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. 2022 Feb;54(2):90-98.
doi: 10.1080/23744235.2021.1981549. Epub 2021 Sep 29.

Lower plasma calcium associated with COVID-19, but not with disease severity: a two-centre retrospective cohort study

Jan Arne Deodatus  1 , Simone Anna Kooistra  1 , Steef Kurstjens  2 , Joram Cornèl Leon Mossink  1 , Joris David van Dijk  1 , Paul Hendrik Pieter Groeneveld  1 , Brigitta Britt Yarine Maxime van der Kolk  1
Affiliations

Lower plasma calcium associated with COVID-19, but not with disease severity: a two-centre retrospective cohort study

Jan Arne Deodatus et al. Infect Dis (Lond). 2022 Feb.

Abstract

Background: Previous studies indicate hypocalcaemia as a potential diagnostic and prognostic marker of corona-virus disease 2019 (COVID-19). Our aim was to investigate these relations in more detail in a large test cohort and an independent validation cohort.

Methods: We retrospectively included 2792 COVID-19 suspected patients that presented to the emergency department (ED) of two hospitals. Plasma calcium and ionized plasma calcium levels were compared between COVID-19 positive and negative patients, and between severe and non-severe COVID-19 patients using univariate and multivariate analyses in the first hospital (N = 1363). Severe COVID-19 was defined as intensive care unit (ICU) admission or death within 28 d after admission. The results were validated by repeating the same analyses in the second hospital (N = 1429).

Results: A total of 693 (24.8%) of the enrolled patients were COVID-19 positive, of whom 238 (34.3%) had severe COVID-19. In both hospitals, COVID-19 positive patients had lower plasma calcium levels than COVID-19 negative patients, regardless of correction for albumin, in univariate and multivariate analysis (Δ0.06-0.13 mmol/L, p < .001). Ionized plasma calcium concentrations, with and without correction for pH, were also lower in COVID-19 positive patients in multivariate analyses (Δ0.02-0.05 mmol/L, N = 567, p < .001). However, we did not find a significant association between COVID-19 disease severity and plasma calcium in multivariate analyses.

Conclusions: Plasma calcium concentrations were lower in COVID-19 positive than COVID-19 negative patients but we found no association with disease severity in multivariate analyses. Further understanding of plasma calcium perturbation may facilitate the development of new preventive and therapeutic modalities for the current pandemic.

Keywords: COVID-19; SARS-CoV-2; hypocalcaemia; plasma calcium; severe acute respiratory syndrome coronavirus-2.

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Conflict of interest statement

The authors declare that there is no conflict of interest. This study was not supported by external funding or sponsorship.

Figures

Figure 1.
Figure 1.
(A–D) distribution of plasma calcium in COVID-19 positive vs. COVID-19 negative patients. (E–H) distribution of plasma calcium in severe COVID-19 vs. non-severe COVID-19 patients. Data from test cohort. Plasma calcium on x-axis. Relative frequency of measurements on y-axis. ***p value < .001 and *p value < .05.
Figure 2.
Figure 2.
(A,B) Percentage of patients with hypocalcaemia. Data from test cohort. Hypocalcaemia defined as total plasma calcium <2.12 mmol/L or ionized plasma calcium < 1.17 mmol/L). ***p value < .001 and **p value < .01.
See this image and copyright information in PMC

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