Description of COVID-19 and brain injury

In a recent study published in brain Journal, US researchers analyzed neurovascular injury in coronavirus disease 2019 (COVID-19).

study: Neurovascular injury with complement activation and inflammation in COVID-19.. Image Credit: DOERS / Shutterstock

Background

Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can experience many neurological problems. In fact, 1-5% of hospitalized COVID-19 patients suffer from stroke, and some do not have existing risk factors. However, it remains unclear how SARS-CoV-2 causes short-term and long-term neurological symptoms. In addition, it is still unclear whether SARS-CoV-2 infects brain cells or whether these abnormalities are secondary to immunostimulatory events.

About research

Current studies aim to define neuropathological abnormalities in patients with COVID-19 and to identify the pathophysiological processes that cause these changes. Researchers conducted a comprehensive immunohistopathological and virological study of autopsy brain tissue in dead COVID-19 patients.

Scientists evaluated nine COVID-19 patients who died during the first COVID-19 wave from March to July 2020. SARS-CoV-2 infection was confirmed by post-mortem or pre-mortem screening. In addition, they performed a descriptive assessment of pathological changes and a quantitative assessment of infiltration and vascular modification.

In a current brain autopsy study, the team used immunohistochemistry to explain vascular pathology, changes in neuroinflammation, humoral and cell-mediated immune responses. Autopsy brain tissue, including the temporal and frontal lobes, olfactory sphere, basal ganglia, thalamus, hippocampus, midbrain, cerebellum, pons, and medulla oblongata, was subjected to immunohistochemical examination.

Researchers investigated whether angiopathy may be associated with endothelial cell dysfunction. In addition, they searched for immunoglobulin accumulation to assess whether endothelial cell damage was an immune-induced process.

Results, discussions, conclusions

Taken together, multiple large proteins, such as immunoglobulin M (IgM), that normally do not cross the blood-brain barrier, are present in the perivascular region of deceased COVID-19 patients and are of vascular integrity in these patients. Showed a decline. High fibrinogen levels were found near the blood vessels, and the concentration gradually decreased with increasing distance from the vasculature, indicating a porous blood-brain barrier. In addition, indicators of vascular injury were more frequent throughout the posterior brain.

Endothelial cells had high platelet endothelial cell adhesion molecule 1 (PECAM-1) titers. However, the cause of the increase in PECAM-1 is unknown. In particular, this study found that PECAM-1 functions as an deposit on platelets and their aggregates attached to endothelial cells.

Stimulated platelets occasionally caused blockage of small blood vessels confirmed by spatial transcriptional data. Tissue factor (TF) and the CD74 gene help distinguish COVID-19 patients from controls and help develop thrombi.

Compared to controls, COVID-19 patients had higher levels of signaling pathways for semaphores and ras homologous guanosine diphosphate dissociation inhibitors (RhoGDI) that correlated with vascular permeability. These inferences explained the microinfarcts observed by magnetic resonance imaging (MRI) in some SARS-CoV-2 patients.

Interestingly, the team discovered 25 angiogenesis-related genes that are contrastingly expressed in the brains of COVID-19 patients. This corresponded to previous studies on the lungs. They also identified dysregulation of signaling pathways involved in angiogenesis. Histopathological findings were comparable to dysregulation of these vascular genes.

Endothelial cells and platelet aggregates had a mass of IgM and IgG that co-localized with many complement cascade components. The presence of C4d, C1q, and C5b-9 was a sign of an activated classical complement network. The team also discovered C1q and C3 deposition in macrophages and endothelial cells caused by the SARS-CoV-2 spike (S) protein.

Immunohistochemistry, consistent with previous reports, revealed cell infiltration of macrophages, CD8 +, and CD4 + T cells in COVID-19 patients. Similarly, spatial transcriptomics data showed that regions with high concentrations of PECAM-1 + or CD45 + cells, such as RhoGDI, enhance signaling pathways involved in the migration or transport of these cells.

Despite the low amount of T cells, CD8 + cells outnumber CD4 + cells, B cells are relatively rare, and inflammatory infiltration into the perivascular zone as macrophages act as scavengers and assist repair procedures. It has been shown to be secondary to the release of serum proteins in.

Neurons and glia absorbed serum proteins such as complement and fibrinogen. Similarly, astrogliosis is the most common in the perivascular domain, indicating that this condition is associated with vascular injury. The cerebellum and other hindbrain regions have experienced multifocal depletion of neurons.

COVID-19 increased sirtuins and other genes, as well as signaling pathways associated with oxidative stress and deoxyribonucleic acid (DNA) disorders. Interestingly, most pathological observations were more frequent in the posterior brain, consistent with previous reports, but the reason is still unknown.

Importantly, five participants in the study died suddenly, most of them during sleep, so it is necessary to consider central apnea, even if autonomic imbalance or cardiac arrhythmia may be involved. there is. According to spatial transcriptional data, most of the differently regulated pathways were associated with immune response.

The authors suggested that antibody-induced cytotoxicity targeting endothelial cells probably causes nerve inflammation, vascular leakage, platelet aggregation, and nerve damage.

Overall, the findings show that immune complexes with complement activation that damage the microvasculature are the main causes of blood-brain barrier disruption, microthrombosis, perivascular inflammation, and nerve damage in SARS-CoV-2 patients. I showed that it was the cause. The authors suggested that these events significantly affect the neurological symptoms seen in acute COVID-19 and possibly long-term COVID. Importantly, current findings indicate the need for treatments that target the development of immune complexes.