Background The COVID-19 pandemic represents a major public health threat. Risk of death from the infection is associated with age and pre-existing comorbidities such as diabetes, dementia, cancer, and impairment of immunological, hepatic or renal function. It remains incompletely understood why some patients survive the disease, while others do not. As such, we sought to identify novel prognostic factors for COVID-19 mortality. Methods We performed an unbiased, observational retrospective analysis of real world data. Our multivariable and univariable analyses make use of U.S. electronic health records from 122,250 COVID-19 patients in the early stages of the pandemic. Results Here we show that a priori diagnoses of fluid, pH and electrolyte imbalance during the year preceding the infection are associated with an increased risk of death independently of age and prior renal comorbidities. Conclusions We propose that future interventional studies should investigate whether the risk of death can be alleviated by diligent and personalized management of the fluid and electrolyte balance of at-risk individuals during and before COVID-19.

The threat of COVID-19 has harried the world since early 2020. Risk of death from the infection is associated with age and pre-existing comorbidities such as diabetes, dementia, cancer, and impairment of immunological, hepatic or renal function. It still remains incompletely understood why some patients survive the disease, while others perish. Our univariate and multivariate analyses of real world data from U.S. electronic health records indicate that a priori diagnoses of fluid, pH and electrolyte imbalance are highly and independently associated with COVID-19 mortality. We propose that pre-existing homeostatic aberrations are magnified upon the loss of ACE2, which is a core component of the electrolyte management system as well as the entry point of internalizing SARS-CoV-2 viruses. Moreover, we also suggest such fragility of electrolyte homeostasis may increase the risk of plasma volume disturbances during the infection. Future interventional studies should investigate whether the risk of death can be alleviated by personalized management of the fluid and electrolyte balance of at-risk individuals before and during COVID-19.