|Year : 2022 | Volume
| Issue : 3 | Page : 214-217
Correlation between Levels of Vitamin D and Disease Severity and Outcome in COVID 19 Patients at a Tertiary Hospital in North India
Tamoghna Ghosh, Rahul Krishnan, Souradeep Chowdhury, Arvind Kumar, Upendra Baitha, Shweta Sharma, Naveet Wig
Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||19-May-2022|
|Date of Decision||07-Sep-2022|
|Date of Acceptance||16-Oct-2022|
|Date of Web Publication||07-Dec-2022|
Department of Medicine, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
Introduction: COVID-19 disease is more prevalent and severe in people who are more likely to be deficient in vitamin D, people with obesity and diabetes mellitus, and people who live in higher latitudes. Materials and methods: The study was an ambispective, analytical, observational study conducted at a tertiary care teaching hospital in New Delhi, India. The study population consisted of adults with a confirmed diagnosis of COVID-19. Results and conclusion: Eighty eight patients diagnosed with COVID-19 between February and July 2021 were enrolled, with mean (SD) age being 40(2) years and there were 55 (62.5%) males. The most common co-morbidities were hypertension, diabetes mellitus, and chronic obstructive pulmonary disease (COPD) and the most common symptoms were fever, cough, and myalgia. Twelve (13.6%) patients had severe disease. Seven (7.9%) patients died. Sixty one (69.3%) patients had vitamin D levels <30 ng/mL and had severe disease, more symptoms, and increased oxygen requirement, but did not affect laboratory parameters and mortality.
Keywords: COVID-19, deficiency, outcome, vitamin D
|How to cite this article:|
Ghosh T, Krishnan R, Chowdhury S, Kumar A, Baitha U, Sharma S, Wig N. Correlation between Levels of Vitamin D and Disease Severity and Outcome in COVID 19 Patients at a Tertiary Hospital in North India. MAMC J Med Sci 2022;8:214-7
|How to cite this URL:|
Ghosh T, Krishnan R, Chowdhury S, Kumar A, Baitha U, Sharma S, Wig N. Correlation between Levels of Vitamin D and Disease Severity and Outcome in COVID 19 Patients at a Tertiary Hospital in North India. MAMC J Med Sci [serial online] 2022 [cited 2023 Feb 1];8:214-7. Available from: https://www.mamcjms.in/text.asp?2022/8/3/214/362894
| Introduction|| |
The COVID-19 pandemic has affected 416 million people and caused >5.8 million deaths as of now. Approximately 20% of COVID-19 patients require hospitalization and 5% of them become critically ill and it is associated with a mortality rate of 2–5%. The nutritional status of the host is known to be associated with both severity and susceptibility to viral infection, as inadequate nutrition impairs the functioning of the immune system and results in increased susceptibility to infection. In the previous influenza pandemic, metabolic and hormonal derangements have shown increased susceptibility to viral infections. There is evidence from influenza A and severe acute respiratory syndrome (SARS) epidemics suggesting a role for vitamin D in these diseases. Previous studies have suggested an association between vitamin D deficiency and an increased chance of developing bacterial and/or viral pneumonia due to viruses such as SARS, MERS, and Influenza A. Previous studies have shown that low vitamin D levels lead to increased inflammatory cytokines and increased risk of pneumonia and upper respiratory tract viral infections., Vitamin D deficiency is associated with an increase in thrombotic episodes, which are frequently observed in COVID-19 and thus may carry a higher mortality in COVID-19., A case control study from India showed that vitamin D deficiency is strongly associated with COVID-19 clinical severity. However, in contrast, a meta-analysis by Chen et al. found that low vitamin D level is not related to the severity of COVID-19 infection. Also, low vitamin D level does not aggravate COVID-19 risk or death and vitamin D supplementation does not improve outcomes in hospitalized patients with COVID-19.
COVID-19 disease is more prevalent and severe in winter and is more common in people with obesity and diabetes mellitus, and people who live in higher latitudes. These subgroups of people are also more susceptible to vitamin D deficiency., Thus, there is a need of studies from Indian perspective related to the effect of vitamin D levels on COVID-19 severity and outcomes.
| Methods|| |
The study was an ambispective, analytical, observational study conducted at the COVID-19 designated ward of a tertiary care teaching hospital in New Delhi, India. The study population consisted of adults (age >18 years) with a confirmed diagnosis of COVID-19 by real time reverse transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal specimens. Mild illness is defined as a room air saturation of >94% and a respiratory rate of ≤24 breaths/min. Moderate/severe COVID-19 was defined as respiratory rate >24 breaths/min or room air saturation of ≤94% or new onset oxygen requirement. Severe illness is defined as respiratory rate >30 breaths/min or room air saturation of <90%. In view of the infectious nature of the disease telephonic consent was obtained. The study was approved by the Ethics Committee of the Institute (Ref no: IECPG-582/21.10.2020).
