Monitoring, outcomes, and follow-ups
death, acute lung injury
ADVERSE EVENTS, DISEASE, SECONDARY
Data on vital signs, disease severity according to WHO scale, clinical improvement, admission to ICU, and requirement for non-invasive or invasive ventilation were prospectively obtained. Virological clearance (time from positive to negative PCR test results in nasopharyngeal samples), hematological, liver, renal, and inflammatory parameters in laboratory examinations were monitored during the first 14 days of hospitalization or until discharge. C1INH antigen and C4 concentrations were determined on semi-automated platforms in the clinical laboratories in all except two study centers (not monitored in Monterrey, Mexico and Zurich, Switzerland). Additional EDTA- and citrate-plasma as well as serum samples were frozen at −80°C and subsequently analyzed for concentrations of C4d (Svar Life Sciences, Malmö, Sweden), sC5b-9 (BD Biosciences Pharmingen, San Diego, CA, USA), VCAM-1 and E-selectin (ProteinSimple, Bio-techne, Minneapolis, MN, USA), and kallikrein-like activity (Unitest, Haemochrome Diagnostica, Essen, Germany) according to the manufacturer’s instruction.Final follow-up included a structured telephone interview or study visit (if still hospitalized) 28 days after enrollment to assess adverse events (AEs) and outcome. Afterwards, serious adverse events (SAEs) were followed until resolution, stabilization, or death, whichever occurred first.The primary endpoint was disease severity on the WHO Ordinal Scale on day 7. For statistical analysis, the scores 6 and 7 were combined into one score. Secondary endpoint included time to clinical improvement within 14 days after enrollment. It was defined as improvement of two points on the WHO Ordinal Scale or live hospital discharge, whatever occurred first. Other secondary endpoints included the proportion of participants alive and not having required invasive or non-invasive ventilation at day 14 day, and the proportion of subjects with an acute lung injury. The latter was defined by the presence of PaO