Association between calcium and vitamin D in geriatric patients hospitalized for Covid-19: Results from the GERIA-COVID study (preprint)

The deficiency of 25OH vitamin D (25[OH]D) is common in the older population. It physiologically triggers secondary hyperparathyroidism resulting in normal circulating calcium levels. Adjusted calcium (CaA) is estimated by the PAYNE method and several studies report a misclassification of calcium status by corrected calcium compared to ionized calcium (CaI) in older patients. Hypocalcemia is common in older COVID-19 patients. Blunted secondary hyperparathyroidism explain this high prevalence of hypocalcemia in COVID-19. However, no studies have focused on patients older than 75 years despite the high mortality rate in this population. In the present study, the association between the different types of calcium (CaI, CaA, and total calcium [CaT]) and 25(OH)D deficiency (below 50 nmol/L) was investigated. The study of the correlation between each type of calcium was performed secondarily. Observational monocentric study focused on the GERIA-COVID database during the second wave of COVID-19 in France from October 2020 to March 2021. COVID-19 was diagnosed with RT-PCR and/or chest CT-scan. A population of 181 older COVID-19 patients (86.4 years {+/-} 5.7) was analyzed. Sixty-three patients (34.8%) were deficient in 25(OH)D. The prevalence of total and ionized hypocalcemia was 44.1% and 39.2%, respectively. A negative association was reported in linear regression between 25(OH)D deficiency and CaA ({beta} =-0.052 [-0.093; -0.010], p = 0.015) as well as with CaT ({beta} = -0.05 [-0.09; -0.01], p =0.034) in the multivariate model. No association was found between vitamin D deficiency and CaI. In the multivariate models, there was no association between each type of calcium and PTH. CaI was correlated with CaT (r = 0.39, p < 0.001) and with CaA (r = 0.15, p = 0.043). Secondary hyperparathyroidism was not activated in the context of COVID-19 in this study. After reviewing the literature, this appears to be the first study in older patients to expose such results.

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.

Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics.

BACKGROUND: In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. METHODS: A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. RESULTS: The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6-27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97-1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. CONCLUSIONS: Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.