Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients

Ali Daneshkhah, Vasundhara Agrawal, Adam Eshein, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman, Ali Daneshkhah, Vasundhara Agrawal, Adam Eshein, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman

Abstract

Objectives: We present evidence for a possible role of Vitamin D (VitD) deficiency in unregulated cytokine production and inflammation leading to complications in COVID-19 patients.

Design: The time-adjusted case mortality ratio (T-CMR) was estimated as the ratio of deceased patients on day N to the confirmed cases on day N-8. The adaptive average of T-CMR (A-CMR) was calculated as a metric of COVID-19 associated mortality. A model based on positivity change (PC) and an estimated prevalence of COVID-19 was used to determine countries with similar screening strategies. A possible association of A-CMR with the mean concentration of 25-hydroxyvitamin D (25(OH)D) in elderly individuals in countries with similar screening strategy was investigated. We considered high C-reactive protein (CRP) in severe COVID-19 patients (CRP ≥ 1 mg/dL) as a surrogate of a cytokine storm. We considered high-sensitivity CRP (hs-CRP) in healthy subjects as hs-CRP ≥ 0.2 mg/dL.

Results: A link between 25(OH)D and A-CMR in countries with similar screening strategy is evidence for VitD's possible role in reducing unregulated cytokine production and inflammation among patients with severe COVID-19. We observed an odds ratio (OR) of 1.8 with 95% confidence interval (95% CI) (1.2 to 2.6) and an OR of 1.9 with 95% CI (1.4 to 2.7) for hs-CRP in VitD deficient elderly from low-income families and high-income families, respectively. COVID-19 patient-level data show an OR of 3.4 with 95% CI (2.15 to 5.4) for high CRP in severe COVID-19 patients.

Conclusion: We conclude that future studies on VitD's role in reducing cytokine storm and COVID-19 mortality are warranted.

Keywords: C-reactive protein; COVID-19; Case mortality ratio; Cytokine storm; SARS-CoV-2; Vitamin D.

Conflict of interest statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
a T-CMR (8 days) as of April 21. A 2-week variability (100 × (T-CMRApril 20 – T-CMRApril 6)/T-CMRApril 6) calculated at different T-CMR delays of 0 days, 8 days and 14 days. b A-CMR as of April 21 [26]. c Percentage of confirmed to tested ratio suggests an impact of screening strategy on A-CMR [32, 36]. France testing data are the number of tests [34]. England reported the number of tests (from April 1, 2020–April 21, 2020) and we estimated number tests before April 1, 2020 by multiplying the number of patients by 1.24 (the ratio obtained from average ratio of number of tests to the number of patients from April 1, 2020, to April 7, 2020 [33]. US data are mainly the number of people tested (some labs have reported the number of tests) [34]. Iran and Spain testing data are estimated from two reported statements by public authorities [–36]
Fig. 2
Fig. 2
PC over time compares growth rate of COVID-19
Fig. 3
Fig. 3
PC against rc for 2 weeks after each country reaches 10,000 patients (except S. Korea > 5,000 patients)
Fig. 4
Fig. 4
a Mean 25(OH)D in the elderly population in the US [61], Iran [62], France [63] and the UK [64]. Estimated 25(OH)D concentration of elderly in Italy [–51, 65], and Spain [52]. b A-CMR for the US, Iran, France, England, Italy, and Spain
Fig. 5
Fig. 5
Mean 25(OH)D concentration in the elderly population in Germany [53, 68], Switzerland [70] and S. Korea [54]
Fig. 6
Fig. 6
Regression analysis based on a 25(OH)D, b Diabetes prevalence among men and women (age-standardized), CHD death rate per 100,000 (age-standardized), and Elderly ratio (age ≥ 70 yo) in the countries with less aggressive screening strategy. c Regression analysis based on 25(OH)D in countries with more aggressive screening strategy
Fig. 7
Fig. 7
Age distribution of the a hospitalized, b admitted to ICU or deceased in Spain based on data from 145,429 cases [44]
Fig. 8
Fig. 8
Age distribution of the hospitalized in a the USA [37, 38], b Italy [40], c France [39], d the UK [43] and e Switzerland [41, 42]
Fig. 9
Fig. 9
a Estimated death rate among hospitalized elderly patients, b estimated concentration of 25(OH)D in elderly, c total number of confirmed cases in the country at the end of study interval and d number of critical beds per 100,000 population in the UK [43], Italy [40], Spain [44], France [39], and Iran [45]
Fig. 10
Fig. 10
High hs-CRP and possible low-grade inflammation association with VitD status
Fig. 11
Fig. 11
Possible impact of improving VitD status on the reduction of cytokines and CRP

