The Impact of Serum Levels of Vitamin D3 and Its Metabolites on the Prognosis and Disease Severity of COVID-19

Khojah et al., Nutrients, doi:10.3390/nu14245329

Dec 2022

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Analysis of 103 COVID-19 patients and 50 healthy controls in Saudi Arabia, showing significantly lower vitamin D and vitamin D metabolite levels in COVID-19 patients, and correlations between vitamin D levels and ACE2 levels, IL-6, and NLR in COVID-19 patients.

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Khojah et al., 15 Dec 2022, retrospective, Saudi Arabia, peer-reviewed, 5 authors, study period October 2020 - December 2021.

Contact: shassan@taibahu.edu.sa (corresponding author).

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The Impact of Serum Levels of Vitamin D3 and Its Metabolites on the Prognosis and Disease Severity of COVID-19

Hani M J Khojah, Sameh A Ahmed, Sultan S Al-Thagfan, Yaser M Alahmadi, Yasser A Abdou

Nutrients, doi:10.3390/nu14245329

Vitamin D is among the increasingly consumed dietary supplements during the COVID-19 pandemic. It plays a regulatory role in the immune system and moderates the renin-angiotensin system, which is implicated in infection pathogenesis. However, the investigation of serum levels of vitamin D3 forms and their relative ratios in COVID-19 patients is worth investigation to understand the impacts of disease severity. Hence, we investigated the serum levels of vitamin D3 (cholecalciferol) and its metabolites (calcifediol and calcitriol), in addition to their relative ratios and correlations with angiotensin-converting enzyme 2 (ACE2), interleukin-6 (Il-6), and neutrophil-lymphocyte ratio (NLR) in COVID-19 patients compared with healthy controls. Oropharyngeal specimens were collected from the study subjects for polymerase chain reaction testing for COVID-19. Whole blood samples were obtained for blood count and NLR testing, and sera were used for the analysis of the levels of the vitamin and its metabolites, ACE2, and IL-6. We enrolled 103 patients and 50 controls. ACE2, Il-6, and NLR were significantly higher in the patients group (72.37 ± 18.67 vs. 32.36 ± 11.27 U/L, 95.84 ± 25.23 vs. 2.76 ± 0.62 pg/mL, and 1.61 ± 0.30 vs. 1.07 ± 0.16, respectively). Cholecalciferol, calcifediol, and calcitriol were significantly lower in patients (18.50 ± 5.36 vs. 29.13 ± 4.94 ng/mL, 14.60 ± 3.30 vs. 23.10 ± 3.02 ng/mL, and 42.90 ± 8.44 vs. 65.15 ± 7.11 pg/mL, respectively). However, their relative ratios were normal in both groups. Levels of the vitamin and metabolites were strongly positively, strongly negatively, and moderately negatively correlated with ACE2, Il-6, and NLR, respectively. COVID-19 infection severity is associated with a significant decrease in vitamin D3 and its metabolites in a parallel pattern, and with a significant increase in ACE2, Il-6, and NLR. Higher levels of vitamin D and its metabolites are potentially protective against severe infection.

Conflicts of Interest: The authors declare no conflict of interest.

References

Ahmed, Butler, Dargham, Latif, Chidiac et al., Vitamin D3 metabolite ratio as an indicator of vitamin D status and its association with diabetes complications, BMC Endocr. Disord, doi:10.1186/s12902-020-00641-1

Ahmed, Khojah, Al-Thagfan, Alahmadi, Mohammed, An ultrasensitive UHPLC-ESI-MS/MS method augmented with a controlled microwave derivatization reaction for quantitation of vitamin D3 and its major metabolites in COVID-19 patients, Talanta, doi:10.1016/j.talanta.2022.123497

Al-Thagfan, Alolayan, Ahmed, Emara, Awadallah, Impacts of deficiency in vitamin D derivatives on disease severity in adult bronchial asthma patients, Pulm. Pharmacol. Ther, doi:10.1016/j.pupt.2021.102073

Ali, Role of vitamin D in preventing of COVID-19 infection, progression and severity, J. Infect. Public Health

