Meningoencephalitis associated with COVID-19: a systematic review

Authors: Ritwick Mondal 1Upasana Ganguly 1Shramana Deb 2Gourav Shome 3Subhasish Pramanik 1Deebya Bandyopadhyay 1Durjoy Lahiri 4

Abstract

With the growing number of COVID-19 cases in recent times. significant set of patients with extra pulmonary symptoms has been reported worldwide. Here we venture out to summarize the clinical profile, investigations, and radiological findings among patients with SARS-CoV-2-associated meningoencephalitis in the form of a systemic review. This review was carried out based on the existing PRISMA (Preferred Report for Systematic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase, and Cochrane library and Preprint servers up till 30 June 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes “SARS-COV-2,” “COVID-19,” and “meningoencephalitis.” All peer reviewed, case-control, case report, pre print articles satisfying our inclusion criteria were involved in the study. Quantitative data was expressed in mean ± SD, while the qualitative date in percentages. Paired t test was used for analyzing the data based on differences between mean and respective values with a p < 0.05 considered to be statistically significant. A total of 61 cases were included from 25 studies after screening from databases and preprint servers, out of which 54 of them had completed investigation profile and were included in the final analysis. Clinical, laboratory findings, neuroimaging abnormalities, and EEG findings were analyzed in detail. This present review summarizes the available evidences related to the occurrence of meningoencephalitis in COVID-19.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33367960/

Some COVID-19 patients have brain complications, study suggests

Authors: Mary Van Beusekom | News Writer | CIDRAP News  | Jun 26, 2020

Some COVID-19 patients, including those younger than 60 years old, appear to develop neurologic and neuropsychiatric complications such as stroke, brain inflammation, psychosis, and dementia-like symptoms, according to a study published yesterday in The Lancet Psychiatry.

The early-stage study of 153 hospitalized patients with confirmed, probable, or possible COVID-19 in the United Kingdom (UK) from Apr 2 to 26 identified 125 patients with complete data, of whom 77 (62%) had a stroke.

Of 125 patients, 114 (92%) had confirmed coronavirus infection, 5 (4%) had probable infection, and 5 (4%) were classified as possibly infected.

Stroke, encephalopathy, psychiatric diagnoses

Fifty-seven of 77 stroke patients (74%) had an ischemic stroke caused by a blood clot in the brain, 9 (12%) had a stroke caused by a brain hemorrhage, and 1 (1%) had a stroke caused by inflammation in the brain’s blood vessels. Sixty-one of the 77 stroke patients for whom age was available (82%) were older than 60 years.

Thirty-nine of 125 patients (31%) had behavioral changes indicative of an altered mental state, of whom 9 (23%) had unspecified brain dysfunction known as encephalopathy, and 7 (18%) had brain inflammation, or encephalitis.

The remaining 23 patients with altered mental states had psychiatric diagnoses, including 10 with new-onset psychosis, 7 with depression or anxiety, and 6 with a dementia-like syndrome. Only 2 patients (9%) had exacerbations of a chronic mental illness, although the authors noted that they cannot exclude the possibility that cases classified as new were simply undiagnosed before the pandemic.

Of the 37 of 39 COVID-19 patients with an altered mental state for whom age was available, 18 (49%) were younger than 60 years, which could be because they were more likely to be referred to a psychiatrist or other specialist, while physicians may be likely to attribute confusion or behavioral changes in older patients to delirium without further investigation, the authors said.

Altered mental states in younger patients

While altered mental states are not uncommon in hospitalized patients with infections, especially those requiring intensive care, they occur most often in older patients.

“In this study, we observed a disproportionate number of neuropsychiatric presentations in younger patients and a predominance of cerebrovascular complications in older patients, which might reflect the state of health of the cerebral vasculature and associated risk factors, exacerbated by critical illness in older patients,” the authors said.

For More Information: https://www.cidrap.umn.edu/news-perspective/2020/06/some-covid-19-patients-have-brain-complications-study-suggests

Coronavirus and the Nervous System

What is SARS-CoV-2 and COVID-19?

Coronaviruses are common causes of usually mild to moderate upper respiratory tract illnesses like the common cold, with symptoms that may include runny nose, fever, sore throat, cough, or a general feeling of being ill. However, a new coronavirus called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) emerged and spread to cause the COVID-19 pandemic.

