Background: The 2019 novel coronavirus (SARS-CoV-2) is reported to result in both respiratory and non-respiratory severe health outcomes, but quantitative assessment of the risk - while adjusting for underlying risk driven by comorbidities - is not yet established .

Methods: A retrospective observational study using electronic health records of 9,344,021 individuals across the U.S. with at-least 1 year of clinical history and followed up throughout 2020 .

Results: 131,329 individuals were associated with SARS-CoV-2 infection by January 6 , 2021 in three distinct surges . While the age and number of preexisting conditions had decreased throughout the pandemic, the characteristics of those who experienced severe health events did not . During the second surge, between June 7 and November 18 , 2020, 425,988 individuals in the base cohort were admitted to emergency rooms or hospitals . Among them , 15,486 were detected with SAR-CoV-2 within few days of admission . Significant adjusted odds ratios were observed between SARS-CoV-2 infection and the following severe health events: respiratory (4.38 , 95% confidence interval 4.16-4.62), bacterial pneumonia (3.25 , 2.76-3.83), sepsis (1.71 , 1.53-1.91), renal (1.69 , 1.57-1.83), hematologic/immune (1.32 , 1.20-1.45), and neurological (1.23 , 1.09-1.38).

Conclusions: SARS-CoV-2 infection among hospitalized patients is associated with non-negligible increased risk of severe events including multiple non-respiratory ones . These associations, which complement recent studies, are persistent even after accounting for sources of selection and confounding bias, increasing the confidence they are not spurious.