Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis

Mok, Chee Keng; Ng, Yan Ling; Ahidjo, Bintou Ahmadou; Lee, Regina Ching Hua; Loe, Marcus Wing Choy; Liu, Jing; Tan, Kai Sen; Kaur, Parvinder; Chng, Wee Joo; Wong, John; Wang, De Yun; Hao, Er Wei; Xin, Hao; Tan, Yong Kiam; Mak, Tze Minn; Cui, Lin; Lin, Rita; Tambyah, Paul Ananth; Deng, Jiagang; Chu, Justin Jang Hann

doi:10.1101/2020.06.21.162396

Cited by 58 publications

(52 citation statements)

References 21 publications

(11 reference statements)

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“…This mechanism may be relevant in COVID-19 as low plasma levels of vitamin D are reported in SARS-CoV-2 infected individuals and significantly contribute to the risk of infection and hospitalization ( Merzon et al., 2020 ). Calcitriol, the active form of vitamin D, is also reported to directly reduce the virus-induced cytopathic effect of SARS-CoV-2 infection in cultured human respiratory epithelial cells ( Mok et al., 2020 ). The combination of melatonin and vitamin D has been proposed as a potentially synergistic intervention in COVID-19 ( Martín Giménez et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention

2020

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With the objective of linking early findings relating to the novel SARS-CoV-2 coronavirus with potentially informative findings from prior research literature and to promote investigation toward therapeutic response, a coherent cellular and molecular pathway is proposed for COVID-19. The pathway is consistent with a broad range of observed clinical features and biological markers and captures key mediators of pathophysiology. In this proposed pathway, membrane fusion and cytoplasmic entry of SARS-CoV-2 virus via ACE2 and TMPRSS2-expressing respiratory epithelial cells, including pulmonary type-II pneumocytes, provoke an initial immune response featuring inflammatory cytokine production coupled with a weak interferon response, particularly in IFN-l-dependent epithelial defense. Differentiation of non-classic pathogenic T-cells and pro-inflammatory intermediate monocytes contributes to a skewed inflammatory profile, mediated by membrane-bound immune receptor subtypes (e.g., FcgRIIA) and downstream signaling pathways (e.g., NF-kB p65 and p38 MAPK), followed by chemotactic infiltration of monocyte-derived macrophages and neutrophils into lung tissue. Endothelial barrier degradation and capillary leakage contribute to alveolar cell damage. Inflammatory cytokine release, delayed neutrophil apoptosis, and NETosis contribute to pulmonary thrombosis and cytokine storm. These mechanisms are concordant with observed clinical markers in COVID-19, including high expression of inflammatory cytokines on the TNF-a/ IL-6 axis, elevated neutrophil-to-lymphocyte ratio (NLR), diffuse alveolar damage via cell apoptosis in respiratory epithelia and vascular endothelia, elevated lactate dehydrogenase (LDH) and CRP, high production of neutrophil extracellular traps (NETs), depressed platelet count, and thrombosis. Although certain elements are likely to be revised as new findings emerge, the proposed pathway suggests multiple points of investigation for potential therapeutic interventions. Initial candidate interventions include prophylaxis to augment epithelial defense (e.g., AT1 receptor blockade, type III and type I interferons, melatonin, calcitriol, camostat, and lopinavir) and to reduce viral load (e.g., remdesivir, ivermectin, emetine, Abelson kinase inhibitors, dopamine D2 antagonists, and selective estrogen receptor modulators). Additional interventions focus on tempering inflammatory signaling and injury (e.g., dexamethasone, doxycycline, Ang1-7, estradiol, alpha blockers,

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Section: Discussionmentioning

confidence: 99%

Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention

2020

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“…Furthermore, while existing data had already shown that vitamin D enhances the anti-viral activity of bronchial epithelial cells in vitro [39], recent research examining 2191 candidate compounds also identified a potential role for vitamin D in the specific inhibition of Covid-19 viral replication. The authors of this study concluded that calcitriol exhibits "significant, potent anti-viral activity" against SARS-CoV-2 in cultured human nasal epithelial cells in vitro [40].…”

Section: Infectionmentioning

confidence: 92%

Vitamin D and SARS-CoV-2 infection—evolution of evidence supporting clinical practice and policy development

et al. 2020

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“…Recently, Mok et al . [8] extended this line of research to SARS‐CoV‐2, the cause of COVID‐19. They demonstrated for the first time that calcitriol, the active form of vitamin D, exhibits potent activity against SARS‐CoV‐2.…”

Section: The Role Of Vitamin D In the Covid‐19 Pandemicmentioning

confidence: 99%

Vitamin D to prevent COVID‐19: recommendations for the design of clinical trials

Camargo

Martineau

2020

The FEBS Journal

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The coronavirus disease 2019 (COVID‐19) pandemic has focused attention on the potential role of vitamin D supplementation to prevent COVID‐19. In this issue, Merzon and colleagues report epidemiologic data on the vitamin D status of 7807 individuals and their risk of developing COVID‐19. In multivariable analyses, low vitamin D status was associated with increased risk of both COVID‐19 infection and hospitalization. The authors call for clinical trials of vitamin D supplementation. In this Commentary, we discuss some of the challenges of vitamin D research and provide recommendations for the design of randomized controlled trials of vitamin D supplementation to prevent COVID‐19.

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Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis

Cited by 58 publications

References 21 publications

Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention

Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention

Vitamin D and SARS-CoV-2 infection—evolution of evidence supporting clinical practice and policy development

Vitamin D to prevent COVID‐19: recommendations for the design of clinical trials

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