Role of vitamin D in treating COVID-19-associated coagulopathy: problems and perspectives

Abstract

Aggressive inflammatory response leading to hypercoagulability has been found to be associated with disease severity in COVID-19 patients and portends bad treatment outcome. A state of acute disseminated intravascular coagulation (DIC), along with pulmonary embolism and/or deep vein thrombosis, has been observed in critically ill ICU patients. Autopsy reports of COVID-19 patients demonstrated microthrombi in lungs and in other organs, as well as marked inflammatory changes, characteristic clinicopathological features that exacerbate disease severity. Vitamin D supplementation was recommended by many clinicians across the globe to improve clinical symptoms of COVID-19 patients, mainly because of its immunomodulatory roles on immune cells. Furthermore, vitamin D and its associated molecules are also known to directly or indirectly regulate various thrombotic pathways. We propose that vitamin D supplementation not only attenuates the risk of Acute Respiratory Disease Syndrome (ARDS) but it also may have a role in reducing coagulation abnormalities in critically ill COVID-19 patients. The overarching goal of this review is to discuss the effects of vitamin D on coagulation pathways and other intertwined processes leading to thrombosis. Many clinical trials are currently investigating the efficacy of vitamin D supplementation in reducing the risk of COVID-19 infection. However, randomized placebo control clinical trials are also necessary to ascertain the effect of vitamin D supplementation on reducing the risk of coagulopathy in COVID-19 patients.

Keywords: COVID-19; Coagulation; Hypercoagulability; Inflammation; Thromboinflammation; Thrombosis; Venous thromboembolism (VTE); Vitamin D.

Fig. 1

Vitamin D as an anti-inflammatory and anti-thrombotic agent. Active metabolite of vitamin D (a) suppresses the inflammatory response of T-effector cell by inhibiting the maturation and activity of DCs in VDR-dependent manner; (b) activates the production of anti-inflammatory IL-10 in B cell; (c) downregulates TNF, IL-6, NFkB, MCP-1 and activates the antimicrobial peptide cathelicidin in macrophages; (d) downregulates IFNγ, IL-17, and IL-21 in T lymphocytes; (e) upregulates the natural anticoagulants TM and TFPI and deactivates TF and thereby reduces hypercoagulability