Exploring the link between vitamin D and clinical outcomes in COVID-19
Prateek Lohia, Paul Nguyen, Neel Patel, Shweta Kapur
American Journal of Physiology-Endocrinology and Metabolism, doi:10.1152/ajpendo.00517.2020
The immunomodulating role of vitamin D might play a role in COVID-19 disease. We studied the association between vitamin D and clinical outcomes in COVID-19 patients. This is a retrospective cohort study on COVID-19 patients with documented vitamin D levels within the last year. Vitamin D levels were grouped as ! 20 ng/mL or < 20 ng/mL. Main outcomes were mortality, need for mechanical ventilation, new DVT or pulmonary embolism, and ICU admission. A total of 270 patients (mean ± SD) age, 63.81 (14.69) years); 117 (43.3%) males; 216 (80%) Blacks; 139 (51.5%) in 65 and older age group were included. Vitamin D levels were less than 20 ng/mL in 95 (35.2%) patients. During admission, 72 patients (26.7%) died, 59 (21.9%) needed mechanical ventilation, and 87 (32.2%) required ICU. Vitamin D levels showed no significant association with mortality (OR = 0.69; 95% CI, 0.39-1.24; P = 0.21), need for mechanical ventilation (OR = 1.23; 95% CI, 0.68-2.24; P = 0.49), new DVT or PE(OR= 0.92; 95% CI, 0.16-5.11; P = 1.00) or ICU admission (OR = 1.38; 95% CI, 0.81-2.34; P = 0.23). We did not find any significant association of vitamin D levels with mortality, the need for mechanical ventilation, ICU admission and the development of thromboembolism in COVID-19 patients. NEW & NOTEWORTHY Low vitamin D has been associated with increased frequency and severity of respiratory tract infections in the past. Current literature linking clinical outcomes in COVID-19 with low vitamin D is debatable. This study evaluated the role of vitamin D in severe disease outcomes among COVID-19 patients and found no association of vitamin D levels with mortality, the need for mechanical ventilation, ICU admission, and thromboembolism in COVID-19.
AUTHOR CONTRIBUTIONS P.L., P.N., and N.P. conceived and designed research; P.L. and S.K. analyzed data; P.L. and S.K. interpreted results of experiments; P.L., P.N., N.P., and S.K. prepared figures; P.L., P.N., and S.K. drafted manuscript; P.L., P.N., N.P., and S.K. edited and revised manuscript; P.L., P.N., N.P., and S.K. approved final version of manuscript.
References
Adams, Ren, Liu, Chun, Lagishetty et al., Vitamin D-directed rheostatic regulation of monocyte antibacterial responses, J Immunol,
doi:10.4049/jimmunol.0803736Anderson, Geleris, Anderson, Zucker, Nobel et al., Body mass index and risk for intubation or death in SARS-CoV-2 infection: a retrospective cohort study, Ann Intern Med,
doi:10.7326/M20-3214Blondon, Rodabough, Budrys, Johnson, Berger et al., The effect of calcium plus vitamin D supplementation on the risk of venous thromboembolism: from the Women's Health Initiative Randomized Controlled Trial, Thromb Haemost,
doi:10.1160/TH14-05-0478Braun, Chang, Mahadevappa, Gibbons, Liu et al., Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill, Crit Care Med,
doi:10.1097/CCM.0b013e318206ccdfBrodin, Lerstad, Grimnes, Braekkan, Vik et al., Serum levels of vitamin D are not associated with future risk of venous thromboembolism: the Tromsø study, Thromb Haemost,
doi:10.1160/TH12-10-0728Brøndum-Jacobsen, Benn, Tybjaerg-Hansen, Nordestgaard, 25-Hydroxyvitamin D concentrations and risk of venous thromboembolism in the general population with 18,791 participants, J Thromb Haemost,
doi:10.1111/jth.12118Cantorna, Snyder, Lin, Yang, Vitamin D and 1,25(OH)2D regulation of T cells, Nutrients,
doi:10.3390/nu7043011Carpagnano, Lecce, Quaranta, Zito, Buonamico et al., Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19, J Endocrinol Invest,
doi:10.1007/s40618-020-01370-xCharan, Goyal, Saxena, Yadav, Vitamin D for prevention of respiratory tract infections: a systematic review and meta-analysis, J Pharmacol Pharmacother,
