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In Vitro |
Morita et al., Viruses, doi:10.3390/v13081669 (Peer Reviewed) (In Vitro) |
in vitro |
All-Trans Retinoic Acid Exhibits Antiviral Effect against SARS-CoV-2 by Inhibiting 3CLpro Activity |
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In Vitro and In Silico study showing that all-trans retinoic acid is a potent SARS-CoV-2 3CLpro inhibitor, inhibits SARS-CoV-2 replication in VeroE6/TMPRSS2 cells, and is effective against alpha, beta, gamma, and delta variants in Calu-3 .. |
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In Vitro
In Vitro
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| Morita et al., Viruses, doi:10.3390/v13081669 (Peer Reviewed) (In Vitro) |
| All-Trans Retinoic Acid Exhibits Antiviral Effect against SARS-CoV-2 by Inhibiting 3CLpro Activity |
In Vitro and In Silico study showing that all-trans retinoic acid is a potent SARS-CoV-2 3CLpro inhibitor, inhibits SARS-CoV-2 replication in VeroE6/TMPRSS2 cells, and is effective against alpha, beta, gamma, and delta variants in Calu-3 cells.
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Morita et al., 8/23/2021, peer-reviewed, 9 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Levels |
Tepasse et al., Nutrients, doi:10.3390/nu13072173 (Peer Reviewed) |
death, ↓69.7%, p=0.04 |
Vitamin A Plasma Levels in COVID-19 Patients: A Prospective Multicenter Study and Hypothesis |
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Prospective analysis of 40 hospitalized patients and 47 age-matched convalescent patients, showing significantly lower vitamin A levels in critical patients, and significantly lower vitamin A levels in hospitalized patients vs. controls. .. |
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Levels
Analysis of outcomes based on serum levels
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| Tepasse et al., Nutrients, doi:10.3390/nu13072173 (Peer Reviewed) |
| Vitamin A Plasma Levels in COVID-19 Patients: A Prospective Multicenter Study and Hypothesis |
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Prospective analysis of 40 hospitalized patients and 47 age-matched convalescent patients, showing significantly lower vitamin A levels in critical patients, and significantly lower vitamin A levels in hospitalized patients vs. controls. Low vitamin A levels were significantly associated with ARDS and mortality in hospitalized patients.
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risk of death, 69.7% lower, RR 0.30, p = 0.04, treatment 4 of 29 (13.8%), control 5 of 11 (45.5%), OR converted to RR, >2mg/L, logistic regression.
risk of disease progression, 45.2% lower, RR 0.55, p = 0.05, treatment 13 of 29 (44.8%), control 9 of 11 (81.8%), OR converted to RR, progression to ARDS, >2mg/L, logistic regression.
Tepasse et al., 6/24/2021, prospective, Germany, Europe, peer-reviewed, 8 authors.
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PrEPPEP |
Holt et al., medRxiv, doi:10.1101/2021.03.27.21254452 (Preprint) |
cases, ↓56.3%, p=0.41 |
Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK) |
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Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistica.. |
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Prophylaxis study
Prophylaxis study
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| Holt et al., medRxiv, doi:10.1101/2021.03.27.21254452 (Preprint) |
| Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK) |
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Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Results are subject to confounding, with only the vitamin D result fully adjusted. NCT04330599. COVIDENCE UK.
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risk of case, 56.3% lower, RR 0.44, p = 0.41, treatment 1 of 91 (1.1%), control 445 of 15,136 (2.9%), adjusted, OR converted to RR, minimally adjusted, group sizes approximated.
Excluded in after exclusion results of meta analysis:
significant unadjusted confounding possible.
Holt et al., 3/30/2021, prospective, United Kingdom, Europe, preprint, 31 authors.
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Levels |
Muhammad et al., SAGE Open Medicine, doi:10.1177/2050312121991246 (Peer Reviewed) |
Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria |
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Case control study with 50 symptomatic COVID-19 patients and 21 healthy controls in Nigeria, showing that COVID-19 patients had significantly lower levels of selenium and zinc, and vitamins A, C, and E. Control patients were younger than .. |
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Levels
Analysis of outcomes based on serum levels
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| Muhammad et al., SAGE Open Medicine, doi:10.1177/2050312121991246 (Peer Reviewed) |
| Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria |
Case control study with 50 symptomatic COVID-19 patients and 21 healthy controls in Nigeria, showing that COVID-19 patients had significantly lower levels of selenium and zinc, and vitamins A, C, and E. Control patients were younger than COVID-19 patients. The p value for zinc in Table 2 appears to be a typo.
