Hypocalcemia is associated with adverse outcomes in patients hospitalized with COVID-19

Abstract

Purpose Calcium ions are involved in the regulation of several cellular processes and may also influence viral replication. Hypocalcemia has been frequently reported during infectious diseases and in critically ill patients, including also COVID-19 patients, significantly related with the pro-inflammatory state and mortality. The aim of this study is to investigate the prevalence of hypocalcemia at admission in patients hospitalized for COVID-19 (Coronavirus disease 2019) and to evaluate association of hypocalcemia with in-hospital COVID-19 outcomes. Methods Retrospective analysis on 118 consecutive patients, hospitalized for COVID-19 between March and May 2020. Clinical characteristics, inflammation markers, biochemical routine and mineral metabolism parameters at admission were collected. Hypocalcemia was defined as total serum calcium <2.2 mmol/L. Population was stratified by tertiles of total serum calcium. Primary outcome was the composite of in-hospital death or admission to intensive care unit (ICU). Secondary outcomes included in-hospital death, admission to ICU and need for non-invasive ventilation as separate events. Associations were tested by logistic regression and Cox-regression analysis with survival curves. Results Overall prevalence of hypocalcemia was 76.6%, with just 6.7% of patients reporting levels of 25-(OH)-vitamin D > 30 ng/ml. Total serum calcium was inversely related with selected inflammatory biomarkers (p < 0.05) and poorer outcome of COVID-19 during hospitalization. Lower tertile of total calcium (≤2.02 mmol/L) had increased risk of in-hospital mortality (HR 2.77; 1.28–6.03, p = 0.01) compared with other groups. Conclusion Total serum calcium detected on admission is inversely related with proinflammatory biomarkers of severe COVID-19 and is useful to better define risk stratification for adverse in-hospital outcome.

Metallomic analysis of urine from individuals with and without Covid-19 infection reveals extensive alterations in metal homeostasis

“…In individuals a icted by the illness, studies conducted by Elham et al [35]; Alkattan et al [36], and Sun et al [37] revealed reduced serum calcium levels comparing patients with non-severe and severe Covid-19. The occurrence of hypocalcemia in critically ill patients with Covid-19 is further substantiated by the research of Bennouar et al [38] and Minasi [39], which each linked hypocalcemia to disease severity. Despite this, the precise mechanisms underlying hypocalcemia in the progression of the disease remain to be elucidated.…”

Therapeutic effects of vitamin D supplementation on COVID-19 aggravation: a systematic review and meta-analysis of randomized controlled trials

“…Malnutrition such as hypocalcemia, hypovitaminosis D in patients has been consistently linked to COVID-19 progression and a worsened prognosis. In a retrospective study conducted by Minasi et al (Minasi et al, 2023), the relationship between hypocalcemia and adverse clinical Summary of risk of bias.…”

Calcium, Phosphorus and Magnesium Abnormalities Associated with COVID-19 Infection, and Beyond

“…This highlights the importance of calcium as a reliable and easily measurable biomarker for assessing disease severity in COVID-19. The results of this study provide valuable insights into the potential role of calcium in predicting and managing COVID-19 outcomes [ 25 ]. The findings of this research were supported by subsequent systematic reviews and meta-analyses, which also concluded that there is a significant correlation between hypocalcemia and various indicators of disease severity ( Table 1 ) [ 26 , 27 ].…”