Waning antibody responses in COVID-19: what can we learn from the analysis of other coronaviruses?

Abstract

Objectives: The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due to the continuing surge in incidence and mortality globally, determining whether protective, long-term immunity develops after initial infection or vaccination has become critical.

Methods/results: In this narrative review, we evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS-CoV, Middle East respiratory syndrome coronavirus and the four endemic human coronaviruses) in order to predict the consequences of antibody waning on long-term immunity against SARS-CoV-2. We summarise their antibody dynamics, including the potential effects of cross-reactivity and antibody waning on vaccination and other public health strategies. At present, based on our comparison with other coronaviruses we estimate that natural antibody-mediated protection for SARS-CoV-2 is likely to last for 1-2 years and therefore, if vaccine-induced antibodies follow a similar course, booster doses may be required. However, other factors such as memory B- and T-cells and new viral strains will also affect the duration of both natural and vaccine-mediated immunity.

Conclusion: Overall, antibody titres required for protection are yet to be established and inaccuracies of serological methods may be affecting this. We expect that with standardisation of serological testing and studies with longer follow-up, the implications of antibody waning will become clearer.

Keywords: Antibodies; COVID-19; HCoV; MERS; SARS.

Fig. 1

Graphical representation of the longevity and magnitude of the nAb antibody response to coronaviruses. a Shows trends in antibody kinetics to SARS-CoV, MERS-CoV and HCoVs, highlighting the relatively rapid waning of HCoV nAbs as well as higher titres generated in severe SARS-CoV/MERS-CoV infection [–, –, –42, 44, 52]. The dotted line indicates a lack of serological data for common cold coronavirus infections in individuals naïve to the infection. b Compares antibody titre trends in severe and mild SARS-CoV-2 and their waning over time, highlighting the higher titres generated in severe infection [–, , –64]. Neither graph drawn to scale. SARS-CoV severe acute respiratory syndrome coronavirus, MERS-CoV Middle East respiratory syndrome coronavirus, HCoV human coronavirus