It is becoming clear that the majority of neurological complications involve neuroinflammation and sometimes hypoxic-ischemic damage which are is not driven by direct SARS-CoV-2 infection, but indirect effects of anti-viral and inflammatory responses. The correlation of heightened immune response with severe disease indicates that host response factors could be responsible for pathology (4). Although the heterogenous pathologies likely have different mechanisms and therapeutic targets, it is promising that at least the pulmonary manifestations of COVID-19 are amenable to immunosuppressant treatment, such as dexamethasone and anti-IL-6R. The more delayed range of neurological complications, especially demyelinating disease, implicates that the adaptive immune response is likely involved in pathology in certain individuals. 

 Human immunodeficiency virus, antinuclear antibody screening, anti-DNA, rapid plasma reagin, Lyme serology, anti-SSA, and anti-SSB antibodies were unremarkable. Serum aquaporin-4 immunoglobulin G was negative, and myelin oligodendrocyte glycoprotein (MOG) antibodies were positive. The patient was treated with intravenous methylprednisolone and oral gabapentin and was discharged after five days when his urinary retention improved. Most previously reported cases of COVID-19-related TM were negative for autoimmune workup. Although the exact pathophysiology of COVID-19-related TM remains unclear, one hypothesis suggests that it is a consequence of the direct viral invasion. However, our patient had MOG antibodies, suggesting the possible involvement of a different mechanism. In MOG-associated TM, it has been suggested that MOG antibodies gain access to the CNS through disruption of the blood-brain barrier. This unique presentation demonstrates that further studies are needed to understand the effects of SARS-CoV-2 infection on the immune and nervous systems. It also highlights that young and otherwise healthy patients are at risk of severe COVID-19-related complications, including CNS disorders.

Conclusion: In this systematic review, characteristics of COVID-19-associated encephalitis including clinical symptoms, diagnosis, treatment, and outcome were described. COVID-19-associated encephalitis can accompany with other neurological symptoms and involve different brain. Although majority of encephalitis condition are reversible, but it can lead to life-threatening status. Therefore, further investigation of COVID-19-associated encephalitis is required.

During COVID-19 pandemic, a lot of newly discovered symptoms and presentations are emerging. Neurological symptoms of corona virus disease 19 (COVID19) have been reported including central nervous symptoms (CNS), peripheral nervous symptoms (PNS), and skeletal muscular symptoms; however, data are scarce about the exact occurrence of neurological affection during COVID-19 infection.

We present a case of a 67-year-old male patient with proven COVID-19 infection who developed acute confusion state, behavioral changes, agitation, and one attack of loss of consciousness 8 days following the infection. 

Conclusion: This clinical case emphasizes the possible relationship between COVID-19 infection and autoimmune encephalitis.

We set out to provide practical guidance to
answer the following clinical questions:  What is the pathophysiology of COVID-19 encephalopathy?  Which clinical features suggest COVID-19 encephalopathy?  Which clinical features suggest a primary Central Nervous System (CNS) pathology?  What investigations should be performed to establish these CNS diagnoses?  How should patients suffering from COVID-19 encephalopathy be managed?  What is the prognosis for patients with COVID-19 encephalopathy?  What is the role of rehabilitation for these patients?

During the past year, the novel coronavirus disease 2019 (COVID 19) has infected more than 100 million people worldwide. In December 2020, the first two vaccines were approved by the FDA through emergency use authorization in the United States. These vaccines are based on the mRNA vaccine platform and were developed by Pfizer/BioNTech and Moderna. Published safety and efficacy trials reported high efficacy rates of 94-95% after two interval doses, in conjunction with limited side effects and a low rate of adverse reactions.

Herein, we report a 48 years old man presenting with rapidly progressive cognitive decline and hyponatremia diagnosed with anti LGI1 AE, occurring shortly after the second dose of mRNA COVID -19 vaccine.

OBJECTIVE: Here, we systematically review the literature on autoimmune encephalitis that developed in the background of SARS-CoV-2 infections and also the possible pathophysiological mechanisms of auto-immune mediated damage to the nervous system.