COVID-19, which means Coronavirus disease 2019, is an infectious disease that can affect people of all ages in many ways. It is most dangerous when the virus spreads from the upper respiratory tract into the lungs to cause viral pneumonia and lung damage leading to Acute Respiratory Distress Syndrome (ARDS). When severe, this impairs the body’s ability to maintain critical levels of oxygen in the blood stream—which can cause multiple body systems to fail and can be fatal.

What do we know about the effects of SARS-CoV-2 and COVID-19 on the nervous system?

Much of the research to date has focused on the acute infection and saving lives. These strategies have included preventing infection with vaccines, treating COVID-19 symptoms with medicines or antibodies, and reducing complications in infected individuals.

Research shows the many neurological symptoms of COVID-19 are likely a result of the body’s widespread immune response to infection rather than the virus directly infecting the brain or nervous system. In some people, the SARS-CoV-2 infection causes an overreactive response of the immune system which can also damage body systems. Changes in the immune system have been seen in studies of the cerebrospinal fluid, which bathes the brain, in people who have been infected by SARS-CoV-2. This includes the presence of antibodies—proteins made by the immune system to fight the virus—that may also react with the nervous system. Although still under intense investigation, there is no evidence of widespread viral infection in the brain. Scientists are still learning how the virus affects the brain and other organs in the long-term. Research is just beginning to focus on the role of autoimmune reactions and other changes that cause the set of symptoms that some people experience after their initial recovery. It is unknown if injury to the nervous system or other body organs cause lingering effects that will resolve over time, or whether COVID-19 infection sets up a more persistent or even chronic disorder.

What are the immediate (acute) effects of SARS-CoV-2 and COVID-19 on the brain?

Most people infected with SARS-CoV-2 virus will have no or mild to moderate symptoms associated with the brain or nervous system. However, most individuals hospitalized due to the virus do have symptoms related to the brain or nervous system, most commonly including muscle aches, headaches, dizziness, and altered taste and smell. Some people with COVID-19 either initially have, or develop in the hospital, a dramatic state of confusion called delirium. Although rare, COVID-19 can cause seizures or major strokes. Muscular weakness, nerve injury, and pain syndromes are common in people who require intensive care during infections. There are also very rare reports of conditions that develop after SARS-CoV-2 infection, as they sometimes do with other types of infections. These disorders of inflammation in the nervous system include Guillain-Barré syndrome (which affects nerves), transverse myelitis (which affects the spinal cord), and acute necrotizing leukoencephalopathy (which affects the brain).

Bleeding in the brain, weakened blood vessels, and blood clots in acute infection

The SARS-CoV-2 virus attaches to a specific molecule (called a receptor) on the surface of cells in the body. This molecule is concentrated in the lung cells but is also present on certain cells that line blood vessels in the body. The infection causes some arteries and veins—including those in the brain—to  become thin, weaken, and leak. Breaks in small blood vessels have caused bleeding in the brain (so-called microbleeds) in some people with COVID-19 infection. Studies in people who have died due to COVID-19 infection show leaky blood vessels in different areas of the brain that allow water and a host of other molecules as well as blood cells that are normally excluded from the brain to move from the blood stream into the brain. This leak, as well as the resulting inflammation around blood vessels, can cause multiple small areas of damage. COVID-19 also causes blood cells to clump and form clots in arteries and veins throughout the body. These blockages reduce or block the flow of blood, oxygen, and nutrients that cells need to function and can lead to a stroke or heart attack.

stroke is a sudden interruption of continuous blood flow to the brain. A stroke occurs either when a blood vessel in the brain becomes blocked or narrowed or when a blood vessel bursts and spills blood into the brain. Strokes can damage brain cells and cause permanent disability. The blood clots and vascular (relating to the veins, capillaries, and arteries in the body) damage from COVID-19 can cause strokes even in young healthy adults who do not have the common risk factors for stroke.

COVID-19 can cause blood clots in other parts of the body, too. A blood clot in or near the heart can cause a heart attack. A heart attack orInflammation in the heart, called myocarditis, can causeheart failure, and reduce the flow of blood to other parts of the body. A blood clot in the lungs can impair breathing and cause pain. Blood clots also can damage the kidneys and other organs.

Low levels of oxygen in the body (called hypoxia) can permanently damage the brain and other vital organs in the body. Some hospitalized individuals require artificial ventilation on respirators. To avoid chest movements that oppose use of the ventilator it may be necessary to temporarily “paralyze” the person and use anesthetic drugs to put the individual to sleep. Some individuals with severe hypoxia require artificial means of bringing oxygen into their blood stream, a technique called extra corporeal membrane oxygenation (ECMO). Hypoxia combined with these intensive care unit measure generally cause cognitive disorders that show slow recovery.

