Omicron variants escape the persistent SARS-CoV-2-specific antibody response in 2-year COVID-19 convalescents regardless of vaccination

ABSTRACT

With the ongoing COVID-19 pandemic and the emergence of various SARS-CoV-2 variants, a comprehensive evaluation of long-term efficacy of antibody response in convalescent individuals is urgently needed. Several longitudinal studies had reported the antibody dynamics after SARS-CoV-2 acute infection, but the follow-up was mostly limited to 1 year or 18 months at the maximum. In this study, we investigated the durability, potency, and susceptibility to immune evasion of SARS-CoV-2-specific antibody in COVID-19 convalescents for 2 years after discharge. These results showed the persistent antibody-dependent immunity could protect against the WT and Delta variant to some extent. However, the Omicron variants (BA.1, BA.2, and BA.4/5) largely escaped this preexisting immunity in recovered individuals. Furthermore, we revealed that inactivated vaccines (BBIBP-CorV, CoronaVac, or KCONVAC) could improve the plasma neutralization and help to maintain the broadly neutralizing antibodies at a certain level. Notably, with the time-dependent decline of antibody, 1-dose or 2-dose vaccination strategy seemed not to be enough to provide immune protection against the emerging variants. Overall, these results facilitated our understanding of SARS-CoV-2-induced antibody memory, contributing to the development of immunization strategy against SARS-CoV-2 variants for such a large number of COVID-19 survivors.

KEYWORDS:

• SARS-CoV-2
• Omicron variants
• COVID-19 convalescent
• 2 years after discharge
• antibody response
• inactivated vaccines

Acknowledgements

The authors thank all the patients for their contribution to this study and all of the health care providers from the Shenzhen Third People’s Hospital for the work they have done. We also thank the biological sample bank (BioBank) of the Shenzhen Third People’s Hospital for bio-samples and services provided. Z.Z. is the principal investigator of this study. Z.Z. and B.J. conceived and designed the study. M.W., B.Z., Q.F., X.Z., and X.L. performed all experiments and analyzed the data together with assistance from J.L., Z.M., J.D., H.W., and X.G.. M.W., B.J., and Z.Z. wrote the manuscript and all authors read and approved this version of the manuscript.

Disclosure statement

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

Data availability statement

We are happy to share reagents and information in this study upon request.

Additional information

Funding

This work was supported by the National Science Fund for Distinguished Young Scholars [grant number 82025022], the National Natural Science Foundation of China [grant numbers 92169204, 82002140, 82171752, 82101861], the National Key Plan for Scientific Research and Development of China [grant number 2021YFC0864500], the Guangdong Basic and Applied Basic Research Foundation [grant numbers 2021B1515020034, 2019A1515011197, 2021A1515011009, 2020A1515110656], the Shenzhen Science and Technology Program [grant numbers RCYX20200714114700046, RCBS20210706092345028], the Science and Technology Innovation Committee of Shenzhen Municipality [grant numbers JSGG20220226085550001, JSGG20200207155251653, JSGG20200807171401008, JSGG20210901145200002, KQTD20200909113758004], and the Shenzhen Natural Science Foundation [grant numbers JCYJ20190809115617365, JCYJ20210324115611032, JCYJ20220530163405012].