doi:10.4103/0976-500X.103685Charoenngam, Holick, Immunologic effects of vitamin D on human health and disease, Nutrients,
doi:10.3390/nu12072097D'avolio, Avataneo, Manca, Cusato, Nicol O et al., 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2, Nutrients,
doi:10.3390/nu12051359Dancer, Parekh, Lax, Souza, Zheng et al., Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS), Thorax,
doi:10.1136/thoraxjnl-2014-206680De Haan, Groeneveld, De Geus, Egal, Struijs, Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis, Crit Care,
doi:10.1186/s13054-014-0660-4Ginde, Mansbach, Camargo, Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey, Arch Intern Med,
doi:10.1001/archinternmed.2008.560Grasselli, Zangrillo, Zanella, Antonelli, Cabrini et al., Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy, JAMA,
doi:10.1001/jama.2020.5394Greiller, Martineau, Modulation of the immune response to respiratory viruses by vitamin D, Nutrients,
doi:10.3390/nu7064240Hansdottir, Monick, Hinde, Lovan, Look et al., Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense, J Immunol,
doi:10.4049/jimmunol.181.10.7090Hastie, Mackay, Ho, Celis-Morales, Katikireddi et al., Vitamin D concentrations and COVID-19 infection in UK Biobank, Diabetes Metab Syndr,
doi:10.1016/j.dsx.2020.04.050Hwang, Hu, Hu, Zhu, Liu et al., Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirusinfected pneumonia in Wuhan, China, JAMA,
doi:10.1001/jama.2020.1585Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin Exp Res,
doi:10.1007/s40520-020-01570-8Janssens, Bouillon, Claes, Carremans, Lehouck et al., Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene, Thorax,
doi:10.1136/thx.2009.120659Jeffery, Burke, Mura, Zheng, Qureshi et al., 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3, J Immunol,
doi:10.4049/jimmunol.0803217Jolliffe, Griffiths, Martineau, Vitamin D in the prevention of acute respiratory infection: systematic review of clinical studies, J Steroid Biochem Mol Biol,
doi:10.1016/j.jsbmb.2012.11.017Khunti, Singh, Pareek, Hanif, Is ethnicity linked to incidence or outcomes of covid-19?, BMJ,
doi:10.1136/bmj.m1548Klok, Kruip, Van Der Meer, Arbous, Gommers et al., Incidence of thrombotic complications in critically ill ICU patients with COVID-19, Thromb Res,
doi:10.1016/j.thromres.2020.04.013Laird, Rhodes, Kenny, Vitamin D and inflammation: potential implications for severity of Covid-19, Ir Med J
Lei, Zhang, Cheng, Lee, Mechanisms of action of vitamin D as supplemental therapy for pneumocystis pneumonia, Antimicrob Agents Chemother,
doi:10.1128/AAC.01226-17Lemire, Adams, Kermani-Arab, Bakke, Sakai et al., 1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro, J Immunol
Liu, Stenger, Li, Wenzel, Tan et al., Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response, Science,
doi:10.1126/science.1123933Lucidarme, Messai, Mazzoni, Arcade, Cheyron, Incidence and risk factors of vitamin D deficiency in critically ill patients: results from a prospective observational study, Intensive Care Med,
doi:10.1007/s00134-010-1875-8Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ,
doi:10.1136/bmj.i6583Mckinney, Bailey, Garrett, Peiris, Manning et al., Relationship between vitamin D status and ICU outcomes in veterans, J Am Med Dir Assoc,
doi:10.1016/j.jamda.2010.04.004Mehta, Mcauley, Brown, Sanchez, Tattersall et al., and HLH Across Speciality Collaboration UK. COVID-19: consider cytokine storm syndromes and immunosuppression, Lancet,
doi:10.1016/S0140-6736(20)30628-0Meltzer, Best, Zhang, Vokes, Arora et al., Association of vitamin D status and other clinical characteristics with COVID-19 test results, JAMA Netw Open,
doi:10.1001/jamanetworkopen.2020.19722Munshi, Hussein, Toraih, Elshazli, Jardak et al., Vitamin D insufficiency as a potential culprit in critical COVID-19 patients, J Med Virol,
doi:10.1002/jmv.26360Olliver, Spelmink, Hiew, Meyer-Hoffert, Henriques-Normark et al., Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae, J Infect Dis,