Bartley, Vitamin, Emerging roles in infection and immunity, Expert Rev. Anti-Infect. Ther, doi:10.1586/eri.10.102

Bartoszko, Siemieniuk, Kum, Qasim, Zeraatkar et al., Prophylaxis against covid-19: Living systematic review and network meta-analysis, BMJ, doi:10.1136/bmj.n949

Beyerstedt, Casaro, Rangel, COVID-19: Angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection, Eur. J. Clin. Microbiol. Infect. Dis. Off. Publ. Eur. Soc. Clin. Microbiol, doi:10.1007/s10096-020-04138-6

Brown, Therapeutic uses of vitamin D analogues, Am. J. Kidney Dis. Off. J. Natl. Kidney Found, doi:10.1053/ajkd.2001.28111

Cantorna, Snyder, Lin, Yang, Vitamin D and 1,25(OH)2D Regulation of T cells, Nutrients, doi:10.3390/nu7043011

Demir, Durmaz, A Comparison of vitamin D deficiency with neutrophil lymphocyte ratio and CRP levels in Covid-19 patients, Med. Sci. Discov, doi:10.36472/msd.v8i5.537

Feldman, Pike, None

Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients, doi:10.3390/nu12040988

Guo, Cao, Hong, Tan, Chen et al., The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak-An update on the status, Mil. Med. Res

Holick, Vitamin D in Health and Disease: Vitamin D for Health and in Chronic Kidney Disease, Semin. Dial, doi:10.1111/j.1525-139X.2005.18402.x

Honardoost, Ghavideldarestani, Khamseh, Role of vitamin D in pathogenesis and severity of COVID-19 infection, Arch. Physiol. Biochem, doi:10.1080/13813455.2020.1792505

Hunter, Jones, IL-6 as a keystone cytokine in health and disease, Nat. Immunol, doi:10.1038/ni.3153

Ismailova, White, Vitamin, infections and immunity, Rev. Endocr. Metab. Disord, doi:10.1007/s11154-021-09679-5

Jones, Prosser, Chapter 3-The Activating Enzymes of Vitamin D Metabolism (25-and 1α-Hydroxylases

Kamphuis, Junt, Waibler, Forster, Kalinke, Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia, Blood, doi:10.1182/blood-2006-06-027599

Khojah, Community pharmacy services and preparedness during COVID-19 outbreak in Madinah, Saudi Arabia, Saudi Pharm. J, doi:10.1016/j.jsps.2020.09.004

Kuhn, Li, Choe, Farzan, Angiotensin-Converting Enzyme 2: A Functional Receptor for SARS Coronavirus, Cell Mol. Life Sci, doi:10.1007/s00018-004-4242-5

Kulda, Vitamin D metabolism, Vnitr. Lek

Lagunas-Rangel, Neutrophil-to-lymphocyte ratio and lymphocyte-to-C-reactive protein ratio in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis, J. Med. Virol, doi:10.1002/jmv.25819

Magro, SARS-CoV-2 and COVID-19: Is interleukin-6 (IL-6) the 'culprit lesion' of ARDS onset? What is there besides Tocilizumab? SGP130Fc, Cytokine X, doi:10.1016/j.cytox.2020.100029

Malek Mahdavi, A brief review of interplay between vitamin D and angiotensin-converting enzyme 2: Implications for a potential treatment for COVID-19, Rev. Med. Virol, doi:10.1002/rmv.2119

Mardani, Alamdary, Nasab, Gholami, Ahmadi et al., Association of vitamin D with the modulation of the disease severity in COVID-19, Virus Res, doi:10.1016/j.virusres.2020.198148

Mukattash, Alkhalidy, Alzu'bi, Abu-Farha, Itani et al., Dietary supplements intake during the second wave of COVID-19 pandemic: A multinational Middle Eastern study, Eur. J. Integr. Med, doi:10.1016/j.eujim.2022.102102

Munshi, Hussein, Toraih, Elshazli, Jardak et al., Vitamin D insufficiency as a potential culprit in critical COVID-19 patients, J. Med. Virol

