxicity. Tamoxifen itself may deposit in the retina and make the macula more susceptible to the potentially toxic effects of HCQ.

'No Complacency' on COVID-19 After Death of 13-Year-Old-Boy

April-1-2020

“It is essential that we undertake research to determine why a proportion of deaths occur outside of the groups expected to succumb to infection as it may indicate an underlying genetic susceptibility of how the immune system interacts with the virus.

“Determining if this is the case could help us to learn more about the interaction of the virus with the immune system and subsequently what further treatments may be suitable in patients with severe infection.”

Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms

Autopsies of the COVID-19 patients, detailed neurological investigation, and attempts to isolate SARS-CoV-2 from the endothelium of cerebral microcirculation, cerebrospinal fluid, glial cells, and neuronal tissue can clarify the role played by this novel COVID-19 causing coronavirus in the ongoing mortalities as has been in the recent outbreak.

A dominant cerebral involvement alone with the potential of causing cerebral edema in COVID-19 can take a lead in causing death long before systemic homeostatic dysregulation sets in.

Also, a staging system based on the severity and organ involvement is needed in COVID-19 in order to rank the patients for aggressive or conventional treatment modalities.

COVID-19: Neurologists in Italy to Colleagues in US: Look for Poorly-Defined Neurologic Conditions in Patients with the Coronavirus

“There are some recent data suggesting that COVID-19 virus also reaches the central nervous system. Neurological symptoms in patients with COVID-19 infection fall into three categories: neurological expressions of the symptoms of the underlying disease (headache, dizziness, disturbances of the state of consciousness, ataxia, epileptic manifestations, and stroke;) symptoms of neuro-peripheral origin (hypo-ageusia, hyposmia, neuralgia;) symptoms of skeletal muscle damage, often associated with liver and kidney damage.”

Australia's Trialing a TB Vaccine Against COVID-19, And Health Workers Get It First

Australian researchers are fast-tracking large-scale human testing to see if a vaccine used for decades to prevent tuberculosis can protect health workers from COVID-19.

Similar trials are being conducted in several other countries including the Netherlands, Germany and the United Kingdom.

“This trial will allow the vaccine’s effectiveness against COVID-19 symptoms to be properly tested, and may help save the lives of our heroic frontline healthcare workers,”

Meningitis as an Initial Presentation of COVID-19: A Case Report

This case indicates that in addition to common presenting symptoms of fever, fatigue, and mild respiratory symptoms like dry cough and shortness of breath, patients with COVID-19 can also develop neurological manifestations like headache, anosmia, hyposmia, dysgeusia, meningitis, encephalitis, and acute cerebrovascular accidents during the course of the disease, which highlights the neurotropic potential of SARS-CoV-2. To date, the underlying pathophysiological mechanisms through which SARS-CoV-2 implicates the central nervous system (CNS) are not fully understood.

Time to get ill: the intersection of viral infections, sex, and the X chromosome

Females have more robust immune responses than males, and viral infections are more severe for males.

Risk of COVID-19 During Air Travel

The risk of contracting coronavirus disease 2019 (COVID-19) during air travel is lower than from an office building, classroom, supermarket, or commuter train.

Steps Passengers Can Take

Wear a mask, don’t travel if you feel unwell, and limit carry-on baggage. Keep distance from others wherever possible; report to staff if someone is clearly unwell. If there is an overhead air nozzle, adjust it to point straight at your head and keep it on full. Stay seated if possible, and follow crew instructions. Wash or sanitize hands frequently and avoid touching your face.

Coronavirus Can Survive on Surfaces for Weeks, Study Says

The coronavirus can remain on some surfaces for 28 days, including phone screens, banknotes and stainless steel, according to a new study published in the Virology Journal.

The study also found that the virus survived longer at lower temperatures and tended to last longer on non-porous or smooth surfaces such as glass and stainless steel rather than porous or rough surfaces such as cotton.

Efficacy of masks and face coverings in controlling outward aerosol particle emission from expiratory activities

These observations directly demonstrate that wearing of surgical masks or KN95 respirators, even without fit-testing, substantially reduce the number of particles emitted from breathing, talking, and coughing. While the efficacy of cloth and paper masks is not as clear and confounded by shedding of mask fibers, the observations indicate it is likely that they provide some reductions in emitted expiratory particles, in particular the larger particles (> 0.5 μm). We have not directly measured virus emission; nonetheless, our results strongly imply that mask wearing will reduce emission of virus-laden aerosols and droplets associated with expiratory activities, unless appreciable shedding of viable viruses on mask fibers occurs. The majority of the particles emitted were in the aerosol range (< 5 μm). As inertial impaction should increase as particle size increases, it seems likely that the emission reductions observed here provide a lower bound for the reduction of particles in the droplet range (> 5 μm). Our observations are consistent with suggestions that mask wearing can help in mitigating pandemics associated with respiratory disease. Our results highlight the importance of regular changing of disposable masks and washing of homemade masks, and suggests that special care must be taken when removing and cleaning the masks.

Plasmapheresis treatment in COVID-19–related autoimmune meningoencephalitis: Case series

Autoimmune encephalitis has now been identified as being triggered by COVID-19. To the best of the author’s knowledge, this is the first relatively large series (6 patients) on the effect of plasmapheresis treatment in COVID-19–related autoimmune encephalitis.
In conclusion, the presented cases emphasize the importance of suspecting neurological involvement in severely affected COVID-19 patients and the potential benefit of plasmapheresis in such patients. Furthermore, the CSF results observed here point toward an autoimmune/antibody-mediated involvement hypothesis for both the meninges and the cerebral parenchyma during severe COVID-19 infection. Further studies are necessary to support or refute this hypothesis and thus augment the therapeutic approach in these patients. 

Convalescent Blood Plasma Safe, Effective for COVID-19

Convalescent blood plasma is a useful and relatively safe therapy for COVID-19, and perhaps should be used more widely, according to Prof Arturo Casadevall, Chair of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health.

Blood plasma is currently the only therapy against COVID-19 associated with a major reduction in mortality if given before ICU admission. 

COVID is harming sperm, Israeli researchers say, raising infertility worries

COVID-19 is harming the sperm of patients, even weeks after recovery, Israeli doctors have concluded, raising concerns that the disease could reduce fertility.

Literature suggests that the virus is found in the sperm of 13% of male patients who have the disease, and 8.6% of those who are recovering a week or two after the active disease. A month later, there are no traces of coronavirus ribonucleic acid (RNA) in the sperm.

80 Percent of Hospitalized Covid Patients Had Neurological Symptoms, Study Finds

This article is an easy read that references the research paper:

Frequent neurologic manifestations and encephalopathy‐associated morbidity in Covid‐19 patients

Frequent neurologic manifestations and encephalopathy‐associated morbidity in Covid‐19 patients

Neurologic manifestations were present at Covid‐19 onset in 215 (42.2%), at hospitalization in 319 (62.7%), and at any time during the disease course in 419 patients (82.3%). The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%). Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each). Severe respiratory disease requiring mechanical ventilation occurred in 134 patients (26.3%). Independent risk factors for developing any neurologic manifestation were severe Covid‐19 (OR 4.02; 95% CI 2.04–8.89; P < 0.001) and younger age (OR 0.982; 95% CI 0.968–0.996; P = 0.014). Of all patients, 362 (71.1%) had a favorable functional outcome at discharge (modified Rankin Scale 0–2). However, encephalopathy was independently associated with worse functional outcome (OR 0.22; 95% CI 0.11–0.42; P < 0.001) and higher mortality within 30 days of hospitalization (35 [21.7%] vs. 11 [3.2%] patients; P < 0.001).

Interpretation

Neurologic manifestations occur in most hospitalized Covid‐19 patients. Encephalopathy was associated with increased morbidity and mortality, independent of respiratory disease severity.

SARS-CoV2 Pandemic: An International Experience

We describe the first international cohort of 55 pediatric patients with multi-system inflammatory syndrome (MIS-C) during the SARS-CoV2 pandemic with a range of cardiac manifestations. This paper brings awareness and alertness to the global medical community to recognize these children during the pandemic and understand the need for early cardiology evaluation and follow-up.

Possible autoimmune encephalitis with claustrum sign in case of acute SARS CoV-2 infection

Case Study: An 18-year-old woman presented to the hospital after a one-week history of fever, fatigue,malaise, and loss of appetite that progressed to include drowsiness and confusion. There was  history of exposure to COVID-19 in a sick family member six days prior to symptom onset. Autoimmune encephalitis has rarely been reported as a presentation of COVID-, and the possibility of a coincidental association in this and other described cases cannot be excluded. 

The finding of the claustrum sign on brain MRI, not previously reported in a COVID-patient,provides further support for the idea that acute SARS-CoV-2 infection may present as an autoimmune encephalitis.

Autoimmune Encephalitis Presenting with Acute Excited Catatonia in a 40-Year-Old Male Patient with Covid-19

This case raises the possibility that this may be a novel form of autoimmune encephalitis induced by infection with SARS-CoV-2.

Acute malignant catatonia with autonomic instability developed in a previously healthy man. CT and MRI were normal, EEG showed slowing and cerebrospinal fluid showed a subtle indication of inflammation. 18F-FDG-PET conveyed high bilateral uptake in the striatum. Antibody testing revealed antibodies attacking healthy brain cells in the hippocampus, thalamus, striatum and cortex. Early treatment with plasmapheresis and corticosteroid reversed disease progression and may have prevented large-scale neurological damage.

(Note: This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.)

Surgical, N95 masks block most particles, homemade cloth masks release their own

The results confirm that masks and face coverings are effective in reducing the spread of airborne particles, Ristenpart said, and also the importance of regularly washing cloth masks.

Video: Testing a surgical mask is included in article.

The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission

Speech droplets generated by asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasingly considered to be a likely mode of disease transmission. Highly sensitive laser light scattering observations have revealed that loud speech can emit thousands of oral fluid droplets per second. In a closed, stagnant air environment, they disappear from the window of view with time constants in the range of 8 to 14 min, which corresponds to droplet nuclei of ca. 4 μm diameter, or 12- to 21-μm droplets prior to dehydration. These observations confirm that there is a substantial probability that normal speaking causes airborne virus transmission in confined environments.

Covid-19: Do many people have pre-existing immunity?

It seemed a truth universally acknowledged that the human population had no pre-existing immunity to SARS-CoV-2, but is that actually the case?
Not so novel coronavirus? 
At least six studies have reported T cell reactivity against SARS-CoV-2 in 20% to 50% of people with no known exposure to the virus. Other studies in the Netherlands, Germany and Singapore have also shown T cell reactivity. Though these studies are small and do not yet provide precise estimates of pre-existing immunological responses to SARS-CoV-2, they are hard to dismiss, with several being published in Cell and Nature.
 
Maybe there is more immunity to COVID-19 around the world than first thought at the beginning of the pandemic.

