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

PLoS One. 2024 Jul 15;19(7):e0304990. doi: 10.1371/journal.pone.0304990. eCollection 2024.

Abstract

Background: After initial COVID-19, 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.

Methods: RECoVERED 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 COVID-19 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.

Results: 186/349 (53%) participants had ≥2 serum samples and were included in current analyses. Of these, 101/186 (54%: 45/101[45%] female, median age 55 years [IQR = 45-64]) reported PASC at 12 and 24 weeks after COVID-19 onset. We included 37 reference samples (17/37[46%] female, median age 49 years [IQR = 40-56]). In a multivariate model, PASC was associated with raised CRP and abnormal diffusion capacity with raised IL10, IL17, IL6, IP10 and TNFα at 24 weeks. Early (0-4 week) IL-1β and BMI at COVID-19 onset were predictive of PASC at 24 weeks.

Conclusions: Our findings indicate that immune dysregulation plays an important role in PASC pathogenesis, especially among individuals with reduced pulmonary function. Early IL-1β shows promise as a predictor of PASC.

MeSH terms

  • Adult
  • Aged
  • COVID-19* / blood
  • COVID-19* / epidemiology
  • COVID-19* / immunology
  • Cytokines* / blood
  • Female
  • Humans
  • Inflammation / blood
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Post-Acute COVID-19 Syndrome
  • Prospective Studies
  • SARS-CoV-2* / isolation & purification

Substances

  • Cytokines

Grants and funding

This work was supported by the Netherlands Organization for Health Research and Development (ZonMw) [10150062010002 to M.D.d.J. and 10430072110003 to G.J.d.B] and the Public Health Service of Amsterdam [R&D grants in 2021 and 2022 to M.P.]. The funders had no role in study design, data collection, data analysis, data interpretation or data reporting. ZonMw website: https://projecten.zonmw.nl/nl/project/recovered GGD Amsterdam website: https://www.ggd.amsterdam.nl/ggd/.