Abstract
In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.
Highlights
In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent
We examined the relationship between pre-exposure to HKU1, OC43, and 229E viruses and the induction of SARS-CoV-2 S, receptor-binding domain (RBD), and N antibodies in our cohort, and determined Pearson correlation coefficients between IgG levels at baseline against seasonal human coronaviruses and the fold induction of SARS-CoV-2 antigens at days 3, 7 and convalescence
Our findings provide a dynamic characterization of the antibody response to SARS-CoV-2 in COVID-19 patients and provide evidence of immune imprinting in these patients
Summary
In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. We longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. Serum cross-reactivity between conserved epitopes from SARS-CoV-2 and seasonal human coronaviruses is still under investigation[23,31,32,33] and the role of preexisting humoral immunity and immunodominance for B cell responses needs to be addressed. This study provides a dynamic characterization of the co-evolving nature of antibody responses to human coronaviruses, both seasonal and pandemic, and contributes to a better understanding of cross-reactive antibody responses and B cells immunodominance against human coronaviruses
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