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Prevention and control of seasonal influenza with vaccines: Recommendations of the Advisory Committee On Immunization Practices — United States, 2023–24 influenza season
Grohskopf LA , Blanton LH , Ferdinands JM , Chung JR , Broder KR , Talbot HK . MMWR Recommendations and Reports 2023 72 (2) This report updates the 2022–23 recommendations of the Advisory Committee on Immunization Practices (ACIP) concerning the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2022;71[No. RR-1]:1–28). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. All seasonal influenza vaccines expected to be available in the United States for the 2023–24 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. 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. Influenza vaccines might be available as early as July or August, but 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 during these months if vaccine is available. ACIP recommends that all persons aged ≥6 months who do not have contraindications receive a licensed and age-appropriate seasonal influenza vaccine. 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. 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. Primary updates to this report include the following two topics: 1) the composition of 2023–24 U.S. seasonal influenza vaccines and 2) updated recommendations regarding influenza vaccination of persons with egg allergy. First, the composition of 2023–24 U.S. influenza vaccines includes an update to the influenza A(H1N1)pdm09 component. U.S.-licensed influenza vaccines will contain HA derived from 1) an influenza A/Victoria/4897/2022 (H1N1)pdm09-like virus (for egg-based vaccines) or an influenza A/Wisconsin/67/2022 (H1N1)pdm09-like virus (for cell culture-based and recombinant vaccines); 2) 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 and recombinant vaccines); 3) an influenza B/Austria/1359417/2021 (Victoria lineage)-like virus; and 4) an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus. Second, ACIP recommends that all persons aged ≥6 months with egg allergy should receive influenza vaccine. Any influenza vaccine (egg based or nonegg based) that is otherwise appropriate for the recipient’s age and health status can be used. It is no longer recommended that persons who have had an allergic reaction to egg involving symptoms other than urticaria should be vaccinated in an inpatient or outpatient medical setting supervised by a health care provider who is able to recognize and man ge severe allergic reactions if an egg-based vaccine is used. Egg allergy alone necessitates no additional safety measures for influenza vaccination beyond those recommended for any recipient of any vaccine, regardless of severity of previous reaction to egg. All vaccines should be administered in settings in which personnel and equipment needed for rapid recognition and treatment of acute hypersensitivity reactions are available. © (2023). All Rights Reserved. |
Estimating the burden of influenza hospitalizations across multiple seasons using capture-recapture
Howa AC , Zhu Y , Wyatt D , Markus T , Chappell JD , Halasa N , Trabue CH , Olson S , Ferdinands J , Garg S , Schaffner W , Grijalva CG , Talbot HK . J Infect Dis 2023 INTRODUCTION: Influenza remains an important cause of hospitalizations in the United States. Estimating the number of influenza hospitalizations is vital for public health decision making. Combining existing surveillance systems through capture-recapture methods allows for more comprehensive burden estimations. METHODS: Data from independent surveillance systems were combined using capture-recapture methods to estimate influenza hospitalization rates for children and adults in Middle Tennessee during consecutive influenza seasons from 2016-17 through 2019-20. EIP identified cases through surveillance of laboratory results for hospitalized children and adults. HAIVEN and NVSN recruited hospitalized patients with respiratory symptoms or fever. Population-based influenza rates and the proportion of cases detected by each surveillance system were calculated. RESULTS: Estimated overall influenza hospitalization rates ranged from 23 influenza-related hospitalizations per 10,000 persons in 2016-17 to 40 per 10,000 persons in 2017-18. Adults age ≥65 years had the highest hospitalization rates across seasons and experienced a rate of 170 hospitalizations per 10,000 persons during the 2017-18 season. EIP consistently identified a higher proportion of influenza cases for adults and children compared with HAIVEN and NVSN, respectively. CONCLUSION: Current surveillance systems underestimate the influenza burden. Capture-recapture provides an alternative approach to use data from independent surveillance systems and complement population-based burden estimates. |
Effectiveness of Influenza Vaccine for Preventing Laboratory-Confirmed Influenza Hospitalizations in Immunocompromised Adults (preprint)
Hughes K , Middleton DB , Nowalk MP , Balasubramani GK , Martin ET , Gaglani M , Talbot HK , Patel MM , Ferdinands JM , Zimmerman RK , Silveira FP . medRxiv 2020 2020.10.08.20208579 Background Yearly influenza immunization is recommended for immunocompromised (IC) individuals, although immune responses are lower than that for the non-immunocompromised and the data on vaccine effectiveness (VE) in the IC is scarce. We evaluated VE against influenza-associated hospitalization among IC adults.Methods We analyzed data from adults ≥ 18 years hospitalized with acute respiratory illness (ARI) during the 2017-2018 influenza season at 10 hospitals in the United States. IC adults were identified using pre-specified case-definitions, utilizing electronic medical record data. VE was evaluated with a test-negative case-control design using multivariate logistic regression with PCR-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, enrolling site, illness onset date, race, days from onset to specimen collection, self-reported health, and self-reported hospitalizations.Results Of 3,524 adults hospitalized with ARI, 1,210 (34.3%) had an immunocompromising condition. IC adults were more likely to be vaccinated than non-IC (69.5% vs 65.2%), and less likely to have influenza (22% vs 27.8%). The mean age did not differ among IC and non-IC (61.4 vs 60.8 years old). The overall VE against influenza hospitalization, including immunocompetent adults, was 33% (95% CI, 21% to 44%). VE among IC vs non-IC adults was lower at 5% (−29% to 31%) vs. 41% (27% to 52%) (p<0.05 for interaction term).Conclusions VE in one influenza season was very low among IC individuals. Future efforts should include evaluation of VE among the different immunocompromising conditions and whether enhanced vaccines improve the suboptimal effectiveness among the immunocompromised.Competing Interest StatementDBM has received personal fees from Sequris, Pfizer, and Sanofi Pasteur, and grants from Pfizer. JF reports non-financial support from the Institute for Influenza Epidemiology. RKZ has received grants from Sanofi Pasteur and Merck & Co. All other authors report no potential conflicts.Clinical TrialThis study was not registered in ClinicalTrials.gov because it doesn't meet NIH's definition of a clinical trial.Funding StatementThis study was funded by the CDC (cooperative agreement IP15-002). Vanderbilt also received support from CTSA award number UL1 TR002243 from the National Center for Advancing Translational Sciences.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study protocol was reviewed by the Institutional Review Board at each participating institution and CDC, as detailed below: CDC's IRB: ethical approval given University of Pittsburgh IRB: ethical approval given University of Michigan IRB: ethical approval given Baylor Scott & White Health IRB: ethical approval given Vanderbilt University IRB: ethical approval given All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData may be made available after completion of the study. |
Evaluation of correlates of protection against influenza A(H3N2) and A(H1N1)pdm09 infection: Applications to the hospitalized patient population (preprint)
Petrie JG , Martin ET , Truscon R , Johnson E , Cheng CK , McSpadden EJ , Malosh RE , Lauring AS , Lamerato LE , Eichelberger MC , Ferdinands JM , Monto AS . bioRxiv 2018 416628 Background Influenza vaccines are important for prevention of influenza-associated hospitalization. Assessments of serologic correlates of protection can support interpretation of influenza vaccine effectiveness evaluations in hospitalized populations.Methods Serum specimens collected at admission from adults hospitalized for treatment of acute respiratory illnesses during two influenza seasons were tested in hemagglutination-inhibition (HAI) and neuraminidase-inhibition (NAI) assays. We evaluated the suitability of these specimens as proxies for pre-infection immune status, and measured associations between antibody titers and influenza vaccination and infectionResults Specimens were collected within 3 days of illness onset from 65% of participants; geometric mean titers (GMTs) did not vary by day of collection. In both seasons, vaccinated participants had higher HAI and NAI GMTs than unvaccinated participants. HAI titers against the 2014-2015 A(H3N2) vaccine strain did not correlate with protection from infection with antigenically-drifted A(H3N2) viruses that circulated that season. In contrast, higher HAI titers against the A(H1N1)pdm09 vaccine strain were associated with reduced odds of A(H1N1)pdm09 infection in 2015-2016.Conclusions Serum collected after hospital admission can be used to assess correlates of protection against influenza infection. Broader implementation of similar studies would provide an opportunity to understand the successes and shortcomings of current influenza vaccines.We thank Jin Gao and Laura Couzens for technical support and are indebted to St Jude Children’s Research Hospital for plasmids that were used to generate reassortant influenza viruses. |
