Predicting SARS-CoV-2 Variant Spread in a Completely Seropositive Population Using Semi-Quantitative Antibody Measurements in Blood Donors

Abstract

SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants, which nears 100% in many settings. New approaches are required to fully exploit serosurvey data. Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titers in serial cross-sectional monthly samples of blood donations across seven Brazilian state capitals (March 2021−November 2021). Using an ecological analysis, we assessed the contributions of prior attack rate and vaccination to antibody titer. We compared anti-S titer across the seven cities during the growth phase of the Delta variant and used this to predict the resulting age-standardized incidence of severe COVID-19 cases. We tested ~780 samples per month, per location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven by vaccination, mean antibody titer increased 16-fold over the study, with the greatest increases occurring in cities with the highest prior attack rates. Mean anti-S IgG was strongly correlated (adjusted R2 = 0.89) with the number of severe cases caused by Delta. Semi-quantitative anti-S antibody titers are informative about prior exposure and vaccination coverage and may also indicate the potential impact of future SARS-CoV-2 variants.

Keywords: SARS-CoV-2; delta; immunity; seroprevalence; vaccines; variants of concern.

Figure 1

SARS-CoV-2 infection and vaccination across seven Brazilian capital cities. (A) Location of the seven state capitals with participating blood donation centers. (B) Proportion of the population within the donation-eligible age group (15–65 years) having received one or two doses of SARS-CoV-2 vaccine in each of the seven cities. (C) The relative share of vaccine types cumulative through December 2021. BH—Belo Horizonte, RJ—Rio de Janeiro, J&J—Johnson and Johnson, AZ—AstraZeneca. Vaccination data were extracted from OpenDataSUS (https://opendatasus.saude.gov.br/). (D) Incidence of cases and deaths due to severe acute respiratory syndrome (SARI, data are from SIVEP-Gripe national reporting system) multiplied by 10 (for visualization alongside total cases) and total cases reported by the Brazilian Ministry of Health (https://covid.saude.gov.br/). Periods of variant dominance start from the date at which each variant reached a 10% share of all sequences deposited on GISAID (https://www.gisaid.org/), based on predictions from a multinomial model fit to these data (Figure S1). Anti-S seropositivity is calculated based on monthly blood donor samples and is shown with exact 95% binomial confidence intervals (error bars). (E)—estimated cumulative attack rate in December 2020 based on anti-N serosurveillance in the same blood donor population [14]. 95% confidence intervals are shown as error bars.

Figure 2

Monthly convalescent-normalized mean antibody titer in blood donors across seven Brazilian cities. (A) Mean anti-S IgG antibody titer in blood donors normalized against mean convalescent anti-S IgG level shortly following infection. (B) Convalescent-normalized anti-S IgG when first dose coverage reached 50% in all cities (July 2021, triangles) and second dose vaccination reached 50% (September or October, squares) against estimated attack rate in December 2020 [14]. (C) Symbols as in B but grouped by city on x-axis. Vaccine efficacy estimates (horizontal dashed lines) are based on the relationship between convalescent-normalized mean anti-S IgG following vaccine administration and protection against PCR-confirmed symptomatic infections (as described in [22]).

Figure 3

Predictors of epidemic size of the Delta growth phase across seven Brazilian cities. Convalescent-normalized mean anti-S IgG signal to cut-off was calculated for the month when Delta reached 10% dominance in each of the cities (range 19 June 2021 in Curitiba to 16 August 2021 in Manaus). Percentage coverage with the first and second doses was also calculated up to (and inclusive of) the month of 10% dominance in each city. Total severe acute respiratory syndrome (SARI) cases, within the age range of blood donors (15–65 years) were age-standardized using the direct method and the age structure of São Paulo as the reference population. A two-month period starting from the date of 10% dominance was used to calculate epidemic size. R-squared terms are from separate simple linear models fit to the seven points shown on the figure.