Neuropathology associated with SARS-CoV-2 infection

Claus Hann von Weyhern and colleagues¹ describe autopsy findings of six patients who died of COVID-19. Better understanding of the central effects of COVID-19 is crucial, and we read with great interest their findings that included pan-encephalitis and meningitis in all six patients, regardless of whether cause of death was due to cardiorespiratory failure, pulmonary embolism, or intracranial haemorrhage. However, the images provided in the appendix of the Correspondence¹ do not clearly show meningitis or encephalitis. Shrunken neurons are a common histological finding in autopsy brains and are often observed in neurologically normal cases without any specific pathological change, and the small cells indicated as infiltrating lymphocytes are difficult to distinguish from glial cells in the absence of an immunostain showing interstitial lymphocytes. For example, we show similar findings in a section of a normal neocortex (appendix). Although neuron loss was observed by von Weyhern and colleagues, neuronophagia and microglial nodules were not described. Additionally, perivascular lymphocytes are not diagnostic of viral meningitis or encephalitis but perhaps suggest that COVID-19 is associated with vascular alterations.

The findings of published cases and our own limited experience with COVID-19 disease pathology support that when brain pathology is present, it is apparently often associated with vascular changes, such as thrombi or thromboemboli, rather than primary involvement of the CNS. Although instances with neuropathology consistent with severe acute respiratory syndrome coronavirus 2 encephalitis have been reported, these changes are generally mild and variable.2, 3, 4