Low serum calcium: new, important indicator of COVID-19 patients from mild to severe

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally.¹ Confirmed cases and deaths have been reported in more than 200 countries worldwide.²  While 80% of COVID-19 infections have less severe clinical symptoms (low-grade fever, cough, fatigue) with no evidence of pneumonia or even asymptomatic, those mild or moderate cases are still contagious and move toward severe/critical.³ Once the mild/moderate case becomes severe/critical, it is always accompanied by pneumonia and multiorgan injuries. As the virus is still spreading, finding out the initial hits of viral infection is important to minimize the mild/moderate population, prevent disease aggravation and organs dysfunction. As the virus is still spreading, finding out the initial hits of viral infection is important to minimize the mild/moderate population, prevent disease aggravation and organs dysfunction.

A report showed that 70% of acutely ill patients had decreased levels of serum calcium which is associated with a poor prognosis.⁴ Previous studies of COVID-19 patients showed that severe/critical cases with electrolyte disturbance including calcium unbalance,⁵ hypokalemia in COVID-19 patients had been associated with ECG changes including long QT.⁶ But the role of abnormal calcium level in COVID-19 is unknown.

Zhou et al⁷ investigated COVID-19 patients with different serum calcium levels. They found that both mild/moderate and severe critical cases observed showed low calcium level in the early stage of viral infection, while the severe/critical cases showed significant lower calcium level than mild/moderate cases in the early stage. They also found that low calcium level related to severe/critical multiorgan injuries especially in the mild/moderate population. Proinflammatory cytokine IL-6 also correlated to calcium change in both mild/moderate and severe/critical cases.

In conclusion, calcium balance is a primal hit of COVID-19 and a biomarker of clinical severity at the beginning of symptom onset. Calcium is closely associated with virus-associated multiple organ injuries and the increase in inflammatory cytokines. Results provide a new, important indicator of COVID-19 patients from mild/moderate to severe/critical: serum calcium.

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References:

1. Guan, W.J., Ni, Z.Y., Hu, Y. et al. (2020) Clinical characteristics of coronavirus disease 2019 in China. Engl. J. Med. 382, 1708–1720, https://doi.org/10.1056/NEJMoa2002032.
2. World Health Organization Coronavirus disease 2019 (COVID-19) Situation Report 124. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200523-covid-19-sitrep-124.pdf?sfvrsn=9626d639
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6. Chen, D., Li, X., Song, Q., Hu, C., Su, F., Dai, J. et al. (2020) Assessment of hypokalemia and clinical characteristics in patients with coronavirus disease 2019 in Wenzhou, China. JAMA Netw. Open 3, e2011122, https://doi.org/10.1001/jamanetworkopen.2020.11122.
7. Zhou X., Chen D., Wang L., Zhao Y., Wei L., Chen Z. Yang B. (2020) Low serum calcium: a new, important indicator of COVID-19 patients from mild/moderate to severe/critical. Bioscience Reports (2020) 40 BSR20202690, https://doi.org/10.1042/BSR20202690