Importance: Estimates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease burden are needed to help guide interventions .

Objective: To estimate the number of SARS-CoV-2 infections, symptomatic infections, hospitalizations, and deaths in the US as of November 15 , 2020 . Design, Setting, and Participants: In this cross-sectional study of respondents of all ages, data from 4 regional and 1 nationwide Centers for Disease Control and Prevention (CDC) seroprevalence surveys (April [n = 16 596], May, June, and July [n = 40 817], and August [n = 38 355] ) were used to estimate infection underreporting multipliers and symptomatic underreporting multipliers . Community serosurvey data from randomly selected members of the general population were also used to validate the underreporting multipliers . Main Outcomes and Measures: SARS-CoV-2 infections, symptomatic infections, hospitalizations, and deaths . The median of underreporting multipliers derived from the 5 CDC seroprevalence surveys in the 10 states that participated in 2 or more surveys were applied to surveillance data of reported coronavirus disease 2019 (COVID-19) cases for 5 respective time periods to derive estimates of SARS-CoV-2 infections and symptomatic infections, which were summed to estimate SARS-CoV-2 infections and symptomatic infections in the US . Estimates of infections and symptomatic infections were combined with estimates of the hospitalization ratio and fatality ratio to derive estimates of SARS-CoV-2 hospitalizations and deaths . External validity of the surveys was evaluated with the April CDC survey by comparing results to 5 serosurveys (n = 22 118) that used random sampling of the general population . Internal validity of the multipliers from the 10 specific states was assessed in the August CDC survey by comparing multipliers from the 10 states to all states . A sensitivity analysis was conducted using the interquartile range of the multipliers to derive a high and low estimate of SARS-CoV-2 infections and symptomatic infections . The underreporting multipliers were then used to adjust the reported COVID-19 infections to estimate the full SARS-COV-2 disease burden .

Results: Adjusting reported COVID-19 infections using underreporting multipliers derived from CDC seroprevalence studies in April (n = 16 596), May (n = 14 291), June (n = 14 159), July (n = 12 367), and August (n = 38 355), there were estimated medians of 46 910 006 (interquartile range [IQR], 38 192 705-60 814 748) SARS-CoV-2 infections , 28 122 752 (IQR , 23 014 957-36 438 592) symptomatic infections , 956 174 (IQR , 782 509-1 238 912) hospitalizations, and 304 915 (IQR , 248 253-395 296) deaths in the US through November 15 , 2020 . An estimated 14.3% (IQR , 11.6% -18.5 %) of the US population were infected by SARS-CoV-2 as of mid-November 2020 . Conclusions and Relevance: The SARS-CoV-2 disease burden may be much larger than reported COVID-19 cases owing to underreporting . Even after adjusting for underreporting, a substantial gap remains between the estimated proportion of the population infected and the proportion infected required to reach herd immunity . Additional seroprevalence surveys are needed to monitor the pandemic, including after the introduction of safe and efficacious vaccines.