Impact of Serum 25-Hydroxyvitamin D Levels and Body Mass Index on COVID-19 Hospitalization and Severity: Implications for Healthcare Strategies
Mehdi Ahmadi, Ramin Shahbahrami, Fatemeh Khajeh, Mehrdad Naghizadeh, Zahra Hashami, Fatemeh Javaheri-Ghezeldizaj, Somayeh Hajinezhad, Reza Hazrati Raziabad, Seyede Marzieh Hosseiniintroduction:
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed significant challenges to global healthcare systems since its emergence in late 2019 (Nimavat et al., 2022). The disease manifests with a broad spectrum of severity, ranging from asymptomatic infections to critical conditions requiring intensive care, resulting in substantial morbidity and mortality (Chen et al., 2020). Identifying risk factors associated with adverse outcomes is essential for optimizing treatment strategies and improving patient prognosis(Simonnet et al., 2020; Yang et al., 2020). Among these, vitamin D deficiency and body mass index (BMI) have emerged as potential modulators of COVID-19 severity and hospitalization duration (Yang et al., 2020). Vitamin D, primarily recognized for its role in bone health and calcium metabolism, also serves as a critical immunomodulator in infectious diseases (Singh et al., 2021). Low serum 25-hydroxyvitamin D levels are associated with increased inflammatory cytokine production, heightened risk of viral respiratory infections, and acute respiratory distress syndrome (ARDS), a key determinant of COVID-19 severity (Bayraktar et al., 2022; El-Din et al., 2024; Hamed et al., 2024). Vitamin D deficiency is prevalent among older adults, individuals with obesity(Zhang et al., 2025), and those with chronic conditions such as diabetes(Dominguez et al., 2024; Fei et al., 2024) and hypertension (Alagacone et al., 2020). Furthermore, low vitamin D levels correlate with thrombosis which is a common complication in COVID-19 patients, suggesting a mechanistic link to disease progression (AlNafea & Korish, 2023; Mohd et al., 2021). Obesity, defined by the World Health Organization as a BMI ≥30 kg/m², is a well-established risk factor for severe viral infections, including the 2009 influenza A (H1N1) and Middle East respiratory syndrome (MERS-CoV) pandemics (Guglielmi et al., 2021; Magdy Beshbishy et al., 2020; Pugliese et al., 2022; Yu et al., 2021). In COVID-19, obesity is associated with increased hospitalization rates and mechanical ventilation needs, potentially due to impaired immune responses and Obesity could drive the direction of severe COVID-19 symptoms to younger people (Aghili et al., 2021). Few studies have concurrently examined the combined effects of 25-hydroxyvitamin D levels and BMI on COVID-19 outcomes. Given their shared associations with immune function and inflammation, investigating these factors together may provide insights into their synergistic impact on disease severity and hospitalization duration. This study aims to evaluate the associations between serum 25-hydroxyvitamin D levels, BMI, and the severity and duration of hospitalization among COVID-19 patients admitted to Besat Hospital in Tehran, Iran.
materials and methods:
Study Design and Population This retrospective, cross-sectional study was conducted at Besat Hospital in Tehran, Iran, from April 1, 2022, to June 30, 2022. The study included 96 patients hospitalized with confirmed COVID-19, diagnosed via nasopharyngeal polymerase chain reaction (PCR) testing for SARS-CoV-2. Eligible patients had documented serum 25-hydroxyvitamin D levels and body mass index (BMI) data available in hospital records. Exclusion criteria included incomplete medical records or concurrent conditions significantly affecting vitamin D metabolism (e.g., severe renal or hepatic disease). Demographic data, comorbidities, hospitalization duration, and disease severity (defined by admission to general or intensive care unit [ICU]) were extracted from electronic medical records. Data Collection Serum 25-hydroxyvitamin D levels were measured using standardized laboratory assays, with levels categorized as deficient (<20 ng/mL), insufficient (20–40 ng/mL), or sufficient (≥40 ng/mL). BMI was calculated as weight (kg) divided by height squared (m²) and classified according to World Health Organization criteria: underweight (<18.5 kg/m²), healthy weight (18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²), or obese (≥30.0 kg/m²). Hospitalization duration was recorded as the number of days from admission to discharge or death. Statistical Analysis Baseline characteristics were compared using chi-square tests for categorical variables (e.g., gender, BMI categories) and Student’s t-tests for continuous variables (e.g., age, 25-hydroxyvitamin D levels). Multivariate logistic regression was performed to assess the associations between 25-hydroxyvitamin D levels, BMI, and hospitalization duration, adjusting for age, gender, and comorbidities (e.g., diabetes, hypertension). Statistical significance was set at p < 0.05. All analyses were conducted using SPSS Statistics, version 24.0 (IBM Corp., Armonk, NY, USA). Descriptive Distribution Analysis To assess the normality and central tendency of the dataset, Gaussian kernel density plots were generated for each continuous variable, including age, BMI, vitamin D levels, hospitalization duration, weight, and height. Ethical Considerations The study was approved by the Institutional Review Board of Shahid Beheshti University of Medical Sciences (IRB number unavailable in original data). Informed consent was waived due to the retrospective design and use of anonymized data.
