Rifampicin for COVID-19.

Vaccinations for coronavirus disease-2019 (COVID-19) have begun more than a year before, yet without specific treatments available. Rifampicin, critically important for human medicine (World Health Organization's list of essential medicines), may prove pharmacologically effective for treatment and chemoprophylaxis of healthcare personnel and those at higher risk. It has been known since 1969 that rifampicin has a direct selective antiviral effect on viruses which have their own RNA polymerase (severe acute respiratory syndrome coronavirus 2), like the main mechanism of action of remdesivir. This involves inhibition of late viral protein synthesis, the virion assembly, and the viral polymerase itself. This antiviral effect is dependent on the administration route, with local application resulting in higher drug concentrations at the site of viral replication. This would suggest also trying lung administration of rifampicin by nebulization to increase the drug's concentration at infection sites while minimizing systemic side effects. Recent in silico studies with a computer-aided approach, found rifampicin among the most promising existing drugs that could be repurposed for the treatment of COVID-19.

Association between population vitamin D status and SARS-CoV-2 related serious-critical illness and deaths: An ecological integrative approach.

BACKGROUND: Vitamin D population status may have possible unappreciated consequences to the coronavirus disease 2019 (COVID-19) pandemic. Α significant association between vitamin D sufficiency and reduction in clinical severity and inpatient mortality from COVID-19 disease has recently been shown, while a recent study has claimed lower COVID-19 cases in European countries with a better vitamin D status. Low serum 25-hydroxyvitamin-D [25(OH)D] was identified as an independent risk factor for COVID-19 infection and hospitalization, and administration of 0.532 mg (21280 IU) of calcifediol or 25(OH)D, followed by 0.266 mg on days 3 and 7 and then weekly until discharge or intensive care unit admission significantly reduced the need for intensive care unit treatment. AIM: To elucidate the role of vitamin D European population status in the COVID-19 pandemic, data from the Worldometer were analyzed. METHODS: Linear regression explored the correlation between published representative-standardized population vitamin D concentrations and the number of total cases/million (M), recovered/M, deaths/M and serious-critically ill/M from COVID-19 for 26 European countries populated > 4 M (Worldometer). Life expectancy was analyzed with semi-parametric regression. Weighted analysis of variance/analysis of covariance evaluated serious-critical/M and deaths/M by the vitamin D population status: Deficient < 50, insufficient: 50-62.5, mildly insufficient > 62.5-75 and sufficient > 75 nmol/L, while controlling for life expectancy for deaths/M. Statistical analyses were performed in XLSTAT LIFE SCIENCE and R (SemiPar Library). RESULTS: Linear regression found no correlation between population vitamin D concentrations and the total cases-recovered/M, but negative correlations predicting a reduction of 47%-64%-80% in serious-critical illnesses/M and of 61%-82%-102.4% in deaths/M further enhanced when adapting for life expectancy by 133-177-221% if 25(OH)D concentrations reach 100-125-150 nmol/L, sustained on August 15, 2020, indicating a truthful association. Weighted analysis of variance was performed to evaluate serious-critical/M (r 2 = 0.22) by the vitamin D population status and analysis of covariance the deaths/M (r 2 = 0.629) controlling for life expectancy (r 2 = 0.47). Serious-critical showed a decreasing trend (P < 0.001) from population status deficient (P < 0.001) to insufficient by 9.2% (P < 0.001), to mildly insufficient by 47.6% (P < 0.044) and to sufficient by 100% (reference, P < 0.001). For deaths/M the respective decreasing trend (P < 0.001) was 62.9% from deficient (P < 0.001) to insufficient (P < 0.001), 65.15% to mildly insufficient (P < 0.001) and 78.8% to sufficient (P = 0.041). CONCLUSION: Achieving serum 25(OH)D 100-150 nmol/L (40-60 ng/mL) (upper tolerable daily doses followed by maintenance proposed doses not requiring medical supervision, Endocrine Society) may protect from serious-critical illness/death from COVID-19 disease.

Association Between Population Vitamin D Status and SARS-CoV-2 Related Serious-Critical Illness and Deaths

Background: Vitamin-D population status may have possible unappreciated consequences to the COVID-19 pandemic. Α significant association between vitamin-D sufficiency and reduction in clinical severity and inpatient mortality from COVID-19 disease was recently shown while a recent study has claimed lower COVID-19 cases in European countries with a better vitamin D status. Aims: To further elucidate the possible role of vitamin D population status in the COVID-19 pandemic, we examined the associations between published representative and standardized population vitamin D data on European population vitamin D status and the Worldometer COVID-19 data. Methods: Data from the Worldometer on 26 European countries populated &gt;4 million (M) were analyzed. Results: On 19-June-2020, linear regression found no correlation between published representative-standardized population vitamin-D concentrations and the total cases-recovered/M, but negative correlations predicting a reduction of 47-64-80% in serious-critical illnesses/M and of 61-82-102.4% in deaths/M, further enhanced when adapting for life expectancy by 133-177-221% if 25(OH)D concentrations reach 100-125-150 nmol/L. On 15-August-2020 these correlations were sustained indicating a truthful association, yet not proving causality. Weighted ANOVA was performed to evaluate serious-critical/M (R2=0.22) by the vitamin-D population status (deficient-D &lt;50, insufficient-IN 50–62.5, mildly insufficient-MIN &gt;62.5–75 and sufficient-S &gt;75 nmol/L) and ANCOVA the deaths/M (R2=0.629) after controlling for life expectancy (R2=0.47). Serious-critical showed a decreasing trend (p&lt;0.001) from population status D (p&lt;0.001) to IN: 9.2%, p&lt;0.001, MIN: 47.6%, p&lt;0.044 and S: 100% (reference). For deaths/M the respective decreasing trend (p&lt;0.001) was 62.9% from D (p&lt;0.001) to IN (p&lt;0.001), 65.15% to MIN (p&lt;0.001) and 78.8% to S (p=0.041). Conclusions: Following the Endocrine Society’s expert committee recommendations, without previous testing being necessary, reaching and maintaining a serum 25(OH)D of 100–150 nmol/L (40–60 ng/ml) could be achieved by an initial supplementation with the upper tolerable daily intake doses (IU/day) for up to two months: &lt;1yr 2000, 1-18yrs 4000 and all adults 10,000 (obese x 2–3 times more) and then with the maintenance proposed doses that do not require medical supervision, practically identical with the IOM’s upper tolerable limits: 1000 &lt;6m, 1500 6m-1yr, 2500 1-3yrs, 3000 4-8yrs, and 4000 &gt;8yrs, with adults and adolescents requiring 4000–5000 (obese x 2). Vitamin D may not prevent SARS-CoV-2 from spreading but may protect, without any risk of toxicity, from serious-critical illness and death from COVID-19 disease. While awaiting well-designed prospective studies, following the proposed approach, the gain for global public health and not only against SARS-CoV-2 may just prove invaluable.