Post-Acute Sequelae Patients with Severe COVID-19 History Show a Prolonged Inflammatory, Vascular Injury Pattern

SARS-CoV-2 infection can lead to persistent symptoms (i.e., long/post-COVID), especially in unvaccinated individuals. Little is known about the sustained impact of acute severe COVID-19 on immune signatures and long/post-COVID symptoms, often associated with cardiovascular events and pulmonary impairment. The longitudinal cohort (LC) was obtained from N = 46 patients with previous severe COVID-19 and prior to SARS-CoV-2 vaccination, collected over 5 visits up to 12 months after discharge (n = 139). Long/post-COVID status was assessed by lung function and fatigue scores. Blood was analysed regarding immune cell profiles, SARS-CoV-2 antibodies, and autoantigens. LC patients were compared with 39 acute severe COVID-19 ICU patients and 28 unexposed pre-pandemic donors (UE) and correlated with clinical parameters. LC patients exhibited long-term decreased CD4⁺/CD8⁺ T cell ratio, differentiation from naïve to TEMRA, CD57⁺CCR7^- memory, and HLA-DR⁺CD38⁺ activated CD4⁺ and CD8⁺ T cells. LC plasma profiles displayed elevated levels of markers for chronic inflammation and endothelial injury. Chronic inflammatory chemokines and cardiovascular markers remained high. These markers and autoantibodies against centromere structures negatively correlated with lung function. At 1-year post-discharge, LC patients with a COVID-19 ICU history displayed sustained significant changes in their immune profile at cellular and inflammatory levels, revealing signatures of persistent inflammation and endothelial injury.