The goal of this clinical trial is to investigate the therapeutic efficacy of rapidly
correcting vitamin D deficiency in adults with the use of 25-hydroxyvitamin D3 [25(OH)D3] for
reducing the risk of acquiring the SARS-CoV-2 (COVID-19) viral infection and mitigating
morbidity and mortality associated with this infection. This evidence-based hypothesis is
related to several observations. Macrophages, activated T and B lymphocytes have a vitamin D
receptor and 1,25-dihydroxyvitamin D3 induces defensin protein synthesis, influences
immunoglobulin production and modulates T-cell cytokine production and functions.
1,25-dihydroxyvitamin D3 also reduces the angiotensin-converting enzyme 2 (ACE2) that is
believed to serve as the binding site and gateway for COVID-19 to become infectious. This is
a multicenter randomized3 doubleblinded placebo-controlled study aimed at determining the
benefits of 25(OH)D3 treatment for the prevention of COVID-19 infection and improving
clinical outcomes in infected patients. The investigators plan to recruit 1500 subjects in 3
study groups that include hospital health providers, patients with a positive test for
COVID-19 and their relatives with a negative test. Eligible subjects in each study group with
a documented serum level of 25(OH)D < 20 ng/mL will be randomized. Recruited subjects will be
given 25 mcg of 25(OH)D3 daily or an identically appearing placebo at the time of
randomization for two months. Three hospitals will participate and the sample size is
foreseen to be equally distributed between the three. Since the clinical trial is designed as
minimal risk a formal committee for data monitoring is not foreseen. However, potential
toxicity will be monitored every 4 weeks with a serum calcium, albumin and creatinine by the
PI and the study coordinators. If the corrected serum calcium increases above 10.6 mg/dl and
a repeat confirms that the calcium is above 10.6 mg/dL the subject will be dropped from the
study and referred to his or her PCP. Early signs and symptoms of vitamin D toxicity
associated with hypercalcemia are increased thirst, increase in frequency of urination,
especially at night. The subjects will be followed up weekly by phone to ask about their sign
and symptoms.