doi:10.1093/infdis/jit355Remmelts, Van De Garde, Meijvis, Peelen, Damoiseaux et al., Addition of vitamin D status to prognostic scores improves the prediction of outcome in community-acquired pneumonia, Clin Infect Dis,
doi:10.1093/cid/cis751Schwalfenberg, A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency, Mol Nutr Food Res,
doi:10.1002/mnfr.201000174Scragg, Stewart, Waayer, Lawes, Toop et al., Effect of monthly high-dose vitamin D supplementation on cardiovascular disease in the vitamin D assessment study: a randomized clinical trial, JAMA Cardiol,
doi:10.1001/jamacardio.2017.0175Shi, Liu, Yao, Xing, Zhao et al., Chronic vitamin D deficiency induces lung fibrosis through activation of the renin-angiotensin system, Sci Rep,
doi:10.1038/s41598-017-03474-6Stokes, Zambrano, Anderson, Marder, Raz et al., Coronavirus Disease 2019 Case Surveillance: United States, MMWR Morb Mortal Wkly Rep,
doi:10.15585/mmwr.mm6924e2Tartof, Qian, Hong, Wei, Nadjafi et al., Obesity and mortality among patients diagnosed with COVID-19: results from an integrated health care organization, Ann Intern Med,
doi:10.7326/M20-3742Urashima, Segawa, Okazaki, Kurihara, Wada et al., Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren, Am J Clin Nutr,
doi:10.3945/ajcn.2009.29094Venkatram, Chilimuri, Adrish, Salako, Patel et al., Vitamin D deficiency is associated with mortality in the medical intensive care unit, Crit Care,
doi:10.1186/cc10585Vu Cković, Van Rein, Cannegieter, Rosendaal, Lijfering, Vitamin supplementation on the risk of venous thrombosis: results from the MEGA case-control study, Am J Clin Nutr,
doi:10.3945/ajcn.114.095398Wei, Christakos, Mechanisms underlying the regulation of innate and adaptive immunity by vitamin D, Nutrients,
doi:10.3390/nu7105392Wu, He, Low vitamin D levels are associated with the development of deep venous thromboembolic events in patients with ischemic stroke, Clin Appl Thromb Hemost,
doi:10.1177/1076029618786574Xu, Yang, Chen, Luo, Zhang et al., Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system, Mol Med Rep,
doi:10.3892/mmr.2017.7546Yang, Zheng, Gou, Pu, Chen et al., 2: a systematic review and meta-analysis
Zdrenghea, Makrinioti, Bagacean, Bush, Johnston et al., Vitamin D modulation of innate immune responses to respiratory viral infections, Rev Med Virol,
doi:10.1002/rmv.1909Zhang, Leung, Richers, Liu, Remigio et al., Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1, J Immunol,
doi:10.4049/jimmunol.1102412Zhang, Wan, Sun, Kan, Wang, Association between vitamin D deficiency and mortality in critically ill adult patients: a meta-analysis of cohort studies, Crit Care,
doi:10.1186/s13054-014-0684-9Zhang, Wu, Li, Zhao, Gq, Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2020.105954Zhou, Du, Huang, Wang, Shi et al., Preventive effects of vitamin D on seasonal influenza A in infants: a multicenter, randomized, open, controlled clinical trial, Pediatr Infect Dis J,
doi:10.1097/INF.0000000000001890{ 'indexed': {'date-parts': [[2024, 2, 10]], 'date-time': '2024-02-10T13:43:48Z', 'timestamp': 1707572628339},
'reference-count': 63,
'publisher': 'American Physiological Society',
'issue': '3',
'content-domain': {'domain': ['journals.physiology.org'], 'crossmark-restriction': True},
'published-print': {'date-parts': [[2021, 3, 1]]},
'abstract': '<jats:p>Low vitamin D has been associated with increased frequency and severity of '
'respiratory tract infections in the past. Current literature linking clinical outcomes in '
'COVID-19 with low vitamin D is debatable. This study evaluated the role of vitamin D in '
'severe disease outcomes among COVID-19 patients and found no association of vitamin D levels '
'with mortality, the need for mechanical ventilation, ICU admission, and thromboembolism in '
'COVID-19.</jats:p>',
'DOI': '10.1152/ajpendo.00517.2020',
'type': 'journal-article',
'created': {'date-parts': [[2021, 1, 6]], 'date-time': '2021-01-06T16:56:09Z', 'timestamp': 1609952169000},
'page': 'E520-E526',
