This study represents the first description of the hypocalcemic patients with COVID-19 disease from an apex COVID-19 care centre in north India. The trends in the study show that the COVID-19 positive patients with hypocalcemia were severely affected by the disease and more patients required ventilator support during the hospital stay. Higher mortality was found in the hypocalcemic patients and of all the non-survivors, more than one-third were elderly and more than three-forth were males. Similar to our finding, a study shows that hypocalcemia presents more frequently in maleCOVID-19 patients [12].
In the COVID-19 patients, hypocalcemia may be a result of an imbalance in parathyroid hormone and vitamin D levels in blood [15]. Also, the increased levels of unbound fatty acids and unsaturated fatty acids seen in severe COVID-19 patients may bind with the calcium and result into acute hypocalcemia [16]. In these patients, hypocalcemia positively correlates with reduced pulmonary functional index, lymphopenia, albumin levels, vitamin D levels and negatively correlates with parathyroid hormone, C-reactive protein, lactate dehydrogenase and D-dimer [11, 15, 17]. The current study also found a significant positive correlation between calcium and haemoglobin, hemtatocrit, red cell count, total protein level, albumin level and albumin to globulin ratio and significant a negative correlation of calcium with absolute neutrophil count and neutrophil to lymphocyte ratio.
The consequences inSARS-CoV-2 may be the same as SARS-CoV due to similarities in the genome of both the viruses [18].Various viral pneumonia present with hypocalcemia [19]. Hypocalcemia has been reported in 60% of SARS disease and 62% of Ebola virus disease[20]. Altered calcium concentrations are usually observed during host cell dysfunction after viral infections [21]. Viruses use the calcium signal to generate a better environment for their benefits [22]. Changes of ion homeostasis, mainly in calcium homeostasis promote the viral growth [23]. Forvariousenveloped viruses such as SARS-CoV, MERS-CoV and Ebolavirus, calcium plays a very important role in the viral fusion and promotes their replication by directly interacting with fusion peptides of these viruses [20]. By using the calcium signal system of the host, virus can affect the occurrence and progression of the disease [24]. Calcium is required for the virus structure formation, viral entry, gene expression, virion maturation and release. Calcium ion activity is demonstrated in small transmembrane protein coded by SARS-CoV E gene in animal models infected with SARS-CoV and its synthesis is increased during viral infection [18]. By using calcium channels or pump, viruses disturb the homeostasis of calcium in the body and induced host cell morbidity [21]. A high viral load and prolonged period of viral shedding may present in COVID-19 hypocalcemic patients. Along with hypochloremia and bilateral pneumonia, hypocalcemia on admission has been shown to be an independent risk factor for long-term hospitalization in COVID-19 patients[25].
Abnormal calcium level is commonly observed in the critically ill patients. Studies show the association of hyper and hypocalcemia with higher organ injury and increased mortality in critical illnesses [15, 26, 27]. Up to 85% of the critically ill patients have presented with hypocalcemia and have higher mortality [28]. Very high prevalence of hypocalcemia, nearly up to 80%, has also been observed in the COVID-19 patients [20]. In our study, we found two-thirds of the COVID-19 patients to behypocalcemic. Hypocalcemia has been included among the two most powerful risk factors to assess the severity of COVID-19 disease along with dyspnoea [24].
Calcium levels should be monitored in all cases of acute and recovered COVID-19 patients [29]. Hospitalized patients with serum ionised calcium level below 4.80 mg/dl have increased risk of acute respiratory failure and had more requirement of mechanical ventilation [30]. Timely supplementation of calcium has been suggested in severe COVID-19 patients to prevent organ failure as an early diagnosis and treatment of hypocalcemia may alleviate organ injury [31].
Limitation and future needs: There were a few limitations in this study. One of the potential limitations of our study is that our data comes from a single center study, and the sample size is relatively small, we believe that larger studies are needed to confirm our findings. In addition, measurement of ionized serum calcium should be done because it is more accurate than albumin-corrected calcium. And further studies are needed to find the causes of hypocalcemiain COVID-19 patients and to see whether the correction of hypocalcemia would lead to the improvement of outcomes.