Longitudinal analysis of the LA-SPARTA cohort of high-risk individuals after SARS-CoV-2 infection and vaccination

Abstract

Abstract Questions remain regarding correlates of risk and immune protection against SARS-CoV-2 infection and vaccination response. Thus, we prospectively enrolled 200 participants with a high risk of SARS-CoV-2 occupational exposure. Longitudinal analysis of participant exposure risks, vaccination/infection status, and symptoms were assessed at 3, 6, and 12 months, with blood and saliva collection. Quantitative ELISA assay was used to assess the serological response to the SARS-CoV-2 spike holoprotein (S), S-receptor binding domain (RBD) and nucleocapsid protein (NP). 40 of 200 (20%) participants were found to be infected via serology. Equal incidence of infection was found in healthcare and non-healthcare occupations. In those infected, only 79.5% seroconverted for NP, and 11.5% were unaware they had been infected. The antibody response to S was greater than to RBD. Additionally, Hispanic ethnicity was associated with 2-fold greater incidence of infection despite vaccination. Booster vaccination significantly increased the avidity of RBD-specific responses to variant spike proteins. No differences in avidity were found if a participant was boosted via vaccination or natural infection. Collectively, our results indicate that antibody quality and holoprotein response may reveal meaningful determinants of protection beyond RBD antibody titer alone. Additionally, determinants of infection risk may include race/ethnicity, and remain independent of comorbidity and humoral response in this cohort. This study received funding from Center for Influenza Vaccine Research for High Risk Populations- CIVIC 75N93019C00052 (EFR), Lundquist Institute Institutional Funds (MRY), UCLA W. M. Keck Foundation COVID 19 Research Award Program (EFR), and the Community Engagement Alliance Against COVID-19 (CEAL) (MRY, EFR). The project described was supported by the National Center for Advancing Translational Sciences through the UCLA CTSI Grant UL1TR001881. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding sources. MMJ is supported by the NIH grants TL 1 DK132768 and U2C DK129496.