ABSTRACT
Aim . Assess the association of plasma vitamin D levels or
vitamin D supplementation with the outcomes of COVID- 19.Methods . PubMed, EMBASE, and Cochrane Library databases were
searched. Studies with COVID-19 patients that reported an association
between plasma vitamin D levels or vitamin D supplementation and
mortality, need of hospitalization, ICU admission, or ventilation
requirement published until December 8, 2020, were included. The risk
ratio (RR) and confidence interval (CI) were pooled using a
fixed-effects model. Results . A total of 16 studies were
included in the meta-analysis, eleven cohorts, one case-control, one
randomized clinical trial, and two quasi-experimental studies. Low
plasma vitamin D levels in patients with COVID-19 were associated with
mortality (RR=1.42, 95%CI 1.14 – 1.71), need for ICU admission
(RR=1.76, 95%CI 1.03-2.49), and need for ventilation (RR=3.58, 95%CI
1.45-5.70). Regular vitamin D supplementation showed a decreased risk of
death, and vitamin D treatment in patients with COVID-19 showed a
decrease in the need for ICU admission. Conclusion . Sufficient
vitamin D level is associated with better outcomes in patients with
COVID-19. Vitamin D supplementation in patients with COVID-19 appears to
reduce the risk of ICU admission and regular supplementation reduces
mortality.
Keywords : 25-hydroxyvitamin D; Cholecalciferol;
Ergocalciferols; Meta-analysis. SARS-Cov2.
INTROducTion
Since the first case registered in December 2019 in the city of Wuhan,
Hubei Province, China, COVID-19 has spread rapidly throughout the world
for presenting strong contagious and infectious characteristics1–3, which have caused 1,663,474 deaths until
December 19th, 2020 in 198 countries4.
Worldwide data from the pandemic demonstrate a mortality rate of 0.9%
in patients without comorbidities, which increases progressively based
on the number of comorbidities and the age of the
patients5. The existence of studies relating vitamin D
levels to Acute respiratory infections6, led to the
carrying out an ecological study wich showed that countries, where the
plasma mean vitamin D population is low, had higher rates of infection
and mortality from SARS-CoV27.
Isaia et al8 found a correlation between regions with
higher levels of solar ultraviolet (UV) radiation and lower rates of
morbidity and mortality related to COVID-19, the hypothesis discussed by
the authors is that it may be related to vitamin D levels. Exposure to
UV radiation determines the photo-conversion of the pro-vitamin D3
(7-dehydrocholesterol) in the skin to pre-vitamin D39.
In addition, many observational studies relating vitamin D level to
COVID-19 outcomes have emerged with divergent
results10–14 and in the absence of randomized
clinical trials, we proposed conducting a systematic review to assess
the association of plasma vitamin D levels or vitamin D supplementation
in the mortality, and severity of COVID- 19.
METHODS
Data Search
Two investigators searched MEDLINE, EMBASE, and Cochrane Library.
Studies published until December 8, 2020 were included. The following
search strategy was used: (coronavirus OR “coronavirus infections” OR
COVID-19 OR “severe acute respiratory syndrome coronavirus 2”) AND
(“vitamin D” OR “ergocalciferol” OR “cholecalciferol” OR “vitamin
D deficiency” OR calcitriol OR calcifediol OR alfacalcidol OR
paricalcitol OR doxercalciferol). The language of the searches was
limited to English, Spanish and Portuguese.
Study selection
The studies were screened by two independent authors. Disagreements were
resolved through discussion among all authors. Summaries of retrieved
articles were reviewed to exclude irrelevant studies, followed by
reading full text for screening.
Studies were included if they met the following inclusion criteria: (1)
enrolled COVID-19 patients with plasma vitamin D level
(25-hydroxyvitamin D) or COVID-19 patients in vitamin D or analogs use.
All studies used throat swab SARS-CoV-2 real-time reverse
transcription-polymerase chain reaction (RT-PCR) nucleic acid to confirm
COVID-19; (2) examined the association between vitamin D use or plasma
vitamin D level with mortality or disease severity (death,
hospitalization, intensive care unit - ICU admission and ventilation
requirement); (3) observational or interventional studies. Ecological,
cross-sectional, and studies that plasma vitamin D level was measured
more than a year ago were excluded.