Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multicentre cohort study

Abstract

Objectives: Highly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections.

Methods: We conducted a multicentre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals.

Results: Out of 218 individuals with B.1.617.2 infection, 84 received an mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and four received a non-mRNA vaccine. Despite significantly older age in the vaccine breakthrough group, only 2.8% (2/71) developed severe COVID-19 requiring oxygen supplementation compared with 53.1% (69/130) in the unvaccinated group (p < 0.001). Odds of severe COVID-19 following vaccination were significantly lower (adjusted odds ratio 0.07 95% CI 0.015-0.335, p 0.001). PCR cycle threshold values were similar between vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients; however, these titres were significantly lower against B.1.617.2 than the wildtype vaccine strain.

Discussion: The mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of the COVID-19 pandemic.

Keywords: Breakthrough infection; COVID-19; Delta; SARS-CoV-2; Vaccination; Vaccine breakthrough; Variants of concern.

Fig. 1

Scatterplot of Ct values and marginal effect of day of illness of COVID-19 B1.617.2 infected patients with 95% confidence intervals from generalized additive mixed model with interaction term between vaccination status and day of illness. A negative PCR result was coded as Ct value of 45. n = 200; vaccine breakthrough = 71, unvaccinated = 129.

Fig. 2

(A) Spaghetti plot of surrogate virus neutralization (sVNT) inhibition % as measured by cPass; (B) Scatterplot of sVNT inhibition % and marginal effect of day of illness by vaccine breakthrough and unvaccinated groups of COVID-19 B1.617.2 infected patients with 95% confidence intervals from generalized additive mixed models. For both plots, n = 127; vaccine breakthrough = 67, unvaccinated = 60.

Fig. 3

Violin plots of surrogate virus neutralisation (sVNT) inhibition % against wildtype SARS-CoV-2 and variants of concern for 36 patients with vaccine breakthrough infection median day of sample collection from infection onset 6 days (interquartile range (IQR) 3–7). Titres against the four variants were significantly lower than against wildtype SARS-CoV-2 [median sVNT, B.1.1.7 98.5% (IQR 96.3–99.5); B.1.351 98.2% (IQR 95.3–99.5); B.1.617.2 96.0% (IQR 90.9–99.3); P.1 95.5% (IQR 91.3–98.9); Wildtype 99.4% (IQR 98.5–99.7); Kruskal–Wallis p 0.00055; post hoc pairwise comparison (Conover) wildtype versus each variant p < 0.05].