Pasquali, Tartaglione, Rotondi, Muci, Mandanici et al., Calcitriol/calcifediol ratio: An indicator of vitamin D hydroxylation efficiency?, BBA Clin, doi:10.1016/j.bbacli.2015.03.004

Pollard, Morran, Nestor-Kalinoski, The COVID-19 pandemic: A global health crisis, Physiol. Genom, doi:10.1152/physiolgenomics.00089.2020

Rafiullah, Can a Combination of AT1R Antagonist and Vitamin D Treat the Lung Complication of COVID-19?, Am. J. Med. Sci, doi:10.1016/j.amjms.2020.07.018

Raisi-Estabragh, Martineau, Curtis, Moon, Darling et al., Vitamin D and coronavirus disease 2019 (COVID-19): Rapid evidence review, Aging Clin. Exp. Res, doi:10.1007/s40520-021-01894-z

Sabaka, Koščálová, Straka, Hodosy, Lipták et al., Role of interleukin 6 as a predictive factor for a severe course of Covid-19: Retrospective data analysis of patients from a long-term care facility during Covid-19 outbreak, BMC Infect. Dis, doi:10.1186/s12879-021-05945-8

Scialo, Daniele, Amato, Pastore, Matera et al., ACE2: The Major Cell Entry Receptor for SARS-CoV-2, Lung, doi:10.1007/s00408-020-00408-4

Shenoy, Ferreira, Qi, Fraga-Silva, Díez-Freire et al., The Angiotensin-Converting Enzyme 2/Angiogenesis-(1-7)/Mas Axis Confers Cardiopulmonary Protection against Lung Fibrosis and Pulmonary Hypertension, Am. J. Respir. Crit. Care Med, doi:10.1164/rccm.200912-1840OC

Shroff, Wan, Rees, Can vitamin D slow down the progression of chronic kidney disease?, Pediatr. Nephrol, doi:10.1007/s00467-011-2071-y

Smit, Marinosci, Agoritsas, Calmy, Prophylaxis for COVID-19: A systematic review, Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis, doi:10.1016/j.cmi.2021.01.013

Smolders, Van Den Ouweland, Geven, Pickkers, Kox, Letter to the Editor: Vitamin D deficiency in COVID-19: Mixing up cause and consequence, Metabolism, doi:10.1016/j.metabol.2020.154434

Szarpak, Rafique, Gasecka, Chirico, Gawel et al., A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19, Cardiol. J

Słomka, Kowalewski, Żekanowska, Coronavirus Disease 2019 (COVID-19): A Short Review on Hematological Manifestations, Pathogens, doi:10.3390/pathogens9060493

Takayama, Kato, The Vitamin D3 1alpha-Hydroxylase Gene and Its Regulation by Active Vitamin D3, Biosci. Biotechnol. Biochem, doi:10.1271/bbb.100684

Teymoori-Rad, Shokri, Salimi, Marashi, The interplay between vitamin D and viral infections, Rev. Med. Virol, doi:10.1002/rmv.2032

Thomas, Stefanoni, Dzieciatkowska, Issaian, Nemkov et al., Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19

Turner, Hiscox, Hooper, ACE2: From vasopeptidase to SARS virus receptor, Trends Pharmacol. Sci, doi:10.1016/j.tips.2004.04.001

Urena-Torres, Souberbielle, Pharmacologic role of vitamin D natural products, Curr. Vasc. Pharmacol

Vanherwegen, Gysemans, Mathieu, Regulation of Immune Function by Vitamin D and Its Use in Diseases of Immunity, Endocrinol. Metab. Clin. N. Am, doi:10.1016/j.ecl.2017.07.010

Wacker, Holick, Sunlight, Vitamin, None, Dermato-Endocrinol, doi:10.4161/derm.24494

Warner, Rajapaksha, Shackel, Herath, ACE2: From protection of liver disease to propagation of COVID-19, Clin. Sci, doi:10.1042/CS20201268

Xiao, Li, Su, Mu, Qu, Could SARS-CoV-2-induced lung injury be attenuated by vitamin D?, Int. J. Infect. Dis, doi:10.1016/j.ijid.2020.10.059

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