How many are at increased risk of severe COVID-19 disease? Rapid global, regional and national estimates for 2020

Andrew Clark; Mark Jit; Charlotte Warren-Gash; Bruce Guthrie; Harry HX Wang; Stewart W Mercer; Colin Sanderson; Martin McKee; Christopher Troeger; Kanyin I Ong; Francesco Checchi; Pablo Perel; Sarah Joseph; Hamish P Gibbs; Amitava Banerjee; Rosalind M Eggo

The copyright holder for this preprint . https://doi.org/10.1101/2020.04. 18.20064774 doi: medRxiv preprint to be exhaustive, and deliberately permit clinical judgement. As our understanding of this disease evolves, it should be possible to provide greater clarity on the risk of severe COVID -19 disease associated with different underlying conditions at different severities e.g. early stage CKD, compensated liver cirrhosis, moderately severe asthma etc. 6 A detailed multivariate analysis of risk is urgently needed because nearly all underlying conditions are likely to be at least partly confounded by age. Knowledge of the mode of action of the virus is increasing rapidly, especially in relation to its action on cells with ACE2 receptors other than in the lung, in particular in the endothelium and pancreas, which the inflammatory processes associated with diabetes may be involved in cytokine storms that can be fatal. 30 We estimated a similar number of males and females to be at increased risk, although early evidence from China, and later studies in other countries show a higher proportion of deaths in males. 31 Earlier research in mice infected with SARS coronavirus also found an increased male susceptibility mediated by differences in oestrogen receptor signalling, 32 while others have noted the concentration of genes involved in the immune system on the x chromosome. 33 This is a clearly priority for further research.