COVID-19: A Global Threat to the Nervous System

Authors: Igor J. Koralnik MD,Kenneth L. Tyler MD 07 June 2020 Annals of NeurologyVolume 88, Issue 1 p. 1-11


In less than 6 months, the severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID-19) also involves multiple other organs, including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS-CoV-2 infection is rapidly accumulating. These may result from a variety of mechanisms, including virus-induced hyperinflammatory and hypercoagulable states, direct virus infection of the central nervous system (CNS), and postinfectious immune mediated processes. Example of COVID-19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis, and endothelialitis. In the peripheral nervous system, COVID-19 is associated with dysfunction of smell and taste, muscle injury, the Guillain-Barre syndrome, and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID-19 poses a global threat to the entire nervous system. Although our understanding of SARS-CoV-2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID-19. ANN NEUROL 2020;88:1–11 ANN NEUROL 2020;88:1–11

The novel coronavirus, now called severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2), is the agent of coronavirus disease 2019 (COVID-19), that was first diagnosed on December 8, 2019, in a patient in the city of Wuhan in central China. Common symptoms of COVID-19 include fevercoughfatigue, and shortness of breath. Whereas most affected individuals have no or minor symptoms, some go on to develop pneumonia, acute respiratory distress syndrome (ARDS), and succumb from multiple organ failure. On January 30, 2020, the World Health Organization (WHO) declared it a Public Health Emergency of international concern. It has been estimated that the number of infected individuals during the early epidemic doubled every 2.4 days, and the R0 value, or number of people that can be infected by a single individual, may be as high as 4.7 to 6.6.1 After spreading throughout China, the disease took hold in Europe and the United States, and in view of this alarming development and the rapid growth of cases, public health officials in many jurisdictions ordered people to shelter in place beginning with the state of California on March 19, 2020. As of May 29, 2020, there have been 5.88 million confirmed cases in 188 countries and 363,000 reported deaths, and most countries are in various phases of relaxing quarantine requirements while continuing some social distancing measures.

What are coronaviruses and what makes SARS-CoV-2 so contagious? Coronaviruses, which have a diameter of approximately 100 nm, are named after their crown-like appearance on electron microscopy. They infect many animal species and are part of the family of Coronaviridae that contain four distinct Genera. Coronaviruses are positive strand, single stranded ribonucleic acid (+ss-RNA) viruses. They have the largest genome of all RNA viruses, approximately 30 kilobases in length. The full sequence of SARS-CoV-2 was published on January 7, 2020, and revealed that it is was a β-coronavirus, similar to other human coronaviruses that are responsible for 15% of all cases of acute viral nasopharyngitis, also known as “common cold.”2 However, SARS-CoV-2 contains unique sequences, including a polybasic cleavage site in the spike protein, which is a potential determinant of increased transmissibility.3

Coronaviruses have caused deadly outbreaks in the past. The first one caused by SARS-CoV, occurred in China in 2003 and affected approximately 8,000 people, with a 10% mortality rate. The Middle-East Respiratory Syndrome (MERS) outbreak began in Saudi Arabia in 2012, and affected 2,500 individuals with a 35% mortality rate. SARS-CoV-2 has approximately 80% sequence homology with SARS-CoV, but 96% homology with a bat coronavirus and 92% with a pangolin coronavirus, suggesting it arouse in animals and then spread between species to humans. The spike protein of SARS-CoV-2 binds to its cellular receptor, the angiotensin converting enzyme 2 (ACE2), which also acts as receptor for SARS-CoV. Viral entry occurs after proteolytic cleavage of the spike protein by the transmembrane protease TMPRSS2. ACE2 is expressed abundantly in lung alveolar cells, but also in many cell types and organs in the body, including the cerebral cortex, digestive tract, kidney, gallbladder, testis, and adrenal gland.4

Experience with the neurological complications of MERS and SARS provides a framework for considering both reported and potential neurological complications with SARS-CoV-2 and COVID-19.510 In both MERS and SARS, significant neurological complications were fortunately extremely rare. Reported cases of neurological disease suggests a minimum incidence of ~1:200 cases (MERS) -1:1,000 cases (SARS). It is important to recognize, however, that the total number of confirmed cases of MERS and SARS together is only ~10,500 cases. It is likely that the sheer numeracy of COVID-19 compared to MERS and SARS, with nearly 6 million cases reported worldwide to date, will bring out a broader spectrum of neurological manifestations. In MERS and SARS neurological disease could be considered in three major categories: (1) the neurological consequences of the associated pulmonary and systemic diseases, including encephalopathy and stroke, (2) direct central nervous system (CNS) invasion by virus, including encephalitis, and (3) postinfectious and potentially immune-mediated complications, including Guillain-Barre syndrome (GBS) and its variants and acute disseminated encephalomyelitis (ADEM).

Neurological Complications of Systemic COVID-19

In a review of 214 patients hospitalized in 3 dedicated COVID-19 hospitals in Wuhan, China, 36% of patients had nerurologic.11 These were further subdivided into those thought to reflect CNS, peripheral nervous system (PNS), and skeletal muscle injury. Overall, 25% of patients had symptoms considered as evidence of CNS dysfunction, including dizziness (17%), headache (13%), impaired consciousness (7.5%), acute cerebrovascular disease (3%), ataxia (0.5%), and seizures (0.5%). Confirming this low incidence of seizures, no cases of status epilepticus or new onset seizures were reported in a large cohort of over 304 hospitalized patients with COVID-19 in Hubei Province, China,12 although there have been isolated case reports describing seizures at presentation in both adult and pediatric patients with COVID-19.1314

In the series by Mao and colleagues,11 the patients were subdivided based on the severity of their pneumonia and pulmonary impairment, and among those with “severe” disease (n = 88) the incidence of CNS symptoms was higher (31%) compared to the non-severe group (21%), although the results were not statistically significant (p = 0.09). Although all the categorized CNS symptoms occurred more frequently in patients with severe disease compared to non-severe disease, only impaired consciousness (15% in severe vs 2% in non-severe, p < 0.001) and acute cerebrovascular disease (5.7% vs 0.8%; p = 0.03) were significantly different between the two groups. Diagnostic studies were limited, but the impairment of consciousness seems most consistent with encephalopathy. Not surprisingly, when compared to those with non-severe disease, the severe cohort were older (58 ± 15 years vs 49 ± 15 years), and more likely to have comorbidities, including hypertension, diabetes, malignancy, cardiac, cerebrovascular, or kidney disease (48% vs 33%; p = 0.03). The severe group also had more evidence of systemic inflammation, including elevated C-reactive protein (CRP; median 37 mg/L) and D-dimer (median 0.9 mg/L) compared to non-severe cases, and were also more likely to have evidence of hepatic (elevated alanine and aspartate aminotransferases) and renal (elevated BUN and creatinine) dysfunction.

