PT - JOURNAL ARTICLE AU - Kevin Ng AU - Nikhil Faulkner AU - Georgina Cornish AU - Annachiara Rosa AU - Christopher Earl AU - Antoni Wrobel AU - Donald Benton AU - Chloe Roustan AU - William Bolland AU - Rachael Thompson AU - Ana Agua-Doce AU - Philip Hobson AU - Judith Heaney AU - Hannah Rickman AU - Stavroula Paraskevopoulou AU - Catherine F. Houlihan AU - Kirsty Thomson AU - Emilie Sanchez AU - Gee Yen Shin AU - Moira J Spyer AU - Philip A. Walker AU - Svend Kjaer AU - Andrew Riddell AU - Rupert Beale AU - Charles Swanton AU - Sonia Gandhi AU - Brigitta Stockinger AU - Steve Gamblin AU - Laura E. McCoy AU - Peter Cherepanov AU - Eleni Nastouli AU - George Kassiotis TI - Pre-existing and <em>de novo</em> humoral immunity to SARS-CoV-2 in humans AID - 10.1101/2020.05.14.095414 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.05.14.095414 4099 - http://biorxiv.org/content/early/2020/05/15/2020.05.14.095414.short 4100 - http://biorxiv.org/content/early/2020/05/15/2020.05.14.095414.full AB - Several related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections1. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic spread2,3. Zoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population. Using diverse assays for detection of antibodies reactive with the SARS-CoV-2 Spike (S) glycoprotein, we demonstrate the presence of pre-existing immunity in uninfected and unexposed humans to the new coronavirus. SARS-CoV-2 S-reactive antibodies, exclusively of the IgG class, were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals with recent HCoV infection and targeted the S2 subunit. In contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, as well as concomitant IgM and IgA antibodies throughout the observation period of 6 weeks since symptoms onset. HCoV patient sera also variably reacted with SARS-CoV-2 S and nucleocapsid (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays. Notably, HCoV patient sera exhibited specific neutralising activity against SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera. Distinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for serology, seroprevalence and vaccine studies, as well as for our understanding of susceptibility to and natural course of SARS-CoV-2 infection.Competing Interest StatementThe authors have declared no competing interest.