Impact of Hypocalcemia on the Prognosis of Patients with Acute Myocarditis.

Acute viral myocarditis is a serious complication of viral infectious diseases, including coronavirus disease 2019 (COVID-19). To better understand the pathogenesis of acute viral myocarditis, we retrospectively analyzed the incidence and prognostic significance of hypocalcemia among patients with acute myocarditis, most of whom were considered to have acute viral myocarditis. We retrospectively reviewed the demographic and clinical data of patients with clinically confirmed acute myocarditis treated in our hospital over a 13-year period from 2006 to 2019, including laboratory results, cardiac imaging findings, and clinical outcomes. These data were compared between lower, middle, and higher calcium groups depending on the minimum calcium level measured during hospitalization. Among the 288 patients with acute myocarditis included, the hypocalcemia group (lower calcium group) had poorer clinical and laboratory results, received more medications and device support, and experienced poorer outcomes, including heart failure, arrhythmias, and death. Specifically, the left ventricular ejection fraction was significantly lower, and the length of hospital stay was significantly longer in the hypocalcemia group than in the other two groups. Furthermore, the incidence rates of atrioventricular block, ventricular tachycardia/ventricular fibrillation, cardiogenic shock, and mortality were significantly higher in the hypocalcemia group. Multivariate Cox regression analysis identified hypocalcemia as an independent risk factor for 30-day mortality in patients with acute myocarditis. In conclusion, the clinical evidence provided by the present study indicates that hypocalcemia is a risk factor for poorer outcomes in patients with acute myocarditis that should be considered carefully in the diagnosis and treatment of these patients.

Hypocalcemia in hospitalized patients with COVID-19: roles of hypovitaminosis D and functional hypoparathyroidism.

INTRODUCTION: Despite the high prevalence of hypocalcemia in patients with COVID-19, very limited studies have been designed to evaluate etiologies of this disorder. This study was designed to evaluate the status of serum parameters involved in calcium metabolism in patients with COVID-19 and hypocalcemia. MATERIALS AND METHODS: This cross-sectional study was conducted on 123 hospitalized patients with COVID-19. Serum concentrations of PTH, 25 (OH) D, magnesium, phosphate, and albumin were assessed and compared across three groups of moderate/severe hypocalcemia (serum total calcium < 8 mg/dl), mild hypocalcemia (8 mg/dl ≤ serum total calcium < 8.5 mg/dl) and normocalcemia (serum total calcium ≥ 8.5 mg/dl). Multivariate analyses were performed to evaluate the independent roles of serum parameters in hypocalcemia. RESULTS: In total, 65.9% of the patients had hypocalcemia. Vitamin D deficiency was found in 44.4% and 37.7% of moderate/severe and mild hypocalcemia cases, respectively, compared to 7.1% in the normal serum total calcium group (P = 0.003). In multivariate analysis, vitamin D deficiency was independently associated with 6.2 times higher risk of hypocalcemia (P = 0.001). Only a minority of patients with hypocalcemia had appropriately high PTH (15.1% and 14.3% in mild and moderate/severe hypocalcemia, respectively). Serum PTH was low/low-normal in 40.0% of patients with moderate/severe low-corrected calcium group. Magnesium deficiency was not associated with hypocalcemia in univariate and multivariate analysis. CONCLUSION: Vitamin D deficiency plays a major role in hypocalcemia among hospitalized patients with COVID-19. Inappropriately low/low-normal serum PTH may be a contributing factor in this disorder.

Hypocalcemia in COVID-19 is associated with low vitamin D levels and impaired compensatory PTH response.

