Homologous and Heterologous Covid-19 Booster Vaccinations.

BACKGROUND: Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients. METHODS: In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 µg, Ad26.COV2.S (Johnson & Johnson-Janssen) at a dose of 5×1010 virus particles, or BNT162b2 (Pfizer-BioNTech) at a dose of 30 µg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29. RESULTS: Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients. CONCLUSIONS: Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).

Safety and Immunogenicity of a Delayed Heterologous Avian Influenza A(H7N9) Vaccine Boost Following Different Priming Regimens: A Randomized Clinical Trial.

BACKGROUND: Influenza A (H7N9) has caused multiple disease waves with evidence of strain diversification. Optimal influenza A (H7N9) prime-boost vaccine strategies are unknown. METHODS: We recruited participants who had received monovalent inactivated A/Shanghai/2/2013 (H7N9) vaccine (MIV) approximately 5 years earlier, as follows: MIV with MF59 (MF59 × 2 group), MIV with AS03 (AS03 × 2 group), unadjuvanted MIV (No Adj group), MIV with MF59 or AS03 followed by unadjuvanted MIV (Adjx1 group), and A/H7-naive (unprimed group). Participants were randomized to receive 1 dose of AS03-adjuvanted or unadjuvanted A/Hong Kong/125/2017 (H7N9) MIV and were followed for safety and immunogenicity using hemagglutination inhibition (HAI) and neutralizing antibody assays. RESULTS: We enrolled 304 participants: 153 received the adjuvanted boost and 151 received the unadjuvanted boost. At 21 days postvaccination, the proportion of participants with HAI antibody titers against the boosting vaccine strain of ≥40 in the adjuvanted and unadjuvanted arms, respectively, were 88% and 49% in MF59 × 2 group, 89% and 75% in AS03 × 2 group, 59% and 20% in No Adj group, 94% and 55% in Adjx1group, and 9% and 11% in unprimed group. CONCLUSIONS: Serologic responses to a heterologous A(H7N9) MIV boost were highest in participants primed and boosted with adjuvant-containing regimens. CLINICAL TRIALS REGISTRATION: NCT03738241.

Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase.

BACKGROUND: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported. METHODS: We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 µg) or placebo, 28 days apart, at 99 centers across the United States. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021. RESULTS: The trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified. CONCLUSIONS: The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

Professionalism-training in undergraduate medical education in a multi-cultural, multi-ethnic setting in the Gulf Region: an exploration of reflective essays.

BACKGROUND: Despite the established need to prioritize professionalism-training in developing future physicians, very few medical programs in the Gulf Region embed in their curricula discrete contextualized courses aimed at developing the corresponding competencies, while fostering self-directed learning. This study aims at exploring the perception of undergraduate medical students in a multi-cultural, multi-ethnic setting regarding their understanding of, and personal experience with professionalism through their engagement with the content of an innovative curriculum-based professionalism course, offered at a Medical School in Dubai, United Arab Emirates. METHODS: The study used a qualitative phenomenological research design. Out of 33 students, 29 students had submitted reflective essays. The content of these essays was inductively analyzed following a six-step framework for conducting thematic analysis. The framework's steps include familiarizing oneself with the data, generating initial codes, searching for themes, reviewing themes, defining and naming themes, and producing the report. FINDINGS: The inductive qualitative analysis generated the Professionalism Learning Journey model. This conceptual model includes four interconnected themes: Awareness, Acknowledgement, Realization, and Application. The generated model depicts the trajectory that the learners appear to experience while they are engaging with the content of the course. CONCLUSION: Integrating a professionalism-training course into an undergraduate medical curriculum is likely to be positively appraised by the learners. It raises their awareness, enables them to value the subject matter and the sophistication of its application, and empowers them to put into practice the taught principles, on an individual basis and collectively. This is especially true when the course is entrenched in constructivism experiential learning theory and designed to foster self-directed learning. The introduced conceptual model, in conjunction with the innovative professionalism-training course curriculum, can serve as a template for other competencies and other schools.

Immunogenicity of a 2-Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial.

We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost.

Immunogenicity of the BA.1 and BA.4/BA.5 Severe Acute Respiratory Syndrome Coronavirus 2 Bivalent Boosts: Preliminary Results From the COVAIL Randomized Clinical Trial.

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wild-type spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.

Active Postlicensure Safety Surveillance for Recombinant Zoster Vaccine Using Electronic Health Record Data.

