Vaccines to prevent herpes zoster have been associated with reduced dementia risk. We conducted a retrospective matched cohort study of Kaiser Permanente Southern California members aged ≥65 years who received two doses of RZV 4 weeks-6 months apart between 01 April 2018 and 31 December 2020, with no dementia diagnoses or dementia medications prior to or within 6 months of their second RZV dose. Cox regression with inverse probability of treatment weighting was used to estimate adjusted hazard ratios (aHRs). The study included 65,800 RZV-vaccinated individuals and 263,200 unvaccinated matches. Vaccination with two doses of RZV was associated with a 51% lower risk of dementia (aHR: 0.49 [95% confidence interval (CI): 0.46-0.51]); aHRs were comparable across age, and racial and ethnic groups, but the risk reduction was stronger in females compared to males. In an evaluation of potential healthy vaccinee bias, the aHR of dementia for RZV compared to Tdap was 0.73 (95% CI: 0.67-0.79). Vaccination with two doses of RZV is associated with a statistically significant reduction in the risk of dementia in adults aged ≥65 years. After accounting for healthy vaccinee bias, RZV vaccination remains associated with a statistically significant lower risk of dementia.

Vaccines to prevent herpes zoster, historically zoster vaccine live (ZVL), have been associated with reduced dementia risk. We evaluated the association between recombinant zoster vaccine (RZV) and reduction in all-cause dementia in adults aged ≥65 years at Kaiser Permanente Southern California. We conducted a retrospective matched cohort study of adults aged ≥65 years who received 2 doses of RZV 4 weeks-6 months apart between 1 April 2018 and 31 December 2020 and were matched 1:4 with unvaccinated individuals on age group, sex, race/ethnicity, and history of ZVL, with no dementia diagnoses or dementia medications prior to or within 6 months of index date (second dose date among vaccinated; same date for matched unvaccinated). Follow-up started 6 months after index date until dementia identification by ≥1 ICD-10 code in electronic health records, receipt of zoster vaccine, membership termination, death, or end of follow-up (31 December 2023), whichever came first. Cox regression with inverse probability of treatment weighting was used to estimate adjusted hazard ratios (aHRs). To evaluate residual confounding, we assessed the relationship between RZV and a composite negative control outcome (NCO). To evaluate potential healthy vaccinee bias, we compared dementia incidence in RZV-vaccinated individuals versus Tdap-vaccinated individuals. This study included 65,800 individuals vaccinated with 2 RZV doses and 263,200 unvaccinated (57.6% female, 61.2% non-Hispanic white, mean age 73.3 years). The mean follow-up time in vaccinated and unvaccinated individuals was 3.4 and 1.8 years, respectively. The incidence rate of dementia among vaccinated was 10.74 (95% confidence interval [CI]: 10.32-11.18) per 1000 person-years compared to 23.04 (95% CI: 22.61-23.48) among unvaccinated individuals. The aHR of 2 doses of RZV against dementia was 0.49 (95% CI: 0.46-0.51; Figure 1); aHRs were comparable across age and racial/ethnic groups. The aHR for the NCO was 0.94 (0.89-1.00; Figure 2). The aHR of 2 doses of RZV compared to Tdap was 0.73 (0.67-0.79; Figure 3). 2 RZV doses were significantly associated with a reduction in risk of dementia in adults aged ≥65 years. After accounting for healthy vaccinee bias, RZV vaccination remained associated with a statistically significant lower risk of dementia.

