Abstract: medRxiv preprint doi: https://doi.org/10.1101/2022.06.14.22276393; this version posted June 16, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . Title: Nirmatrelvir plus ritonavir for early COVID-19 and hospitalization in a large US health system Authors: Scott Dryden-Peterson, MD, MSc Andy Kim, BS Arthur Y. Kim, MD Ellen C. Caniglia, ScD Inga Lennes, MD, MPH, MBA Rajesh Patel, MD, MPH Lindsay Gainer, RN Lisa Dutton, RN Elizabeth Donahue, RN, MSN, NP-C Rajesh T. Gandhi, MD Lindsey R. Baden, MD Ann E. Woolley, MD, MPH Author Affiliations: Brigham and Women’s Hospital, Boston, Massachusetts (Dryden-Peterson, Kim, Baden, Dutton, Donahue, Woolley); Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health (Dryden-Peterson); NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. 1 medRxiv preprint doi: https://doi.org/10.1101/2022.06.14.22276393; this version posted June 16, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . Botswana Harvard AIDS Institute (Dryden-Peterson); Massachusetts General Hospital, Boston, Massachusetts (Kim, Lennes, Gandhi); Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (Caniglia) Mass General Brigham Integrated Care (Gainer); Beth Israel Lahey Health, Cambridge, Massachusetts (Patel) Corresponding Author: Scott Dryden-Peterson, MD, MSc, Division of Infectious Diseases, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115. Work: (617) 732-8881. sldrydenpeterson@bwh.harvard.edu Acknowledgement: This work was made possible with help from the Harvard University Center for AIDS Research (CFAR), a funded program of the National Institutes of Health (P30 AI060354) and the National Cancer Institute (R01 CA236546). The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or the institutions with which the authors are affiliated. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Drs. Dryden-Peterson and Woolley had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. 2 medRxiv preprint doi: https://doi.org/10.1101/2022.06.14.22276393; this version posted June 16, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . Abstract: Background: In the EPIC-HR trial, nirmatrelvir plus ritonavir led to an 88% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. Clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. Objective: To assess..