Inflammation: the key factor that explains vulnerability to severe COVID

  • While access to healthcare, occupational exposure, and environmental risks such as pollution all affect survival rate, for many at-risk groups, the key factor is inflammation.
  • Cytokines, a key player in the immune response, can help stop viruses reproducing.
  • Yet when too many are produced at once, this causes inflammation which can severely damage the lungs.
  • Studies like these highlight how different people are. The more we understand about these differences and vulnerabilities, the more we can consider how best to treat each patient. Data like these also highlight the need to consider variation in immune function and include people of varied demographics in drug and vaccine trials.

Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia

We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S). We aimed to assess the safety and immunogenicity of two formulations (frozen and lyophilised) of this vaccine.

Interpretation

The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong humoral and cellular immune responses in participants. Further investigation is needed of the effectiveness of this vaccine for prevention of COVID-19.

Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)

Findings  In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.

Mysterious Post-COVID Syndrome Affecting Kids Appears to Be Even Worse Than We Thought

Easy Read –

After contracting and beating a coronavirus infection, a body needs time to rest, to recover its health and strength. Sadly, for some children, that isn’t what happens next.

A mysterious, new disease called multisystem inflammatory syndrome in children (MIS-C, and also known as a paediatric multisystem inflammatory syndrome or PIMS) has affected hundreds of children around the world since it was first discovered earlier this year.

The condition, thought to be somehow linked to COVID-19, can emerge in kids even after very mild coronavirus infections. But a light case of coronavirus is no guarantee that a subsequent case of MIS-C won’t be very serious, and sometimes even fatal.

“Children did not need to exhibit the classic upper respiratory symptoms of COVID-19 to develop MIS-C, which is frightening,” says neonatologist Alvaro Moreira from the University of Texas Health Science Centre at San Antonio.

“Children might have no symptoms, no one knew they had the disease, and a few weeks later, they may develop this exaggerated inflammation in the body.”

Covid-19: UK studies find gastrointestinal symptoms are common in children

Gastrointestinal symptoms are common in children infected with SARS-CoV-2 and should trigger tests for the virus, researchers have said.

A prospective study of 992 healthy children (median age 10.1 years) of healthcare workers from across the UK found that 68 (6.9%) tested positive for SARS-CoV-2 antibodies.1 Half of the children testing positive reported no symptoms, but for those that did the commonest were fever (21 of 68, 31%); gastrointestinal symptoms, including diarrhoea, vomiting, and abdominal cramps (13 of 68, 19%); and headache (12 of 68, 18%).

 

Neuropathological Features of Covid-19 - to the editor

Neurologic symptoms, including headache, altered mental status, and anosmia, occur in many patients with Covid-19.1-3 We report the neuropathological findings from autopsies of 18 consecutive patients with SARS-CoV-2 infection who died in a single teaching hospital between April 14 and April 29, 2020.

In conclusion, histopathological examination of brain specimens obtained from 18 patients who died 0 to 32 days after the onset of symptoms of Covid-19 showed only hypoxic changes and did not show encephalitis or other specific brain changes referable to the virus. There was no cytoplasmic viral staining on immunohistochemical analysis. The virus was detected at low levels in 6 brain sections obtained from 5 patients; these levels were not consistently related to the interval from the onset of symptoms to death. Positive tests may have been due to in situ virions or viral RNA from blood.

 

A Supercomputer Analyzed Covid-19 — and an Interesting New Theory Has Emerged

Easy Read Article:

Covid-19 is like a burglar who slips in your unlocked second-floor window and starts to ransack your house. Once inside, though, they don’t just take your stuff — they also throw open all your doors and windows so their accomplices can rush in and help pillage more efficiently.

Oxford vaccine trial on hold because of potential safety issue

The decision to pause the trials comes after a study participant in the U.K. reportedly developed a spinal cord injury.

“Our standard review process was triggered and we voluntarily paused vaccination to allow review of safety data by an independent committee,” AstraZeneca, which is developing the vaccine in partnership with the U.K.’s University of Oxford, said in a statement. “This is a routine action which has to happen whenever there is a potentially unexplained illness in one of the trials, while it is investigated, ensuring we maintain the integrity of the trials.”

Postinfectious brainstem encephalitis associated with SARS-CoV-2

Immune-mediated neurological sequelae following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are becoming increasingly evident and can affect both the peripheral and central nervous system. We report a postinfectious brainstem syndrome in a patient with COVID-19 who presented with generalized myoclonus, ocular flutter with convergence spasm, and acquired hyperekplexia. Clinical improvement was seen following corticosteroids, highlighting this as a possible treatment in patients where a post-COVID-19 autoimmune encephalitis is suspected.

Five common skin manifestations of COVID‐19 identified

An initial 120 images were reviewed by four dermatologists, without knowing any other clinical information, and they identified patterns of symptoms associated with COVID‐19. These patterns were then applied to the rest of the images and further refined. Five common skin symptoms were identified in this way.

These symptoms are chilblain‐like lesions, outbreaks of small blisters, wheals, rashes comprised of small flat and raised red bumps, and livedo and necrosis. Livedo is a skin condition where circulation is impaired within the blood vessels of the skin, necrosis refers to the premature death of skin tissue.

These symptoms are associated with different severity of COVID‐19 infection, from less severe disease in the chilblain‐like lesions, to most severe in patients with livedo.

The researchers noted that some of the skin symptoms associated with COVID‐19 are common and can have many causes, particularly wheals and rashes. As such, they may not be particularly helpful as an aid to diagnosis

High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms

A study conducted by German researchers has shown that the neurological symptoms observed in some patients with coronavirus disease 2019 (COVID-19) may be caused by autoantibodies targeting the brain.

Antigens for the autoantibodies included proteins that are well-known in clinical practice, such as the glutamate receptor NMDA, as well as various undetermined antigens in several parts of the brain.

The team says that although some autoantibodies still need to be identified, they may at least partly explain the multiple organ disease that can occur in COVID-19 patients and help to inform immunotherapy decisions in certain cases.

In most patients, increased CSF protein, lactate or white blood cells with negative SARSCoV-2 PCR indicated inflammatory changes compatible with autoimmune encephalitis.

Recent findings suggest that several viral infections can lead to secondary autoimmune encephalitis, including EBV, HHV-6, enterovirus, adenovirus, hepatitis C or HIV infections. Thus, the present findings suggest that SARS-CoV-2 is no exception to this general principle. The following months will show whether such autoreactivity can cause persisting neurological morbidity even after
clearance of SARS-CoV-2 and remission of COVID-19, in a way reminiscent of the
unexplained severe ‘encephalitis lethargica’ – commonly with postencephalitic parkinsonism – in more than a million patients of the influenza pandemic in 1918. Together, the high frequency of autoantibodies targeting the brain in the absence of other explanations suggests a
causal association with clinical symptoms, in particular with hyperexcitability (myoclonus, seizures). While several underlying autoantigens still await identification in future studies,
the presence of autoantibodies may explain some aspects of multi-organ disease in COVID-19 and guide immunotherapy in selected cases.

COVID-19: dealing with a potential risk factor for chronic neurological disorders

The analysis provided compelling evidence on the CNS involvement during SARS-CoV2 infection, which definitely supports the hypothesis of a neuropathogenic effect of the virus. Early experimental data on SARS-CoV2 and existing literature about other coronaviruses allow supposing several mechanisms of neuroinvasion of the virus, including the trans-synaptic spread from peripheral nerves, the BBB passage mediated by ACE2 receptors or abnormal permeability, and the “Trojan horse” strategy due to the brain entrance of immune cells infected through ACE2 receptors

Neurological manifestations of coronavirus infections – a systematic review Conclusions

Our systematic review provides high level evidence that HCoVs, particularly SARSCoV1 and SARSCoV2, have a common ground on neurological symptomatology and complications. Particularly, clinicians treating these patients should be vigilant for at least five classes of neurological complications: (1) Cerebrovascular disorders including ischemic stroke and macro/microhemorrhages, (2) encephalopathies, likely caused by combinatorial effects of sepsis, hypoxia, and immune hyperstimulation, (3) para/postinfectious immunemediated complications such as GBS and ADEM, (4) (meningo)encephalitis, potentially with concomitant seizures, and (5) neuropsychiatric complications such as mood disorders or psychosis. Thus, the clinical neuroimaging protocol, as herein recommended, should include appropriate MRI sequences for early diagnosis and monitoring of patients. Our results also underscore the need to further research and optimize treatment regarding modulation of the coagulation and immune systems in order to reduce the risk of neurological complications.

Coronavirus Disease 2019 (COVID‐19) in autoimmune hepatitis: a lesson from immunosuppressed patients

Chronic immunosuppression is associated with increased and more severe viral infections. However, little is known about the association between immunosuppression and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection.

Ten patients from six different hospitals in Italy were diagnosed with COVID‐19 during the outbreak of SARS‐CoV‐2 in March 2020. All patients were taking immunosuppressive therapy.

Conclusion:

Patients under immunosuppressive therapy for AIH developing COVID‐19 show a disease course presumptively similar to that reported in non‐immunosuppressed population. These data might help medical decision when dealing with SARS‐CoV‐2 infection in immunocompromised .

A case of limbic encephalitis associated with asymptomatic COVID-19 infection

Neurological manifestations of COVID-19 appear more common in patients with severe respiratory disease. However, our patient had minimal respiratory involvement. No common COVID-19 symptoms developed, despite immunosuppressive treatment. This case illustrates the fact that neurological manifestations associated with COVID-19 infection are not a reflection of critical illness, and makes a case for actively looking for evidence of COVID-19 infection in patients presenting with neurological illness.

Our case suggests that neurological manifestations can be the initial symptom of COVID-19 and that COVID-19 infection should be considered in patients presenting with limbic encephalitis.

COVID-19 Linked to Development of Myasthenia Gravis

Easy Read article: Clinicians from Italy have described what they believe are the first three reported cases of acetylcholine receptor (AChR) antibody-positive myasthenia gravis after COVID-19 infection.

We note that symptoms of myasthenia gravis appeared within 5 to 7 days after fever onset in all 3 patients, and the time from presumed infection with SARS-CoV-2 to the beginning of myasthenia gravis symptoms is consistent with the time from infection to symptoms in other neurologic disorders triggered by infections.

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19

Conclusions: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care.

Tocilizumab for treatment of mechanically ventilated patients with COVID-19

CONCLUSIONS:

 In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.

Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

CONCLUSIONS:

In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.

Remdesivir Reduces Time to Recovery in Adults Hospitalized With COVID-19: A Meaningful Step in Therapeutic Discovery

Conclusion. The study found that remdesivir, compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.

COVID-19 Update: New Symptom, Test to Guide Steroid Treatment

Hospitalized COVID-19 patients with high levels of inflammation may benefit significantly from dexamethasone and other steroids, new research indicates — but there is still a need for more clarity about which patients are the best candidates for steroids. 