Diagnostic imaging of some people who have had COVID-19 show changes in the brain’s white matter that contains the long nerve fibers, or “wires,” over which information flows from one brain region to another. These changes may be due to a lack of oxygen in the brain, the inflammatory immune system response to the virus, injury to blood vessels, or leaky blood vessels. This “diffuse white matter disease” might contribute to cognitive difficulties in people with COVID-19. Diffuse white matter disease is not uncommon in individuals requiring intensive hospital care but it not clear if it also occurs in those with mild to moderate severity of COVID-19 illness.

For More Information: https://www.ninds.nih.gov/Current-Research/Coronavirus-and-NINDS/nervous-system

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

Authors: Amy D. Proal1 and Michael B. VanElzakker1,2*

The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC). It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive. This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development. Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis.

Introduction

The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic of coronavirus disease 2019 (COVID-19) (Hiscott et al., 2020). Classic cases of acute COVID-19 are characterized by respiratory symptoms, fever, and gastrointestinal problems (Larsen et al., 2020). However, patients can present with a wide range of other symptoms, including neurological issues suggesting central nervous system (CNS) involvement (Harapan and Yoo, 2021). Acute COVID-19 cases range in length and severity. Many patients are asymptomatic, while others require hospitalization and ventilation (Cunningham et al., 2021). Overall, an average case of COVID-19 lasts between 1 and 4 weeks. However, across the globe, a subset of patients who sustain an acute SARS CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months (Carfì et al., 2020Davis et al., 2020Huang C. et al., 2021) (Figure 1). One study of COVID-19 patients who were followed for up to 9 months after illness found that approximately 30% reported persistent symptoms (Logue et al., 2021). These patients are being given the diagnosis Long COVID, post-acute COVID-19 syndrome (PACS), or post-acute sequelae of COVID-19.

For More Information: https://www.frontiersin.org/articles/10.3389/fmicb.2021.698169/full

The Impact of the Covid 19 Pandemic on Cerebrovascular Disease: CORD-Papers-2021-06-28

Abstract:           

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a systemic disease that affects nearly all organ systems through infection and subsequent dysregulation of the vascular endothelium. One of the most striking phenomena has been a coronavirus disease 2019 (COVID-19)associated coagulopathy. Given these findings, questions naturally emerged about the prothrombotic impact of COVID-19 on cerebrovascular disease and whether ischemic stroke is a clinical feature specific to COVID-19 pathophysiology. Early reports from China and several sites in the northeastern United States seemed to confirm these suspicions. Since these initial reports, many cohort studies worldwide observed decreased rates of stroke since the start of the pandemic, raising concerns for a broader impact of the pandemic on stroke treatment. In this review, we provide a comprehensive assessment of how the pandemic has affected stroke presentation, epidemiology, treatment, and outcomes to better understand the impact of COVID-19 on cerebrovascular disease. Much evidence suggests that this decline in stroke admissions stems from the global response to the virus, which has made it more difficult for patients to get to the hospital once symptoms start. However, there does not appear to be a demonstrable impact on quality metrics once patients arrive at the hospital. Despite initial concerns, there is insufficient evidence to ascribe a causal relationship specific to the pathogenicity of SARS-CoV-2 on the cerebral vasculature. Nevertheless, when patients infected with SARS-CoV-2 present with stroke, their presentation is likely to be more severe, and they have a markedly higher rate of in-hospital mortality than patients with either acute ischemic stroke or COVID-19 alone.

For More Information: https://covid19-data.nist.gov/pid/rest/local/paper/the_impact_of_the_covid_19_pandemic_on_cerebrovascular_disease

The OC43 human coronavirus envelope protein is critical for infectious virus production and propagation in neuronal cells and is a determinant of neurovirulence and CNS pathology

Authors:Jenny K.Stodola1GuillaumeDubois1AlainLe CoupanecMarcDesforgesPierre J.Talbot

Highlights

Coronavirus structural envelope (E) protein specific motifs involved in protein-protein interaction or in homo-oligomeric ion channel formation are needed for optimal production of recombinant infectious virus.•

Fully functional E protein of HCoV-OC43 is crucial for viral propagation in the CNS and neurovirulence.•

Fully functional E protein of HCoV-OC43 is crucial for efficient viral propagation in the central nervous system and thereby for neurovirulence.