A second survey of 58 hospitalized patients (median age 63 years) with COVID-19 ARDS at Strasbourg University Hospital found that 69% of patients had agitation, 67% had corticospinal tract signs, and 36% had a “dysexecutive” syndrome with difficulty in concentration, attention, orientation, and following commands.15 All patients studied (11/11) had evidence of frontal hypoperfusion on arterial spin label and dynamic susceptibility-weighted perfusion magnetic resonance imaging (MRI). Only seven patients had a cerebrospinal fluid (CSF) examination, none had a pleocytosis, and none had SARS-CoV-2 RNA detected by reverse transcriptase-polymerase chain reaction (RT-PCR). One patient did have elevated immunoglobulin G (IgG) levels and “mildly” elevated total protein. CSF specific oligoclonal bands (OCBs) were not detected, but one patient had “mirror pattern” OCBs in CSF and serum.

In a study of MRI abnormalities in patients in the intensive care unit (ICU) with COVID-19, 21% (50/235) of patients developed neurological symptoms.16 In this group of neurologically symptomatic patients, only 27 had MRIs performed, and of these 44% (12/27) had new acute findings. Surprisingly, 56% (15/27) had no new MRI changes. The most common new abnormalities were multifocal areas of cortical fluid-attenuated inversion recovery (FLAIR) signal (10/12), accompanied in three patients by areas of increased FLAIR signal in the subcortical and deep white matter. One patient each had new transverse sinus thrombosis and acute middle cerebral artery infarction. Five of the 10 patients with cortical FLAIR abnormalities had a CSF examination, and none of these patients had a pleocytosis elevated IgG index, or OCBs (0/3 tested), although 4 patients had an elevated protein (mean 80 mg/dl; range = 60–110). RT-PCR for SARS-CoV-2 was negative in all 5 cases tested. In another MRI series of critically ill patients on mechanical ventilation, many were found to have confluent T2 hyperintensities and restricted diffusion in the deep and subcortical white matter, in some cases, accompanied by punctate microhemorrhages in the juxtacortical and callosal white matter that resembled findings seen in delayed post-hypoxic leukoencephalopathy.17

The mechanism of encephalopathy in COVID-19 remains to be determined. From available studies, COVID-19 encephalopathy seems to be more common in patients with more severe disease, associated comorbidities, evidence of multi-organ system dysfunction, including hypoxemia, and renal and hepatic impairment, and elevated markers of systemic inflammation. Virus is not detected in CSF by RT-PCR and pleocytosis is usually absent. Some patients may have altered perfusion detectable by MRI, others have leukoencephalopathy with or without punctate microhemorrhages. This group needs to be distinguished from patients with encephalitis (who have a pleocytosis) and postinfectious immune-mediated encephalitis (see below).

In a series of five consecutive patients with COVID-19 with delayed awakening post-mechanical ventilation for ARDS, MRI showed enhancement of the wall of basal skull arteries without enlargement of the vessel wall or stenosis. Toxic-metabolic derangements and seizures were ruled out, CSF SARS-CoV-2 RT-PCR was negative in all and they showed marked improvement in alertness 48 to 72 hours after treatment with methylprednisolone 0.5 g/days iv for 5 days. These findings suggest that an endothelialitis rather than a vasculitis was responsible for the encephalopathy.18 Direct infection of endothelial cells by SARS-CoV-2 and associated endothelial inflammation has been demonstrated histologically in postmortem specimens from a variety of organs, which did not include the brain.19

However, in an autopsy series, including examination of the brain, of 20 patients with COVID-19, six had microthrombi and acute infarctions and two focal parenchymal infiltrates of T-lymphocytes, whereas the others mainly had minimal inflammation and slight neuronal loss without acute hypoxic–ischemic changes in most cases. There was no evidence of meningoencephalitis, microglial nodules, or viral inclusions, including in the olfactory bulbs and brainstem, and no demyelination. ACE2 was expressed in lung and brain capillaries. All cases had evidence of systemic inflammation.20

A second major manifestation of systemic COVID-19 disease is acute cerebrovascular disease. In the study by Mao and colleagues,11 this was present in 6 of the 214 (3%) hospitalized cases, but 5 of the 6 events occurred in those with severe disease (incidence 6%; p = 0.03 vs non-severe disease).11 Five of the six reported events were ischemic strokes, and one was hemorrhagic. In the review of cases at Strasbourg University Hospital,15 3 of 13 (23%) had cerebral ischemic stroke. In a single center retrospective study from China of 221 patients hospitalized with COVID-19, 13 had acute strokes, including 11 ischemic, 1 hemorrhagic, and 1 venous sinus thrombosis.21 The stroke patients were older, had more comorbidities, including diabetes, hypertension, and a prior stroke, and elevated inflammatory markers, including D-dimer and CRP. Another review of six consecutive patients with COVID-19 admitted to the National Hospital in Queen Square with stroke, noted that occlusions typically involved large vessels and often occurred in multiple vascular territories.22 In 5 of 6 cases, the strokes occurred 8 to 24 days after onset of COVID-19 symptoms. All patients had a highly prothrombotic state with very high D-dimer levels and elevated ferritin. Five of the six patients had detectable lupus anticoagulant, suggesting another potential prothrombotic mechanism for stroke in COVID-19. Anticardiolipin IgA and antiphospholipid IgA and IgM antibodies directed against β2-glycoprotein-1 were also found in three patients with COVID-associated multiple territory large vessel infarctions.23 Finally, a postmortem MRI study showed subcortical micro- and macro-bleeds (two decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES; one decedent), and nonspecific deep white matter changes (one decedent).24

Although initial reports emphasized acute cerebrovascular disease in older patients with COVID-19, a recent report described five cases of large vessel stroke as a presenting feature of COVID-19 in younger individuals, two of whom lacked classic stroke risk factors.25 These patients ranged in age from 33 to 49 years. Two of the five patients had diabetes, one of whom had had a mild prior stroke, and one had hypertension and dyslipidemia. The infarcts involved large vessel territories, including the middle cerebral artery (3), posterior cerebral artery (1), and internal carotid artery (1). Two patients had preceding COVID-19 symptoms, including fever, chills, cough, and headache; one patient had only lethargy. Surprisingly, two of the five patients had no COVID-19-related symptoms preceding their stroke presentation. These five patients had elevated prothrombin (range = 12.8–15.2 seconds) and activated partial thromboplastin times (range = 25–42.7 seconds), elevated fibrinogen (range = 370–739 mg/dl), D-dimer (range = 52–13,800 ng/ml) and ferritin (range = 7–1,564 ng/ml) consistent with a hypercoagulable state and the presence of disseminated intravascular coagulation (DIC).

COVID-19 cerebrovascular disease seems to be predominantly ischemic and to involve large vessels. In older individuals, it reflects the underlying severity of systemic disease as well as the hyperinflammatory state, whereas in younger patients, it seems to be due to hypercoagulopathy. Children with a Kawasaki disease-like multisystem inflammatory syndrome (MIS) have recently been described.2627 Patients with Kawasaki disease can develop cerebral vasculopathy and forms of neurological involvement, and in one series of 10 COVID-19 associated cases of MIS, two patients had meningeal symptoms.27 As noted, in addition to hypercoagulable states, SARS-CoV-2 can infect and injure endothelial cells. However, it remains to be determined whether virus-induced injury to endothelial cells (a vasculopathy) or even true vasculitis contributes to COVID-19 related cerebrovascular syndromes, and this determination will require additional detailed vessel imaging and neuropathological analyses. Similarly, the number of cases is too small to determine the comparative therapeutic benefit, if any, of antiplatelet or anticoagulant drugs or immunomodulatory therapies in COVID-19 associated neurovascular syndromes.

