Effectiveness of a 'test-and-treat' approach for identification and treatment of vitamin D insufficiency for prevention of COVID-19

In a recent study posted to the medRxiv* preprint server, researchers determined the impact of vitamin D status in preventing all-cause acute respiratory infection (ARI) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. 

Study: Vitamin D Supplements for Prevention of Covid-19 or other Acute Respiratory Infections: a Phase 3 Randomized Controlled Trial (CORONAVIT). Image Credit: Alrandir/Shutterstock


The SARS-CoV-2 pandemic has refocused attention on prevention approaches for ARI. Vaccination against coronavirus disease 2019 (COVID-19) is the gold standard for controlling SARS-CoV-2 infection. Yet, its global efficacy is hampered by many issues such as vaccine reluctance, cost, vaccine failure, and availability. Hence, low-cost alternative treatments are needed to boost the immune responses to SARS-CoV-2 and other ARI-causing pathogens.

Vitamin D metabolites aid natural immunity to CoVs that causes SARS-CoV-2 and similar respiratory pathogens. Existing longitudinal analyses provided mixed results regarding the impact of vitamin D in COVID-19 prophylaxis. Multiple meta-analyses reported an overall protective mechanism of vitamin D against SARS-CoV-2. Nevertheless, there have been no randomized controlled trials (RCT) evaluating the impact of vitamin D in preventing COVID-19.

About the study

In the present phase 3 pragmatic RCT named CORONAVIT, the researchers evaluated the efficacy of a test-and-tear strategy for detecting and managing vitamin D deficiency for preventing SARS-CoV-2 and other ARI. The study was conducted from December 2020 to June 2021 in those above 16 years of age in the United Kingdom (UK). The trial period corresponded to a time of high SARS-CoV-2 incidence and low vaccine coverage in the UK. The present study was nested inside the population-based COVIDENCE UK cohort investigation employing a trial within cohort strategy.

The study's exclusion criteria were existing vitamin D supplementation, known pregnancy, renal failure needing dialysis, known sarcoidosis diagnosis, nephrolithiasis, allergies to any chemical in the trial capsule, and primary hyperparathyroidism. The subjects were enrolled and followed up using online questionnaires. 

The scientists randomly offered 6200 individuals a postal finger-prick 25-hydroxyvitamin D (25[OH]D) evaluation. This was followed by an offer for six-month supplementation of low-dose vitamin D (800 IU/d) in 1550 subjects, high-dose vitamin D (3200 IU/d) in 1550 subjects, or 3100 individuals with no offer of supplementation or testing. 

The follow-up survey gathered information regarding incidents of ARIs, asthma exacerbations, chronic SARS-CoV-2 symptoms, chronic obstructive pulmonary disease (COPD), adverse events, and adherence. The main outcome of the investigation was the percentage of subjects with at least one doctor- or swab test-validated acute respiratory infection (ARI) of any origin at last six months. The occurrence of swab test-validated SARS-CoV-2 was among the secondary outcomes of the study.


The results showed that among the 6200 subjects, the median age was 60.2 years, 4156 were females, and 2.5% were vaccinated with one or more doses of COVID-19 vaccines. Among participants in whom baseline vitamin D level was evaluated, the mean 25(OH)D concentration was 39.7nmol/L, and 97.4% exhibited 25(OH)D concentration less than 75nmol/L.

Among the 3100 subjects offered postal vitamin D testing, 2958 individuals accepted. Of these participants, blood 25(OH)D levels of 2690 were less than 75nmol/L. High-dose and low-dose vitamin D supplements were sent to 1356 and 1334 subjects, respectively.

At least one incidence of ARI from any cause or COVID-19 was observed in 76, 87, and 136 subjects in high-dose vitamin D, low-dose vitamin D, and no-offer cohort, respectively. Neither vitamin D doses had a statistically relevant impact on the swab test- or doctor-confirmed ARI or SARS-CoV-2 infection. These data indicate that previous observational studies' positive results might probably be due to collider or confounding bias. 

Supplementation of vitamin D orally was well-tolerated and safe at both doses evaluated. The frequency of adverse reactions was similar across the two arms, and no significant adverse event was linked to the study supplements. Nearly 90.9% of subjects took vitamin D supplements with good adherence. 

Only 0.6% of the subjects withdrew from the study without any follow-up. At the end of the monitoring period, 5523 of 6200 participants received at least one COVID-19 vaccine dose. Additionally, mean 25(OH)D levels were dramatically enhanced in the high- and low-dose vitamin D group compared to the no-offer cohort by the end of the study.


According to the authors, this was the first RCT in the UK to assess the effectiveness of a test-and-treat method to correct vitamin D deficiency in ARI and SARS-CoV-2 prophylaxis. The study findings implied that executing a test-and-treat strategy for vitamin D replacement did not lower the incidence of COVID-19 or all-cause ARI in persons with a high baseline incidence of vitamin D deficiency. However, the current strategy was efficient in correcting the vitamin D deficiency among individuals with baseline 25(OH)D levels <75nmol/L.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Jolliffe, D. et al. (2022) "Vitamin D Supplements for Prevention of Covid-19 or other Acute Respiratory Infections: a Phase 3 Randomized Controlled Trial (CORONAVIT)". medRxiv. doi: 10.1101/2022.03.22.22271707. https://www.medrxiv.org/content/10.1101/2022.03.22.22271707v1

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Asthma, Blood, Chronic, Chronic Obstructive Pulmonary Disease, Coronavirus, Coronavirus Disease COVID-19, covid-19, Dialysis, Doctor, Efficacy, Frequency, Hyperparathyroidism, immunity, Metabolites, Pandemic, Pregnancy, Primary Hyperparathyroidism, Prophylaxis, Renal Failure, Respiratory, Sarcoidosis, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Supplements, Syndrome, Vaccine, Vitamin D, Vitamin D Deficiency

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Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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