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Muhammad et al., 2/1/2021, Nigeria, Africa, peer-reviewed, 8 authors.
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Late |
Sarohan et al., medRxiv, doi:10.1101/2021.01.30.21250844 (Preprint) |
death, ↑282.5%, p=0.001 |
Retinol Depletion in Severe COVID-19 |
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Retrospective 27 severe COVID-19 patients and 23 non-COVID-19 patients, showing signifcantly lower vitamin A levels in COVID-19 patients (0.37mg/L vs. 0.52 mg/L, p<0.001). 10 of 27 COVID-19 patients received vitamin A, with higher mortali.. |
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Late treatment study
Late treatment study
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| Sarohan et al., medRxiv, doi:10.1101/2021.01.30.21250844 (Preprint) |
| Retinol Depletion in Severe COVID-19 |
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Retrospective 27 severe COVID-19 patients and 23 non-COVID-19 patients, showing signifcantly lower vitamin A levels in COVID-19 patients (0.37mg/L vs. 0.52 mg/L, p<0.001). 10 of 27 COVID-19 patients received vitamin A, with higher mortality. Group details are not provided but authors note that 8 of 10 had comorbidities.
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risk of death, 282.5% higher, RR 3.83, p = 0.001, treatment 9 of 10 (90.0%), control 4 of 17 (23.5%).
Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Sarohan et al., 2/1/2021, retrospective, Turkey, Europe, preprint, 4 authors.
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Early |
Al-Sumiadai, Systematic Reviews in Pharmacy, 12:1 (Preprint) |
progression, ↓66.7%, p=0.27 |
Therapeutic effect of vitamin A on COVID-19 patients and its prophylactic effect on contacts |
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Treatment and prophylaxis studies of vitamin A in Iraq.
The treatment study contained 100 patients, 50 treated with 200,000IU vitamin A for two days, showing lower progression to severe disease, and shorter duration of symptoms.
The pro.. |
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Early treatment study
Early treatment study
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| Al-Sumiadai, Systematic Reviews in Pharmacy, 12:1 (Preprint) |
| Therapeutic effect of vitamin A on COVID-19 patients and its prophylactic effect on contacts |
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Treatment and prophylaxis studies of vitamin A in Iraq.The treatment study contained 100 patients, 50 treated with 200,000IU vitamin A for two days, showing lower progression to severe disease, and shorter duration of symptoms.The prophylaxis study contained 209 contacts of COVID-19 patients, 97 treated with vitamin A, showing significantly lower cases with treatment, and shorter duration of symptoms.
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risk of disease progression, 66.7% lower, RR 0.33, p = 0.27, treatment 2 of 50 (4.0%), control 6 of 50 (12.0%), progression to severe disease.
recovery time, 37.5% lower, relative time 0.62, treatment 50, control 50.
Al-Sumiadai et al., 1/31/2021, prospective, Iraq, Middle East, preprint, 3 authors.
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Review |
Stephensen et al., British Journal of Nutrition, doi:10.1017/S0007114521000246 (Review) (Peer Reviewed) |
review |
Vitamin A in resistance to and recovery from infection: relevance to SARS-CoV2 |
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Review of the potential benefits of vitamin A for COVID-19, including maintaining innate and adaptive immunity, minimizing inflammation, supporting repair of respiratory epithelium and preventing fibrosis, and counteracting adverse effect.. |
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Review
Review
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| Stephensen et al., British Journal of Nutrition, doi:10.1017/S0007114521000246 (Review) (Peer Reviewed) |
| Vitamin A in resistance to and recovery from infection: relevance to SARS-CoV2 |
Review of the potential benefits of vitamin A for COVID-19, including maintaining innate and adaptive immunity, minimizing inflammation, supporting repair of respiratory epithelium and preventing fibrosis, and counteracting adverse effects of SARS-CoV-2 on the angiotensin system.
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Stephensen et al., 1/20/2021, peer-reviewed, 2 authors.
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Early |
Al-Sumiadai et al., EurAsian Journal of Biosciences, 14:7347-7350 (Peer Reviewed) |
death, ↓85.7%, p=0.002 |
Therapeutic effect of Vitamin A on severe COVID-19 patients |
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Retrospective 70 severe condition patients treated with vitamin A (200,000IU for two days), salbutamol, and budesonide, and 70 patients not treated with vitamin A, showing significantly lower mortality with the addition of vitamin A. |
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Early treatment study
Early treatment study
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| Al-Sumiadai et al., EurAsian Journal of Biosciences, 14:7347-7350 (Peer Reviewed) |
| Therapeutic effect of Vitamin A on severe COVID-19 patients |
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Retrospective 70 severe condition patients treated with vitamin A (200,000IU for two days), salbutamol, and budesonide, and 70 patients not treated with vitamin A, showing significantly lower mortality with the addition of vitamin A.
