• J. Intern. Med. · Mar 2024

    Escalated complement activation during hospitalization is associated with higher risk of 60-day mortality in SARS-CoV-2-infected patients.

    • Andreas Barratt-Due, Kristin Pettersen, Tuva Børresdatter-Dahl, Jan Cato Holter, Renathe H Grønli, Anne Ma Dyrhol-Riise, Tøri Vigeland Lerum, Aleksander Rygh Holten, Kristian Tonby, Marius Trøseid, Ole H Skjønsberg, Beathe Kiland Granerud, Lars Heggelund, Anders Benjamin Kildal, Camilla Schjalm, Trond Mogens Aaløkken, Pål Aukrust, Thor Ueland, Tom Eirik Mollnes, Bente Halvorsen, and NOR‐Solidarity study groupThe Norwegian SARS‐CoV‐2 study group.
    • Department of Anesthesia and Intensive Care Medicine, Oslo University Hospital, Oslo, Norway.
    • J. Intern. Med. 2024 Mar 27.

    BackgroundThe complement system, an upstream recognition system of innate immunity, is activated upon SARS-CoV-2 infection. To gain a deeper understanding of the extent and duration of this activation, we investigated complement activation profiles during the acute phase of COVID-19, its persistence post-recovery and dynamic changes in relation to disease severity.MethodsSerial blood samples were obtained from two cohorts of hospitalized COVID-19 patients (n = 457). Systemic complement activation products reflecting classical/lectin (C4d), alternative (C3bBbP), common (C3bc) and terminal pathway (TCC and C5a) were measured during hospitalization (admission, days 3-5 and days 7-10), at 3 months and after 1 year. Levels of activation and temporal profiles during hospitalization were related to disease severity defined as respiratory failure (PO2/FiO2 ratio <26.6 kPa) and/or admission to intensive care unit, 60-day total mortality and pulmonary pathology after 3 months.FindingsDuring hospitalization, TCC, C4d, C3bc, C3bBbP and C5a were significantly elevated compared to healthy controls. Severely ill patients had significantly higher levels of TCC and C4d (p < 0.001), compared to patients with moderate COVID-19. Escalated levels of TCC and C4d during hospitalization were associated with a higher risk of 60-day mortality (p < 0.001), and C4d levels were additionally associated with chest CT changes at 3 months (p < 0.001). At 3 months and 1 year, we observed consistently elevated levels of most complement activation products compared to controls.ConclusionHospitalized COVID-19 patients display prominent and long-lasting systemic complement activation. Optimal targeting of the system may be achieved through enhanced risk stratification and closer monitoring of in-hospital changes of complement activation products.© 2024 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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