SUMMARY
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the COVID-19 pandemic. Here, we quantified levels of SARS-CoV-2-reactive antibodies and hCoV-reactive antibodies in serum samples collected from 204 humans before the COVID-19 pandemic. We then quantified pre-pandemic antibody levels in serum from a separate cohort of 252 individuals who became PCR-confirmed infected with SARS-CoV-2. Finally, we longitudinally measured hCoV and SARS-CoV-2 antibodies in the serum of hospitalized COVID-19 patients. Our studies indicate that most individuals possessed hCoV-reactive antibodies before the COVID-19 pandemic. We determined that ∼23% of these individuals possessed non-neutralizing antibodies that cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins. These antibodies were not associated with protection against SARS-CoV-2 infections or hospitalizations, but paradoxically these hCoV cross-reactive antibodies were boosted upon SARS-CoV-2 infection.
Competing Interest Statement
The authors have declared no competing interest.
Clinical Trial
leftover samples from other studies, no trial ID
Funding Statement
EMA and TBM were supported by the NIH Training in Virology T32 Program through grant number T32-AI-007324. PH was supported by the NIH Emerging Infectious Diseases T32 Program T32-AI055400. PB was supported by a Peer Reviewed Medical Research Program award PR182551 and grants from the NIH (R21AI129531 and R21AI142638). This work was supported by institutional funds from the University of Pennsylvania and NIH HL137006 (NJM) and HL137915 (NJM). We thank J. Lurie, J. Embiid, J. Harris, and D. Blitzer for philanthropic support.
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:
All studies were approved by the University of Pennsylvania Institutional Review Board.
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.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
Footnotes
↵10 The UPenn COVID Processing Unit is a composed of individuals at the University of Pennsylvania who volunteered time and effort to enable the study of COVID-19 patients during the pandemic. Members are listed in the acknowledgement section of this paper.
Data Availability
The article includes all data generated or analyzed during this study.