Background. Influenza causes substantial morbidity, particularly among older individuals. Updated data on the effectiveness of currently licensed vaccines in this population are needed. Methods. At Kaiser Permanente Southern California, we conducted a retrospective cohort study to evaluate comparative vaccine effectiveness (cVE) of high-dose (HD), adjuvanted, and standard-dose (SD) cell-based influenza vaccines, relative to the SD egg-based vaccine. We included adults aged >= 65 years who received an influenza vaccine between 1 August 2022 and 31 December 2022, with follow-up up to 20 May 2023. Primary outcomes were: (1) influenza-related medical encounters and (2) polymerase chain reaction (PCR)-confirmed influenza-related hospitalization. Adjusted hazard ratios (aHR) were estimated by Cox proportional hazards regression, adjusting for confounders using inverse probability of treatment weighting (IPTW). cVE (%) was calculated as (1-aHR) x 100 when aHR <= 1, and ([1/aHR]-1) x 100 when aHR >1. Results. Our study population (n = 495 119) was 54.9% female, 46.3% non-Hispanic White, with a median age of 73 years (interquartile range [IQR] 69-79). Characteristics of all groups were well balanced after IPTW. Adjusted cVEs against influenza-related medical encounters in the HD, adjuvanted, and SD cell-based vaccine groups were 9.1% (95% confidence interval [CI]: .9, 16.7), 16.9% (95% CI: 1.7, 29.8), and -6.3 (95% CI: -18.3, 6.9), respectively. Adjusted cVEs against PCR-confirmed hospitalization in the HD, adjuvanted, and SD cell-based groups were 25.1% (95% CI: .2, 43.8), 61.6% (95% CI: 18.1, 82.0), and 26.4% (95% CI: -18.3, 55.7), respectively. Conclusions. Compared to the SD egg-based vaccine, HD and adjuvanted vaccines conferred additional protection against influenza-related outcomes in the 2022-2023 season in adults >= 65 years. Our results provide real-world evidence of the comparative effectiveness of currently licensed vaccines.

Emerging SARS-CoV-2 sublineages continue to cause serious COVID-19 disease, but most individuals have not received any COVID-19 vaccine for >1 year. Assessment of long-term effectiveness of bivalent COVID-19 vaccines against circulating sublineages is important to inform the potential need for vaccination with updated vaccines. In this test-negative study at Kaiser Permanente Southern California, sequencing-confirmed BA.4/BA.5- or XBB-related SARS-CoV-2-positive cases (September 1, 2022 to June 30, 2023), were matched 1:3 to SARS-CoV-2-negative controls. We assessed mRNA-1273 bivalent relative (rVE) and absolute vaccine effectiveness (VE) compared to >= 2 or 0 doses of original monovalent vaccine, respectively. The rVE analysis included 20,966 cases and 62,898 controls. rVE (95%CI) against BA.4/BA.5 at 14-60 days and 121-180 days was 52.7% (46.9-57.8%) and 35.5% (-2.8-59.5%) for infection, and 59.3% (49.7-67.0%) and 33.2% (-28.2-68.0%) for Emergency Department/Urgent Care (ED/UC) encounters. For BA.4/BA.5-related hospitalizations, rVE was 71.3% (44.9-85.1%) and 52.0% (-1.2-77.3%) at 14-60 days and 61-120 days, respectively. rVE against XBB at 14-60 days and 121-180 days was 48.8% (33.4-60.7%) and -3.9% (-18.1-11.3%) for infection, 70.7% (52.4-82.0%) and 15.7% (-6.0-33.2%) for ED/UC encounters, and 87.9% (43.8-97.4%) and 57.1% (17.0-77.8%) for hospitalization. VE and subgroup analyses (age, immunocompromised status, previous SARS-CoV-2 infection) results were similar to rVE analyses. rVE of mRNA-1273 bivalent vaccine against BA.4/BA.5 and XBB infections, ED/UC encounters, and hospitalizations waned over time. Periodic revaccination with vaccines targeting emerging variants may be important in reducing COVID-19 morbidity and mortality.

This retrospective cohort study evaluated the comparative vaccine effectiveness (cVE) of licensed standard-dose cell-based versus egg-based influenza vaccines in preventing influenza hospitalization among adults 18-64 years during the 2022-2023 season. The cohort included eligible Kaiser Permanente Southern California members who received ≥ 1 dose of influenza vaccine (n = 848,334). The adjusted cVE against influenza hospitalization was -10.1% (95% CI: -49.8%, 37.8%) in the 18- to 49-year-old cohort. In the 50- to 64-year-old cohort, the adjusted cVE was 14.9% (-33.8%, 52.1%). Cell-based and egg-based influenza vaccines conferred comparable protection against influenza hospitalization in adults 18-64 years of age in the 2022-2023 season.

