Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings.

BACKGROUND: There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. METHODS: We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients' vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. RESULTS: The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. CONCLUSIONS: Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.).

Standard-dose versus MF59-adjuvanted, high-dose or recombinant-hemagglutinin influenza vaccine immunogenicity in older adults: comparison of A(H3N2) antibody response by prior season's vaccine status.

BACKGROUND: Annual influenza vaccination is recommended for older adults but repeated vaccination with standard-dose influenza vaccine has been linked to reduced immunogenicity and effectiveness, especially against A(H3N2) viruses. METHODS: Community-dwelling Hong Kong adults aged 65-82 years were randomly allocated to receive 2017/18 standard-dose quadrivalent, MF59-adjuvanted trivalent, high-dose trivalent, and recombinant-HA quadrivalent vaccination. Antibody response to unchanged A(H3N2) vaccine antigen was compared among participants with and without self-reported prior year (2016/17) standard-dose vaccination. RESULTS: Mean fold rise (MFR) in antibody titers from Day 0 to Day 30 by hemagglutination inhibition and virus microneutralization assays were lower among 2017/18 standard-dose and enhanced vaccine recipients with (range, 1.7-3.0) vs. without (range, 4.3-14.3) prior 2016/17 vaccination. MFR was significantly reduced by about one half to four fifths for previously vaccinated recipients of standard-dose and all three enhanced vaccines (ß range, 0.21-0.48). Among prior-year vaccinated older adults, enhanced vaccines induced higher 1.43 to 2.39-fold geometric mean titers and 1.28 to 1.74-fold MFR vs. standard-dose vaccine by microneutralization assay. CONCLUSIONS: In the context of unchanged A(H3N2) vaccine strain, prior-year vaccination was associated with reduced antibody response among both standard-dose and enhanced influenza vaccine recipients. Enhanced vaccines improved antibody response among older adults with prior-year standard-dose vaccination.

Effect of Repeat Vaccination on Immunogenicity of Quadrivalent Cell-Culture and Recombinant Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized, Open-Label Trial.

BACKGROUND: Antibody responses to non-egg-based standard-dose cell-culture influenza vaccine (containing 15 µg hemagglutinin [HA]/component) and recombinant vaccine (containing 45 µg HA/component) during consecutive seasons have not been studied in the United States. METHODS: In a randomized trial of immunogenicity of quadrivalent influenza vaccines among healthcare personnel (HCP) aged 18-64 years over 2 consecutive seasons, HCP who received recombinant-HA influenza vaccine (RIV) or cell culture-based inactivated influenza vaccine (ccIIV) during the first season (year 1) were re-randomized the second season of 2019-2020 (year 2 [Y2]) to receive ccIIV or RIV, resulting in 4 ccIIV/RIV combinations. In Y2, hemagglutination inhibition antibody titers against reference cell-grown vaccine viruses were compared in each ccIIV/RIV group with titers among HCP randomized both seasons to receive egg-based, standard-dose inactivated influenza vaccine (IIV) using geometric mean titer (GMT) ratios of Y2 post-vaccination titers. RESULTS: Y2 data from 414 HCP were analyzed per protocol. Compared with 60 IIV/IIV recipients, 74 RIV/RIV and 106 ccIIV/RIV recipients showed significantly elevated GMT ratios (Bonferroni corrected P < .007) against all components except A(H3N2). Post-vaccination GMT ratios for ccIIV/ccIIV and RIV/ccIIV were not significantly elevated compared with IIV/IIV except for RIV/ccIIV against A(H1N1)pdm09. CONCLUSIONS: In adult HCP, receipt of RIV in 2 consecutive seasons or the second season was more immunogenic than consecutive egg-based IIV for 3 of the 4 components of quadrivalent vaccine. Immunogenicity of ccIIV/ccIIV was similar to that of IIV/IIV. Differences in HA antigen content may play a role in immunogenicity of influenza vaccination in consecutive seasons. CLINICAL TRIALS REGISTRATION: NCT03722589.

