ABSTRACT
While the current pandemic remains a thread to human health, the polyclonal nature of the antibody response against SARS-CoV-2 is not fully understood. Other than SARS-CoV-2, humans are susceptible to six different coronaviruses, and previous exposure to antigenically related and divergent seasonal coronaviruses is frequent. We longitudinally profiled the early humoral immune response against SARS-CoV-2 on hospitalized COVID-19 patients, and quantify levels of pre-existing immunity to OC43, HKU1 and 223E seasonal coronaviruses. A strong back-boosting effect to conserved, but not variable regions of OC43 and HKU1 betacoronaviruses spike protein was observed. All patients developed antibodies against SARS-CoV-2 spike and nucleoprotein, with peak induction at day 7 post hospitalization. However a negative correlation was found between antibody memory boost to human coronaviruses and induction of IgG and IgM against SARS-CoV-2 spike. Our findings provide evidence of immunological imprinting that determine the antibody profile to COVID-19 patients in an original antigenic sin fashion.
Competing Interest Statement
AG-S is inventor of patents owned by the Icahn School of Medicine at Mount Sinai in the field of influenza virus vaccines. The AG-S lab has received research funds from Avimex, GSK and 7Hills to investigate novel influenza virus vaccines. FK is a named as inventor on IP covering serological assays and vaccines for SARS-CoV-2 which have been filed by the Icahn School of Medicine at Mount Sinai. Other authors declare no competing interests.
Funding Statement
This work was partly funded by CRIP (Center for Research on Influenza Pathogenesis), a NIAID funded Center of Excellence for Influenza Reserch and Surveillance (CEIRS, contract #HHSN272201400008C), by SEM-CIVIC, a NIAID funded Collaborative Influenza Vaccine Innovation Center (contract #75N93019C00051), and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)) and anonymous donors to AG-S.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The study protocol was approved by the Institutional Review Board of University Hospital of Bellvitge, Barcelona, Spain; and by the Icahn School of Medicine at Mount Sinai, New York, US.
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data Availability
All data is available in the manuscript or the supplementary materials. Serum samples are available upon reasonable request from Dr. Garcia-Sastre under a material agreement with Icahn School of Medicine at Mount Sinai. Reagents used are almost exclusively commercially available and non-proprietary.