PURPOSE: Data on vaccine-associated corneal transplant rejections are limited. We examined the association between graft rejection and vaccination. DESIGN: Matched case-control METHODS: We used electronic health records to identify corneal transplant recipients between January 2008 and August 2022 at Kaiser Permanente Southern California. Cases were transplant recipients who experienced a graft rejection (outcome) during the study period. Randomly selected controls who did not experience a corneal graft rejection at their matched cases' index date (rejection date) were matched in a 3:1 ratio to cases. For controls, index date was determined by adding the number of days between transplant and graft rejection of their matched case to the control's transplant date. RESULTS: The study included 601 cases and 1803 matched controls (mean age 66 years [s.d. 17.0], 52% female, 47% non-Hispanic white). Twenty-three% of cases and 22% of controls received >= 1 vaccinations within 12 weeks prior to the index date. The adjusted odds ratio (aOR) for vaccination in the 12 weeks prior to index date, comparing cases to controls was 1.17 (95% CI: 0.91, 1.50]). The aOR was 1.09 (0.84, 1.43) for 1 vaccination, 1.53 (0.90, 2.61) for 2 vaccinations, and 1.79 (0.55, 5.57) for >= 3 vaccinations. The aOR was 1.60 (0.81, 3.14) for mRNA vaccines, and 1.19 (0.80, 1.78) for adjuvanted/high dose vaccines. CONCLUSIONS: We found no evidence to suggest an association between vaccination and graft rejection. Our findings provide support for the completion of recommended vaccinations for corneal transplant recipients, without significantly increasing the risk of graft rejection.

Abstract Background Vaccination is recommended for prevention of infectious diseases. For individuals with a history of corneal transplantation, however, there are concerns that vaccination may trigger allograft rejection through elevated immune activity. The association between vaccination and graft rejection remains unclear. Methods We conducted a nested case-control study to evaluate the association between graft rejection and vaccination in corneal transplant recipients at Kaiser Permanente Southern California (KPSC) between January 2008 and August 2022. We identified all KPSC members who received a corneal transplant during the study period, with no history of prior transplant or rejection. Cases were those who experienced a graft rejection during the study period and eligible controls were those who had not experienced a rejection at the time of a given case. Controls were randomly selected via risk-set sampling and matched in a 3:1 ratio to cases on age, sex, and transplant date (±12 weeks). Index date was the date of rejection for cases. For controls, index date was determined by adding the number of days between transplant and rejection of the matched case to the control’s transplant date. We performed multivariable conditional logistic regression to compare the odds of vaccination (all types) in the 12 weeks prior to the index date in cases and controls, while adjusting for potential confounders. Results Our study included 601 corneal transplant recipients with rejection (cases), and 1,803 matched controls. The overall cohort was 48% female and 47% white, with a mean age of 66 years (s.d. 17) (Table 1). A total of 136 (23%) cases and 373 (21%) controls received vaccination within 12 weeks of the index date (adjusted odds ratio 1.17, 95% CI: 0.91, 1.50) (Table 2).Table 1.Characteristics of corneal transplant recipients who experienced graft rejection (cases) and who did not experience graft rejection (controls), Kaiser Permanente Southern California, 01/01/2008 - 08/31/2022. a Defined in the 12 months prior to index date unless otherwise indicated b Defined in the 12 weeks prior to index date c HIV/AIDS, leukemia, lymphoma, congenital immunodeficiencies, asplenia/hypospenia, or organ transplant at any time prior to index date, or immunosuppressant medication used during 12 weeks prior to index date d Includes dexamethasone, fluorometholone, loteprednol, difluprednate, prednisolone, methylprednisolone, and prednisone.Table 2.Vaccination among corneal transplant recipients who experienced graft rejection (cases) and who did not experience graft rejection (controls), Kaiser Permanente Southern California, 01/01/2008 - 08/31/2022. a Adjusted for race/ethnicity, Charlson comorbidity score, immunocompromised status, corneal transplant type, oral/ocular steroids received 12 weeks prior to index date (yes/no), non-index vaccinations received 12 weeks prior to index date (yes/no), and medical center and area. Conclusion We did not find evidence of an elevated risk of graft rejection associated with vaccination given in the 12 weeks prior to the index date. Although our study is the largest study examining the association between corneal transplant rejection and vaccination to our knowledge, this study may be underpowered to detect a minimal increase in risk. Our findings provide support for completion of recommended vaccinations for patients who are planning or have received a corneal transplant. Disclosures Jennifer H. Ku, PhD MPH, GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support Julia Tubert, MPH, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Yi Luo, PhD, GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Kevin L. Winthrop, MD, MPH, AN2: Advisor/Consultant|AN2: Grant/Research Support|Insmed: Advisor/Consultant|Insmed: Grant/Research Support|Insmed: This study was funded by Insmed Inc.|Paratek: Advisor/Consultant|Paratek: Grant/Research Support|Red Hill Biopharma: Advisor/Consultant|Red Hill Biopharma: Board Member|Red Hill Biopharma: Grant/Research Support|Renovion: Advisor/Consultant|Renovion: Grant/Research Support|Spero: Advisor/Consultant|Spero: Grant/Research Support Divya Srikumaran, MD, Alcon: Advisor/Consultant|Claris Biotherpeautics: Grant/Research Support Ana Florea, PhD MPH, Gilead: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Hung Fu Tseng, PhD MPH, GSK: Grant/Research Support|Moderna: Grant/Research Support

