Enough already: T cell inflammation and SARS-CoV-2 virus persist in Long Covid

It is estimated that 6% of American adults currently suffer from persistent symptoms that can linger for weeks to years after COVID-19 infection. Some studies suggest that viral persistence and immune dysregulation may be to blame. Peluso and co-authors carried out whole-body positron emission tomography (PET) imaging of 24 patients 27 to 910 days after COVID-19 infection using a radioactive tracer that specifically identifies activated CD8 and CD4 lymphocytes. Imaging identified persistent T cell activation in patients after COVID compared with prepandemic controls. Post-COVID inflammation was detected in many tissues, including the brainstem, spinal cord, bone marrow, lymphoid tissues, heart, lungs, and gut. Inflammation was even observed in patients who did not have persistent COVID symptoms. Patients with symptomatic Long Covid tended to have persistent inflammation in the spinal cord and intestinal wall; uptake in the lower lungs was only observed in patients with persistent pulmonary symptoms. Five individuals with Long Covid consented to biopsies of the rectum or sigmoid colon 158 to 676 days after COVID infection. Viral spike protein–encoding single-stranded RNA was detected in multiple biopsies from four of five patients, and biopsies from three patients had viral double-stranded RNA, suggesting ongoing productive viral infection. The results suggest that tissue-based inflammation and viral persistence contribute to Long Covid symptoms and that even clinically mild COVID infection can cause lingering inflammation in peripheral tissues. Additional studies are needed to determine where and how the virus persists in peripheral tissues and identify why dysfunctional T cells cause inflammation but fail to clear the infection.