Neuroinvasion by SARS-CoV-2

In contrast to encephalopathy, in which evidence for direct invasion by virus of the CNS is absent, encephalitis occurs when direct invasion of the CNS by virus produces tissue injury and neurological dysfunction. Evidence for direct invasion of the CNS was seen in patients with SARS. Xu and colleagues described a fatal case in a 39-year-old man with delirium that progressed to somnolence and coma.10 At postmortem, the SARS-CoV antigen was detected in brain tissue by immunohistochemistry (IHC) and viral RNA by in situ hybridization (ISH). SARS-CoV virions were seen by transmission electron microscopy of brain tissue inoculated cell culture. In a postmortem analysis of four patients with SARS, low level infection of cerebral neurons with SARS-CoV (1–24% of cells) was seen in the cerebrum in all four cases by IHC and ISH, although none of the cases had virus detected in the cerebellum.28

By definition, encephalitis is an inflammatory process, with supportive evidence, including the presence of a CSF pleocytosis and elevated protein. However, in studies of transgenic mice expressing the human SARS-CoV receptor, ACE2, infection with SARS-CoV was associated with viral entry into the CNS, spread within the CNS, and neuronal injury with relatively limited inflammation.29 This suggests the possibility that, in some cases of SARS-CoV-2 CNS invasion, that signs of inflammation could be modest or even absent. Regardless of the presence or absence of inflammation, diagnostic studies may show evidence of either a generalized or focal CNS process, including areas of attenuation on computed tomography (CT), hyperintense signal on FLAIR, or T2-weighted sequences on MRI, and focal patterns, including seizures on electroencephalogram (EEG). Definitive evidence supporting direct viral invasion would include a positive CSF RT-PCR for SARS-CoV-2, demonstration of intrathecal synthesis of SARS-CoV-2-specific antibodies, or detection of SARS-CoV-2 antigen or RNA in brain tissue obtained at biopsy or autopsy.

Cases meeting strict criteria for encephalitis resulting from direct SARS-CoV-2 are currently extremely rare, although several plausible case reports have now surfaced. Moriguchi et al described a 24-year-old man with COVID-19 disease who developed nuchal rigidity, progressively decreased consciousness (Glasgow Coma Scale [GCS] = 6), and generalized seizures.30 CSF showed a slight mononuclear predominant pleocytosis (12 cells/μl3) and elevated opening pressure (>320 mm H20). Neuroimaging showed hippocampal and mesial temporal increased FLAIR signal and the CSF RT-PCR was positive for SARS-CoV-2. Unfortunately, studies to exclude other viral etiologies of encephalitis were limited. A second case involved a 41-year-old woman with headache, fever, a new onset seizure, and photophobia and nuchal rigidity, followed by hallucinations and disorientation. A head CT scan was normal and MRI was not performed. An EEG showed generalized slowing. The CSF examination showed a lymphocytic pleocytosis (70 cells/μl; 100% lymphocytes), and elevated protein (100 mg/dl), and a positive SARS-CoV-2 RT-PCR.3132

Several cases have emerged in which patients had inflammatory features consistent with encephalitis, but who did not have evidence of direct viral CNS invasion. Bernard-Valnet et al reported on two patients with “meningoencephalitis concomitant to SARS-CoV2.”33 These patients had nuchal rigidity, altered mental status, mild CSF lymphocytic pleocytosis (17–21 cells/μl3 on initial lumbar puncture [LP]), and mildly elevated CSF protein (46–47 mg/dl). However, in both patients, the MRI was normal and neither patient had a positive CSF RT-PCR for SARS-CoV-2. Similarly, Pilotto et al describe a 60-year-old man with COVID-19 who developed confusion, irritability, and then apathy progressing to “akinetic mutism” with nuchal rigidity.34 The CSF showed a mild lymphocytic pleocytosis (18 cells/μl3) and elevated protein (70 mg/dl). An EEG showed generalized slowing with an anterior predominance. The CT and MRI were normal, and CSF RT-PCR was negative twice for SARS-CoV-2. Although treated with a wide variety of medications, this patient showed improvement coincident to administration of high dose methylprednisolone.34 Another study reported on six critically ill patients with severe ARDS, elevated inflammatory markers, and depressed consciousness and/or agitation, who were considered to have “autoimmune meningoencephalitis.”35 No patient had a CSF pleocytosis but five had elevated CSF protein (52–131 mg/dL) and three had an MRI that showed cortical hyperintensities with sulcal effacement. There were no controls but patients were felt to have responded to plasma exchange. In one report, a patient with neuropsychiatric symptoms and COVID-19 had a “hematic” CSF tap with 960 “red and white blood cells” and an elevated protein (65 mg/dL) and detectable N-methyl-D-aspartate (NMDA) receptor antibodies. This currently isolated case also raises the possibility that COVID-19 may trigger auto-antibody production.36

The available studies suggest that SARS-CoV-2 can rarely produce a true encephalitis or meningoencephalitis with associated evidence of direct viral invasion of the CNS. The failure to detect virus in CSF in the other reported cases, despite evidence of inflammation as evidenced by CSF pleocytosis and elevated protein, raises the possibility that some cases of COVID-19 encephalitis may occur in the absence of direct virus invasion, and could potentially result from immune-mediated inflammatory mechanisms (see below). It is important to realize that techniques, including detection of intrathecal SARS-CoV-2 antibody synthesis or of viral antigen or nucleic acid in brain tissue, may establish evidence for viral invasion when CSF RT-PCR studies are negative. For example, detection of intrathecal antibody synthesis is significantly more sensitive than CSF nucleic acid amplification tests for diagnosis of both West Nile Virus neuroinvasive disease and Enterovirus (EV)-D68 associated acute flaccid myelitis (AFM).3739 In the case of EV-D68-associated AFM, nasopharyngeal and throat swabs are frequently positive for virus by RT-PCR when obtained early after disease onset, yet, CSF RT-PCR tests are only positive in a small minority (<3%) of cases.40 The sensitivity of SARS-CoV-2 RT-PCR in properly performed nasopharyngeal swabs for detection of acute COVID-19 is high, but data are currently too limited to evaluate sensitivity of this technique in CSF in patients with neurological disease.