Recombinant zoster vaccine (RZV) (Shingrix; GlaxoSmithKline, Brentford, United Kingdom) is an adjuvanted glycoprotein vaccine that was licensed in 2017 to prevent herpes zoster (shingles) and its complications in older adults. In this prospective, postlicensure Vaccine Safety Datalink study using electronic health records, we sequentially monitored a real-world population of adults aged ≥50 years who received care in multiple US Vaccine Safety Datalink health systems to identify potentially increased risks of 10 prespecified health outcomes, including stroke, anaphylaxis, and Guillain-Barré syndrome (GBS). Among 647,833 RZV doses administered from January 2018 through December 2019, we did not detect a sustained increased risk of any monitored outcome for RZV recipients relative to either historical (2013-2017) recipients of zoster vaccine live, a live attenuated virus vaccine (Zostavax; Merck & Co., Inc., Kenilworth, New Jersey), or contemporary non-RZV vaccine recipients who had an annual well-person visit during the 2018-2019 study period. We confirmed prelicensure trial findings of increased risks of systemic and local reactions following RZV. Our study provides additional reassurance about the overall safety of RZV. Despite a large sample, uncertainty remains regarding potential associations with GBS due to the limited number of confirmed GBS cases that were observed.

An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. METHODS: We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 µg, 100 µg, or 250 µg. There were 15 participants in each dose group. RESULTS: After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti-S-2P antibody geometric mean titer [GMT], 40,227 in the 25-µg group, 109,209 in the 100-µg group, and 213,526 in the 250-µg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-µg dose group reported one or more severe adverse events. CONCLUSIONS: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).

Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.

BACKGROUND: Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age. METHODS: We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 µg or 100 µg of vaccine administered 28 days apart. RESULTS: Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-µg dose, the anti-S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-µg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. CONCLUSIONS: In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-µg dose induced higher binding- and neutralizing-antibody titers than the 25-µg dose, which supports the use of the 100-µg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.).

PfSPZ-CVac efficacy against malaria increases from 0% to 75% when administered in the absence of erythrocyte stage parasitemia: A randomized, placebo-controlled trial with controlled human malaria infection.

PfSPZ-CVac combines 'PfSPZ Challenge', which consists of infectious Plasmodium falciparum sporozoites (PfSPZ), with concurrent antimalarial chemoprophylaxis. In a previously-published PfSPZ-CVac study, three doses of 5.12x104 PfSPZ-CVac given 28 days apart had 100% vaccine efficacy (VE) against controlled human malaria infection (CHMI) 10 weeks after the last immunization, while the same dose given as three injections five days apart had 63% VE. Here, we conducted a dose escalation trial of similarly condensed schedules. Of the groups proceeding to CHMI, the first study group received three direct venous inoculations (DVIs) of a dose of 5.12x104 PfSPZ-CVac seven days apart and the next full dose group received three DVIs of a higher dose of 1.024x105 PfSPZ-CVac five days apart. CHMI (3.2x103 PfSPZ Challenge) was performed by DVI 10 weeks after the last vaccination. In both CHMI groups, transient parasitemia occurred starting seven days after each vaccination. For the seven-day interval group, the second and third vaccinations were therefore administered coincident with parasitemia from the prior vaccination. Parasitemia was associated with systemic symptoms which were severe in 25% of subjects. VE in the seven-day group was 0% (7/7 infected) and in the higher-dose, five-day group was 75% (2/8 infected). Thus, the same dose of PfSPZ-CVac previously associated with 63% VE when given on a five-day schedule in the prior study had zero VE here when given on a seven-day schedule, while a double dose given on a five-day schedule here achieved 75% VE. The relative contributions of the five-day schedule and/or the higher dose to improved VE warrant further investigation. It is notable that administration of PfSPZ-CVac on a schedule where vaccine administration coincided with blood-stage parasitemia was associated with an absence of sterile protective immunity. Clinical trials registration: NCT02773979.

Using team-based learning to optimize undergraduate family medicine clerkship training: mixed methods study.

