Association between 25-OH Vitamin D Deficiency and COVID-19 Severity in Pregnant Women
Johana Vásquez-Procopio, Johnatan Torres-Torres, Hector Borboa-Olivares, Salvador Espino Y Sosa, Raigam Jafet Martínez-Portilla, Mario Solis-Paredes, Mari-Cruz Tolentino-Dolores, Addy Cecilia Helguera-Repetto, Karla Cecilia Marrufo-Gallegos, Fanis Missirlis, Otilia Perichart-Perera, Guadalupe Estrada-Gutierrez
International Journal of Molecular Sciences, doi:10.3390/ijms232315188
Evidence from studies in the general population suggests an association between vitamin D insufficiency/deficiency and COVID-19 susceptibility and disease severity. The present study was performed on 165 third-trimester pregnant women at the time of delivery. Seventy-nine women tested negative for SARS-CoV-2. From 86 women testing positive, 32 were asymptomatic, 44 presented a mild form of the disease, and 10 experienced severe symptoms. Serum 25-OH vitamin D levels were measured on blood samples collected on admission. Low vitamin D levels were detected in symptomatic but not asymptomatic COVID-19 patients compared to healthy women (p = 0.0227). In addition, 20 (45.4%) pregnant women in the mild COVID-19 group and 6 (60%) in the severe group were vitamin D deficient (p = 0.030). On the other hand, lasso regression analysis showed that 25-OH vitamin D deficiency is an independent predictor of severe COVID-19 with an odds ratio (OR) of 5.81 (95% CI: 1.108-30.541; p = 0.037). These results show the relationship between vitamin D deficiency in pregnant women and the severity of COVID-19 infection and support the recommendation to supplement with vitamin D to avoid worse COVID-19 outcomes during pregnancy.
Conflicts of Interest: The authors declare no conflict of interest.
References
Aguilar-Cordero, Lasserrot-Cuadrado, Mur-Villar, León-Ríos, Rivero-Blanco et al., preeclampsia and prematurity: A systematic review and meta-analysis of observational and interventional studies, Midwifery,
doi:10.1016/j.midw.2020.102707
Alkhafaji, Argan, Albaker, Elq, Hariri et al., The Impact of Vitamin D Level on the Severity and Outcome of Hospitalized Patients with COVID-19
Annweiler, Beaudenon, Simon, Guenet, Otekpo et al., Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2021.105958
Annweiler, Hanotte, Eprevier, Sabatier, Lafaie et al., Vitamin D and survival in COVID-19 patients: A quasi-experimental study, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2020.105771
Bae, Choe, Holick, Lim, Association of vitamin D status with COVID-19 and its severity: Vitamin D and COVID-19: A narrative review, Rev. Endocr. Metab. Disord,
doi:10.1007/s11154-021-09705-6
Belderbos, Houben, Wilbrink, Lentjes, Bloemen et al., Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis, Pediatrics,
doi:10.1542/peds.2010-3054
Bui, Zhu, Hawkins, Cortez-Resendiz, Bellon, Vitamin D regulation of the immune system and its implications for COVID-19: A mini review, SAGE Open Med,
doi:10.1177/20503121211014073
Bushnaq, Algethami, Qadhi, Mustafa, Ghafouri et al., The Impact of Vitamin D Status on COVID-19 Severity among Hospitalized Patients in the Western Region of Saudi Arabia: A Retrospective Cross-Sectional Study, Int. J. Environ. Res. Public Health,
doi:10.3390/ijerph19031901
Chen, Mei, Xie, Yuan, Ma 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,
