Systemic Complement Activation Associated With Respiratory Failure in COVID-19

SARS-CoV-2, COVID-19, coronavirus
Systemic complement activation is associated with respiratory failure in patients with coronavirus disease 2019.

Systemic complement activation is associated with respiratory failure in patients with coronavirus disease 2019 (COVID-19), according to the results of a recent study published in the journal PNAS.

According to the researchers, the complement system plays a key role in the innate immune response, and has been previously associated with respiratory failure, acute respiratory distress syndrome development, and severity in bacterial and viral pneumonia. Therefore, the investigators sought to identify the degree and specific time point of systemic complement activation in COVID-19, particularly as the activation relates to the clinical course of disease.

Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data from were abstracted from electronic medical records from patients hospitalized with COVID-19. Blood samples were obtained at hospital admission (within 48 hours), at days 3 to 5, and days 7 to 10. Patients were divided according to the presence of respiratory failure, and associations for outcomes were examined between the 2 groups.

Of the 39 patients who were positive for SARS-CoV-2 included in the study, respiratory failure was either prominent at admission or developed while hospitalized in 23 patients. Baseline characteristics revealed significant differences in myalgia, fatigue, arterial oxygen partial pressure /fractional inspired oxygen ratio, need for oxygen therapy, and Sequential Organ Failure Assessment (SOFA) score between patients with and without respiratory failure.

At admission, complement activation markers sC5b-9 (common pathway) and C4d (classical/lectin pathway) were significantly higher in patients with respiratory failure than in those without. Furthermore, logistic regression showed increasing odds of respiratory failure with sC5b-9 (P =.03) and need for oxygen therapy with C4d (P =.045).

“[H]ere we show that the complement system is activated systemically in the majority of COVID-19 patients admitted to hospital,” the study authors wrote. “All complement activation products were increased, but, especially, the terminal complement sC5b-9 was associated with respiratory failure and systemic inflammation.”

Disclosure: Some study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Holter JC, Pischke SE, de Boer E, et al. Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients. Proc Natl Acad Sci U S A. Published online September 17, 2020. doi:10.1073/pnas.2010540117

This article originally appeared on Pulmonology Advisor