98. COVID-19 Vaccine Breakthrough Hospitalizations and Deaths in the Veterans Health Administration

Abstract Background A COVID-19 vaccine breakthrough infection is defined as SARS-CoV-2 RNA or antigen detected ≥ 14 days after completion of a final vaccine dose. CDC’s May 25 MMWR report of 10,262 vaccine breakthrough infections in the U.S. is likely an underestimate. Herein, we report Veterans Health Administration (VHA) breakthrough cases, focusing on hospitalizations and deaths. Methods We extracted COVID-19 vaccine breakthrough infections tested between 1/19/2021 and 4/30/2021 from the VHA Corporate Data Warehouse (including screening tests). We reviewed medical records of cases who died and/or were hospitalized within 14 days of SARS-CoV-2 positive test for clinician documentation of conditions deemed high risk for COVID-19 and to confirm hospitalization or death was related to COVID-19. SARS-CoV-2 whole genome sequencing (Clear Labs platform) and antigen testing (Abbott BinaxNOW) from available patient samples were performed and Pangolin lineage determined. Results 1,142 COVID-19 vaccine breakthrough infections were identified. 357/1,142 (31.3%) were hospitalized and/or died. 1,085 (95%) were male (Table 1), and median age was 72.5 years (74 years for hospitalized/deceased patients). COVID-19 infection contributed to hospitalization and/or death in 139 (38.9%) cases. The remaining 218 (61.1%) were hospitalized or died of causes apparently unrelated to COVID-19. Smoking and heart conditions were seen most frequently among hospitalized/deceased breakthrough cases (Table 2). Variant B.1.1.7 was predominant, present in 17/27 (63%) total samples sequenced, and 13/21 (61.9%) hospitalized/deceased. (Table 3). Of 21 sequenced hospitalized/deceased cases, SARS-CoV-2 antigen positivity was present in 11 (52.4%). Conclusion Compared to CDC reported breakthrough infections, VHA cases were more male, older, and hospitalized/died at higher frequency. Further study is needed to determine the contribution of specific underlying conditions, COVID-19 vaccine formulations and variants on hospitalization and death among COVID-19 vaccine breakthrough infections. Sequencing efforts for breakthrough cases should be intensified, particularly for those presenting with more severe infections. Disclosures All Authors: No reported disclosures

Background. Changes in the influenza hemagglutinin protein during replication of influenza in eggs during vaccine production may contribute to low vaccine effectiveness (VE). This phenomenon, egg adaptation, can explain VE differences between egg-based (QIVe-SD) and cell-based (QIVc) quadrivalent influenza vaccines. This research evaluated the relative vaccine effectiveness (rVE) of QIVc versus QIVe-SD in the reduction of influenza-related and any respiratory-related hospitalizations/emergency room (ER) visits among subjects 4-64 years old during the 2019/20 influenza season.
Methods. A retrospective cohort analysis was conducted among subjects 4-64 years old vaccinated with QIVc or QIVe-SD using administrative claims data in the U.S. (IQVIA PharMetrics ® Plus). The adjusted number of events and rates of influenza-related hospitalizations/ER visits and respiratory-related hospitalizations/ER visits were assessed using inverse probability of treatment weighting (IPTW). Poisson regression was used to estimate relative vaccine effectiveness (rVE). In the main analysis, the study period was from Aug 4, 2019 to Mar 7, 2020 (ending early to avoid any influenza outcome misclassification with COVD-19 infection). In the assessment of the high influenza activity period (HIAP), the analysis period was restricted to Dec 8, 2019 to Mar 7, 2020.
Conclusion. QIVc was more effective in preventing influenza-related and respiratory-related hospitalizations/ER visits compared to QIVe-SD, using either a broad influenza season definition or restricting to the HIAP.

Session: O-21. Innovations and Advancements in Vaccines
Background. Dengue fever is a mosquito-borne viral disease endemic in 128 countries. An unmet clinical need remains for an effective vaccine that can be used more broadly than the vaccine presently available. A clinical development program has evaluated the long-term safety, immunogenicity, and vaccine efficacy (VE) of TAK-003, a live attenuated tetravalent dengue vaccine with a DENV-2 backbone engineered to elicit immune responses to all 4 dengue serotypes.
Methods. 18 clinical trials in 13 countries have involved 28,175 seropositive/seronegative participants aged from 1.5-60 years from endemic/non-endemic regions. In the ongoing pivotal phase III study, 4-16-year-old healthy children (N=20,099) were randomized 2:1 to receive two doses of TAK-003 or placebo, 3 months apart for an evaluation of VE and safety over a multi-year period stratified pre-vaccination dengue serostatus. Active surveillance throughout the trial detected symptomatic dengue. The trial will continue up to 4-4.5 years post 2 nd dose, and for another 25 months after a booster dose. Data up to 3 years after the second vaccination are currently available.
Conclusion. TAK-003 is immunogenic against all 4 dengue serotypes and continues to be efficacious, well-tolerated, and with no evidence of disease enhancement in seronegative population up to 3 years post-vaccination. Methods. We extracted COVID-19 vaccine breakthrough infections tested between 1/19/2021 and 4/30/2021 from the VHA Corporate Data Warehouse (including screening tests). We reviewed medical records of cases who died and/or were hospitalized within 14 days of SARS-CoV-2 positive test for clinician documentation of conditions deemed high risk for COVID-19 and to confirm hospitalization or death was related to COVID-19. SARS-CoV-2 whole genome sequencing (Clear Labs platform) and antigen testing (Abbott BinaxNOW) from available patient samples were performed and Pangolin lineage determined.
Conclusion. Compared to CDC reported breakthrough infections, VHA cases were more male, older, and hospitalized/died at higher frequency. Further study is needed to determine the contribution of specific underlying conditions, COVID-19 vaccine formulations and variants on hospitalization and death among COVID-19 vaccine breakthrough infections. Sequencing efforts for breakthrough cases should be intensified, particularly for those presenting with more severe infections.
Disclosures. Background. Immune responses to influenza vaccines (IV) are influenced by pre-existing antibodies to vaccine components. Immune responses to vaccines were evaluated following vaccination with quadrivalent egg-based live-attenuated influenza vaccine (LAIV4) and cell-culture inactivated influenza vaccine (ccIIV4).
Results. Day 0 GMTs were similar for LAIV4 and ccIIV4. Day 28 GMTs were higher for ccIIV4 (p< 0.05) and increased following vaccination for all 5 antigens (p< 0.05) except B/Phuket following LAIV4. The GMFR range was 2.4 to 3.0 for ccIIV4 and 1.0 to 1.3 for LAIV4. In linear regression controlling for age and prior season vaccination for both vaccines, baseline titers inversely predicted GMFR. The GMFR to A/ H3N2 cell-grown and egg-grown antigens were similar within vaccine type. Day 0 and Day 28 A(H1N1) titers for LAIV4 Conclusion. The HI response to ccIIV4 was greater than LAIV4 in this study of mostly older children. Day 0 HI titers were 1) a significant determinant of GMFR;