Escalated complement activation during hospitalization is associated with higher risk of 60-day mortality in SARS-CoV-2-infected patients.
| Autor: | Barratt-Due A; Department of Anesthesia and Intensive Care Medicine, Oslo University Hospital, Oslo, Norway., Pettersen K; Research Laboratory, Nordland Hospital Trust, Bodø, Norway., Børresdatter-Dahl T; Research Institute for Internal Medicine, Oslo University Hospital, Oslo, Norway., Holter JC; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Microbiology, Oslo University Hospital, Oslo, Norway., Grønli RH; Research Laboratory, Nordland Hospital Trust, Bodø, Norway., Dyrhol-Riise AM; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway., Lerum TV; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Pulmonary Medicine, Oslo University Hospital, Oslo, Norway., Holten AR; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Acute Medicine, Oslo University Hospital, Oslo, Norway., Tonby K; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway., Trøseid M; Research Institute for Internal Medicine, Oslo University Hospital, Oslo, Norway.; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, University of Oslo, Oslo, Norway., Skjønsberg OH; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Pulmonary Medicine, Oslo University Hospital, Oslo, Norway., Granerud BK; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Microbiology, Oslo University Hospital, Oslo, Norway., Heggelund L; Department of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway.; Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway., Kildal AB; Department of Anesthesiology and Intensive Care, University Hospital of North Norway, Tromsø, Norway.; Department of Clinical Medicine, Faculty of Health Sciences, UIT-The Arctic University of Norway, Tromsø, Norway., Schjalm C; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Immunology, Oslo University Hospital, Oslo, Norway., Aaløkken TM; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway., Aukrust P; Research Institute for Internal Medicine, Oslo University Hospital, Oslo, Norway.; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, University of Oslo, Oslo, Norway., Ueland T; Research Institute for Internal Medicine, Oslo University Hospital, Oslo, Norway.; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway., Mollnes TE; Research Laboratory, Nordland Hospital Trust, Bodø, Norway.; Department of Immunology, Oslo University Hospital, Oslo, Norway., Halvorsen B; Research Institute for Internal Medicine, Oslo University Hospital, Oslo, Norway.; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Journal of internal medicine [J Intern Med] 2024 Jul; Vol. 296 (1), pp. 80-92. Date of Electronic Publication: 2024 Mar 27. |
| DOI: | 10.1111/joim.13783 |
| Abstrakt: | Background: The 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. Methods: Serial 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 (PO Findings: During 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. Conclusion: Hospitalized 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.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|
Plný text