Risk for Infection in Humans after Exposure to Birds Infected with Highly Pathogenic Avian Influenza A(H5N1) Virus, United States, 2022.

During February 7─September 3, 2022, a total of 39 US states experienced outbreaks of highly pathogenic avian influenza A(H5N1) virus in birds from commercial poultry farms and backyard flocks. Among persons exposed to infected birds, highly pathogenic avian influenza A(H5) viral RNA was detected in 1 respiratory specimen from 1 person.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022-23 Influenza Season.

THIS REPORT UPDATES THE 2021-22 RECOMMENDATIONS OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) CONCERNING THE USE OF SEASONAL INFLUENZA VACCINES IN THE UNITED STATES: (MMWR Recomm Rep 2021;70[No. RR-5]:1-24). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. With the exception of vaccination for adults aged ≥65 years, ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. All seasonal influenza vaccines expected to be available in the United States for the 2022-23 season are quadrivalent, containing hemagglutinin (HA) derived from one influenza A(H1N1)pdm09 virus, one influenza A(H3N2) virus, one influenza B/Victoria lineage virus, and one influenza B/Yamagata lineage virus. Inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) are expected to be available. Trivalent influenza vaccines are no longer available, but data that involve these vaccines are included for reference. INFLUENZA VACCINES MIGHT BE AVAILABLE AS EARLY AS JULY OR AUGUST, BUT FOR MOST PERSONS WHO NEED ONLY 1 DOSE OF INFLUENZA VACCINE FOR THE SEASON, VACCINATION SHOULD IDEALLY BE OFFERED DURING SEPTEMBER OR OCTOBER. HOWEVER, VACCINATION SHOULD CONTINUE AFTER OCTOBER AND THROUGHOUT THE SEASON AS LONG AS INFLUENZA VIRUSES ARE CIRCULATING AND UNEXPIRED VACCINE IS AVAILABLE. FOR MOST ADULTS (PARTICULARLY ADULTS AGED ≥65 YEARS) AND FOR PREGNANT PERSONS IN THE FIRST OR SECOND TRIMESTER, VACCINATION DURING JULY AND AUGUST SHOULD BE AVOIDED UNLESS THERE IS CONCERN THAT VACCINATION LATER IN THE SEASON MIGHT NOT BE POSSIBLE. CERTAIN CHILDREN AGED 6 MONTHS THROUGH 8 YEARS NEED 2 DOSES; THESE CHILDREN SHOULD RECEIVE THE FIRST DOSE AS SOON AS POSSIBLE AFTER VACCINE IS AVAILABLE, INCLUDING DURING JULY AND AUGUST. VACCINATION DURING JULY AND AUGUST CAN BE CONSIDERED FOR CHILDREN OF ANY AGE WHO NEED ONLY 1 DOSE FOR THE SEASON AND FOR PREGNANT PERSONS WHO ARE IN THE THIRD TRIMESTER IF VACCINE IS AVAILABLE DURING THOSE MONTHS: UPDATES DESCRIBED IN THIS REPORT REFLECT DISCUSSIONS DURING PUBLIC MEETINGS OF ACIP THAT WERE HELD ON OCTOBER 20, 2021; JANUARY 12, 2022; FEBRUARY 23, 2022; AND JUNE 