Background Excessive activation of immune responses in coronavirus disease 2019 (COVID-19) is considered to be related to disease severity, complications and mortality. The complement system is an important component of innate immunity and can stimulate inflammation, but its role in COVID-19 is unknown. Methods A prospective, longitudinal, single center study was performed in hospitalized COVID-19 patients. Plasma concentrations of complement factors C3a, C3c, and terminal complement complex (TCC) were assessed at baseline and during hospital admission. In parallel, routine laboratory and clinical parameters were collected from medical files and analyzed. Results Complement factors C3a, C3c and TCC were significantly increased in plasma of COVID-19 patients compared to healthy controls (p<0.05). These complement factors were especially elevated in ICU patients during the entire disease course (p<0.005 for C3a and TCC). More intense complement activation was observed in patients that deceased and in patients with thromboembolic events. Conclusions COVID-19 patients demonstrate activation of the complement system, which is related to disease severity. This pathway may be involved in the dysregulated pro-inflammatory response associated with increased mortality and thromboembolic complications. Components of the complement system might have potential as prognostic markers for disease severity and as therapeutic targets in COVID-19.

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Objective To describe clinical characteristics, disease course and outcomes in a large and well-documented cohort of hospitalized COVID-19 patients in the Netherlands. Methods We conducted a multicentre retrospective cohort study in The Netherlands including 952 of 1183 consecutively hospitalized patients that were admitted to participating hospitals between March 2nd, 2020, and May 22nd, 2020. Clinical characteristics and laboratory parameters upon admission and during hospitalization were collected until July 1st. Results The median age was 69 years (IQR 58–77 years) and 605 (63.6%) were male. Cardiovascular disease was present in 558 (58.6%) patients. The median time of onset of symptoms prior to hospitalization was 7 days (IQR 5–10). A non ICU admission policy was applicable in 312 (32.8%) patients and in 165 (56.3%) of the severely ill patients admitted to the ward. At admission and during hospitalization, severely ill patients had higher values of CRP, LDH, ferritin and D-dimer with higher neutrophil counts and lower lymphocyte counts. Overall in-hospital mortality was 25.1% and 183 (19.1%) patients were admitted to ICU, of whom 56 (30.6%) died. Patients aged ≥70 years had high mortality, both at the ward (52.4%) and ICU (47.4%). The median length of ICU stay was 8 days longer in patients aged ≥70 years compared to patients aged ≤60 years. Conclusion Hospitalized COVID-19 patients aged ≥70 years had high mortality and longer ICU stay compared to patients aged ≤60 years. These findings in combination with the patient burden of an ICU admission and possible long term complications after discharge should encourage us to further investigate the benefit of ICU admission in elderly and fragile COVID-19-patients.

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