Antibodies against egg- and cell-grown influenza A(H3N2) viruses in adults hospitalized during the 2017-2018 season (preprint)
Levine MZ , Martin ET , Petrie JG , Lauring AS , Holiday C , Jefferson S , Fitzsimmons WJ , Johnson E , Ferdinands JM , Monto AS . bioRxiv 2018 439471 Background The 2017-2018 US influenza season was severe with low vaccine effectiveness. Circulating A(H3N2) viruses from multiple genetic groups were antigenically similar to cell-grown vaccine strains. However, most influenza vaccines are egg-propagated.Methods Serum was collected shortly after illness onset from 15 PCR confirmed A(H3N2) infected cases and 15 uninfected (controls) hospitalized adults enrolled in an influenza vaccine effectiveness study.Geometric mean titers against egg- and cell-grown A/Hong Kong/4801/2014 A(H3N2) vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by microneutralization (MN) assays. Independent effects of strain-specific titers on susceptibility were estimated by logistic regression.Results MN titers against egg-A/Hong Kong were significantly higher among those who were vaccinated (MN GMT: 173 vs 41; P = 0.01). However, antibody titers to cell-grown viruses were much lower in all individuals (P>0.05) regardless of vaccination. In unadjusted models, a 2-fold increase in MN titers against egg-A/Hong Kong was not significantly protective against infection (29% reduction; p=0.09), but a similar increase in cell-A/Washington titer (3C.2a2) was protective (60% reduction; p=0.02). A similar increase in egg-A/Hong Kong titer was not significantly associated with odds of infection when adjusting for MN titers against A/Washington (15% reduction; P=0.61). A 54% reduction of odds of infection was observed with a 2-fold increase in A/Washington (not significant; P=0.07), adjusted for egg-A/Hong Kong titer.Conclusion Although individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain, antibody responses to cell-grown circulating viruses may not be sufficient to provide protection, likely due to egg-adaptation in the vaccine.We thank Maryna Eichelberger, Hongquan Wan, Jin Gao, and Laura Couzens (Food and Drug Administration) for technical support and providing reassortant influenza viruses for use in the enzyme-linked lectin assays. St Jude Children’s Research Hospital provided plasmids that were used to generate these reassortant influenza viruses. We thank Mrs F Liaini Gross, Lauren Horner and Makeda Kay from Influenza Division, Centers for Disease Control and Prevention for technical support for virus propagation and specimen management. |
K-medoids clustering of hospital admission characteristics to classify severity of influenza virus infection
Leis AM , McSpadden E , Segaloff HE , Lauring AS , Cheng C , Petrie JG , Lamerato LE , Patel M , Flannery B , Ferdinands J , Karvonen-Gutierrez CA , Monto A , Martin ET . Influenza Other Respir Viruses 2023 17 (3) e13120 BACKGROUND: Patients are admitted to the hospital for respiratory illness at different stages of their disease course. It is important to appropriately analyse this heterogeneity in surveillance data to accurately measure disease severity among those hospitalized. The purpose of this study was to determine if unique baseline clusters of influenza patients exist and to examine the association between cluster membership and in-hospital outcomes. METHODS: Patients hospitalized with influenza at two hospitals in Southeast Michigan during the 2017/2018 (n = 242) and 2018/2019 (n = 115) influenza seasons were included. Physiologic and laboratory variables were collected for the first 24 h of the hospital stay. K-medoids clustering was used to determine groups of individuals based on these values. Multivariable linear regression or Firth's logistic regression were used to examine the association between cluster membership and clinical outcomes. RESULTS: Three clusters were selected for 2017/2018, mainly differentiated by blood glucose level. After adjustment, those in C(17)1 had 5.6 times the odds of mechanical ventilator use than those in C(17)2 (95% CI: 1.49, 21.1) and a significantly longer mean hospital length of stay than those in both C(17)2 (mean 1.5 days longer, 95% CI: 0.2, 2.7) and C(17)3 (mean 1.4 days longer, 95% CI: 0.3, 2.5). Similar results were seen between the two clusters selected for 2018/2019. CONCLUSION: In this study of hospitalized influenza patients, we show that distinct clusters with higher disease acuity can be identified and could be targeted for evaluations of vaccine and influenza antiviral effectiveness against disease attenuation. The association of higher disease acuity with glucose level merits evaluation. |
Evaluating potential impacts of a preferential vaccine recommendation for adults aged 65 and older on United States influenza burden
Morris SE , Grohskopf LA , Ferdinands JM , Reed C , Biggerstaff M . Epidemiology 2023 34 (3) 345-352 BACKGROUND: High-dose, adjuvanted, and recombinant influenza vaccines may offer improved effectiveness among older adults compared to standard-dose, unadjuvanted, inactivated vaccines. However, the Advisory Committee on Immunization Practices (ACIP) only recently recommended preferential use of these 'higher-dose or adjuvanted' vaccines. One concern was that individuals might delay or decline vaccination if a preferred vaccine is not readily available. METHODS: We mathematically model how a recommendation for preferential use of higher-dose or adjuvanted vaccines in adults ≥65 years might impact influenza burden in the United States during exemplar 'high-' and 'low-' severity seasons. We assume higher-dose or adjuvanted vaccines are more effective than standard vaccines and that such a recommendation would increase uptake of the former but could cause (i) delays in administration of additional higher-dose or adjuvanted vaccines relative to standard vaccines and/or (ii) reductions in overall coverage if individuals only offered standard vaccines forego vaccination. RESULTS: In a best-case scenario, assuming no delay or coverage reduction, a new recommendation could decrease hospitalizations and deaths in adults ≥65 years by 0-4% compared with current uptake. However, intermediate and worst-case scenarios, with assumed delays of 3 or 6 weeks and/or 10 or 20% reductions in coverage, included projections in which hospitalizations and deaths increased by over 7%. CONCLUSIONS: We estimate that increased use of higher-dose or adjuvanted vaccines could decrease influenza burden in adults ≥65 in the United States provided there is timely and adequate access to these vaccines, and that standard vaccines are administered when they are unavailable. |
Prevalence and clinical outcomes of respiratory syncytial virus versus influenza in adults hospitalized with acute respiratory illness from a prospective multicenter study
Begley KM , Monto AS , Lamerato LE , Malani AN , Lauring AS , Talbot HK , Gaglani M , McNeal T , Silveira FP , Zimmerman RK , Middleton DB , Ghamande S , Murthy K , Kim L , Ferdinands JM , Patel MM , Martin ET . Clin Infect Dis 2023 BACKGROUND: Current understanding of severe RSV infections in adults is limited by clinical under-recognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses in a prospective national surveillance network. METHODS: Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across three respiratory seasons from hospitals participating across all sites of the U.S. Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN, 2016-2019). All participants were tested for RSV and influenza by RT-PCR. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes. RESULTS: Among 10,311 hospitalized adults, 6% tested positive for RSV (n=622), 18.8% positive for influenza (n=1,940), and 75.1% negative for RSV and influenza (n=7,749). Congestive Heart Failure (CHF) or Chronic Obstructive Pulmonary Disease (COPD) was more frequent among adults with RSV than influenza (CHF: 37.3% vs. 28.8%, p<0.0001; COPD: 47.6% vs. 35.8%, p<0.0001). Patients with RSV more frequently had longer admissions [OR=1.38 (95% CI: 1.06-1.80) for stays >one week] and mechanical ventilation [OR=1.45 (95% CI: 1.09-1.93)] compared with influenza, but not compared to the influenza negative group [OR=1.03 (95% CI: 0.82-1.28); OR=1.17 (0.91-1.49), respectively.]. CONCLUSIONS: The prevalence of RSV across three recent respiratory illness seasons was considerable. Our findings suggest those with RSV might incur worse outcomes than influenza in hospitalized adults and frequently have pre-existing cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults experiencing severe ARI. |
Waning of vaccine effectiveness against moderate and severe covid-19 among adults in the US from the VISION network: test negative, case-control study.