22, 2022. PRIMARY UPDATES TO THIS REPORT INCLUDE THE FOLLOWING THREE TOPICS: 1) THE COMPOSITION OF 2022-23 U.S. SEASONAL INFLUENZA VACCINES; 2) UPDATES TO THE DESCRIPTION OF INFLUENZA VACCINES EXPECTED TO BE AVAILABLE FOR THE 2022-23 SEASON, INCLUDING ONE INFLUENZA VACCINE LABELING CHANGE THAT OCCURRED AFTER THE PUBLICATION OF THE 2021-22 ACIP INFLUENZA RECOMMENDATIONS; AND 3) UPDATES TO THE RECOMMENDATIONS CONCERNING VACCINATION OF ADULTS AGED ≥65 YEARS. FIRST, THE COMPOSITION OF 2022-23 U.S. INFLUENZA VACCINES INCLUDES UPDATES TO THE INFLUENZA A(H3N2) AND INFLUENZA B/VICTORIA LINEAGE COMPONENTS. U.S.-LICENSED INFLUENZA VACCINES WILL CONTAIN HA DERIVED FROM AN INFLUENZA A/VICTORIA/2570/2019 (H1N1)PDM09-LIKE VIRUS (FOR EGG-BASED VACCINES) OR AN INFLUENZA A/WISCONSIN/588/2019 (H1N1)PDM09-LIKE VIRUS (FOR CELL CULTURE-BASED OR RECOMBINANT VACCINES); AN INFLUENZA A/DARWIN/9/2021 (H3N2)-LIKE VIRUS (FOR EGG-BASED VACCINES) OR AN INFLUENZA A/DARWIN/6/2021 (H3N2)-LIKE VIRUS (FOR CELL CULTURE-BASED OR RECOMBINANT VACCINES); AN INFLUENZA B/AUSTRIA/1359417/2021 (VICTORIA LINEAGE)-LIKE VIRUS; AND AN INFLUENZA B/PHUKET/3073/2013 (YAMAGATA LINEAGE)-LIKE VIRUS. SECOND, THE APPROVED AGE INDICATION FOR THE CELL CULTURE-BASED INACTIVATED INFLUENZA VACCINE, FLUCELVAX QUADRIVALENT (CCIIV4), WAS CHANGED IN OCTOBER 2021 FROM ≥2 YEARS TO ≥6 MONTHS. THIRD, RECOMMENDATIONS FOR VACCINATION OF ADULTS AGED ≥65 YEARS HAVE BEEN MODIFIED. ACIP RECOMMENDS THAT ADULTS AGED ≥65 YEARS PREFERENTIALLY RECEIVE ANY ONE OF THE FOLLOWING HIGHER DOSE OR ADJUVANTED INFLUENZA VACCINES: QUADRIVALENT HIGH-DOSE INACTIVATED INFLUENZA VACCINE (HD-IIV4), QUADRIVALENT RECOMBINANT INFLUENZA VACCINE (RIV4), OR QUADRIVALENT ADJUVANTED INACTIVATED INFLUENZA VACCINE (AIIV4). IF NONE OF THESE THREE VACCINES IS AVAILABLE AT AN OPPORTUNITY FOR VACCINE ADMINISTRATION, THEN ANY OTHER AGE-APPROPRIATE INFLUENZA VACCINE SHOULD BE USED: THIS REPORT FOCUSES ON RECOMMENDATIONS FOR THE USE OF VACCINES FOR THE PREVENTION AND CONTROL OF SEASONAL INFLUENZA DURING THE 2022-23 INFLUENZA SEASON IN THE UNITED STATES. A BRIEF SUMMARY OF THE RECOMMENDATIONS AND A LINK TO THE MOST RECENT BACKGROUND DOCUMENT CONTAINING ADDITIONAL INFORMATION ARE AVAILABLE AT: https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration-licensed indications. Updates and other information are available from CDC's influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check this site periodically for additional information.

Leveraging International Influenza Surveillance Systems and Programs during the COVID-19 Pandemic.

A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season.

