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

Abstract

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 (Ca 2+ ), 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 Ca 2+ 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 Ca 2+ 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.

The osteo-metabolic phenotype of COVID-19: an update

“…1 ). These mechanisms include calcium-dependent viral mechanisms of action determining intra and extra-cellular cation dysmetabolism [ 22 – 24 ], tissues calcium deposits detected at autoptic evaluation [ 25 ], acute muscle calcium precipitation [ 26 ], calcium role in coagulation and prothrombotic status [ 27 , 28 ], acute malnutrition during critical illness [ 29 ], high levels of unbound and unsaturated fatty acids in inflammatory responses [ 30 ] and high prevalence of hypovitaminosis D with an impaired compensatory PTH response [ 31 ]. Furthermore, severe hypocalcemia, although not frequently found in COVID-19 [ 3 , 13 ], may compromise outcome per se due to its additional negative cardiovascular and neurological impact [ 3 , 13 ].…”

“…Interestingly, a recent study reported that hypocalcemia occurred prevalently in a context of a marked hypovitaminosis D not adequately compensated by secondary hyperparathyroidism, since, despite most of patients presented with quite severe VD deficiency and hypocalcemia, only one-fifth of them had secondary hyperparathyroidism [ 31 ]. Other observational studies seem to confirm this evidence: in fact, PTH median levels of 44.2 pg/mL were reported in 162 COVID-19 patients with VD levels below 20 ng/mL [ 79 ] and secondary hyperparathyroidism occurred in only 43.3% of 97 COVID-19 patients characterized by a median VD level of 21 ng/mL [ 80 ].…”

Endocrine Follow-up During Post-Acute COVID-19: Practical Recommendations Based on Available Clinical Evidence

“…Hypovitaminosis D has been linked to an increased risk of COVID-19 infection, disease severity, and poor outcomes ( 63 , 64 ). In fact, hypocalcemia in the context of COVID-19 is associated with hypovitaminosis D, along with an inadequate compensatory parathyroid hormone (PTH) response ( 65 ). Vitamin D supplementation, either in the form of cholecalciferol or calcifediol, has also been shown to improve clinical outcomes in COVID-19, although robust and consistent data are lacking ( 66 ).…”

Vitamin D: Dosing, levels, form, and route of administration: Does one approach fit all?

“…Future studies are needed to confirm these observations, taking into account possible confounding factors. In COVID-19 patients, vitamin D deficiency has been observed also to be associated, with an impaired PTH response, with hypocalcemia [ 147 – 151 ]. COVID-19 related hypocalcemia has been recently identified by several studies, reviews and meta-analyses as a potentially useful biomarker for disease severity and outcome in patients with SARS-CoV-2 infection [ 152 – 154 ].…”