Combination Therapy Quells COVID-19 Cytokine Storm

These data from the Netherlands are quite interesting and provide another signal to support the use of corticosteroids, with tocilizumab if needed, among hospitalized patients with COVID-19 to improve outcomes.

While these data are not randomized and have a relatively small sample size, we had recently seen the results of the RECOVERY trial, a UK-based randomized trial demonstrating the benefit of steroids in COVID-19,”.

“Taken together, these studies seem to suggest that there is a benefit with steroid therapy.” Further validation of these results is warranted

The COVID-19 Cytokine Storm; What We Know So Far

As IL-6 is the most frequently reported cytokine to be increased in COVID-19 patients and as IL-6 elevated levels have been associated to higher mortalities, tocilizumab is a candidate drug to be used in managing the cytokine storm accompanying COVID-19.

Researchers: COVID-19 spreads ten meters or more by breathing

Easy Read Article ~
A plea issued by 239 scientists from around the world to recognize and mitigate airborne transmission of COVID-19 addressed to international health authorities is to be published in the journal Clinical Infectious Diseases.
Studies by the signatories and other scientists have demonstrated beyond any reasonable doubt that viruses are exhaled in microdroplets small enough to remain aloft in the air and pose a risk of exposure beyond 1 to 2m (6.5 feet) by an infected person.
The measures that need to be taken to mitigate airborne transmission include:
 
Provide sufficient and effective ventilation (supply clean outdoor air, minimize recirculating air) particularly in public buildings, workplace environments, schools, hospitals, and aged care homes.
 
Supplement general ventilation with airborne infection controls such as local exhaust, high-efficiency air filtration, and germicidal ultraviolet lights.
 
“We are concerned that people may think they are fully protected by following the current recommendations, but in fact, additional airborne precautions are needed to further reduce the spread of the virus.”

The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness.  Of 43 patients Five major categories emerged: (i) encephalopathies (n = 10) with
delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or
partial recovery with supportive care only; (ii) inflammatory CNS syndromes
including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis, with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis.

SARS-CoV-2 infection is
associated with a wide spectrum of neurological syndromes affecting the whole neuraxis,
including the cerebral vasculature and, in some cases, responding to immunotherapies. The
high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic
change, is striking.

COVID-19 Antibodies Can Disappear After 2-3 Months, Study Shows

Easy Read – Business Insider reported that the researchers tested for two types of antibodies: immunoglobulin G (IgG) and immunoglobulin M (IgM). IgG usually develops over a longer time period, meaning it’s a better indicator of long-term immunity, Business Insider said.

The decrease in detectable antibodies was sharp after 8 weeks, with a 71% median drop for IgG levels in the asymptomatic group and a 76% median drop in the symptomatic group, the study said.

The findings call into question the idea of “immunity passports,” which some countries want to issue to people who test positive for antibodies. These people would be allowed to go back to work and travel because they’re supposedly immune to the virus.

“Together, these data might indicate the risks of using COVID-19 ‘immunity passports’ and support the prolongation of public health interventions, including social distancing, hygiene, isolation of high-risk groups and widespread testing,” the authors wrote.

Neuroinvasive potential of SARS-CoV-2 revealed in a human brain organoid model

SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Reports indicate that 30-60% of patients with COVID-19 suffer from CNS symptoms. Yet, there is no consensus whether the virus can infect the brain, or what the consequences of infection are. Following SARS-CoV-2 infection of human brain organoids, clear evidence of infection was observed, with accompanying metabolic changes in the infected and neighboring neurons. Further, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Finally, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV2.

Neurological associations of COVID-19

Highly Recommended

17 page review. The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is
of a scale not seen since the 1918 influenza pandemic.  Encephalopathy
has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan,
China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described
in eight patients to date, and Guillain-Barré syndrome in 19 patients

Overall, the proportion of patients with neurological
manifestations is small compared with that with respiratory disease. However, the continuing pandemic, and the
expectation that 50–80% of the world’s population might
be infected before herd immunity develops, suggest that
the overall number of patients with neurological disease could become large. Neurological complications,
particularly encephalitis and stroke, can cause lifelong
disability, with associated long-term care needs and potentially large health, social, and economic costs. Health-care
planners and policy makers need to be aware of the
growing burden.

Three Stages to COVID-19 Brain Damage, New Review Suggests

In stage 1, viral damage is limited to epithelial cells of the nose and mouth, and in stage 2 blood clots that form in the lungs may travel to the brain, leading to stroke. In stage 3, the virus crosses the blood–brain barrier and invades the brain.

“Our major take-home points are that patients with COVID-19 symptoms, such as shortness of breath, headache, or dizziness, may have neurological symptoms that, at the time of hospitalization, might not be noticed or prioritized, or whose neurological symptoms may become apparent only after they leave the hospital,”

Hospitalized patients with COVID-19 should have a neurological evaluation and ideally a brain MRI before leaving the hospital; and, if there are abnormalities, they should follow up with a neurologist in 3 to 4 months.

Prevalence of Asymptomatic SARS-CoV-2 Infection A Narrative Review

Key Summary Points

The likelihood that approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.

Asymptomatic persons can transmit SARS-CoV-2 to others for an extended period, perhaps longer than 14 days.

The absence of COVID-19 symptoms in persons infected with SARS-CoV-2 might not necessarily imply an absence of harm. More research is needed to determine the significance of subclinical lung changes visible on computed tomography scans.

The focus of testing programs for SARS-CoV-2 should be substantially broadened to include persons who do not have symptoms of COVID-19.

COVID-19 May Be Triggering Diabetes in Healthy People, Experts Warn

A letter published today in the New England Journal of Medicine and signed by an international group of 17 leading diabetes experts involved in the CoviDiab project, a collaborative international research initiative, announces the establishment of a Global Registry of new cases of diabetes in patients with COVID-19.

Clinical observations so far show a bi-directional relationship between COVID-19 and diabetes. On the one hand, diabetes is associated with increased risk of COVID-19 severity and mortality. Between 20 and 30% of patients who died with COVID-19 have been reported to have diabetes. On the other hand, new-onset diabetes and atypical metabolic complications of pre-existing diabetes, including life-threatening ones, have been observed in people with COVID-19.

Guillain-Barr´e syndrome: The first documented COVID-19–triggered autoimmune neurologic disease

Emerging data indicate that COVID-19 can trigger not only GBS but other autoimmune neurological diseases necessitating vigilance for early diagnosis and therapy initiation. Although
COVID-19 infection, like most other viruses, can potentially worsen patients with pre-existing
autoimmunity, there is no evidence that patients with autoimmune neurological diseases stable on
common immunotherapies are facing increased risks of infection

COVID Testing FAQ, From Reinfection to Persistent Positives

“My patient is still positive for COVID-19 a month and a half later. Why?”

“Has my patient been reinfected, or is this just delayed recovery?”

Medscape spoke with Paul Auwaerter, MD, to get the answers to our readers’ frequently asked questions about coronavirus testing. This interview has been edited for length and clarity.

Acute disseminated encephalomyelitis after SARS-CoV-2 infection

We report a rare case of an immune-mediated CNS disease that occurs after SARS-CoV-2 infection. Phenotypically, the disease resembled an atypical form of neuromyelitis optica spectrum disorder; however, (1) the hyperacute dynamic of the disease, (2) the presence of multiple, synchronous, enhancing brain lesions, (3) the lack of anti-AQ4 or anti-MOG abs, (4) the absence of longitudinally extended transverse myelitis, and (5) the presence of a viral infection preceding the development of neurologic symptoms do not support this hypothesis, favoring ADEM diagnosis.

Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019 A Review

Published – May 29, 2020

This review serves to summarize available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system, and describe the range of clinical neurological complications that have been reported thus far in COVID-19 and their potential pathogenesis.

The most common neurologic complaints in COVID-19 are anosmia, ageusia, and headache, but other diseases, such as stroke, impairment of consciousness, seizure, and encephalopathy, have also been reported.

The understanding of neurologic disease in patients with COVID-19 is evolving, and clinicians should continue to monitor patients closely for neurological disease. Early detection of neurological deficits may lead to improved clinical outcomes and better treatment algorithms

COVID-19—White matter and globus pallidum lesions Demyelination or small-vessel vasculitis?

Besides demyelination, the associated punctiform lesions might be consistent with ischemic lesions because of small-vessel vasculitis. SARS-CoV-2 infects the host using the angiotensin-converting enzyme 2 receptor that is expressed in several organs, especially in endothelial cells. Recently, Varga et al.7 have showed direct viral infection of the endothelial cell and diffuse endothelial inflammation. This endothelial dysfunction can lead to vasoconstriction and break of the blood-brain barrier with cerebral ischemia and inflammation. Although mechanisms remain obscure, our case shows the importance of the MRI in the exploration of neurologic symptoms in COVID-19. Demyelination or small-vessel CNS vasculitis might be a rare but silent complication of sedated patients with COVID-19.

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

Key Points

Question:  What are the characteristics, clinical presentation, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) in the US?

Findings  In this case series that included 5700 patients hospitalized with COVID-19 in the New York City area, the most common comorbidities were hypertension, obesity, and diabetes. Among patients who were discharged or died (n = 2634), 14.2% were treated in the intensive care unit, 12.2% received invasive mechanical ventilation, 3.2% were treated with kidney replacement therapy, and 21% died.

Meaning  This study provides characteristics and early outcomes of patients hospitalized with COVID-19 in the New York City area.

Conjunctivitis Can Be Sole Covid-19 Symptom

Acute, non-remitting conjunctivitis may be the only presenting symptom of Covid-19 infections in some instances, according to case reports on five patients in Italy.

Because these patients were treated during the current SARS-CoV-2 pandemic, they also inquired about recent travels and discovered that all five of the patients had recently traveled to Lombardy, a Covid-19 hotspot. None had fever, respiratory symptoms, or other symptoms of Covid-19.

Still, tests performed using naso-pharyngeal swabs were done for all five patients, and all five came back positive for SARS-CoV-2.

MedTech FDA names 28 antibody tests to be taken off the market

The FDA changed its policy May 4, giving test makers with active products 10 days to submit applications for review. The agency said it expects its list of removed products to be updated in the future.

“Our action today is an important step the agency has taken to ensure that Americans have access to trustworthy tests,” FDA Commissioner Stephen Hahn, M.D.

To date, 12 antibody tests have passed the FDA’s emergency authorization process, while the agency works with the National Institutes of Health and the Centers for Disease Control and Prevention to independently validate certain serology tests.

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial

The first human trial of COVID-19 vaccine finds it is safe and induces  rapid immune response. Phase 1 human trial of a COVID-19 vaccine called Ad5-nCoV shows that it is safe, well-tolerated, and able to generate an immune response against SARS-CoV-2 in participants.

The trial demonstrates that a single dose of the new vaccine produces virus-specific antibodies and T cells in 14 days, making it a potential candidate for further investigation.

