An early portrait of neuropathological features of COVID-19

An outbreak of atypical pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was initially reported in December 2019 from Wuhan in China.1 Since then, over 44 million people worldwide have been affected by the novel coronavirus disease 2019 (COVID-19).2 Owing to a high proportion of cases being asymptomatic or mildly symptomatic, the complete denominator of COVID-19 remains unknown.1 While literature is replete with pulmonary manifestations of COVID-19, its neurological complications are being increasingly recognized.1

Frequent neurological symptoms including headache, nausea and altered mental status have already been reported early on during the COVID-19 pandemic.3-5 Neurologic symptoms were observed in 36.4% of patients and more common in patients with severe infection according to their respiratory status, which included acute cerebrovascular events, impaired consciousness and muscle injury.5 The increasing presence of neurological symptoms being reported therefore established a further need to assess the viral-mediated neuropathogenesis of COVID-19 to facilitate better management and outcome improvement.1

A study conducted by Ms. Erica Normandin, a PhD candidate at Broad Institute, Cambridge, United States, and her colleagues, aimed to characterize the distribution of SARS-CoV-2 in the brain and identify the histopathological indications of its infection. Ms. Normandin further highlighted that, “We envisioned a study that would provide a comprehensive early portrait of the presence of virus in the brain, how much, where, how, and why it got there.”

The neuropathological findings from autopsies of 18 consecutive patients with SARS-CoV-2 infection who died in the period of April 14 and April 29, 2020 were reported. Patients were presented with neurologic symptoms including myalgia, headache and decreased taste. Coexisting conditions included diabetes mellitus, hypertension, cardiovascular disease, hyperlipidemia, chronic kidney disease, prior stroke, dementia, and treated anaplastic astrocytoma. Specimens from the frontal/olfactory lobe and medulla were collected from the 18 subjects and testing of the brain tissue was performed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and metagenomic sequencing.5

From the study analysis, both qRT-PCR and metagenomic sequencing identified limited SAR-CoV-2 in the brain. In contrast to >10,000 SARS-CoV-2 reads in COVID-19-positive lung samples identified through metagenomic sequencing, brain samples only contained 0-12 SARS-CoV-2 reads. Therefore, there was limited evidence of COVID-19 infection in the brain despite symptoms of neuropathology.

Immunohistochemical analysis was also performed in the same tissue blocks analyzed by qRT-PCR and found no staining of SARS-CoV-2 in the neurons, glia, endothelium or immune cells. While nonspecific staining in the choroid plexus was observed among 8 sections obtained from 7 patients, this signal was also present in the negative control brain samples and did not correlate with the qRT-PCR results. The only common observation between all patients was the presence of hypoxic ischemia identified in multiple regions, indicating that non-central nervous system organ damage is the most likely cause of the observed neurological symptoms.

Ms. Normandin thus concluded that, “This is a really early report of whether the virus is affecting neuropathology directly and we did not find any strong evidence for that. Many reports since then have been consistent with these results.” To identify the underlying cause of the observed neurological findings, Ms. Normandin commented that there have been hypotheses but more research is needed to consolidate the true association between SAR-CoV-2 infection and neurological complications.

  1. Desai I et al. Neurological manifestations of coronavirus disease 2019: exploring past to understand present. Neurol Sci. 2021;42(3):773-785.
  2. Wildwing T et al. The neurological symptoms of COVID-19: a systematic overview of systematic reviews, comparison with other neurological conditions and implications for healthcare services. Ther Adv Chronic Dis. 2021;12:2040622320976979.
  3. Giacomelli A et al. Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study. Clin Infect Dis. 2020;71(15):889-890.
  4. Lechien JR et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;277(8):2251-2261.
  5. Mao L et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683-690.