References

    1. Tang X, Wu C, Li X, et al. On the origin and continuing evolution of SARS-CoV-2. Natl Sci Rev. 2020 doi: 10.1093/nsr/nwaa036.
    1. Yao H, Lu X, Chen Q, et al. Patient-derived mutations impact pathogenicity of SARS-CoV-2. medRxiv. 2020 doi: 10.1101/2020.04.14.20060160.
    1. Coronavirus has mutated into 30 strains and ones in US are less deadlier than those in Europe, finds study. In: News Break. . Accessed 21 Apr 2020
    1. Dowd JB, Andriano L, Brazel DM, et al. Demographic science aids in understanding the spread and fatality rates of COVID-19. Proc Natl Acad Sci. 2020 doi: 10.1073/pnas.2004911117.
    1. Kanchan T, Kumar N, Unnikrishnan B. Encyclopedia of forensic and legal medicine. Amsterdam: Elsevier Inc.; 2015. Mortality: statistics; pp. 572–577.
    1. Baud D, Qi X, Nielsen-Saines K, et al. Real estimates of mortality following COVID-19 infection. Lancet Infect Dis. 2020 doi: 10.1016/S1473-3099(20)30195-X.
    1. Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020 doi: 10.1001/jama.2020.4683.
    1. Gomez CR, Nomellini V, Faunce DE, Kovacs EJ. Innate immunity and aging. Exp Gerontol. 2008;43:718–728. doi: 10.1016/j.exger.2008.05.0168.05.016.
    1. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034. doi: 10.1016/S0140-6736(20)30628-0.
    1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5.
    1. Aranow C. Vitamin D and the immune system. J Investig Me. 2011;59:881–886. doi: 10.2310/JIM.0b013e31821b8755.
    1. Grant WB, Giovannucci E. The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918–1919 influenza pandemic in the United States. Dermatoendocrinol. 2009;1:215–219. doi: 10.4161/derm.1.4.9063.
    1. Goncalves-Mendes N, Talvas J, Dualé C, et al. Impact of vitamin D supplementation on influenza vaccine response and immune functions in deficient elderly persons: a randomized placebo-controlled trial. Front Immunol. 2019 doi: 10.3389/fimmu.2019.00065.
    1. Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 2008;37:113–119. doi: 10.1093/ije/dym247.
    1. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi: 10.1136/bmj.i6583.
    1. Charan J, Goyal JP, Saxena D, Yadav P. Vitamin D for prevention of respiratory tract infections: a systematic review and meta-analysis. J Pharmacol Pharmacother. 2012;3:300–303. doi: 10.4103/0976-500X.103685.
    1. Bergman P, Lindh ÅU, Björkhem-Bergman L, Lindh JD. Vitamin D and respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials. PLoS ONE. 2013;8:e65835. doi: 10.1371/journal.pone.0065835.
    1. Gunville CF, Mourani PM, Ginde AA. the role of vitamin d in prevention and treatment of infection. Inflamm Allergy Drug Targets. 2013;12:239–245. doi: 10.2174/18715281113129990046.
    1. Hoe E, Nathanielsz J, Toh ZQ, et al. Anti-inflammatory effects of vitamin d on human immune cells in the context of bacterial infection. Nutrients. 2016 doi: 10.3390/nu8120806.
    1. Yusupov E, Li-Ng M, Pollack S, et al (2010) Vitamin d and serum cytokines in a randomized clinical trial. Int. J. Endocrinol 2010: 305054. . Accessed 12 Jul 2020
    1. Yegorov S, Bromage S, Boldbaatar N, Ganmaa D. Effects of vitamin d supplementation and seasonality on circulating cytokines in adolescents: analysis of data from a feasibility trial in mongolia. Front Nutr. 2019;6:166. doi: 10.3389/fnut.2019.00166.
    1. Parlak E, Ertürk A, Çağ Y, et al. The effect of inflammatory cytokines and the level of vitamin D on prognosis in Crimean-Congo hemorrhagic fever. Int J Clin Exp Med. 2015;8:18302–18310.
