Open AccessSystemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients
Author(s) -
Jan Cato Holter,
Søren Erik Pischke,
Eline de Boer,
Andreas Lind,
Synne Jenum,
Aleksander Rygh Holten,
Kristian Tonby,
Andreas BarrattDue,
Marina Sokolova,
Camilla Schjalm,
Viktoriia Chaban,
Anette Kolderup,
Trung Tran,
Torleif Tollefsrud Gjølberg,
Linda Gail 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 LundJohansen,
Lars Heggelund,
Anne Ma DyrholRiise,
Tom Eirik Mollnes
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2010540117
Subject(s) - complement system , complement (music) , innate immune system , immunology , medicine , respiratory failure , respiratory system , alternative complement pathway , immunity , covid-19 , immune system , biology , disease , biochemistry , complementation , gene , phenotype , infectious disease (medical specialty)
Respiratory 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 PO 2 /FiO 2 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.