Steroid-responsive Encephalitis in Covid-19 Disease

Here we described the case of a 60-year old subject with SARS-CoV-2 infection but only mild respiratory abnormalities who developed an akinetic mutism due to encephalitis. MRI was negative whereas EEG showed generalized theta slowing. CSF analyses during the acute stage were negative for SARS-CoV-2, positive for pleocytosis and hyperproteinorrachia, and showed increased IL-8 and TNF-α concentrations while other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of CSF parameters was observed after high-dose steroid treatment, thus arguing for an inflammatory-mediated brain involvement related to Covid-19.

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic

Interpretation

If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term.

Trending Clinical Topic: Kawasaki Disease and COVID-19

UK pediatricians have published a working definition of the inflammatory syndrome. No one sign or symptom can be used to identify the children who are affected, and they may or may not test positive for COVID-19. See Image at top of page.

New Focus on Renin-Angiotensin System Role in COVID-19

“As we believe the renin–angiotensin system is being over-activated by the virus, this could also explain why patients with underlying cardiovascular diseases are having worse outcomes and would suggest that taking an ACE inhibitor or ARB would actually be protective.”

On the influenza study, Oudit said: “The influenza virus may well also activate the renin–angiotensin system. That study suggests that ACE inhibitors and ARBs may be protective here as well.”

Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients

Background: Convalescent plasma is the only antibody-based therapy currently
available for COVID-19 patients. It has robust historical precedence and sound
biological plausibility. Although promising, convalescent plasma has not yet been shown
to be safe as a treatment for COVID-19.

Conclusion: Given the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive.
These early indicators suggest that transfusion of convalescent plasma is safe in
hospitalized patients with COVID-19.

Coronavirus Disease 2019 (COVID-19) in Children

Signs and symptoms of COVID-19 in children. Common symptoms of COVID-19 in children are cough and fever. It is important to note, however, that these symptoms may not always be present; thus, a high index of suspicion for SARS-CoV-2 infection is required in children. Other symptoms include the following:
  • Shortness of breath
  • Pharyngeal erythema/sore throat
  • Diarrhea
  • Myalgia
  • Fatigue
  • Rhinorrhea
  • Vomiting
  • Nasal congestion
  • Abdominal pain
  • Conjunctivitis
  • Rash

Researchers Have Discovered a Strong Correlation Between Severe Vitamin D Deficiency and COVID-19 Mortality Rates

By analyzing publicly available patient data from around the globe, Backman and his team discovered a strong correlation between vitamin D levels and cytokine storm — a hyperinflammatory condition caused by an overactive immune system — as well as a correlation between vitamin D deficiency and mortality.

Backman is careful to note that people should not take excessive doses of vitamin D, which might come with negative side effects. He said the subject needs much more research to know how vitamin D could be used most effectively to protect against COVID-19 complications.

Neurological Implications of COVID 19 Infections

We strongly encourage the concerted surveillance for such conditions. Additional to the direct neurological complications of COVID‑19 infection, neurological patients are at risk of harm from both structural limitations (such as number of intensive care beds), and a hesitancy to treat with certain necessary medications given risk of nosocomial COVID‑19 infection. We therefore also outline the specific management of patients with neuroinflammatory diseases in the context of the pandemic.

Therapeutic strategies for critically ill patients with COVID-19

In the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of COVID-19 in the ICU based on the previous experience of treating other viral infections and infuenza. These treatments are referable before the vaccine and specifc drugs are available for COVID-19.

COVID-19 Panel: Helmet CPAP, Pronation Key Tools for Some Patients

Noninvasive ventilation with helmet continuous positive air pressure (CPAP) deserves to be embraced as an effective strategy in preventing self-induced lung injury, often a key factor in progression from the early milder expression of COVID-19 disease to classic severe acute respiratory Distress Syndrome.

Compassionate Use of Remdesivir for Patients with Severe Covid-19

CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy.

'Silent Hypoxemia' and Other Curious Clinical Observations in COVID-19

Podcast and transcript- Gary S. Ferenchick, MD, MS, a professor of medicine at Michigan State University, interviewed his daughter, Hannah R.B. Ferenchick, MD, an emergency and critical care physician working on the frontline in a busy Detroit hospital, about some of the unusual clinical features of patients with suspected or confirmed COVID-19.

A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19

A scientific rationale existed for investigating HCQ in COVID-19. However, other methodological flaws may affect the validity of the findings, even in the current setting, where an efficacious treatment is desperately needed. Thus another explanation is that the baseline viral load, not therapy with HCQ + AZM, affects viral load at day 6.

Despite the study’s substantial limitations, a simplification and probable overinterpretation of these findings was rapidly disseminated by the lay press and amplified on social media, ultimately endorsed by many government and institutional leaders.

A major consequence has been an inadequate supply of HCQ for patients in whom efficacy is established. Hydroxychloroquine is an essential treatment of rheumatoid arthritis and of systemic lupus erythematosus, reducing flares and preventing organ damage in the latter disease. HCQ shortages could place these patients at risk for severe and even life-threatening flares; some may require hospitalization when hospitals are already at capacity. There currently are no data to recommend the use of HCQ as prophylaxis for COVID-19.

Neurologic Features in Severe SARS-CoV-2 Infection

We report the neurologic features in an observational series of 58 of 64 consecutive patients admitted to the hospital because of acute respiratory distress syndrome (ARDS) due to Covid-19.

In this consecutive series of patients, ARDS due to SARS-CoV-2 infection was associated with encephalopathy, prominent agitation and confusion, and corticospinal tract signs. Two of 13 patients who underwent brain MRI had single acute ischemic strokes. Data are lacking to determine which of these features were due to critical illness–related encephalopathy, cytokines, or the effect or withdrawal of medication, and which features were specific to SARS-CoV-2 infection.

IDSA: No Recommendations for COVID-19 Treatment for Now, 'Knowledge Gaps' Cited

There is currently insufficient evidence to recommend any particular medication for treatment of COVID-19, an expert panel of the Infectious Diseases Society of America (IDSA) has concluded.

Many pharmacologic therapies are being used or considered for the treatment of patients with COVID-19. Given the rapidly emerging literature on treatment, the IDSA convened the panel to develop interim evidence-based guidelines to support clinicians in making decisions about treatment and management of patients with COVID-19.

This is a “living document” that represents the best understanding to date on the treatment of patients with COVID-19, and it will be updated frequently as new information becomes available

Warning of Higher COVID-19 Problems From Glucocorticoid Use

Adults prescribed glucocorticoid therapy for common conditions, such as asthma and arthritis, as well as individuals with adrenal insufficiency, are at high risk for developing serious complications from COVID-19 due to an inability to mount a normal stress response.

If any doctor or healthcare professional is coming across people who received steroid therapy for the previous 3 months, they need to be regarded as an ‘at risk’ individual in terms of the progression of their illness, with a fairly low threshold for giving them supplemental steroid therapy, which might be life-saving. That’s the plea here.

Cardiology Groups Push Back on Hydroxychloroquine, Azithromycin for COVID-19

The nation’s leading cardiology associations urged caution with hydroxychloroquine and azithromycin for COVID-19 in patients with cardiovascular disease.

“Hydroxychloroquine and azithromycin have been touted for potential prophylaxis or treatment for COVID-19; both drugs are listed as definite causes of torsade de pointes” and increase in the risk of other arrhythmias and sudden death, the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society said in a joint statement April 8 in Circulation.

The statement came amid ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite lack of strong data.

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

April 10-2020  Key Points

Question  What are neurologic manifestations of patients with coronavirus disease 2019?

Findings  In a case series of 214 patients with coronavirus disease 2019, neurologic symptoms were seen in 36.4% of patients and were more common in patients with severe infection (45.5%) according to their respiratory status, which included acute cerebrovascular events, impaired consciousness, and muscle injury.

Meaning  Neurologic symptoms manifest in a notable proportion of patients with coronavirus disease 2019.

Nephrologists on Lessons Learned With Kidney Disease in COVID-19

Although lung damage is the main feature of severe COVID-19, it is becoming crystal clear that the kidney is one of the other major organs involved.

“The mortality we’re seeing with these [dialysis and transplant] patients is because COVID-19 pneumonia/disease can be very aggressive with a severe distress syndrome,” Soler told Medscape Medical News. Discusses Dialysis/Transplant COVID-19 Experience in Spain

COVID-19: Facing Hard Truths on the Front Line

The Royal Society of Medicine (RSM) has launched a series of webinars for members to help support them with the difficult life and death decisions they are going to have to make in the coming months during the height of the COVID-19 pandemic. All health care professionals are having to make decisions during COVID-19 that they never thought they would, and the decision in life and death situations nearly always rests ultimately with the doctor in charge of the case.

The article includes: Ethical guidance published for frontline staff dealing with the pandemic

COVID-19 Linked to Multiple Cardiovascular Presentations

It’s becoming clear that COVID-19 infection can involve the cardiovascular system in many different ways, and this has “evolving” potential implications for treatment, say a team of cardiologists on the frontlines of the COVID-19 battle in New York City.

COVID-19 Daily: More Will Die, First Antibody Test Authorized

A newly available antibody test may help evaluate the SARS-CoV-2 virus in 20 minutes or less. The US Food and Drug Administration has granted Cellex an emergency use authorization to market the first rapid antibody test for
COVID-19.

COVID-19: More Hydroxychloroquine Data From France, More Questions

There was a  Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients. This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.

Personally, I really believe in hydroxychloroquine. It would nevertheless be a shame to think we had found the fountain of youth and realize, in 4 weeks, that we have the same number of deaths. That is the problem. I hope that we will soon have solid data so we do not waste time focusing solely on hydroxychloroquine.

Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies

April 7-2020

No drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19. Numerous antiviral agents, immunotherapies, and vaccines are being investigated and developed as potential therapies. Searching for effective therapies for COVID-19 infection is a complex process.

Coronavirus on Fabric: What You Should Know

April 2-2020

If you suspect you got too close for too long, or someone coughed on you, there’s no harm in changing your clothing and washing it right away, especially if there are hard surfaces like buttons and zippers where the virus might linger. Wash your hands again after you put everything into the machine. Dry everything on high, since the virus dies at temperatures above 133°F. File these steps under “abundance of caution”: They’re not necessary, but if it gives you peace of mind, it may be worth it.

Michigan woman with coronavirus develops rare complication affecting brain

April 1-2020 A 58-year-old woman hospitalized in the Henry Ford Health System who has the new coronavirus developed a rare complication: encephalitis.

It is believed to be the first published case linking COVID-19 and acute necrotizing encephalitis. The rare and serious brain disease can develop in people who have a viral infection, and causes lesions to form in the brain, tissue death and symptoms such as seizures, drowsiness, confusion and coma.

Should We All Be Wearing Masks In Public? Health Experts Revisit The Question

March 31-2020   “Cotton masks constructed in a proper way should provide a reasonable degree of protection from people being able to transmit the virus. ” CDC to issue guidelines

At least 8 strains of the coronavirus are spreading across the globe

Scientists have identified at least eight strains of coronavirus as the bug wreaks havoc spreading across the globe.