Post-Infectious and Immune-Mediated Complications of SARS-CoV-2

The identification of postinfectious complications of SARS-CoV-2 would be expected to temporally lag behind those resulting from acute infection. Occasional cases of GBS and its variants and of ADEM were reported after MERS and SARS.579 Reports are now emerging of similar associations with COVID-19 and GBS, and with GBS variants, including the Miller-Fisher syndrome.4146 The largest series to date, describes five patients.47 In this series, all patients developed GBS 5 to 10 days following COVID-19 symptom onset. The clinical presentation included bilateral multi-limb flaccid weakness with areflexia. Three patients had associated respiratory failure and two had associated facial weakness. MRI showed caudal root nerve enhancement in two cases and enhancement of the facial nerve in a third case. The CSF was normocellular in all five cases, and had an elevated protein consistent with albuminocytological dissociation in three cases. Electrophysiological studies showed reduced compound motor amplitudes and prolonged distal latencies, and the overall pattern was felt to be consistent with demyelination in two cases and axonal neuropathy in three cases. Fibrillation potentials were seen by electromyography (EMG) acutely in three patients and later in a fourth patient. None of the patients had SARS-CoV-2 detected in the CSF by RT-PCR. Antiganglioside antibodies were absent in the three tested patients. All patients received intravenous immunoglobulin (ivIG) and one plasma exchange, although improvement was noted in only two cases (one “mild improvement” only).

Cases of acute necrotizing encephalopathy (ANE) have been reported in COVID-19.4849 One patient was a 50-year-old woman with COVID-19 confirmed by nasopharyngeal RT-PCR who developed altered mental status and MRI and CT findings typical of ANE, including bilateral thalamic lesions. Unfortunately, CSF studies were limited and CSF RT-PCR testing for SARS-CoV-2 was not performed. A second case occurred in a 59-year-old woman with aplastic anemia who developed seizures and reduced consciousness 10 days after onset of her COVID-19 symptoms.49 The mechanism behind ANE remains unknown, and either direct viral or postinfectious inflammatory processes have been postulated to play a role, and many cases have been reported after upper respiratory infections, including influenza. Some patients have mutations in RAN binding protein-2 (RANBP2), indicating that host genetic factors may also play a role in susceptibility.

Rare cases of ADEM were associated with MERS.6 The first case of “COVID-19 associated disseminated encephalomyelitis” was reported in a 40-year-old woman.50 This individual had COVID-19 symptoms followed 11 days later by dysarthria, dysphagia, facial weakness, and a gaze preference. A chest X-ray showed pneumonia and nasopharyngeal RT-PCR was positive for SARS-CoV-2. Head CT showed multiple areas of patchy hypoattenuation and an MRI showed areas of increased FLAIR and T2 signal in the subcortical and deep white matter that were felt to be consistent with demyelination. Her CSF was normal. A second reported case was in a 54-year-old woman who developed seizures and neurological deterioration (GCS = 12) and had chest X-ray lesions consistent with COVID-19 and a positive nasopharyngeal RT-PCR for SARS-CoV-2.51 Her MRI showed multiple periventricular T2 hyperintense, nonenhancing, lesions in the white matter of the cerebrum, brainstem, and spinal cord consistent with multifocal demyelination. Her CSF studies were unremarkable, including a negative CSF RT-PCR for SARS CoV-2. She was treated with high dose dexamethasone and her symptoms gradually resolved. A single case of acute flaccid myelitis has also been described in COVID-19.52 This patient developed upper limb weakness and a flaccid areflexic lower limb paralysis, urinary and bowel incontinence, and a T10 sensory level. Unfortunately, neither spine imaging nor CSF studies were available so the mechanism remains unknown. The most convincing example of ADEM-like pathology associated with COVID-19 was in a 71-year-old man who developed symptoms immediately following coronary bypass graft surgery that progressed to respiratory failure and a hyperinflammatory state. A postmortem examination showed brain swelling and disseminated hemorrhagic lesions and subcortical white matter pathology with perivenular myelin injury but also necrotic blood vessels and perivascular inflammation. The lesions had features of both acute hemorrhagic leukoencephalitis and of acute disseminated encephalomyelitis.53

The rarity of postinfectious potentially immune-mediated cases following COVID-19 other than GBS and its variants, and the general paucity of details, makes their status unclear. The cases of ADEM-like illness are hard to distinguish from some of the patients with acute encephalopathy and associated MRI white matter lesions, but can be differentiated from cases of encephalitis by the absence of CSF pleocytosis. GBS is a common neurological disease even in the absence of COVID-19, and identifying the magnitude of the COVID-19 risk and association will require better epidemiological data. However, the 5 cases of GBS occurring in a population of 1,000 to 1,200 patients with COVID-19 seen over a 1 month period by Toscano et al in Northern Italy suggest an incidence that is much higher than that can be expected in the general population (~1/100,000 person-years).54 The mechanism of pathogenesis will need to be identified, and the efficacy of conventional therapies, including ivIG and plasma exchange, evaluated.

Other COVID-19 Related Neurological Disorders

One of the more striking reported symptom manifestations in patients with COVID-19 is loss or perturbation of smell (anosmia or hyposmia) and/or taste (dysgeusia). The frequency of these symptoms, their specificity as a potential diagnostic clue for COVID-19 infection as opposed to influenza or other symptomatologic similar diseases, and their implication for understanding viral pathogenesis all remain uncertain. In the Wuhan COVID-19 series, impairment of smell was noted in 5% and of taste in 6% of the 214 hospitalized patients.11 It is likely that the frequency was under-represented due to incomplete evaluations in these hospitalized sick patients. A later study of 31 patients, suggested that disorders of taste occurred in 81% of COVID-19 cases (46% anosmia, 29% hyposmia, and 6% dysosmia) and disorders of taste in 94% (ageusia 45%, hypogeusia 23%, and dysgeusia 26%).55 The average duration of smell and taste disorders in the COVID-19 cases was 7.1 ± 3.1 days. A multicenter European study of 417 cases with “mild-to-moderate” COVID-19 disease found a similarly high frequency of olfactory dysfunction (86%), with 80% of those affected having anosmia and 20% hyposmia.56 Approximately 70% of patients had recovered within 8 days of symptom onset. It has been suggested that olfactory and/or gustatory dysfunction may be indicative of neuro-invasion and provide a route from the nasopharynx or oropharynx to cardiorespiratory centers in the medulla, based on studies of transgenic mice expressing the human SARS virus receptor (ACE2) and infected with SARS-CoV, however, no evidence supporting host entry via this pathway yet exists in man.29 The transient nature of the dysfunction in most patients would seem to make direct viral infection and subsequent killing of olfactory or gustatory neurons unlikely. MRI of the olfactory bulb was normal in one RT-PCR confirmed patient with anosmia.57

In the Wuhan COVID-19 series, 11% of patients were reported to have evidence of skeletal muscle injury (defined as a creatine kinase [CK] >200 U/L and skeletal muscle pain).11 Injury was significantly more common in patients with “severe” disease (19%) compared to non-severe disease (5%; p < 0.001). Unfortunately, almost no clinical details were provided beyond the presence of associated muscle pain. Subsequently two reports have emerged of rhabdomyolysis as either a presenting feature or a late complication of COVID-19.5859 One patient had limb pain and weakness with a peak CK of ~12,000 U/L and myoglobulin >12,000 μg/L, and the other had a peak CK of 13,581 U/L. Neither patient had muscle biopsy performed. The mechanism of injury remains to be determined.