Ferdinands JM , Rao S , Dixon BE , Mitchell PK , DeSilva MB , Irving SA , Lewis N , Natarajan K , Stenehjem E , Grannis SJ , Han J , McEvoy C , Ong TC , Naleway AL , Reese SE , Embi PJ , Dascomb K , Klein NP , Griggs EP , Liao IC , Yang DH , Fadel WF , Grisel N , Goddard K , Patel P , Murthy K , Birch R , Valvi NR , Arndorfer J , Zerbo O , Dickerson M , Raiyani C , Williams J , Bozio CH , Blanton L , Link-Gelles R , Barron MA , Gaglani M , Thompson MG , Fireman B . BMJ 2022 379 e072141 OBJECTIVE: To estimate the effectiveness of mRNA vaccines against moderate and severe covid-19 in adults by time since second, third, or fourth doses, and by age and immunocompromised status. DESIGN: Test negative case-control study. SETTING: Hospitals, emergency departments, and urgent care clinics in 10 US states, 17 January 2021 to 12 July 2022. PARTICIPANTS: 893 461 adults (≥18 years) admitted to one of 261 hospitals or to one of 272 emergency department or 119 urgent care centers for covid-like illness tested for SARS-CoV-2. MAIN OUTCOME MEASURES: The main outcome was waning of vaccine effectiveness with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine during the omicron and delta periods, and the period before delta was dominant using logistic regression conditioned on calendar week and geographic area while adjusting for age, race, ethnicity, local virus circulation, immunocompromised status, and likelihood of being vaccinated. RESULTS: 45 903 people admitted to hospital with covid-19 (cases) were compared with 213 103 people with covid-like illness who tested negative for SARS-CoV-2 (controls), and 103 287 people admitted to emergency department or urgent care with covid-19 (cases) were compared with 531 168 people with covid-like illness who tested negative for SARS-CoV-2. In the omicron period, vaccine effectiveness against covid-19 requiring admission to hospital was 89% (95% confidence interval 88% to 90%) within two months after dose 3 but waned to 66% (63% to 68%) by four to five months. Vaccine effectiveness of three doses against emergency department or urgent care visits was 83% (82% to 84%) initially but waned to 46% (44% to 49%) by four to five months. Waning was evident in all subgroups, including young adults and individuals who were not immunocompromised; although waning was morein people who were immunocompromised. Vaccine effectiveness increased among most groups after a fourth dose in whom this booster was recommended. CONCLUSIONS: Effectiveness of mRNA vaccines against moderate and severe covid-19 waned with time after vaccination. The findings support recommendations for a booster dose after a primary series and consideration of additional booster doses. |
Prevention and control of seasonal influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022-23 Influenza Season
Grohskopf LA , Blanton LH , Ferdinands JM , Chung JR , Broder KR , Talbot HK , Morgan RL , Fry AM . MMWR Recomm Rep 2022 71 (1) 1-28 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. |
Effectiveness of Homologous and Heterologous COVID-19 Booster Doses Following 1 Ad.26.COV2.S (Janssen [Johnson & Johnson]) Vaccine Dose Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults - VISION Network, 10 States, December 2021-March 2022.
Natarajan K , Prasad N , Dascomb K , Irving SA , Yang DH , Gaglani M , Klein NP , DeSilva MB , Ong TC , Grannis SJ , Stenehjem E , Link-Gelles R , Rowley EA , Naleway AL , Han J , Raiyani C , Benitez GV , Rao S , Lewis N , Fadel WF , Grisel N , Griggs EP , Dunne MM , Stockwell MS , Mamawala M , McEvoy C , Barron MA , Goddard K , Valvi NR , Arndorfer J , Patel P , Mitchell PK , Smith M , Kharbanda AB , Fireman B , Embi PJ , Dickerson M , Davis JM , Zerbo O , Dalton AF , Wondimu MH , Azziz-Baumgartner E , Bozio CH , Reynolds S , Ferdinands J , Williams J , Schrag SJ , Verani JR , Ball S , Thompson MG , Dixon BE . MMWR Morb Mortal Wkly Rep 2022 71 (13) 495-502 CDC recommends that all persons aged ≥18 years receive a single COVID-19 vaccine booster dose ≥2 months after receipt of an Ad.26.COV2.S (Janssen [Johnson & Johnson]) adenovirus vector-based primary series vaccine; a heterologous COVID-19 mRNA vaccine is preferred over a homologous (matching) Janssen vaccine for booster vaccination. This recommendation was made in light of the risks for rare but serious adverse events following receipt of a Janssen vaccine, including thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome(†) (1), and clinical trial data indicating similar or higher neutralizing antibody response following heterologous boosting compared with homologous boosting (2). Data on real-world vaccine effectiveness (VE) of different booster strategies following a primary Janssen vaccine dose are limited, particularly during the period of Omicron variant predominance. The VISION Network(§) determined real-world VE of 1 Janssen vaccine dose and 2 alternative booster dose strategies: 1) a homologous booster (i.e., 2 Janssen doses) and 2) a heterologous mRNA booster (i.e., 1 Janssen dose/1 mRNA dose). In addition, VE of these booster strategies was compared with VE of a homologous booster following mRNA primary series vaccination (i.e., 3 mRNA doses). The study examined 80,287 emergency department/urgent care (ED/UC) visits(¶) and 25,244 hospitalizations across 10 states during December 16, 2021-March 7, 2022, when Omicron was the predominant circulating variant.** VE against laboratory-confirmed COVID-19-associated ED/UC encounters was 24% after 1 Janssen dose, 54% after 2 Janssen doses, 79% after 1 Janssen/1 mRNA dose, and 83% after 3 mRNA doses. VE for the same vaccination strategies against laboratory-confirmed COVID-19-associated hospitalizations were 31%, 67%, 78%, and 90%, respectively. All booster strategies provided higher protection than a single Janssen dose against ED/UC visits and hospitalizations during Omicron variant predominance. Vaccination with 1 Janssen/1 mRNA dose provided higher protection than did 2 Janssen doses against COVID-19-associated ED/UC visits and was comparable to protection provided by 3 mRNA doses during the first 120 days after a booster dose. However, 3 mRNA doses provided higher protection against COVID-19-associated hospitalizations than did other booster strategies during the same time interval since booster dose. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when eligible. Adults who received a primary Janssen vaccine dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable. Further investigation of the durability of protection afforded by different booster strategies is warranted. |
Influence of disease attenuation on relative influenza vaccine effectiveness by vaccine type
Ferdinands JM , Patel M . Vaccine 2022 40 (19) 2797-2801 Benefit conferred by "enhanced" influenza vaccines is often measured by relative vaccine effectiveness, (rVE), which compares disease risk among groups of people who received alternative vaccines. Differences in attenuation of illness severity by vaccine types could manifest as differences in rVE. Using a simulated VE study and cohort of adults aged ≥ 65 years, we examined how rVE varied with assumptions about attenuation of disease severity conferred by standard and enhanced vaccines and how this variation could lead to differing estimates of rVE for prevention of moderate (i.e., outpatient) versus severe (i.e., inpatient) influenza illness. We found that if enhanced vaccines attenuated severe illness more than moderate illness, then rVE observed against severe disease could be higher than rVE observed against moderate disease. Thus, if differences in disease attenuation by vaccine type occurs, estimates of rVE may vary for influenza outcomes of differing levels of severity. |
Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA Vaccination in Preventing COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Nonimmunocompromised Children and Adolescents Aged 5-17 Years - VISION Network, 10 States, April 2021-January 2022.