More than 2,000 genetic sequences of the virus have been submitted from labs to the open database NextStrain, which shows it mutating on maps in real-time, according to the site.

Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies

No drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19. Numerous antiviral agents, immunotherapies, and vaccines are being investigated and developed as potential therapies. Searching for effective therapies for COVID-19 infection is a complex process. Gordon et al identified 332 high-confidence SARS-CoV-2 human protein-protein interactions. Among these, they identified 66 human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials, and/or preclinical compounds. As of March 22, 2020, these researchers are in the process of evaluating the potential efficacy of these drugs in live SARS-CoV-2 infection assays.

How long coronavirus survives on surfaces - and what it means for handling money, food and more

The article includes: How can we reduce risk from surfaces and objects? While it’s best to stay home, details tips to enact if you must leave the house.

What Neurologists Can Expect From COVID-19

In rare cases, complications including ADEM (acute disseminated encephalomyelitis)-like demyelination, encephalitis, and brainstem encephalitis were reported. They also saw some peripheral and non–central nervous system stuff, including things that looked like Guillain-Barre syndrome or what they would sometimes call critical illness polyneuropathy.

The data are still limited on whether coronaviruses have a significant neurologic component. There are reports of other coronaviruses entering the brain of patients and experimental animals. Does that mean anything? Right now, we simply don’t know.

You could be spreading the coronavirus without realising you’ve got it

What all this makes clear is that advising only people with a cough or fever and their families to self-isolate won’t prevent the coronavirus from spreading, thanks to its fiendish ability to cause very mild symptoms in people, and to peak in infectiousness before people even realise they are sick.

Read more: https://www.newscientist.com/article/2238473-you-could-be-spreading-the-coronavirus-without-realising-youve-got-it/#ixzz6IHqPt4lV

Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma

These preliminary findings raise the possibility that convalescent plasma transfusion may be helpful in the treatment of critically ill patients with COVID-19 and ARDS, but this approach requires evaluation in randomized clinical trials.

Limbic encephalitis and Post-Acute neuropsychology rehabilitation: A review and case examples

Rehabilitation research on limbic encephalitis (LE), a rare disorder characterized by inflammation of the brain caused by autoimmunity or infection, has focused on acute rather than post-acute management of symptoms. The frequency of clinical relapse in encephalitis ranges from 12% to 35%. Commonly, individuals diagnosed with LE experience relapses or breakthrough seizures during their post-acute treatment. The treating neuropsychologist will often need to do family and staff education regarding the disorder, a possible unusual pattern of recovery, and discuss the risk of relapse. Additionally, staff may need help with behavior management and the potential need for a behavior management plan.

Relapse involving need for re-admission to an acute setting occurred in four cases and medication side effects (sedation) in three. As a whole, these cases highlight the complex and potentially unusual course of recovery in individuals with LE.

Stop testing for autoantibodies to the VGKC-complex: only request LGI1 and CASPR2

(VGKC) antibodies that lack LGI1 or CASPR2 reactivities (‘double-negative’) are common in healthy controls and have no consistent associations with distinct syndromes. These antibodies target intracellular epitopes and lack pathogenic potential. Moreover, the clinically important LGI1 and CASPR2 antibodies comprise only ~15% of VGKC-positive results, meaning that most VGKC-antibody positive results mislead rather than help. Further, initial VGKC testing misses some cases that have LGI1 and CASPR2 antibodies. These collective observations confirm that laboratories should stop testing for VGKC antibodies and instead, test only for LGI1 and CASPR2 antibodies. This change in practice will lead to significant patient benefit.

Double-negative VGKC antibodies usually target intracellular epitopes and lack pathogenic potential. The VGKC antibody titre is not a clinically reliable measure. The concept of a ‘clinically relevant’ VGKC antibody titre has created many misdiagnoses, often where finding the antibody has overruled the clinical diagnosis. The evidence from multiple international groups suggests there are no longer clinical reasons to test for VGKC antibodies. Stopping this test will reduce clinically irrelevant results, improve diagnostic accuracy and limit the use of unnecessary, potentially toxic, immunotherapies in patients.

The Clinical Value of 18 F-FDG-PET in Autoimmune Encephalitis Associated With LGI1 Antibody

The initial 18F-FDG-PET scan indicated a significant abnormal metabolic pattern in 31 LGI1 AE patients (91%), whereas only 20 patients (59%) showed an abnormal MRI. The 18F-FDG-PET metabolic pattern was reversible after treatment; most of the patients showed an almost normal uptake of 18F-FDG-PET after discharge.

Regarding the abnormal metabolic pattern in LGI1 AE subjects exhibiting hypermetabolism was specifically located in the basal ganglia (BG) and medial temporal lobe (MTL). BG hypermetabolism was observed in 28 subjects (82%), and 68% of patients showed MTL hypermetabolism. A total of 17 patients (50%) exhibited faciobrachial dystonic seizures (FBDS), and the remaining subjects showed non-FBDS symptoms (50 and 50%). BG-only hypermetabolism was detected in seven subjects in the FBDS subgroup (7/16) but in only one subject in the non-FBDS subgroup

Psychiatric Manifestation of Anti-LGI1 Encephalitis

Conclusion: This case study describes a patient with anti-LGI1 encephalitis in the chronified stage and a predominant long-lasting psychiatric course with atypical symptoms of psychosis and typical neurocognitive deficits. The patient’s poor response to anti-inflammatory drugs was probably due to the delayed start of treatment. This delay in diagnosis and treatment may also have led to the FDG-PET findings, which were compatible with frontotemporal dementia (“state of damage”). In similar future cases, newly occurring epileptic seizures associated with psychiatric symptoms should trigger investigations for possible autoimmune encephalitis, even in patients with addiction or other pre-existing psychiatric conditions. This should in turn result in rapid organic clarification and-in positive cases-to anti-inflammatory treatment. Early treatment of anti-LGI1 encephalitis during the “inflammatory activity state” is crucial for overall prognosis and may avoid the development of dementia in some cases.

Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms

Overall, in this study, focused molecular hypotheses have been accurately dissected via the generation of patient-derived mAbs. The findings have highlighted intriguing aspects of the immunology and neuroscience, which inform multiple mechanisms underlying this highly amnesic and epileptogenic disease. While several mechanisms remain to be explored, these findings provide insights into the potential of mAbs to inform many aspects of the underlying disease biology which could not easily be highlighted by the study of polyclonal sera and CSFs.

IVIG Shows Efficacy for Autoimmune Encephalitis and Epilepsy

Intravenous immunoglobulin (IVIG) is an effective acute treatment strategy for reducing seizures in patients with seizures tied to two rare types of antibody-associated encephalitis, LGI1, and CASPR2, according to results from a small, double-blinded randomized, placebo-controlled trial featured as part of the 2020 AAN Science Advances.

Limbic encephalitis in a neuroscientist: CASPR 2 antibody-associated disease after antigen exposure

Autoimmune limbic encephalitis is part of CASPR 2 antibody-associated disease. A man with this rare disorder and a very high antibody titre had a unique history of laboratory exposure to the antigen. Together with earlier observations this case calls for caution in laboratory handling of nerve tissue.

Pilomotor Seizures in a Patient With LGI1 Encephalitis

The majority of these patients present faciobrachial dystonic seizures (FBDS), which are regarded as a characteristic symptom. A few cases have reported pilomotor seizures as the main manifestation of anti-LGI1 encephalitis. Here, we described a Chinese woman with frequent pilomotor seizures who was finally diagnosed as having anti-LGI1 encephalitis. Our report emphasizes the possible significance of pilomotor seizures in anti-LGI1 encephalitis.

Intrathecal B-cell activation in LGI1 antibody encephalitis

Our findings suggest that plasmablasts and plasma cells (which do not express CD20) are active in the CSF, and therefore, novel drugs that actively target these prolific protein synthesizers in the CNS compartment might be more effective than selective anti-CD20 treatments. Conversely, given that affinity maturation is an ongoing process in LGI1 antibody encephalitis and could result in increasingly efficient pathogenic antibodies, therapeutic depletion of CD20-expressing B-cell populations early in this disease might prevent development of chronic or progressive clinical phenotypes. Accordingly, early diagnosis of intrathecal immune activation in patients with mild clinical signs would be highly desirable.

 

Psychosis associated to CASPR2 autoantibodies and ovarian teratoma: A case report

First report of CASPR2 associated psychosis related to an ovarian teratoma. Prompt reduction of psychotic symptoms after excision of teratoma. The diagnosis of autoimmune psychosis can be made in the presence of autoantibodies in the serum while CSF is unremarkable.

Patients with depressive and psychotic symptoms non-responding to antidepressant and antipsychotic treatment should be screened for neuronal autoantibodies including CASPR2.

 

Daratumumab treatment for therapy-refractory anti-CASPR2 encephalitis

The anti-CD38 antibody daratumumab is approved for treatment of refractory multiple myeloma and acts by depletion of plasma cells and modification of various T-cell functions. Its safety, immunological effects and therapeutic potential was evaluated in a 60-year old patient with life-threatening and treatment-refractory anti-CASPR2 encephalitis requiring medical care and artificial ventilation in an intensive care unit.

Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction.

Recent studies have validated the use of Antibody-Prevalence-in-Epilepsy (APE) and Responsive-to-immunotherapy-in-Epilepsy (RITE) scores in the evaluation and management of autoimmune-epilepsy.

Factors underlying the development of chronic temporal lobe epilepsy in autoimmune encephalitis

LGI1 expression and human brain asymmetry

Distinction between anti-VGKC-complex seropositive patients with and without anti-LGI1/CASPR2 antibodies

Non-inheritable predisposition to LGI1 and Caspr2 antibody diseases

Neuroimmunology 2017: making progress over 20 years

Psychiatric symptoms delay the diagnosis of anti-LGI1 encephalitis

Mechanisms of Caspr2 antibodies in autoimmune encephalitis and neuromyotonia

The importance of early immunotherapy in patients with faciobrachial dystonic seizures (LGI1 Limbic encephalitis)

LGI1, CASPR2 and related antibodies: a molecular evolution of the phenotypes

IVIG treatment for repeated hypothermic attacks associated with LGI1 antibody encephalitis

Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

Autoimmune episodic ataxia in patients with anti-CASPR2 antibody-associated encephalitis

The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis

Anti-LGI1 encephalitis is strongly associated with HLA-DR7 and HLA-DRB4

From VGKC to LGI1 and Caspr2 encephalitis: The evolution of a disease entity over time

Unexplicated neuropsychiatric disorders a case report LGI1

Clinical spectrum and diagnostic value of antibodies against the potassium channel-related protein complex

Long-Term Memory Dysfunction in Limbic Encephalitis

Functional memory impairment seems to be based on the structural integrity of mesiotemporal brain structures, as memory function is known to correlate with reduced hippocampal subfield volumes.

