Classic pathway persistent complement activation is associated with specific symptoms in individuals with post–COVID-19 condition: A case-control study

Abstract

Objectives: The complement system is a crucial part of the immune system. The role of complement activation in post–COVID-19 condition is still not conclusive. We present a case-control study investigating long-lasting complement hyperactivation in COVID-19 survivors with/without post–COVID-19 condition. Methods: A case-control (2:1 design) study was performed. Concentration levels of four proteins from classic complement pathway (C3, C4, C5, C7) and total hemolytic complement (CH50) activity were obtained from blood samples in group of survivors with post–COVID-19 condition and in a comparison group of survivors without post–COVID-19 condition, matched by age, sex, and vaccination status. Post–COVID-19 condition was defined when individuals self-reported at least one of these post–COVID-19 symptoms: fatigue, arthralgia, myalgia, memory problems, new-onset headache, or palpitations. Results: A total of 57 (56.1% women, age: 46.5 years, SD: 9.0 years) survivors with post–COVID-19 condition and 27 (55.5% women, age: 46.5 years, SD: 11.5 years) survivors without post–COVID-19 condition were evaluated 1.7 (SD 1.2) and 2.0 (SD 1.7) years after SARS-CoV-2 infection, respectively. Overall, the results did not reveal differences in complement protein levels and CH50 activity between survivors with or without post–COVID-19 condition. Patients reporting post-COVID fatigue exhibited lower C3 levels (P = 0.025) than those without post-COVID fatigue, whereas survivors with post-COVID dyspnea reported lower levels of C3 (P = 0.001), C5 (P = 0.015), and C7 (P = 0.030) proteins than those without post-COVID dyspnea. Conclusions: This explorative case-control study did not observe overall complement activation from classic pathway in survivors with post–COVID-19 condition up to 2 years after. Some complement proteins were elevated in individuals with specific post-COVID symptoms, such as fatigue or dyspnea.