RESULTS: Autoimmune encephalitis can occur via three possible proposed pathophysiological mechanism and can manifest during or after the acute infection period. It is more common in adult but can also occur in the paediatric patients. There were various spectra of autoantibody panels reported including antineuronal antibody, anti-gangliosides antibody and onconeural antibody. Majority of the patients responded well to the immunomodulating therapy and achieved good recovery.

CONCLUSION: In conclusion, SARSCoV-2 infection can induce various spectrum of autoimmune encephalitis. It is a major concern since there is very limited long-term study on the topic. Hence, this review aims to elucidate on the potential long-term complication of SARS-CoV-2 infection and hopefully to improve the management and prognosis of COVID-19.

Easy read. Often referred to as “long covid,” the adverse health effects vary from person to person. But the research, based on data from 250,351 adults and children, found that more than half experience a decline in general well-being, resulting in weight loss, fatigue, fever or pain.

Recently, COVID-19 has been described as a cause of autoimmune encephalitis including Anti-NMDAR encephalitis. In autoimmune encephalitis, SARS-CoV-2 virus causing COVID-19 disease leads to brain damage due to the cytokine storm mediated by interleukin mostly IL-2 and IL-6 in the CSF. This mechanism may be the cause of hypometabolism in PET related to cortical damage. Early hypermetabolism has been described in the mesial temporal areas and could be a marker of active inflammatory process of limbic encephalitis. On the contrary, the hypometabolism pattern including temporal, parietal and occipital areas was observed in the follow-up. In addition, MRI FLAIR signal abnormity has been described in autoimmune encephalitis caused by COVID-19 in the temporal lobe and in the basal ganglia. The regional infarct involving the right cerebellar cortex may be associated to cerebral thrombotic microangiopathy as a complication in our case.

Results: Eighteen of the laboratory cohort (3%) were SARS-CoV-2 antibody positive. Diagnoses were: AE, 2; post-acute sequelae of SARS CoV-2 infection [PASC], 3; toxic-metabolic encephalopathy during COVID-19 pneumonia, 2; diverse non-COVID-19 relatable neurological diagnoses, 9; unavailable, 2. Five of the encephalopathy cohort had AE (16%, including the 2 laboratory cohort cases which overlapped) representing 0.05% of 10,384 patients diagnosed and cared for with any COVID-19 illness at Mayo Clinic Rochester in 2020. The 5 patients met definite (n=1), probable (n=1), or possible (n=3) AE diagnostic criteria; median symptom onset age was 61 years (range, 46-63), 3 were women. All 5 were neural IgG negative and 4 tested were SARS-CoV-2 PCR/IgG index negative in CSF. Phenotypes (and accompanying MRI and EEG findings) were diverse (delirium [n=5], seizures [n=2], rhombencephalitis [n=1], aphasia [n=1], and ataxia [n=1]). No ADEM cases were encountered. The 3 patients with possible AE had spontaneously resolving syndromes. One with definite limbic encephalitis was immune therapy responsive but had residual mood and memory problems. One patient with probable autoimmune rhombencephalitis died despite immune therapy. The remaining 26 encephalopathy cohort patients had toxic-metabolic diagnoses.

This case illustrates for the first time the clinical and radiological evolution of SARS-CoV-2 meningo-encephalitis. A case of a SARS-CoV-2 meningo-encephalitis is reported. A 65-year-old man with COVID-19 presenting with meningo-encephalitis without respiratory involvement is described. He had fever, diarrhea and vomiting, followed by diplopia, urinary retention and sleepiness. CONCLUSION This case illustrates the clinical and radiological evolution of SARSCoV-2 meningo-encephalitis. It also demonstrates the challenges in diagnosing COVID-19 in patients with predominantly neurological presentations. Read on to see what the examination disclosed.