doi:10.1186/s12937-021-00744-y
Chen, Pang, Li, Zhou, Lin et al., Early pregnancy vitamin D and the risk of adverse maternal and infant outcomes: A retrospective cohort study, BMC Pregnancy Childbirth,
doi:10.1186/s12884-020-03158-6
Chen, Zhou, Dong, Qu, Gong et al., Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study, Lancet,
doi:10.1016/S0140-6736(20)30211-7
Christoph, Challande, Raio, Surbek, High prevalence of severe vitamin D deficiency during the first trimester in pregnant women in Switzerland and its potential contributions to adverse outcomes in the pregnancy, Swiss Med. Wkly,
doi:10.4414/smw.2020.20238
Cui, Zhao, Zhang, Guo, Guo et al., A systematic review and meta-analysis of children with coronavirus disease 2019 (COVID-19), J. Med. Virol,
doi:10.1002/jmv.26398
Cyprian, Lefkou, Varoudi, Girardi, Immunomodulatory Effects of Vitamin D in Pregnancy and Beyond, Front. Immunol,
doi:10.3389/fimmu.2019.02739
Dadras, Seyedalinaghi, Karimi, Shamsabadi, Qaderi et al., COVID-19 mortality and its predictors in the elderly: A systematic review, Health Sci. Rep
Dobson, Giovannoni, Ramagopalan, The month of birth effect in multiple sclerosis: Systematic review, meta-analysis and effect of latitude, J. Neurol. Neurosurg. Psychiatry,
doi:10.1136/jnnp-2012-303934
Drucker, Coronavirus Infections and Type 2 Diabetes-Shared Pathways with Therapeutic Implications, Endocr. Rev,
doi:10.1210/endrev/bnaa011
El Mouhayyar, Dewald, Cabrales, Tighiouart, Moraco et al., Factors Associated with Severity of Acute Kidney Injury and Adverse Outcomes in Critically Ill Patients with COVID-19, Nephron,
doi:10.1159/000524657
Ergür, Berbero Glu, Atasay, Şıklar, Bilir et al., Vitamin D deficiency in Turkish mothers and their neonates and in women of reproductive age, J. Clin. Res. Pediatr. Endocrinol,
doi:10.4274/jcrpe.v1i6.266
Ferrer-Sánchez, Díaz-Goicoechea, Mayoral-Cesar, García-Solbas, Nievas-Soriano et al., Serum 25(OH) Vitamin D Levels in Pregnant Women with Coronavirus Disease 2019 (COVID-19): A Case-Control Study, Int. J. Environ. Res. Public Health,
doi:10.3390/ijerph19073965
Gong, Zhou, Hu, Ren, Ren et al., Elastic net-based identification of GAMT as potential diagnostic marker for early-stage gastric cancer, Biochem. Biophys. Res. Commun,
doi:10.1016/j.bbrc.2021.12.055
Hastie, Mackay, Ho, Celis-Morales, Katikireddi et al., Vitamin D concentrations and COVID-19 infection in UK Biobank, Diabetes Metab. Syndr
Hernández, Nan, Fernandez-Ayala, García-Unzueta, Hernández-Hernández et al., Vitamin D Status in Hospitalized Patients with SARS-CoV-2
Hewison, Vitamin D and immune function: Autocrine, paracrine or endocrine?, Scand. J. Clin. Lab. Investig. Suppl
Holick, Binkley, Bischoff-Ferrari, Gordon, Hanley et al., Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline, J. Clin. Endocrinol. Metab,
doi:10.1210/jc.2011-0385
Jevalikar, Mithal, Singh, Sharma, Farooqui et al., Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19, Sci. Rep,
doi:10.1038/s41598-021-85809-y
Jolliffe, Camargo, Jr, Sluyter, Aglipay et al., Vitamin D supplementation to prevent acute respiratory infections: A systematic review and meta-analysis of aggregate data from randomised controlled trials, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(21)00051-6
