key: cord-0895085-75rhjcz5
authors: Demir, Mustafa; Demir, Fadime; Aygun, Hatice
title: Vitamin D deficiency is associated with COVID‐19 positivity and severity of the disease
date: 2021-02-09
journal: J Med Virol
DOI: 10.1002/jmv.26832
sha: 7286c50700a06519fef5ede1723973f57ab63b0c
doc_id: 895085
cord_uid: 75rhjcz5

The present study examined the relationship between polymerase chain reaction (PCR) test positivity and clinical outcomes of vitamin D levels measured within the 6 months before the PCR test in coronavirus disease 2019 (COVID‐19)‐positive patients. In this retrospective cohort study, COVID‐19 (227) and non‐COVID‐19 patients (260) were divided into four groups according to their vitamin D levels: Group I (0–10 ng/ml), Group II (10–20 ng/ml), Group III (20–30 ng/ml), and Group IV (vitamin D > 30 ng/ml). Laboratory test results and the radiological findings were evaluated. In addition, for comparative purposes, medical records of 1200 patients who had a hospital visit in the November 1, 2019–November 1, 2020 period for complaints due to reasons not related to COVID‐19 were investigated for the availability of vitamin D measurements. This search yielded 260 patients with tested vitamin D levels. Vitamin D levels were below 30 ng/ml in 94.27% of 227 COVID‐19‐positive patients (average age, 46.32 ± 1.24 years [range, 20–80 years] and 56.54% women) while 93.07% of 260 non‐COVID‐19 patients (average age, 44.63 ± 1.30 years [range, 18–75 years] and 59.50% women) had vitamin D levels below 30 ng/ml. Nevertheless, very severe vitamin D deficiency (<10 ng/ml) was considerably more common in COVID‐19 patients (44%) (average age, 44.15 ± 1.89 years [range, 23–80 years] and 57.57% women) than in non‐COVID‐19 ones (31%) (average age, 46.50 ± 2.21 years [range, 20–75 years] and 62.5% women). Among COVID‐19‐positive patients, the group with vitamin D levels of >30 ng/ml had significantly lower D‐dimer and C‐reactive protein (CRP) levels, number levels, number of affected lung segments and shorter hospital stays. No difference was found among the groups in terms of age and gender distribution. Elevated vitamin D levels could decrease COVID‐19 PCR positivity, D‐dime and CRP levels and the number of affected lung segments in COVID‐19‐positive patients, thereby shortening the duration of hospital stays and alleviating the intensity of COVID‐19.

The novel coronavirus has infected millions of people, and World Health Organization (WHO) has declared COVID-19 as a pandemic in March 2020. 1 COVID-19 is an RNA virus, which affects multiple organs including lung, liver, kidney, brain, and heart in humans, and has resulted in the death of about 1.8 million people worldwide (WHO COVID-19 Dashboard). The etiology of COVID- 19 has not yet been fully elucidated. The main cause of death in COVID-19 patients is inflammation, especially in the lung which leads to acute respiratory distress syndrome (ARDS). 1 No specific treatment is available for fatal and fast-spreading COVID-19 infection. Antimalarial (chloroquine and hydroxychloroquine), antiviral drugs (remdesivir), and dexamethasone (corticosteroid) are being used clinically for the treatment of COVID-19 patients. 2 Considering the fact that an adequate immune response is crucial for overcoming this viral infection, it is important to identify the existing and known substances that strengthen immune system activity.

Vitamin D, a steroid and versatile hormone, plays crucial roles in phosphorus-calcium metabolism and in the immune system of both humans and animals. 3 Numerous studies have revealed a wide range of pharmacological and physiological functions of vitamin D. It has anti-inflammatory, antioxidant, and antiviral effects. Besides this, it has crucial regulatory roles in the adaptive and innate immune systems. 4 It was shown that vitamin D deficiency is quite common among COVID-19 patients. 5 A recent clinical study showed that COVID-19 patients supplemented with vitamin D had less severe symptoms of the disease. 6 In the present study, we aimed to identify possible associations of vitamin D levels with laboratory test parameters, radiological findings, length of hospital stays, and the average age of the patients infected with COVID-19. 