BACKGROUND: Team-Based Learning (TBL) is an established educational strategy which has become increasingly popular in the training of healthcare professionals. TBL is highly suitable for teaching Family Medicine (FM) especially that teamwork and collaborative care, in this medical discipline, are at the core of safe and effective practice. Despite the established suitability of TBL for teaching FM, there are no empirical studies that capture the students' perception of a TBL in FM undergraduate learning experience in the Middle East and North Africa region (MENA). OBJECTIVE: The overall objective of this study was to investigate the perception of students regarding a TBL in FM intervention (in Dubai, United Arab Emirates), that was designed and implemented in alignment with a constructivist learning theory. METHODS: A convergent mixed methods study design was utilized to develop a thorough understanding of the students' perceptions. Qualitative and quantitative data were concurrently collected and independently analyzed. The output of thematic analysis was systematically merged with the quantitative descriptive and inferential findings using the iterative joint display process. RESULTS: The qualitative findings shed light on the students' perception of TBL in FM, and the interplay between team cohesion and engagement with the course. As for the quantitative findings, they showed that the percentage of the total average of the Satisfaction with TBL in FM score was 88.80%. As for change in impression of FM discipline, the percentage of the total average was 83.10%. The perception of team cohesion, with a mean of agreement of 8.62(1.34), seemed to be significantly associated with the students' perception of the team test phase component, only (P < 0.05). As for the perception of the level of engagement with the course, with a mean of agreement of 9.29(0.84), it turned out to be significantly associated with the change in impression of FM discipline (P < 0.05). Lastly, the joint display analysis showed how the quantitative and qualitative findings built upon each other, revealing how best to leverage TBL in FM trainings. CONCLUSION: The current study showed that TBL embedded in a FM clinical clerkship was well-received by students. It is worth leveraging the lessons learned from the first-hand experience reported upon in the current study to optimize the utilization of TBL in FM.

Clinical learning environments across two different healthcare settings using the undergraduate clinical education environment measure.

BACKGROUND: The clinical placements of our medical students are almost equally distributed across private and public sectors. This study aims to assess medical students' perceptions of their Clinical learning Environment (CLE) across these two different healthcare settings, using the Undergraduate Clinical Education Environment Measure (UCEEM). METHODS: 76 undergraduate medical students (Year 5 and 6), were invited to participate. Data were collected using an online UCEEM with additional questions related to demographics and case load exposure. The UCEEM consists of two overarching domains of experiential learning and social participation, with four subdomains of learning opportunities, preparedness, workplace interaction, and inclusion. RESULTS: 38 questionnaires were received. Of 225 responses to the individual UCEEM items, 51 (22.6%) scored a mean of ≥ 4 (range 4-4.5, representing strong areas), 31 (13.7%) scored a mean of ≤ 3 (range 2.1-3, needing attention) and 143 (63.6%) scored a mean of 3.1-3.9 (areas that could be improved). The majority (63%) of the case load exposure responses scored a mean of ≥ 4 (range 4-4.5). Compared to the private sittings, there is a significant reduction in total UCEEM (p = 0.008), preparedness for student entry (p = 0.003), and overarching dimension of social participation (p = 0.000) scores for the public sector. Similarly, both workplace interaction patterns and student inclusion and equal treatment scored significantly lower for the public sector (p = 0.000 and p = 0.011 respectively). Two out of three case load exposure items scored significantly higher for the public sector (p = 0.000). DISCUSSION: The students' CLE perceptions were generally positive. The lower UCEEM ratings in the public sector items were related to student entry preparedness, workplace interactions, student inclusiveness and workforce equity of treatment. In contrast the students were exposed to more variety and larger number of patients in the public sector. These differences indicated some significantly different learning environments between the two sectors.

Role of Age in the Spread of Influenza, 2011-2019: Data From the US Influenza Vaccine Effectiveness Network.

Intraseason timing of influenza infection among persons of different ages could reflect relative contributions to propagation of seasonal epidemics and has not been examined among ambulatory patients. Using data from the US Influenza Vaccine Effectiveness Network, we calculated risk ratios derived from comparing weekly numbers of influenza cases prepeak with those postpeak during the 2010-2011 through 2018-2019 influenza seasons. We sought to determine age-specific differences during the ascent versus descent of an influenza season by influenza virus type and subtype. We estimated 95% credible intervals around the risk ratios using Bayesian joint posterior sampling of weekly cases. Our population consisted of ambulatory patients with laboratory-confirmed influenza who enrolled in an influenza vaccine effectiveness study at 5 US sites during 9 influenza seasons after the 2009 influenza A virus subtype H1N1 (H1N1) pandemic. We observed that young children aged <5 years tended to more often be infected with H1N1 during the prepeak period, while adults aged ≥65 years tended to more often be infected with H1N1 during the postpeak period. However, for influenza A virus subtype H3N2, children aged <5 years were more often infected during the postpeak period. These results may reflect a contribution of different age groups to seasonal spread, which may differ by influenza virus type and subtype.

Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth - Eight Integrated Health Care Organizations, United States, December 15, 2020-July 22, 2021.