Abstract

The OC43 strain of human coronavirus (HCoV-OC43) is an ubiquitous respiratory tract pathogen possessing neurotropic capacities. Coronavirus structural envelope (E) protein possesses specific motifs involved in protein-protein interaction or in homo-oligomeric ion channel formation, which are known to play various roles including in virion morphology/assembly and in cell response to infection and/or virulence. Making use of recombinant viruses either devoid of the E protein or harboring mutations either in putative transmembrane domain or PDZ-binding motif, we demonstrated that a fully functional HCoV-OC43 E protein is first needed for optimal production of recombinant infectious viruses. Furthermore, HCoV-OC43 infection of human epithelial and neuronal cell lines, of mixed murine primary cultures from the central nervous system and of mouse central nervous system showed that the E protein is critical for efficient and optimal virus replication and propagation, and thereby for neurovirulence.

For More Information: https://www.sciencedirect.com/science/article/pii/S0042682217304361

Late Complications of COVID-19; a Systematic Review of Current Evidence

Authors: SeyedAhmad SeyedAlinaghi,1Amir Masoud Afsahi,2Mehrzad MohsseniPour,1Farzane Behnezhad,3Mohammad Amin Salehi,1Alireza Barzegary,4Pegah Mirzapour,1Esmaeil Mehraeen,5,* and Omid Dadras6

Introduction

Introduction:

COVID-19 is a new rapidly spreading epidemic. The symptoms of this disease could be diverse as the virus can affect any organ in the body of an infected person. This study aimed to investigate the available evidence for long-term complications of COVID-19.

Methods:

This study was a systematic review of current evidence conducted in November 2020 to investigate probable late and long-term complications of COVID-19. We performed a systematic search, using the keywords, in online databases including PubMed, Scopus, Science Direct, Up to Date, and Web of Science, to find papers published from December 2019 to October 2020. Peer-reviewed original papers published in English, which met the eligibility criteria were included in the final report. Addressing non-human studies, unavailability of the full-text document, and duplicated results in databases, were characteristics that led to exclusion of the papers from review.

Results:

The full-texts of 65 articles have been reviewed. We identified 10 potential late complications of COVID-19. A review of studies showed that lung injuries (n=31), venous/arterial thrombosis (n=28), heart injuries (n=26), cardiac/brain stroke (n=23), and neurological injuries (n=20) are the most frequent late complications of COVID-19.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927752/

Neurologic Features in Severe SARS-CoV-2 Infection

Authors: Julie Helms, M.D., Ph.D., Stéphane Kremer, M.D., Ph.D., Hamid Merdji, M.D., Raphaël Clere-Jehl, M.D., Malika Schenck, M.D., Christine Kummerlen, M.D., Olivier Collange, M.D., Ph.D., Clotilde Boulay, M.D., Samira Fafi-Kremer, Pharm.D., Ph.D., Mickaël Ohana, M.D., Ph.D., Mathieu Anheim, M.D., Ph.D. Strasbourg University Hospital, Strasbourg, France, Ferhat Meziani, M.D., Ph.D.
University of Strasbourg, Strasbourg, France

Reported here are 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. The patients received similar evaluations by intensivists in two intensive care units (ICUs) in Strasbourg, France, between March 3 and April 3, 2020.

Six patients were excluded because of paralytic neuromuscular blockade when neurologic data were collected or because they had died without a neurologic examination having been performed. In all 58 patients, reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays of nasopharyngeal samples were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The median age of the patients was 63 years, and the median Simplified Acute Physiology Score II at the time of neurologic examination was 52 (interquartile range, 37 to 65, on a scale ranging from 0 to 163, with higher scores indicating greater severity of illness). Seven patients had had previous neurologic disorders, including transient ischemic attack, partial epilepsy, and mild cognitive impairment.

The neurologic findings were recorded in 8 of the 58 patients (14%) on admission to the ICU (before treatment) and in 39 patients (67%) when sedation and a neuromuscular blocker were withheld. Agitation was present in 40 patients (69%) when neuromuscular blockade was discontinued (Table 1). A total of 26 of 40 patients were noted to have confusion according to the Confusion Assessment Method for the ICU; those patients could be evaluated when they were responsive (i.e., they had a score of −1 to 1 on the Richmond Agitation and Sedation Scale, on a scale of −5 [unresponsive] to +4 [combative]). Diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, and bilateral extensor plantar reflexes were present in 39 patients (67%). Of the patients who had been discharged at the time of this writing, 15 of 45 (33%) had had a dysexecutive syndrome consisting of inattention, disorientation, or poorly organized movements in response to command.