A formal sample size calculation was not done and instead convenience sampling was used. After the patients were admitted to the isolation ward, the presenting history, comorbidity status, and vitals were recorded. The laboratory parameters, including vitamin D level, complete blood count, liver and renal function test, serum electrolytes, lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, erythrocyte sedimentation rate (ESR), and coagulation profile were obtained at admission. Vitamin D levels <30 ng/mL was considered as low.
Statistical analysis was performed using Stata Corp. 2015 (Stata Statistical Software: Release 14. College Station, TX: StataCorp LP). A P-value <0.05 was considered statistically significant. Chi-square tests were used to examine the relationship between vitamin D level and various parameters.
| Results|| |
Demography and clinical features
We enrolled a total of 88 patients diagnosed with COVID-19 between February and July 2021. The mean (SD) age was 40 (2) years and there were 55 (62.5%) males. The most common comorbidities were hypertension (27.3%), diabetes mellitus (18.2%), and COPD (3.4%). The most common symptoms were fever (72.7%), cough (60.2%), myalgia (52.3%), sore throat (47.7%), and fatigue (43.2%). Fifty four (61.4%) patients had mild disease, 22 (25.0%) patients had moderate disease, and 12 (13.6%) patients had severe disease. Details are highlighted in [Table 1].
|Table 1 Comparison of low versus normal vitamin D leveled patients with SARS-CoV-2 (n = 88)|
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Treatment and outcome
The majority of symptomatic patients received supportive therapy and were treated as per the National Clinical Management Protocol for COVID-19 by the Ministry of Health and Family Welfare, Government of India. Twenty four (27.3%) patients received oxygen. The mean (SD) duration of hospital stay was 12 (2) days. Seven (7.9%) patients died.
Vitamin D level comparison
Sixty one (69.3%) patients had vitamin D levels <30 ng/mL, while 27 (30.7%) had vitamin D levels ≥30 ng/mL. The comparison between these two groups is shown in [Table 1]. Patients with lower vitamin D levels had more moderate (34.4%) and severe (13.6%) diseases, more symptoms (myalgia and fatigue) and more oxygen requirements (37.7%). Lower vitamin D was however not associated with statistically significant increase in COVID-19 mortality and abnormal laboratory parameters.
| Discussion|| |
Our study shows that lower vitamin D levels at the time of hospital admission leads to more severe disease, more symptoms (myalgia and fatigue), and more oxygen requirement, but did not affect laboratory parameters and mortality.
In the present study, 69.3% of patients had 25(OH)D <30 ng/mL. The reason can be attributed to the lack of intake through food, reduced synthesis of this vitamin in the skin, and the type of clothing, and lack of widespread supplementation, which is common in some countries including India.
In our study, all the severe disease patients had vitamin D levels lower than 30 ng/mL. None of the patients with vitamin D level >30 ng/mL had severe disease. This finding is similar to Nimavat et al. who found that vitamin D deficiency was 37% in severe cases compared to 20% and 10% in moderate and mild cases respectively. Another study found that vitamin D deficiency is associated with COVID-19 positivity and severity of the disease. The relationship between vitamin D and COVID-19 severity and outcome can be explained by different pathways and mechanisms. Vitamin D can modulate the immune system and reduce the production of pro-inflammatory markers. Vitamin D supplementation has reduced interleukin-6 levels in several clinical trials. Vitamin D may reduce the risk of acute respiratory distress syndrome (ARDS) and mortality from COVID-19 by raising ACE2 levels. Vitamin D reduces the lung damage due to COVID-19 by stimulating the proliferation and migration of alveolar epithelial cells type II and reducing their apoptosis. It also inhibits the mesenchymal transition of an epithelial cell induced by TGF-β (transforming growth factor).
In our study, we also found that low vitamin D level is positively correlated and significantly associated with symptoms like fatigue and myalgia. Previous studies have shown a positive correlation between low vitamin D levels and fatigue in cancer patients and in patients with myasthenia gravis; and improvement in fatigue symptom scores after normalization of vitamin D levels.,, Vitamin D is essential in calcium homeostasis. A low vitamin D level reduces serum total and ionized calcium which leads to an increase in parathormone level, decrease in bone density, increase in bone turnover, decrease in urinary calcium excretion, increase in urinary phosphate excretion, and decrease in serum phosphate level. This ultimately results into skeletal demineralization and muscle weakness, manifesting as myalgia and fatigue.
Although we found that lower vitamin D levels lead to more severe disease, it was not associated with increased death. This is in agreement with the meta-analysis by Chen et al., who found that low vitamin D level does not aggravate COVID-19 risk or death. However this is in contrast to another study which found that compared to those with sufficient vitamin D status, COVID-19 patients with vitamin D insufficiency and deficiency had strongly increased respiratory mortality.
