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

Author(s): Wei Chong Tan, MBBS1; Janice Yu Jin Tan, BSS (Hons)2; Joline Si Jing Lim, MBBS3,4,5; Ryan Ying Cong Tan, MBBS1; Ainsley Ryan Yan Bin Lee, MBBS (Hons)5; Fun Loon Leong, BSc1; Soo Chin Lee, MBBS3,4; Louis Yi Ann Chai, MBBS, PhD3,6,7,8; Thuan Tong Tan, PhD9; Muhammad Ismail Bin Abdul Malek, BSc2; Benjamin Ong, MBBS2,5; David Chien Lye, MBBS9,10,11,12; Calvin J. Chiew, MPH2,10; Wee Joo Chng, MBChB, PhD3,4,5; Soon Thye Lim, MBBS1; Lavina D. Bharwani, MD13; Iain Beehuat Tan, MBBS, PhD1,14,15,19; Raghav Sundar, MBBS, PhD3,5,16,17,18; Kelvin Bryan Tan, PhD2,19
Source: JAMA Oncol. 2023;9(9):1221-1229. doi:10.1001/jamaoncol.2023.2271
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

A study from Singapore showing that each COVID-19 booster protected cancer patients for approximately five months after receiving third and fourth vaccine doses. Interest in the COVID-19 booster in 2023 has waned, and although infection is not as common today, many patients will die due to COVID-19 this year.


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.


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.


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, 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.


Vaccine doses received, from zero to 4 doses, and time elapsed since last vaccine dose.


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.


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 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.


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.

Author Affiliations

1Division of Medical Oncology, National Cancer Centre Singapore, Singapore; 2Ministry of Health, Singapore; 3Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore; 4Experimental Therapeutics Programme, Cancer Science Institute, National University of Singapore, Singapore; 5Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 6Division of Infectious Diseases, Department of Medicine, National University Health System, Singapore; 7Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 8Synthetic Biology for Clinical and Technological Innovation, National University of Singapore, Singapore; 9Department of Infectious Diseases, Singapore General Hospital, Singapore; 10National Centre for Infectious Diseases, Singapore; 11Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 12Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore; 13Department of Medical Oncology, Tan Tock Seng Hospital, Singapore; 14Genome Institute of Singapore, Singapore; 15Duke-NUS Medical School, Singapore; 16Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore; 17The N.1 Institute for Health, National University of Singapore, Singapore; 18Singapore Gastric Cancer Consortium, Singapore; 19Saw Swee Hock School of Public Health, National University of Singapore, Singapore

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