Work Attendance with Acute Respiratory Illness Before and During COVID-19 Pandemic, United States, 2018-2022.

Both SARS-CoV-2 and influenza virus can be transmitted by asymptomatic, presymptomatic, or symptomatic infected persons. We assessed effects on work attendance while ill before and during the COVID-19 pandemic in the United States by analyzing data collected prospectively from persons with acute respiratory illnesses enrolled in a multistate study during 2018-2022. Persons with previous hybrid work experience were significantly less likely to work onsite on the day before through the first 3 days of illness than those without that experience, an effect more pronounced during the COVID-19 pandemic than during prepandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other acute respiratory illnesses. Among persons with positive COVID-19 test results available by the second or third day of illness, few worked onsite. Hybrid and remote work policies might reduce workplace exposures and help reduce spread of respiratory viruses.

Influenza Vaccine Effectiveness Against Influenza A(H3N2)-Related Illness in the United States During the 2021-2022 Influenza Season.

BACKGROUND: In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness (VE) for the first time since the beginning of the coronavirus disease 2019 pandemic. We estimated influenza VE against laboratory-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. METHODS: Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged ≥6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, participants who tested positive for SARS-CoV-2 were excluded from VE estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity, and general health status. RESULTS: Among 6260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1948 SARS-CoV-2-positive patients, 4312 patients were included in analyses of influenza VE; 2463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95% confidence interval, 20%-49%) overall. CONCLUSIONS: Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons.

Burden of medically attended influenza infection and cases averted by vaccination - United States, 2016/17 through 2018/19 influenza seasons.

BACKGROUND: Epidemics of seasonal influenza vary in intensity annually, and influenza vaccine effectiveness (VE) fluctuates based in part on antigenic match to circulating viruses. We estimated the incidence of influenza and influenza cases averted by vaccination in four ambulatory care sites in the United States, during seasons when overall influenza VE ranged from 29% to 40%. METHODS: We conducted active surveillance for influenza at ambulatory care settings at four sites within the United States Influenza Vaccine Effectiveness Network. We extrapolated the total number of influenza cases in the source populations served by these organizations based on incidence of medically attended acute respiratory illness in the source population and influenza test results in those actively tested for influenza. We estimated the number of medically attended influenza cases averted based on incidence, vaccine coverage, and VE. RESULTS: From 2016/17 through 2018/19, incidence of ambulatory visits for laboratory-confirmed influenza ranged from 31 to 51 per 1,000 population. Incidence was highest in children aged 9-17 years (range, 56 to 81 per 1,000) and lowest in adults aged 18-49 years (range, 23-32 per 1,000). Medically attended cases averted by vaccination ranged from a high of 46.6 (95 % CI, 12.1- 91.9) per 1,000 vaccinees in children aged 6 months to 8 years, to a low of 6.9 (95 % CI, -5.1- 27.3) per 1,000 vaccinees in adults aged ≥ 65 years. DISCUSSION: Even in seasons with low vaccine effectiveness for a particular virus subtype, influenza vaccines can still lead to clinically meaningful reductions in ambulatory care visits for influenza.

Interim Estimates of 2021-22 Seasonal Influenza Vaccine Effectiveness - United States, February 2022.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months except when contraindicated (1). Currently available influenza vaccines are designed to protect against four influenza viruses: A(H1N1)pdm09 (the 2009 pandemic virus), A(H3N2), B/Victoria lineage, and B/Yamagata lineage. Most influenza viruses detected this season have been A(H3N2) (2). With the exception of the 2020-21 season, when data were insufficient to generate an estimate, CDC has estimated the effectiveness of seasonal influenza vaccine at preventing laboratory-confirmed, mild/moderate (outpatient) medically attended acute respiratory infection (ARI) each season since 2004-05. This interim report uses data from 3,636 children and adults with ARI enrolled in the U.S. Influenza Vaccine Effectiveness Network during October 4, 2021-February 12, 2022. Overall, vaccine effectiveness (VE) against medically attended outpatient ARI associated with influenza A(H3N2) virus was 16% (95% CI = -16% to 39%), which is considered not statistically significant. This analysis indicates that influenza vaccination did not reduce the risk for outpatient medically attended illness with influenza A(H3N2) viruses that predominated so far this season. Enrollment was insufficient to generate reliable VE estimates by age group or by type of influenza vaccine product (1). CDC recommends influenza antiviral medications as an adjunct to vaccination; the potential public health benefit of antiviral medications is magnified in the context of reduced influenza VE. CDC routinely recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating, even when VE against one virus is reduced, because vaccine can prevent serious outcomes (e.g., hospitalization, intensive care unit (ICU) admission, or death) that are associated with influenza A(H3N2) virus infection and might protect against other influenza viruses that could circulate later in the season.

Incidence of Medically Attended Acute Respiratory Illnesses Due to Respiratory Viruses Across the Life Course During the 2018/19 Influenza Season.

BACKGROUND: Although multiple respiratory viruses circulate in humans, few studies have compared the incidence of different viruses across the life course. We estimated the incidence of outpatient illness due to 12 different viruses during November 2018 through April 2019 in a fully enumerated population. METHODS: We conducted active surveillance for ambulatory care visits for acute respiratory illness (ARI) among members of Kaiser Permanente Washington (KPWA). Enrolled patients provided respiratory swab specimens which were tested for 12 respiratory viruses using reverse transcription polymerase chain reaction (RT-PCR). We estimated the cumulative incidence of infection due to each virus overall and by age group. RESULTS: The KPWA population under surveillance included 202 562 individuals, of whom 2767 (1.4%) were enrolled in the study. Influenza A(H3N2) was the most commonly detected virus, with an overall incidence of 21 medically attended illnesses per 1000 population; the next most common viruses were influenza A(H1N1) (18 per 1000), coronaviruses (13 per 1000), respiratory syncytial virus (RSV, 13 per 1000), and rhinovirus (9 per 1000). RSV was the most common cause of medically attended ARI among children aged 1-4 years; coronaviruses were the most common among adults aged ≥65 years. CONCLUSIONS: Consistent with other studies focused on single viruses, we found that influenza and RSV were major causes of acute respiratory illness in persons of all ages. In comparison, coronaviruses and rhinovirus were also important pathogens. Prior to the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronaviruses were the second-most common cause of medically attended ARI during the 2018/19 influenza season.

