The purpose of this study is to evaluate how useful vitamin D supplementation is inreducing the severity of COVID-19 symptoms and the body's inflammatory andinfection-fighting response to COVID-19. Individuals ≥50 years of age and older who aretested for COVID-19 and negative will be randomized (like flipping a coin) to eitherdaily high dose vitamin D supplementation (6000 IU vitamin D3/day) vs. standard of care.Those individuals ≥50 years of age or older who test positive for COVID-19 at baselinewill be randomized to bolus vitamin D (20,000 IU/day for 3 days) followed by high dose(6000 IU vitamin D/day) vs. standard of care for 12 months. All participants will receivea multivitamin containing vitamin D.
Vitamin D (vitD) deficiency is more prevalent among African Americans and Latinx and in
the elderly who have low exposure to sunlight. African Americans and nursing home
residents who contract SARS-CoV-2, the novel virus that first appeared in Wuhan, China,
and who develop the disease designated COVID-19 experience a much worse clinical outcome
than other groups. Some have speculated that low vitD status could exacerbate COVID-19
infection, especially if the viral infection reaches the lower respiratory tract.
Sufficient vitD may help to improve the pulmonary immune response to the virus, reduce
the dangerous cytokine storm, and lessen surfactant dysregulation, potentially preventing
or ameliorating the acute syndrome. To maximize the benefits of vitD on host response to
SARS-CoV-2, prophylactic supplementation to ensure sufficiency before COVID-19 would be
the preferable public health option. Yet, vitD supplementation during acute infection may
also improve overall clinical outcome in some infected patients. It is a relatively
inexpensive therapy that has a large safety profile when given in doses of 4000-6000
international units/day to adults.
To date, there is no effective cure or preventive vaccine for COVID-19. Given the risk of
disease and death, any intervention that reduces the morbidity and mortality from
COVID-19 would be of immense value. We hypothesize that achieving and sustaining vitD
sufficiency through dietary supplementation will result in improved immune function and a
decrease in COVID-19 incidence and symptomatology. Importantly, this objective will
address the significant health disparity of vitD deficiency among black, Latina and the
elderly. We further hypothesize that those individuals with a circulating 25(OH)D of ≥40
ng/mL will have less severe COVID-19 symptoms, particularly among higher risk
populations. We will compare the effectiveness of higher dose vitD vs. standard of care
dosing.To test these hypotheses, we propose the following Aims:
1. Focusing on prevention, this Aim will test whether achieving vitD sufficiency (as
defined by total circulating 25(OH)D ≥40-60 ng/mL) in individuals at risk for
deficiency will improve clinical outcomes in those who subsequently develop
COVID-19.
2. Focusing on vitD as mitigation therapy, this Aim will evaluate the effectiveness of
bolus dosing followed by daily vitD supplementation in achieving the target 25(OH)D
range of ≥40-60 ng/mL in those individuals testing positive for COVID-19 at
MUSC/affiliated hospital facilities, but do not require admission to a hospital
(outpatient) and will examine whether achieving this target range is associated with
less severe COVID-19 and differences in inflammatory cytokine profiles.
In the prevention arm of this project (Aim 1), individuals at higher risk ≥50 years of
age who test negative for COVID-19 at MUSC/its affiliate hospitals, and agree to daily
vitD supplementation for a 12-month period, with vitD status measured monthly will be
randomized to placebo or prescribed vitD (6000 IU/day) to achieve a total circulating
25(OH) concentration of ≥40-60 ng/mL. We will compare study groups regarding subsequent
infection with COVID-19, severity of symptoms, need and duration of hospitalization
(LOS), admission to the ICU, need for ventilatory support, and mortality, along with
return to baseline activities and/or work, as a function of age, BMI, and other
recognized COVID-19 risk factors. In the mitigation arm of this project (Aim 2),
non-hospitalized individuals ≥50 years of age who test COVID-19 positive will be
randomized to placebo or a bolus of oral vitD (20,000 IU X 3 days) followed by 6000 IU
vitD/day, and we will compare study groups on measures of disease severity as in Aim 1.
All participants in both Aims 1 and 2 will receive a daily multivitamin (MVI) containing
800 IU VitD for the 12-month period.
Following the completion of these Aims, we will be able to answer the following
questions:
1. Are individuals with vitD deficiency more likely to be diagnosed with COVID-19
infection?
2. Does being vitD replete make a person more likely to have asymptomatic COVID-19?
3. Does vitD sufficiency status account for why African Americans, Latina, and the
elderly more likely to experience complications related to COVID-19?
4. Is vitD deficiency in COVID-19 positive outpatients associated with increased
severity of symptoms and differences in inflammatory cytokine profiles that is
mitigated by bolus and then sustained vitD supplementation?
The long-term impact of these studies will influence public policy regarding more
widespread vitD supplementation is a means of reducing the severity of COVID-19. Given
its low cost and the ease with which widespread supplementation could be instituted, oral
vitD supplementation may represent a rapid and inexpensive means by which to reduce both
the COVID-19 incidence and severity.
Drug: Daily Vitamin D3
6000 IU vitamin D3 daily
Other Name: Daily cholecalciferol
Drug: Daily placebo
Placebo daily
Drug: Bolus vitamin D3
Bolus 20,000 IU vitamin D3 daily for 3 days
Other Name: Bolus cholecalciferol
Drug: Bolus placebo
Bolus placebo daily for 3 days
Entry Criteria:
---Adults aged 50 years of age or older who presents to MUSC or its affiliate hospitals
(or associated testing centers) for COVID-19 testing during the recruitment period is
eligible for participation.
Exclusion Criteria:
- Hospitalization at the time of study recruitment.
- Any individual less than 50 years of age. The reason that the participants ≥50 years
are being excluded from this study is because those who are ≥50 years have a higher
risk of being symptomatic with COVID-19 and have the potential for the greatest
benefit. The disease appears to manifest differently in children and its occurrence
is quite rare.
- Only those patients tested for COVID-19 initially will be eligible to participate;
therefore, anyone wanting to participate in the trial must have had a COVID-19 test
prior to enrollment/participation in the study.
- Any individual who is not capable of making independent decisions and who is
considered cognitively impaired.
Medical University of South Carolina
Charleston, South Carolina, United States
Carol L Wagner, MD, Principal Investigator
Medical University of South Carolina