Perspective: Vitamin D deficiency and COVID‐19 severity – plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis

Rhodes, Jonathan M.; Subramanian, Sreedhar; Laird, Éamon; Griffin, George E.; Kenny, Rose Anne

doi:10.1111/joim.13149

Cited by 219 publications

(247 citation statements)

References 128 publications

(162 reference statements)

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“…In this context, vitamin D's dual roles of initially controlling viral replication and later dampening the hyper-inflammation are tantalising. This is consistent with the observation that low levels of vitamin D (or indeed polymorphisms in the VDR) may adversely impact the outcome of patients with COVID-19 [17,[24][25][26][27][28][29][30].…”

Section: Resultssupporting

confidence: 88%

Exploring links between vitamin D deficiency and COVID-19

2020

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Coronavirus Disease 2019 (COVID-19) pandemic remains a major public health threat in most countries. The causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can lead to acute respiratory distress syndrome and result in mortality in COVID-19 patients. Vitamin D is an immunomodulator hormone with established effectiveness against various upper respiratory infections. Vitamin D can stall hyper-inflammatory responses and expedite healing process of the affected areas, primarily in the lung tissue. Thus, there are ecological and mechanistic reasons to promote exploration of vitamin D action in COVID-19 patients. As no curative drugs are available currently for COVID-19, we feel that the potential of vitamin D to alter the course of disease severity needs to be investigated. Clinical studies may be undertaken to address the value of vitamin D supplementation in deficient, high-risk COVID-19 patients.

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Section: Resultssupporting

confidence: 88%

Exploring links between vitamin D deficiency and COVID-19

2020

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“…More recently, another study reported a highly significant, positive correlation between lower death rates and a country’s proximity to the equator [ 179 ]. Rhodes et al described that more northerly countries are currently showing relatively high COVID-19 mortality, with an estimated 4.4% increase in mortality for each 1-degree latitude north of 28 degrees North [ 180 ].…”

Section: Vitamin Dmentioning

confidence: 99%

The Role of Micronutrients in Support of the Immune Response against Viral Infections

et al. 2020

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Viral infections are a leading cause of morbidity and mortality worldwide, and the importance of public health practices including handwashing and vaccinations in reducing their spread is well established. Furthermore, it is well known that proper nutrition can help support optimal immune function, reducing the impact of infections. Several vitamins and trace elements play an important role in supporting the cells of the immune system, thus increasing the resistance to infections. Other nutrients, such as omega-3 fatty acids, help sustain optimal function of the immune system. The main aim of this manuscript is to discuss of the potential role of micronutrients supplementation in supporting immunity, particularly against respiratory virus infections. Literature analysis showed that in vitro and observational studies, and clinical trials, highlight the important role of vitamins A, C, and D, omega-3 fatty acids, and zinc in modulating the immune response. Supplementation with vitamins, omega 3 fatty acids and zinc appears to be a safe and low-cost way to support optimal function of the immune system, with the potential to reduce the risk and consequences of infection, including viral respiratory infections. Supplementation should be in addition to a healthy diet and fall within recommended upper safety limits set by scientific expert bodies. Therefore, implementing an optimal nutrition, with micronutrients and omega-3 fatty acids supplementation, might be a cost-effective, underestimated strategy to help reduce the burden of infectious diseases worldwide, including coronavirus disease 2019 (COVID-19).

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“…In light of accruing evidence that vitamin D3 status is inversely correlated with severity of COVID-19 ( 23 – 26 ), it is significant that, via its hormone-like actions on gene expression, D3 has been shown to be a potent activator of both TXNRD1 and GCLC. In a microarray study, 6 h after exposure to 1,25-dihydroxyvitamin D3, TXNRD1 mRNA was upregulated 7.1X, and GCLC was upregulated 2.5X ( 27 ).…”

Section: The Potential M Pro Targets Txnrd1 and Gcmentioning

confidence: 99%

Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?

Taylor

Radding

2020

Front. Nutr.

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Glutathione peroxidases (GPX), a family of antioxidant selenoenzymes, functionally link selenium and glutathione, which both show correlations with clinical outcomes in COVID-19. Thus, it is highly significant that cytosolic GPX1 has been shown to interact with an inactive C145A mutant of M pro , the main cysteine protease of SARS-CoV-2, but not with catalytically active wild-type M pro . This seemingly anomalous result is what might be expected if GPX1 is a substrate for the active protease, leading to its fragmentation. We show that the GPX1 active site sequence is substantially similar to a known M pro cleavage site, and is identified as a potential cysteine protease site by the Procleave algorithm. Proteolytic knockdown of GPX1 is highly consistent with previously documented effects of recombinant SARS-CoV M pro in transfected cells, including increased reactive oxygen species and NF-κB activation. Because NF-κB in turn activates many pro-inflammatory cytokines, this mechanism could contribute to increased inflammation and cytokine storms observed in COVID-19. Using web-based protease cleavage site prediction tools, we show that M pro may be targeting not only GPX1, but several other selenoproteins including SELENOF and thioredoxin reductase 1, as well as glutamate-cysteine ligase, the rate-limiting enzyme for glutathione synthesis. This hypothesized proteolytic knockdown of components of both the thioredoxin and glutaredoxin systems is consistent with a viral strategy to inhibit DNA synthesis, to increase the pool of ribonucleotides for RNA synthesis, thereby enhancing virion production. The resulting “collateral damage” of increased oxidative stress and inflammation would be exacerbated by dietary deficiencies of selenium and glutathione precursors.

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Perspective: Vitamin D deficiency and COVID‐19 severity – plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis

Cited by 219 publications

References 128 publications

Exploring links between vitamin D deficiency and COVID-19

Exploring links between vitamin D deficiency and COVID-19

The Role of Micronutrients in Support of the Immune Response against Viral Infections

Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?

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