The bivalent (original and Omicron BA.4/BA.5) mRNA-1273 COVID-19 vaccine was authorized to offer broader protection against COVID-19. We conducted a matched cohort study to evaluate the effectiveness of the bivalent vaccine in preventing hospitalization for COVID-19 (primary outcome) and medically attended SARS-CoV-2 infection and hospital death (secondary outcomes). Compared to individuals who did not receive bivalent mRNA vaccination but received ≥2 doses of any monovalent mRNA vaccine, the relative vaccine effectiveness (rVE) against hospitalization for COVID-19 was 70.3% (95% confidence interval, 64.0%-75.4%). rVE was consistent across subgroups and not modified by time since last monovalent dose or number of monovalent doses received. Protection was durable ≥3 months after the bivalent booster. rVE against SARS-CoV-2 infection requiring emergency department/urgent care and against COVID-19 hospital death was 55.0% (50.8%-58.8%) and 82.7% (63.7%-91.7%), respectively. The mRNA-1273 bivalent booster provides additional protection against hospitalization for COVID-19, medically attended SARS-CoV-2 infection, and COVID-19 hospital death.

The bivalent (original and Omicron BA.4/BA.5) mRNA-1273 COVID-19 vaccine was authorized to offer broader protection against COVID-19. We conducted a matched cohort study to evaluate the effectiveness of the bivalent vaccine in preventing hospitalization for COVID-19 (primary outcome) and medically attended SARS-CoV-2 infection and hospital death (secondary outcomes). Compared to individuals who did not receive bivalent mRNA vaccination but received ≥2 doses of any monovalent mRNA vaccine, the relative vaccine effectiveness (rVE) against hospitalization for COVID-19 was 70.3% (95% confidence interval, 64.0%-75.4%). rVE was consistent across subgroups and not modified by time since last monovalent dose or number of monovalent doses received. Protection was durable ≥3 months after the bivalent booster. rVE against SARS-CoV-2 infection requiring emergency department/urgent care and against COVID-19 hospital death was 55.0% (50.8%-58.8%) and 82.7% (63.7%-91.7%), respectively. The mRNA-1273 bivalent booster provides additional protection against hospitalization for COVID-19, medically attended SARS-CoV-2 infection, and COVID-19 hospital death.

Studies have reported reduced natural SARS-CoV-2 infection- and vaccine-induced neutralization against omicron BA.4/BA.5 compared with earlier omicron subvariants. This test-negative case–control study evaluates mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with omicron subvariants. The study includes 30,809 SARS-CoV-2 positive and 92,427 SARS-CoV-2 negative individuals aged ≥18 years tested during 1/1/2022-6/30/2022. While 3-dose VE against BA.1 infection is high and wanes slowly, VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection is initially moderate to high (61.0%-90.6% 14-30 days post third dose) and wanes rapidly. The 4-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranges between 64.3%-75.7%, and is low (30.8%) against BA.5 14-30 days post fourth dose, disappearing beyond 90 days for all subvariants. The 3-dose VE against hospitalization for BA.1, BA.2, and BA.4/BA.5 is 97.5%, 82.0%, and 72.4%, respectively; 4-dose VE against hospitalization for BA.4/BA.5 is 88.5%. Evaluation of the updated bivalent booster is warranted.