results:
Baseline Characteristics Data were analyzed for 96 patients hospitalized with confirmed COVID-19 at Besat Hospital, Tehran, Iran, from April 1, 2022, to June 30, 2022. The cohort comprised 59.4% males (n=57) and 40.6
discussion:
In our hospital cohort of 96 COVID-19 patients (median age 59.5 years, 59.4% male), the mean 25-hydroxyvitamin D level was 28 ng/mL and mean BMI was 24.7 kg/m². Vitamin D deficiency (<20 ng/mL) was present in 8.3%, and insufficiency (20–29 ng/mL) in 51%. Surprisingly, the normal-weight group exhibited the highest infection rate in our sample, and patients under 45 years comprised only 15.6% of cases despite being healthier on average. Those over 60 were almost universally vitamin D insufficient. We found that lower vitamin D levels tended to be associated with longer hospital stays (although this difference was not statistically significant). These findings suggest that both low vitamin D status and excess body weight may influence COVID-19 outcomes, in line with pervious. Many studies have investigated vitamin D’s role in COVID-19. Consistent with our observations, large retrospective cohorts have reported that hospitalized COVID-19 patients tend to have significantly lower 25(OH)D levels than non-hospitalized individuals. The analysis of over 80,000 people in UK found that median vitamin D was about 50 nmol/L in non-hospitalized SARS-CoV-2 cases versus only 35 nmol/L in those admitted to hospital (P<0.005). And more Importantly, the concentration of 25(OH)D <50 nmol/L was associated with roughly 2.3–2.4 times higher odds of hospital admission for COVID-19 (Jude et al., 2021). Similarly, in an urban U.S. medical center cohort, patients with likely deficient vitamin D status (<20 ng/mL) had a 1.77-fold higher risk of testing positive for SARS-CoV-2 compared to vitamin D–sufficient patients (Meltzer et al., 2020). These studies indicate that vitamin D deficiency often coexists with more severe COVID-19 presentations. Meta-analyses of supplementation trials provide mixed but noteworthy results. A 2022 systematic review of meta-analyses found that vitamin D supplementation was associated with substantially lower mortality (pooled OR ~0.48) and reduced ICU admissions and ventilation requirements(Shah et al., 2022). Similar to their results, a 2024 meta-analysis of randomized controlled trials showed that among moderate-to-severe COVID-19 patients, vitamin D (especially multi-dose regimens) significantly decreased the risk of ICU transfer (OR ≈0.43), mechanical ventilation (OR ≈0.44), and reduced the patient’s hospital stays. They also observed trends toward reduced mortality rate but it was not statistically significance(Yang et al., 2024). However, other studies have found no clear benefit of vitamin D on hard outcomes. When analyses adjust for confounders like age, comorbidities, and baseline health, the link between low vitamin D and mortality often disappears. A 2023 meta-analysis reported that although unadjusted data showed association between higher COVID-19 mortality with vitamin D deficiency, this association without adjustments of confounding factors such as older age or higher BMI may have led to many observational studies incorrectly estimating the association (Bignardi et al., 2023). Likewise, a randomized trial in Brazil found that a single high dose of vitamin D3 did not reduce hospital length of stay compared to placebo (median 7 days for both groups) (Murai et al., 2021). Even in severe cases, one multicenter cohort study found no survival advantage from adjunctive vitamin D therapy; and surprisingly patients given vitamin D tended to have longer ventilation and ICU stays(Al Sulaiman et al., 2023). These discrepant findings suggest that despite low vitamin D often accompanies severe COVID-19, it may largely be a marker of poor health or older age rather than a direct cause of worse outcomes. It is also possible that a One-time high-dose vitamin D supplementation (as used in some trials) was insufficient to overcome deficiency, whereas maintaining the adequate levels of vitamin D before infection could be more protective. Biologically, vitamin D has plausible mechanisms to modulate COVID-19: it dampens renin–angiotensin activity, upregulates ACE2 and antimicrobial peptides, and generally suppresses pro-inflammatory cytokines. Vitamin D–deficient COVID-19 patients often exhibit higher CRP, IL-6, and D-dimer levels. Experimental data even show that 1,25-dihydroxyvitamin D could inhibit SARS-CoV-2 replication in cultured respiratory cells(Fatemi et al., 2021; Mora et al., 2008; Singh et al., 2021). However, whether these mechanistic effects could be translated into clinical benefit remains uncertain. Adjusted observational data indicate that when controlling for confounders, vitamin D levels alone are not a reliable predictor of mortality (Bignardi et al., 2023). Our finding align with previous studies that have identified a high prevalence of vitamin D deficiency among hospitalized patients(Jude et al., 2021).