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Several reports suggest that vitamin D (VitD) deficiency could increase the predisposition to systemic infection, including respiratory tract infections and impaired immune response.1–4 A recent meta-analysis demonstrated that VitD supplementation can reduce the risk of respiratory tract infections overall based on data from randomised controlled trials.5 Moreover, an article reported a possible association of VitD level with cytokine storm and unregulated inflammation in elderly patients with COVID-19.6 It supported the potential protective impact of VitD by enhancing the immune system and possibly reducing the risk of complications associated with cytokine storm and unregulated inflammation in patients with severe COVID-19. VitD is a lipid-soluble vitamin that acts as a ligand to the intranuclear receptor superfamily and plays a significant role in regulating between innate and acquired immunity.1 25-Hydroxy vitamin D (25(OH)D) is the major circulating form of VitD in humans and currently accepted as the best marker of VitD status.7 To date, there are only a few reports focusing on nutritional status including 25(OH)D in healthcare workers (HCWs) during the COVID-19 pandemic.8
During the COVID-19 pandemic, we conducted a prospective observational study to evaluate several blood markers in HCWs at high risk of SARS-CoV-2 infection at the National Center for Child Health and Development in Tokyo, Japan.7 Blood sampling was performed from the enrolled participants from 1 March 2021 to 5 March 2021, and all clinical laboratory testing of the blood including VitD, zinc and natural killer (NK) cell activity were examined at the SRL Hachioji Laboratory Complex, in Tokyo, Japan. 25(OH)D was measured using chemiluminescent enzyme immunoassay, and serum zinc level was determined using the colorimetric method. Also, chromium-51 release assay was used to assess the NK cell activity. We analysed the relationship between gender and VitD levels using the Fisher’s exact test. In addition, the correlationship between VitD levels and age was calculated by the Pearson’s product–moment correlation coefficient and that between VitD levels and NK cell activity by the Spearman’s rank correlation coefficient. All the statistical analyses were performed using SPSS V.22.0 software package (IBM). A two-sided p<0.05 was considered statistically significant. In the study, 361 HCWs were enrolled, of whom 274 (75.9%) were women. The median age was 35 years (range, 22–67 years). The measured blood markers are summarised in table 1. Most of the measured data were within their normal ranges in most cases except for the blood markers of decreased ability to protect against infections. The NK cell activity widely varied between the participants and was below the lower limit of normal in 42.5% (37/87) of the male participants and 58.4% (76/274) of the female participants. However, there was no correlation between the NK cell activity and 25(OH)D level (r=–0.047, p=0.374). The zinc level was deficient in 17.2% (15/87) of the male participants and 27.7% (76/274) of the female participants. Surprisingly, the 25(OH)D level was remarkably low in our study participants. The 25(OH)D level was deficient (<20 ng/mL) in 89.7% (78/87) of the male participants (figure 1A) and in 92.7% (254/274) of the female participants (figure 1B). In addition, 25.3% (22/87) of the male participants and 48.2% (132/274) of the female participants had severe 25(OH)D deficiency (<10 ng/mL). The rate of the female participants with severe 25(OH)D deficiency was significantly higher than that of the male participants (p=0.001). Additionally, there was no correlation between age and serum 25(OH)D level (r=0.094, p=0.074). A recent article from the UK showed that HCWs with VitD deficiency were more likely to develop COVID-19.8 In the study population, HCWs in the black, Asian and minority ethnic groups were VitD deficient (70%), compared with Caucasians (30%).8 A study targeting Japanese women aged 39–64 years reported a mean 25(OH)D level of 24.63 ng/mL and that 31.6%, 27.0% and 14.9% of women aged 39–49, 50–59 and 60–64 years, respectively.9
Approximately 90% of the participants in this study had VitD deficiency regardless of sex. This might have resulted from long-term indoor activities, both in medical care and daily life, in compliance with the state-of-emergency declaration over COVID-19 and our institutional infection prevention and control measures against COVID-19. From the article mentioned previously,8 VitD deficiency was reported as an independent risk factor for developing COVID-19 seroconversion. Also, VitD potentially plays a significant role in preventing or alleviating acute respiratory tract infections including COVID-19, meanwhile, VitD levels could strongly account for variability COVID-19 severity: negative correlation between mean VitD levels and number of COVID-19 cases for one million population or outcomes/prognosis of patients with COVID-19.1 2 8 Thus, clinical trials for investigating the efficacy of VitD supplementation targeting at-risk VitD deficient HCWs for developing COVID-19 are warranted. This study has several limitations, such as those of a single-centre observational study in Japan in a single period; lack of assessment of medical history, including COVID-19 and VitD-related diseases; lack of evaluation on the impact of seasonality on VitD level; and lack of information about lifestyle and VitD supplementation. However, given the decreasing ultraviolet absorption and possible contributions to treatment and prevention of COVID-19 of sun exposure and VitD supplementation10 in addition to immediate COVID-19 vaccination, these measures should be considered to improve HCWs’ lifestyles, particularly in VitD-deficient HCWs.
Patient consent for publication
This study involves human participants and was approved by the National Center for Child Health and Development Institutional review Board. The reference number: 2020-266. Participants gave informed consent to participate in the study before taking part.
Contributors Concept and design: KY. Acquisition, analysis or interpretation of data: all authors. Drafting of the manuscript: TF and KY. Critical revision of the manuscript for important intellectual content: TF and KY. Statistical analysis: TF. Administrative, technical or material support: all authors. Supervision: KY.
Funding This work was supported by a grant from the Japan Health Research Promotion Bureau Research Fund (2020-B-09).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.