Pre COVID 19 humoral immunity to common coronaviruses does not confer cross protection against SARS CoV 2

It is currently unknown whether acquired immunity to common alpha- and beta-coronaviruses provides cross-protection against SARS-CoV-2. In this study, we found that certain patient sera and intravenous immunoglobulins (IVIG) collected prior to the COVID-19 outbreak were cross-reactive to SARS-CoV-2 full-length Spike, S2 domain, and Nucleocapsid. However, their presence did not translate into neutralizing activity against SARS-CoV-2 in vitro . Importantly, we detected serum IgG reactivity to common coronaviruses in the early sera of patients with severe COVID-19 before the appearance of anti-SARS-CoV-2 antibodies. Collectively, the results of our study indicate that pre-existing immunity to common coronaviruses does not confer cross-protection against SARS-CoV-2 in vivo . ### Competing Interest Statement M.M. received consulting fees from Genalyte Inc. ### Funding Statement MM and GG are supported by the Programme hospitalier de recherche clinique (PHRC: AOR17082,PHRCN 190321), DIM therapie genique Ile de France and AFPCA (Association Francaise de la PolyChondrite Atrophiante). D.S. was supported for this work by a Pasteur/APHP interface fellowship. The study was supported by Fondation de France, Tous unis contre le virus framework Alliance (Fondation de France, AP-HP, Institut Pasteur) in collaboration with Agence Nationale de la Recherche (ANR Flash COVID19 program), and by the SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University : ICOViD programs, PI: G.G.). ### 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: CPP - Ile de France- VI at the Pitie-Salpetriere Hospital local ethical committee of Sorbonne Universite (n 2020-CER2020-21) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.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 All raw data are available in supplementary data or upon request