Immunopathogenesis of SARS-CoV-2 and Implication for Management and Treatment of Neurologic Manifestations

One of the most puzzling features of SARS-CoV-2 infection is that it is asymptomatic or associated with minor symptoms in approximately 80% of patients, especially children and young adults, whereas 20% will develop COVID-19 with various degrees of severity. Can knowledge gathered on SARS-CoV inform us about the immunopathogenesis of SARS-CoV-2? A successful production of type I interferon (IFN) response is a key first line defense for suppressing replication of many neurotropic viruses at the site of entry and dissemination. SARS-CoV suppresses type I IFN response and downstream signaling using multiple strategies, and this dampening is closely associated with disease severity.60

Because SARS-CoV-2 shares an overall genomic similarity of 80% with SARS-CoV and uses the same receptor, it is reasonable to expect that the innate immune mechanisms involved in pathogenesis will be similar for the two viruses. SARS-CoV has developed multiple strategies to evade the innate immune response in order to optimize its replication capacity.61 It seems likely that SARS-CoV-2 uses the same strategy. The magnitude of the immune response against SARS-CoV-2 needs to be precisely calibrated to control viral replication without triggering immunopathogenic injury. A hyperinflammatory response likely plays a major role in ARDS and, in a subset of children, may contribute to the development of a Kawasaki-like multisystem inflammatory disorder.20 In a mouse model of SARS, rapid SARS-CoV replication and delay in IFN-I signaling led to inflammatory monocyte–macrophage accumulation, resulting in elevated lung cytokine/chemokine levels and associated vascular leakage and lethal pneumonia. This “cytokine storm,” in turn, was associated with a decrease in T cell counts and suboptimal T cell responses to SARS-CoV infection.62

The same pattern is found in 522 patients with COVID-19, where the number of total T cells, CD4+ and CD8+ T cells, were dramatically reduced, especially in those requiring ICU care, and T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-α concentration. Conversely, patients in the disease resolution period showed reduced IL-6, IL-10, and TNF-α levels and restored T cell counts.63 These data were corroborated by other groups who also noticed a decrease in type 1 interferon response in severely affected patients.6465 It has been suggested that reduced and delayed IFN gamma production (“too little and too late”) in the lungs and depletion of both CD4+ and CD8+ T cells may combine to potentiate viral injury, by reducing control of viral replication and enhancing the upregulation of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-10 (“cytokine storm”), and that it may be the immune dysregulation as much or more than the direct viral infection that results in pulmonary epithelial cell injury, and similar mechanisms could be operative in the CNS.66

What are the possible mechanisms for the apparent immune dysregulation seen in those patients and could they have a role in the neuropathogenesis of COVID-19? The source of cytokines found in the serum in unclear, but they could be produced by lung macrophages. IL-6 could also come from infected neurons, as seen in a transgenic mouse model of SARS-Cov.29 A high level of circulating cytokines, in turn, could lead to lymphocytopenia. TNF-α, a pro-inflammatory cytokine, may cause T cell apoptosis via interacting with its receptor, TNFR1, which expression is increased in aged T cells.6768 IL-6, that has both pro-inflammatory and anti-inflammatory properties, contributes to host defense in response to infections. However, continual synthesis of IL-6 has been shown to play a pathological role in chronic inflammation and infection.6970 IL-10, an inhibitory cytokine that prevents T cell proliferation, can also induce T cell exhaustion. Interestingly, patients with COVID-19 have high levels of the PD-1 and Tim-3 exhaustion markers on their T cells.63 In turn, decreased numbers of CD4+ and CD8+ T lymphocytes will considerably weaken the cellular immune response to SARS-CoV-2 in severe cases, allowing further viral replication. This can be compounded by the use of corticosteroids. Of note, a study in convalescent patients with SARS-CoV showed that CD8+ T cell responses were more frequent and had a greater magnitude of response than CD4+ T cells.71 Finally, one autopsy series of patients with COVID-19 showed histological features suggestive of secondary hemophagocytic lymphohistiocytosis (sHLH), also known as macrophage activation syndrome. This syndrome is characterized by an imbalance of innate and adaptive immune responses with aberrant activation of macrophages, and a blunted adaptive immune response.20

This dysregulated immune response may have a role in the pathogenesis of the COVID-19 encephalopathy. High levels of circulating pro-inflammatory cytokines can cause a confusion and alteration of consciousness, whereas a weakened T cell response may be unable to eliminate virus-infected cells in the brain causing further neurologic dysfunction. Careful studies of the CSF cytokine profile and T cell response to SARS-CoV-2 as well as postmortem studies, including CNS and muscle tissues, are urgently needed to better understand the neuropathogenesis of COVID-19. These will help inform whether therapeutic strategies aimed at blocking pro-inflammatory cytokines, including the IL-6 inhibitors tocilizumab and sarilumab, could have a beneficial effect on encephalopathy or whether corticosteroids that dampened the adaptive cellular immune response to viruses are contra-indicated. As we strive to find medications to counter the deleterious inflammatory state triggered by SARS-CoV-2, lessons can also be learned from COVID-19 outcomes in patients with neurological diseases, such as multiple sclerosis or myasthenia gravis, treated with immunomodulatory therapies.

Although we are only starting to grasp the complexity of SARS-CoV-2 biology, it is already apparent that COVID-19 causes a global threat to the entire nervous system, both through its worldwide distribution and multifactorial pathogenic mechanisms (Fig). As we hope for a vaccine or a cure, neurologists will play an important role in diagnosing, investigating, and treating the many neurologic manifestations of COVID-19 (Table).72

Details are in the caption following the image
FIGURE 1Open in figure viewerPowerPointMechanisms of severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) neuropathogenesis. SARS-CoV-2 pathogenic effects on the nervous system are likely multifactorial, including manifestations of systemic disease, direct neuro-invasion of the central nervous system (CNS), involvement of the peripheral nervous system (PNS) and muscle, as well as through a postinfectious, immune-mediated mechanism. MOF = multi-organ failure; GBS = Guillain-Barre syndrome. *CNS inflammation (CSF pleocytosis and proteinorrachia) with no evidence of direct viral infection of CNS; §direct evidence of viral invasion (reverse transcriptase-polymerase chain reaction positive [RT-PCR+], biopsy); ADEM = acute disseminated encephalomyelitis; ANE = acute necrotizing encephalopathy. [Color figure can be viewed at]

