“Long COVID” caused by hidden viral reservoirs

Surviving a COVID-19 infection is only half the battle. About 20-30% of people who get COVID-19 develop post-acute sequelae of COVID-19 (PASC), commonly called “long COVID.”

Common symptoms of long COVID include fatigue, brain fog, shortness of breath, cough, chest pain, heart palpitations, headache, insomnia, and loss of taste or smell. These and other long COVID symptoms can be debilitating, with an estimated 1 million Americans out of work due to long COVID.

A recent study, published in PLOS pathogenscompared the frequencies of COVID-19-specific T cells and inflammatory markers with lung function in patients with pulmonary PASC or resolved COVID-19.

“The persistence of high numbers of virus-specific T cells in people with long COVID suggests that there may be hidden viral reservoirs that sustain and lead to long-term symptoms,” said Brent Palmer. , PhD, lead study author and associate. Professor of Allergy and Clinical Immunology at the University of Colorado School of Medicine.

“Current treatments for long COVID, by necessity, focus on treating specific symptoms and not on the root cause of the disease. This evidence indicates that reservoirs are an important factor causing long COVID, which may guide future treatments.

Palmer and his fellow researchers found that patients who suffered from long COVID had virus-specific T cell levels that were more than 100 times higher than in patients who fully recovered. Patients with PASC had frequencies of SARS-CoV-2-specific CD4+ and CD8+ T cells producing IFN-γ and TNF-α in peripheral blood that were 6 to 105 times higher.

In long COVID patients, higher levels of SARS-CoV-2 T cells correlated with higher levels of inflammation, indicating that T cells may be the source of these and other symptoms. The researchers concluded that elevated SARS-CoV-2 T-cell frequencies in patients with long-term COVID are associated with increased systemic inflammation and decreased lung function.

This study is the first to determine that COVID-19-specific T cells can affect lung function, causing long COVID. The findings may change COVID-19 treatment recommendations, leading to prioritization of vaccines and antivirals that target long-lasting COVID symptoms and eliminate the virus.

“Our findings hope to help shift the focus of treatment toward therapies that improve viral clearance,” Plamer explained. “For example, antiviral drugs like Paxlovid could help reduce symptoms in people burdened by long COVID, helping to clear the virus from their system and return them to a more normal life.”

Palmer and his team applied for a National Institutes of Health (NIH) grant to continue this long-running COVID research. If approved, they would investigate washing out T cells from the lungs with a noninvasive procedure, allowing them to compare cells from patients with and without long COVID.