We evaluated relative vaccine effectiveness (rVE) of 4- vs. 3-dose mRNA-1273 against SARS-CoV-2 infection, and COVID-19 hospitalization and death in immunocompetent adults aged >50 years at Kaiser Permanente Southern California. We included 178,492 individuals who received a fourth dose of mRNA-1273, and 178,492 randomly selected 3-dose recipients who were matched to 4-dose recipients by age, sex, race/ethnicity, and third dose date. Adjusted 4- vs. 3-dose rVE against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospitalization death were 25.9 % (23.5 %, 28.2 %), 67.3 % (58.7 %, 74.1 %), and 72.5 % (-35.9 %, 95.2 %), respectively. Adjusted rVE against SARS-CoV-2 infection ranged between 19.8 % and 39.1 % across subgroups. Adjusted rVE against SARS-CoV-2 infection and COVID19 hospitalization decreased 2-4 months after the fourth dose. Four mRNA-1273 doses provided significant protection against COVID-19 outcomes compared with 3 doses, consistent in various subgroups of demographic and clinical characteristics, although rVE varied and waned over time.& COPY; 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Abstract Background We conducted a prospective cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of a booster dose vs 2-dose primary series of messenger RNA (mRNA)-1273 in immunocompetent individuals. Methods Immunocompetent adults who received a booster dose of mRNA-1273 from October 2021 through December 2021 were matched 1:1 to randomly selected 2-dose mRNA-1273 recipients by age, sex, race/ethnicity, and second-dose date and followed up through January 2022. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), comparing outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection and coronavirus disease 2019 [COVID-19] hospitalization and hospital death) in the booster-dose and 2-dose groups. Adjusted rVE (%) was calculated as (1 − aHR) × 100. aHRs and rVE were also estimated by subgroup and month of follow-up. Results The study included 431 328 booster-dose vaccinated adults matched to 431 328 2-dose vaccinated adults. rVE was 61.3% (95% CI: 60.5%–62.2%) against SARS-CoV-2 infection, 89.0% (86.2%–91.2%) against COVID-19 hospitalization, and 96.0% (68.0%–99.5%) against COVID-19 hospital death. rVE against SARS-CoV-2 infection ranged from 55.6% to 66.7% across all subgroups. rVE against SARS-CoV-2 infection decreased from 67.1% (0 to <1 month of follow-up) to 30.5% (2 to <3 months). For COVID-19 hospitalization, rVE decreased from 91.2% (0 to <1 month) to 78.7% (2 to <3 months). Conclusions Among immunocompetent adults, the mRNA-1273 booster conferred additional protection against SARS-CoV-2 infection and severe COVID-19 disease compared with the 2-dose mRNA-1273 primary series during periods of Delta and Omicron predominance.

BACKGROUND:Data on the effectiveness of the 3-dose mRNA-1273 primary series are limited, particularly in comparison to 2 doses. Given suboptimal COVID-19 vaccine uptake among immunocompromised populations, it is important to monitor the effectiveness of fewer than the recommended doses in this population. METHODS:We conducted a matched cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of the 3-dose series vs 2 doses of mRNA-1273 in preventing SARS-CoV-2 infection and severe COVID-19 outcomes among immunocompromised individuals. RESULTS:We included 21,942 3-dose recipients who were 1:1 matched with randomly selected 2-dose recipients (third doses accrued 08/12/2021-12/31/2021, with follow-up through 01/31/2022). Adjusted rVE of 3 vs 2 doses of mRNA-1273 against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death were 55.0 % (95 % CI: 50.8-58.9 %), 83.0 % (75.4-88.3 %), and 87.1 % (30.6-97.6 %), respectively. CONCLUSION:Three doses of mRNA-1273 were associated with a significantly higher rVE against SARS-CoV-2 infection and severe outcomes, compared to 2 doses. These findings were consistent across subgroups of demographic and clinical characteristics, and mostly consistent across subgroups of immunocompromising conditions. Our study highlights the importance of completing the 3-dose series for immunocompromised populations.

