Is suboptimal circulating level of vitamin D a risk factor for the poor prognosis of COVID- 19? – A comparison of first and second waves in India
Yashika Charla, Seema Bhagava, Shyamala A Bembey, S P Byotra, Atul Kakar, Atul Gogia, Parul Chugh, Sangeeta Choudhury
doi:10.21203/rs.3.rs-1826271/v1
Background -Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) affects every organ system, especially the lungs. Vitamin D has been shown to modulate both infections and autoimmune diseases. It maintains the balance between angiotensin-1 and angiotensin II, thereby preventing lung tissue damage. Hence arises the question -can adequate circulating vitamin D prevent or modulate SARS-CoV-2 infection? In the present study, we attempted to nd the answer to this question in the Indian population.
Methodology -The study duration was April 1, 2020 to April 30, 2021, including only those patients whose vitamin D levels were estimated. Mann-Whitney test was used to compare age, hospital stay, and total vitamin D levels between the two waves. The gender difference, vitamin D status, pre-existing comorbidities, COVID-19 severity, and mortality were calculated using the chi-square test.
Results -On curating the data, vitamin D levels were found to be estimated in 179 COVID-19 positive patients. In the rst wave, 48.2% of the patients were de cient in vitamin D levels, yet no statistical association was observed for patients' demographics (age, sex, and comorbidities), COVID-19 severity, and mortality. Similar results were observed in the second wave. The correlation coe cient of IL-6 (r=-0.08), CRP (r = 0.033), and ferritin (r = 0.027) was not signi cantly associated with vitamin D levels.
Conclusion -The Indian population is known to be de cient in vitamin D, yet this study showed an absence of vitamin D correlation with severity, morbidity or mortality of COVID-19. Further research into the immunemodulatory effect of vitamin D on disease susceptibility and progression in COVID-19 would be bene cial.
the immune-modulatory effect of vit D in susceptibility and course of disease in COVID-19 would be pertinent as the Indian population is known to have hypovitaminosis D.
Declarations Author contributions: All authors contributed and approved the nal manuscript. YC collated the data, reviewed the literature, and drafted the manuscript; SB conceptualized, guided, edited, and proofread; SAB aided in the collation of data and proofreading; SPB advised and suggested the result outcomes, proofread the manuscript; AK and AG extracted demographic and clinical details; PC performed statistical analyses; SC conceptualized, guided, analyzed the data, framed the questions, edited the manuscript and proofread.
Con ict of interest The authors declare that they do not have any con ict of interest.
References
De Smet, De Smet, Herroelen, Vitamin D de ciency as risk factor for severe COVID-19: A convergence of two pandemics, medRxiv,
doi:10.1101/2020.05.01.20079376Grant, Lahore, Mcdonnell, Evidence that vitamin d supplementation could reduce risk of in uenza and covid-19 infections and deaths, Nutrients,
doi:10.3390/nu12040988Hastie, Mackay, Ho, Diabetes & Metabolic Syndrome: Clinical Research & Reviews Vitamin D concentrations and COVID-19 infection in UK Biobank, Diabetes Metab Syndr Clin Res Rev
Hernández, Nan, Fernandez-Ayala, Vitamin D Status in Hospitalized Patients with SARS-CoV-2 Infection, J Clin Endocrinol Metab,
doi:10.1210/clinem/dgaa733Holick, Binkley, Bischoff-Ferrari, Evaluation, treatment, and prevention of vitamin D de ciency: An endocrine society clinical practice guideline, J Clin Endocrinol Metab,
doi:10.1210/jc.2011-0385Im, Je, Baek, Chung, Kwon et al., Nutritional status of patients with COVID-19, Int J Infect Dis Nov
Israel, Cicurel, Feldhamer, Dror, Shmuel M Giveon et al., The link between vitamin D de ciency and Covid-19 in a large population, medRxiv
Jain, Iyengar, Vr, Differences between First wave and Second wave of COVID-19 in India, Diabetes Metab Syndr