BACKGROUND: Hypocalcemia has been identified as a major distinctive feature of COVID-19, predicting poor clinical outcomes. Among the mechanisms underlying this biochemical finding, high prevalence of vitamin D (VD) deficiency in COVID-19 patients reported so far in several studies was advocated. However, robust data in favor of this hypothesis are still lacking. Therefore, aim of our study was to investigate the role of hypovitaminosis D and parathyroid hormone (PTH) levels in the development of hypocalcemia in COVID-19 patients. METHODS: Patients admitted to IRCCS Ospedale San Raffaele for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing calcium and VD metabolism. Serum levels of total calcium (tCa), ionized calcium (Ca2+), 25-OH-VD, and PTH were evaluated at admission. We defined VD deficiency as VD below 20 ng/mL, hypocalcemia as tCa below 2.2 mmol/L or as Ca2+ below 1.18 mmol/L, and hyperparathyroidism as PTH above 65 pg/mL. RESULTS: A total of 78 patients were included in the study. Median tCa and Ca2+ levels were 2.15 and 1.15 mmol/L, respectively. Total and ionized hypocalcemia were observed in 53 (67.9%) and 55 (70.5%) patients, respectively. VD deficiency was found in 67.9% of patients, but secondary hyperparathyroidism was detected in 20.5% of them, only. tCa levels were significantly lower in patients with VD deficiency and regression analyses showed a positive correlation between VD and tCa. CONCLUSIONS: In conclusion, we confirmed a high prevalence of hypocalcemia in COVID-19 patients and we showed for the first time that it occurred largely in the context of marked hypovitaminosis D not adequately compensated by secondary hyperparathyroidism.

Hypocalcemia in COVID-19: Prevalence, clinical significance and therapeutic implications.

COVID-19 extra-pulmonary features include several endocrine manifestations and these are becoming strongly clinically relevant in patients affected influencing disease severity and outcomes.At the beginning of COVID-19 pandemic no population data on calcium levels in patients affected were available and in April 2020 a first case of severe acute hypocalcemia in an Italian patient with SARS-CoV-2 infection was reported. Subsequently, several studies reported hypocalcemia as a highly prevalent biochemical abnormality in COVID-19 patients with a marked negative influence on disease severity, biochemical inflammation and thrombotic markers, and mortality. Also a high prevalence of vertebral fractures with worse respiratory impairment in patients affected and a widespread vitamin D deficiency have been frequently observed, suggesting an emerging "Osteo-Metabolic Phenotype" in COVID-19.To date, several potential pathophysiological factors have been hypothesized to play a role in determining hypocalcemia in COVID-19 including calcium dependent viral mechanisms of action, high prevalence of hypovitaminosis D in general population, chronic and acute malnutrition during critical illness and high levels of unbound and unsaturated fatty acids in inflammatory responses.Since hypocalcemia is a frequent biochemical finding in hospitalized COVID-19 patients possibly predicting worse outcomes and leading to acute cardiovascular and neurological complications if severe, it is reasonable to assess, monitor and, if indicated, replace calcium at first patient hospital evaluation and during hospitalization.

Hypocalcemia is associated with severe COVID-19: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Hypocalcemia is commonly in critically ill patients and studies have shown that hypocalcemia is prevalent in patients with COVID-19. This meta-analysis aimed to evaluate the prognostic performance of hypocalcemia in patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a systematic literature search on PubMed, Scopus, and Embase with keywords "SARS-CoV-2″ OR″COVID-19″ OR ″2019-nCoV" AND "hypocalcemia" up until 10 December 2020. The key exposure was hypocalcemia, defined as serum calcium below study-defined cut-off points. The main outcome was poor outcome, which was a composite of mortality and severity. The effect estimate of the main outcome was reported as odds ratio (OR) and its 95% confidence interval (95% CI). We also generate sensitivity, specificity, positive and negative likelihood ratio (PLR & NLR), diagnostic odds ratio (DOR), and area under curve (AUC). RESULTS: There are 2032 patients from 7 studies included in this systematic review and meta-analysis. The incidence of poor outcome in this study was 26%. Serum calcium was lower in patients with poor outcome (mean difference -0.173 mmol/L [-0.259, -0.087], p < 0.001; I2: 31.3%). Hypocalcemia was associated with poor outcome (OR 3.19 [2.02, 5.06], p < 0.001; I2: 32.86%); with sensitivity of 0.74 [0.53, 0.88], specificity of 0.54 [0.29, 0.77], PLR of 1.6 [1.1, 2.3], NLR of 0.49 [0.35, 0.66], DOR of 3 [2, 5], and AUC of 0.70 [0.66, 0.74]. In this pooled analysis, the post-test probability was 36% in patients with hypocalcemia and 15% in patients without hypocalcemia. CONCLUSION: Hypocalcemia was associated with poor outcome in COVID-19 patients. PROSPERO ID: CRD42020225506.