'update-policy': 'http://dx.doi.org/10.1152/aps-crossmark-policy',
'source': 'Crossref',
'is-referenced-by-count': 20,
'title': 'Exploring the link between vitamin D and clinical outcomes in COVID-19',
'prefix': '10.1152',
'volume': '320',
'author': [ { 'ORCID': 'http://orcid.org/0000-0003-4148-9597',
'authenticated-orcid': False,
'given': 'Prateek',
'family': 'Lohia',
'sequence': 'first',
'affiliation': [ { 'name': 'Department of Internal Medicine, Wayne State University, '
'Detroit, Michigan'}]},
{ 'given': 'Paul',
'family': 'Nguyen',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Internal Medicine, Wayne State University, '
'Detroit, Michigan'}]},
{ 'given': 'Neel',
'family': 'Patel',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Internal Medicine, Wayne State University, '
'Detroit, Michigan'}]},
{ 'given': 'Shweta',
'family': 'Kapur',
'sequence': 'additional',
'affiliation': [{'name': 'Wayne State University, Detroit, Michigan'}]}],
'member': '24',
'reference': [ {'key': 'B1', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jama.2020.1585'},
{'key': 'B2', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijid.2020.03.017'},
{'key': 'B3', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu7064240'},
{'key': 'B4', 'doi-asserted-by': 'publisher', 'DOI': '10.4049/jimmunol.181.10.7090'},
{'key': 'B5', 'doi-asserted-by': 'publisher', 'DOI': '10.1126/science.1123933'},
{'key': 'B6', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/infdis/jit355'},
{'key': 'B7', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0950268806007175'},
{'key': 'B8', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/archinternmed.2008.560'},
{'key': 'B9', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/thx.2009.120659'},
{'key': 'B10', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jsbmb.2012.11.017'},
{'key': 'B11', 'doi-asserted-by': 'publisher', 'DOI': '10.4103/0976-500X.103685'},
{'key': 'B12', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.i6583'},
{'key': 'B13', 'doi-asserted-by': 'publisher', 'DOI': '10.3945/ajcn.2009.29094'},
{'key': 'B14', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/INF.0000000000001890'},
{'key': 'B15', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/mnfr.201000174'},
{'key': 'B16', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/rmv.1909'},
{'key': 'B17', 'doi-asserted-by': 'publisher', 'DOI': '10.4049/jimmunol.0803736'},
{'key': 'B18', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu7043011'},
{ 'key': 'B19',
'doi-asserted-by': 'crossref',
'first-page': '3032',
'DOI': '10.4049/jimmunol.134.5.3032',
'volume': '134',
'author': 'Lemire JM',
'year': '1985',
'journal-title': 'J Immunol'},
{'key': 'B20', 'doi-asserted-by': 'publisher', 'DOI': '10.4049/jimmunol.1102412'},
{'key': 'B21', 'doi-asserted-by': 'publisher', 'DOI': '10.4049/jimmunol.0803217'},
{'key': 'B22', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu7105392'},
{'key': 'B23', 'doi-asserted-by': 'publisher', 'DOI': '10.1126/science.abb8925'},
{'key': 'B24', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijantimicag.2020.105954'},
{'key': 'B25', 'doi-asserted-by': 'publisher', 'DOI': '10.1128/AAC.01226-17'},
{'key': 'B26', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41598-017-03474-6'},
{'key': 'B27', 'doi-asserted-by': 'publisher', 'DOI': '10.3892/mmr.2017.7546'},
{'key': 'B28', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(20)30628-0'},
{'key': 'B29', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/thoraxjnl-2014-206680'},
{'key': 'B30', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.nutres.2010.12.001'},
{'key': 'B31', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.thromres.2020.04.013'},
{'key': 'B32', 'doi-asserted-by': 'publisher', 'DOI': '10.1177/1076029618786574'},
{'key': 'B33', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/jth.12118'},
{'key': 'B34', 'doi-asserted-by': 'publisher', 'DOI': '10.1160/TH12-10-0728'},