    1. Khare D, Godbole NM, Pawar SD, et al. Calcitriol [1, 25[OH]2 D3] pre- and post-treatment suppresses inflammatory response to influenza A (H1N1) infection in human lung A549 epithelial cells. Eur J Nutr. 2013;52:1405–1415. doi: 10.1007/s00394-012-0449-7.
    1. Stagi S, Rigante D, Lepri G, et al. Severe vitamin D deficiency in patients with Kawasaki disease: a potential role in the risk to develop heart vascular abnormalities? Clin Rheumatol. 2016;35:1865–1872. doi: 10.1007/s10067-015-2970-6.
    1. Li Q, Dai Z, Cao Y, Wang L. Association of C-reactive protein and vitamin D deficiency with cardiovascular disease: a nationwide cross-sectional study from National Health and Nutrition Examination Survey 2007 to 2008. Clin Cardiol. 2019;42:663–669. doi: 10.1002/clc.23189.
    1. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124:188–195. doi: 10.1182/blood-2014-05-552729.
    1. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111:1805–1812. doi: 10.1172/JCI18921.
    1. Yin K, Agrawal DK. Vitamin D and inflammatory diseases. J Inflamm Res. 2014;7:69–87. doi: 10.2147/JIR.S63898.
    1. Meireles MS, Kamimura MA, Dalboni MA, de Carvalho JT, Aoike DT, Cuppari L. Effect of cholecalciferol on vitamin D-regulatory proteins in monocytes and on inflammatory markers in dialysis patients: a randomized controlled trial. Clin Nutr. 2016;35:1251–1258. doi: 10.1016/j.clnu.2016.04.014.
    1. Liu LCY, Voors AA, van Veldhuisen DJ, et al. Vitamin D status and outcomes in heart failure patients. Eur J Heart Fail. 2011;13:619–625. doi: 10.1093/eurjhf/hfr032.
    1. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020 doi: 10.1056/NEJMoa2002032.
    1. Novel Corona Virus 2019 Dataset. . Accessed 21 Apr 2020
    1. Coronavirus (COVID-19) in the UK. . Accessed 28 Jul 2020
    1. To understand the global pandemic, we need global testing – the Our World in Data COVID-19 Testing dataset. In: Our World Data. . Accessed 21 Apr 2020
    1. (2020) Over 6,000 being tested for COVID-19 in Iran per day. In: Tehran Times. . Accessed 21 Apr 2020
    1. La Moncloa. 16/04/2020. “930,230 PCR diagnostic tests have been performed in Spain since the start of the crisis”, says Salvador Illa [Government/News]. . Accessed 28 Jul 2020
    1. CDC (2020) COVIDView, Key Updates for Week 28. In: Cent. Dis. Control Prev. . Accessed 19 Jul 2020
    1. COVIDView: A weekly surveillance summary of U.S. COVID-19 Activity | CDC. . Accessed 19 Jul 2020
    1. SPF COVID-19 : point épidémiologique du 7 mai 2020. /maladies-et-traumatismes/maladies-et-infections-respiratoires/infection-a-coronavirus/documents/bulletin-national/covid-19-point-epidemiologique-du-7-mai-2020. Accessed 19 Jul 2020
    1. Rossi PG, Ferroni E, Alegiani SS, et al. Survival of hospitalized COVID-19 patients in Northern Italy: a population-based cohort study by the ITA-COVID19 Network. medRxiv. 2020 doi: 10.1101/2020.05.15.20103119.
    1. Coronavirus (COVID-19) hospitalizations age group Switzerland 2020. In: Statista. . Accessed 19 Jul 2020
    1. FOPH FO of PH New coronavirus: Situation in Switzerland. . Accessed 19 Jul 2020
    1. Docherty AB, Harrison EM, Green CA, et al. Features of 16,749 hospitalised UK patients with COVID-19 using the ISARIC WHO clinical characterisation protocol. medRxiv. 2020 doi: 10.1101/2020.04.23.20076042.
    1. Informes COVID-19. . Accessed 21 Apr 2020
