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Comparative studies of the impact of COVID-19 outbreaks and interventions on the intensity of influenza activity are needed to augment current understanding. Preliminary studies have reported that COVID-19 NPIs may have reduced the spread of influenza viruses 16, but the evidence was obtained largely from observational modeling studies 17, 18, 19. NPI-based prevention and control of COVID-19 provided an opportunity to observe the real-world effectiveness of NPIs at mitigating seasonal influenza virus transmission using a comparison study design. In contrast, during the same epidemic weeks of the eight influenza seasons during 2011-2019, influenza activity had maintained at a moderate or high level. For example, the percent of influenza-positive tests among US respiratory specimens decreased from >20% between Januand Mato 2.3% during the week of March 22, 2020, and remained at historically low inter-seasonal levels after April 5 15. In most provinces of China and in the US, rates of influenza laboratory test positivity declined sharply during the winter–spring season of 2019–2020 6, 15. Influenza activity is carefully monitored in the US and China through sensitive, laboratory-based surveillance systems 13, 14. Influenza and COVID-19 have similar clinical symptoms and transmission routes 10, 11, 12. By April 1, four US metropolitan areas-Seattle, San Francisco, New York City, and New Orleans-documented significant reductions of new COVID-19 cases after implementing COVID-19 mitigation measures 9. In the US, following a national emergency declaration issued on March 13, 2020, state governments used NPIs to reduce COVID-19 transmission 9. The COVID-19 epidemic was controlled and sustained local SARS-CoV-2 transmission stopped in mainland China by April 2020 with NPIs alone 8. Soon afterward, all provinces in mainland China initiated first-level (highest) emergency responses and adopted stringent NPIs-especially inter-city traffic controls, wearing face masks, and issuing stay-at-home orders 7. Wuhan city was “locked down” on Januby sharply curtailing in and out traffic. People may have adopted more hygienic lifestyles to avoid COVID-19 infection. These measures included social distancing and restrictions of personal movement (e.g., canceling mass gatherings, closing public entertainment venues, closing schools, restricting domestic and international travel, and issuing stay-at-home orders) use of individual protection (e.g., wearing masks, practicing good hand hygiene and respiratory etiquette) and social mobilization (e.g., publicity, education, and risk communication) 5, 6. In the absence of readily available, effective pharmaceutical agents against the emerging virus, countries implemented non-pharmaceutical interventions (NPIs) to contain or slow SARS-CoV-2 transmission. COVID-19 is the first pandemic known to be caused by a coronavirus 1, 2 it spread rapidly worldwide, causing great health and socioeconomic damage due to its clinical severity and ease of transmission 3, 4. World Health Organization named the disease coronavirus disease 2019 (COVID-19) and characterized it as a pandemic in March 2020. In the United States (the US), the first case was reported on January 20, 2020. A novel coronavirus, later named SARS-CoV-2, was identified on Januas the cause of the cluster 1. Wuhan Municipal Health Commission reported a cluster of cases of pneumonia on December 31, 2019.