Infection and Transmission of SARS-CoV-2 B.1.617.2 Lineage (Delta Variant) among Fully Vaccinated Individuals

Abstract

The emergence of the SARS-CoV-2 B.1.617.2 lineage (Delta variant) in 2021 was associated with increased case numbers and test positivity rates, including a large number of infections in fully vaccinated individuals. Here, we describe the findings of an investigation conducted in Tompkins County, New York, to evaluate factors underlying a significant uptick in the number of coronavirus disease 2019 (COVID-19) cases observed in the months of July and August 2021. We performed genomic surveillance and genotyping as well as virological assessments to determine infectivity of the virus in a select number of clinical diagnostic samples. Genomic sequence analyses revealed complete replacement of the B.1.1.7 lineage (Alpha variant) with the B.1.617.2 lineage (Delta variant) between July 1 and August 4 2021. We observed a strong association between viral RNA loads detected by real-time reverse transcriptase PCR and infectious virus detected in respiratory secretions by virus titration. A marked increase in positive cases among fully vaccinated individuals was observed. The sequence divergence between two index Delta variant cases in April and May, and the cases after July 1st, revealed independent Delta variant introductions in Tompkins County. Contact tracing information enabled the detection of clusters of connected cases within closely related phylogenetic clusters. We also found evidence of transmission between vaccinated individuals and between vaccinated and unvaccinated individuals. This was confirmed by detection and isolation of infectious virus from a group of individuals within epidemiologically connected transmission clusters, confirming shedding of high viral loads and transmission of the virus by fully vaccinated individuals. IMPORTANCE The SARS-CoV-2 lineage B.1.617.2 (Delta variant) emerged in Asia and rapidly spread to other countries, becoming the dominant circulating lineage. Worldwide infections with B.1.617.2 peaked at a time in which vaccination rates were increasing. In this study, we present data characterizing the emergence of SARS-CoV-2 lineage B.1.617.2 (Delta variant) in Tompkins County, New York, which has one of the highest vaccination rates in the state. We present evidence demonstrating infection, replication, and transmission of SARS-CoV-2 lineage B.1.617.2 (Delta variant) between fully vaccinated individuals. Importantly, infectious virus loads were determined in a subset of samples and demonstrated shedding of high viral titers in respiratory secretions of vaccinated individuals.

Keywords: B.1.617.2; COVID-19; Delta variant; SARS-CoV-2; VOC; breakthrough infection.

FIG 1

COVID-19 vaccinations rates, SARS-CoV-2 rRT-PCR results, and viral lineages detected in Tompkins County, NY, from 1 May to 9 August 2021. (A) Number of COVID-19 vaccinations. Fully vaccinated was defined as individual received two vaccine doses in a 2-dose vaccine series or one dose of a single-dose vaccine. (B) SARS-CoV-2 rRT-PCR test results and the percentages of positive results. (C) Positive cases of COVID-19 according to individual vaccination status. “Not fully vaccinated” are unvaccinated individuals, those who had not completed the 2-dose series, or those who had a COVID-19-positive test earlier than 2 weeks after their second vaccine dose. “Not eligible” are individuals under age 12 who were not eligible for the vaccine at the time of the study. “Unknown” are individuals for whom vaccination status could not be confirmed. (D) SARS-CoV-2 lineages identified from 1 May to 9 August 2021 in Tompkins County, NY. The population of Tompkins County was estimated at 102,180 in 2019.

FIG 2

Viral RNA load according to vaccination status and infectious virus titers in vaccinated individuals. (A) SARS-CoV-2 RNA load detected by rRT-PCR according to vaccination status. “Not fully vaccinated” are unvaccinated individuals, those who had not completed the 2-dose series, or those who had a COVID-19-positive test earlier than 2 weeks after their second vaccine dose. “Unknown” are individuals for whom vaccination status could not be confirmed. (B) SARS-CoV-2 RNA load in a subset of anterior nares (AN) swabs collected from 14 fully vaccinated individuals and that were conditioned in viral transport medium without an inactivating solution. (C) Infectious SARS-CoV-2 titers in the same subset of AN swabs collected from 14 fully vaccinated individuals and that were conditioned in viral transport medium without an inactivating solution. Virus titers were determined based on fluorescence-positive wells, using the Spearman and Karber method, and are expressed as the TCID₅₀ per milliliter.

FIG 3

Phylogenetic tree and timeline of sequences classified as Delta lineage, detected in Tompkins County, NY, from May 1 to August 9 2021. (A) Nodes in the phylogenetic tree are differentiated by colors representing vaccination status. Nodes with a triangular shape represent samples that were successfully isolated in cell culture. The first column of metadata blocks represents the vaccine brand administered in the individuals with vaccinated status in the phylogenetic tree nodes. The second column of metadata blocks characterizes individuals by epidemiological clusters, differentiated by colors. (B) Timeline panel of detections. All the sequences used to build the phylogenetic tree are represented in the timeline, on the respective date of detection. Each circle or triangle represents an individual.