Abstract Background While a 3-dose mRNA-1273 primary series is recommended for moderately or severely immunocompromised (IC) individuals in the U.S., some IC individuals do not complete the 3-dose series. We conducted a matched cohort study to evaluate the relative vaccine effectiveness (rVE) of the 3-dose mRNA-1273 primary series vs. 2 doses of mRNA-1273 in preventing SARS-CoV-2 infection and severe COVID-19 disease in IC individuals. Methods IC individuals aged ≥18 years with ≥12 months of Kaiser Permanente Southern California membership who received 3 doses of mRNA-1273 ≥24 days apart were 1:1 matched with randomly selected IC 2-dose recipients on age, sex, race/ethnicity, and 2nd dose date. Third doses were accrued from 08/12/2021 to 12/31/2021, with follow-up through 1/31/2022, spanning the delta and omicron periods. Outcomes were SARS-CoV-2 infection (positive molecular test or diagnosis code), COVID-19 hospitalization, and COVID-19 hospital death. Adjusted hazard ratios (aHR) with confidence intervals (CI) were estimated by Cox proportional hazards models. Adjusted rVE (%) was calculated as (1-aHR) x 100. Results Our study included 21,942 3-dose and 21,942 2-dose mRNA-1273 IC recipients. Adjusted rVE of 3 doses compared to 2 doses of mRNA-1273 against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death were 55.0% (95% CI: 50.8–58.9%), 83.0% (75.4–88.3%), and 87.1% (30.6–97.6%), respectively (Table 1). Adjusted rVE against SARS-CoV-2 infection ranged from 43.0% to 59.1% across subgroups of age, sex, race/ethnicity, history of SARS-CoV-2 infection, pregnancy, and comorbidities (Table 2). Point estimates of the 3-dose rVE were higher against COVID-19 infection and hospitalization in the first 3 months, compared to 3–6 months after the 3rd dose (Table 3).Table 1. Incidence rate and relative vaccine effectiveness of the mRNA-1273 3-dose primary series in preventing SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death among immunocompromised population, with 2-dose vaccinated comparisona-Adjusted for covariates age, sex, race/ethnicity, index date (in months), time between second dose and index date, number of outpatient and virtual visits, preventive care, Charlson comorbidity score, and immunocompromising sub-conditions*.b-Adjusted for covariates age, sex, index date (in months), time between second dose and index date, and immunocompromising sub-conditions* (except HIV/AIDS).*Leukemia, lymphoma, congenital immunodeficiencies, asplenia/hyposplenia, HIV/AIDS, transplant (hematopoietic stem cell and solid organ), and/or receipt of immunosuppressive medications.Table 2. Incidence rate and relative vaccine effectiveness of the mRNA-1273 3-dose primary series in preventing SARS-CoV-2 infection by subgroups among immunocompromised population, with 2-dose vaccinated comparisona-Adjusted for covariates age, sex, race/ethnicity, index date (in months), time between second dose and index date, number of outpatient and virtual visits, preventive care, Charlson comorbidity score, and immunocompromising sub-conditions (leukemia, lymphoma, congenital immunodeficiencies, asplenia/hyposplenia, HIV/AIDS, transplant [hematopoietic stem cell and solid organ], and/or receipt of immunosuppressive medications).Table 3. Incidence rate and relative vaccine effectiveness of the mRNA-1273 3-dose primary series in preventing SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death by month after index date among immunocompromised population, with 2-dose vaccinated comparisona-Adjusted for covariates age, sex, race/ethnicity, index date (in months), time between second dose and index date, number of outpatient and virtual visits, preventive care, Charlson comorbidity score, and immunocompromising sub-conditions*b-Adjusted for covariates age, sex, index date (in months), preventive care, Charlson comorbidity score, and immunocompromising sub-conditions*c-Adjusted for covariates age, sex, index date (in months), time between second dose and index date, and immunocompromising sub-conditions* (except HIV/AIDS)Vaccine effectiveness (%) was calculated as (1 – hazard ratio) × 100 when the hazard ratio was less than or equal to 1; vaccine effectiveness (%) was calculated as ([1/hazard ratio] – 1) × 100 when the hazard ratio was greater than 1.*Leukemia, lymphoma, congenital immunodeficiencies, asplenia/hyposplenia, HIV/AIDS, transplant (hematopoietic stem cell and solid organ), and/or receipt of immunosuppressive medications Conclusion Three doses of mRNA-1273 provide additional protection against SARS-CoV-2 infection and severe outcomes for IC individuals, compared to 2 doses, highlighting the importance of completing 3-doses for IC populations. However, possible waning of protection against SARS-CoV-2 infection and severe outcomes after 3 months supports the ACIP recommendation of a booster dose at least 3 months after the 3rd primary series dose for adequate protection of IC individuals. Disclosures Jennifer H. Ku, PhD MPH, GSK: Grant/Research Support|Moderna: Grant/Research Support Lina S. Sy, MPH, Dynavax: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Seqirus: Grant/Research Support Lei Qian, PhD, Dynavax: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support Bradley Ackerson, MD, Dynavax: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support Yi Luo, PhD, Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support Julia Tubert, MPH, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Gina Lee, MPH, Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support Ana Florea, PhD MPH, Gilead: Grant/Research Support|GSK: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Carla Talarico, PhD, Moderna: Employee of and a shareholder in Moderna Inc. Sijia Qiu, MS, Dynavax: Grant/Research Support|Moderna: Grant/Research Support Yun Tian, MS, Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support Hung Fu Tseng, PhD MPH, GSK: Grant/Research Support|Janssen: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Seqirus: Grant/Research Support.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant is highly transmissible with potential immune escape. We conducted a test-negative case–control study to evaluate mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with Omicron or Delta. The large, diverse study population included 26,683 SARS-CoV-2 test-positive cases with variants determined by S gene target failure status (16% Delta and 84% Omicron). The two-dose VE against Omicron infection at 14–90 days was 44.0% (95% confidence interval, 35.1–51.6%) but declined quickly. The three-dose VE was 93.7% (92.2–94.9%) and 86.0% (78.1–91.1%) against Delta infection and 71.6% (69.7–73.4%) and 47.4% (40.5–53.5%) against Omicron infection at 14–60 days and >60 days, respectively. The three-dose VE was 29.4% (0.3–50.0%) against Omicron infection in immunocompromised individuals. The three-dose VE against hospitalization with Delta or Omicron was >99% across the entire study population. Our findings demonstrate high, durable three-dose VE against Delta infection but lower effectiveness against Omicron infection, particularly among immunocompromised people. However, three-dose VE of mRNA-1273 was high against hospitalization with Delta and Omicron variants.