    1. Nikpouraghdam M, Jalali Farahani A, Alishiri G, et al. Epidemiological characteristics of coronavirus disease 2019 (COVID-19) patients in IRAN: a single center study. J Clin Virol. 2020;127:104378. doi: 10.1016/j.jcv.2020.104378.
    1. Hospital beds (per 10 000 population). ). Accessed 19 Jul 2020
    1. Phua J, Faruq MO, Kulkarni AP, et al. Critical care bed capacity in Asian countries and regions. Crit Care Med. 2020;48:654–662. doi: 10.1097/CCM.0000000000004222.
    1. Rhodes A, Ferdinande P, Flaatten H, et al. The variability of critical care bed numbers in Europe. Intensive Care Med. 2012;38:1647–1653. doi: 10.1007/s00134-012-2627-8.
    1. Basile M, Ciardi L, Crespi I, et al. Assessing serum concentrations of 25-hydroxy-vitamin D in North-Western Italy. J Frailty Aging. 2013;2:174–178. doi: 10.14283/jfa.2013.25.
    1. Toffanello ED, Perissinotto E, Sergi G, et al. Vitamin D and physical performance in elderly subjects: the ProVA study. PLoS ONE. 2012;7:e34950. doi: 10.1371/journal.pone.0034950.
    1. Adami S, Viapiana O, Gatti D, et al. Relationship between serum parathyroid hormone, vitamin D sufficiency, age, and calcium intake. Bone. 2008;42:267–270. doi: 10.1016/j.bone.2007.10.003.
    1. González-Molero I, Morcillo S, Valdés S, et al. Vitamin D deficiency in Spain: a population-based cohort study. Eur J Clin Nutr. 2011;65:321–328. doi: 10.1038/ejcn.2010.265.
    1. Rabenberg M, Scheidt-Nave C, Busch MA, et al. Vitamin D status among adults in Germany—results from the German health interview and examination survey for adults (DEGS1) BMC Public Health. 2015 doi: 10.1186/s12889-015-2016-7.
    1. Park J-H, Hong IY, Chung JW, Choi HS. Vitamin D status in South Korean population. Medicine (Baltimore) 2018 doi: 10.1097/MD.0000000000011032.
    1. Centers for Disease Control and Prevention (CDC). National Center for Health Statistics (NCHS). National Health and Nutrition Examination Survey Data. Hyattsville, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, NHANES 2009–2010 Laboratory Data. . Accessed 13 May 2020
    1. Zhou B, Bentham J, Cesare MD, et al. Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants. Lancet. 2017;389:37–55. doi: 10.1016/S0140-6736(16)31919-5.
    1. Abarca-Gómez L, Abdeen ZA, Hamid ZA, et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017;390:2627–2642. doi: 10.1016/S0140-6736(17)32129-3.
    1. Zhou B, Lu Y, Hajifathalian K, et al. Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants. Lancet. 2016;387:1513–1530. doi: 10.1016/S0140-6736(16)00618-8.
    1. Coronary heart disease death rate by country. In: World Life Expect. . Accessed 13 May 2020
    1. Wu JT, Leung K, Bushman M, et al. Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan. China Nat Med. 2020 doi: 10.1038/s41591-020-0822-7.
    1. Wei J, Zhu A, Ji JS. A comparison study of vitamin D deficiency among older adults in China and the United States. Sci Rep. 2019;9:1–11. doi: 10.1038/s41598-019-56297-y.
    1. Hovsepian S, Amini M, Aminorroaya A, et al. Prevalence of vitamin d deficiency among adult population of Isfahan city. Iran J Health Popul Nutr. 2011;29:149–155.
    1. Souberbielle J-C, Massart C, Brailly-Tabard S, et al. Prevalence and determinants of vitamin D deficiency in healthy French adults: the VARIETE study. Endocrine. 2016;53:543–550. doi: 10.1007/s12020-016-0960-3.
    1. NDNS: results from Years 5 and 6 (combined). In: . . Accessed 26 Apr 2020
