Further to Ulfberg & Stehlik’s letter of September 29th, further evidence supports the role of Se in COVID-19 virulence^{(Reference Ulfberg and Stehlik1)}. In their pre-print analysis by machine learning of Medicare patients, Dun et al. found that the leading comorbidity associated with COVID-19 mortality, adjusted for age and race, was sickle cell disease (aOR, 1·73; (95 % CI 1·21, 2·47)), followed by chronic kidney disease (aOR, 1·32; (95 % CI 1·29, 1·36))^{(Reference Dun, Walsh and Bae2)}.

Both SCD and kidney disease can lower Se levels by decreasing tubular Se resorption and are associated with deficient Se status^{(Reference Delesderrier, Cople-Rodrigues and Omena3,Reference Iglesias, Selgas and Romero4)} .

Se status or intake has been correlated with COVID-19 outcomes, including mortality and recovery rates, in four patient groups in China, Germany, South Korea and southern India^{(Reference Zhang, Taylor and Bennett5–Reference Majeed, Nagabhushanam and Gowda8)}. SARS-CoV-2, like other RNA viruses, sequesters Se causing Se levels to drop during infection^{(Reference Moghaddam, Heller and Sun6,Reference Wang, Huang and Sun9)} . SARS-CoV-2 may infect cells in bone marrow, supressing red blood cell formation^{(Reference Reva, Yamamoto and Rasskazova10)}. Se status is inversely associated with haemolysis in SCD and may both inhibit haemolysis and enhance erythropoiesis in SCD^{(Reference Delesderrier, Cople-Rodrigues and Omena3,Reference Jagadeeswaran, Lenny and Zhang11)} .

Se is required for the actions of both vitamin D and dexamethasone^{(Reference Schütze, Fritsche and Ebert-Dümig12,Reference Rock and Moos13)} . Se infusion is safe, including in critically ill and dialysis patients, and Se supplementation has had favourable effects in other RNA virus infections^{(Reference Zhao, Yang and Mao14–Reference Steinbrenner, Al-Quraishy and Dkhil16)}.

It should be noted that vitamin C and Mg are also commonly deficient nutrients and are required for the activation of vitamin D₃ by hydroxylation^{(Reference Cantatore, Loperfido and Magli17–Reference Cooper, Crofts and DiNicolantonio19)}. Deficiency of ascorbate has been associated with COVID-19 and COVID-19 outcomes in hospital populations^{(Reference Carr and Rowe20)}.

Se, supplemented if necessary with its cofactors in vitamin D metabolism, is proposed to be an important protective factor in the general population, but has the potential to reduce mortality from SARS CoV-2 infection in the sickle cell disease population to an even greater extent.