COVID-19 Severity and Waning Immunity After up to 4 mRNA Vaccine Doses in 73 608 Patients With Cancer and 621 475 Matched Controls in Singapore

Abstract

ImportanceDespite 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.ObjectiveTo 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 ParticipantsA 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, 73 608 patients with cancer (23 217 active treatment, 50 391 cancer survivors) and 621 475 controls matched by age, sex, race and ethnicity, and socioeconomic status were included.ExposureVaccine doses received, from zero to 4 doses, and time elapsed since last vaccine dose.OutcomesCompeting-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.ResultsThe 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 73 608 patients with cancer, 27 170 (36.9%) were men; 60 100 (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.ConclusionThis 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.

Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals

“…A study described a similar finding in relation to the time since second vaccine dose [41]. This finding is consistent with waning vaccine immunity that has been previously described [42][43][44][45][46]. Our study also highlights the increased risk of Omicron SARS-CoV-2 infection among vaccinated individuals from Hispanic, Asian, and Black ethnic/racial groups.…”

Serological Response to COVID-19 Vaccination is Impaired in Adults with Hematologic Malignancies when Compared to Adults with Solid Tumors and HIV: Observations from a Single Tertiary Institution

“…Our study revealed that those who did not seroconvert after they completed a primary vaccination series and booster doses as recommended by the US FDA for immunocompromised individuals [19] may develop antibodies with additional vaccine doses. Our data are supported by a larger nationwide cohort study conducted in Singapore which showed that cancer patients received significant protection against severe COVID-19 with a third dose of vaccine and were further protected after a fourth dose of vaccine [20] . Although the benefit of fifth and sixth doses of vaccine is still uncertain, one of our patients acquired additional vaccine doses outside of existing guidelines and successfully seroconverted after six total doses of vaccine.…”

Humoral Response and Safety after a Fourth Dose of the SARS-CoV-2 BNT162b2 Vaccine in Cancer Patients Undergoing Active Treatment—Results of a Prospective Observational Study

“…All but one of these patients, three weeks after the fourth dose, developed positive levels of anti-spike antibodies [ 25 ]. Recently, a nationwide cohort study from Singapore has provided evidence of the clinical effectiveness of mRNA-based fourth booster dose vaccines against COVID-19 in patients with cancer [ 26 ]. However, this study revealed some limitations, as reported by the authors themselves: the study may have been objected to confounding variables that could not be controlled for [ 26 ].…”

“…Recently, a nationwide cohort study from Singapore has provided evidence of the clinical effectiveness of mRNA-based fourth booster dose vaccines against COVID-19 in patients with cancer [ 26 ]. However, this study revealed some limitations, as reported by the authors themselves: the study may have been objected to confounding variables that could not be controlled for [ 26 ]. In our hospital, a task force charged with promoting the importance of the COVID-19 vaccine for cancer patients has been established since February 2021.…”