COVID-19 symptom relationship to antibody response and ACE2 neutralization in recovered health systems employees before and after mRNA BNT162b2 COVID-19 vaccine.

Background: The humoral response to SARS-CoV-2 can provide immunity and prevent reinfection. However, less is known about how the diversity, magnitude, and length of the antibody response after a primary infection is associated with symptoms, post-infection immunity, and post-vaccinated immunity.
Methods: Cook County Health employees provided blood samples and completed an online survey 8-10 weeks after a PCR-confirmed positive SARS-CoV-2 test (pre-vaccinated, N = 41) and again, 1-4 weeks after completion of a 2-dose series mRNA BNT162b2 COVID-19 vaccine (post-vaccinated, N = 27). Associations were evaluated between SARS-CoV-2 antibody titers, participant demographics, and clinical characteristics. Antibody titers and angiotensin-converting enzyme 2 (ACE2) neutralization were compared before and after the mRNA BNT162b2 COVID-19 vaccine.
Results: Antibody titers to the spike protein (ST4), receptor binding domain (RBD), and RBD mutant D614G were significantly associated with anosmia and ageusia, cough, and fever. Spike protein antibody titers and ACE2 neutralization were significantly higher in participants that presented with these symptoms. Antibody titers to the spike protein N-terminal domain (NTD), RBD, and ST4, and ACE2 IC50 were significantly higher in all post-vaccinated participant samples compared to pre-vaccinated participant sample, and not dependent on previously reported symptoms.
Conclusions: Spike protein antibody titers and ACE2 neutralization are associated with the presentation of anosmia and ageusia, cough, and fever after SARS-CoV-2 infection. Symptom response to previous SARS-CoV-2 infection did not influence the antibody response from subsequent vaccination. These results suggest a relationship between infection severity and the magnitude of the immune response and provide meaningful insights into COVID-19 immunity according to discrete symptom presentation.
Competing Interests: This research was funded by a commercial entity, Eli Lilly and Company. Lin Zhang, Josh Poorbaugh, Stephanie Beasley, Ajay Nirula, and Robert J. Benschop are all employees and/or shareholders of Eli Lilly and Company. Acknowledged contributors (Paul Anderson, Liliana Weber Jeffrey Boyles, Denisa Foster, Peter Vaillancourt, and Carmen Deveau) are also employees and/or shareholders of Eli Lilly and Company. Gregory Huhn reports receiving grants from Eli Lilly and Company, Viiv, Janssen, Ridgeback, and Gilead; and receiving payments for participating on advisory boards for Eli Lilly and Company, Viiv, Janssen, Merck, and Gilead. No other disclosures were reported. This does not alter our adherence to PLOS ONE policies on sharing data and materials.