ABSTRACT
The inflammatory response to SARS/CoV-2 (COVID-19) infection may contribute to the risk of thromboembolic complications. α-Defensins, antimicrobial peptides released from activated neutrophils, are anti-fibrinolytic and prothrombotic in vitro and in mouse models. In this prospective study of 176 patients with COVID-19 infection, we found that plasma levels of α-defensins were elevated, tracked with disease progression/mortality or resolution and with plasma levels of interleukin-6 (IL-6) and D-dimers. Immunohistochemistry revealed intense deposition of α-defensins in lung vasculature and thrombi. IL-6 stimulated the release of α-defensins from neutrophils, thereby accelerating coagulation and inhibiting fibrinolysis in human blood, imitating the coagulation pattern in COVID-19 patients. The procoagulant effect of IL-6 was inhibited by colchicine, which blocks neutrophil degranulation. These studies describe a link between inflammation and the risk of thromboembolism, and they identify a potential new approach to mitigate this risk in patients with COVID-19 and potentially in other inflammatory prothrombotic conditions.
Subject(s)
COVID-19/metabolism , Inflammation/metabolism , Thromboembolism/prevention & control , alpha-Defensins/blood , Adult , Aged , Animals , Blood Coagulation/drug effects , COVID-19/complications , COVID-19/diagnosis , COVID-19/virology , Case-Control Studies , Colchicine/pharmacology , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Inflammation/complications , Interleukin-6/blood , Interleukin-6/pharmacology , Male , Mice , Middle Aged , Models, Animal , Neutrophils/drug effects , Prospective Studies , Risk Factors , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thromboembolism/etiology , Thrombosis/etiology , Thrombosis/metabolism , Tubulin Modulators/pharmacology , alpha-Defensins/pharmacologyABSTRACT
Currently, there is no widely acceptable and proven effective treatment for coronavirus disease 2019 (COVID-19). Colchicine has been shown to offer a benefit in reducing the inflammation in several inflammatory diseases. This study aims to analyze the efficacy of colchicine administration and outcomes of COVID-19. We systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until January 29, 2021. All articles published on COVID-19 and colchicine treatment were retrieved. The quality of the study was assessed using the Newcastle-Ottawa Scale (NOS) tool for observational studies and Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) for clinical trial studies. Statistical analysis was done using Review Manager 5.4 software. A total of eight studies with 5778 COVID-19 patients were included in this meta-analysis. This meta-analysis showed that the administration of colchicine was associated with improvement of outcomes of COVID-19 [OR 0.43 (95% CI 0.34-0.55), p < 0.00001, I2 = 0%, fixed-effect modelling] and its subgroup which comprised of reduction from severe COVID-19 [OR 0.44 (95% CI 0.31-0.63), p < 0.00001, I2 = 0%, fixed-effect modelling] and reduction of mortality rate from COVID-19 [OR 0.43 (95% CI 0.32-0.58), p < 0.00001, I2 = 0%, fixed-effect modelling]. Our study suggests the routine use of colchicine for treatment modalities of COVID-19 patients. More randomized clinical trial studies are still needed to confirm the results from this study.