COVID-19 vaccines are recommended during pregnancy to prevent severe maternal morbidity and adverse birth outcomes; however, vaccination coverage among pregnant women has been low (1). Concerns among pregnant women regarding vaccine safety are a persistent barrier to vaccine acceptance during pregnancy. Previous studies of maternal COVID-19 vaccination and birth outcomes have been limited by small sample size (2) or lack of an unvaccinated comparison group (3). In this retrospective cohort study of live births from eight Vaccine Safety Datalink (VSD) health care organizations, risks for preterm birth (<37 weeks' gestation) and small-for-gestational-age (SGA) at birth (birthweight <10th percentile for gestational age) after COVID-19 vaccination (receipt of ≥1 COVID-19 vaccine doses) during pregnancy were evaluated. Risks for preterm and SGA at birth among vaccinated and unvaccinated pregnant women were compared, accounting for time-dependent vaccine exposures and propensity to be vaccinated. Single-gestation pregnancies with estimated start or last menstrual period during May 17-October 24, 2020, were eligible for inclusion. Among 46,079 pregnant women with live births and gestational age available, 10,064 (21.8%) received ≥1 COVID-19 vaccine doses during pregnancy and during December 15, 2020-July 22, 2021; nearly all (9,892; 98.3%) were vaccinated during the second or third trimester. COVID-19 vaccination during pregnancy was not associated with preterm birth (adjusted hazard ratio [aHR] = 0.91; 95% CI = 0.82-1.01). Among 40,627 live births with birthweight available, COVID-19 vaccination in pregnancy was not associated with SGA at birth (aHR = 0.95; 95% CI = 0.87-1.03). Results consistently showed no increased risk when stratified by mRNA COVID-19 vaccine dose, or by second or third trimester vaccination, compared with risk among unvaccinated pregnant women. Because of the small number of first-trimester exposures, aHRs for first-trimester vaccination could not be calculated. These data add to the evidence supporting the safety of COVID-19 vaccination during pregnancy. To reduce the risk for severe COVID-19-associated illness, CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant (including those who are lactating), who are trying to become pregnant now, or who might become pregnant in the future (4).

Altered Thalamocortical Connectivity in 6-Week-Old Infants at High Familial Risk for Autism Spectrum Disorder.

Converging evidence from neuroimaging studies has revealed altered connectivity in cortical-subcortical networks in youth and adults with autism spectrum disorder (ASD). Comparatively little is known about the development of cortical-subcortical connectivity in infancy, before the emergence of overt ASD symptomatology. Here, we examined early functional and structural connectivity of thalamocortical networks in infants at high familial risk for ASD (HR) and low-risk controls (LR). Resting-state functional connectivity and diffusion tensor imaging data were acquired in 52 6-week-old infants. Functional connectivity was examined between 6 cortical seeds-prefrontal, motor, somatosensory, temporal, parietal, and occipital regions-and bilateral thalamus. We found significant thalamic-prefrontal underconnectivity, as well as thalamic-occipital and thalamic-motor overconnectivity in HR infants, relative to LR infants. Subsequent structural connectivity analyses also revealed atypical white matter integrity in thalamic-occipital tracts in HR infants, compared with LR infants. Notably, aberrant connectivity indices at 6 weeks predicted atypical social development between 9 and 36 months of age, as assessed with eye-tracking and diagnostic measures. These findings indicate that thalamocortical connectivity is disrupted at both the functional and structural level in HR infants as early as 6 weeks of age, providing a possible early marker of risk for ASD.

Messenger RNA Vaccine Effectiveness Against Coronavirus Disease 2019 Among Symptomatic Outpatients Aged ≥16 Years in the United States, February-May 2021.

Evaluations of vaccine effectiveness (VE) are important to monitor as coronavirus disease 2019 (COVID-19) vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, the VE of messenger RNA vaccines against COVID-19 was 91% (95% confidence interval, 83%-95%) for full vaccination and 75% (55%-87%) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.

Effects of Prior Season Vaccination on Current Season Vaccine Effectiveness in the United States Flu Vaccine Effectiveness Network, 2012-2013 Through 2017-2018.

