Epidemiological and Serological Analysis of a SARS-CoV-2 Outbreak in a Nursing Home: Impact of SARS-CoV-2 Vaccination and Enhanced Neutralizing Immunity Following Breakthrough Infection

Abstract

Background: Despite a vaccination rate of 82.0% (n = 123/150), a SARS-CoV-2 (Alpha) outbreak with 64.7% (n = 97/150) confirmed infections occurred in a nursing home in Bavaria, Germany. Objective: the aim of this retrospective cohort study was to examine the effects of the Corminaty vaccine in a real-life outbreak situation and to obtain insights into the antibody response to both vaccination and breakthrough infection. Methods: the antibody status of 106 fully vaccinated individuals (54/106 breakthrough infections) and epidemiological data on all 150 residents and facility staff were evaluated. Results: SARS-CoV-2 infections (positive RT-qPCR) were detected in 56.9% (n = 70/123) of fully vaccinated, compared to 100% (n = 27/27) of incompletely or non-vaccinated individuals. The proportion of hospitalized and deceased was 4.1% (n = 5/123) among fully vaccinated and therewith lower compared to 18.5% (n = 5/27) hospitalized and 11.1% (n = 3/27) deceased among incompletely or non-vaccinated. Ct values were significantly lower in incompletely or non-vaccinated (p = 0.02). Neutralizing antibodies were detected in 99.1% (n = 105/106) of serum samples with significantly higher values (p < 0.001) being measured post-breakthrough infection. α-N-antibodies were detected in 37.7% of PCR positive but not in PCR negative individuals. Conclusion: Altogether, our data indicate that SARS-CoV-2 vaccination does provide protection against infection, severe disease progression and death with regards to the Alpha variant. Nonetheless, it also shows that infection and transmission are possible despite full vaccination. It further indicates that breakthrough infections can significantly enhance α-S- and neutralizing antibody responses, indicating a possible benefit from booster vaccinations.

Keywords: Comirnaty® COVID-19 vaccine; SARS-CoV-2 Alpha variant; SARS-CoV-2 antibodies; breakthrough infection; epidemiology; neutralizing antibodies; nursing home; outbreak; serology.

Figure A1

Relationship between measurement values for each assay with cPass neutralizing antibodies. Dashed line represents cut-off value. Corresponding Spearman Rank correlation coefficients are summarized in Table A1.

Figure A2

Relationship between measurement values for each assay with age. Dashed line represents cut-off value. Corresponding Spearman Rank correlation coefficients are summarized in Table A2.

Figure A3

Relationship between measurement values for each assay with Ct values (PCR positive only). Dashed line represents cut-off value. Corresponding Spearman Rank correlation coefficients are summarized in Table A3.

Figure A4

Measurement values for each assay in dependence of time difference between PCR and blood-draw. Dashed line represents cut-off value. Wilcoxon rank sum test with *: p < 0.05, **: p < 0.01, ***: p < 0.001.

Figure 1

(A) Overview of the individuals considered in the investigated outbreak outlining the share of fully vaccinated and incompletely or non-vaccinated and the proportion of hospitalized and deceased by vaccination status. (B) Vaccination and infection status by age group. Fully vaccinated individuals can be divided into PCR positive (dark blue) and PCR negative (light blue) while all incompletely or non-vaccinated were PCR positive (orange). (C) Proportion of incompletely or non-vaccinated (orange) among PCR positive individuals in each Ct value group (fully vaccinated in blue). (D) Ct value distribution in relation to age among fully vaccinated (n = 123, blue) and incompletely or non-vaccinated (n = 27, orange).

Figure 2

Measurements of all antibody assays performed represented as percent of the cut-off value (indicated by dashed line), subdivided by infection status (PCR positive: dark blue, PCR negative light blue). Wilcoxon rank sum test with *: p < 0.05, **: p < 0.01, ***: p < 0.001. (A) Mikrogen Lineblot with antigens: N protein, S1 subunit and RBD, Architect with N protein as antigen, (B) Cobas N Protein, Cobas S Protein and Liaison TrimericS S Protein, plotted on a logarithmic scale for better representation of the wide range of measured values, and (C) Virachip with N protein, S1 subunit, S2 subunit and RBD as antigens and cPass surrgat neutralization assay.

Figure 3

(A) Correlation of neutralizing antibodies with $\alpha$-N antibodies (exemplified by Cobas N protein), Spearman Rank correlation coefficient r = 0.648 (p < 0.001) (all samples), r = −0.025 (p = 0.859) (PCR Negatives) and r = 0.277 (p = 0.045) (PCR Positives), (B) correlation of neutralizing antibodies with $\alpha$-RBD antibodies (exemplified by Mikrogen Lineblot), Spearman Rank correlation coefficient r = 0.587 (p < 0.001) (all samples), r = 0.713 (p < 0.001) (PCR Negatives) and r = 0.194 (p = 0.165) (PCR Positives), (C) correlation of neutralizing antibodies with age. Spearman rank correlation coefficient r = 0.062 (p = 0.531) (all samples), r = −0.321 (p = 0.019) (PCR Negatives) and r = −0.141 (p = 0.323) (PCR Positives). (D) correlation of $\alpha$-N antibodies (exemplified by Cobas N protein) with Ct values, Spearman Rank correlation coefficient r = 0.417 (p = 0.002) (PCR Positives only).