304 - Pediatric Specific Antibody Responses in Post Acute Sequelae of SARS-CoV-2 Infection

Publication Number: 2294.304

Hanna Oppenheimer, Ben Gurion university, Beer Sheva, HaDarom, Israel; Tianci Guan, Columbia University Irving Medical Center, New York, NY, United States; Sindhu Mohandas, Children's Hospital Los Angeles, Los Angeles, CA, United States; John Wood, Childrens Hospital Los Angeles, Los Angeles, CA, United States; Lawrence C. Kleinman, Rutgers RWJMS, New Brunswick, NJ, United States; Kyung E.. Rhee, UC San Diego School of Medicine, LA JOLLA, CA, United States; Kelan Tantisira, Rady Children's Hospital San Diego, San Diego, CA, United States; Amy L. Salisbury, Virginia Commonwealth University, Richmond, VA, United States; Patricia Kinser, Virginia Commonwealth University School of Nursing, Richmond, VA, United States; Katherine Irby, Arkansas Children's Research Institute/ UAMS, Little Rock, AR, United States; Rachel Atchley-Challenner, MGH Biostatistics, Data Resource Core, Boston, MA, United States; Rachel S. Gross, New York University Grossman School of Medicine, New York, NY, United States; Joshua D.. Milner, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States; Melissa Stockwell, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States; Tomer Hertz, Ben Gurion University of the Negev, Beer-Sheva, HaDarom, Israel; Thomas J. Connors, Columbia University Medical Center, New York, NY, United States

Background: Long COVID, or post-acute sequelae of SARS-CoV-2 (PASC), has become a major health crisis affecting 10-20% of children following SARS-Cov-2 infection. Aberrant immune responses to distinct peptides of SARS-CoV-2 and reactivation of latent viruses (CMV/EBV) have been identified as potential mechanisms of PASC in adults. Immune responses in children are distinct from those in adults and there is little understanding of pediatric specific causes of PASC.

Objective: Profile antibody responses against SARS-CoV-2 antigens and common pathogens to examine associations to pediatric PASC.

Design/Methods: Plasma obtained from children (n=95, median age 12.2 years, range 5-17) were obtained in collaboration with the NIH RECOVER initiative. Subjects were divided into 3 cohorts: SARS-CoV-2 infected with PASC (n=47) or without PASC (n=32) and uninfected (n=16). We performed multiplexed antigen microarrays to assess IgG and IgA responses to 1) ancestral SARS-CoV-2, variants, and seasonal coronaviruses and 2) common pathogens including viral respiratory infections, vaccine antigens, and herpes viruses (Table 1). Geometric mean magnitudes for antigen groups were computed from either raw or mean-centered (normalized) antigen signals, with normalization performed by dividing each antigen value by the mean response across all antigens within the same sample. Data were analyzed by cohort and using a multivariate model including sex, age, and SARS-CoV-2 vaccination status.

Results: PASC subjects had significantly increased IgG and IgA to seasonal coronaviruses and elevated IgA to SARS-CoV-2 variants (Fig. 1A). Age was a significant driver of both IgG and IgA responses (Fig. 1B). We did not observe differences in responses to chronic herpesviruses (CMV/EBV) by PASC status (Fig. 2). In multivariate models Ig responses were most strongly correlated with age. IgG responses to SARS-CoV-2 were significantly increased by vaccination.

Conclusion(s): PASC subjects have robust responses to seasonal coronaviruses and increased IgA responses to all coronaviruses. Age associations with antibody responses highlight the need to account for developmental differences in immunity even within pediatric cohorts. Contrasting to adults, pediatric PASC subjects do not demonstrate differential responses to distinct SARS antigens or chronic herpesviruses. Differences in IgA responses, typically associated with mucosal immunity, could indicate differences in immune responses within the respiratory tract of PASC subjects and warrant exploration.

Table 1
Table 1: Antigen Microarray proteins. Abbreviations; S = spike, RBD = receptor binding domain, NTD = N-terminal domain

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