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.

Vitamin D Deficiency and Low Serum Calcium as Predictors of Poor Prognosis in Patients with Severe COVID-19.

BACKGROUND: The severity of Coronavirus Disease 2019 (COVID-19) is a multifactorial condition. An increasing body of evidence argues for a direct implication of vitamin D deficiency, low serum calcium on poor outcomes in COVID-19 patients. This study was designed to investigate the relationship between these two factors and COVID-19 in-hospital mortality. MATERIALS: This is a prospective study, including 120 severe cases of COVID-19, admitted at the department of Reanimation-Anesthesia. Vitamin D was assessed by an immuno-fluoroassay method. Total serum calcium by a colorimetric method, then, corrected for serum albumin levels. The association with in-hospital mortality was assessed using the Kaplan-Meier survival curve, proportional Cox regression analyses and the receiver operating characteristic curve. RESULTS: Hypovitaminosis D and hypocalcemia were very common, occurring in 75% and 35.8% of patients. When analyzing survival, both were significantly associated with in-hospital mortality in a dose-effect manner (pLog-Rank = 0.009 and 0.001 respectively). A cutoff value of 39 nmol/l for vitamin D and 2.05 mmol/l for corrected calcemia could predict poor prognosis with a sensitivity of 76% and 84%, and a specificity of 69% and 60% respectively. Hazard ratios were (HR = 6.9, 95% CI [2.0-24.1], p = 0.002 and HR = 6.2, 95% CI [2.1-18.3], p = 0.001) respectively. CONCLUSION: This study demonstrates the high frequency of hypocalcemia and hypovitaminosis D in severe COVID-19 patients and provides further evidence of their potential link to poor short-term prognosis. It is, therefore, possible that the correction of hypocalcemia, as well as supplementation with vitamin D, may improve the vital prognosis.

Hypocalcaemia, alcohol drinking and viroimmune responses in ART recipients.

Metabolic perturbations associated with HIV and antiretroviral therapies are widespread. Unfortunately, research has predominantly focused in cardiometabolic problems, neglecting other important areas. In fact, the immune-calcium-skeletal interface has been understudied despite its potential relevance in people living with HIV (PLWH). Using a case-control methodology, 200 PLWH receiving medical care were enrolled and stratified according to hazardous vs. non-hazardous alcohol intake (HAU vs. non-HAU) and calcium (Ca) levels by analyzing baseline data. The group was chosen to represent relatively "pure" HAU with minimal drug use and no psychiatric diagnoses. With these narrow parameters in place, we found evidence that HAU significantly increases TNF-α levels compared to Non-HAU (2.8 ± 0.6 vs. 1.9 ± 0.3 pg/ml, p = 0.05) and decreases blood Ca levels (9 ± 0.6 vs. 9.4 ± 0.5, p = 0.03). Our analyses also suggest that chronic inflammation, as indicated by increased TNF-α levels, is associated with hypocalcemia (hypoCa <8.6). Despite the limited prevalence of hypoCa, these findings are clinically significant given that hypoCA PLWH exhibited decreased CD4 (253 ± 224 vs. 417.7 ± 281, p = 0.02), B cells (147 ± 58 vs. 248 ± 151, p = 0.03) and NK cells (146.8 ± 90 vs. 229 ± 148, p = 0.008) and elevated CD8 (902.5 ± 438 vs. 699 ± 510, p = 0.09) compared to those with normal calcium. Furthermore, calcium effects on viral load were also evident with hypoCA exhibiting the highest loads (140,187 ± 111 vs. 35,622 ± 7770 HIV copies, p = 0.01). Multivariate analyses confirmed the significance of hypoCa in predicting viroimmune parameters. This paper provides the first evidence that hypoCa accounts for some of the variation in viroimmune measures in HAART recipients and suggests that hypoCa may be mediating alcohol's deleterious effects.

Hypocalcaemia in HIV infection and AIDS.

OBJECTIVES: To study the prevalence and possible mechanisms of hypocalcaemia in HIV infection and AIDS. SUBJECTS: 828 patients with HIV infection or AIDS and 549 controls. INTERVENTIONS: Measurements of total serum calcium and albumin levels. Parameters of calcium homeostatis were determined in a subgroup of 21 hypocalcaemic AIDS patients. RESULTS: Mean serum calcium was 2.34 +/- 0.13 mmol L-1 in the HIV group vs. 2.46 +/- 0.10 mmol L-1 in controls (P < 0.0001). After adjusting for serum albumin, hypocalcaemia was present in 6.5% of the HIV group vs. 1.1% of controls. Mean serum calcium was declining according to CDC groups, and differed significantly from controls in each group. Regression coefficients of cacium vs. albumin were 0.147 amongst HIV-infected patients and 0.106 for controls. In the subgroup of hypocalcaemic patients with AIDS, 10/21 had vitamin D deficiency, six of these with low ionized calcium levels. Low serum PTH was found in 2/21 patients. Magnesium deficiency in 1/21. Of the remaining eight patients, only one had secondary hyperparathyroidism, while the other seven lacked an adequate PTH response, despite low ionized calcium levels in four subjects. CONCLUSIONS: Mean serum calcium concentrations were lower through all CDC stages, irrespective of albumin, resulting in a higher prevalence of hypocalcaemia in HIV-positive patients compared with controls. In a considerable number, this seems to be caused by vitamin D deficiency and potentially a lack of adequate PTH secretion, but further studies are needed to confirm this.