The study sample was selected retrospectively among 2600 patients over 18 years of age with COVID-19 positivity based on real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay performed in Tokat State Hospital on March 30, 2020-November 1, 2020 period. The patients whose vitamin D levels were measured within the 6-month period before their COVID-19 test were identified and 227 such patients were found. COVID-19-positive patients whose vitamin D levels were not measured within the 6-month before the PCR test were excluded. Data of the participants regarding daily medical knowledge, laboratory and radiological results were retrieved from the electronic medical records. The studied parameters were the laboratory tests and radiological findings at the first arrival of COVID-19 patients to the hospital along with their age (over 18 years old), genders, and hospital stay.

The study covered patients who had PCR positivity for COVID-19 in the March 30-November 1, 2020 period and whose vitamin D levels were measured in the 6 months before the PCR test. However, to make comparisons, non-COVID-19 patients whose vitamin D levels were measured in the November 1, 2019-November 1, 2020 period in Tokat State Hospital were screened retrospectively using the hospital automation system and included in the study. Age (over the 18-year old), gender, and vitamin D levels of the patients were recorded. When more than one vitamin D measurement was available, only the first one was used. 7, 8 The patients were divided into four groups based on their vitamin D levels:

Group I: patients with vitamin D levels less than 10 ng/ml. 

Computed tomography (CT) scans were performed using a 16-slice CT scanner (Toshiba) for all participants who were admitted to the hospital. One or more ground-glass opacities, consolidation, and reticular pattern were accepted as the diagnostic criteria of typical CT manifestations of COVID-19. CT Scans were performed just after admission to the hospital. An expert specialist evaluated all CT images.

All statistical analyses were performed using SPSS software (version 15) . The data were presented as mean ± SEM. Moreover, the number (n) and percentages (%) of the patients were calculated for study groups established for vitamin D level. Normality of distributions in the groups was determined. When a normal distribution was involved, ANOVA and subsequent LSD testing were performed to compare group means. When the distribution was not normal, Kruskal-Wallis variance analysis test and Mann-Whitney U test were used. The gender distribution among the groups were compared using the χ 2 -test with continuity correction.

A total of 2600 patients whose RT-PCR tests for COVID-19 were positive were screened, and medical records of these patients were examined to identify those who had their vitamin D levels tested anytime within the 6-month period before the COVID- 19 women) of non-COVID-19 patients ( Figure 1 , Table 2 ).

The laboratory tests examined included hemograms, biochemical, and inflammatory markers, which were assayed when patients first arrived at the hospital ( Table 1) 

The mean number of affected lung segments were 2.33 ± 0.20 in 

The present retrospective study examined the associations of vitamin D levels measured within 6 months before the COVID-19 test Ground-glass opacity is the most common CT feature of patients with COVID-19 viral pneumonia. 30 It becomes apparent in patients a few days after the onset of the disease. CT images in the present study were obtained at the first arrival of the patients to the hospital.

In the group with vitamin D level of >30 ng/ml, there were fewer lung segments with ground-glass opacity appearance than in groups with vitamin D levels of <30 ng/ml.

Areas of ground-glass opacity on CT scans show pathological diffuse alveolar damage. 31 Pulmonary edema is the most common cause of diffuse ground-glass opacity. 32 

In the present single-centered retrospective cohort study, vitamin D deficiency was found to be associated with a higher COVID-19

risk. The COVID-19-positive individuals with sufficient vitamin D levels had significantly lower blood levels of D-dimer, inflammatory marker CRP, reduced frequencies of ground-glass opacity appearance in chest CT scans and shorter hospital stays.

The findings of the study indicated the need for randomized studies to determine whether the vitamin D level could affect COVID-19 risk.

The present study had some limitations. Vitamin D deficiency could be due to various chronic conditions or behavioral factors, which themselves might be associated with a higher COVID-19 risk. In addition, the study covered a limited amount of data in the electronic database of Tokat State Hospital only.

The authors declare that there are no conflict of interests.

Hatice Aygun conceived and designed the research. Hatice Aygun, Fadime Demir, Mustafa Demir collected, analyzed and interpreted the data. Hatice Aygun wrote the article. All authors read and approved the manuscript.

The peer review history for this article is available at https://publons. com/publon/10.1002/jmv.26832

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

The study was approved by the 

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Vitamin D deficiency is associated with COVID-19 positivity and severity of the disease