High Prevalence of Hypocalcemia in Non-severe COVID-19 Patients: A Retrospective Case-Control Study

DOI record: { "DOI": "10.3389/fmed.2020.590805", "ISSN": [ "2296-858X" ], "URL": "http://dx.doi.org/10.3389/fmed.2020.590805", "abstract": "<jats:p><jats:bold>Purpose:</jats:bold> To compare serum total calcium and phosphate levels in patients with non-severe COVID-19 with age, sex, and serum 25-hydroxyvitamin D level matched healthy adult cohort.</jats:p><jats:p><jats:bold>Methods:</jats:bold> In this retrospective case-control study, medical records of patients (≥18 years) diagnosed as non-severe COVID-19 admitted at and discharged from our tertiary care institution during the period from April 10, 2020 and June 20, 2020 were retrieved. Baseline investigations, notably, serum calcium, phosphate, albumin, magnesium, 25-hydroxyvitamin D, and C-reactive protein (CRP), were performed at admission before any form of calcium or vitamin D supplementation were considered. The biochemical parameters were compared with age, sex, and 25-hydroxyvitamin D matched healthy adult controls (1:1 ratio) derived from the Chandigarh Urban Bone Epidemiological Study (CUBES).</jats:p><jats:p><jats:bold>Results:</jats:bold> After exclusion, 72 patients with non-severe COVID-19 (63 mild and 9 moderate disease) and an equal number of healthy controls were included in the final analysis. Age, sex, serum 25-hydroxyvitamin D, and albumin levels were matched between the 2 groups. Hypovitaminosis D and hypocalcemia were seen in 97 and 67% of the patients, respectively. The patients had lower serum calcium (<jats:italic>P</jats:italic> value &amp;lt;0.001) and phosphate (<jats:italic>P</jats:italic> = 0.007) compared with the controls. There was no statistically significant correlation between serum calcium and CRP.</jats:p><jats:p><jats:bold>Conclusions:</jats:bold> Hypocalcemia is highly prevalent even in COVID-19 patients with non-severe disease probably implying that hypocalcemia is intrinsic to the disease. Prospective studies with larger number of patients are required to prove this hypothesis and unravel the underlying pathophysiological mechanisms.</jats:p>", "alternative-id": [ "10.3389/fmed.2020.590805" ], "author": [ { "affiliation": [], "family": "Pal", "given": "Rimesh", "sequence": "first" }, { "affiliation": [], "family": "Ram", "given": "Sant", "sequence": "additional" }, { "affiliation": [], "family": "Zohmangaihi", "given": "Deepy", "sequence": "additional" }, { "affiliation": [], "family": "Biswas", "given": "Indranil", "sequence": "additional" }, { "affiliation": [], "family": "Suri", "given": "Vikas", "sequence": "additional" }, { "affiliation": [], "family": "Yaddanapudi", "given": "Laxmi N.", "sequence": "additional" }, { "affiliation": [], "family": "Malhotra", "given": "Pankaj", "sequence": "additional" }, { "affiliation": [], "family": "Soni", "given": "Shiv L.", "sequence": "additional" }, { "affiliation": [], "family": "Puri", "given": "Goverdhan D.", "sequence": "additional" }, { "affiliation": [], "family": "Bhalla", "given": "Ashish", "sequence": "additional" }, { "affiliation": [], "family": "Bhadada", "given": "Sanjay K.", "sequence": "additional" } ], "container-title": "Frontiers in Medicine", "container-title-short": "Front. Med.", "content-domain": { "crossmark-restriction": true, "domain": [ "frontiersin.org" ] }, "created": { "date-parts": [ [ 2021, 1, 7 ] ], "date-time": "2021-01-07T07:57:19Z", "timestamp": 1610006239000 }, "deposited": { "date-parts": [ [ 2021, 1, 7 ] ], "date-time": "2021-01-07T07:57:41Z", "timestamp": 1610006261000 }, "indexed": { "date-parts": [ [ 2024, 3, 25 ] ], "date-time": "2024-03-25T19:25:31Z", "timestamp": 1711394731219 }, "is-referenced-by-count": 