COVID-19 Associated Hypercalcemia, A Rare Yet Interesting Case

ABSTRACT

Introduction: Hypercalcemia is a common clinical diagnosis. Hyperparathyroidism is one of the most common etiologies. Rarely hypercalcemia is associated with intense inflammation secondary to IL-6 production. Herein we present an interesting case of hypercalcemia associated with COVID-19. Case Description 36-year-old woman with history of Cirrhosis secondary to hepatitis C and alcohol abuse initially admitted for COVID/ARDS and cryptococcemia without CNS involvement. She was initially treated with amphotericin B and continued on fluconazole. Patient was re-admitted after 2 weeks with abdominal pain, constipation and hypercalcemia (Ca 14.2 mg/dl (normal range 8.7-10.1mg/dl). Her ionized calcium was 1.78 mmol/L (normal range 1.12-1.32 mmol/L). Serum phosphorus was 2.5 mg/dl (normal range 2.5-4.5mg/dl). Intact PTH level was 6.7 pg/ml (normal range 6-48pg/ml). Vitamin D 25-OH level was 26.8 ng/ml (sufficient range 32-100 ng/ml);Vitamin D 1,25-OH level was 7.4 pg/ml (normal 19.9-79.3pg/ml). PTH-rp was unmeasurable (< 2pmol/l). CRP was elevated at 31.7mg/L (normal range 0.2-8 mg/L). She was not on calcium, Vitamin D supplementation or thiazide diuretics. Her renal functions were normal. She was given Intravenous fluids & Intravenous pamidronate. Steroids were not used due to an ongoing fungal infection. It was proposed that the patient had Interleukin-induced hypercalcemia secondary to COVID-19 infection. Her serum calcium normalized with improvement in clinical status Discussion: Recent literature suggests COVID-19 is associated with inflammatory response with cytokines & interleukins production. IL-6 production is significantly upregulated especially in severe cases of COVID-19 known as “Cytokine storm”. IL-6 is produced by bronchial epithelial cells. High levels of IL-6 are associated with worse outcomes and much more severe disease. IL-6 in turn causes osteoclast activation, bone resorption & hypercalcemia. In our patient other potential causes of hypercalcemia were ruled out. The proposed mechanism of her hypercalcemia is an intense inflammatory response associated with COVID-19 infection. Conclusion: We present a rare sequelae of COVID-19 infection which presents a teaching point for clinicians to consider while managing such novel disease