A small autopsy study examining brain tissue from patients who died from COVID-19 is offering new clues to how this novel coronavirus can lead to brain damage. The findings suggest an abnormal immune response could be damaging vascular cells in the blood-brain barrier, leading to many neurological symptoms associated with COVID-19.
“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” noted senior author Avindra Nath.
As the pandemic has progressed researchers have discovered COVID-19 is not just a straightforward respiratory disease. The short- and long-term effects of SARS-CoV-2 on the brain has been the focus of much recent study as doctors have seen COVID patients experience significantly high rates of blood clots and stroke.
A key study last year found COVID-19 patients showed significant damage to cerebral vascular endothelial cells, crucial components of the blood-brain barrier. It has been hypothesized that this endothelial cell damage could be the trigger that leads to neurological symptoms associated with COVID, but a pair of key questions still remained unanswered: How could this endothelial cell damage lead to neuron damage, and was it the virus directly causing the damage, or was this related autoimmune damage?
This new research, led by scientists from the National Institutes of Health, sheds some light on those questions. Following a close investigation of brain tissue from a small number of deceased COVID-19 patients, the research indicates the primary endothelial cell damage is likely linked to an abnormal immune response.
The study revealed immune biomarkers could be detected on the surface of these damaged endothelial cells. This initial damage to the cells activates them, triggering a cascade of events that is thought to result in the neurological symptoms we associate with both acute and long COVID.
“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur,” Nath explained. “At the same time the tight junctions between the endothelial cells get disrupted causing them to leak. Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”
Despite some prior studies suggesting SARS-CoV-2 could be detected in the brain, this study found no trace of the virus in any tissue. So it still is a mystery as to why the immune system would suddenly target healthy cells following a SARS-CoV-2 infection. One hypothesis offered is that immune antibodies generated to target the coronavirus may also be incidentally attacking healthy tissue that share the ACE2 receptor used by the virus to infect our cells.
Although this study offers the most robust characterization of the events that could lead to the neurological problems associated with COVID-19, it certainly isn’t the first to suggest an inflammatory cause is behind these symptoms. A detailed study from scientists at Stanford last year pointed to “profound molecular markers of inflammation” in the brains of deceased COVID patients.
Another small study earlier this year found markers of inflammation in the cerebrospinal fluid of several long COVID patients experiencing symptoms of “brain fog”. All of these findings present strong evidence to suggest a persistent immune response to SARS-CoV-2 infection could be responsible for many aspects of acute and long COVID.
“It is quite possible that this same immune response persists in Long COVID patients resulting in neuronal injury,” Nath said. “There could be a small indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So these findings have very important therapeutic implications.”
These findings do not mean some kind of broad immunosuppressive therapy is the cure for long COVID. Instead, the new research points to the potential development of more novel targeted treatments designed to specifically prevent these immune responses from damaging the brain.
The new study was published in the journal Brain.
Source: NIH