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Before the emergence of SARS-CoV-2, the virus that causes COVID-19, influenza activity in the United States typically began to increase in the fall and peaked in February. During the 2021-22 season, influenza activity began to increase in November and remained elevated until mid-June, featuring two distinct waves, with A(H3N2) viruses predominating for the entire season. This report summarizes influenza activity during October 3, 2021-June 11, 2022, in the United States and describes the composition of the Northern Hemisphere 2022-23 influenza vaccine. Although influenza activity is decreasing and circulation during summer is typically low, remaining vigilant for influenza infections, performing testing for seasonal influenza viruses, and monitoring for novel influenza A virus infections are important. An outbreak of highly pathogenic avian influenza A(H5N1) is ongoing; health care providers and persons with exposure to sick or infected birds should remain vigilant for onset of symptoms consistent with influenza. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.The United States influenza surveillance system is a collaborative effort between CDC and its many partners in state, local, and territorial health departments, public health and clinical laboratories, vital statistics offices, health care providers, hospitals, clinics, emergency departments, and long-term care facilities. This report is a summary of the 2021-22 influenza season. This report was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. †

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R esistance to antiviral drugs for infl uenza is an ongoing public health concern. The neuraminidase (NA) inhibitor oseltamivir is the most prescribed antiviral drug for controlling infl uenza. However, during 2007-2009, oseltamivir-resistant infl uenza A(H1N1) viruses rapidly spread worldwide (1). Molecular mechanisms implicated in this event were acquisition of NA-permissive mutations that alleviated deleterious fi tness effects of the resistance-conferring mutation NA-H275Y (N1 numbering) (2); changes that improved balance of hemagglutinin (HA) and NA activities (3); and a "hitchhiking" mechanism, in which HA antigenic drift promoted the spread of oseltamivir-resistant viruses (4). Oseltamivir-resistant H1N1 viruses were later displaced by the 2009 pandemic virus, infl uenza A(H1N1)pdm09 (pH1N1), which was antigenically distinct and oseltamivir sensitive (5). The emergence and transmission of oseltamivir-resistant pH1N1 carrying a NA-H275Y mutation was fi rst reported early in the 2009 pandemic (6). In the following years, transmission of oseltamivir-resistant viruses within healthcare settings and communities, or between close contacts, was occasionally observed (1); clusters were reported in Australia in 2011 ( 7) and Japan in 2013 (8). Despite these incidents, widespread circulation of oseltamivir-resistant viruses has yet to occur. The StudyThe Centers for Disease Control and Prevention (CDC) receives infl uenza-positive specimens collected globally for virological surveillance. Viral genomes are analyzed using next-generation sequencing (NGS) to identify strains of epidemiologic, virologic, and clinical importance (9). To supplement US national antiviral surveillance, pyrosequencing is used by public health laboratories to screen additional viruses either in-house or by the National Infl uenza Reference Center (10).During the 2019-20 infl uenza season, the pH1N1 subtype predominated in the United States. Later in the season, fewer infl uenza samples were identifi ed, likely because of COVID-19 pandemic mitigation strategies. Of 951 pH1N1 isolates collected nationwide during October 2019-September 2020, 4 (0.4%) had the NA-H275Y marker. Supplemental surveillance, conducted on 282 viruses from 18 states collected November 2019-March 2020, detected another 6 (2.1%) NA-H275Y viruses, bringing the total detected nationwide to 10 (10/1,233;