Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity.
Ellen L ShrockEric FujimuraTomasz KulaRichard T TimmsI-Hsiu LeeYumei LengMatthew L RobinsonBrandon M SieMamie Z LiYuezhou ChenJennifer LogueAdam ZuianiDenise J McCullochFelipe J N LelisStephanie HensonDaniel R MonacoMeghan TraversShaghayegh HabibiWilliam A ClarkePatrizio CaturegliOliver LaeyendeckerAlicja Piechocka-TrochaJonathan Z LiAshok KhatriHelen Y Chunull nullAlexandra-Chloé VillaniKyle KaysMarcia B GoldbergNir HacohenMichael R FilbinXu G YuBruce D WalkerDuane R WesemannH Benjamin LarmanJames A LedererStephen J ElledgePublished in: Science (New York, N.Y.) (2020)
Understanding humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics, therapeutics, and vaccines. Deep serological profiling of 232 coronavirus disease 2019 (COVID-19) patients and 190 pre-COVID-19 era controls using VirScan revealed more than 800 epitopes in the SARS-CoV-2 proteome, including 10 epitopes likely recognized by neutralizing antibodies. Preexisting antibodies in controls recognized SARS-CoV-2 ORF1, whereas only COVID-19 patient antibodies primarily recognized spike protein and nucleoprotein. A machine learning model trained on VirScan data predicted SARS-CoV-2 exposure history with 99% sensitivity and 98% specificity; a rapid Luminex-based diagnostic was developed from the most discriminatory SARS-CoV-2 peptides. Individuals with more severe COVID-19 exhibited stronger and broader SARS-CoV-2 responses, weaker antibody responses to prior infections, and higher incidence of cytomegalovirus and herpes simplex virus 1, possibly influenced by demographic covariates. Among hospitalized patients, males produce stronger SARS-CoV-2 antibody responses than females.