Q&A: Controlling inflammation ‘might be key’ in neurological complications of COVID-19

Postmortem testing in a convenience sample of patients who died of COVID-19 demonstrated multifocal microvascular injury in the brain and olfactory bulbs without evidence of viral infection.

The findings reported in the correspondence, which was published in The New England Journal of Medicine, “may inform the interpretation of changes observed on MRI of punctate hyperintensities and linear hypointensities in patients with COVID-19,” according to the researchers. However, because of the limited clinical information available, the researchers also noted that “no conclusions” could be made regarding the neurological features of COVID-19.

Healio Neurology spoke with Avindra Nath, MD, chief of the section of infections of the nervous system and clinical director of the National Institute of Neurological Disorders and Stroke at the NIH, to learn more about the findings.

Q: What prompted this research?

A: Most patients with COVID-19 have neurological manifestations; however, the mechanisms by which they occur is largely unknown. We sought to determine the underlying pathology in the brain to look for clues, particularly to determine the extent to which the virus could be present in brain cells, determine the integrity of the brain cells and blood vessels in the brain and if there was evidence for inflammation in the brain.

Q: What did the results demonstrate?

A: Patients with COVID-19 frequently have neuropathological findings that may have been asymptomatic at the time of the acute infection. Some patients can die suddenly of the infection with no prior warning. For example, in our study, some patients died in their sleep, one was found dead in the New York subway and another patient who was lifting his sister fell down and died.

Patients often have multifocal brain disease that can easily be missed on pathological examination. However, we used postmortem high-resolution MRI scans that pinpointed where the lesions were. That allowed us to home into the regions of the brain to study by histological examination.

We found that there were many foci of small blood vessel damage, from which there was leakage of blood products into the brain tissue. The cause of this was not clear but is most likely due to damage from the immune cells or lymphocytes. We found some lymphocytes attached to the endothelial cells in the blood vessels and in the perivascular regions. The inflammatory response is key to the neuropathogenesis of this syndrome, since we were unable to find virus in the brain.

The study potentially has important implications for long-term damage to several structures in the brain, particularly the olfactory bulb and the brainstem.

Q: How might these findings be used in clinical practice?

A: The important practical implication is that controlling the inflammation might be key to managing the neurological complications of COVID-19.

Q: What are the next steps in this research?

A: We are further characterizing the inflammation in the brain of these patients to determine what triggered it and to determine the types of inflammatory molecules that are being produced. We are recruiting a cohort of the so-called COVID-19 “long-haulers” to determine if microvascular injury and inflammation might be driving their illness.