RESUMEN
IMPORTANCE: Assessing population-wide risk-benefit ratio of COVID-19 vaccination remains relevant in the current era of Omicron endemicity and boosting. Assessments of mortality risk and cardiovascular events post-vaccination/infection were generally made prior to emergence of milder Omicron and booster rollout. METHODS: Retrospective cohort study from 6th January to 31st December 2022 (Omicron-predominant transmission), amongst adult Singaporeans aged ≥18 years. Cox regression models adjusted for demographics/comorbidities were used to estimate risk of all-cause mortality and cardiovascular events 0-180 days post-mRNA vaccination/SARS-CoV-2 infection, compared to >180 days post-mRNA vaccination. Risk periods post-vaccination were further stratified by presence/absence of SARS-CoV-2 infection in the preceding 180 days; similarly, risk periods post-infection were further stratified by vaccination in the 180 days preceding infection. RESULTS: 3,137,210 adults participated, with 2,047,008 vaccine doses administered (99 % being booster doses) and 1,189,846 infections. 23,028 deaths and 54,017 cardiac events were recorded. No elevated risk of all-cause mortality/cardiovascular events was observed across all age strata post-vaccination. Conversely, all-cause mortality post-infection remained elevated up to >180 days in older adults (≥60 years), compared to person-time > 180 days post-vaccination. For vaccine-breakthrough SARS-CoV-2 infection in older adults vaccinated <180 days prior, risk of mortality was only elevated up to 60 days post-infection, but not beyond. Elevated risk of cardiovascular events 1-2 months after any SARS-CoV-2 infection was observed across all age strata, with elevated risk observed in older adults >180 days post-infection (adjusted-hazards-ratio, aHR = 1.18, 95 %CI = 1.04-1.34). Preceding vaccination within 180 days prior to infection attenuated this risk, with no significantly elevated post-acute risk of cardiovascular events (>180 days: aHR = 1.10, 95 %CI = 0.95-1.07). CONCLUSION: No increased risk of all-cause mortality or cardiovascular events was observed up to 180 days after any mRNA vaccination dose in the Omicron era; vaccination attenuated post-acute cardiovascular risk in older adults. The risk-benefit ratio of vaccination remained positive during Omicron.
RESUMEN
Importance: Despite patients with cancer being at risk of poor outcomes from COVID-19, there are few published studies for vaccine efficacy in this group, with suboptimal immunogenicity and waning vaccine efficacy described in small studies being a concern. Objective: To assess the incidence rate of severe COVID-19 disease outcomes associated with the number of vaccine doses received and the waning of protection over time. Design, Setting, and Participants: A prospective multicenter observational cohort study was carried out over 2 time periods (September 15, 2021, to December 20, 2021 [delta wave], and January 20, 2022, to November 11, 2022 [omicron wave]) predominated by SARS-CoV-2 delta and omicron variants, respectively. Overall, 73â¯608 patients with cancer (23â¯217 active treatment, 50â¯391 cancer survivors) and 621â¯475 controls matched by age, sex, race and ethnicity, and socioeconomic status were included. Exposure: Vaccine doses received, from zero to 4 doses, and time elapsed since last vaccine dose. Outcomes: Competing-risk regression analyses were employed to account for competing risks of death in patients with cancer. Main outcomes were incidence rate ratios (IRRs) of COVID-19 infection, hospitalization, and severe disease (defined as requirement for supplemental oxygen, intensive care, or death). The IRRs stratified by time from last vaccine dose served as indicators of waning of vaccine effectiveness over time. Results: The mean (SD) age of actively treated patients with cancer, cancer survivors, and controls were 62.7 (14.7), 62.9 (12.6), and 61.8 (14.7) years, respectively. Of 73â¯608 patients with cancer, 27â¯170 (36.9%) were men; 60â¯100 (81.6%) were Chinese, 7432 (10.1%) Malay, 4597 (6.2%) Indian, and 1479 (2.0%) were of other races and ethnicities. The IRRs for the 3-dose and 4-dose vs the 2-dose group (reference) for COVID-19 hospitalization and severe disease were significantly lower during both the delta and omicron waves in cancer and control populations. The IRRs for severe disease in the 3-dose group for active treatment, cancer survivors, and controls were 0.14, 0.13, and 0.07 during the delta wave and 0.29, 0.19, and 0.21 during omicron wave, respectively. The IRRs for severe disease in the 4-dose group during the omicron wave were even lower at 0.13, 0.10 and 0.10, respectively. No waning of vaccine effectiveness against hospitalization and severe disease was seen beyond 5 months after a third dose, nor up to 5 months (the end of this study's follow-up) after a fourth dose. Conclusion: This cohort study provides evidence of the clinical effectiveness of mRNA-based vaccines against COVID-19 in patients with cancer. Longevity of immunity in preventing severe COVID-19 outcomes in actively treated patients with cancer, cancer survivors, and matched controls was observed at least 5 months after the third or fourth dose.