TABLE 1. Neurologic Conditions Associated with SARS-CoV-2 Infection

Disease entityPresentationSupportive Neurodiagnostic testingPathogenesis
EncephalopathyAltered mental statusMRI: non-specificEEG: abnormal (slow)CSF: nl cells and ProCSF SARS-CoV-2 RT-PCR: NEGMultiple organ failureHypoxemiaSystemic InflammationEndothelialitis
EncephalitisAltered mental status and CNS dysfunctionMRI: non-specific (? WM changes)EEG: abnormal (slow, +focal)CSF: pleocytosis & elev. ProCSF SARS-CoV-2 RT-PCR: NEGCNS inflammation
Viral encephalitisAltered mental status and CNS dysfunctionMRI: new abnormalityEEG: abnormal (slow, ±focal)CSF: Pleocytosis and elev. ProCSF SARS-CoV-2 RT-PCR: POSBrain Tissue: POS (Ag or RNA)Brain parenchymal neuro-invasion
Viral meningitisHeadache, nuchal rigidityMRI: meningeal enhancement, CSF: pleocytosis & elev. ProCSF SARS-CoV-2 RT PCR: POSSubarachnoid invasion
StrokeFocal motor or sensory deficitMRI: ischemia or bleed, abnormal coagulation factors, increased inflammatory markersCoagulopathy
Anosmia/ageusiaOlfactory or taste dysfunctionAbnormal smell/taste tests? Peripheral vs central neuro-invasion
ADEMHeadache, acute neurologic symptomsMRI: hyperintense FLAIR lesions with variable enhancementPostinfectious
Guillain-Barre syndromeFlaccid muscle weaknessCSF: increased protein, nl WBC CSF SARS-CoV-2 RT-PCR: NEGEMG/NCS: abnormalPostinfectious
Muscle injuryMyalgiaCK elevatedMyopathy or myositis?
  • ADEM = acute disseminated encephalomyelitis; CNS = central nervous system; CK= creatinine kinase; CSF = cerebrospinal fluid; EEG = electroencephalogram; EMG = electromyogram; FLAIR = fluid-attenuated inversion recovery; MRI = magnetic resonance imaging; NCS = nerve conduction study; NEG = negative; POS = positive; pro = protein; RT-PCR = reverse transcriptase-polymerase chain reaction; SARS-CoV-2 = severe acute respiratory syndrome-coronavirus type 2; WBC = white blood cell; WM = white matter.

40-Year-Old British Columbia Man Diagnosed with Guillain-Barré Syndrome Is Awarded Compensation for Vaccine Injury (VIDEO)

Authors: Jim Hoft Published June 16, 2022  The Gateway Pundit

A 40-year-old father from British Columbia was one of the first people in Canada to be compensated after suffering an adverse reaction connected to the COVID-19 vaccine.

Ross Wightman, a former pilot and realtor was diagnosed with Guillain-Barré Syndrome (GBS), which is a rare disorder in which your body’s immune system attacks your nerves, after receiving a first dose of the Oxford AstraZeneca COVID-19 vaccine last April 2021.

Wightman became partially paralyzed from the waist down and suffered full facial paralysis after being diagnosed with the disease due to the COVID-19 vaccine.

40-Year-Old British Columbia Man Diagnosed with Guillain-Barré Syndrome Is Awarded Compensation for Vaccine Injury (VIDEO)

By Jim Hoft
Published June 16, 2022 at 7:23a
Here is a story you won’t hear in mainstream media.

A 40-year-old father from British Columbia was one of the first people in Canada to be compensated after suffering an adverse reaction connected to the COVID-19 vaccine.

Ross Wightman, a former pilot and realtor was diagnosed with Guillain-Barré Syndrome (GBS), which is a rare disorder in which your body’s immune system attacks your nerves, after receiving a first dose of the Oxford AstraZeneca COVID-19 vaccine last April 2021.

Wightman became partially paralyzed from the waist down and suffered full facial paralysis after being diagnosed with the disease due to the COVID-19 vaccine.

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“He said his symptoms started with severe back pain 10 days after his shot. He went to the emergency room multiple times and was admitted on a Saturday when he reported facial tingling,” Calgary Herald reported.

Last month, Wightman posted a letter he received from the federal Vaccine Injury Support Program on his social media account stating that “there is a probable causal association between the injuries sustained and the vaccination.”

“The maximum lump-sum amount a person can receive through the VISP is $284,000. Though Wightman chose not to disclose the specific amount he was given for privacy reasons, he said he did not qualify for the maximum payout,” according to Calgary Herald.

“I’m the first person in Canada to ever receive this letter! Some long-awaited recognition from the government. We were very skeptical as to where this process would go early on, as the service we were getting was appalling. That being said, I have to give credit where credit is due, and our current case manager and project lead has been excellent. Thanks to Nicole “pit bull” Wightman for staying on top of this, and ensuring everyone got the required paperwork they asked for,” Wightman wrote in his caption.

“Following an assessment of your case, it has been determined by our Medical Review Board that there is a probable causal association between the injury(ies) sustained and the vaccination. As such your claim has been approved for compensation,” the letter stated.

“The Medical Review Board has also determined the severity of the injury(ies) based on the medical documentation available at the time of assessment. Based on this assessment, you qualify for an injury indemnity totaling *******. This indemnity will be paid as a lump sum and is tax exempt. The details of the Medical Review Board’s decision can be found in the Appendix attached to this letter,” the letter continued.

40-Year-Old British Columbia Man Diagnosed with Guillain-Barré Syndrome Is Awarded Compensation for Vaccine Injury (VIDEO)

By Jim Hoft
Published June 16, 2022 at 7:23am

A 40-year-old father from British Columbia was one of the first people in Canada to be compensated after suffering an adverse reaction connected to the COVID-19 vaccine.

Ross Wightman, a former pilot and realtor was diagnosed with Guillain-Barré Syndrome (GBS), which is a rare disorder in which your body’s immune system attacks your nerves, after receiving a first dose of the Oxford AstraZeneca COVID-19 vaccine last April 2021.

Wightman became partially paralyzed from the waist down and suffered full facial paralysis after being diagnosed with the disease due to the COVID-19 vaccine.

“He said his symptoms started with severe back pain 10 days after his shot. He went to the emergency room multiple times and was admitted on a Saturday when he reported facial tingling,” Calgary Herald reported.

Last month, Wightman posted a letter he received from the federal Vaccine Injury Support Program on his social media account stating that “there is a probable causal association between the injuries sustained and the vaccination.”

“The maximum lump-sum amount a person can receive through the VISP is $284,000. Though Wightman chose not to disclose the specific amount he was given for privacy reasons, he said he did not qualify for the maximum payout,” according to Calgary Herald.

“I’m the first person in Canada to ever receive this letter! Some long-awaited recognition from the government. We were very skeptical as to where this process would go early on, as the service we were getting was appalling. That being said, I have to give credit where credit is due, and our current case manager and project lead has been excellent. Thanks to Nicole “pit bull” Wightman for staying on top of this, and ensuring everyone got the required paperwork they asked for,” Wightman wrote in his caption.

“Following an assessment of your case, it has been determined by our Medical Review Board that there is a probable causal association between the injury(ies) sustained and the vaccination. As such your claim has been approved for compensation,” the letter stated.

“The Medical Review Board has also determined the severity of the injury(ies) based on the medical documentation available at the time of assessment. Based on this assessment, you qualify for an injury indemnity totaling *******. This indemnity will be paid as a lump sum and is tax exempt. The details of the Medical Review Board’s decision can be found in the Appendix attached to this letter,” the letter continued.

“Wightman is one of only a handful of Canadians to have the illness validated as a vaccine-related injury by the federal government,” Global News reported

1000 Peer Reviewed Studies Questioning Covid-19 Vaccine Safety

Peer Reviewed Medical Papers Submitted To Various Medical Journals, Evidencing A Multitude Of Adverse Events In Covid-19 Vaccine Recipients.