This report updates the 2020-21 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2020;69[No. RR-8]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. During the 2021-22 influenza season, the following types of vaccines are expected to be available: inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4).The 2021-22 influenza season is expected to coincide with continued circulation of SARS-CoV-2, the virus that causes COVID-19. Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient visits, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html. Recommendations for the use of COVID-19 vaccines are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html, and additional clinical guidance is available at https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html.Updates described in this report reflect discussions during public meetings of ACIP that were held on October 28, 2020; February 25, 2021; and June 24, 2021. Primary updates to this report include the following six items. First, all seasonal influenza vaccines available in the United States for the 2021-22 season are expected to be quadrivalent. Second, the composition of 2021-22 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09 and influenza A(H3N2) components. U.S.-licensed influenza vaccines will contain hemagglutinin derived from an influenza A/Victoria/2570/2019 (H1N1)pdm09-like virus (for egg-based vaccines) or an influenza A/Wisconsin/588/2019 (H1N1)pdm09-like virus (for cell culture-based and recombinant vaccines), an influenza A/Cambodia/e0826360/2020 (H3N2)-like virus, an influenza B/Washington/02/2019 (Victoria lineage)-like virus, and an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus. Third, the approved age indication for the cell culture-based inactivated influenza vaccine, Flucelvax Quadrivalent (ccIIV4), has been expanded from ages ≥4 years to ages ≥2 years. Fourth, discussion of administration of influenza vaccines with other vaccines includes considerations for coadministration of influenza vaccines and COVID-19 vaccines. Providers should also consult current ACIP COVID-19 vaccine recommendations and CDC guidance concerning coadministration of these vaccines with influenza vaccines. Vaccines that are given at the same time should be administered in separate anatomic sites. Fifth, guidance concerning timing of influenza vaccination now states that vaccination soon after vaccine becomes available can be considered for pregnant women in the third trimester. As previously recommended, children who need 2 doses (children aged 6 months through 8 years who have never received influenza vaccine or who have not previously received a lifetime total of ≥2 doses) should receive their first dose as soon as possible after vaccine becomes available to allow the second dose (which must be administered ≥4 weeks later) to be received by the end of October. For nonpregnant adults, vaccination in July and August should be avoided unless there is concern that later vaccination might not be possible. Sixth, contraindications and precautions to the use of ccIIV4 and RIV4 have been modified, specifically with regard to persons with a history of severe allergic reaction (e.g., anaphylaxis) to an influenza vaccine. A history of a severe allergic reaction to a previous dose of any egg-based IIV, LAIV, or RIV of any valency is a precaution to use of ccIIV4. A history of a severe allergic reaction to a previous dose of any egg-based IIV, ccIIV, or LAIV of any valency is a precaution to use of RIV4. Use of ccIIV4 and RIV4 in such instances should occur in an inpatient or outpatient medical setting under supervision of a provider who can recognize and manage a severe allergic reaction; providers can also consider consulting with an allergist to help identify the vaccine component responsible for the reaction. For ccIIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any ccIIV of any valency or any component of ccIIV4 is a contraindication to future use of ccIIV4. For RIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any RIV of any valency or any component of RIV4 is a contraindication to future use of RIV4. This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2021-22 influenza season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration-licensed indications. Updates and other information are available from CDC's influenza website (https://www.cdc.gov/flu); vaccination and health care providers should check this site periodically for additional information.

United States Centers for Disease Control and Prevention support for influenza surveillance, 2013-2021.

Objective: To assess the stability of improvements in global respiratory virus surveillance in countries supported by the United States Centers for Disease Control and Prevention (CDC) after reductions in CDC funding and with the stress of the coronavirus disease 2019 (COVID-19) pandemic. Methods: We assessed whether national influenza surveillance systems of CDC-funded countries: (i) continued to analyse as many specimens between 2013 and 2021; (ii) participated in activities of the World Health Organization's (WHO) Global Influenza Surveillance and Response System; (iii) tested enough specimens to detect rare events or signals of unusual activity; and (iv) demonstrated stability before and during the COVID-19 pandemic. We used CDC budget records and data from the WHO Global Influenza Surveillance and Response System. Findings: While CDC reduced per-country influenza funding by about 75% over 10 years, the number of specimens tested annually remained stable (mean 2261). Reporting varied substantially by country and transmission zone. Countries funded by CDC accounted for 71% (range 61-75%) of specimens included in WHO consultations on the composition of influenza virus vaccines. In 2019, only eight of the 17 transmission zones sent enough specimens to WHO collaborating centres before the vaccine composition meeting to reliably identify antigenic variants. Conclusion: Great progress has been made in the global understanding of influenza trends and seasonality. To optimize surveillance to identify atypical influenza viruses, and to integrate molecular testing, sequencing and reporting of severe acute respiratory syndrome coronavirus 2 into existing systems, funding must continue to support these efforts.