Klein NP , Stockwell MS , Demarco M , Gaglani M , Kharbanda AB , Irving SA , Rao S , Grannis SJ , Dascomb K , Murthy K , Rowley EA , Dalton AF , DeSilva MB , Dixon BE , Natarajan K , Stenehjem E , Naleway AL , Lewis N , Ong TC , Patel P , Konatham D , Embi PJ , Reese SE , Han J , Grisel N , Goddard K , Barron MA , Dickerson M , Liao IC , Fadel WF , Yang DH , Arndorfer J , Fireman B , Griggs EP , Valvi NR , Hallowell C , Zerbo O , Reynolds S , Ferdinands J , Wondimu MH , Williams J , Bozio CH , Link-Gelles R , Azziz-Baumgartner E , Schrag SJ , Thompson MG , Verani JR . MMWR Morb Mortal Wkly Rep 2022 71 (9) 352-358 The efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine against laboratory-confirmed COVID-19 exceeded 90% in clinical trials that included children and adolescents aged 5-11, 12-15, and 16-17 years (1-3). Limited real-world data on 2-dose mRNA vaccine effectiveness (VE) in persons aged 12-17 years (referred to as adolescents in this report) have also indicated high levels of protection against SARS-CoV-2 (the virus that causes COVID-19) infection and COVID-19-associated hospitalization (4-6); however, data on VE against the SARS-CoV-2 B.1.1.529 (Omicron) variant and duration of protection are limited. Pfizer-BioNTech VE data are not available for children aged 5-11 years. In partnership with CDC, the VISION Network* examined 39,217 emergency department (ED) and urgent care (UC) encounters and 1,699 hospitalizations(†) among persons aged 5-17 years with COVID-19-like illness across 10 states during April 9, 2021-January 29, 2022,(§) to estimate VE using a case-control test-negative design. Among children aged 5-11 years, VE against laboratory-confirmed COVID-19-associated ED and UC encounters 14-67 days after dose 2 (the longest interval after dose 2 in this age group) was 46%. Among adolescents aged 12-15 and 16-17 years, VE 14-149 days after dose 2 was 83% and 76%, respectively; VE ≥150 days after dose 2 was 38% and 46%, respectively. Among adolescents aged 16-17 years, VE increased to 86% ≥7 days after dose 3 (booster dose). VE against COVID-19-associated ED and UC encounters was substantially lower during the Omicron predominant period than the B.1.617.2 (Delta) predominant period among adolescents aged 12-17 years, with no significant protection ≥150 days after dose 2 during Omicron predominance. However, in adolescents aged 16-17 years, VE during the Omicron predominant period increased to 81% ≥7 days after a third booster dose. During the full study period, including pre-Delta, Delta, and Omicron predominant periods, VE against laboratory-confirmed COVID-19-associated hospitalization among children aged 5-11 years was 74% 14-67 days after dose 2, with wide CIs that included zero. Among adolescents aged 12-15 and 16-17 years, VE 14-149 days after dose 2 was 92% and 94%, respectively; VE ≥150 days after dose 2 was 73% and 88%, respectively. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations, including a booster dose for those aged 12-17 years. |
Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance - VISION Network, 10 States, August 2021-January 2022.
Ferdinands JM , Rao S , Dixon BE , Mitchell PK , DeSilva MB , Irving SA , Lewis N , Natarajan K , Stenehjem E , Grannis SJ , Han J , McEvoy C , Ong TC , Naleway AL , Reese SE , Embi PJ , Dascomb K , Klein NP , Griggs EP , Konatham D , Kharbanda AB , Yang DH , Fadel WF , Grisel N , Goddard K , Patel P , Liao IC , Birch R , Valvi NR , Reynolds S , Arndorfer J , Zerbo O , Dickerson M , Murthy K , Williams J , Bozio CH , Blanton L , Verani JR , Schrag SJ , Dalton AF , Wondimu MH , Link-Gelles R , Azziz-Baumgartner E , Barron MA , Gaglani M , Thompson MG , Fireman B . MMWR Morb Mortal Wkly Rep 2022 71 (7) 255-263 CDC recommends that all persons aged ≥12 years receive a booster dose of COVID-19 mRNA vaccine ≥5 months after completion of a primary mRNA vaccination series and that immunocompromised persons receive a third primary dose.* Waning of vaccine protection after 2 doses of mRNA vaccine has been observed during the period of the SARS-CoV-2 B.1.617.2 (Delta) variant predominance(†) (1-5), but little is known about durability of protection after 3 doses during periods of Delta or SARS-CoV-2 B.1.1.529 (Omicron) variant predominance. A test-negative case-control study design using data from eight VISION Network sites(§) examined vaccine effectiveness (VE) against COVID-19 emergency department/urgent care (ED/UC) visits and hospitalizations among U.S. adults aged ≥18 years at various time points after receipt of a second or third vaccine dose during two periods: Delta variant predominance and Omicron variant predominance (i.e., periods when each variant accounted for ≥50% of sequenced isolates).(¶) Persons categorized as having received 3 doses included those who received a third dose in a primary series or a booster dose after a 2 dose primary series (including the reduced-dosage Moderna booster). The VISION Network analyzed 241,204 ED/UC encounters** and 93,408 hospitalizations across 10 states during August 26, 2021-January 22, 2022. VE after receipt of both 2 and 3 doses was lower during the Omicron-predominant than during the Delta-predominant period at all time points evaluated. During both periods, VE after receipt of a third dose was higher than that after a second dose; however, VE waned with increasing time since vaccination. During the Omicron period, VE against ED/UC visits was 87% during the first 2 months after a third dose and decreased to 66% among those vaccinated 4-5 months earlier; VE against hospitalizations was 91% during the first 2 months following a third dose and decreased to 78% ≥4 months after a third dose. For both Delta- and Omicron-predominant periods, VE was generally higher for protection against hospitalizations than against ED/UC visits. All eligible persons should remain up to date with recommended COVID-19 vaccinations to best protect against COVID-19-associated hospitalizations and ED/UC visits. |
Effectiveness of a Third Dose of mRNA Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance - VISION Network, 10 States, August 2021-January 2022.