The list includes studies published as of January 20, 2022 concerning the potential adverse reaction from COVID-19 vaccines, such as myocarditis, thrombosis, thrombocytopenia, vasculitis, cardiac, Bell’s Palsy, immune-mediated disease, and many more.

  1. Myocarditis after mRNA vaccination against SARS-CoV-2, a case series:
  2. Myocarditis after immunization with COVID-19 mRNA vaccines in members of the US military. This article reports that in “23 male patients, including 22 previously healthy military members, myocarditis was identified within 4 days after receipt of the vaccine”:
  3. Association of myocarditis with the BNT162b2 messenger RNA COVID-19 vaccine in a case series of children:
  4. Acute symptomatic myocarditis in seven adolescents after Pfizer-BioNTech COVID-19 vaccination:
  5. Myocarditis and pericarditis after vaccination with COVID-19 mRNA: practical considerations for care providers:
  6. Myocarditis, pericarditis and cardiomyopathy after COVID-19 vaccination:
  7. Myocarditis with COVID-19 mRNA vaccines:
  8. Myocarditis and pericarditis after COVID-19 vaccination:
  9. Myocarditis temporally associated with COVID-19 vaccination:
  10. COVID-19 Vaccination Associated with Myocarditis in Adolescents:
  11. Acute myocarditis after administration of BNT162b2 vaccine against COVID-19:
  12. Temporal association between COVID-19 vaccine Ad26.COV2.S and acute myocarditis: case report and review of the literature:
  13. COVID-19 vaccine-induced myocarditis: a case report with review of the literature:
  14. Potential association between COVID-19 vaccine and myocarditis: clinical and CMR findings:
  15. Recurrence of acute myocarditis temporally associated with receipt of coronavirus mRNA disease vaccine 2019 (COVID-19) in a male adolescent:
  16. Fulminant myocarditis and systemic hyper inflammation temporally associated with BNT162b2 COVID-19 mRNA vaccination in two patients:
  17. Acute myocarditis after administration of BNT162b2 vaccine:
  18. Lymphohistocytic myocarditis after vaccination with COVID-19 Ad26.COV2.S viral vector:
  19. Myocarditis following vaccination with BNT162b2 in a healthy male:
  20. Acute myocarditis after Comirnaty (Pfizer) vaccination in a healthy male with previous SARS-CoV-2 infection:
  21. Acute myocarditis after vaccination with SARS-CoV-2 mRNA-1273 mRNA:
  22. Acute myocarditis after SARS-CoV-2 vaccination in a 24-year-old man:
  23. A series of patients with myocarditis after vaccination against SARS-CoV-2 with mRNA-1279 and BNT162b2:
  24. COVID-19 mRNA vaccination and myocarditis:
  25. COVID-19 vaccine and myocarditis:
  26. Epidemiology and clinical features of myocarditis/pericarditis before the introduction of COVID-19 mRNA vaccine in Korean children: a multicenter study e/en/covidwho-1360706.
  27. COVID-19 vaccines and myocarditis:
  28. Myocarditis and other cardiovascular complications of COVID-19 mRNA-based COVID-19 vaccines
  29. Myocarditis and other cardiovascular complications of COVID-19 mRNA-based COVID-19 vaccines
  30. Myocarditis, pericarditis, and cardiomyopathy after COVID-19 vaccination:
  31. Myocarditis with covid-19 mRNA vaccines:
  32. Association of myocarditis with COVID-19 mRNA vaccine in children: vid-19-vaccine-in-children/
  33. Association of myocarditis with COVID-19 messenger RNA vaccine BNT162b2 in a case series of children:
  34. Myocarditis after immunization with COVID-19 mRNA vaccines in members of the U.S. military:
  35. Myocarditis occurring after immunization with COVID-19 mRNA-based COVID-19 vaccines:
  36. Myocarditis following immunization with Covid-19 mRNA:
  37. Patients with acute myocarditis after vaccination withCOVID-19 mRNA:
  38. Myocarditis associated with vaccination with COVID-19 mRNA:
  39. Symptomatic Acute Myocarditis in 7 Adolescents after Pfizer-BioNTech COVID-19 Vaccination:
  40. Cardiovascular magnetic resonance imaging findings in young adult patients with acute myocarditis after COVID-19 mRNA vaccination: a case series:
  41. Clinical Guidance for Young People with Myocarditis and Pericarditis after Vaccination with COVID-19 mRNA:
  42. Cardiac imaging of acute myocarditis after vaccination with COVID-19 mRNA:
  43. Case report: acute myocarditis after second dose of mRNA-1273 SARS-CoV-2 mRNA vaccine:
  44. Myocarditis / pericarditis associated with COVID-19 vaccine:
  45. The new COVID-19 mRNA vaccine platform and myocarditis: clues to the possible underlying mechanism:
  46. Myocarditis associated with COVID-19 vaccination: echocardiographic, cardiac tomography, and magnetic resonance imaging findings:
  47. In-depth evaluation of a case of presumed myocarditis after the second dose of COVID-19 mRNA vaccine:
  48. Occurrence of acute infarct-like myocarditis after COVID-19 vaccination: just an accidental coincidence or rather a vaccination-associated autoimmune myocarditis?:

This list is not meant to be all inclusive of all peer-reviewed potential harms from mRNA vaccines. To access any of the 1,000 Vaccine Harms published in Medical journals Click The Link Below:


Updated_Peer_Reviewed_medical_papers_submitted_to_various_medical.pdfDownload PDF • 1.01MB

Acute inflammatory demyelinating polyneuropathy or Guillain-Barré syndrome associated with COVID-19: a case report

Journal of Medical Case Reports volume 15, Article number: 219 (2021) 



Coronavirus disease 2019 (COVID-19) is a global pandemic. The disease, typically characterized by bilateral pulmonary infiltrates and profound elevation of inflammatory markers, can range in severity from mild or asymptomatic illness to a lethal cytokine storm and respiratory failure. A number of recognized complications of COVID-19 infection are described in the literature. Common neurological complications include headache and anosmia. Guillain-Barré syndrome (GBS) is an uncommon complication described in isolated case reports. However, a causal relationship has yet to be established. This case report adds to the growing body of evidence that GBS is a potential COVID-19 complication.

Case presentation

A 70-year-old Caucasian woman with recently diagnosed COVID-19 infection presented to the emergency department with 4 days of gradually worsening ascending lower extremity weakness. Exam revealed bilateral lower extremity weakness, mute reflexes, and sensory loss. Soon after starting intravenous administration of immunoglobulin (IVIG), the patient developed respiratory distress, eventually requiring intubation. She remained intubated for the duration of her IVIG treatment. After five rounds of treatment, the patient was successfully extubated and transferred to acute rehab. Following 4 weeks of intense physical therapy, she was able to walk with assistance on room air.


At the present time, this is one of the few reports of acute inflammatory demyelinating polyneuropathy (AIDP) or GBS associated with COVID-19 in the United States. It is unclear whether a causal relationship exists given the nature of the syndrome. However, in light of the growing number of reported cases, physicians should be aware of this possible complication when evaluating COVID-19 patients.

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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.