34, "issued": { "date-parts": [ [ 2021, 1, 7 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2021, 1, 7 ] ], "date-time": "2021-01-07T00:00:00Z", "timestamp": 1609977600000 } } ], "link": [ { "URL": "https://www.frontiersin.org/articles/10.3389/fmed.2020.590805/full", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1965", "original-title": [], "prefix": "10.3389", "published": { "date-parts": [ [ 2021, 1, 7 ] ] }, "published-online": { "date-parts": [ [ 2021, 1, 7 ] ] }, "publisher": "Frontiers Media SA", "reference": [ { "key": "B1", "unstructured": "Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in china: summary of a report of 72 314 cases from the chinese center for disease control and prevention\n WuZ\n McGooganJM\n 32091533JAMA2020" }, { "DOI": "10.1016/S0140-6736(20)31856-0", "article-title": "COVID-19 and non-communicable diseases", "author": "Pal", "doi-asserted-by": "publisher", "first-page": "P649", "journal-title": "Postgrad Med J", "key": "B2", "volume": "396", "year": "2020" }, { "DOI": "10.1016/j.ejim.2020.04.043", "article-title": "Factors associated with mortality in patients with COVID-19. A quantitative evidence synthesis of clinical and laboratory data", "author": "Martins-Filho", "doi-asserted-by": "publisher", "first-page": "97", "journal-title": "Eur J Intern Med.", "key": "B3", "volume": "76", "year": "2020" }, { "key": "B4", "unstructured": "Laboratory abnormalities in patients with COVID-2019 infection\n LippiG\n PlebaniM\n 32119647Clin Chem Lab Med CCLM2020" }, { "key": "B5", "unstructured": "Prevalence and predictive value of hypocalcemia in severe COVID-19 patients\n LiuJ\n HanP\n WuJ\n GongJ\n TianD\n 32622796J Infect Public Health.2020" }, { "DOI": "10.1177/0004563220922255", "article-title": "Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19)", "author": "Lippi", "doi-asserted-by": "publisher", "first-page": "262", "journal-title": "Ann Clin Biochem Int J Lab Med.", "key": "B6", "volume": "57", "year": "2020" }, { "DOI": "10.18632/aging.103526", "article-title": "Serum calcium as a biomarker of clinical severity and prognosis in patients with coronavirus disease 2019", "author": "Sun", "doi-asserted-by": "publisher", "first-page": "11287", "journal-title": "Aging", "key": "B7", "volume": "12", "year": "2020" }, { "DOI": "10.1007/s12020-020-02383-5", "article-title": "Hypocalcemia is highly prevalent and predicts hospitalization in patients with COVID-19", "author": "Di Filippo", "doi-asserted-by": "publisher", "first-page": "475", "journal-title": "Endocrine", "key": "B8", "volume": "68", "year": "2020" }, { "DOI": "10.1177/0885066611411543", "article-title": "Hypocalcemia in the critically Ill patient", "author": "Kelly", "doi-asserted-by": "publisher", "first-page": "166", "journal-title": "J Intensive Care Med.", "key": "B9", "volume": "28", "year": "2013" }, { "DOI": "10.1097/00003246-199202000-00014", "article-title": "Hypocalcemia in critically ill patients", "author": "Zaloga", "doi-asserted-by": "publisher", "first-page": "251", "journal-title": "Crit Care Med.", "key": "B10", "volume": "20", "year": "1992" }, { "DOI": "10.1097/00003246-200001000-00015", "article-title": "Hypocalcemia and parathyroid hormone secretion in critically ill patients", "author": "Lind", "doi-asserted-by": "publisher", "first-page": "93", "journal-title": "Crit Care Med.", "key": "B11", "volume": "28", "year": "2000" }, { "DOI": "10.1016/S0272-6386(01)80116-5", "article-title": "Hypocalcemia: a pervasive metabolic abnormality in the critically Ill", "author": "Zivin", "doi-asserted-by": "publisher", "first-page": "689", "journal-title": "Am J Kidney Dis.", "key": "B12", "volume": "37", "year": "2001" }, { "key": "B13", "unstructured": "COVID-19" }, { "key": "B14", "unstructured": "Metabolic