{"doi":"10.1172/jci.insight.146316","title":"A majority of uninfected adults show preexisting antibody reactivity against SARS-CoV-2","abstract":"Preexisting cross-reactivity to SARS-CoV-2 occurs in the absence of prior viral exposure. However, this has been difficult to quantify at the population level due to a lack of reliably defined seroreactivity thresholds. Using an orthogonal antibody testing approach, we estimated that about 0.6% of nontriaged adults from the greater Vancouver, Canada, area between May 17 and June 19, 2020, showed clear evidence of a prior SARS-CoV-2 infection, after adjusting for false-positive and false-negative test results. Using a highly sensitive multiplex assay and positive/negative thresholds established in infants in whom maternal antibodies have waned, we determined that more than 90% of uninfected adults showed antibody reactivity against the spike protein, receptor-binding domain (RBD), N-terminal domain (NTD), or the nucleocapsid (N) protein from SARS-CoV-2. This seroreactivity was evenly distributed across age and sex, correlated with circulating coronaviruses' reactivity, and was partially outcompeted by soluble circulating coronaviruses' spike. Using a custom SARS-CoV-2 peptide mapping array, we found that this antibody reactivity broadly mapped to spike and to conserved nonstructural viral proteins. We conclude that most adults display preexisting antibody cross-reactivity against SARS-CoV-2, which further supports investigation of how this may impact the clinical severity of COVID-19 or SARS-CoV-2 vaccine responses.","journal":"JCI Insight","year":2021,"id":154829,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":61,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":571496,"name":"Christina Michalski","orcid":"0000-0001-9093-5325","position":1,"is_corresponding":false},{"id":323766,"name":"Sarah O’Connell","orcid":"0000-0002-1645-0722","position":2,"is_corresponding":false},{"id":571497,"name":"Sarah Dada","orcid":"0000-0002-3445-2377","position":3,"is_corresponding":false},{"id":480600,"name":"Sandeep Narpala","orcid":"0000-0002-1447-2709","position":4,"is_corresponding":false},{"id":572053,"name":"Jean Gelinas","orcid":null,"position":5,"is_corresponding":false},{"id":571498,"name":"Disha Mehta","orcid":"0000-0002-0856-9512","position":6,"is_corresponding":false},{"id":571499,"name":"Claire Cheung","orcid":"0000-0003-0603-2938","position":7,"is_corresponding":false},{"id":655638,"name":"Dirk Winkler","orcid":"0000-0003-4298-010X","position":8,"is_corresponding":false},{"id":572054,"name":"Manjula Basappa","orcid":null,"position":9,"is_corresponding":false},{"id":266191,"name":"Aaron C. 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