Insights into Immune Response Damaging the Brain after COVID-19 Infection

The peer-review journal Brain published the findings of a new study that focused on the underlying mechanisms by which the SARS-CoV-2 virus leads to acute and long-term neurological manifestations.

This National Institutes of Health study announced on July 5, 2022, describes the immune response triggered by COVID-19 infection that damages the brain's blood vessels and may lead to short- and long-term neurological symptoms.

In this brain autopsy study, these researchers characterized the vascular pathology, neuroinflammatory changes, and cellular and humoral immune responses by immunohistochemistry.

All study participants were found to have multifocal vascular damage as determined by leakage of serum proteins into the brain parenchyma.

'Injury to the microvasculature by immune complexes with complement activation is the key central event that results in the breakdown of the blood-brain barrier, microthromboses, perivascular inflammation, and neuronal injury.'

"Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood," commented Avindra Nath, M.D., clinical director at NINDS and the senior author of the study in an NIH press release.

"We had previously shown blood vessel damage and inflammation in patients' brains at autopsy, but we didn't understand the cause of the damage."

"I think in this paper, we've gained important insight into the cascade of events."

This was accompanied by widespread endothelial cell activation.

Platelet aggregates and microthrombi adhered to the endothelial cells along vascular lumina.

Immune complexes activating the classical complement pathway were found on the endothelial cells and platelets.

Perivascular infiltrates consisted of predominantly macrophages and some CD8+ T cells.

Only rare CD4+ T cells and CD20+ B cells were present.

Astrogliosis was also prominent in the perivascular regions, and microglial nodules were predominant in the hindbrain, which was associated with focal neuronal loss and neuronophagia.

Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely event leading to vascular leakage, platelet aggregation, neuroinflammation, and neuronal injury.

Therapeutic modalities directed against immune complexes should be considered.

The study builds on their previous research, which found evidence of brain damage caused by thinning and leaky blood vessels.

However, they suspected the damage may have been due to the body's natural inflammatory response to the coronavirus.

Importantly, these studies suggest that therapeutic approaches targeted against the development of immune complexes should be considered.

Note: This NIH announcement was manually edited for mobile readership.