Abstract
Post-acute sequelae of COVID-19 (PASC) is emerging as global problem with unknown molecular drivers. Using a digital epidemiology approach, we recruited 8,077 individuals to the cohort study for digital health research in Germany (DigiHero) to respond to a basic questionnaire followed by a PASC-focused survey and blood sampling. We report the first 318 participants, the majority thereof after mild infections. Of those, 67.8% report PASC, predominantly consisting of fatigue, dyspnea, and concentration deficit, which persists in 60% over the mean 8-month follow-up period and resolves independently of post-infection vaccination. PASC is not associated with autoantibodies, but with elevated IL-1β, IL-6, and TNF plasma levels, which we confirm in a validation cohort with 333 additional participants and a longer time from infection of 10 months. Blood profiling and single-cell data from early infection suggest the induction of these cytokines in COVID-19 lung pro-inflammatory macrophages creating a self-sustaining feedback loop.
Keywords: COVID-19; IL-1β; IL-6; PASC; SARS-CoV-2; TNF; cytokine; long covid; macrophage; post-acute sequelae of COVID-19.
【저자키워드】 COVID-19, SARS-CoV-2, Macrophage, IL-6, cytokine, Long COVID, PASC, TNF, IL-1β, post-acute sequelae of COVID-19., 【초록키워드】 vaccination, fatigue, Epidemiology, Infection, lung, cohort study, Health, Germany, autoantibodies, Dyspnea, Research, plasma, molecular, questionnaire, single-cell, Blood, Concentration, early infection, Post-infection, Drivers, Participants, follow-up period, individual, participant, validation cohort, pro-inflammatory, mild infections, approach, recruited, elevated, majority, respond, the mean, creating, persist,