Kastora, Patel, Carter, Delibegovic, Myint, Impact of diabetes on COVID-19 mortality and hospital outcomes from a global perspective: An umbrella systematic review and meta-analysis, Endocrinol. Diabetes Metab
Kucirka, Norton, Sheffield, Severity of COVID-19 in pregnancy: A review of current evidence, Am. J. Reprod. Immunol,
doi:10.1111/aji.13332
Kulda, Vitamin D metabolism, Vnitr Lek
Lin, Mulick, Mathur, Smeeth, Warren-Gash et al., The association between vitamin D status and COVID-19 in England: A cohort study using UK Biobank, PLoS ONE,
doi:10.1371/journal.pone.0269064
Loy, Lek, Yap, Soh, Padmapriya et al., Association of Maternal Vitamin D Status with Glucose Tolerance and Caesarean Section in a Multi-Ethnic Asian Cohort: The Growing Up in Singapore Towards Healthy Outcomes Study, PLoS ONE,
doi:10.1371/journal.pone.0142239
Mansur, Oliveri, Giacoia, Fusaro, Costanzo et al., Before, during and after Pregnancy: Effect on Neonates and Children, Nutrients,
doi:10.3390/nu14091900
Maugeri, Barchitta, Blanco, Agodi, Effects of Vitamin D Supplementation During Pregnancy on Birth Size: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, Nutrients,
doi:10.3390/nu11020442
Meltzer, Best, Zhang, Vokes, Arora et al., Association of Vitamin D Levels, Race/Ethnicity, and Clinical Characteristics With COVID-19 Test Results, JAMA Netw. Open,
doi:10.1001/jamanetworkopen.2021.4117
Merzon, Tworowski, Gorohovski, Vinker, Cohen et al., Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: An Israeli population-based study, FEBS J,
doi:10.1111/febs.15495
Metz, Clifton, Hughes, Sandoval, Grobman et al., Association of SARS-CoV-2 Infection With Serious Maternal Morbidity and Mortality From Obstetric Complications, JAMA,
doi:10.1001/jama.2022.1190
Meyyazhagan, Pushparaj, Balasubramanian, Bhotla, Pappusamy et al., COVID-19 in pregnant women and children: Insights on clinical manifestations, complexities, and pathogenesis, Int. J. Gynaecol. Obstet,
doi:10.1002/ijgo.14007
Mor, Aldo, Alvero, The unique immunological and microbial aspects of pregnancy, Nat. Rev. Immunol,
doi:10.1038/nri.2017.64
Nguyen, Raju, Da Graca, Wang, Mohamed et al., 25-hydroxyvitamin D is a predictor of COVID-19 severity of hospitalized patients, PLoS ONE
Ovies, Semmes, Coyne, Pregnancy influences immune responses to SARS-CoV-2, Sci. Transl. Med
Perichart-Perera, González-Leyva, González-Ludlow, Tolentino-Dolores, Solis-Paredes et al., Vitamin D Deficiency in Mexican Pregnant Women: Is Supplementation with ≤400 IU/day Enough?, Nutrients,
doi:10.3390/nu12092517
Pham, Rahman, Majidi, Waterhouse, Neale, Acute Respiratory Tract Infection and 25-Hydroxyvitamin D Concentration: A Systematic Review and Meta-Analysis, Int. J. Environ. Res. Public Health,
doi:10.3390/ijerph16173020
Ramirez-Sandoval, Castillos-Ávalos, Paz-Cortés, Santillan-Ceron, Hernandez-Jimenez et al., Very Low Vitamin D Levels are a Strong Independent Predictor of Mortality in Hospitalized Patients with Severe COVID-19, Arch. Med. Res,
doi:10.1016/j.arcmed.2021.09.006
Rastogi, Bhansali, Khare, Suri, Yaddanapudi et al., Short term, high-dose vitamin D supplementation for COVID-19 disease: A randomised, placebo-controlled, study (SHADE study), Postgrad. Med. J,
doi:10.1136/postgradmedj-2020-139065
