AUTHOR=Hawerkamp Heike C. , Dyer Adam H. , Patil Neha D. , McElheron Matt , O’Dowd Niamh , O’Doherty Laura , Mhaonaigh Aisling Ui , George Angel M. , O’Halloran Aisling M. , Reddy Conor , Kenny Rose Anne , Little Mark A. , Martin-Loeches Ignacio , Bergin Colm , Kennelly Sean P. , Donnelly Seamas C. , Bourke Nollaig M. , Long Aideen , Sui Jacklyn , Doherty Derek G. , Conlon Niall , Cheallaigh Cliona Ni , Fallon Padraic G. TITLE=Characterisation of the pro-inflammatory cytokine signature in severe COVID-19 JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1170012 DOI=10.3389/fimmu.2023.1170012 ISSN=1664-3224 ABSTRACT=

Clinical outcomes from infection with SARS-CoV-2, the cause of the COVID-19 pandemic, are remarkably variable ranging from asymptomatic infection to severe pneumonia and death. One of the key drivers of this variability is differing trajectories in the immune response to SARS-CoV-2 infection. Many studies have noted markedly elevated cytokine levels in severe COVID-19, although results vary by cohort, cytokine studied and sensitivity of assay used. We assessed the immune response in acute COVID-19 by measuring 20 inflammatory markers in 118 unvaccinated patients with acute COVID-19 (median age: 70, IQR: 58-79 years; 48.3% female) recruited during the first year of the pandemic and 44 SARS-CoV-2 naïve healthy controls. Acute COVID-19 was associated with marked elevations in nearly all pro-inflammatory markers, whilst eleven markers (namely IL-1β, IL-2, IL-6, IL-10, IL-18, IL-23, IL-33, TNF-α, IP-10, G-CSF and YKL-40) were associated with disease severity. We observed significant correlations between nearly all markers elevated in those infected with SARS-CoV-2 consistent with widespread immune dysregulation. Principal component analysis highlighted a pro-inflammatory cytokine signature (with strongest contributions from IL-1β, IL-2, IL-6, IL-10, IL-33, G-CSF, TNF-α and IP-10) which was independently associated with severe COVID-19 (aOR: 1.40, 1.11-1.76, p=0.005), invasive mechanical ventilation (aOR: 1.61, 1.19-2.20, p=0.001) and mortality (aOR 1.57, 1.06-2.32, p = 0.02). Our findings demonstrate elevated cytokines and widespread immune dysregulation in severe COVID-19, adding further evidence for the role of a pro-inflammatory cytokine signature in severe and critical COVID-19.