Vital Signs: Influenza Hospitalizations and Vaccination Coverage by Race and Ethnicity-United States, 2009-10 Through 2021-22 Influenza Seasons.

Introduction: CDC estimates that influenza resulted in 9-41 million illnesses, 140,000-710,000 hospitalizations, and 12,000-52,000 deaths annually during 2010-2020. Persons from some racial and ethnic minority groups have historically experienced higher rates of severe influenza and had lower influenza vaccination coverage compared with non-Hispanic White (White) persons. This report examines influenza hospitalization and vaccination rates by race and ethnicity during a 12-13-year period (through the 2021-22 influenza season). Methods: Data from population-based surveillance for laboratory-confirmed influenza-associated hospitalizations in selected states participating in the Influenza-Associated Hospitalization Surveillance Network (FluSurv-NET) from the 2009-10 through 2021-22 influenza seasons (excluding 2020-21) and influenza vaccination coverage data from the Behavioral Risk Factor Surveillance System (BRFSS) from the 2010-11 through 2021-22 influenza seasons were analyzed by race and ethnicity. Results: From 2009-10 through 2021-22, age-adjusted influenza hospitalization rates (hospitalizations per 100,000 population) were higher among non-Hispanic Black (Black) (rate ratio [RR] = 1.8), American Indian or Alaska Native (AI/AN; RR = 1.3), and Hispanic (RR = 1.2) adults, compared with the rate among White adults. During the 2021-22 season, influenza vaccination coverage was lower among Hispanic (37.9%), AI/AN (40.9%), Black (42.0%), and other/multiple race (42.6%) adults compared with that among White (53.9%) and non-Hispanic Asian (Asian) (54.2%) adults; coverage has been consistently higher among White and Asian adults compared with that among Black and Hispanic adults since the 2010-11 season. The disparity in vaccination coverage by race and ethnicity was present among those who reported having medical insurance, a personal health care provider, and a routine medical checkup in the past year. Conclusions and Implications for Public Health Practice: Racial and ethnic disparities in influenza disease severity and influenza vaccination coverage persist. Health care providers should assess patient vaccination status at all medical visits and offer (or provide a referral for) all recommended vaccines. Tailored programmatic efforts to provide influenza vaccination through nontraditional settings, along with national and community-level efforts to improve awareness of the importance of influenza vaccination in preventing illness, hospitalization, and death among racial and ethnic minority communities might help address health care access barriers and improve vaccine confidence, leading to decreases in disparities in influenza vaccination coverage and disease severity.

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.

Influenza Activity and Composition of the 2022-23 Influenza Vaccine - United States, 2021-22 Season.

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.

Clinical Trends Among U.S. Adults Hospitalized With COVID-19, March to December 2020 : A Cross-Sectional Study.

