Mannose-Binding Lectin is Associated with Thrombosis and Coagulopathy in Critically Ill COVID-19 PatientsFunding The study was funded by grants from SciLifeLab/The Knut and Alice Wallenberg Foundation to M.H. (KAW2020.0182), the Swedish Research Council to R.F. (2014–02569 and 2014–07606), B.N. (2016–01060, 2020–05672), K.N.E. (2016–04519), and O.E. (2015–06429), the Swedish Heart-Lung Foundation to B.N. (HLF 2020–0398), and by faculty grants from Linnaeus University to K.N.E.
The ongoing COVID-19 pandemic has caused significant morbidity and mortality worldwide, as well as profound effects on society. COVID-19 patients have an increased risk of thromboembolic (TE) complications, which develop despite pharmacological thromboprophylaxis. The mechanism behind COVID-19-associated coagulopathy remains unclear. Mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, has been suggested as a potential amplifier of blood coagulation during thromboinflammation. Here we describe data from a cohort of critically ill COVID-19 patients (n = 65) treated at a tertiary hospital center intensive care unit (ICU). A subset of patients had strongly elevated MBL plasma levels, and activity upon ICU admission, and patients who developed symptomatic TE (14%) had significantly higher MBL levels than patients without TE. MBL was strongly correlated to plasma D-dimer levels, a marker of COVID-19 coagulopathy, but showed no relationship to degree of inflammation or other organ dysfunction. In conclusion, we have identified complement activation through the MBL pathway as a novel amplification mechanism that contributes to pathological thrombosis in critically ill COVID-19 patients. Pharmacological targeting of the MBL pathway could be a novel treatment option for thrombosis in COVID-19. Laboratory testing of MBL levels could be of value for identifying COVID-19 patients at risk for TE events.
All authors participated in conception and design of the study. O.E. performed MBL activity assay, analyzed data, and prepared the manuscript. Thereafter, all authors had access to the data and participated in data collection and interpretation. All authors contributed to manuscript revision and gave approval of the final version.
* Equal contribution as first authors.
** Equal contribution as last authors.
Received: 27 June 2020
Accepted: 21 July 2020
01 September 2020 (online)
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