Thompson MG , Natarajan K , Irving SA , Rowley EA , Griggs EP , Gaglani M , Klein NP , Grannis SJ , DeSilva MB , Stenehjem E , Reese SE , Dickerson M , Naleway AL , Han J , Konatham D , McEvoy C , Rao S , Dixon BE , Dascomb K , Lewis N , Levy ME , Patel P , Liao IC , Kharbanda AB , Barron MA , Fadel WF , Grisel N , Goddard K , Yang DH , Wondimu MH , Murthy K , Valvi NR , Arndorfer J , Fireman B , Dunne MM , Embi P , Azziz-Baumgartner E , Zerbo O , Bozio CH , Reynolds S , Ferdinands J , Williams J , Link-Gelles R , Schrag SJ , Verani JR , Ball S , Ong TC . MMWR Morb Mortal Wkly Rep 2022 71 (4) 139-145 Estimates of COVID-19 mRNA vaccine effectiveness (VE) have declined in recent months (1,2) because of waning vaccine induced immunity over time,* possible increased immune evasion by SARS-CoV-2 variants (3), or a combination of these and other factors. CDC recommends that all persons aged ≥12 years receive a third dose (booster) of an mRNA vaccine ≥5 months after receipt of the second mRNA vaccine dose and that immunocompromised individuals receive a third primary dose.(†) A third dose of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine increases neutralizing antibody levels (4), and three recent studies from Israel have shown improved effectiveness of a third dose in preventing COVID-19 associated with infections with the SARS-CoV-2 B.1.617.2 (Delta) variant (5-7). Yet, data are limited on the real-world effectiveness of third doses of COVID-19 mRNA vaccine in the United States, especially since the SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in mid-December 2021. The VISION Network(§) examined VE by analyzing 222,772 encounters from 383 emergency departments (EDs) and urgent care (UC) clinics and 87,904 hospitalizations from 259 hospitals among adults aged ≥18 years across 10 states from August 26, 2021(¶) to January 5, 2022. Analyses were stratified by the period before and after the Omicron variant became the predominant strain (>50% of sequenced viruses) at each study site. During the period of Delta predominance across study sites in the United States (August-mid-December 2021), VE against laboratory-confirmed COVID-19-associated ED and UC encounters was 86% 14-179 days after dose 2, 76% ≥180 days after dose 2, and 94% ≥14 days after dose 3. Estimates of VE for the same intervals after vaccination during Omicron variant predominance were 52%, 38%, and 82%, respectively. During the period of Delta variant predominance, VE against laboratory-confirmed COVID-19-associated hospitalizations was 90% 14-179 days after dose 2, 81% ≥180 days after dose 2, and 94% ≥14 days after dose 3. During Omicron variant predominance, VE estimates for the same intervals after vaccination were 81%, 57%, and 90%, respectively. The highest estimates of VE against COVID-19-associated ED and UC encounters or hospitalizations during both Delta- and Omicron-predominant periods were among adults who received a third dose of mRNA vaccine. All unvaccinated persons should get vaccinated as soon as possible. All adults who have received mRNA vaccines during their primary COVID-19 vaccination series should receive a third dose when eligible, and eligible persons should stay up to date with COVID-19 vaccinations. |
Effectiveness of two-dose vaccination with mRNA COVID-19 vaccines against COVID-19-associated hospitalizations among immunocompromised adults-Nine States, January-September 2021.
Embi PJ , Levy ME , Naleway AL , Patel P , Gaglani M , Natarajan K , Dascomb K , Ong TC , Klein NP , Liao IC , Grannis SJ , Han J , Stenehjem E , Dunne MM , Lewis N , Irving SA , Rao S , McEvoy C , Bozio CH , Murthy K , Dixon BE , Grisel N , Yang DH , Goddard K , Kharbanda AB , Reynolds S , Raiyani C , Fadel WF , Arndorfer J , Rowley EA , Fireman B , Ferdinands J , Valvi NR , Ball SW , Zerbo O , Griggs EP , Mitchell PK , Porter RM , Kiduko SA , Blanton L , Zhuang Y , Steffens A , Reese SE , Olson N , Williams J , Dickerson M , McMorrow M , Schrag SJ , Verani JR , Fry AM , Azziz-Baumgartner E , Barron MA , Thompson MG , DeSilva MB . Am J Transplant 2022 22 (1) 306-314 Immunocompromised persons, defined as those with suppressed humoral or cellular immunity resulting from health conditions or medications, account for approximately 3% of the US adult population.1 Immunocompromised adults are at increased risk for severe COVID-19 outcomes2 and might not acquire the same level of protection from COVID-19 mRNA vaccines as do immunocompetent adults.3 , 4 To evaluate vaccine effectiveness (VE) among immunocompromised adults, data from the VISION Network1 on hospitalizations among persons aged ≥18 years with COVID-19–like illness from 187 hospitals in nine states during January 17–September 5, 2021 were analyzed. Using selected discharge diagnoses,2 VE against COVID-19–associated hospitalization conferred by completing a two-dose series of an mRNA COVID-19 vaccine ≥14 days before the index hospitalization date3 (i.e., being fully vaccinated) was evaluated using a test-negative design comparing 20,101 immunocompromised adults (10,564 [53%] of whom were fully vaccinated) and 69,116 immunocompetent adults (29,456 [43%] of whom were fully vaccinated). VE of two doses of mRNA COVID-19 vaccine against COVID-19–associated hospitalization was lower among immunocompromised patients (77%; 95% confidence interval [CI] = 74%–80%) than among immunocompetent patients (90%; 95% CI = 89%–91%). This difference persisted irrespective of mRNA vaccine product, age group, and timing of hospitalization relative to SARS-CoV-2 (the virus that causes COVID-19) B.1.617.2 (Delta) variant predominance in the state of hospitalization. VE varied across immunocompromising condition subgroups, ranging from 59% (organ or stem cell transplant recipients) to 81% (persons with a rheumatologic or inflammatory disorder). Immunocompromised persons benefit from mRNA COVID-19 vaccination but are less protected from severe COVID-19 outcomes than are immunocompetent persons, and VE varies among immunocompromised subgroups. Immunocompromised persons receiving mRNA COVID-19 vaccines should receive three doses and a booster, consistent with CDC recommendations,5 practice nonpharmaceutical interventions, and, if infected, be monitored closely and considered early for proven therapies that can prevent severe outcomes. |
Interpretation of Relative Efficacy and Effectiveness for Influenza Vaccines
Lewis NM , Chung JR , Uyeki TM , Grohskopf L , Ferdinands JM , Patel MM . Clin Infect Dis 2021 75 (1) 170-175 Relative vaccine effectiveness (rVE) are metrics commonly reported to compare absolute VE (aVE) of two vaccine products. Estimates of rVE for enhanced influenza vaccines (eIV) vs. standard inactivated influenza vaccine (IIV) have been assessed across different seasons, influenza-specific endpoints, and nonspecific endpoints (e.g., all-cause cardiovascular hospitalizations). To illustrate the challenges of comparability across studies, we conducted a scenario analysis to evaluate the effects of varying absolute VE (aVE) of IIV (i.e., as compared with placebo) on the interpretation of rVE of eIV vs IIV. We show that estimates of rVE might not be comparable across studies because additional benefits commensurate with a given estimate of rVE are dependent on the aVE for the comparator vaccine, which can depend on factors such as host response to vaccine, virus type, and clinical endpoint evaluated. These findings have implications for interpretation of rVE across studies and for sample size considerations in future trials. |
Laboratory-Confirmed COVID-19 Among Adults Hospitalized with COVID-19-Like Illness with Infection-Induced or mRNA Vaccine-Induced SARS-CoV-2 Immunity - Nine States, January-September 2021.
