Abstract
The complement system (CS) plays a pivotal role in Coronavirus disease 2019 (COVID-19) pathophysiology. The objective of this study was to provide a comparative, prospective data analysis of CS components in an all-comers cohort and COVID-19 patients. Patients with suspected COVID-19 infection admitted to the Emergency department were grouped for definite diagnosis of COVID-19 and no COVID-19 accordingly. Clinical presentation, routine laboratory and von Willebrand factor (vWF) antigen as well as CS components 3, 4 and activated 5 (C5a) were assessed. Also, total complement activity via the classical pathway (CH50) was determined. Levels of calprotectin in serum were measured using an automated quantitative lateral flow assay. We included 80 patients in this prospective trial. Of those 19 (23.7%) were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with COVID-19 had higher levels of CS components 5a and 4 (54.79 [24.14–88.79] ng/ml vs. 35 [23.15–46.1] ng/ml; p = 0.0433 and 0.3772 [± 0.1056] g/L vs. 0.286 [0.2375–0.3748] g/L; p = 0.0168). COVID-19 patients had significantly higher levels of vWF antigen when compared to the control group (288.3 [± 80.26] % vs. 212 [151–320] %; p = 0.0469). There was a significant correlation between CS C3 and 5a with vWF antigen (rs = 0.5957 [p = 0.0131] and rs = 0.5015 [p = 0.042]) in COVID-19 patients. There was no difference in calprotectin plasma levels (4.786 [± 2.397] µg/ml vs. 4.233 [± 2.142] µg/ml; p = 0.4175) between both groups. This prospective data from a single centre all-comers cohort accentuates altered levels of CS components as a distinct feature of COVID-19 disease. Deregulation of CS component 3 and C5a are associated with increased vWF antigen possibly linking vascular damage to alternative CS activation in COVID-19.
Highlights
The complement system (CS), as part of the innate immune response, plays a profound role in coordinating the inflammatory response to pathogens and its unrestrained activation has been implicated in the pathogenesis of Coronavirus disease 2019 (COVID-19) [1,2,3]
In the nonCOVID-19 group, 4 (6.6%) had symptomatic anemia, 9 (14.8%) patients had pneumonia, 9 (14.8%) patients were hospitalized for cardiac decompensation, 4 (6.6%) had pulmonary embolism, 16 (26.2) patients hat urogenital or gastrointestinal infections and 11 (18%) various forms of cancer. (Supplement Fig. 1)
Highlighting the importance of alternative CS activation pathways through endothelial damage we show an association of CS components and von Willebrand factor antigen in COVID-19 patients
Summary
The complement system (CS), as part of the innate immune response, plays a profound role in coordinating the inflammatory response to pathogens and its unrestrained activation has been implicated in the pathogenesis of Coronavirus disease 2019 (COVID-19) [1,2,3]. Multiple studies have shown increased levels of CS components in patients with COVID-19 as well as deposition of activated complement proteins in injured organs [3, 4]. A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding site affecting a CS activating serine-protease was discovered as possible target for therapy [5]. Understanding CS activation in COVID-19 could provide insights into the pathogenesis of hypercoagulability and increased risk for coagulopathic events, both hallmarks of COVID-19 disease [4, 6,7,8]. Several inhibitors of the CS are in clinical trials for COVID-19 treatment (C3: NCT04395456; C5: NCT04355494 and C5a: NCT04346797) [10]
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