Mannose-Binding Lectin Associated with Coagulopathy in Severe COVID-19

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.

Immunologists at the Uppsala University (Uppsala, Sweden) and their colleagues clarify the role of MBL in COVID-19 and measured plasma MBL levels and activity in a cohort of 65 critically ill COVID-19 patients and investigated its relation to clinical outcome. All patients were over 18 years of age with confirmed or suspected COVID-19 admitted to the ICU between March 13 and April 30, 2020, were screened for inclusion.

Blood was sampled in ethylenediaminetetraacetic acid tubes, and plasma stored at –70 °C until analysis. Plasma MBL levels at day 1 at the ICU (on average COVID-19 day 10) were measured by an in-house enzyme-linked immunosorbent assay (ELISA), and were significantly higher than in healthy controls. Activity of the MBL pathway was assessed by a functional ELISA using mannan as activator and MBL binding capacity and complement C3 deposition as readouts. This assay measures the functional MBL concentration in plasma and its capacity to activate complement, and confirmed elevated MBL activity and MBL-dependent C3 deposition in the patient group.

The team reported that nine (14%) patients who developed symptomatic thromboembolism, despite receiving thromboprophylaxis, had significantly higher MBL levels than patients who did not experience a thromboembolic event (median 1,233 kU/L versus 470 kU/L). All patients in the study received thromboprophylaxis with either dalteparin sodium (n = 64) or apixaban (n = 1). Of the nine patients in the study who developed a symptomatic thromboembolic event during their time at the ICU, two were arterial thrombosis (stroke or myocardial infarction) and seven were pulmonary embolisms (PEs). COVID-19 patients have elevated plasma MBL levels compared with healthy controls: 625 kU/L in the patient group (n = 65) versus. 444 kU/L in the healthy blood donors controls (n = 72).

Interestingly, patients who developed PE all had MBL levels above the 95th percentile compared with controls. MBL showed a significant correlation with total complement factor C3 levels, but not with the activation product C3d (measured as C3d/C3 ratio), a measure of activity of the alternative pathway of complement, nor with C1q, the initiator of the classical pathway. Total C3 levels, C3d/C3 ratio, or C1q were not related to thrombotic events, indicating a specific association between MBL and thrombosis.

The authors concluded that they had 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 thromboembolic events. The study was published on September 1 2020 in the journal Thrombosis and Haemostasis.

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