Background: We conducted a prospective cohort study at Kaiser Permanente Southern California to study the vaccine effectiveness (VE) of mRNA-1273 over time and during the emergence of the Delta variant. Methods: The cohort for this planned interim analysis consisted of individuals aged [≥]18 years receiving 2 doses of mRNA-1273 through June 2021, matched 1:1 to randomly selected unvaccinated individuals by age, sex, and race/ethnicity, with follow-up through September 2021. Outcomes were SARS-CoV-2 infection, and COVID-19 hospitalization and hospital death. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) comparing outcomes in the vaccinated and unvaccinated groups. Adjusted VE (%) was calculated as (1-aHR)x100. HRs and VEs were also estimated for SARS-CoV-2 infection by age, sex, race/ethnicity, and during the Delta period (June-September 2021). VE against SARS-CoV-2 infection and COVID-19 hospitalization was estimated at 0-<2, 2-<4, 4-<6, and 6-<8 months post-vaccination. Results: 927,004 recipients of 2 doses of mRNA-1273 were matched to 927,004 unvaccinated individuals. VE (95% CI) was 82.8% (82.2-83.3%) against SARS-CoV-2 infection, 96.1% (95.5-96.6%) against COVID-19 hospitalization, and 97.2% (94.8-98.4%) against COVID-19 hospital death. VE against SARS-CoV-2 infection was similar by age, sex, and race/ethnicity, and was 86.5% (84.8-88.0%) during the Delta period. VE against SARS-CoV-2 infection decreased from 88.0% at 0-<2 months to 75.5% at 6-<8 months. Conclusions: These interim results provide continued evidence for protection of 2 doses of mRNA-1273 against SARS-CoV-2 infection over 8 months post-vaccination and during the Delta period, and against COVID-19 hospitalization and hospital death.