Mechanistic basis and therapeutic relevance of hypocalcemia during severe COVID-19 infection

Singh, Vijay; Khatua, Biswajit; El-Kurdi, Bara; Rood, Christopher

doi:10.1007/s12020-020-02530-y

Cited by 32 publications

(34 citation statements)

References 6 publications

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“…Besides, elevated levels of unbound and unsaturated fatty acids have been reported in COVID-19 patients. Unsaturated fatty acids can bind calcium, causing hypocalcemia ( 23 , 24 ). An alternate explanation could be a reduction in renal 1α-hydroxylase activity in patients with COVID-19.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Vitamin D status was not likely the only determinant of calcium levels in our hospitalized patients, since the association between lower calcium values and unfavorable pneumonia outcome was independent of vitamin D deficiency. In this context, low calcium levels may be also caused by an interaction of calcium with unsaturated fatty acids [44] released during the disease [45] and potentially involved in the modulation of systemic inflammation induced by SARS-CoV-2 infection [46].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19

Mazziotti

Lavezzi

Brunetti

et al. 2021

J Endocrinol Invest

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Purpose Hypovitaminosis D has emerged as potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population with variable effects on the outcome of the coronavirus disease-19 (COVID-19). The aim of this retrospective single-center study was to investigate the impact of hypovitaminosis D and secondary hyperparathyroidism on respiratory outcomes of COVID-19. Methods Three-hundred-forty-eight consecutive patients hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano, Milan (Italy) were evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum 25hydroxy-vitamin D [25(OH)D], parathyroid hormone (PTH) and inflammatory parameters at study entry and need of ventilation during the hospital stay. Results In the entire population, vitamin D deficiency (i.e., 25(OH)D values < 12 ng/mL) was significantly associated with acute hypoxemic respiratory failure at the study entry [adjusted odds ratio (OR) 2.48, 95% confidence interval 1.29-4.74; P = 0.006], independently of age and sex of subjects, serum calcium and inflammatory parameters. In patients evaluated for serum PTH (97 cases), secondary hyperparathyroidism combined with vitamin D deficiency was significantly associated with acute hypoxemic respiratory failure at study entry (P = 0.001) and need of ventilation during the hospital stay (P = 0.031). Conclusion This study provides evidence that vitamin D deficiency, when associated with secondary hyperparathyroidism, may negatively impact the clinical outcome of SARS-CoV-2-related pneumonia.

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“…The study also demonstrated that use of dihydropyridines results in increased resistance to SARS-Cov-2 infection 51 . Another study hypothesized that elevated unsaturated fatty acids in SARS-CoV-2 infected host cells bind calcium, resulting in hypocalcemia and triggering the production of pro-inflammatory mediators and cytokine storm induction 52,53 .…”

Section: Discussionmentioning

confidence: 99%

Combinatorial analysis of phenotypic and clinical risk factors associated with hospitalized COVID-19 patients

Das¹,

Pearson²,

Taylor³

et al. 2021

Preprint

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Characterization of the risk factors associated with variability in the clinical outcomes of COVID-19 is important. Our previous study using genomic data identified a potential role of calcium and lipid homeostasis in severe COVID-19. This study aimed to identify similar combinations of features (disease signatures) associated with severe disease in a separate patient population with purely clinical and phenotypic data. The PrecisionLife combinatorial analytics platform was used to analyze features derived from de-identified health records in the UnitedHealth Group COVID-19 Data Suite. The platform identified and analyzed 836 disease signatures in two cohorts associated with increased risk of COVID-19 hospitalization. Cohort 1 was formed of cases hospitalized with COVID-19 and a set of controls who developed mild symptoms. Cohort 2 included Cohort 1 individuals for whom additional laboratory test data was available. We found several disease signatures where lower levels of lipids were found co-occurring with lower levels of serum calcium and leukocytes. Many of the low lipid signatures were independent of statin use and 50% of cases with hypocalcemia signatures were reported with vitamin D deficiency. These signatures may be attributed to similar mechanisms linking calcium and lipid signaling where changes in cellular lipid levels during inflammation and infection affect calcium signaling in host cells. This study and our previous genomics analysis demonstrate that combinatorial analysis can identify disease signatures associated with the risk of developing severe COVID-19 separately from genomic or clinical data in different populations. Both studies suggest associations between calcium and lipid signalling in severe COVID-19.

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Mechanistic basis and therapeutic relevance of hypocalcemia during severe COVID-19 infection

Cited by 32 publications

References 6 publications

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

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

Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19

Combinatorial analysis of phenotypic and clinical risk factors associated with hospitalized COVID-19 patients

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