Bozio CH , Grannis SJ , Naleway AL , Ong TC , Butterfield KA , DeSilva MB , Natarajan K , Yang DH , Rao S , Klein NP , Irving SA , Dixon BE , Dascomb K , Liao IC , Reynolds S , McEvoy C , Han J , Reese SE , Lewis N , Fadel WF , Grisel N , Murthy K , Ferdinands J , Kharbanda AB , Mitchell PK , Goddard K , Embi PJ , Arndorfer J , Raiyani C , Patel P , Rowley EA , Fireman B , Valvi NR , Griggs EP , Levy ME , Zerbo O , Porter RM , Birch RJ , Blanton L , Ball SW , Steffens A , Olson N , Williams J , Dickerson M , McMorrow M , Schrag SJ , Verani JR , Fry AM , Azziz-Baumgartner E , Barron M , Gaglani M , Thompson MG , Stenehjem E . MMWR Morb Mortal Wkly Rep 2021 70 (44) 1539-1544 Previous infection with SARS-CoV-2 (the virus that causes COVID-19) or COVID-19 vaccination can provide immunity and protection from subsequent SARS-CoV-2 infection and illness. CDC used data from the VISION Network* to examine hospitalizations in adults with COVID-19-like illness and compared the odds of receiving a positive SARS-CoV-2 test result, and thus having laboratory-confirmed COVID-19, between unvaccinated patients with a previous SARS-CoV-2 infection occurring 90-179 days before COVID-19-like illness hospitalization, and patients who were fully vaccinated with an mRNA COVID-19 vaccine 90-179 days before hospitalization with no previous documented SARS-CoV-2 infection. Hospitalized adults aged ≥18 years with COVID-19-like illness were included if they had received testing at least twice: once associated with a COVID-19-like illness hospitalization during January-September 2021 and at least once earlier (since February 1, 2020, and ≥14 days before that hospitalization). Among COVID-19-like illness hospitalizations in persons whose previous infection or vaccination occurred 90-179 days earlier, the odds of laboratory-confirmed COVID-19 (adjusted for sociodemographic and health characteristics) among unvaccinated, previously infected adults were higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine with no previous documented infection (adjusted odds ratio [aOR] = 5.49; 95% confidence interval [CI] = 2.75-10.99). These findings suggest that among hospitalized adults with COVID-19-like illness whose previous infection or vaccination occurred 90-179 days earlier, vaccine-induced immunity was more protective than infection-induced immunity against laboratory-confirmed COVID-19. All eligible persons should be vaccinated against COVID-19 as soon as possible, including unvaccinated persons previously infected with SARS-CoV-2. |
Effectiveness of 2-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19-Associated Hospitalizations Among Immunocompromised Adults - Nine States, January-September 2021.
Embi PJ , Levy ME , Naleway AL , Patel P , Gaglani M , Natarajan K , Dascomb K , Ong TC , Klein NP , Liao IC , Grannis SJ , Han J , Stenehjem E , Dunne MM , Lewis N , Irving SA , Rao S , McEvoy C , Bozio CH , Murthy K , Dixon BE , Grisel N , Yang DH , Goddard K , Kharbanda AB , Reynolds S , Raiyani C , Fadel WF , Arndorfer J , Rowley EA , Fireman B , Ferdinands J , Valvi NR , Ball SW , Zerbo O , Griggs EP , Mitchell PK , Porter RM , Kiduko SA , Blanton L , Zhuang Y , Steffens A , Reese SE , Olson N , Williams J , Dickerson M , McMorrow M , Schrag SJ , Verani JR , Fry AM , Azziz-Baumgartner E , Barron MA , Thompson MG , DeSilva MB . MMWR Morb Mortal Wkly Rep 2021 70 (44) 1553-1559 Immunocompromised persons, defined as those with suppressed humoral or cellular immunity resulting from health conditions or medications, account for approximately 3% of the U.S. adult population (1). Immunocompromised adults are at increased risk for severe COVID-19 outcomes (2) and might not acquire the same level of protection from COVID-19 mRNA vaccines as do immunocompetent adults (3,4). To evaluate vaccine effectiveness (VE) among immunocompromised adults, data from the VISION Network* on hospitalizations among persons aged ≥18 years with COVID-19-like illness from 187 hospitals in nine states during January 17-September 5, 2021 were analyzed. Using selected discharge diagnoses,(†) VE against COVID-19-associated hospitalization conferred by completing a 2-dose series of an mRNA COVID-19 vaccine ≥14 days before the index hospitalization date(§) (i.e., being fully vaccinated) was evaluated using a test-negative design comparing 20,101 immunocompromised adults (10,564 [53%] of whom were fully vaccinated) and 69,116 immunocompetent adults (29,456 [43%] of whom were fully vaccinated). VE of 2 doses of mRNA COVID-19 vaccine against COVID-19-associated hospitalization was lower among immunocompromised patients (77%; 95% confidence interval [CI] = 74%-80%) than among immunocompetent patients (90%; 95% CI = 89%-91%). This difference persisted irrespective of mRNA vaccine product, age group, and timing of hospitalization relative to SARS-CoV-2 (the virus that causes COVID-19) B.1.617.2 (Delta) variant predominance in the state of hospitalization. VE varied across immunocompromising condition subgroups, ranging from 59% (organ or stem cell transplant recipients) to 81% (persons with a rheumatologic or inflammatory disorder). Immunocompromised persons benefit from mRNA COVID-19 vaccination but are less protected from severe COVID-19 outcomes than are immunocompetent persons, and VE varies among immunocompromised subgroups. Immunocompromised persons receiving mRNA COVID-19 vaccines should receive 3 doses and a booster, consistent with CDC recommendations (5), practice nonpharmaceutical interventions, and, if infected, be monitored closely and considered early for proven therapies that can prevent severe outcomes. |
Clinical Influenza Testing Practices in Hospitalized Children at United States Medical Centers, 2015-2018
Tenforde MW , Campbell AP , Michaels MG , Harrison CJ , Klein EJ , Englund JA , Selvarangan R , Halasa NB , Stewart LS , Weinberg GA , Williams JV , Szilagyi PG , Staat MA , Boom JA , Sahni LC , Singer MN , Azimi PH , Zimmerman RK , McNeal MM , Talbot HK , Monto AS , Martin ET , Gaglani M , Silveira FP , Middleton DB , Ferdinands JM , Rolfes MA . J Pediatric Infect Dis Soc 2021 11 (1) 5-8 At nine US hospitals that enrolled children hospitalized with acute respiratory illness (ARI) during 2015-2016 through 2017-2018 influenza seasons, 50% of children with ARI received clinician-initiated testing for influenza and 35% of cases went undiagnosed due to lack of clinician-initiated testing. Marked heterogeneity in testing practice was observed across sites. |
Influenza vaccine effectiveness within prospective cohorts of healthcare personnel in Israel and Peru 2016-2019
Thompson MG , Soto G , Perez A , Newes-Adeyim G , Yoo YM , Hirsch A , Katz M , Tinoco Y , Shemer Avni Y , Ticona E , Malosh R , Martin E , Matos E , Reynolds S , Wesley M , Ferdinands J , Cheung A , Levine M , Bravo E , Arriola CS , Ester Castillo M , Carlos Castro J , Dawood F , Goldberg D , Manuel Neyra Quijandría J , Azziz-Baumgartner E , Monto A , Balicer R . Vaccine 2021 39 (47) 6956-6967 BACKGROUND: There are limited data on influenza vaccine effectiveness (IVE) in preventing laboratory-confirmed influenza illness among healthcare personnel (HCP). METHODS: HCP with direct patient contact working full-time in hospitals were followed during three influenza seasons in Israel (2016-2017 to 2018-2019) and Peru (2016 to 2018). Trivalent influenza vaccines were available at all sites, except during 2018-2019 when Israel used quadrivalent vaccines; vaccination was documented by electronic medical records, vaccine registries, and/or self-report (for vaccinations outside the hospital). Twice-weekly active surveillance identified acute respiratory symptoms or febrile illness (ARFI); self-collected respiratory specimens were tested by real-time reverse transcription polymerase chain reaction (PCR) assay. IVE was 100 × 1-hazard ratio (adjusted for sex, age, occupation, and hospital). RESULTS: Among 5,489 HCP who contributed 10,041 person-seasons, influenza vaccination coverage was 47% in Israel and 32% in Peru. Of 3,056 ARFIs in Israel and 3,538 in Peru, A or B influenza virus infections were identified in 205 (7%) in Israel and 87 (2.5%) in Peru. IVE against all viruses across seasons was 1% (95% confidence interval [CI] = -30%, 25%) in Israel and 12% (95% CI = -61%, 52%) in Peru. CONCLUSION: Estimates of IVE were null using person-time models during six study seasons in Israel and Peru. |
Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings.
