Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans
Kevin W Ng,
Georgina H. Cornish,
Catherine F Houlihan,
Gee Yen Shin,
Moira J Spyer,
Philip A Walker,
Bethany R Jebson,
Meredyth G.Ll. Wilkinson,
Lucy R Marshall,
Elizabeth C Rosser,
Lucy R Wedderburn,
John P. McCauley,
Laura E McCoy,
Posted 15 May 2020
bioRxiv DOI: 10.1101/2020.05.14.095414
Posted 15 May 2020
Several related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections. 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 proportions. 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 humoral immunity in uninfected and unexposed humans to the new coronavirus. SARS-CoV-2 S-reactive antibodies were readily detectable by a sensitive flow cytometry- based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. These were predominantly of the IgG class and targeted the S2 subunit. In contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, targeting both the S1 and S2 subunits, as well as concomitant IgM and IgA antibodies, lasting throughout the observation period of 6 weeks since symptoms onset. SARS-CoV-2-uninfected donor sera also variably reacted with SARS-CoV-2 S and nucleoprotein (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays. Notably, SARS-CoV-2- uninfected donor sera exhibited specific neutralising activity against SARS-CoV-2 and 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 our understanding of susceptibility to and the natural course of SARS-CoV-2 infection. ### Competing Interest Statement The authors have declared no competing interest.
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