Roffe-Vazquez, Huerta-Delgado, Castillo, Villarreal-Calderón, Gonzalez-Gil et al., Correlation of Vitamin D with Inflammatory Cytokines, Atherosclerotic Parameters, and Lifestyle Factors in the Setting of Heart Failure: A 12-Month Follow-Up Study, Int. J. Mol. Sci,
doi:10.3390/ijms20225811
Sappenfield, Jamieson, Kourtis, Pregnancy and susceptibility to infectious diseases, Infect. Dis. Obstet. Gynecol,
doi:10.1155/2013/752852
Schmitt, Labdouni, Soulimani, Delamare, Bouayed, Oxidative stress status and vitamin D levels of asymptomatic to mild symptomatic COVID-19 infections during the third trimester of pregnancy: A retrospective study in Metz, France, J. Med. Virol,
doi:10.1002/jmv.27606
Seven, Gunduz, Erdinc, Sahin, Tekin et al., Correlation between 25-hydroxy vitamin D levels and COVID-19 severity in pregnant women: A cross-sectional study, J. Matern. Fetal Neonatal Med,
doi:10.1080/14767058.2021.2005564
Shin, Choi, Longtine, Nelson, Vitamin D effects on pregnancy and the placenta, Placenta
Sinaci, Ocal, Yetiskin, Hendem, Buyuk et al., Impact of vitamin D on the course of COVID-19 during pregnancy: A case control study, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2021.105964
Sánchez-Zuno, González-Estevez, Matuz-Flores, Macedo-Ojeda, Hernández-Bello et al., Vitamin D Levels in COVID-19 Outpatients from Western Mexico: Clinical Correlation and Effect of Its Supplementation, J. Clin. Med,
doi:10.3390/jcm10112378
Takase, Tsugawa, Sugiyama, Ikesue, Eto et al., Association between 25-hydroxyvitamin D levels and COVID-19 severity, Clin. Nutr. ESPEN,
doi:10.1016/j.clnesp.2022.04.003
Tekin, Yassa, Birol, Unlu, Sahin et al., Vitamin D status is not associated with clinical severity of COVID-19 in pregnant women, Eur. J. Nutr,
doi:10.1007/s00394-021-02709-7
Tiwari, Pratyush, Gupta, Singh, Vitamin D deficiency is associated with inflammatory cytokine concentrations in patients with diabetic foot infection, Br. J. Nutr,
doi:10.1017/S0007114514003018
Torres-Torres, Martinez-Portilla, Espino Y Sosa, Solis-Paredes, Hernández-Pacheco et al., Maternal Death by COVID-19 Associated with Elevated Troponin T Levels, Viruses,
doi:10.3390/v14020271
Umar, Sastry, Chouchane, Role of Vitamin D Beyond the Skeletal Function: A Review of the Molecular and Clinical Studies, Int. J. Mol. Sci,
doi:10.3390/ijms19061618
Vanegas-Cedillo, Bello-Chavolla, Ramírez-Pedraza, Encinas, Pérez Carrión et al., Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity and Mortality Independent of Whole-Body and Visceral Adiposity, Front. Nutr
Venkatakrishnan, Pawlowski, Zemmour, Hughes, Anand et al., Mapping each pre-existing condition's association to short-term and long-term COVID-19 complications, NPJ Digit. Med,
doi:10.1038/s41746-021-00484-7
Vásquez-Procopio, Espejel-Nuñez, Torres-Torres, Martinez-Portilla, Espino Y Sosa et al., Inflammatory-Metal Profile as a Hallmark for COVID-19 Severity During Pregnancy, Front. Cell Dev. Biol,
doi:10.3389/fcell.2022.935363
Wei, Bilodeau, Julien, Luo, Abenhaim et al., Maternal vitamin D, oxidative stress, and pre-eclampsia, Int. J. Gynaecol. Obstet,
doi:10.1002/ijgo.13559
Wei, Bilodeau-Bertrand, Liu, Auger, The impact of COVID-19 on pregnancy outcomes: A systematic review and meta-analysis, CMAJ,
doi:10.1503/cmaj.202604
Wei, Qi, Luo, Fraser, Maternal vitamin D status and adverse pregnancy outcomes: A systematic review and meta-analysis, J. Matern. Fetal Neonatal Med,
doi:10.3109/14767058.2013.765849