Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study

Abstract

Background: The SARS-CoV-2 delta (B.1.617.2) variant is highly transmissible and spreading globally, including in populations with high vaccination rates. We aimed to investigate transmission and viral load kinetics in vaccinated and unvaccinated individuals with mild delta variant infection in the community.

Methods: Between Sept 13, 2020, and Sept 15, 2021, 602 community contacts (identified via the UK contract-tracing system) of 471 UK COVID-19 index cases were recruited to the Assessment of Transmission and Contagiousness of COVID-19 in Contacts cohort study and contributed 8145 upper respiratory tract samples from daily sampling for up to 20 days. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. We analysed transmission risk by vaccination status for 231 contacts exposed to 162 epidemiologically linked delta variant-infected index cases. We compared viral load trajectories from fully vaccinated individuals with delta infection (n=29) with unvaccinated individuals with delta (n=16), alpha (B.1.1.7; n=39), and pre-alpha (n=49) infections. Primary outcomes for the epidemiological analysis were to assess the secondary attack rate (SAR) in household contacts stratified by contact vaccination status and the index cases' vaccination status. Primary outcomes for the viral load kinetics analysis were to detect differences in the peak viral load, viral growth rate, and viral decline rate between participants according to SARS-CoV-2 variant and vaccination status.

Findings: The SAR in household contacts exposed to the delta variant was 25% (95% CI 18-33) for fully vaccinated individuals compared with 38% (24-53) in unvaccinated individuals. The median time between second vaccine dose and study recruitment in fully vaccinated contacts was longer for infected individuals (median 101 days [IQR 74-120]) than for uninfected individuals (64 days [32-97], p=0·001). SAR among household contacts exposed to fully vaccinated index cases was similar to household contacts exposed to unvaccinated index cases (25% [95% CI 15-35] for vaccinated vs 23% [15-31] for unvaccinated). 12 (39%) of 31 infections in fully vaccinated household contacts arose from fully vaccinated epidemiologically linked index cases, further confirmed by genomic and virological analysis in three index case-contact pairs. Although peak viral load did not differ by vaccination status or variant type, it increased modestly with age (difference of 0·39 [95% credible interval -0·03 to 0·79] in peak log₁₀ viral load per mL between those aged 10 years and 50 years). Fully vaccinated individuals with delta variant infection had a faster (posterior probability >0·84) mean rate of viral load decline (0·95 log₁₀ copies per mL per day) than did unvaccinated individuals with pre-alpha (0·69), alpha (0·82), or delta (0·79) variant infections. Within individuals, faster viral load growth was correlated with higher peak viral load (correlation 0·42 [95% credible interval 0·13 to 0·65]) and slower decline (-0·44 [-0·67 to -0·18]).

Interpretation: Vaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Host-virus interactions early in infection may shape the entire viral trajectory.

Funding: National Institute for Health Research.

Figure 1

Recruitment, SARS-CoV-2 infection, variant status, and vaccination history for ATACCC study participants (A) Study recruitment and variant status confirmed by whole-genome sequencing (ATACCC1 and ATACCC2 combined). (B) ATACCC2: delta-exposed contacts included in secondary attack rate calculation (table 1) and transmission assessment (table 2). NHS=National Health Service. *All index cases were from ATACCC2. † All contacts. ‡The two earliest PCR-positive cases from the ATACCC2 cohort (one index case and one contact) were confirmed as having the alpha variant on whole-genome sequencing (recruited on May 28, 2021). This alpha variant-exposed, PCR-positive contact is excluded from figure 1B. §One PCR-negative contact had no vaccination status data available and one PCR-negative contact's index case had no vaccination data available. ¶Vaccination data were available for 138 index cases of 163. ||The contacts of these 15 index cases are included within the 232 total contacts. **These three index cases without contacts are only included in the viral load kinetics analysis (figure 3) and are not included in tables 1 and 2.

Figure 2

Virological, epidemiological, and genomic evidence for transmission of the SARS-CoV-2 delta variant (B.1.617.2) in households (A) Genomic analysis of the four households with lineage-defining mutations for delta and additional mutations within ORFs displayed to give insight into whether strains from individuals within the household are closely related. Lineages AY.4 and AY.9 are sub-lineages of delta. (B) Viral trajectories and vaccination status of the four index cases infected with the delta variant for whom infection was detected in their epidemiologically linked household contacts. All individuals had non-severe disease. Each plot shows an index case and their household contacts. Undetectable viral load measurements are plotted at the limit of detection (10^1·49). C=contact. I=index case. FV=fully vaccinated. ORF=open reading frame. PV=partially vaccinated. U=unvaccinated.

Figure 3

ORF1ab viral load trajectories from 14 days before to 28 days after peak for 133 participants infected with pre-alpha or alpha variants (uncaccinated), or the delta variant (vaccinated and unvaccinated) variants Black circles are measured values, with the first datapoint for each participant being taken to the day of enrolment. Plots are rooted on the day of peak viral load for each participant, denoted as day 0 on the x-axis. Curves show the model posterior median estimate, with a 95% credible interval shading. 133 infected participants, comprising 114 contacts and 19 index cases. *Index cases.

Figure 3

ORF1ab viral load trajectories from 14 days before to 28 days after peak for 133 participants infected with pre-alpha or alpha variants (uncaccinated), or the delta variant (vaccinated and unvaccinated) variants Black circles are measured values, with the first datapoint for each participant being taken to the day of enrolment. Plots are rooted on the day of peak viral load for each participant, denoted as day 0 on the x-axis. Curves show the model posterior median estimate, with a 95% credible interval shading. 133 infected participants, comprising 114 contacts and 19 index cases. *Index cases.