Thin, leaky cerebral blood vessels found in COVID-19

Microvascular brain injury was found in dead COVID-19 patients, but no evidence of a direct viral attack on the brain was detected, pathological reports showed.

Damage caused by cerebrovascular thinning and leakage consistently appeared on high-resolution MRI, but tissue samples showed no signs of SARS-CoV-2 infection, National Institute of Neurological Disorders and Stroke Studies Clinical director of the institute, Avindra Nath, MD (NINDS), and co-author New England Journal of Medicine letter.

“We found that there were many lesions of small blood vessel injuries that had leaked blood products into brain tissue,” said Nath. “The cause of this is not clear, but it is most likely due to damage from immune cells or lymphocytes. It turns out that some lymphocytes are attached to the endothelial cells of the blood vessels and the perivascular area. “He said. Today’s MedPage..

“The inflammatory response is the key to the neuropathology of this syndrome because we couldn’t find the virus in the brain,” Nath added. “This study may have important implications for some structures in the brain, especially long-term damage to the olfactory bulb and brainstem.”

Other researchers have found that SARS-CoV-2 RNA and proteins Brain and nasopharynx Among the patients who died of COVID-19, the highest levels of viral RNA were found in the olfactory mucosa.

In this study, Nath et al. Found brain tissue samples of COVID-19 patients (16 from the Chief Coroner’s Office in New York City and 3 from the University of Iowa at the University of Iowa) who died between March and July 2020. I checked. Their analysis included 11.7 T MRI images of 13 patients with olfactory bulb resolution of 25 μm and brain resolution of 100 μm, as well as conventional histopathological brain examinations of 18 patients. ..

Ages ranged from 5 to 73 years with a median of 50 years. 14 patients suffered from chronic illnesses such as diabetes and high blood pressure, and 11 died or died suddenly. Of the 16 patients with a medical history, 1 had delirium, 5 had mild respiratory symptoms, 4 had acute respiratory distress syndrome, 2 had pulmonary embolism, and 3 had unknown symptoms.

Magnetic resonance force microscopy showed punctate hyperintensity representing areas of microvascular injury and fibrinogen leakage in 9 patients, correlating with histopathological examinations that showed thinning of the basement membrane of endothelial cells.

In contrast, the punctate low intensity of 10 patients responded to fibrinogen leakage and congested vessels with areas of the “relatively intact vasculature,” the researchers said. They also observed minimal perivascular inflammation, but no vascular occlusion. Other studies..

Perivascularly activated microglia, macrophage infiltration, and hypertrophic astrocytes were found in 13 patients. In eight patients, T cells were observed in the perivascular space and in the lumen adjacent to the endothelial cells.

“We were completely surprised,” Nath said. “Initially, we expected to see damage caused by lack of oxygen. Instead, we saw multiple areas of injury, usually associated with stroke and neuroinflammatory disease.”

SARS-CoV-2 was not detected in brain tissue, but it may have been removed by the time the virus died, or the copy number of the virus was below the level detected by the assay used.

So far, the findings suggest that the injury was not caused by a direct brain infection, Nath observed. Due to the limited clinical information available in this study, it is not possible to conclude how these findings relate to the neurological features of COVID-19.

However, research is underway to “further characterize patterns of inflammatory infiltration and nerve damage in autopsy materials,” Nath said.In addition, NINDS researchers Cohort of COVID-19 patients with neurological sequelae To determine if they also have microvascular injury and if inflammatory infiltration is associated with persistent neurological symptoms.