bone profile of healthy adult north indian population from chandigarh urban bone epidemiological study (CUBES)\n AggarwalA\n RamS\n GargA\n PalR\n BhansaliA\n SinghP\n 10.1007/s12291-019-00857-632504420Indian J Clin Biochem2019" }, { "DOI": "10.4065/mcp.2010.0138", "article-title": "Vitamin D deficiency in adults: when to test and how to treat", "author": "Kennel", "doi-asserted-by": "publisher", "first-page": "752", "journal-title": "Mayo Clin Proc.", "key": "B15", "volume": "85", "year": "2010" }, { "key": "B16", "unstructured": "Hypocalcemia\n GoyalA\n SinghS\n StatPearls2020" }, { "DOI": "10.7326/0003-4819-107-1-36", "article-title": "The multifactorial basis for hypocalcemia during sepsis: studies of the parathyroid hormone-vitamin D axis", "author": "Zaloga", "doi-asserted-by": "publisher", "first-page": "36", "journal-title": "Ann Intern Med.", "key": "B17", "volume": "107", "year": "1987" }, { "article-title": "Parathyroid-vitamin D axis in critically ill patients with unexplained hypocalcemia", "author": "Desai", "first-page": "S225", "journal-title": "Kidney Int Suppl.", "key": "B18", "volume": "22", "year": "1987" }, { "DOI": "10.1074/jbc.M408587200", "article-title": "Calcium-sensing receptor gene transcription is UP-regulated by the Pro-inflammatory Cytokine, Interleukin-1β: role of the NF-κB pathway and κB elements", "author": "Canaff", "doi-asserted-by": "publisher", "first-page": "14177", "journal-title": "J Biol Chem.", "key": "B19", "volume": "280", "year": "2005" }, { "DOI": "10.1074/jbc.M708087200", "article-title": "The proinflammatory cytokine, interleukin-6, Up-regulates calcium-sensing receptor gene transcription via Stat1/3 and Sp1/3", "author": "Canaff", "doi-asserted-by": "publisher", "first-page": "13586", "journal-title": "J Biol Chem.", "key": "B20", "volume": "283", "year": "2008" }, { "key": "B21", "unstructured": "Low levels of total and ionized calcium in blood of COVID-19 patients\n CappelliniF\n BrivioR\n CasatiM\n CavalleroA\n ControE\n BrambillaP\n 32459190Clin Chem Lab Med2020" }, { "DOI": "10.1371/journal.ppat.1004077", "article-title": "Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis", "author": "Nieto-Torres", "doi-asserted-by": "publisher", "first-page": "e1004077", "journal-title": "PLoS Pathog", "key": "B22", "volume": "10", "year": "2014" }, { "key": "B23", "unstructured": "Hypocalcemia: the quest for the cause of a major biochemical feature of COVID-19\n di FilippoL\n FormentiAM\n GiustinaA\n 10.1007/s12020-020-02525-933094473Endocrine2020" }, { "key": "B24", "unstructured": "Mechanistic basis and therapeutic relevance of hypocalcemia during severe COVID-19 infection\n SinghVP\n KhatuaB\n El-KurdiB\n RoodC\n 33099749Endocrine2020" }, { "DOI": "10.1016/j.medidd.2020.100051", "article-title": "Vitamin D levels and COVID-19 susceptibility: is there any correlation?", "author": "Razdan", "doi-asserted-by": "publisher", "first-page": "100051", "journal-title": "Med Drug Discov.", "key": "B25", "volume": "7", "year": "2020" }, { "key": "B26", "unstructured": "Vitamin D status in hospitalized patients with SARS-CoV-2 infection\n HernándezJL\n NanD\n Fernandez-AyalaM\n García-UnzuetaM\n Hernández-HernándezMA\n López-HoyosM\n 33159440J Clin Endocrinol Metab2020" } ], "reference-count": 26, "references-count": 26, "relation": {}, "resource": { "primary": { "URL": "https://www.frontiersin.org/articles/10.3389/fmed.2020.590805/full" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "High Prevalence of Hypocalcemia in Non-severe COVID-19 Patients: A Retrospective Case-Control Study", "type": "journal-article", "update-policy": "http://dx.doi.org/10.3389/crossmark-policy", "volume": "7" }