Thompson MG , Stenehjem E , Grannis S , Ball SW , Naleway AL , Ong TC , DeSilva MB , Natarajan K , Bozio CH , Lewis N , Dascomb K , Dixon BE , Birch RJ , Irving SA , Rao S , Kharbanda E , Han J , Reynolds S , Goddard K , Grisel N , Fadel WF , Levy ME , Ferdinands J , Fireman B , Arndorfer J , Valvi NR , Rowley EA , Patel P , Zerbo O , Griggs EP , Porter RM , Demarco M , Blanton L , Steffens A , Zhuang Y , Olson N , Barron M , Shifflett P , Schrag SJ , Verani JR , Fry A , Gaglani M , Azziz-Baumgartner E , Klein NP . N Engl J Med 2021 385 (15) 1355-1371 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, 85 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.). |
Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season.
Grohskopf LA , Alyanak E , Ferdinands JM , Broder KR , Blanton LH , Talbot HK , Fry AM . MMWR Recomm Rep 2021 70 (5) 1-28 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. |
Vaccine effectiveness against acute respiratory illness hospitalizations for influenza-associated pneumonia during the 2015-2016 to 2017-2018 seasons, US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN)
Ghamande S , Shaver C , Murthy K , Raiyani C , White HD , Lat T , Arroliga AC , Wyatt D , Talbot HK , Martin ET , Monto AS , Zimmerman RK , Middleton DB , Silveira FP , Ferdinands JM , Patel MM , Gaglani M . Clin Infect Dis 2021 74 (8) 1329-1337 BACKGROUND: Evidence for vaccine effectiveness (VE) against influenza-associated pneumonia has varied by season, location, and strain. We estimate VE against hospitalization for radiographically identified influenza-associated pneumonia during 2015-2016 to 2017-2018 seasons in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). METHODS: Among adults aged ≥18 years admitted to 10 US hospitals for acute respiratory illness (ARI), clinician-investigators used keywords from reports of chest imaging performed during 3 days around hospital admission to assign a diagnosis of 'definite/probable pneumonia'. We used a test-negative design to estimate VE against hospitalization for radiographically identified laboratory-confirmed influenza-associated pneumonia, comparing RT-PCR confirmed influenza cases with test-negative subjects. Influenza vaccination status was documented in immunization records or self-reported, including date and location. Multivariable logistic regression models were used to adjust for age, site, season, calendar-time, and other factors. RESULTS: Of 4,843 adults hospitalized with ARI included in the primary analysis, 266 (5.5%) had 'definite/probable pneumonia' and confirmed influenza. Adjusted VE against hospitalization for any radiographically confirmed influenza-associated pneumonia was 38% (95% confidence interval [CI]): 17%-53%); by type/subtype, it was 74% (95% CI: 52%-87%), influenza A (H1N1)pdm09; 25% (-15% to 50%), A (H3N2); and 23% (95% CI: -32% to 54%), influenza B. Adjusted VE against intensive care for any influenza was 57% (95% CI, 19%-77%). CONCLUSIONS: Influenza vaccination was modestly effective among adults in preventing hospitalizations and the need for intensive care associated with influenza pneumonia. VE was significantly higher against A (H1N1)pdm09 and was low against A (H3N2) and B. |
Does influenza vaccination attenuate the severity of breakthrough infections A narrative review and recommendations for further research
Ferdinands JM , Thompson MG , Blanton L , Spencer S , Grant L , Fry AM . Vaccine 2021 39 (28) 3678-3695 The effect of influenza vaccination on influenza severity remains uncertain. We reviewed the literature for evidence to inform the question of whether influenza illness is less severe among individuals who received influenza vaccination compared with individuals with influenza illness who were unvaccinated prior to their illnesses. We conducted a narrative review to identify published findings comparing severity of influenza outcomes by vaccination status among community-dwelling adults and children ≥ 6 months of age with laboratory-confirmed influenza illness. When at least four effect estimates of the same type (e.g., odds ratio) were available for a specific outcome and age category (children versus adults), data were pooled with meta-analysis to generate a summary effect estimate. We identified 38 published articles reporting ≥ 1 association between influenza vaccination status and one of 21 indicators of severity of influenza illness among individuals with laboratory-confirmed influenza. Study methodologies and effect estimates were highly heterogenous, with only five severity indicators meeting criteria for calculating a combined effect. Among eight studies, influenza vaccination was associated with 26% reduction in odds of ICU admission among adults with influenza-associated hospitalization (OR = 0.74, 95% CI 0.58, 0.93). Among five studies of adults with influenza-associated hospitalization, vaccinated patients had 31% reduced risk of death compared with unvaccinated patients (OR = 0.69, 95% CI 0.52, 0.92). Among four studies of children with influenza virus infection, vaccination was associated with an estimated 45% reduction in the odds of manifesting fever (OR = 0.55, 95% CI 0.42, 0.71). Vaccination was not significantly associated with receiving a clinical diagnosis of pneumonia among adults hospitalized with influenza (OR = 0.92, 95% CI 0.82, 1.04) or with risk of hospitalization following outpatient influenza illness among adults (OR = 0.60, 95% CI 0.28, 1.28). Overall, our findings support the hypothesis that influenza vaccination may attenuate the course of disease among individuals with breakthrough influenza virus infection. |
Modeling the impacts of clinical influenza testing on influenza vaccine effectiveness estimates
Feldstein LR , Ferdinands JM , Self WH , Randolph AG , Aboodi M , Baughman AH , Brown SM , Exline MC , Files DC , Gibbs K , Ginde AA , Gong MN , Grijalva CG , Halasa N , Khan A , Lindsell CJ , Newhams M , Peltan ID , Prekker ME , Rice TW , Shapiro NI , Steingrub J , Talbot HK , Halloran ME , Patel M . J Infect Dis 2021 224 (12) 2035-2042 BACKGROUND: Test-negative design studies for evaluating influenza vaccine effectiveness (VE) enroll patients with acute respiratory infection. Enrollment typically occurs before influenza status is determined, resulting in over-enrollment of influenza-negative patients. With availability of rapid and accurate molecular clinical testing, influenza status could be ascertained prior to enrollment, thus improving study efficiency. We estimate potential biases in VE when using clinical testing. METHODS: We simulate data assuming 60% vaccinated, 25% of those vaccinated are influenza positive, and VE of 50%. We show the effect on VE in five scenarios. RESULTS: VE is affected only when clinical testing preferentially targets patients based on both vaccination and influenza status. VE is overestimated by 10% if non-testing occurs in 39% of vaccinated influenza-positive patients and 24% of others; and if non-testing occurs in 8% of unvaccinated influenza-positive patients and 27% of others. VE is underestimated by 10% if non-testing occurs in 32% of unvaccinated influenza-negative patients and 18% of others. CONCLUSIONS: Although differential clinical testing by vaccine receipt and influenza positivity may produce errors in estimated VE, bias in testing would have to be substantial and overall proportion of patients tested would have to be small to result in a meaningful difference in VE. |
Coronavirus disease 2019 (COVID-19) Versus Influenza in Hospitalized Adult Patients in the United States: Differences in Demographic and Severity Indicators.
