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.