COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta-analysis of randomized controlled trials

Varikasuvu, Seshadri Reddy; Thangappazham, Balachandar; Vykunta, Alekya; Duggina, Pragathi; Munikumar, Manne; Raj, Hemanth; Aloori, Sowjanya

doi:10.1080/14787210.2022.2035217

Cited by 60 publications

(52 citation statements)

References 35 publications

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“…Multiple observational and RCTs have demonstrated that serum 25(OH)D concentrations (pre-infection or on admission) inversely correlated with the incidence, severity, and rates of death from COVID-19 [ 45 , 55 , 56 , 153 ]. Meanwhile, vitamin D supplementation significantly reduces complications and deaths [ 33 , 44 , 45 , 150 , 154 ].…”

Section: Discussionmentioning

confidence: 99%

Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections—Sepsis and COVID-19

Wimalawansa¹

2022

Nutrients

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Vitamin D deficiency is a global public health problem, a pandemic that commonly affects the elderly and those with comorbidities such as obesity, diabetes, hypertension, respiratory disorders, recurrent infections, immune deficiency, and malignancies, as well as ethnic minorities living in temperate countries. The same groups were worst affected by COVID-19. Since vitamin D deficiency weakens the immune system, it increases the risk of infections, complications, and deaths, such as from sepsis and COVID-19. Deficiency can be remedied cost-effectively through targeted food fortification, supplementation, and/or daily safe sun exposure. Its endocrine functions are limited to mineral metabolism, musculoskeletal systems, specific cell membrane interactions, and parathyroid gland functions. Except for the rapid, endocrine, and cell membrane-based non-genomic functions, all other biological and physiological activities of vitamin D depend on the adequate intracellular synthesis of 1,25(OH)2D (calcitriol) in peripheral target cells via the genome. Calcitriol mediates autocrine (intracrine) and paracrine signalling in immune cells, which provides broader, protective immune functions crucial to overcoming infections. The synthesis of 1,25(OH)2D (calcitriol) in peripheral target cells is dependent on diffusion and endocytosis of D3 and 25(OH)D from the circulation into them, which requires maintenance of serum 25(OH)D concentration above 50 ng/mL. Therefore, in acute infections such as sepsis and respiratory infections like COVID-19, it is necessary to rapidly provide its precursors, D3 and 25(OH)D, through the circulation to generate adequate intracellular calcitriol. Immune defence is one of the crucial non-hormonal functions of vitamin D. A single oral (bolus) dose or divided upfront loading doses between 100,000 and 500,000 IU, using 50,000 IU vitamin D3 increase the serum 25(OH)D concentrations to a therapeutic level of above 50 ng/mL that lasts between two to three months. This takes three to five days to raise serum 25(OH)D. In contrast, a single oral dose of calcifediol (0.014 mg/kg body weight) can generate the needed 25(OH)D concentration within four hours. Considering both D3 and 25(OH)D enter immune cells for generating calcitriol, using the combination of D3 (medium-term) and calcifediol (immediate) is cost-effective and leads to the best clinical outcome. To maximise protection against infections, particularly to reduce COVID-19-associated complications and deaths, healthcare workers should advise patients on safe sun exposure, adequate vitamin D supplementation and balanced diets containing zinc, magnesium, and other micronutrients to support the immune system. Meanwhile, governments, the World Health Organisation, the Centers for Disease Control, and governments should consider similar recommendations to physicians and the public, change the outdated vitamin D and other micronutrient recommendations directed to their population, and organise targetted food fortification programs for the vulnerable groups. This article discusses a rational approach to maintaining a sustained serum 25(OH)D concentration above 50 ng/mL, necessary to attain a robust immune system for overcoming infections. Such would cost-effectively improve the population’s health and reduce healthcare costs. It also describes three cost-effective, straightforward protocols for achieving and sustaining therapeutic serum 25(OH)D concentrations above 50 ng/mL (>125 nmol/L) to keep the population healthy, reduce absenteeism, improve productivity, and lower healthcare costs.

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Section: Discussionmentioning

confidence: 99%

Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections—Sepsis and COVID-19

Wimalawansa¹

2022

Nutrients

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“…At present, interventional studies assessing the potential role of vitamin D supplementation for preventing infection and death from COVID-19 are few [ 18 – 20 ], and most of them still ongoing [ 21 , 22 ]. A recent review and meta-analysis of randomized controlled trials on COVID-19 and vitamin D (Co-VIVID study) found 6 high-quality studies for a total of 551 COVID-19 patients included [ 23 ]. Despite the limited number of patients, the pooled effect of vitamin D administration resulted in a 40% relative risk reduction of overall COVID-19-related outcomes [RR = 0.60, (95% CI 0.40–0.92)] and a 56% relative risk reduction for RT-PCR positivity [RR = 0.46, (95% CI 0.24–0.89)] [ 23 ].…”

mentioning

confidence: 99%

“…A recent review and meta-analysis of randomized controlled trials on COVID-19 and vitamin D (Co-VIVID study) found 6 high-quality studies for a total of 551 COVID-19 patients included [ 23 ]. Despite the limited number of patients, the pooled effect of vitamin D administration resulted in a 40% relative risk reduction of overall COVID-19-related outcomes [RR = 0.60, (95% CI 0.40–0.92)] and a 56% relative risk reduction for RT-PCR positivity [RR = 0.46, (95% CI 0.24–0.89)] [ 23 ]. However, despite its possible global beneficial effect, analysed data did not find a significant association between vitamin D supplementation and an improvement of hard outcomes (e.g.…”

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Extraosseous effects of vitamin D: a role in the prevention and treatment of COVID-19?

Mirijello

Piscitelli

D’Angelo³

et al. 2022

Intern Emerg Med

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The association between vitamin D intake with inflammatory and biochemical indices and mortality in critically ill patients with COVID‐19: A case‐control study

Rabbani

Ahmadzadeh

Hajipour

et al. 2023

Immunity Inflam & Disease

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Background The coronavirus disease‐2019 (COVID‐19) has become a worldwide health issue with widespread hospitalization and dependence on the intensive care unit (ICU). Vitamin D has a key role in modulating immune cells and modulating the inflammatory responses. This study aimed to investigate the association of vitamin D supplementation with inflammatory, biochemical, and mortality indices in critically ill patients with COVID‐19. Methods This case‐control study was conducted on critically ill COVID‐19 patients hospitalized in the ICU including the survived >30 day patients as the case group and dead patients as the control group. The status of vitamin D supplementation and inflammatory and biochemical indices of the patients were retrieved from the medical records. Logistic regression method was used to assess the association between 30 days survival and vitamin D supplement intake. Results Compared to the group of COVID‐19 patients who died in <30 day, the survived patients had a lower eosinophile level (2.2 ± 0.5 vs. 6 ± 0.0, p < .001) and higher vitamin D supplementation duration (9 ± 4.4 vs. 3.3 ± 1.9 day, p = .001). Vitamin D supplementation had a positive association with survival in COVID‐19 patients (OR: 1.98, 95% CI: 1.15−3.40, p < .05). The association remained significant after adjustments fot age, sex, underlying diseases, and smoking. Conclusion Vitamin D supplementation in critically ill patients with COVID‐19 has the potential to increase survivability within the first 30 days of hospitalization.

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COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta-analysis of randomized controlled trials

Cited by 60 publications

References 35 publications

Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections—Sepsis and COVID-19

Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections—Sepsis and COVID-19

Extraosseous effects of vitamin D: a role in the prevention and treatment of COVID-19?

The association between vitamin D intake with inflammatory and biochemical indices and mortality in critically ill patients with COVID‐19: A case‐control study

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