    1. Semba RD, Houston DK, Bandinelli S, et al. Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults. Eur J Clin Nutr. 2010;64:203–209. doi: 10.1038/ejcn.2009.140.
    1. Farhud DD, Mehrabi A, Sarafnejad A, et al. A comprehensive, epidemiological and ecological descriptive study on vitamin d status in Iran (308005 People, from 2009–2018) Iran J Public Health. 2019;48:644.
    1. Vernay M, Sponga M, Salanave B, et al. O62 Statut en vitamine D de la population adulte en France : l’étude nationale nutrition santé (ENNS, 2006–2007) Nutrition Clinique et Métabolisme. 2011;25:S50–S51. doi: 10.1016/S0985-0562(11)70066-8.
    1. Klenk J, Rapp K, Denkinger MD, et al. Seasonality of vitamin D status in older people in Southern Germany: implications for assessment. Age Ageing. 2013;42:404–408. doi: 10.1093/ageing/aft042.
    1. Wielen RP, et al. Serum vitamin D concentrations among elderly people in Europe. Lancet. 1995;346:207–210. doi: 10.1016/S0140-6736(95)91266-5.
    1. Merlo C, Trummler M, Essig S, Zeller A. Vitamin D deficiency in unselected patients from swiss primary care: a cross-sectional study in two seasons. PLoS ONE. 2015;10:e0138613. doi: 10.1371/journal.pone.0138613.
    1. Burnand B, Sloutskis D, Gianoli F, et al. Serum 25-hydroxyvitamin D: distribution and determinants in the Swiss population. Am J Clin Nutr. 1992;56:537–542. doi: 10.1093/ajcn/56.3.537.
    1. (2020) How many ventilators does the NHS have? In: Metro. . Accessed 18 Jul 2020
    1. Morris L, Booth W, Beck L As coronavirus surges, a frantic Europe scrambles for hospital beds, ventilators, supplies. Wash. Post
    1. (2020) Coronavirus: Swiss hospitals have around 750 breathing ventilators. In: Le News. . Accessed 19 Jul 2020
    1. (2020) Shortage means virus docs in Italy have no more ventilators for over-60s. In: The Sun. . Accessed 19 Jul 2020
    1. CDCMMWR (2020) Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19)—United States, February 12–March 16, 2020. MMWR Morb Mortal Wkly Rep. 10.15585/mmwr.mm6912e2
    1. Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science. 2020;368:473–474. doi: 10.1126/science.abb8925.
    1. Schultz DR, Arnold P. Properties of four acute phase proteins: C-reactive protein, serum amyloid a protein, α1-acid glycoprotein, and fibrinogen. Semin Arthritis Rheum. 1990;20:129–147. doi: 10.1016/0049-0172(90)90055-K.
    1. Panichi V, De Pietro S, Andreini B, et al. Calcitriol modulates in vivo and in vitro cytokine production: a role for intracellular calcium. Kidney Int. 1998;54:1463–1469. doi: 10.1046/j.1523-1755.1998.00152.x.
    1. Wu C-C, Chang J-H, Chen C-C, et al. Calcitriol treatment attenuates inflammation and oxidative stress in hemodialysis patients with secondary hyperparathyroidism. Tohoku J Exp Med. 2011;223:153–159. doi: 10.1620/tjem.223.153.
    1. McGregor R, Chauss D, Freiwald T, et al. An autocrine Vitamin D-driven Th1 shutdown program can be exploited for COVID-19. bioRxiv. 2020 doi: 10.1101/2020.07.18.210161.
    1. Ngo DT, Sverdlov AL, McNeil JJ, Horowitz JD. Does vitamin D modulate asymmetric dimethylarginine and C-reactive protein concentrations? Am J Med. 2010;123:335–341. doi: 10.1016/j.amjmed.2009.09.024.
    1. Mellenthin L, Wallaschofski H, Grotevendt A, Völzke H, Nauck M, Hannemann A. Association between serum vitamin D concentrations and inflammatory markers in the general adult population. Metabolism. 2014;63:1056–1062. doi: 10.1016/j.metabol.2014.05.002.
