COVID-19 breakthrough infections and humoral immune response among BNT162b2 vaccinated healthcare workers in Malaysia

ABSTRACT

The evaluation of breakthrough infection and humoral immunity responses are important outcomes for vaccination policy for healthcare staff. This prospective cohort study collected blood samples at 5-time points; before primary vaccine doses, and at 2, 10 and 24 weeks after BNT162b2 vaccination from 551 HCWs, between March and October 2021. We investigated the association between anti-spike-1 protein receptor-binding domain (anti-S1-RBD) antibody geometric mean titre (GMT) and breakthrough infections. Two weeks post-vaccination, the GMT of anti-S1-RBD antibodies was measured at almost maximum detectable value (3115 BAU/ml [95% CI, 3051–3180]); it decreased to 1486 BAU/ml (95% CI, 1371–1610) at 10 weeks; and to 315 BAU/ml (95% CI, 283–349) at 24 weeks. Prior COVID-19 infection and age significantly affected the antibody titres. Fifty-six participants, none of whom were COVID-19 convalescents, had breakthrough infections between 10 and 24 weeks post-vaccination. Before breakthrough infections, the GMT was not different between the breakthrough and non-breakthrough individuals. After infection, the GMT was significantly higher in individuals with breakthrough infections (2038 BAU/ml [95%CI, 1547–2685]), specifically in symptomatic breakthroughs, compared to those without infection (254 BAU/ml [95%CI, 233–278]). A notable surge in breakthrough infections among healthcare workers coincided with the emergence of the Delta variant and when BNT162b2-elicited antibody responses waned in 10–24 weeks (i.e. approximately 3–6 months). Post-breakthrough, the antibody response was boosted in individuals with symptomatic presentations, but not asymptomatic individuals. The study finding supports administering booster vaccination for healthcare staff, including those who recovered from asymptomatic breakthrough infection.

KEYWORDS:

• COVID-19
• breakthrough
• antibody
• BNT162b2
• healthcare worker
• vaccine
• humoral immunity
• IgG assay

Acknowledgments

The authors thank the Director-General of Health Malaysia for his permission to publish this manuscript. We thank Dr Ravindran Thayan and Dr Rozainanee Mohd Zain for their contributions to this study. We thank Dr Chong Zhuo Lin for his advice on the logistics arrangement of this study; Dr Wan Dalila, Shahedah, Komathy, Firdaus, Azie, Ardilla, who provided laboratory assistance and received compensation; Laditah, Haniza, Fadhilah, Debbie, Rozainah, Sahrin, Emelyne, Cammie, Pamini, Melanie, Mabelle, Normalah, Juhanah, Fui Fui, Thamron, Dr Valerie, Dr Phankit, Ikram, Hafiz, and Shu Han who provided research assistance at study sites. Yang, Leong, Mat Ripen had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Peariasamy, Woon, Yang, Mat Ripen. Acquisition: Yang, Lee, Koh, Abdul Rahim, Gokilavanan, Mohamed, Sevalingam, Yen, Chand, Nadirah. Statistical analysis: Yang, Leong, Mat Ripen. Analysis or interpretation of data: Yang, Mat Ripen, Leong, Peariasamy, Lee, Karina, Yen, Chand. Drafting of the manuscript: Yang, Lee, Koh, Abdul Rahim. Critical revision of the manuscript for important intellectual content: All authors. Supervision: Woon, Peariasamy. Obtained funding: Woon, Yang. Administrative, technical, or material support: Lee, Koh, Abdul Rahim, Gokilavanan, Mohamed, Sevalingam, Yen, Sulaiman, Ab Razak, Mohd Nor, Pong, Tai.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the Medical Research Grant from Ministry of Health Malaysia (MOH-MRG). [NIH/800-3/2/1 Jld.7(38), grant reference no: 58212 and warrant no: 91000377].