Long COVID still affects many people who had a case of COVID-19; even people who had mild cases and were not hospitalized are at risk for the chronic disorder. Scientists and clinicians are still learning about the illness, which causes a wide range of symptoms and happens for unknown reasons. There are several hypotheses, however, and the disorder may also arise in different people for different reasons. New research has suggested that long COVID happens because particles of SARS-CoV-2, the virus that causes COVID-19, hide away in parts of the body, and the immune system becomes overactivated trying to eliminate them. The study has been reported in PLOS Pathogens.
Symptoms of long COVID can include fatigue, brain fog, cough, shortness of breath, and chest pain, and these symptoms last more than four weeks after the acute phase of COVID-19. The illness is thought to impact about 20 percent of people who get COVID, noted Brent Palmer, Ph.D., an associate professor at the University of Colorado School of Medicine.
In this study, the researchers followed forty COVID-19 patients; twenty of them totally eliminated the infection and twenty developed long COVID, also known as post-acute sequelae of COVID (PASC). The investigators used blood and stool samples from the study volunteers to identify T cells that were specific to COVID-19 and remained active after the initial infection was over.
These cells were then incubated with bits of the virus, and the scientists were able to see how frequently CD4 and CD8 T cells were reacting by generating cytokines. They found that long COVID patients carried levels of cytotoxic CD8 T cells that were as much as 100 times higher compared to people who cleared the infection.
Palmer also studies HIV infection, and he was astonished to find that about 50 percent of T cells were still directed against COVID-19 six months after their initial infection. "That's an amazingly high frequency, much higher than we typically see in HIV, where you have ongoing viral replication all the time," he added. "These responses were in most cases higher than what we see in HIV."
CU pulmonologist Sarah Jolley, MD was a study co-author who obtained pulmonary data for the study volunteers. The researchers found that pulmonary function decreased as the level of COVID-19-specific T cells increased.
"That showed a really strong connection between these T cells that were potentially driving disease and an actual readout of disease, which was reduced pulmonary function. That was a critical discovery."
The researchers have suggested that long COVID is drive by the immune system, which is increasing inflammation as it attempts to remove residual SARS-CoV-2 particles that cannot be detected with a nasal swab, but nonetheless remain. Palmer noted that some autopsies of COVID-19 patients have revealed the virus in many organs including the lungs, gut and kidney.
Additional work by Palmer and colleagues was reported in the journal Gut; this study indicated that the composition of the gut microbiomes of long COVID patients reflects an elevation of inflammatory markers. There may also be a link between the gut microbiome and the inflammation that is observed in long COVID, noted the researchers.
Palmer added that some studies have shown that antiviral medications like Paxlovid, or doses of vaccine may help relieve the symptoms of long COVID patients. This may happen because their immune systems are being given enough of a stimulatory bump to finally remove the infection, and it would show that a hidden reservoir of virus likely exists in these patients.
Sources: CU Anschutz Medical Campus, PLOS Pathogens, Gut