KEY POINTS

• Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome.
• Although effective vaccines have been developed for COVID-19 and are being distributed, millions of people will have long-term complications from the infection, some of which will be neurologic.
• Myalgia and fatigue are seen in about 50% of patients with COVID-19 and may persist even after recovery from the other symptoms. Headache occurs in 8% of patients.
• Anosmia and ageusia may be heralding manifestations of COVID-19.
• Mortality in COVID-19 is higher with advanced age and underlying comorbidities, including diabetes, cardiac and respiratory disorders, and immunosuppressed states.
• The neurologic manifestations of COVID-19 can be broadly divided into two categories: those that occur during the acute phase of the infection (parainfectious complications) and the postviral manifestations that occur following the acute phase (post–acute phase complications).
• Anosmia and ageusia are the most common early symptoms of COVID-19 infection. Nearly 40% to 60% of patients develop loss of smell, and, upon testing, nearly 90% have alteration of smell.
• Encephalopathy is the most common neurologic manifestation in patients who are hospitalized with COVID-19, with nearly one-third of patients who are hospitalized developing encephalopathic symptoms ranging from alteration in consciousness to delirium and seizures.
• Direct viral invasion of the brain in COVID-19 is rare.
• Acute necrotizing hemorrhagic encephalopathy is a feared complication of several viruses, most notably influenza. It is thought to result from cytokine release syndrome rather than direct viral invasion of brain parenchyma, which is especially salient given the propensity of SARS-CoV-2 for causing similar cytokine storms in the lungs.
• Acute disseminated encephalomyelitis is a rare demyelinating disease; it is often postviral and is more common in children than adults. However, in patients with COVID-19, it has been described mainly in adults.
• Patients with COVID-19 develop a hypercoagulable syndrome causing both arterial and venous occlusions in the brain vasculature. Ischemic stroke, hemorrhagic stroke, and cerebral venous sinus thrombosis have all been reported.
• Cerebrovascular complications of COVID-19 are likely due to altered coagulation pathways as demonstrated by observations of elevated d-dimer, increased prothrombin time and activated partial thromboplastin time, and disseminated intravascular coagulation.
• Variants of Guillain-Barré syndrome seem to be more common when associated with preceding COVID-19 infection.
• Myositis can occur at any time during the course of COVID-19; it can be quite extensive and associated with myalgia and muscle weakness that can persist after recovery of the other symptoms.
• Long-haul COVID is a distinct postviral syndrome that is independent of the severity of the acute phase of the illness. This syndrome can emerge even in patients who have relatively mild symptoms during the acute phase.
• A distinction needs to be made between patients with long-haul COVID and patients who were hospitalized, who often have a large number of lingering symptoms from respiratory disease, other organ damage, and prolonged hospitalization.

Neurological and neuropsychiatric adverse events have been reported in clinical trials of various SARS-CoV-2 vaccines and, more often, in open-label monitoring. In many cases, no definitive evidence has yet supported causality. Despite this, there are recognised rare adverse events that have been causally linked to SARS-CoV-2 vaccines, for example, VITT. The necessary ongoing surveillance work is in progress; however, the current advice that the benefit of the vaccination outweighs the risk appears to be accurate from a neurological standpoint. Heightened reporting of adverse events, for example, via the Yellow Card system, may be in part due to increased pharmacovigilance.

Highly Recommended

We provide here the ten recommendations with explanations (Table 1): the first five are directed toward the general public, whereas the remaining five are meant for physicians managing COVID-19. 

The first two recommendations are most relevant in regions of high community spread and low vaccine coverage, whereas the remaining eight are relevant regardless of the setting.

In summary, the Choosing Wisely for COVID-19 initiative has identified ten key recommendations for the control of COVID-19 through inputs and systematic development process from diverse stakeholders. Adopting and implementing this list will promote more evidence-based implementation of policy and practices in managing the COVID-19 pandemic in various parts of the world. Most importantly, this list emphasizes the critical role that evidence-based medicine should serve, even during a raging pandemic.