(Meltzer et al., 2020).furthermore it also resonate with meta-analyses evidences that supplementation can reduce ICU needs and possibly mortality(Shah et al., 2022; Yang et al., 2024). our findings highlight that vitamin D status must be interpreted alongside age, adiposity, and comorbidities, as confounding can explain some of the observed associations (Bignardi et al., 2023). Our analysis of BMI among hospitalized COVID-19 patients revealed that the majority of individuals fell within the healthy weight category (18.5–24.9 kg/m²), accounting for nearly 60% of cases. This distribution likely reflects the relatively low prevalence of obesity in the study population rather than suggesting a protective effect of excess body weight. There was a clear association between BMI and gender, with obesity observed exclusively among female patients (10.3% of females vs. 0% of males; p = 0.028). Conversely, males were more likely to be overweight (42.1%) than females (28.2%), indicating possible gender-based differences in body composition or healthcare-seeking behavior during infection. Additionally, BMI was significantly associated with hospital unit assignment (p = 0.032): overweight patients were more frequently admitted to the ICU (47.7%), while obese patients were only found in the general ward. Although this may reflect sampling limitations—given the small number of obese patients (n=4)—it aligns with broader research suggesting that overweight and obesity contribute to more severe disease progression and increased need for intensive care. a substantial body of evidence from large-scale studies indicates that excess body weight is a significant risk factor for more severe COVID-19 outcomes, with overweight and obesity consistently linked to worse clinical progression. A meta-analysis of 208 studies (3.5 million participants) found that overweight individuals had a modestly higher risk of COVID-19–related hospitalization (OR≈1.19) but no significant increase in mortality, whereas obese patients had much higher risks of both hospitalization (OR≈1.72) and death (OR≈1.25)(Sawadogo et al., 2022). Another large-scale study indicated that obesity remains a clear adverse factor. A meta-regression of more than 3 million cases demonstrated that obesity was associated with a 52% higher risk of severe COVID-19 (RR≈1.52) and a smaller but still significant increase in mortality rate (RR≈1.09)(Singh et al., 2022) These consistent findings leave little doubt that higher BMI predisposes patients to worse COVID-19 outcomes. In practical terms, this means that an obese patient is far more likely to require ICU admission or ventilation once infected. For example, one study matching obese versus non-obese patients found that those with obesity stayed in the hospital significantly longer (median 23 vs. 18 days) and had a higher proportion of severe cases. (Yu et al., 2021). The reasons for this association are multifactorial. Obesity is a chronic inflammatory state: excessive adipose tissue produces high levels of leptin and pro-inflammatory cytokines (TNF-α, IL-6, etc.) and is characterized by macrophage infiltration and T-cell dysregulation(Maurya et al., 2021). This pre-existing inflammation can amplify the cytokine storm triggered by SARS-CoV-2. Adipose tissue also serves as a viral reservoir in some infections and may impair antiviral immune responses. Additionally, obesity is commonly accompanied by conditions like diabetes and hypertension, which themselves worsen COVID-19. Mechanistically, obesity alters renin–angiotensin signaling and impairs respiratory function – fat deposition around the diaphragm and chest wall increases work of breathing and promotes hypoventilation. These effects make obese patients more prone to acute respiratory distress syndrome and oxygen desaturation. Indeed, obesity has been associated with higher rates of mechanical ventilation and ICU admission in multiple reports(Guglielmi et al., 2021; Soeroto et al., 2020; Yu et al., 2021).
conclusion:
The present study examined the relationship between serum 25-hydroxyvitamin D levels, body mass index (BMI), and clinical outcomes in patients hospitalized with COVID-19. Although vitamin D deficiency and insufficiency were more common among patients admitted to the ICU, no statistically significant association was found between vitamin D levels and hospitalization duration or admission to intensive care. Similarly, while patients with sufficient vitamin D had a shorter average hospital stay, this difference did not reach statistical significance. In contrast, BMI showed a stronger association with disease severity. Overweight patients were more likely to be admitted to the ICU, suggesting that elevated BMI may be a more reliable predictor of severe disease than vitamin D status alone. No significant difference was observed between genders regarding hospitalization duration or ICU admission, though female patients had significantly higher serum vitamin D levels. Overall, the findings suggest that while vitamin D insufficiency is prevalent among hospitalized COVID-19 patients, its isolated role as a prognostic marker is limited. BMI may serve as a more robust indicator of hospitalization risk and severity. Further studies with larger sample sizes and controlled designs are necessary to clarify the independent and combined effects of vitamin D status and BMI on COVID-19 outcomes and any suggestion of protective role of vitamin D should be interpreted cautiously and cannot be considered conclusive without further analysis.