    1. Beilfuss J, Jorde R, Kamycheva E. High-sensitivity CRP is associated with serum 25-hydroxyvitamin D levels, but is not affected by 5-Year supplementation with cholecalciferol. J Nutr Health Food Sci. 2017;5(5):1–8. doi: 10.15226/jnhfs.2017.001108.
    1. Palaniswamy S, Gill D, De Silva NM, et al. Could vitamin D reduce obesity-associated inflammation? Observational and Mendelian randomization study. Am J Clin Nutr. 2020;111:1036–1047. doi: 10.1093/ajcn/nqaa056.
    1. Bellia A, Garcovich C, D’Adamo M, et al. Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects. Intern Emerg Med. 2013;8:33–40. doi: 10.1007/s11739-011-0559-x.
    1. Xu S, Song J, Zhang Z-H, et al. The Vitamin D status is associated with serum C-reactive protein and adhesion molecules in patients with renal cell carcinoma. Sci Rep. 2019;9:16719. doi: 10.1038/s41598-019-53395-9.
    1. Yu Y, Tian L, Xiao Y, et al. Effect of vitamin d supplementation on some inflammatory biomarkers in type 2 diabetes mellitus subjects: a systematic review and meta-analysis of randomized controlled trials. Ann Nutr Metab. 2018;73:62–73. doi: 10.1159/000490358.
    1. Rhodes JM, Subramanian S, Laird E, Kenny RA. Editorial: low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity. Aliment Pharmacol Ther. 2020 doi: 10.1111/apt.15777.
    1. D’Avolio A, Avataneo V, Manca A, et al. 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2. Nutrients. 2020;12:1359. doi: 10.3390/nu12051359.
    1. Fasano A, Cereda E, Barichella M, et al. COVID-19 in Parkinson’s disease patients living in lombardy. Italy: Mov Disord; 2020.
    1. Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Rochester: Social Science Research Network; 2020.
    1. Mahbub S, Brubaker AL, Kovacs EJ. Aging of the innate immune system: an update. Curr Immunol Rev. 2011;7:104–115. doi: 10.2174/157339511794474181.
    1. Chen X, Liu S, Goraya MU, et al. Host immune response to influenza a virus infection. Front Immunol. 2018 doi: 10.3389/fimmu.2018.00320.
    1. Little P. Non-steroidal anti-inflammatory drugs and covid-19. BMJ. 2020 doi: 10.1136/bmj.m1185.
    1. Mortensen R, Clemmensen HS, Woodworth JS, et al. Cyclooxygenase inhibitors impair CD4 T cell immunity and exacerbate Mycobacterium tuberculosis infection in aerosol-challenged mice. Commun Biol. 2019;2:1–10. doi: 10.1038/s42003-019-0530-3.
    1. Bancos S, Bernard MP, Topham DJ, Phipps RP. Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells. Cell Immunol. 2009;258:18–28. doi: 10.1016/j.cellimm.2009.03.007.
    1. Lee Y-J, Chuang Y-C. Ibuprofen augments pro-inflammatory cytokine release in a mouse model of Vibrio vulnificus infection. Microbiol Immunol. 2010;54:542–550. doi: 10.1111/j.1348-0421.2010.00249.x.
    1. Sirota L, Shacham D, Punsky I, Bessler H. Ibuprofen affects pro- and anti-inflammatory cytokine production by mononuclear cells of preterm newborns. Biol Neonate. 2001;79:103–108. doi: 10.1159/000047075.
    1. World first coronavirus treatment approved for NHS use by government. In: . . Accessed 18 Jun 2020
    1. Aluisio AR, Maroof Z, Chandramohan D, et al. Vitamin D3 supplementation and childhood diarrhea: a randomized controlled trial. Pediatrics. 2013;132:e832–e840. doi: 10.1542/peds.2012-3986.
    1. Litonjua AA, Carey VJ, Laranjo N, et al. Effect of prenatal supplementation with vitamin D on asthma or recurrent wheezing in offspring by Age 3 Years: The VDAART Randomized Clinical Trial. JAMA. 2016;315:362–370. doi: 10.1001/jama.2015.18589.

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