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risk of death, 85.7% lower, RR 0.14, p = 0.002, treatment 2 of 70 (2.9%), control 14 of 70 (20.0%).
Excluded in after exclusion results of meta analysis:
minimal details of groups provided.
Al-Sumiadai et al., 12/31/2020, retrospective, Iraq, Middle East, peer-reviewed, 3 authors.
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Review |
Midha et al., Reviews in Medical Virology, doi:10.1002/rmv.2204 (Review) (Peer Reviewed) |
review |
Mega doses of retinol: A possible immunomodulation in Covid-19 illness in resource-limited settings |
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Review of the potential benefits of vitamin A for COVID-19, including the effect of vitamin A on ACE2 expression in the respiratory tract, potentially improving the generation of protective immune responses to vaccines, and dosage and saf.. |
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Review
Review
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| Midha et al., Reviews in Medical Virology, doi:10.1002/rmv.2204 (Review) (Peer Reviewed) |
| Mega doses of retinol: A possible immunomodulation in Covid-19 illness in resource-limited settings |
Review of the potential benefits of vitamin A for COVID-19, including the effect of vitamin A on ACE2 expression in the respiratory tract, potentially improving the generation of protective immune responses to vaccines, and dosage and safety analysis.
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Midha et al., 12/31/2020, peer-reviewed, 4 authors.
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Levels |
Tomasa-Irriguible et al., Metabolites, doi:10.3390/metabo11090565 (preprint 10/26/2020) (Peer Reviewed) |
ventilation, ↓71.4%, p=0.001 |
Low Levels of Few Micronutrients May Impact COVID-19 Disease Progression: An Observational Study on the First Wave |
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Retrospective 120 hospitalized patients in Spain showing vitamin A deficiency associated with higher ICU admission. |
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Levels
Analysis of outcomes based on serum levels
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| Tomasa-Irriguible et al., Metabolites, doi:10.3390/metabo11090565 (preprint 10/26/2020) (Peer Reviewed) |
| Low Levels of Few Micronutrients May Impact COVID-19 Disease Progression: An Observational Study on the First Wave |
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Retrospective 120 hospitalized patients in Spain showing vitamin A deficiency associated with higher ICU admission.
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risk of mechanical ventilation, 71.4% lower, RR 0.29, p = 0.001, treatment 4 of 34 (11.8%), control 48 of 86 (55.8%), adjusted, OR converted to RR, ≥0.3 mg/L, multivariate logistic regression.
risk of ICU admission, 61.3% lower, RR 0.39, p = 0.004, treatment 6 of 34 (17.6%), control 54 of 86 (62.8%), adjusted, OR converted to RR, ≥0.3 mg/L, multivariate logistic regression.
Tomasa-Irriguible et al., 10/26/2020, retrospective, Spain, Europe, peer-reviewed, 7 authors.
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In Silico |
Li et al., Aging, doi:10.18632/aging.103888 (Peer Reviewed) |
Revealing the targets and mechanisms of vitamin A in the treatment of COVID-19 |
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Bioinformatics and network pharmacology analysis identifying potential mechanisms of action of vitamin A for COVID-19. |
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In Silico
In Silico
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| Li et al., Aging, doi:10.18632/aging.103888 (Peer Reviewed) |
| Revealing the targets and mechanisms of vitamin A in the treatment of COVID-19 |
Bioinformatics and network pharmacology analysis identifying potential mechanisms of action of vitamin A for COVID-19.
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Li et al., 8/15/2020, peer-reviewed, 7 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
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Review |
Andrade et al., SciELO preprints, doi:10.1590/SciELOPreprints.839 (Review) (Peer Reviewed) |
review |
Vitamin A and D deficiencies in the prognosis of respiratory tract infections: A systematic review with perspectives for COVID-19 and a critical analysis on supplementation |
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Systematic review showing deficiencies of vitamins A and D negatively affecting the prognosis of respiratory tract infections. |
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Review
Review
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| Andrade et al., SciELO preprints, doi:10.1590/SciELOPreprints.839 (Review) (Peer Reviewed) |
| Vitamin A and D deficiencies in the prognosis of respiratory tract infections: A systematic review with perspectives for COVID-19 and a critical analysis on supplementation |
Systematic review showing deficiencies of vitamins A and D negatively affecting the prognosis of respiratory tract infections.
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Andrade et al., 6/24/2020, peer-reviewed, 6 authors.
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