The strength of this study is that it is one of the largest single center studies on COVID-19 in India, measuring the effect of vitamin D. Second, we have a variety of laboratory investigations in our cohort. However, this study had some limitations. First, Being an ambispective study, few clinical and laboratory data were missing. Second, vitamin D levels were measured once, and if repeated in the course of the disease we might be able to better answer its relationship to the severity and outcome of the disease. Thus, possible confounders cannot be ruled out. Third, vitamin D levels are lower during the winter and spring than the summer and autumn. Fourth, this study is a single-center study and as a result, it may have low external validity.
| Conclusion|| |
We found that lower vitamin D level at the time of hospital admission was significantly associated with severe disease. Symptoms like myalgia fatigue and high oxygen requirements were significantly associated with low vitamin D level. However we found no association of lower vitamin D level with increased mortality.
All listed authors meet the ICMJE criteria. We attest that all authors contributed significantly to the creation of this manuscript, each having fulfilled criteria as established by the ICMJE.
The authors express their sincere gratitude to the Department of Medicine, All India Institute of Medical Sciences, New Delhi, India, for their continuous encouragement and support.
Ethics approval statement
The study was approved by the Institute Ethics Committee, AIIMS, New Delhi, India.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Beck MA, Levander OA. Host nutritional status and its effect on a viral pathogen. J Infect Dis 2000; 182(supplement_1):S93-6.
Paich HA, Sheridan PA, Handy J et al.
Overweight and obese adult humans have a defective cellular immune response to pandemic H1N1 Influenza a virus. Obesity 2013;21:2377-86.
Peterson CA, Heffernan ME. Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women. J Inflamm Lond Engl 2008;5:10.
Alhassan Mohammed H, Mirshafiey A, Vahedi H et al.
Immunoregulation of inflammatory and inhibitory cytokines by Vitamin D3 in patients with inflammatory bowel diseases. Scand J Immunol 2017;85:386-94.
Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol Off Publ Pan Am Soc Clin Virol. 2020;127:104362.
Mohammad S, Mishra A, Ashraf MZ. Emerging role of Vitamin D and its associated molecules in pathways related to pathogenesis of thrombosis. Biomolecules 2019;9:E649.
Nimavat N, Singh S, Singh P, Singh SK, Sinha N. Vitamin D deficiency and COVID-19: a case-control study at a tertiary care hospital in India. Ann Med Surg 2021;68:102661.
Chen J, Mei K, Xie L et al.
Low vitamin D levels do not aggravate COVID-19 risk or death, and vitamin D supplementation does not improve outcomes in hospitalized patients with COVID-19: a meta-analysis and GRADE assessment of cohort studies and RCTs. Nutr J 2021;20:89.
Grant WB, Lahore H, McDonnell SL et al.
Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 2020;12:E988.
McCartney DM, Byrne DG. Optimisation of Vitamin D status for enhanced immuno-protection against Covid-19. Ir Med J 2020;113:58.
Aparna P, Muthathal S, Nongkynrih B, Gupta SK. Vitamin D deficiency in India. J Fam Med Prim Care 2018;7:324-30.
Demir M, Demir F, Aygun H. Vitamin D deficiency is associated with COVID-19 positivity and severity of the disease. J Med Virol 2021;93:2992-9.
Wong NA, Saier MH. The SARS-Coronavirus infection cycle: a survey of viral membrane proteins, their functional interactions and pathogenesis. Int J Mol Sci 2021;22:1308.
Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients 2015;7:4240-70.
Miroliaee AE, Salamzadeh J, Shokouhi S, Sahraei Z. The study of vitamin D administration effect on CRP and Interleukin-6 as prognostic biomarkers of ventilator associated pneumonia. J Crit Care 2018;44:300-5.
Dev R, Del Fabbro E, Schwartz GG et al.
Preliminary report: vitamin D deficiency in advanced cancer patients with symptoms of fatigue or anorexia. Oncologist 2011;16:1637-41.
Khan QJ, Reddy PS, Kimler BF et al.
Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Res Treat 2010;119:111-8.
Askmark H, Haggård L, Nygren I, Punga AR. Vitamin D deficiency in patients with myasthenia gravis and improvement of fatigue after supplementation of vitamin D3: a pilot study. Eur J Neurol 2012;19:1554-60.
Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Harrison’s Principles of Internal Medicine, Vol. 1. New York, NY, USA: Mcgraw-hill; 2015 p. 19e.
Brenner H, Holleczek B, Schöttker B. Vitamin D insufficiency and deficiency and mortality from respiratory diseases in a cohort of older adults: potential for limiting the death toll during and beyond the COVID-19 Pandemic? Nutrients. 2020;12:2488.
Malacova E, Cheang PR, Dunlop E et al.
Prevalence and predictors of vitamin D deficiency in a nationally representative sample of adults participating in the 2011–2013 Australian Health Survey. Br J Nutr 2019;121:894-904.