Predictors for Reactogenicity and Humoral Immunity to SARS-CoV-2 Following Infection and mRNA Vaccination: A Regularized Mixed-Effects Modelling Approach

Abstract

BackgroundThe influence of pre-existing humoral immunity, inter-individual demographic factors, and vaccine-associated reactogenicity on immunogenicity following COVID vaccination remains poorly understood.MethodsTen-fold cross-validated least absolute shrinkage and selection operator (LASSO) and linear mixed effects models were used to evaluate symptoms experienced during natural infection and following SARS-CoV-2 mRNA vaccination along with demographics as predictors for antibody (AB) responses in COVID+ participants in a longitudinal cohort study.ResultsIn previously infected individuals, AB were more durable and robust following vaccination when compared to natural infection alone. Higher AB were associated with experiencing dyspnea during natural infection, as was the total number of symptoms reported during the COVID-19 disease course. Both local and systemic symptoms following 1st and 2nd dose of SARS-CoV-2 mRNA vaccines were predictive of higher AB after vaccination, as were the demographic factors of age and Hispanic ethnicity. Lastly, there was a significant temporal relationship between AB and days since infection or vaccination.ConclusionVaccination in COVID+ individuals ensures a more robust immune response. Experiencing systemic and local symptoms post-vaccine is suggestive of higher AB, which may confer greater protection. Age and Hispanic ethnicity are predictive of higher AB.

Predictors for reactogenicity and humoral immunity to SARS-CoV-2 following infection and mRNA vaccination: A regularized, mixed-effects modelling approach

“…We also thank the core research team that have made this study logistically possible, including Margaret Roach, Elizabeth Varghese, Celeste Sanchez, Ailet Reyes, and the entire team of phlebotomists at the University of Miami’s Clinical Translational Research Site. This work has been previously published ( 51 ) on the pre-print server, medRxiv.…”

Predictive Value of Reactogenicity for Anti-SARS-CoV-2 Antibody Response in mRNA-1273 Recipients: A Multicenter Prospective Cohort Study

“…In those studies, AEs were assessed as a total score or severity level, and more than half of the participants were elderly individuals (aged ≥ 80 years) [18,[31][32][33]41]. Although the statistical significance of such an association was variable in other studies, systemic reactogenicity was related to a higher immune response, and the correlation was more prominent after the second dose [11,12,20,28,[34][35][36][37][38][39][40]42,43]. Up to now, the association of mRNA-1273 vaccine immunogenicity with reactogenicity has been investigated in only three studies.…”

“…Both mRNA-1273 and BNT162b2 vaccines are the first human mRNA vaccines, which raised concerns about their immunological correlates with reactogenicity [ 3 , 30 ]. After the introduction of mRNA vaccines, several studies have investigated the correlation between immunogenicity and reactogenicity, with inconsistent results [ 11 , 18 , 20 , 28 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Some studies did not show a significant association, but those studies had limitations.…”

“…Up to now, the association of mRNA-1273 vaccine immunogenicity with reactogenicity has been investigated in only three studies. Two of them included both kinds of mRNA vaccines (mRNA-1273 and BNT162b2) [ 12 , 40 ], while Coronavirus Efficacy (COVE) trial in the United States just focused on the mRNA-1273 vaccine [ 11 ]. According to the results of COVE trial, several systemic symptoms after the second dose were significantly associated with both the neutralizing and binding antibody titers at day 28 after the second dose.…”