Conflicts over calcium and the treatment of COVID-19

Several recent studies have provided evidence that use of calcium channel blockers (CCBs), especially amlodipine and nifedipine, can reduce mortality from coronavirus disease 2019 (COVID-19). Moreover, hypocalcemia (a reduced level of serum ionized calcium) has been shown to be strongly positively associated with COVID-19 severity. Both effectiveness of CCBs as antiviral therapy, and positive associations of hypocalcemia with mortality, have been demonstrated for many other viruses as well. We evaluate these findings in the contexts of virus-host evolutionary conflicts over calcium metabolism, and hypocalcemia as either pathology, viral manipulation or host defence against pathogens. Considerable evidence supports the hypothesis that hypocalcemia represents a host defence. Indeed, hypocalcemia may exert antiviral effects in a similar manner as do CCBs, through interference with calcium metabolism in virus-infected cells. Prospective clinical studies that address the efficacy of CCBs and hypocalcemia should provide novel insights into the pathogenicity and treatment of COVID-19 and other viruses.