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Acute respiratory tract infections (ARIs) are a leading cause of ill-health and death globally. Individual or multiple micronutrients have been shown to modulate immune function and affect the risk and severity of a number of infectious diseases. We systematically reviewed the evidence on the impact of micronutrient supplements to reduce the occurrence of ARIs and shorten the duration of ARI symptoms among adults. Random effects meta-analyses were conducted to estimate the pooled effects of vitamin D, vitamin C, zinc and multiple micronutrient supplementation (MMS) on the occurrence of ARIs and the duration of ARI symptoms. Vitamin D supplementation reduced the risk of ARI (risk ratio (RR)=0.97; 95% CI 0.94 to 1.00; p=0.028) and shortened the duration of symptoms (per cent difference: −6% (95% CI −9% to −2%; p=0.003)). The RR of vitamin D to prevent ARI was farther from the null when diagnosis was based on clinical diagnosis or laboratory testing, compared with self-report and when the loading dose was p=0.0004)). Our synthesis of global evidence from randomised controlled trials indicates that micronutrient supplements including zinc, vitamins C and D, and multiple micronutrient supplements may be modestly effective in preventing ARIs and improving their clinical course. Further research is warranted to better understand the effectiveness that individual or multiple micronutrients have on SARS-CoV-2 infection and treatment outcomes.

IntroductionVitamin D status may be an important determinant of multidrug-resistant tuberculosis (MDR-TB) infection, progression to disease and treatment outcomes. Novel and potentially cost-effective therapies such as vitamin D supplementation are needed to stem the tide of TB and MDR-TB globally, particularly in India, a country that accounts for the largest fraction of the world’s TB incidence and MDR-TB incidence, and where vitamin D deficiency is endemic. While vitamin D has shown some promise in the treatment of MDR-TB, its role in the context of MDR-TB infection and progression to disease is largely unknown.Methods and analysisThrough a case–control study in Mumbai, India, we aim to examine associations between vitamin D status and active MDR-TB and to investigate vitamin D status and TB infection among controls. Cases are adult outpatient pulmonary patients with MDR-TB recruited from two public TB clinics. Controls are recruited from the cases’ household contacts and from non-respiratory departments of the facilities where cases were recruited. Cases and controls are assessed for serum 25-hydroxyvitamin D concentration, nutrient intake, diet quality, anthropometry and other relevant clinical and sociodemographic parameters. Controls undergo additional clinical assessments to rule out active TB and laboratory assessments to determine presence of TB infection. Statistical analysis investigates associations between vitamin D status and active MDR-TB and between vitamin D status and TB infection among controls, accounting for potential confounding effects of diet, anthropometry and other covariates.Ethics and disseminationThis study has been approved by Harvard T.H. Chan School of Public Health Institutional Review Board; Foundation for Medical Research Institutional Research Ethics Committee and Health Ministry’s Screening Committee of the Indian Council for Medical Research. Permission was granted by the Municipal Corporation of Greater Mumbai, India, a collaborating partner on this research. Outcomes will be disseminated through publication and scientific presentation.Trial registration numberNCT04342598.

Introduction and objectives Existing trials of adjunctive vitamin D to enhance response to antimicrobial therapy for pulmonary tuberculosis are variously limited by relatively small sample sizes, inadequate dosing regimens and low baseline prevalence of vitamin D deficiency among participants. Our objective was to conduct a large randomised controlled trial of high-dose vitamin D in a setting where profound vitamin D deficiency was common in patients with pulmonary TB. Methods We conducted a double-blind randomised placebo-controlled trial of high-dose adjunctive vitamin D3 in adults with sputum smear-positive pulmonary tuberculosis in Ulaanbaatar, Mongolia. 390 participants were allocated to receive 3.5 mg vitamin D3 (n = 190) or placebo (n = 200) at baseline and at 2, 4 and 6 weeks after starting standard tuberculosis treatment. The primary endpoint of the trial was time from initiation of antimicrobial therapy to sputum culture conversion. Secondary endpoints were time to sputum smear conversion, resolution of infiltrates on chest radiograph and serum 25-hydroxyvitamin D (25[OH]D) concentrations. This trial was registered with ClinicalTrials.gov (NCT01657656). Results At baseline, 81% of participants had profound vitamin D deficiency (serum 25[OH]D Conclusions This is the largest randomised controlled trial to investigate effects of adjunctive vitamin D on time to sputum culture conversion in pulmonary tuberculosis conducted to date. Adjunctive high-dose vitamin D was effective in elevating serum 25(OH)D concentrations to high-physiological levels, but did not influence time to sputum culture conversion.