P-1849. Investigating the Impact of SARS-CoV-2 on the Immune Response to Other Pathogens Using VirScan Epitope Profiling
Authors: Sircy Linda M , Krantz Elizabeth M , Basom Ryan S , Kimball Louise E , Blazevic Rachel , Yahya Khaleel , Stevens-Ayers Terry L , Han Peter D , Prentice Robin A , Starita Lea , Bedford Trevor , Viboud Cecile , Boeckh Michael J , Waghmare Alpana 
Published: January 2025

Abstract

Background
The emergence and rapid spread of SARS-CoV-2 since 2019 caused substantial global morbidity and mortality and continues to burden healthcare systems worldwide. Public health measures implemented to reduce SARS-CoV-2 spread also reduced circulation of other seasonal respiratory viruses, likely causing gaps in population-level immunity. Whether SARS-CoV-2 infection may dampen immune responses against other pathogens is highly debated and not well understood.Figure 1.VirScan analyses of serum samples pre- and post- clinically confirmed SARS-CoV-2 infection. (A) VirScan total epitope hits and geometric mean (gMean) of epitope binding (EB) scores for SARS-CoV-2 pre- and post- clinically confirmed SARS-CoV-2 infection. (B) gMean of EB scores for select pathogens pre- and post- clinically confirmed SARS-CoV-2 infection. Timepoints included in the VirScan analyses were between 15-174 days prior to and 31-155 days after clinically confirmed SARS-CoV-2 infection. Gray lines denote paired samples for individual subjects. Statistically significant adjusted p values of &lt; 0.05 were determined using paired t test with Holm correction.

Methods
In 2022, we conducted a longitudinal study of immunocompetent adults ( &gt; 18 years) with recent SARS-CoV-2 infection or vaccination history and increased risk of social or occupational exposure to respiratory viruses. Subjects were followed for 6 months and weekly symptom surveys, blood samples at enrollment, 3 and 6 months post-enrollment, and nasal swabs at report of symptoms were collected. Swabs were tested by RT-PCR (OpenArray) for 27 respiratory pathogens, including SARS-CoV-2. Serum antibodies were assessed by VirScan PhIP-seq for specificity to a broad library of antigen epitopes for clinically relevant pathogens, measuring total epitope hits and epitope binding (EB) scores, a measure similar to antibody titer.

Results
Of 43 subjects with paired serum samples &gt; 1 week prior to and &gt; 28 days after clinically confirmed SARS-CoV-2 infection, 32 subjects with viral load &lt; Ct 22.2 were assessed by VirScan. SARS-CoV-2 epitope hits and EB scores were significantly increased post-infection compared to pre-infection (Fig 1A). SARS-CoV-2 infection was associated with reduced EB scores for adenovirus D and S. aureus (Fig 1B). However, SARS-CoV-2 infection was not associated with a statistically significant decline of epitope hits or EB scores for most other clinically relevant pathogens.

Conclusion
We assessed broad changes in the antibody repertoires of subjects prior to and after SARS-CoV-2 infection for clinically relevant pathogens at the epitope level by VirScan. Together these data suggest that SARS-CoV-2 infection is not associated with differential patterns of antibody repertoire kinetics for most non-coronavirus respiratory pathogens in immunocompetent adults. Further analyses in larger cohorts with longer follow-up are needed to confirm these findings.

Disclosures
Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Symbio: Advisor/Consultant Alpana waghmare, MD, Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|GlaxoKlineSmith: Advisor/Consultant|GlaxoKlineSmith: Grant/Research Support|Pfizer: Grant/Research Support|Vir: Advisor/Consultant