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Within a multistate viral genomic surveillance program, we evaluated whether proportions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections attributed to the JN.1 variant and to XBB-lineage variants (including HV.1 and EG.5) differed between inpatient and outpatient care settings during periods of cocirculation. Both JN.1 and HV.1 were less likely than EG.5 to account for infections among inpatients versus outpatients (adjusted odds ratio [aOR], 0.60 [95% confidence interval (CI), .43-.84; P = .003] and 0.35 [.21-.58; P < .001], respectively). JN.1 and HV.1 variants may be associated with a lower risk of severe illness. The severity of coronavirus disease 2019 may have attenuated as predominant circulating SARS-CoV-2 lineages shifted from EG.5 to HV.1 to JN.1., Competing Interests: Potential conflicts of interest . M. E. L., V. C., L. M. M., E. T. C., D. W., A. D. R., H. D., M. I., N. L. W., T. B., K. T., J. N., J. R., E. S., W. L., J. L., and S. L. are employees of Helix. M. E. L., E. T. C., D. W., M. I., J. L., and S. L. report support for attending meetings and/or travel from Helix. M. E. L., E. T. C., D. W., A. D. R., M. I., N. L. W., W. L., J. L., and S. L. report stock or stock options from Helix. M. E. L., M. I., W. L., and S. L. report contracted research from Pfizer. M. E. L., M. I., W. L., and S. L. report contracted research from the Centers for Disease Control and Prevention. M. E. L. reports contracted research and travel support from Novavax. R. E. D. reports consulting fees from Health Advances. P. R. H. reports contracted research from Seegene USA and Helix. J. D. G. reports contracted research from Helix, Gilead, Eli Lilly, and Regeneron; grants from Merck (BARDA) and Gilead; speaking honoraria and personal fees from Gilead Sciences and Eli Lilly; and collaborative services agreements with Adaptive Biotechnologies, Monogram Biosciences, and LabCorp; and service as a speaker or advisory board member for Gilead and Eli Lilly. C. A. S. reports giving educational lectures sponsored by Eli Lilly. M. I., N. L. W., and S. L. report patents pending or issued to Helix (M. I. and S. L.: US-11776694-B2 and US-20230178236-A1). P. A. P. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Within a multistate clinical cohort, SARS-CoV-2 antiviral prescribing patterns were evaluated from April 2022-June 2023 among nonhospitalized patients with SARS-CoV-2 with risk factors for severe COVID-19. Among 3247 adults, only 31.9% were prescribed an antiviral agent (87.6% nirmatrelvir/ritonavir, 11.9% molnupiravir, 0.5% remdesivir), highlighting the need to identify and address treatment barriers., Competing Interests: Potential conflicts of interest. M. E. L., V. C., L. M. M., D. W., A. D. R., H. D., M. I., N. L. W., T. B., K. T., J. N., J. R., E. S., W. L., J. L., and S. L. are employees of Helix, Inc. M. E. L., M. I., and S. L. report contracted research from Pfizer. M. E. L., M. I., W. L., and S. L. report contracted research from the Centers for Disease Control and Prevention (CDC). M. I., M. E. L., J. L., D. W., and S. L. report support for attending meetings and/or travel from Helix. M. I., M. E. L., W. L., A. D. R., J. L., D. W., and N. L. W. report stock or stock options from Helix. M. E. L. reports contracted research and travel support from Novavax. E. B. is an employee of Janssen Pharmaceuticals and a prior employee of Helix, Inc. P. R. H. reports contracted research from Seegene USA and Helix, Inc. J. G. is employed by the University of Nevada, Reno, and Renown Health, and reports a professional relationship with the Desert Research Institute and research funding from Gilead Sciences and the National Institute of Environmental Health Sciences (NIEHS); reports consulting fees from Renown Health; and US Patent Application 63/467,250 “Dynamic risk management for breast cancer based on multi-factor genetic testing” with Dr. Alexandre Bolze. J. D. G. reports contracted research from Helix, Gilead, Eli Lilly, and Regeneron; grants from Merck (BARDA) and Gilead; speaking honoraria and personal fees from Gilead Sciences, Inc, and Eli Lilly & Co; and collaborative services agreements with Adaptive Biotechnologies, Monogram Biosciences, and LabCorp; and serving as a speaker or advisory board member for Gilead and Eli Lilly. J. G., M. I., N. L. W., and S. L. report patents pending or issued to Helix, Inc (M. I. and S. L.: US-11776694-B2 and US-20230178236-A1). P. A. P. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality., Competing Interests: Declaration of interests N.L.W., A.B., E.T.C., K.M.S.B., S.W., C.R.-G., E. Sandoval, T.C., X.W., J.N., J.M.R., G.L., D.W., D.B., M.L., M.I., S.J., J.T.L., and W.L. are employees of Helix. K. Gietzen, B.S., J.A., K.H., J.L., E.d.F., and P.G.F. are employees of Illumina. J.N., C.R.-G., and M.L. own stock in ILMN. K.G.A. has received consulting fees for advising on SARS-CoV-2, variants, and the COVID-19 pandemic., (Copyright © 2021 Elsevier Inc. All rights reserved.)