LE involves frontal lobe structures also, but the main underlying brain pathology involving infiltrating lymphocytes affects the amygdalohippocampal complex indicating that dysfunctional LTM is more probable than impaired working-memory pathways. In particular, some LE forms are susceptible to LTM dysfunction as their disease-mediating antibodies against membrane receptors are critically involved in hippocampal synaptic long-term plasticity and LTM formation. It is thus not surprising that some AMPAR-antibodies associated LE patients present with an amnestic syndrome, such as the unique clinical manifestation of autoimmunity. Antibody-mediated immunopathology involving distinct memory phenotypes fluctuates.

Anti-CASPR2 clinical phenotypes correlate with HLA and immunological features

Antibodies against contactin-associated protein-like 2 (CASPR2-Abs) have been described in acquired neuromyotonia, limbic encephalitis (LE) and Morvan syndrome (MoS). However, it is unknown whether these constitute one sole spectrum of diseases with the same immunopathogenesis or three distinct entities with different mechanisms.

Interpretation Symptoms’ distribution supports specific clinical phenotypes without overlap between LE and MoS. The distinct immunogenetic characteristics shared by all patients with LE and the particular oncological and autoimmune associations of MoS suggest two very different aetiopathogenesis.

Synaptic autoimmunity: new insights into LGI1 antibody-mediated neuronal dysfunction

This scientific commentary refers to ‘Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms’, by Ramberger et al. (doi:10.1093/brain/awaa104).

The neuropsychological spectrum of anti-LGI1 antibody mediated autoimmune encephalitis

This review provides a comprehensive summary of the currently available literature, conceptualising our current understanding of the neuropsychological manifestations of anti LGI-1 AE and summarises methodological limitations of the current research to inform and improve future investigations.

Novel Findings of HLA Association With anti-LGI1 Encephalitis: HLA-DRB1*03:01 and HLA-DQB1*02:01

These results indicated that HLA subtypes were only associated with anti-LGI1 encephalitis.

Clinical and Electroencephalographic Features of the Seizures in Neuronal Surface Antibody-Associated Autoimmune Encephalitis

To investigate clinical and electroencephalographic features of the seizures in different types of neuronal surface antibody (NSAb)-associated autoimmune encephalitis

Leucine-rich glioma-inactivated protein 1 (LGI-1) mediated limbic encephalitis associated with syndrome of inappropriate antidiuretic hormone secretion: a case report

We report a 57-year-old man who presented to the ER with recurrent seizures, visual hallucinations, and severe memory impairment over a seven-week period. Initial investigations revealed hyponatremia, indicating syndrome of inappropriate antidiuretic hormone secretion. MRI of the brain revealed bilateral asymmetrical high-T2 and low-T1 signal in the medial temporal lobes. Serum immunofluorescence assay tested positive for LGI-1 antibody. The patient responded to treatment with levetiracetam, intravenous methylprednisolone, and five plasma exchange sessions. The patient remains on a maintenance dose of prednisolone and azathioprine. It is imperative that clinicians recognize signs of autoimmune encephalitis in order to curb long-term sequelae and improve clinical outcomes.

Pathologic tearfulness after limbic encephalitis A novel disorder and its neural basis

Pathologic tearfulness was reported by 50% of the patients, while no patient-reported pathologic laughing. People with LE may cry their eyes out over the simplest things. Dr. Irani’s Oxford group said, “We coined the term ‘Disney syndrome’ when we saw the first few patients as they were tearful while watching kiddie movies with their children.”

Beyond the limbic system: disruption and functional compensation of large-scale brain networks in patients with anti-LGI1 encephalitis

Hippocampal Functional Dynamics Are Clinically Implicated in Autoimmune Encephalitis With Faciobrachial Dystonic Seizures

Distinct HLA associations of LGI1 and CASPR2-antibody diseases

Genetic predisposition in anti-LGI1 and anti-NMDA receptor encephalitis

Immune or Genetic-Mediated Disruption of CASPR2 Causes Pain Hypersensitivity Due to Enhanced Primary Afferent Excitability

Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies

A Genetic Disposition for Autoimmune Encephalitis: Searching for Human Leukocyte Antigen (HLA) Complex Subtype

AE with LGI1 or CASPR2 (formerly called voltage-gated potassium channel-complex antibodies)

Clinical features of limbic encephalitis with LGI1 antibody

Delayed LGI1 seropositivity in voltage-gated potassium channel (VGKC)-complex antibody limbic encephalitis

Emergence of new-onset psychotic disorder following recovery from LGI1 antibody-associated limbic encephalitis

What are the emerging features of anti-VGKC autoimmune encephalitis?

VGKC-Complex Antibodies in the Absence of LGI1 and Caspr2 Antibodies

Creutzfeldt-Jakob Disease-Like Periodic Sharp Wave Complexes in VGKC Antibodies Encephalitis: A Case Report

What we know about the new Covid-19-linked illness in children

A rare, Kawasaki-like disease is striking kids who have coronavirus antibodies.

Doctors in 17 US states are reporting that at least 164 children have fallen sick with a rare inflammatory illness similar to a condition known as Kawasaki disease. Symptoms include fever and inflammation and can affect organs, including the heart. Some of the children have tested positive for Covid-19 or antibodies to the virus, and three have died.

“As in any infection, it is important for parents to seek care with their pediatrician if their child has high fevers, new rash, significant abdominal pain, persistent vomiting, persistent diarrhea, or any other concerning symptom.”

But she and other doctors underscore that despite the increased incidence of the pediatric syndrome, it is still quite rare, “probably affecting no more than one in 1,000 children exposed to SARS-CoV-2.”

Convalescent plasma in Covid-19: Possible mechanisms of action

Highlights:  Coronavirus disease 19 (COVID-19) is an emerging viral threat with major repercussions for public health.

There is not specific treatment for COVID-19.

Convalescent plasma (CP) emerges as the first option of management for hospitalized patients with COVID-19.

Transference of neutralizing antibodies helps to control COVID-19 infection and modulates inflammatory response.

Other plasma components may enhance the antiviral and anti-inflammatory properties of CP.

Children are falling sick with a rare mystery inflammatory syndrome linked to Coronavirus

The new condition that’s being linked to COVID-19 got an official name this week: pediatric multisystem inflammatory syndrome.

Children and teens with the rare but potentially dangerous complication have been identified in at least seven states and the Washington, D.C., area as well as some parts of Europe. The condition can resemble features of other inflammatory illnesses like the Kawasaki Disease and toxic shock-like syndrome.

Physicians and scientists are working hard to understanding the mechanisms at play, and why only some children are so severely affected,” she said. Dr. John revealed that “the feature that’s been most concerning is that they have problems with their heart function.”

Dr. John added: “In general, families do not need to worry about this. I doubt that this is really new. I think it’s just really newly recognized. I hope what comes of this is that, because we’re seeing more cases, it will not take long before we will be better at recognizing this and treating it.”

Immunomodulation in COVID-19

Here, we expand on the theoretical basis of IL-6 inhibition and propose potential benefits from other immunomodulators that could, in theory, prove more efficacious.

 

As insight is gained into the clinical phenotypes associated with COVID-19, we propose JAK and IL-1 inhibitors as therapeutic targets warranting rapid investigation. Multidisciplinary collaboration with experts in haematology, inflammation, tissue damage, and repair and resolution is paramount.

Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children.

Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged.

Rapid development of an inactivated vaccine candidate for SARS-CoV-2

We developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.

FDA Authorizes Emergency Use of Remdesivir for COVID-19

The FDA writes, “Based on evaluation of the emergency use authorization criteria and the scientific evidence available, it was determined that it is reasonable to believe that remdesivir may be effective in treating COVID-19, and that, given there are no adequate, approved, or available alternative treatments, the known and potential benefits to treat this serious or life-threatening virus currently outweigh the known and potential risks of the drug’s use.”

Neurons promote encephalitogenic CD4 + lymphocyte infiltration in experimental autoimmune encephalomyelitis

To our knowledge, we for the first time adopted inhibitory DREADD and a migration assay using embryonic cerebral cortex neurons with CD4+ T cells. This methodology will pave a new way to investigate the pathophysiological role of excitatory neurons in EAE.

'Hypercoagulation,' Antiphospholipid Antibodies Seen in COVID-19

Researchers from China describe three patients admitted to the intensive care unit (ICU) with confirmed SARS-CoV-2 infection, severe COVID-19, and clinically significant coagulopathy, antiphospholipid antibodies, and multiple cerebral infarcts.

“Antiphospholipid antibodies abnormally target phospholipid proteins, and the presence of these antibodies is central to the diagnosis of the antiphospholipid syndrome.

Why Some People Get Sicker Than Others

Personal storytelling of COVID-19 cases. Includes a podcast and overview of clinical trials for therapies. An easy and worthwhile read for the layperson.

Sudden Loss of Taste and Smell Should Be Part of COVID-19 Screen

In her survey of patients who presented to UC San Diego Health for SARS-CoV-2 testing, Yan and colleagues reported that 68% (40 of 59) of COVID-19-positive patients reported olfactory impairment and 71% (42 of 59) reported taste impairment.

“Based on our study, if you have smell and taste loss, you are more than 10 times more likely to have COVID-19 infection than other causes of infection. The most common first sign of a COVID-19 infection remains fever, but fatigue and loss of smell and taste follow as other very common initial symptoms,” said Yan.

More Evidence Supports COVID-19/Guillain-Barré Link

Five more cases of  Guillain–Barré syndrome (GBS) in association with COVID-19 have been identified, further supporting a link between the virus and neurologic complications, including GBS.

Three of the patients developed a demyelinating form of GBS; the other two had findings generally consistent with an axonal variant. All five patients received intravenous immune globulin treatment.

Hydroxychloroquine for COVID-19: What's the Evidence?

The bottom line is that we don’t need to abandon evidence-based medicine in the face of the pandemic. We need to embrace it more than ever. But in that embrace, we need to realize what we’ve known all along: Evidence-based medicine is not just about randomized trials; it’s about appreciating the strengths and weaknesses of all data, and allowing the data to inch us closer and closer toward truth.

Remdesivir Prevents Disease Progression in Monkeys With COVID-19

Early treatment with the experimental antiviral drug remdesivir significantly reduced clinical disease and damage to the lungs of rhesus macaques infected with SARS-CoV-2, the coronavirus that causes COVID-19, according to National Institutes of Health scientists.

Twelve hours after the initial treatment, the scientists examined all animals and found the six treated animals in significantly better health than the untreated group, a trend that continued during the seven-day study.

The investigators note that the data supports initiating remdesivir treatment in COVID-19 patients as early as possible to achieve maximum treatment effect. “This finding is of great significance for patient management, where a clinical improvement should not be interpreted as a lack of infectiousness,” they write.