BACKGROUND: We compared effects of prior vaccination and added or lost protection from current season vaccination among those previously vaccinated. METHODS: Our analysis included data from the US Flu Vaccine Effectiveness Network among participants ≥9 years old with acute respiratory illness from 2012-2013 through 2017-2018. Vaccine protection was estimated using multivariate logistic regression with an interaction term for effect of prior season vaccination on current season vaccine effectiveness. Models were adjusted for age, calendar time, high-risk status, site, and season for combined estimates. We estimated protection by combinations of current and prior vaccination compared to unvaccinated in both seasons or current vaccination among prior vaccinated. RESULTS: A total of 31 819 participants were included. Vaccine protection against any influenza averaged 42% (95% confidence interval [CI], 38%-47%) among those vaccinated only the current season, 37% (95% CI, 33-40) among those vaccinated both seasons, and 26% (95% CI, 18%-32%) among those vaccinated only the prior season, compared with participants vaccinated neither season. Current season vaccination reduced the odds of any influenza among patients unvaccinated the prior season by 42% (95% CI, 37%-46%), including 57%, 27%, and 55% against A(H1N1), A(H3N2), and influenza B, respectively. Among participants vaccinated the prior season, current season vaccination further reduced the odds of any influenza by 15% (95% CI, 7%-23%), including 29% against A(H1N1) and 26% against B viruses, but not against A(H3N2). CONCLUSIONS: Our findings support Advisory Committee on Immunization Practices recommendations for annual influenza vaccination. Benefits of current season vaccination varied among participants with and without prior season vaccination, by virus type/subtype and season.

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.

Influenza Vaccine Effectiveness in Inpatient and Outpatient Settings in the United States, 2015-2018.

BACKGROUND: Demonstration of influenza vaccine effectiveness (VE) against hospitalized illness in addition to milder outpatient illness may strengthen vaccination messaging. Our objective was to compare patient characteristics and VE between United States (US) inpatient and outpatient VE networks. METHODS: We tested adults with acute respiratory illness (ARI) for influenza within 1 outpatient-based and 1 hospital-based VE network from 2015 through 2018. We compared age, sex, and high-risk conditions. The test-negative design was used to compare vaccination odds in influenza-positive cases vs influenza-negative controls. We estimated VE using logistic regression adjusting for site, age, sex, race/ethnicity, peak influenza activity, time to testing from, season (overall VE), and underlying conditions. VE differences (ΔVE) were assessed with 95% confidence intervals (CIs) determined through bootstrapping with significance defined as excluding the null. RESULTS: The networks enrolled 14 573 (4144 influenza-positive) outpatients and 6769 (1452 influenza-positive) inpatients. Inpatients were older (median, 62 years vs 49 years) and had more high-risk conditions (median, 4 vs 1). Overall VE across seasons was 31% (95% CI, 26%-37%) among outpatients and 36% (95% CI, 27%-44%) among inpatients. Strain-specific VE (95% CI) among outpatients vs inpatients was 37% (25%-47%) vs 53% (37%-64%) against H1N1pdm09; 19% (9%-27%) vs 23% (8%-35%) against H3N2; and 46% (38%-53%) vs 46% (31%-58%) against B viruses. ΔVE was not significant for any comparison across all sites. CONCLUSIONS: Inpatients and outpatients with ARI represent distinct populations. Despite comparatively poor health among inpatients, influenza vaccination was effective in preventing influenza-associated hospitalizations.

Effect of Antigenic Drift on Influenza Vaccine Effectiveness in the United States-2019-2020.

BACKGROUND: At the start of the 2019-2020 influenza season, concern arose that circulating B/Victoria viruses of the globally emerging clade V1A.3 were antigenically drifted from the strain included in the vaccine. Intense B/Victoria activity was followed by circulation of genetically diverse A(H1N1)pdm09 viruses that were also antigenically drifted. We measured vaccine effectiveness (VE) in the United States against illness from these emerging viruses. METHODS: We enrolled outpatients aged ≥6 months with acute respiratory illness at 5 sites. Respiratory specimens were tested for influenza by reverse-transcriptase polymerase chain reaction (RT-PCR). Using the test-negative design, we determined influenza VE by virus subtype/lineage and genetic subclades by comparing odds of vaccination in influenza cases versus test-negative controls. RESULTS: Among 8845 enrollees, 2722 (31%) tested positive for influenza, including 1209 (44%) for B/Victoria and 1405 (51%) for A(H1N1)pdm09. Effectiveness against any influenza illness was 39% (95% confidence interval [CI]: 32-44), 45% (95% CI: 37-52) against B/Victoria and 30% (95% CI: 21-39) against A(H1N1)pdm09-associated illness. Vaccination offered no protection against A(H1N1)pdm09 viruses with antigenically drifted clade 6B.1A 183P-5A+156K HA genes (VE 7%; 95% CI: -14 to 23%) which predominated after January. CONCLUSIONS: Vaccination provided protection against influenza illness, mainly due to infections from B/Victoria viruses. Vaccine protection against illness from A(H1N1)pdm09 was lower than historically observed effectiveness of 40%-60%, due to late-season vaccine mismatch following emergence of antigenically drifted viruses. The effect of drift on vaccine protection is not easy to predict and, even in drifted years, significant protection can be observed.