• Proc. Natl. Acad. Sci. U.S.A. · Oct 2020

    Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients.

    • Jan C Holter, Soeren E Pischke, Eline de Boer, Andreas Lind, Synne Jenum, Aleksander R Holten, Kristian Tonby, Andreas Barratt-Due, Marina Sokolova, Camilla Schjalm, Viktoriia Chaban, Anette Kolderup, Trung Tran, Torleif Tollefsrud Gjølberg, Linda G Skeie, Liv Hesstvedt, Vidar Ormåsen, Børre Fevang, Cathrine Austad, Karl Erik Müller, Cathrine Fladeby, Mona Holberg-Petersen, Bente Halvorsen, Fredrik Müller, Pål Aukrust, Susanne Dudman, Thor Ueland, Jan Terje Andersen, Fridtjof Lund-Johansen, Lars Heggelund, Anne M Dyrhol-Riise, and Tom E Mollnes.
    • Department of Microbiology, Oslo University Hospital, 0424 Oslo, Norway.
    • Proc. Natl. Acad. Sci. U.S.A. 2020 Oct 6; 117 (40): 25018-25025.

    AbstractRespiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO2/FiO2 ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure (P = 0.008 and P = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, P = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, P = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin (r = 0.64, P < 0.001; r = 0.69, P < 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials.Copyright © 2020 the Author(s). Published by PNAS.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…