BACKGROUND: The COVID-19 pandemic has caused substantial morbidity and mortality. OBJECTIVE: To describe monthly clinical trends among adults hospitalized with COVID-19. DESIGN: Pooled cross-sectional study. SETTING: 99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET). PATIENTS: U.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020. MEASUREMENTS: Monthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100 000 persons in the population; monthly trends in weighted percentages of interventions, including ICU admission, mechanical ventilation, and vasopressor use, among an age- and site-stratified random sample of hospitalized case patients. RESULTS: Among 116 743 hospitalized adults with COVID-19, the median age was 62 years, 50.7% were male, and 40.8% were non-Hispanic White. Monthly rates of hospitalization (105.3 per 100 000 persons), ICU admission (20.2 per 100 000 persons), and death (11.7 per 100 000 persons) peaked during December 2020. Rates of all 3 outcomes were highest among adults aged 65 years or older, males, and Hispanic or non-Hispanic Black persons. Among 18 508 sampled hospitalized adults, use of remdesivir and systemic corticosteroids increased from 1.7% and 18.9%, respectively, in March to 53.8% and 74.2%, respectively, in December. Frequency of ICU admission, mechanical ventilation, and vasopressor use decreased from March (37.8%, 27.8%, and 22.7%, respectively) to December (20.5%, 12.3%, and 12.8%, respectively); use of noninvasive respiratory support increased from March to December. LIMITATION: COVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country. CONCLUSION: Rates of COVID-19-associated hospitalization, ICU admission, and death were highest in December 2020, corresponding with the third peak of the U.S. pandemic. The frequency of intensive interventions for management of hospitalized patients decreased over time. These data provide a longitudinal assessment of clinical trends among adults hospitalized with COVID-19 before widespread implementation of COVID-19 vaccines. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Shedding of Culturable Virus, Seroconversion, and 6-Month Follow-up Antibody Responses in the First 14 Confirmed Cases of Coronavirus Disease 2019 in the United States.

We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to 6 months after symptom onset, among 14 early patients with coronavirus disease 2019 in the United States. We isolated viable severe acute respiratory syndrome coronavirus 2 from real-time reverse-transcription polymerase chain reaction-positive respiratory specimens collected during days 0-8 after onset, but not after. All 13 patients with 2 or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodies. Eight participants provided serum at 6 months after onset; all retained detectable anti-spike immunoglobulin G, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at 6 months.

Estimated Incidence of Coronavirus Disease 2019 (COVID-19) Illness and Hospitalization-United States, February-September 2020.

BACKGROUND: In the United States, laboratory-confirmed coronavirus disease 2019 (COVID-19) is nationally notifiable. However, reported case counts are recognized to be less than the true number of cases because detection and reporting are incomplete and can vary by disease severity, geography, and over time. METHODS: To estimate the cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, symptomatic illnesses, and hospitalizations, we adapted a simple probabilistic multiplier model. Laboratory-confirmed case counts that were reported nationally were adjusted for sources of underdetection based on testing practices in inpatient and outpatient settings and assay sensitivity. RESULTS: We estimated that through the end of September, 1 of every 2.5 (95% uncertainty interval [UI]: 2.0-3.1) hospitalized infections and 1 of every 7.1 (95% UI: 5.8-9.0) nonhospitalized illnesses may have been nationally reported. Applying these multipliers to reported SARS-CoV-2 cases along with data on the prevalence of asymptomatic infection from published systematic reviews, we estimate that 2.4 million hospitalizations, 44.8 million symptomatic illnesses, and 52.9 million total infections may have occurred in the US population from 27 February-30 September 2020. CONCLUSIONS: These preliminary estimates help demonstrate the societal and healthcare burdens of the COVID-19 pandemic and can help inform resource allocation and mitigation planning.

Effectiveness of Trivalent and Quadrivalent Inactivated Vaccines Against Influenza B in the United States, 2011-2012 to 2016-2017.