Imaging Recommendations Issued for COVID-19 Patients

  • Recommendations: Imaging is indicated for patients with features of moderate to severe COVID-19 regardless of COVID-19 test results.
  • Imaging is indicated for patients with COVID-19 and evidence of worsening respiratory status.
  • When access to CT is limited, chest radiography may be preferred for COVID-19 patients unless features of respiratory worsening warrant using CT.
  • Additional recommendations: Daily chest radiographs are not indicated in stable, intubated patients with COVID-19.
  • CT is indicated in patients with functional impairment, hypoxemia, or both, after COVID-19 recovery.
  • COVID-19 testing is warranted in patients incidentally found to have findings suggestive of COVID-19 on a CT scan.

COVID-19: First Data Confirm Neurologic Symptoms Common

Investigators based in Wuhan, China, analyzed data from more than 200 adult patients with COVID-19 and found that 36.4% had neurologic manifestations. In addition, close to half of those with severe disease had neurologic symptoms, compared to roughly one-third of those with less severe disease.

Nervous system manifestations of COVID-19 were “significantly more common” in severe versus nonsevere infection.

The public and medical personnel alike need to be aware that there may be neurological manifestations of COVID-19 and such symptoms indicate a need for prompt medical attention.

COVID-19: Exercise may protect against deadly complication

Regular exercise may reduce the risk of acute respiratory distress syndrome, a major cause of death in patients with the COVID-19 virus, a top exercise researcher reports. He is urging people to exercise based on his findings, which also suggest a potential treatment approach.

Hydroxychloroquine for COVID-19 Study Did Not Meet 'Expected Standard'

The paper that appears to have triggered the Trump administration’s obsession with hydroxychloroquine as a treatment for infection with the novel coronavirus has received a statement of concern from the society that publishes the journal in which the work appeared.

Elisabeth Bik took a close look at the IJAA article and detailed a long list of serious problems with the study, including questions about its ethical underpinnings, messy confounding variables, missing patients, rushed and conflicted peer review, and confusing data.

COVID-19:Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism

This paper  explains the action of the virus from a hematological point of view, meaning that the severe hypoxia is because of the desaturation in oxygen of the red blood cells being attacked by the virus and not because of pulmonary inflammation.

A first Case of Meningitis/Encephalitis associated with SARS-Coronavirus-2

Highlights

Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly.
This is the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance.
The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF.
This case warns the physicians of patients who have CNS symptoms.

Responding to stress experienced by hospital staff working with Covid-19

Drawing on research, best practice guidelines and expert clinical opinions, the COVID Trauma Response Working Group has created rapid guidance for planners putting in place psychological support for staff in the early stages of dealing with the Covid-19 outbreak.

Download Graphic here https://www.kingsfund.org.uk/sites/default/files/2020-04/rapid-guidance-stress-diagram.pdf

The Spectrum of Neurologic Disease in the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic Infection

April 10-2020  In these 214 patients, they report 36.4% had some nervous system-related clinical finding.1 These neurologic manifestations ranged from fairly specific symptoms (eg, loss of sense of smell or taste, myopathy, and stroke) to more nonspecific symptoms (eg, headache, depressed level of consciousness, dizziness, or seizure).1 Whether these more nonspecific symptoms are manifestations of the disease itself or consistent with a systemic inflammatory response in patients who were quite ill will need to be defined in future studies. Importantly, the authors found that patients in their series with some of the more common specific symptoms, including smell or taste impairment and myopathy, tended to have these symptoms early in their clinical course; this appears to be quite distinct from SARS, where manifestations appeared quite late in established disease.

Coronavirus disease 2019 has now reached pandemic status and is common all over the world; thus, with so many affected patients, we can expect as neurologists to be confronted with these patients commonly in coming months and years.

Many Children With COVID-19 Don't Have Cough or Fever

The characteristic COVID-19 symptoms of cough, fever, and shortness of breath are less common in children than adults, according to the Centers for Disease and Prevention Control.

Among pediatric patients younger than 18 years in the United States, 73% had at least one of the trio of symptoms, compared with 93% of adults aged 18-64, noted Lucy A. McNamara, PhD, and the CDC’s COVID-19 response team, based on a preliminary analysis of the 149,082 cases reported as of April 2.

Neurologic Symptoms and COVID-19: What's Known, What Isn't

Since the Centers for Disease Control and Prevention (CDC) confirmed the first US case of novel coronavirus infection on January 20, much of the clinical focus has naturally centered on the virus’ prodromal symptoms and severe respiratory effects.

However, US neurologists are now reporting that COVID-19 symptoms may also could include encephalopathy, ataxia, and other neurologic signs.

Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know

The looming public health crisis for people with rheumatic diseases who will be unable to obtain HCQ is the result of a perfect storm of fear and dissemination of overpromised data. However, there is still time to mitigate the damage. Physicians should educate themselves about the strength of available data regarding HCQ and CQ in treating COVID-19. They should avoid misuse of HCQ and CQ for the prophylaxis of COVID-19, because there are absolutely no data to support this. Public figures should refrain from promoting unproven therapies to the public, and instead provide clear messages around the uncertainties we face in testing and using experimental treatments during the current pandemic, including the risk for serious adverse events. Well-done, randomized clinical trials should be performed urgently to test potential therapies, including HCQ. In the meantime, physicians should remember that first, we must do no harm to the patients with rheumatic disease for whom high-quality evidence shows that HCQ improves health.

Risk Factors for Death From COVID-19 Identified in Wuhan Patients

Nonsurvivors compared with survivors had higher frequencies of respiratory failure (98% vs 36%), sepsis (100%, vs 42%), and secondary infections (50% vs 1%).

The average age of survivors was 52 years compared to 69 for those who died. Liu cited weakening of the immune system and increased inflammation, which damages organs and also promotes viral replication, as explanations for the age effect.

From the time of initial symptoms, median time to discharge from the hospital was 22 days. Average time to death was 18.5 days.

The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro

Highlights:

Ivermectin is an inhibitor of the COVID-19 causative virus (SARS-CoV-2) in vitro.

A single treatment able to effect ∼5000-fold reduction in virus at 48h in cell culture.

Ivermectin is FDA-approved for parasitic infections, and therefore has a potential for repurposing.

Ivermectin is widely available, due to its inclusion on the WHO model list of essential medicines.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.

Coronavirus survivors' plasma could save lives

This paper: The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study

Two independent research studies have shown the benefit of receiving infusions of blood from COVID-19 survivors.

The teams – both based in China – extracted blood plasma from patients who had recovered from COVID-19, which contained antibodies against the disease. The first study from the National Engineering Technology Research Center for Combined Vaccines in Wuhan   gave plasma to 10 patients who were severely ill with COVID-19. Six days after receiving the infusion, the COVID-19 virus was undetectable in seven of the 10 patients.

Hydroxychloroquine: Possible COVID Drug Can Be Toxic to Retinas

Comorbidities Increase Likelihood of Retinal Toxicity

While a detailed patient history may be impossible to obtain if HCQ is used in the treatment of COVID-19, certain comorbidities do place patients at an increased risk for retinal toxicity. HCQ is excreted through renal clearance, so the dosage should be reduced in those with compromised kidney function to minimize the risk for toxicity. The presence of macular disease, such as age-related macular degeneration, has also been demonstrated to be a risk factor for the development of toxic maculopathy. The concurrent use of tamoxifen also increases the risk for retinal toxicity. Tamoxifen itself may deposit in the retina and make the macula more susceptible to the potentially toxic effects of HCQ.

'No Complacency' on COVID-19 After Death of 13-Year-Old-Boy

April-1-2020

“It is essential that we undertake research to determine why a proportion of deaths occur outside of the groups expected to succumb to infection as it may indicate an underlying genetic susceptibility of how the immune system interacts with the virus.

“Determining if this is the case could help us to learn more about the interaction of the virus with the immune system and subsequently what further treatments may be suitable in patients with severe infection.”

Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms

Autopsies of the COVID-19 patients, detailed neurological investigation, and attempts to isolate SARS-CoV-2 from the endothelium of cerebral microcirculation, cerebrospinal fluid, glial cells, and neuronal tissue can clarify the role played by this novel COVID-19 causing coronavirus in the ongoing mortalities as has been in the recent outbreak.

A dominant cerebral involvement alone with the potential of causing cerebral edema in COVID-19 can take a lead in causing death long before systemic homeostatic dysregulation sets in.

Also, a staging system based on the severity and organ involvement is needed in COVID-19 in order to rank the patients for aggressive or conventional treatment modalities.

COVID-19: Neurologists in Italy to Colleagues in US: Look for Poorly-Defined Neurologic Conditions in Patients with the Coronavirus

“There are some recent data suggesting that COVID-19 virus also reaches the central nervous system. Neurological symptoms in patients with COVID-19 infection fall into three categories: neurological expressions of the symptoms of the underlying disease (headache, dizziness, disturbances of the state of consciousness, ataxia, epileptic manifestations, and stroke;) symptoms of neuro-peripheral origin (hypo-ageusia, hyposmia, neuralgia;) symptoms of skeletal muscle damage, often associated with liver and kidney damage.”

Australia's Trialing a TB Vaccine Against COVID-19, And Health Workers Get It First

Australian researchers are fast-tracking large-scale human testing to see if a vaccine used for decades to prevent tuberculosis can protect health workers from COVID-19.

Similar trials are being conducted in several other countries including the Netherlands, Germany and the United Kingdom.

“This trial will allow the vaccine’s effectiveness against COVID-19 symptoms to be properly tested, and may help save the lives of our heroic frontline healthcare workers,”

Trending Clinical Topic: Kawasaki Disease and COVID-19

UK pediatricians have published a working definition of the inflammatory syndrome. No one sign or symptom can be used to identify the children who are affected, and they may or may not test positive for COVID-19. See Image at top of page.

New Focus on Renin-Angiotensin System Role in COVID-19

“As we believe the renin–angiotensin system is being over-activated by the virus, this could also explain why patients with underlying cardiovascular diseases are having worse outcomes and would suggest that taking an ACE inhibitor or ARB would actually be protective.”

On the influenza study, Oudit said: “The influenza virus may well also activate the renin–angiotensin system. That study suggests that ACE inhibitors and ARBs may be protective here as well.”

Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients

Background: Convalescent plasma is the only antibody-based therapy currently
available for COVID-19 patients. It has robust historical precedence and sound
biological plausibility. Although promising, convalescent plasma has not yet been shown
to be safe as a treatment for COVID-19.

Conclusion: Given the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive.
These early indicators suggest that transfusion of convalescent plasma is safe in
hospitalized patients with COVID-19.

Coronavirus Disease 2019 (COVID-19) in Children

Signs and symptoms of COVID-19 in children. Common symptoms of COVID-19 in children are cough and fever. It is important to note, however, that these symptoms may not always be present; thus, a high index of suspicion for SARS-CoV-2 infection is required in children. Other symptoms include the following:
  • Shortness of breath
  • Pharyngeal erythema/sore throat
  • Diarrhea
  • Myalgia
  • Fatigue
  • Rhinorrhea
  • Vomiting
  • Nasal congestion
  • Abdominal pain
  • Conjunctivitis
  • Rash

Researchers Have Discovered a Strong Correlation Between Severe Vitamin D Deficiency and COVID-19 Mortality Rates

By analyzing publicly available patient data from around the globe, Backman and his team discovered a strong correlation between vitamin D levels and cytokine storm — a hyperinflammatory condition caused by an overactive immune system — as well as a correlation between vitamin D deficiency and mortality.

