300 - Pre-pandemic coronavirus antibodies in children and adults

Poster Number: 300
Publication Number: 300.215

Karen E. Ocwieja, Boston Children's Hospital, Boston, MA, United States; Yannic C. Bartsch, Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States; Ying-Jie Lu, Boston Children's Hospital, Boston, MA, United States; Fan Zhang, Boston Children's Hospital, 188 Corey St, MA, United States; CLAUDETTE M. THOMPSON, Boston Children's Hospital, BOSTON, MA, United States; Nairuti Jhala, Massachusetts Institute of Technology, Ahmedabad, Gujarat, India; Yichen Zhang, MIT, Boston, MA, United States; Aaron G. Schmidt, Harvard Medical School, Cambridge, MA, United States; Galit Alter, Ragon Institute, Winchester, MA, United States; Richard Malley, Boston Children's Hospital, Boston, MA, United States

Background: A striking finding from the earliest days of the COVID-19 pandemic was that children are relatively spared from severe disease, despite being readily infected. At the same time, several lines of evidence suggest that an overly exuberant immune response to coronaviruses may be responsible for aggravation of disease among elderly patients.  

Objective: Here, we explore two of many hypotheses that emerged to explain these observations. First, children, due to their frequent exposure to endemic coronaviruses in daycares and schools, might carry abundant protective anti-coronavirus antibodies that cross-react with SARS-CoV-2. Second, adults, exposed over their lifetime to a variety of endemic coronaviruses, might carry detrimental pro-inflammatory non-neutralizing anti-coronavirus antibodies that cross-react with SARS-CoV-2.

Design/Methods: Using a custom Luminex assay, we tested pre-COVID serum samples from 100 children and 100 adults for antibodies against the viral nucleocapsid protein (N), spike protein (S), and subdomains of S from SARS-COV-2 and other coronaviruses. Additionally, we developed a whole virus SARS-CoV-2 ELISA to screen pre-COVID samples for antibodies to other SARS-CoV-2 targets. Positive serum samples were tested for neutralization activity using a pseudotype assay. Since infection may boost pre-existing humoral immunity, we also performed these assays on samples from acutely infected children and adults.

Results: Using sera from individuals pre-pandemic and from Covid-19 patients, we identified more adults than children with humoral reactivity to SARS-CoV-2. We found no evidence of cross-protective antibodies in the pediatric samples. Together these findings refute the idea that children are protected by pre-existing anti-coronavirus antibodies. We did detect rare pre-pandemic adult serum samples with cross-reactive antibodies, none of which neutralized the virus. It remains unclear whether these antibodies have an etiologic role in symptomatic COVID-19 disease. Conclusion(s): Our results suggest that adults, rather than children, have more broadly active circulating anti-coronavirus antibodies, arguing against the hypothesis that milder disease in children is due to cross-reactive antibodies.