BACKGROUND: Since 2013, quadrivalent influenza vaccines containing 2 B viruses gradually replaced trivalent vaccines in the United States. We compared the vaccine effectiveness of quadrivalent to trivalent inactivated vaccines (IIV4 to IIV3, respectively) against illness due to influenza B during the transition, when IIV4 use increased rapidly. METHODS: The US Influenza Vaccine Effectiveness (Flu VE) Network analyzed 25 019 of 42 600 outpatients aged ≥6 months who enrolled within 7 days of illness onset during 6 seasons from 2011-2012. Upper respiratory specimens were tested for the influenza virus type and B lineage. Using logistic regression, we estimated IIV4 or IIV3 effectiveness by comparing the odds of an influenza B infection overall and the odds of B lineage among vaccinated versus unvaccinated participants. Over 4 seasons from 2013-2014, we compared the relative odds of an influenza B infection among IIV4 versus IIV3 recipients. RESULTS: Trivalent vaccines included the predominantly circulating B lineage in 4 of 6 seasons. During 4 influenza seasons when both IIV4 and IIV3 were widely used, the overall effectiveness against any influenza B was 53% (95% confidence interval [CI], 45-59) for IIV4 versus 45% (95% CI, 34-54) for IIV3. IIV4 was more effective than IIV3 against the B lineage not included in IIV3, but comparative effectiveness against illnesses related to any influenza B favored neither vaccine valency. CONCLUSIONS: The uptake of quadrivalent inactivated influenza vaccines was not associated with increased protection against any influenza B illness, despite the higher effectiveness of quadrivalent vaccines against the added B virus lineage. Public health impact and cost-benefit analyses are needed globally.

Changes in Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence Over Time in 10 Sites in the United States, March-August, 2020.

BACKGROUND: Monitoring of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody prevalence can complement case reporting to inform more accurate estimates of SARS-CoV-2 infection burden, but few studies have undertaken repeated sampling over time on a broad geographic scale. METHODS: We performed serologic testing on a convenience sample of residual serum obtained from persons of all ages, at 10 sites in the United States from 23 March through 14 August 2020, from routine clinical testing at commercial laboratories. We standardized our seroprevalence rates by age and sex, using census population projections and adjusted for laboratory assay performance. Confidence intervals were generated with a 2-stage bootstrap. We used bayesian modeling to test whether seroprevalence changes over time were statistically significant. RESULTS: Seroprevalence remained below 10% at all sites except New York and Florida, where it reached 23.2% and 13.3%, respectively. Statistically significant increases in seroprevalence followed peaks in reported cases in New York, South Florida, Utah, Missouri, and Louisiana. In the absence of such peaks, some significant decreases were observed over time in New York, Missouri, Utah, and Western Washington. The estimated cumulative number of infections with detectable antibody response continued to exceed reported cases in all sites. CONCLUSIONS: Estimated seroprevalence was low in most sites, indicating that most people in the United States had not been infected with SARS-CoV-2 as of July 2020. The majority of infections are likely not reported. Decreases in seroprevalence may be related to changes in healthcare-seeking behavior, or evidence of waning of detectable anti-SARS-CoV-2 antibody levels at the population level. Thus, seroprevalence estimates may underestimate the cumulative incidence of infection.

Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization: COVID-19-Associated Hospitalization Surveillance Network and Behavioral Risk Factor Surveillance System.

BACKGROUND: Data on risk factors for coronavirus disease 2019 (COVID-19)-associated hospitalization are needed to guide prevention efforts and clinical care. We sought to identify factors independently associated with COVID-19-associated hospitalizations. METHODS: Community-dwelling adults (aged ≥18 years) in the United States hospitalized with laboratory-confirmed COVID-19 during 1 March-23 June 2020 were identified from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a multistate surveillance system. To calculate hospitalization rates by age, sex, and race/ethnicity strata, COVID-NET data served as the numerator and Behavioral Risk Factor Surveillance System estimates served as the population denominator for characteristics of interest. Underlying medical conditions examined included hypertension, coronary artery disease, history of stroke, diabetes, obesity, severe obesity, chronic kidney disease, asthma, and chronic obstructive pulmonary disease. Generalized Poisson regression models were used to calculate adjusted rate ratios (aRRs) for hospitalization. RESULTS: Among 5416 adults, hospitalization rates (all reported as aRR [95% confidence interval]) were higher among those with ≥3 underlying conditions (vs without) (5.0 [3.9-6.3]), severe obesity (4.4 [3.4-5.7]), chronic kidney disease (4.0 [3.0-5.2]), diabetes (3.2 [2.5-4.1]), obesity (2.9 [2.3-3.5]), hypertension (2.8 [2.3-3.4]), and asthma (1.4 [1.1-1.7]), after adjusting for age, sex, and race/ethnicity. Adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults aged ≥65 or 45-64 years (vs 18-44 years), males (vs females), and non-Hispanic black and other race/ethnicities (vs non-Hispanic whites). CONCLUSIONS: Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.