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CDC Study: Side Effects Of Covid Far More Dangerous Than Any Of Vaccines

The possibility of experiencing a serious adverse effect from the covid shots approved in the U.S. is significantly lower than the chances of severe illness, hospitalization or death from contracting covid, new research from the Centers for Disease Control and Prevention shows. Other studies show covid’s pregnancy impact and vaccine protection against the delta variant.

Bay Area News Group: COVID-19 Far Riskier Than Vaccines, New CDC Study SaysHow risky are the COVID-19 vaccines? A new study by the U.S. Centers for Disease Control and Prevention found that the risk of illness, hospitalization and death following the shots is far lower than the danger from becoming infected with the highly contagious and often deadly virus. Three health threats have surfaced among some vaccinated people: Blood clots and the Guillain-Barre Syndrome neurologic disorder after the Johnson & Johnson shot, and heart inflammation after the Pfizer or Moderna shots, which use a messenger-RNA technology. But the CDC analysis found that the risk in adults from the vaccines to be minimal compared to the virus that causes COVID-19, which has infected 35 million Americans and killed more than 614,000. (Woolfolk, 8/10)

San Francisco Chronicle: Devastating Impact Of COVID On Pregnancy Highlighted By Large UCSF StudyPregnant women infected with the coronavirus are at significantly higher risk for adverse complications, including preterm birth, according to a University of California San Francisco analysis of all documented births in the state between July 2020 and January 2021. In the largest study of its kind, researchers found the risk of very preterm birth, which occurs at less than 32 weeks of gestation, was 60% higher for people infected with the coronavirus during their pregnancy. The risk of giving birth at less than 37 weeks — which is any preterm birth — was 40% higher. (Vaziri, 8/10)

USA Today: Study Showing Antibody Levels Protecting Against COVID-19 Could Speed Creation Of New Vaccines, BoostersEagerly anticipated new research pinpoints antibodies scientists can test for to see if a COVID-19 vaccine is effective. These “correlates of protection” could speed the development of new vaccines or boosters without requiring the enormous clinical trials used to create the first COVID-19 vaccines. Instead, researchers could vaccinate people with a new vaccine or booster, measure their antibodies over the course of several months, and know if it worked. This is “the Holy Grail” in terms of vaccines, and one that hasn’t yet been set for the virus that causes COVID-19, said Peter Gilbert, co-author of the study posted Tuesday to medRxiv, a preprint site where scientific articles can be published prior to being accepted by peer-reviewed journals. (Weise, 8/10)

Reuters: Moderna May Be Superior To Pfizer Against Delta; Breakthrough Odds Rise With TimeThe mRNA vaccine from Pfizer and BioNTech may be less effective than Moderna’s against the Delta variant of the coronavirus, according to two reports posted on medRxiv on Sunday ahead of peer review. In a study of more than 50,000 patients in the Mayo Clinic Health System, researchers found the effectiveness of Moderna’s vaccine against infection had dropped to 76% in July – when the Delta variant was predominant – from 86% in early 2021. Over the same period, the effectiveness of the Pfizer/BioNTech vaccine had fallen to 42% from 76%, researchers said. While both vaccines remain effective at preventing COVID hospitalization, a Moderna booster shot may be necessary soon for anyone who got the Pfizer or Moderna vaccines earlier this year, said Dr. Venky Soundararajan of Massachusetts data analytics company nference, who led the Mayo study. (Aug. 9)

Also —

The Washington Post: Johnson & Johnson Coronavirus Vaccine Recipients Worry They Chose The Wrong Brand New research offers encouraging evidence about how the Johnson & Johnson vaccine stacks up against its competitors — and the delta variant — according to infectious-disease specialists. However, there are still lingering questions about booster shots. Earlier clinical trials showed the Johnson & Johnson vaccine was 66 percent effective overall in preventing moderate to severe disease four weeks after the shot, with effectiveness varying depending on location. Its competitors from Pfizer and Moderna, on the other hand, recorded 90 percent-plus effectiveness against the coronavirus. Anthony S. Fauci, the nation’s leading infectious-disease expert, has said all three vaccines are effective. (Beachum, Bever and Iati, 8/10)

CIDRAP: Viral COVID-19 Detected In Singing, Talking, Breathing Between breathing, singing, and talking, researchers detected SARS-CoV-2 RNA copies mostly from talking and singing (94%), and 85% of all viral particles were detected in fine aerosols, according to a small study late last week in Clinical Infectious Diseases. The researchers had 22 COVID-19 patients at Singapore’s National Centre for Infectious Diseases breathe for 30 minutes, talk for 15 minutes, or sing for 15 minutes into a G-II exhaled breath collector. Thirteen patients (59%) had detectable SARS-CoV-2 levels, of whom three were asymptomatic and one was presymptomatic. Variables such as age, sex, virus variant, and clinical symptoms were not significantly associated with detectable viral RNA in aerosols, but median day of illness was, with a higher likelihood earlier on in a patient’s illness (median, 3 vs 5 days after illness onset). (8/9)

Biden team’s misguided and deadly COVID-19 vaccine strategy

Vaccination ‘arms race’ could prove dangerous to the American public

Authors: Dr. Robert Malone and Peter Navarro

The Biden administration’s strategy to universally vaccinate in the middle of the pandemic is bad science and badly needs a reboot.

This strategy will likely prolong the most dangerous phase of the worst pandemic since 1918 and almost assuredly cause more harm than good – even as it undermines faith in the entire public health system.

Four flawed assumptions drive the Biden strategy. The first is that universal vaccination can eradicate the virus and secure economic recovery by achieving herd immunity throughout the country (and the world).  However, the virus is now so deeply embedded in the world population that, unlike polio and smallpox, eradication is unachievable. SARS-CoV-2 and its myriad mutations will likely continually circulate, much like the common cold and influenza.

The second assumption is that the vaccines are (near) perfectly effective. However, our currently available vaccines are quite “leaky.” While good at preventing severe disease and death, they only reduce, not eliminate, the risk of infection, replication, and transmission. As a slide deck from the Centers for Disease Control has revealed, even 100% acceptance of the current leaky vaccines combined with strict mask compliance will not stop the highly contagious Delta variant from spreading.

The third assumption is that the vaccines are safe.  Yet scientists, physicians, and public health officials now recognize risks that are rare but by no means trivial.  Known side effects include serious cardiac and thrombotic conditions, menstrual cycle disruptions, Bell’s Palsy, Guillain Barre syndrome, and anaphylaxis.

Unknown side effects which virologists fear may emerge include existential reproductive risks, additional autoimmune conditions, and various forms of disease enhancement, i.e., the vaccines can make people more vulnerable to reinfection by SARS-CoV-2 or reactivation of latent viral infections and associated diseases such as shingles.  With good reason, the FDA has yet to approve the vaccines now administered under Emergency Use Authorization.

The failure of the fourth “durability” assumption is the most alarming and perplexing.  It now appears our current vaccines are likely to offer a mere 180-day window of protection – a decided lack of durability underscored by scientific evidence from Israel and confirmed by  Pfizer, the Department of Health and Human Services, and other countries. 

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