We report a rare case of NORSE after the first dose of the ChAdOx1
nCoV-19 vaccine. We attribute the occurrence of NORSE to the vaccine
due to the temporal relationship and the lack of risk factors for epilepsy
in the patient. This report adds to the literature a possible rare side effect
of a COVID-19 vaccine and contributes to the extremely limited literature on potential neurological side effects of viral vector vaccines.
Healthcare providers should be aware of the possibility of postvaccination epilepsy. The patient had recurrent seizures that were refractory to conventional antiepileptic drug therapy with a dramatic
response to immunotherapy with pulse steroids and plasmapheresis.
This likely reflects an underlying autoimmune mechanism in the genesis
of post-vaccination generalized seizures without fever. Further research
is needed to probe and study the exact mechanism at a more molecular
level.

Neurological and psychiatric sequelae of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis.

Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% with 12·84% receiving their first such diagnosis.

Interpretation

This study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19.

This is a case report of a 23-year old man with a history of childhood non-febrile seizures, presented to the hospital because of cognitive slowing and personality changes. Five weeks prior, he gradually developed a moderate but nearly constant, left-sided headache associated with dysesthesias. During this timeframe, he had known exposure to SARS-CoV-2 infected coworkers.

This case expands the spectrum of parainfectious neurological consequences associated with SARS-CoV-2 infection and highlights possible links between SARS-CoV-2 and autoimmune neurologic disease.

A variety of neurologic manifestations of COVID-19 infections have been reported. Here, we present a case of steroid-responsive MOG-antibody associated encephalitis, characterized by cognitive decline, headaches, fever, unilateral FLAIR-hyperintensities, and leptomeningeal enhancement, that occurred in the setting of recent COVID-19 infection.

The research team found that the virus was located in the brains of mice at a level that was 1,000 times higher than in any other part of the body. Viral loads in the lungs began to drop after three days but remained high in the brain on the fifth and sixth days after infection, which is when the disease became more severe.

“Once it infects the brain, it can affect anything because the brain is controlling your lungs, the heart, everything,” he said. “The brain is a very sensitive organ. It’s the central processor for everything.”

Evidence-based practice in the approach to COVID-19 is mercurial. Current literature focuses on the inpatient evaluation, treatment, and disposition of these patients. Interpretation and adaptation of current recommendations to patients in the ED is a crucial target for future literature. After our review of available literature, we have proposed an ED-specific flowsheet to assist clinicians during this time of medical ambiguity (Figure 3).

Both patients showed significant recovery following immunotherapy with steroids and IVIG. At the time of publication, the authors are unaware of other cases of anti-NMDAR encephalitis with recent SARS-CoV-2 infection in pediatric populations. As the understanding of both the neurological and non-neurological manifestations of SARS-CoV-2 in children are evolving, we report a child with SARS-CoV-2-associated anti-NMDAR encephalitis.

IL-6 plays an important part in antibody production, and antibodies are the body’s most direct and effective immune weapon against viruses. Therefore, whether IL-6 blockade by tocilizumab will affect the antiviral immune response of COVID-19 patients (especially the formation of antiviral antibodies) has become an important concern for targeted IL-6 immunotherapy in COVID-19 patients. The increase in the level of antiviral antibodies may have been related to blockade of the excessive IL-6 signal, alleviation of the IS.

• So-called ‘long COVID’ might actually be four different syndromes, doctors say.
• While the illness starts in the respiratory system, symptoms can fluctuate around the brain, cardiovascular system and heart, the kidneys, the gut, the liver and the skin.
• It’s vital both doctors and patients continue to report these symptoms, so medical researchers can better understand COVID-19.

Ongoing illness after infection with COVID-19, sometimes called “long COVID”, may not be one syndrome but possibly up to four causing a rollercoaster of symptoms affecting all parts of the body and mind.

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.

• 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%.

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.

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.”

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.

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.

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.

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.

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.

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.

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.”

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’

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

“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.

“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,”

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.

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.”

“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”.

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.

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.

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.”

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.

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

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.

“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.

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.”

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

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.

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.

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.

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

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 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.”

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.

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

“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.

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.

• 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.

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.

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.

Highlights

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

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.

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.

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

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.

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.

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

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.

“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.”

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.

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,”

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.”

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 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.”

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.

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

“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.

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.

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.

• 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.

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.

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.

Highlights

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

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.

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.

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

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.

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.

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

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.

“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.”

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.

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,”