(Higher Education Institutional Excellence Programme of the Ministry of Human Capacities
in Hungary, within the framework of the molecular biology thematic program of the
Semmelweis University)
(KH130355)
(2020-1.1.6-JOVO-2021-00013)
(PPD2018-016/2018)
Objectives Uncontrolled thromboinflammation plays an important role in the pathogenesis
of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus. Complement was implicated
as key contributor to this process, therefore we hypothesized that markers of the
complement profile, indicative for the activation state of the system, may be related
to the severity and mortality of COVID-19. Methods In this prospective cohort study
samples of 102 hospitalized and 26 outpatients with PCR-confirmed COVID-19 were analyzed.
Primary outcome was in-hospital, COVID-19 related mortality, and secondary outcome
was COVID-19 severity as assessed by the WHO ordinal scale. Complement activity of
alternative and classical pathways, its factors, regulators, and activation products
were measured by hemolytic titration, turbidimetry, or enzyme-immunoassays. Clinical
covariates and markers of inflammation were extracted from hospital records. Results
Increased complement activation was characteristic for hospitalized COVID-19 patients.
Complement activation was significantly associated with markers of inflammation, such
as interleukin-6, C-reactive protein, and ferritin. Twenty-five patients died during
hospital stay due to COVID-19 related illness. Patients with uncontrolled complement
activation leading to consumption of C3 and decrease of complement activity were more
likely to die, than those who had complement activation without consumption. Cox models
identified anaphylatoxin C3a, and C3 overactivation and consumption (ratio of C3a/C3)
as predictors of in-hospital mortality [HR of 3.63 (1.55-8.45, 95% CI) and 6.1 (2.1-17.8),
respectively]. Conclusion Increased complement activation is associated with advanced
disease severity of COVID-19. Patients with SARS-CoV-2 infection are more likely to
die when the disease is accompanied by overactivation and consumption of C3. These
results may provide observational evidence and further support to studies on complement
inhibitory drugs for the treatment of COVID-19.