Backman is careful to note that people should not take excessive doses of vitamin D, which might come with negative side effects. He said the subject needs much more research to know how vitamin D could be used most effectively to protect against COVID-19 complications.

Neurological Implications of COVID 19 Infections

We strongly encourage the concerted surveillance for such conditions. Additional to the direct neurological complications of COVID‑19 infection, neurological patients are at risk of harm from both structural limitations (such as number of intensive care beds), and a hesitancy to treat with certain necessary medications given risk of nosocomial COVID‑19 infection. We therefore also outline the specific management of patients with neuroinflammatory diseases in the context of the pandemic.

Therapeutic strategies for critically ill patients with COVID-19

In the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of COVID-19 in the ICU based on the previous experience of treating other viral infections and infuenza. These treatments are referable before the vaccine and specifc drugs are available for COVID-19.

COVID-19 Panel: Helmet CPAP, Pronation Key Tools for Some Patients

Noninvasive ventilation with helmet continuous positive air pressure (CPAP) deserves to be embraced as an effective strategy in preventing self-induced lung injury, often a key factor in progression from the early milder expression of COVID-19 disease to classic severe acute respiratory Distress Syndrome.

Compassionate Use of Remdesivir for Patients with Severe Covid-19

CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy.

'Silent Hypoxemia' and Other Curious Clinical Observations in COVID-19

Podcast and transcript- Gary S. Ferenchick, MD, MS, a professor of medicine at Michigan State University, interviewed his daughter, Hannah R.B. Ferenchick, MD, an emergency and critical care physician working on the frontline in a busy Detroit hospital, about some of the unusual clinical features of patients with suspected or confirmed COVID-19.

A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19

A scientific rationale existed for investigating HCQ in COVID-19. However, other methodological flaws may affect the validity of the findings, even in the current setting, where an efficacious treatment is desperately needed. Thus another explanation is that the baseline viral load, not therapy with HCQ + AZM, affects viral load at day 6.

Despite the study’s substantial limitations, a simplification and probable overinterpretation of these findings was rapidly disseminated by the lay press and amplified on social media, ultimately endorsed by many government and institutional leaders.

A major consequence has been an inadequate supply of HCQ for patients in whom efficacy is established. Hydroxychloroquine is an essential treatment of rheumatoid arthritis and of systemic lupus erythematosus, reducing flares and preventing organ damage in the latter disease. HCQ shortages could place these patients at risk for severe and even life-threatening flares; some may require hospitalization when hospitals are already at capacity. There currently are no data to recommend the use of HCQ as prophylaxis for COVID-19.

Neurologic Features in Severe SARS-CoV-2 Infection

We report the neurologic features in an observational series of 58 of 64 consecutive patients admitted to the hospital because of acute respiratory distress syndrome (ARDS) due to Covid-19.

In this consecutive series of patients, ARDS due to SARS-CoV-2 infection was associated with encephalopathy, prominent agitation and confusion, and corticospinal tract signs. Two of 13 patients who underwent brain MRI had single acute ischemic strokes. Data are lacking to determine which of these features were due to critical illness–related encephalopathy, cytokines, or the effect or withdrawal of medication, and which features were specific to SARS-CoV-2 infection.

IDSA: No Recommendations for COVID-19 Treatment for Now, 'Knowledge Gaps' Cited

There is currently insufficient evidence to recommend any particular medication for treatment of COVID-19, an expert panel of the Infectious Diseases Society of America (IDSA) has concluded.

Many pharmacologic therapies are being used or considered for the treatment of patients with COVID-19. Given the rapidly emerging literature on treatment, the IDSA convened the panel to develop interim evidence-based guidelines to support clinicians in making decisions about treatment and management of patients with COVID-19.

This is a “living document” that represents the best understanding to date on the treatment of patients with COVID-19, and it will be updated frequently as new information becomes available

Warning of Higher COVID-19 Problems From Glucocorticoid Use

Adults prescribed glucocorticoid therapy for common conditions, such as asthma and arthritis, as well as individuals with adrenal insufficiency, are at high risk for developing serious complications from COVID-19 due to an inability to mount a normal stress response.

If any doctor or healthcare professional is coming across people who received steroid therapy for the previous 3 months, they need to be regarded as an ‘at risk’ individual in terms of the progression of their illness, with a fairly low threshold for giving them supplemental steroid therapy, which might be life-saving. That’s the plea here.

Cardiology Groups Push Back on Hydroxychloroquine, Azithromycin for COVID-19

The nation’s leading cardiology associations urged caution with hydroxychloroquine and azithromycin for COVID-19 in patients with cardiovascular disease.

“Hydroxychloroquine and azithromycin have been touted for potential prophylaxis or treatment for COVID-19; both drugs are listed as definite causes of torsade de pointes” and increase in the risk of other arrhythmias and sudden death, the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society said in a joint statement April 8 in Circulation.

The statement came amid ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite lack of strong data.

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

April 10-2020  Key Points

Question  What are neurologic manifestations of patients with coronavirus disease 2019?

Findings  In a case series of 214 patients with coronavirus disease 2019, neurologic symptoms were seen in 36.4% of patients and were more common in patients with severe infection (45.5%) according to their respiratory status, which included acute cerebrovascular events, impaired consciousness, and muscle injury.

Meaning  Neurologic symptoms manifest in a notable proportion of patients with coronavirus disease 2019.

Nephrologists on Lessons Learned With Kidney Disease in COVID-19

Although lung damage is the main feature of severe COVID-19, it is becoming crystal clear that the kidney is one of the other major organs involved.

“The mortality we’re seeing with these [dialysis and transplant] patients is because COVID-19 pneumonia/disease can be very aggressive with a severe distress syndrome,” Soler told Medscape Medical News. Discusses Dialysis/Transplant COVID-19 Experience in Spain

COVID-19: Facing Hard Truths on the Front Line

The Royal Society of Medicine (RSM) has launched a series of webinars for members to help support them with the difficult life and death decisions they are going to have to make in the coming months during the height of the COVID-19 pandemic. All health care professionals are having to make decisions during COVID-19 that they never thought they would, and the decision in life and death situations nearly always rests ultimately with the doctor in charge of the case.

The article includes: Ethical guidance published for frontline staff dealing with the pandemic

COVID-19 Linked to Multiple Cardiovascular Presentations

It’s becoming clear that COVID-19 infection can involve the cardiovascular system in many different ways, and this has “evolving” potential implications for treatment, say a team of cardiologists on the frontlines of the COVID-19 battle in New York City.

COVID-19 Daily: More Will Die, First Antibody Test Authorized

A newly available antibody test may help evaluate the SARS-CoV-2 virus in 20 minutes or less. The US Food and Drug Administration has granted Cellex an emergency use authorization to market the first rapid antibody test for
COVID-19.

COVID-19: More Hydroxychloroquine Data From France, More Questions

There was a  Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients. This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.

Personally, I really believe in hydroxychloroquine. It would nevertheless be a shame to think we had found the fountain of youth and realize, in 4 weeks, that we have the same number of deaths. That is the problem. I hope that we will soon have solid data so we do not waste time focusing solely on hydroxychloroquine.

Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies

April 7-2020

No drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19. Numerous antiviral agents, immunotherapies, and vaccines are being investigated and developed as potential therapies. Searching for effective therapies for COVID-19 infection is a complex process.

Coronavirus on Fabric: What You Should Know

April 2-2020

If you suspect you got too close for too long, or someone coughed on you, there’s no harm in changing your clothing and washing it right away, especially if there are hard surfaces like buttons and zippers where the virus might linger. Wash your hands again after you put everything into the machine. Dry everything on high, since the virus dies at temperatures above 133°F. File these steps under “abundance of caution”: They’re not necessary, but if it gives you peace of mind, it may be worth it.

Michigan woman with coronavirus develops rare complication affecting brain

April 1-2020 A 58-year-old woman hospitalized in the Henry Ford Health System who has the new coronavirus developed a rare complication: encephalitis.

It is believed to be the first published case linking COVID-19 and acute necrotizing encephalitis. The rare and serious brain disease can develop in people who have a viral infection, and causes lesions to form in the brain, tissue death and symptoms such as seizures, drowsiness, confusion and coma.

Should We All Be Wearing Masks In Public? Health Experts Revisit The Question

March 31-2020   “Cotton masks constructed in a proper way should provide a reasonable degree of protection from people being able to transmit the virus. ” CDC to issue guidelines

At least 8 strains of the coronavirus are spreading across the globe

Scientists have identified at least eight strains of coronavirus as the bug wreaks havoc spreading across the globe.

More than 2,000 genetic sequences of the virus have been submitted from labs to the open database NextStrain, which shows it mutating on maps in real-time, according to the site.

Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies

No drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19. Numerous antiviral agents, immunotherapies, and vaccines are being investigated and developed as potential therapies. Searching for effective therapies for COVID-19 infection is a complex process. Gordon et al identified 332 high-confidence SARS-CoV-2 human protein-protein interactions. Among these, they identified 66 human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials, and/or preclinical compounds. As of March 22, 2020, these researchers are in the process of evaluating the potential efficacy of these drugs in live SARS-CoV-2 infection assays.

How long coronavirus survives on surfaces - and what it means for handling money, food and more

The article includes: How can we reduce risk from surfaces and objects? While it’s best to stay home, details tips to enact if you must leave the house.

What Neurologists Can Expect From COVID-19

In rare cases, complications including ADEM (acute disseminated encephalomyelitis)-like demyelination, encephalitis, and brainstem encephalitis were reported. They also saw some peripheral and non–central nervous system stuff, including things that looked like Guillain-Barre syndrome or what they would sometimes call critical illness polyneuropathy.

The data are still limited on whether coronaviruses have a significant neurologic component. There are reports of other coronaviruses entering the brain of patients and experimental animals. Does that mean anything? Right now, we simply don’t know.

You could be spreading the coronavirus without realising you’ve got it

What all this makes clear is that advising only people with a cough or fever and their families to self-isolate won’t prevent the coronavirus from spreading, thanks to its fiendish ability to cause very mild symptoms in people, and to peak in infectiousness before people even realise they are sick.

Read more: https://www.newscientist.com/article/2238473-you-could-be-spreading-the-coronavirus-without-realising-youve-got-it/#ixzz6IHqPt4lV

Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma

These preliminary findings raise the possibility that convalescent plasma transfusion may be helpful in the treatment of critically ill patients with COVID-19 and ARDS, but this approach requires evaluation in randomized clinical trials.

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