Talbot HK , Martin ET , Gaglani M , Middleton DB , Ghamande S , Silveira FP , Murthy K , Zimmerman RK , Trabue CH , Olson SM , Petrie JG , Ferdinands JM , Patel MM , Monto AS . Clin Infect Dis 2021 73 (12) 2240-2247 BACKGROUND: Novel coronavirus disease 2019 (COVID-19) is frequently compared with influenza. The Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) conducts studies on the etiology and characteristics of U.S. hospitalized adults with influenza. It began enrolling patients with COVID-19 hospitalizations in March 2020. Patients with influenza were compared with those with COVID-19 in the first months of the U.S. epidemic. METHODS: Adults aged ≥ 18 years admitted to hospitals in 4 sites with acute respiratory illness were tested by real-time reverse transcription polymerase chain reaction for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Demographic and illness characteristics were collected for influenza illnesses during 3 seasons 2016-2019. Similar data were collected on COVID-19 cases admitted before June 19, 2020. RESULTS: Age groups hospitalized with COVID-19 (n = 914) were similar to those admitted with influenza (n = 1937); 80% of patients with influenza and 75% of patients with COVID-19 were aged ≥50 years. Deaths from COVID-19 that occurred in younger patients were less often related to underlying conditions. White non-Hispanic persons were overrepresented in influenza (64%) compared with COVID-19 hospitalizations (37%). Greater severity and complications occurred with COVID-19 including more ICU admissions (AOR = 15.3 [95% CI: 11.6, 20.3]), ventilator use (AOR = 15.6 [95% CI: 10.7, 22.8]), 7 additional days of hospital stay in those discharged alive, and death during hospitalization (AOR = 19.8 [95% CI: 12.0, 32.7]). CONCLUSIONS: While COVID-19 can cause a respiratory illness like influenza, it is associated with significantly greater severity of illness, longer hospital stays, and higher in-hospital deaths. |
Differences between Frequentist and Bayesian inference in routine surveillance for influenza vaccine effectiveness: a test-negative case-control study
Jackson ML , Ferdinands J , Nowalk MP , Zimmerman RK , Kieke B , Gaglani M , Murthy K , Petrie JG , Martin ET , Chung JR , Flannery B , Jackson LA . BMC Public Health 2021 21 (1) 516 BACKGROUND: Routine influenza vaccine effectiveness (VE) surveillance networks use frequentist methods to estimate VE. With data from more than a decade of VE surveillance from diverse global populations now available, using Bayesian methods to explicitly account for this knowledge may be beneficial. This study explores differences between Bayesian vs. frequentist inference in multiple seasons with varying VE. METHODS: We used data from the United States Influenza Vaccine Effectiveness (US Flu VE) Network. Ambulatory care patients with acute respiratory illness were enrolled during seasons of varying observed VE based on traditional frequentist methods. We estimated VE against A(H1N1)pdm in 2015/16, dominated by A(H1N1)pdm; against A(H3N2) in 2017/18, dominated by A(H3N2); and compared VE for live attenuated influenza vaccine (LAIV) vs. inactivated influenza vaccine (IIV) among children aged 2-17 years in 2013/14, also dominated by A(H1N1)pdm. VE was estimated using both frequentist and Bayesian methods using the test-negative design. For the Bayesian estimates, prior VE distributions were based on data from all published test-negative studies of the same influenza type/subtype available prior to the season of interest. RESULTS: Across the three seasons, 16,342 subjects were included in the analyses. For 2015/16, frequentist and Bayesian VE estimates were essentially identical (41% each). For 2017/18, frequentist and Bayesian estimates of VE against A(H3N2) viruses were also nearly identical (26% vs. 23%, respectively), even though the presence of apparent antigenic match could potentially have pulled Bayesian estimates upward. Precision of estimates was similar between methods in both seasons. Frequentist and Bayesian estimates diverged for children in 2013/14. Under the frequentist approach, LAIV effectiveness was 62 percentage points lower than IIV, while LAIV was only 27 percentage points lower than IIV under the Bayesian approach. CONCLUSION: Bayesian estimates of influenza VE can differ from frequentist estimates to a clinically meaningful degree when VE diverges substantially from previous seasons. |
Antibody Landscape Analysis following Influenza Vaccination and Natural Infection in Humans with a High-Throughput Multiplex Influenza Antibody Detection Assay.
Li ZN , Liu F , Gross FL , Kim L , Ferdinands J , Carney P , Chang J , Stevens J , Tumpey T , Levine MZ . mBio 2021 12 (1) To better understand the antibody landscape changes following influenza virus natural infection and vaccination, we developed a high-throughput multiplex influenza antibody detection assay (MIADA) containing 42 recombinant hemagglutinins (rHAs) (ectodomain and/or globular head domain) from pre-2009 A(H1N1), A(H1N1)pdm09, A(H2N2), A(H3N2), A(H5N1), A(H7N7), A(H7N9), A(H7N2), A(H9N2), A(H13N9), and influenza B viruses. Panels of ferret antisera, 227 paired human sera from vaccinees (children and adults) in 5 influenza seasons (2010 to 2018), and 17 paired human sera collected from real-time reverse transcription-PCR (rRT-PCR)-confirmed influenza A(H1N1)pdm09, influenza A(H3N2), or influenza B virus-infected adults were analyzed by the MIADA. Ferret antisera demonstrated clear strain-specific antibody responses to exposed subtype HA. Adults (19 to 49 years old) had broader antibody landscapes than young children (<3 years old) and older children (9 to 17 years old) both at baseline and post-vaccination. Influenza vaccination and infection induced the strongest antibody responses specific to HA(s) of exposed strain/subtype viruses and closely related strains; they also induced cross-reactive antibodies to an unexposed influenza virus subtype(s), including novel viruses. Subsequent serum adsorption confirmed that the cross-reactive antibodies against novel subtype HAs were mainly induced by exposures to A(H1N1)/A(H3N2) influenza A viruses. In contrast, adults infected by influenza B viruses mounted antibody responses mostly specific to two influenza B virus lineage HAs. Median fluorescence intensities (MFIs) and seroconversion in MIADA had good correlations with the titers and seroconversion measured by hemagglutination inhibition and microneutralization assays. Our study demonstrated that antibody landscape analysis by the MIADA can be used for influenza vaccine evaluations and characterization of influenza virus infections.IMPORTANCE Repeated influenza vaccination and natural infections generate complex immune profiles in humans that require antibody landscape analysis to assess immunity and evaluate vaccines. However, antibody landscape analyses are difficult to perform using traditional assays. Here, we developed a high-throughput, serum-sparing, multiplex influenza antibody detection assay (MIADA) and analyzed the antibody landscapes following influenza vaccination and infection. We showed that adults had broader antibody landscapes than children. Influenza vaccination and infection not only induced the strongest antibody responses to the hemagglutinins of the viruses of exposure, but also induced cross-reactive antibodies to novel influenza viruses that can be removed by serum adsorption. There is a good correlation between the median fluorescence intensity (MFI) measured by MIADA and hemagglutination inhibition/microneutralization titers. Antibody landscape analysis by the MIADA can be used in influenza vaccine evaluations, including the development of universal influenza vaccines and the characterization of influenza virus infections. |
Waning vaccine effectiveness against influenza-associated hospitalizations among adults, 2015-2016 to 2018-2019, US Hospitalized Adult Influenza Vaccine Effectiveness Network
Ferdinands JM , Gaglani M , Martin ET , Monto AS , Middleton D , Silveira F , Talbot HK , Zimmerman R , Patel M . Clin Infect Dis 2021 73 (4) 726-729 We observed decreased effectiveness of influenza vaccine with increasing time since vaccination for prevention of influenza A(H3N2), influenza A(H1N1)pdm09, and influenza B(Yamagata)-associated hospitalizations among adults. Maximum VE was observed shortly after vaccination, followed by an absolute decline in VE of about 8 to 9% per month post-vaccination. |
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