Inflammatory profiles are associated with long COVID up to 6 months after illness onset: a prospective cohort study of individuals with mild to critical COVID-19

BackgroundAfter initial COVID-19 disease, immune dysregulation may persist and drive post-acute sequelae of COVID-19 (PASC). We described longitudinal trajectories of cytokines in adults up to 6 months following SARS-CoV-2 infection and explored early predictors of PASC. MethodsRECoVERED is a prospective cohort of individuals with laboratory-confirmed SARS-CoV-2 infection between May 2020 and June 2021 in Amsterdam, the Netherlands. Serum was collected at weeks 4, 12 and 24 of follow-up. Monthly symptom questionnaires were completed from month 2 after illness onset onwards; lung diffusion capacity (DLCO) was tested at 6 months. Cytokine concentrations were analysed by human magnetic Luminex screening assay. We used a linear mixed-effects model to study log-concentrations of cytokines over time, assessing their association with socio-demographic and clinical characteristics that were included in the model as fixed effects. Results186/349 (53%) participants had [≥]2 serum samples and were included. Of these, 101 (54%: 45/101[45%] female, median age 55 years [IQR=45-64]) reported PASC at 12 and 24 weeks after illness onset. We included 37 reference samples (17/37[46%] female, median age 49 years [IQR=40-56]). PASC was associated with raised CRP and abnormal diffusion capacity with raised IL10, IL17, IL6, IP10 and TNF at 24 weeks in the multivariate model. Early (0-4 week) IL-1{beta} and BMI at illness onset were predictive of PASC at 24 weeks. ConclusionsOur findings indicate that immune dysregulation plays an important role in PASC pathogenesis, especially among those individuals with reduced pulmonary function. Early IL-1{beta} shows promise as predictors of PASC.