Two unrelated COVID-19 studies across the globe–a German post-mortem study and one following hospitalized patients at the peak of the epidemic in New York City—found neuropathological changes in patients with the virus, but no evidence that the SARS-CoV2 virus itself causes these changes in the central nervous system. Instead, both studies concluded that injuries to the brain were likely sequelae of severe systemic illness caused by the virus

Morbidity Analysis

Neurological complications occurred in just over 13 percent of 4,491 hospitalized patients in New York City with COVID-19 between March and May 2020, according to data appearing in the Oct. 5 online edition of Neurology. Furthermore, these neurological injuries raised patients' risk of death by 38 percent while in the hospital. However, in patients who were tested, cerebrospinal fluid specimens were negative for SARS-CoV-2 on real-time reverse transcription polymerase chain reaction (RT-PCR tests).
“The results of our study showed no signs that the coronavirus directly attacks the nervous system,” lead investigator Jennifer A. Frontera, MD, professor of neurology at NYU Grossman School of Medicine, told Neurology Today. “The neurological complications seen in COVID-19 are predominately the secondary effects of being severely ill and suffering from low oxygen levels in the body for prolonged periods of time,” she said.In comments to Neurology Today, Dr. Liotta remarked that historically, based on the literature, between 20 and 30 percent of patients admitted to the ICU are considered delirious or are diagnosed with some type of encephalopathy.
Commenting on the German postmortem study, Dr. Mukerji noted that it is important to note that the neuroinflammation located in the brainstem was not associated with identifying SARS-CoV-2. “While brainstem inflammation has been identified in other COVID-19 autopsy cohorts, we and others caution about overinterpreting this finding. Many patients included in autopsy cohorts had respiratory failure and were intubated, and findings may not apply to patients who did not experience critical illness. It is absolutely critical to compare COVID-19 brain autopsies with COVID-19-negative autopsy studies from patients who have had systemic inflammatory/septic shock to understand the possible direct effects of the virus versus consequences of critical illness.”
Dr. Frontera, who was not involved with the study from Germany, commented that “the areas where they identified the virus was not located in the spots with the most pathological abnormalities.” She also noted that the number of RNA copies at 4,500 was low and “raises the specter of blood contamination.” She speculated that it could be possible for “brain injury from hypoxia, for instance, which caused the blood-barrier breakdown, thus enabling the virus can pass through and possibly worsen the hypoxia or perhaps be an innocent bystander because it's not sitting near the worse pathological areas.”
“When you are dealing with virus and infections, you must ask whether the virus is directly affecting the brain structure or the spinal cord or the nerves, or are these all factors associated with the systemic infection that impacts the brain or spinal cord,” said Carlos A. Pardo, MD, professor of neurology and pathology at Johns Hopkins University. “The answer is the latter in COVID-19. The SARS-CoV2 is producing is causing systemic infection resulting in systemic inflammation.” This, he noted, is demonstrated somewhat in both the New York study as well as the German post-mortem study.
“The neurologic problems practitioners are seeing are due to systemic complications such as strokes, coagulation problems, or systemic inflammation. There is no evidence that this disease is producing encephalitis in the strict sense of the word, which could cause coma and produce damage of neurons or brain structure. But the situation we are seeing with COVID- 19 is a dramatic effect of the systemic effects of patients' illness,” Dr. Pardo said.