Comparison of the Immunogenicity of Cell Culture-Based and Recombinant Quadrivalent Influenza Vaccines to Conventional Egg-Based Quadrivalent Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized Open-Label Trial.

BACKGROUND: RIV4 and cell-culture based inactivated influenza vaccine (ccIIV4) have not been compared to egg-based IIV4 in healthcare personnel, a population with frequent influenza vaccination that may blunt vaccine immune responses over time. We conducted a randomized trial among healthcare personnel (HCP) aged 18-64 years to compare humoral immune responses to ccIIV4 and RIV4 to IIV4. METHODS: During the 2018-2019 season, participants were randomized to receive ccIIV4, RIV4, or IIV4 and had serum samples collected prevaccination, 1 and 6 months postvaccination. Serum samples were tested by hemagglutination inhibition (HI) for influenza A/H1N1, B/Yamagata, and B/Victoria and microneutralization (MN) for A/H3N2 against cell-grown vaccine reference viruses. Primary outcomes at 1 month were seroconversion rate (SCR), geometric mean titers (GMT), GMT ratio, and mean fold rise (MFR) in the intention-to-treat population. RESULTS: In total, 727 participants were included (283 ccIIV4, 202 RIV4, and 242 IIV4). At 1 month, responses to ccIIV4 were similar to IIV4 by SCR, GMT, GMT ratio, and MFR. RIV4 induced higher SCRs, GMTs, and MFRs than IIV4 against A/H1N1, A/H3N2, and B/Yamagata. The GMT ratio of RIV4 to egg-based vaccines was 1.5 (95% confidence interval [CI] 1.2-1.9) for A/H1N1, 3.0 (95% CI: 2.4-3.7) for A/H3N2, 1.1 (95% CI: .9-1.4) for B/Yamagata, and 1.1 (95% CI: .9-1.3) for B/Victoria. At 6 months, ccIIV4 recipients had similar GMTs to IIV4, whereas RIV4 recipients had higher GMTs against A/H3N2 and B/Yamagata. CONCLUSIONS: RIV4 resulted in improved antibody responses by HI and MN compared to egg-based vaccines against 3 of 4 cell-grown vaccine strains 1 month postvaccination, suggesting a possible additional benefit from RIV4. CLINICAL TRIALS REGISTRATION: NCT03722589.

Characteristics of Adults Aged 18-49 Years Without Underlying Conditions Hospitalized With Laboratory-Confirmed Coronavirus Disease 2019 in the United States: COVID-NET-March-August 2020.

Among 513 adults aged 18-49 years without underlying medical conditions hospitalized with coronavirus disease 2019 (COVID-19) during March 2020-August 2020, 22% were admitted to an intensive care unit, 10% required mechanical ventilation, and 3 patients died (0.6%). These data demonstrate that healthy younger adults can develop severe COVID-19.

Comparison of Estimated Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence Through Commercial Laboratory Residual Sera Testing and a Community Survey.

We compared severe acute respiratory syndrome coronavirus 2 seroprevalence estimated from commercial laboratory residual sera and a community household survey in metropolitan Atlanta during April and May 2020 and found these 2 estimates to be similar (4.94% vs 3.18%). Compared with more representative surveys, commercial sera can provide an approximate measure of seroprevalence.