For More Information: https://www.nejm.org/doi/full/10.1056/NEJMc2008597

Bell’s Palsy after second dose of Pfizer COVID-19 vaccination in a patient with history of recurrent Bell’s palsy

Authors: Michael Repajic,a Xue Lei Lai,a Prissilla Xu,b and Antonio Liua,∗

Abstract

Objective

To report a patient with history of recurrent Bell’s Palsy who developed Bell’s Palsy 36 ​h after the administration of the second dose of the Pfizer-BioNTech COVID-19 vaccine.

Case

The patient is a 57-year-old female with past medical history of 3 episodes of Bell’s Palsy. She responded to prednisone treatment and returned to her baseline after each occurrence. Less than 36 ​h following the second dose of the vaccine, the patient developed a left Bell’s Palsy. The facial droop progressed in severity over the next 72 ​h.

Conclusion

Given the expedited production of the vaccine and the novelty associated with its production, there may be information pertaining to side effects and individual response that remain to be discovered. Since both the Moderna and Pfizer Vaccine trials reported Bell’s Palsy as medically attended adverse events, the association between vaccine administration and onset of symptomatic Bell’s Palsy may warrant further investigation.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874945/

Bell’s palsy following COVID-19 vaccination

Authors: Giuseppe Colella,1Massimiliano Orlandi,2 and Nicola Cirillo1,3

Currently two Coronavirus Disease 2019 (COVID-19) vaccines have been granted emergency use and marketing authorization by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) [12]. Initial efficacy and safety data for both BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines have been published [34]. To the best of our knowledge, there is no mention of facial paralysis in the article describing safety and efficacy of the BNT162b2 vaccine [3], however, four such adverse events were eventually highlighted in product monographs published by the relevant regulatory bodies [15]. Although FDA vaccine review memoranda do mention the occurrence of facial paralysis in the test group for both vaccines [12], consumer/patient information sheets of neither of the vaccines distributed in North America warn about Bell’s palsy as a possible adverse effect [6].

Here, we report a case of an otherwise healthy 37-year-old white Caucasian male who developed facial palsy within days after COVID-19 vaccination. We were given written, explicit informed consent to disclose the information reported in this letter. The patient received the first injection of the mRNA Vaccine BNT162b2 on 8th January, 2021, and the following day he developed symptoms including malaise, fatigue, and headache, but not hyperpyrexia. From the 11th, he complained of ingravescent left-sided latero-cervical pain irradiating ipsilaterally to the mastoid, ear, and retro-maxillary region. On 13th January upon awakening, he noticed a marked monolateral muscle weakness and attended the Maxillofacial Unit at our University Hospital. He presented with a left-sided facial droop accompanied by reduced mobility (paresis), with flattening of forehead’s skin and marionette line (labial-buccal sulcus) ipsilaterally as well as mild flattening of the nasolabial fold (Fig. 1). Lagophthalmos and mild labial hypomobility was also recorded. This clinical presentation was accompanied by a moderate Bell’s sign (failure to close the eye on the affected side with exposure of the sclera). No history of trauma, cold or other identifiable triggers was reported and no other signs or symptoms were present. Specifically, no history of a preceding infection, including recent SARS-CoV-2 infection, was reported and there was no evidence of a cutaneous rash suggestive of Herpes Zoster infection. The patient was referred to the Neurology Department with a provisional diagnosis of hemifacial paresis and discharged the same day with a clinical diagnosis of Bell’s palsy—an acute unilateral facial nerve paresis or paralysis with onset in less than 72 h and without identifiable cause [7]. No data are available concerning neurophysiological and cerebrospinal fluid investigations, as these were not deemed essential given that Bell’s palsy is fundamentally a clinical diagnosis and that there is no specific laboratory test to confirm the disorder. Laboratory or other diagnostic tests can surely be useful in excluding other conditions such as Lyme disease (not common in our geographical area) or neuropathies such as Gillian–Barre’ syndrome, or also brain tumors. These are especially useful when clinical presentation is not typical, and hence were not undertaken in our patient.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897359/