Jayawardena, Jeyakumar, Francis, Ma, Impact of the vitamin D de ciency on COVID-19 infection and mortality in Asian countries, Diabetes Metab Syndr Clin Res Rev
Jevalikar, Mithal, Singh, Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19, Sci Rep
Kamboj, Dwivedi, Prevalence of hypovitaminosis D in India & way forward, Inidan J Med Res,
doi:10.4103/ijmr.IJMRKaufman, Niles, Kroll, Bi, Hm, SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels, PLoS One
Lau, Majumder, Torabi, Saeg, Vitamin D insu ciency is prevalent in severe COVID-19
Macaya, Paeres, Valls, Fernández-Ortiz, Del Castillo et al., Interaction between age and vitamin D de ciency in severe COVID-19 infection, Nutr Hosp
Maghbooli, Sahraian, Ebrahimi, Vitamin D su ciency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection, PLoS One
Panagiotou, Tee, Ihsan, Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID-19 are associated with greater disease severity, Clin Endocrinol (Oxf),
doi:10.1111/cen.14276Pereira, Dantas Damascena, Mirella, Azevedo, De et al., Vitamin D De ciency Aggravates COVID-19 : A Systematic Review and Meta-Vitamin D de ciency aggravates COVID-19 : systematic review and meta-analysis, Crit Rev Food Sci Nutr
Pizzini, Aichner, Sahanic, Impact of vitamin d de ciency on covid-19-a prospective analysis from the covild registry, Nutrients,
doi:10.3390/nu12092775Radujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger et al., Vitamin D De ciency and Outcome of COVID-19 Patients, Nutrients,
doi:10.7861/CLINMED.LET.20.6.9Sabetta, Depetrillo, Cipriani, Serum 25-hydroxyvitamin D and the incidence of acute viral respiratory tract infections in healthy adults, PLoS One,
doi:10.1371/journal.pone.0011088Talwalkar, Deshmukh, Deepak, Prevalence and clinico-epidemiology of vitamin D de ciency in patients with type 2 diabetes mellitus and hypertension -a Pan-India study, Endocr Abstr,
doi:10.1530/endoabs.56.p218Wang, Nestel, Bourdeau, Cutting Edge: 1,25-Dihydroxyvitamin D 3 Is a Direct Inducer of Antimicrobial Peptide Gene Expression, J Immunol,
doi:10.4049/jimmunol.173.5.2909Who, TECHNICAL FOCUS: COVID-19 Early Epidemiologic and Clinical investigations for public health response, World Heal Organ
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' <jats:p>Background\n'
' - Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) affects every organ system, '
'especially the lungs. Vitamin D has been shown to modulate both infections and autoimmune '
'diseases. It maintains the balance between angiotensin-1 and angiotensin II, thereby '
'preventing lung tissue damage. Hence arises the question - can adequate circulating vitamin D '
'prevent or modulate SARS-CoV-2 infection? In the present study, we attempted to find the '
'answer to this question in the Indian population.\n'
'Methodology\n'
' -The study duration was April 1, 2020 to April 30, 2021, including only those patients whose '
'vitamin D levels were estimated. Mann-Whitney test was used to compare age, hospital stay, '
'and total vitamin D levels between the two waves. The gender difference, vitamin D status, '
'pre-existing comorbidities, COVID-19 severity, and mortality were calculated using the '
'chi-square test.\n'
'Results\n'
' - On curating the data, vitamin D levels were found to be estimated in 179 COVID-19 positive '
'patients. In the first wave, 48.2% of the patients were deficient in vitamin D levels, yet no '
'statistical association was observed for patients’ demographics (age, sex, and '
'comorbidities), COVID-19 severity, and mortality. Similar results were observed in the second '
'wave. The correlation coefficient of IL-6 (r=-0.08), CRP (r\u2009=\u20090.033), and ferritin '
'(r\u2009=\u20090.027) was not significantly associated with vitamin D levels.\n'
'Conclusion\n'
' - The Indian population is known to be deficient in vitamin D, yet this study showed an '
'absence of vitamin D correlation with severity, morbidity or mortality of COVID-19. Further '
'research into the immune-modulatory effect of vitamin D on disease susceptibility and '
'progression in COVID-19 would be beneficial.</jats:p>',
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