{'key': 'B35', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.b5664'},
{'key': 'B36', 'doi-asserted-by': 'publisher', 'DOI': '10.7326/M20-3214'},
{'key': 'B37', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jama.2020.5394'},
{'key': 'B38', 'doi-asserted-by': 'publisher', 'DOI': '10.7326/M20-3742'},
{ 'key': 'B39',
'first-page': '81',
'volume': '113',
'author': 'Laird E',
'year': '2020',
'journal-title': 'Ir Med J'},
{'key': 'B40', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s40520-020-01570-8'},
{'key': 'B41', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu12051359'},
{'key': 'B42', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.dsx.2020.04.050'},
{'key': 'B43', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jamanetworkopen.2020.19722'},
{'key': 'B44', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.m1548'},
{'key': 'B45', 'doi-asserted-by': 'publisher', 'DOI': '10.15585/mmwr.mm6924e2'},
{'key': 'B46', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jama.2020.8598'},
{'key': 'B47', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmjnph-2020-000096'},
{'key': 'B48', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/CCM.0b013e318206ccdf'},
{'key': 'B49', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s13054-014-0660-4'},
{'key': 'B50', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMc0809996'},
{'key': 'B51', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s00134-010-1875-8'},
{'key': 'B52', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jamda.2010.04.004'},
{'key': 'B53', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/cc10585'},
{'key': 'B54', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s13054-014-0684-9'},
{'key': 'B55', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/j.1440-1843.2011.01924.x'},
{'key': 'B56', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/cid/cis751'},
{'key': 'B57', 'doi-asserted-by': 'publisher', 'DOI': '10.2174/18715281113129990049'},
{'key': 'B58', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/jmv.26360'},
{'key': 'B59', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s40618-020-01370-x'},
{'key': 'B60', 'doi-asserted-by': 'publisher', 'DOI': '10.1160/TH14-05-0478'},
{'key': 'B61', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jamacardio.2017.0175'},
{'key': 'B62', 'doi-asserted-by': 'publisher', 'DOI': '10.3945/ajcn.114.095398'},
{'key': 'B63', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu12072097'}],
'container-title': 'American Journal of Physiology-Endocrinology and Metabolism',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://journals.physiology.org/doi/pdf/10.1152/ajpendo.00517.2020',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2023, 10, 17]],
'date-time': '2023-10-17T02:22:26Z',
'timestamp': 1697509346000},
'score': 1,
'resource': {'primary': {'URL': 'https://journals.physiology.org/doi/10.1152/ajpendo.00517.2020'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 3, 1]]},
'references-count': 63,
'journal-issue': {'issue': '3', 'published-print': {'date-parts': [[2021, 3, 1]]}},
'alternative-id': ['10.1152/ajpendo.00517.2020'],
'URL': 'http://dx.doi.org/10.1152/ajpendo.00517.2020',
'relation': {},
'ISSN': ['0193-1849', '1522-1555'],
'subject': ['Physiology (medical)', 'Physiology', 'Endocrinology, Diabetes and Metabolism'],
'container-title-short': 'American Journal of Physiology-Endocrinology and Metabolism',
'published': {'date-parts': [[2021, 3, 1]]},
'assertion': [ { 'value': '2020-10-21',
'order': 0,
'name': 'received',
'label': 'Received',
'group': {'name': 'publication_history', 'label': 'Publication History'}},
{ 'value': '2021-01-03',
'order': 2,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'publication_history', 'label': 'Publication History'}},
{ 'value': '2021-03-04',
'order': 3,
'name': 'published',
'label': 'Published',
'group': {'name': 'publication_history', 'label': 'Publication History'}}]}