Burden of medically attended influenza infection and cases averted by vaccination - United States, 2013/14 through 2015/16 influenza seasons.

BACKGROUND: In addition to preventing hospitalizations and deaths due to influenza, influenza vaccination programs can reduce the burden of outpatient visits for influenza. We estimated the incidence of medically-attended influenza at three geographically diverse sites in the United States, and the cases averted by vaccination, for the 2013/14 through 2015/16 influenza seasons. METHODS: We defined surveillance populations at three sites from the United States Influenza Vaccine Effectiveness Network. Among these populations, we identified outpatient visits laboratory-confirmed influenza via active surveillance, and identified all outpatient visits for acute respiratory illness from healthcare databases. We extrapolated the total number of outpatient visits for influenza from the proportion of surveillance visits with a positive influenza test. We combined estimates of incidence, vaccine coverage, and vaccine effectiveness to estimate outpatient visits averted by vaccination. RESULTS: Across the three sites and seasons, incidence of medically attended influenza ranged from 14 to 54 per 1000 population. Incidence was highest in children aged 6 months to 9 years (33 to 70 per 1000) and lowest in adults aged 18-49 years (21 to 27 per 1000). Cases averted ranged from 9 per 1000 vaccinees (Washington, 2014/15) to 28 per 1000 (Wisconsin, 2013/14). DISCUSSION: Seasonal influenza epidemics cause a considerable burden of outpatient medical visits. The United States influenza vaccination program has caused meaningful reductions in outpatient visits for influenza, even in years when the vaccine is not well-matched to the dominant circulating influenza strain.

The impact of selection bias on vaccine effectiveness estimates from test-negative studies.

INTRODUCTION: Estimates of vaccine effectiveness (VE) from test-negative studies may be subject to selection bias. In the context of influenza VE, we used simulations to identify situations in which meaningful selection bias can occur. We also analyzed observational study data for evidence of selection bias. METHODS: For the simulation study, we defined a hypothetical population whose members are at risk for acute respiratory illness (ARI) due to influenza and other pathogens. An unmeasured "healthcare seeking proclivity" affects both probability of vaccination and probability of seeking care for an ARI. We varied the direction and magnitude of these effects and identified situations where meaningful bias occurred. For the observational study, we reanalyzed data from the United States Influenza VE Network, an ongoing test-negative study. We compared "bias-naïve" VE estimates to bias-adjusted estimates, which used data from the source populations to correct for sampling bias. RESULTS: In the simulation study, an unmeasured care-seeking proclivity could create selection bias if persons with influenza ARI were more (or less) likely to seek care than persons with non-influenza ARI. However, selection bias was only meaningful when rates of care seeking between influenza ARI and non-influenza ARI were very different. In the observational study, the bias-naïve VE estimate of 55% (95% CI, 47--62%) was trivially different from the bias-adjusted VE estimate of 57% (95% CI, 49--63%). CONCLUSIONS: In combination, these studies suggest that while selection bias is possible in test-negative VE studies, this bias in unlikely to be meaningful under conditions likely to be encountered in practice. Researchers and public health officials can continue to rely on VE estimates from test-negative studies.

Influenza Vaccine Effectiveness in the United States during the 2015-2016 Season.

BACKGROUND: The A(H1N1)pdm09 virus strain used in the live attenuated influenza vaccine was changed for the 2015-2016 influenza season because of its lack of effectiveness in young children in 2013-2014. The Influenza Vaccine Effectiveness Network evaluated the effect of this change as part of its estimates of influenza vaccine effectiveness in 2015-2016. METHODS: We enrolled patients 6 months of age or older who presented with acute respiratory illness at ambulatory care clinics in geographically diverse U.S. sites. Using a test-negative design, we estimated vaccine effectiveness as (1-OR)×100, in which OR is the odds ratio for testing positive for influenza virus among vaccinated versus unvaccinated participants. Separate estimates were calculated for the inactivated vaccines and the live attenuated vaccine. RESULTS: Among 6879 eligible participants, 1309 (19%) tested positive for influenza virus, predominantly for A(H1N1)pdm09 (11%) and influenza B (7%). The effectiveness of the influenza vaccine against any influenza illness was 48% (95% confidence interval [CI], 41 to 55; P<0.001). Among children 2 to 17 years of age, the inactivated influenza vaccine was 60% effective (95% CI, 47 to 70; P<0.001), and the live attenuated vaccine was not observed to be effective (vaccine effectiveness, 5%; 95% CI, -47 to 39; P=0.80). Vaccine effectiveness against A(H1N1)pdm09 among children was 63% (95% CI, 45 to 75; P<0.001) for the inactivated vaccine, as compared with -19% (95% CI, -113 to 33; P=0.55) for the live attenuated vaccine. CONCLUSIONS: Influenza vaccines reduced the risk of influenza illness in 2015-2016. However, the live attenuated vaccine was found to be ineffective among children in a year with substantial inactivated vaccine effectiveness. Because the 2016-2017 A(H1N1)pdm09 strain used in the live attenuated vaccine was unchanged from 2015-2016, the Advisory Committee on Immunization Practices made an interim recommendation not to use the live attenuated influenza vaccine for the 2016-2017 influenza season. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health.).