Brain inflammation seen in fatal COVID-19 cases

By Angela Betsaida B. Laguipo, BSNSep 9 2020

The coronavirus disease (COVID-19) is primarily a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in the pandemic, most of the symptoms reported were cough, fever, and difficulty of breathing, and in worse cases, patients develop pneumonia and acute respiratory distress syndrome (ARDS).

As the illness evolved, gastrointestinal and neurological symptoms were also reported in some patients. Previous studies have shown that due to the expression of the angiotensin-converting enzyme 2 (ACE2) receptors in many cell types, it allows the entry of the virus into cells.

SARS-CoV-2 viruses binding to ACE-2 receptors on a human cell, the initial stage of COVID-19 infection, conceptual 3D illustration. Image Credit: Kateryna Kon / Shutterstock

Now, a new study by researchers at the Barts Health NHS Trust and the University of Cambridge in the United Kingdom shows that some patients develop neurological complications tied to COVID-19.

The study, published as an ‘early release’ in the journal Neuropathology and Applied Neurobiology, aims to describe the neuropathological findings in two patients who died from the coronavirus disease. The two fatalities exhibited a neurological decline.

The researchers gathered information from the two patients who tested positive for SARS-CoV-2 via reverse transcription-polymerase chain reaction (RT-PCR) from nasopharyngeal swabs before their death. To examine the effect of the virus on the brain, the team performed coronial autopsies on both patients, and histological sampling of the brain tissue was done.

The first patient examined showed severe multifocal cortical infarction with extensive perivascular calcification and several megakaryocytes, consistent with a severe multi-territorial cerebral vascular injury. Apart from these, the patient also manifested cerebral thrombotic microangiopathy.

The second patient showed encephalitis of the brain stem, which involves inflammation. The inflammation was focused on the dorsal medulla and a subacute regional infarct of the cerebral cortex. However, in both cases, the tissue samples from the brain showed negative results.

The research findings add to other neuropathological findings seen in some patients with COVID-19. The team did not detect viral RNA of SARS-CoV-2 in the brain tissue of the patients, suggesting that the brain affectations may not be a direct effect of the virus and its proliferation. These complications in the brain may be the cause of para-infectious phenomena tied to systemic hyperinflammatory and hypercoagulable syndromes.

The cytokine storm may have triggered the inflammation in the brain, which is considered an overreaction of the immune system in its battle against an invading pathogen.

“The prevention and treatment of these two conditions would be diametrically different, and only the correlation of post-mortem examination with antemortem clinical features and imaging will provide a robust understanding of the pathophysiological heterogeneity in what may superficially seem like a homogenous clinical phenotype,” the researchers wrote in the paper.

Early in the pandemic, most patients manifested respiratory disease. But, as the disease progressed and spread across the globe, some patients infected with SARS-CoV-2 are experiencing an array of effects on the brain, including confusion, loss of smell and taste, and even strokes.

Other symptoms of neurological affectation from COVID-19 include loss of consciousness, seizures, confusion, headaches, problems with concentration, and changes in behavior.

Scientists believe that there are four ways of how the virus can affect the brain. These include severe infarction, immune system overdrive, physiological changes induced by the virus, and blood clotting abnormalities.

In severe infection, the virus may enter the brain and cause severe infarction. In some cases in China and Japan, virus genetic material or RNA was detected in the spinal fluid. Meanwhile, one case in the United States had a virus in the brain tissue.

The brain can also be affected by the overdrive of the immune system. As mentioned earlier, the immune system may go overdrive in an attempt to fight the virus. As a result, massive inflammation may occur, and the immune system may produce a maladaptive inflammatory response, which can lead to organ damage

Further physiological effects of the virus can overwhelm the body, as it experiences numerous symptoms, such as fever, low oxygen levels, and multiple organ failures, which can affect the brain.

Lastly, blood clotting abnormalities tied to the infection may lead to strokes. When a blood clot forms, it can travel and dislodge in the veins and arteries, impeding blood flow.