High Prevalence of Hypocalcemia in Non-severe COVID-19 Patients: A Retrospective Case-Control Study
Rimesh Pal, Sant Ram, Deepy Zohmangaihi, Indranil Biswas, Vikas Suri, Laxmi N Yaddanapudi, Pankaj Malhotra, Shiv L Soni, Goverdhan D Puri, Ashish Bhalla, Sanjay K Bhadada
Frontiers in Medicine, doi:10.3389/fmed.2020.590805
Purpose: 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.
Methods: 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). Results: 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 (P value <0.001) and phosphate (P = 0.007) compared with the controls. There was no statistically significant correlation between serum calcium and CRP. Conclusions: 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.
ETHICS STATEMENT The studies involving human participants were reviewed and approved by Post Graduate Institute of Medical Education and Research, Chandigarh, India. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.
AUTHOR CONTRIBUTIONS RP is the primary author. SR and SB had conceptualized and had edited the manuscript. DZ, IB, VS, LY, SS, PM, and AB had helped in data collection. GP had edited the manuscript. All the authors approved the final version of the manuscript.
Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Copyright © 2021 Pal, Ram, Zohmangaihi, Biswas, Suri, Yaddanapudi, Malhotra, Soni, Puri, Bhalla and Bhadada. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
References
Aggarwal, Ram, Garg, Pal, Bhansali et al., Metabolic bone profile of healthy adult north indian population from chandigarh urban bone epidemiological study (CUBES), Indian J Clin Biochem,
doi:10.1007/s12291-019-00857-6Canaff, Hendy, Calcium-sensing receptor gene transcription is UP-regulated by the Pro-inflammatory Cytokine, Interleukin-1β: role of the NF-κB pathway and κB elements, J Biol Chem,
doi:10.1074/jbc.M408587200Canaff, Zhou, Hendy, The proinflammatory cytokine, interleukin-6, Up-regulates calcium-sensing receptor gene transcription via Stat1/3 and Sp1/3, J Biol Chem,
doi:10.1074/jbc.M708087200Cappellini, Brivio, Casati, Cavallero, Contro et al., Low levels of total and ionized calcium in blood of COVID-19 patients, Clin Chem Lab Med
Desai, Carlson, Geheb, Parathyroid-vitamin D axis in critically ill patients with unexplained hypocalcemia, Kidney Int Suppl
Filippo, Formenti, Rovere-Querini, Carlucci, Conte et al., Hypocalcemia is highly prevalent and predicts hospitalization in patients with COVID-19, Endocrine,
doi:10.1007/s12020-020-02383-5Goyal, Singh, Hypocalcemia
Hernández, Nan, Fernandez-Ayala, García-Unzueta, Hernández-Hernández et al., Vitamin D status in hospitalized patients with SARS-CoV-2 infection, J Clin Endocrinol Metab,
doi:10.1210/clinem/dgaa733/5934827Kennel, Drake, Hurley, Vitamin D deficiency in adults: when to test and how to treat, Mayo Clin Proc,
doi:10.4065/mcp.2010.0138Lind, Carlstedt, Rastad, Stiernström, Stridsberg et al., Hypocalcemia and parathyroid hormone secretion in critically ill patients, Crit Care Med,
doi:10.1097/00003246-200001000-00015Lippi, Plebani, Laboratory abnormalities in patients with COVID-2019 infection, Clin Chem Lab Med CCLM
Lippi, South, Henry, Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19), Ann Clin Biochem Int J Lab Med,
doi:10.1177/0004563220922255Liu, Han, Wu, Gong, Tian, Prevalence and predictive value of hypocalcemia in severe COVID-19 patients, J Infect Public Health
Martins-Filho, Tavares, Santos, Factors associated with mortality in patients with COVID-19. A quantitative evidence synthesis of clinical and laboratory data, Eur J Intern Med,
doi:10.1016/j.ejim.2020.04.043Nieto-Torres, Dediego, Verdiá-Báguena, Jimenez-Guardeño, Regla-Nava et al., Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis, PLoS Pathog,
doi:10.1371/journal.ppat.1004077Singh, Khatua, El-Kurdi, Rood, Mechanistic basis and therapeutic relevance of hypocalcemia during severe COVID-19 infection, Endocrine,
doi:10.1007/s12020-020-02530-ySun, Zhang, Zou, Liu, Li et al., Serum calcium as a biomarker of clinical severity and prognosis in patients with coronavirus disease 2019, Aging,
doi:10.18632/aging.103526Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease
Zaloga, The multifactorial basis for hypocalcemia during sepsis: studies of the parathyroid hormone-vitamin D axis, Ann Intern Med,
doi:10.7326/0003-4819-107-1-36
