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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.
Lancet Infect Dis. 2022 02; 22(2):183-195.LI

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.

Links

PMC Free PDF

Authors+Show Affiliations

Singanayagam A
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK; Department of Infectious Disease, Imperial College London, London, UK; National Infection Service, Public Health England, London, UK.
Hakki S
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Dunning J
NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Oxford, Oxford, UK; National Infection Service, Public Health England, London, UK.
Madon KJ
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Crone MA
Department of Infectious Disease, Imperial College London, London, UK; UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK; London Biofoundry, Imperial College Translation and Innovation Hub, London, UK.
Koycheva A
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Derqui-Fernandez N
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Barnett JL
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Whitfield MG
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Varro R
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Charlett A
Data and Analytical Services, Public Health England, London, UK.
Kundu R
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Fenn J
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Cutajar J
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Quinn V
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Conibear E
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Barclay W
Department of Infectious Disease, Imperial College London, London, UK.
Freemont PS
Department of Infectious Disease, Imperial College London, London, UK; UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK; London Biofoundry, Imperial College Translation and Innovation Hub, London, UK.
Taylor GP
Department of Infectious Disease, Imperial College London, London, UK.
Ahmad S
Department of Virology, Manchester Medical Microbiology Partnership, Manchester Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK.
Zambon M
National Infection Service, Public Health England, London, UK.
Ferguson NM
NIHR Health Protection Research Unit in Modelling and Health Economics, MRC Centre for Global Infectious Disease Analysis, Jameel Institute, Imperial College London, London, UK.
Lalvani A
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK. Electronic address: a.lalvani@imperial.ac.uk.
ATACCC Study Investigators
No affiliation info available

MeSH

AdultCOVID-19Cohort StudiesEnglandFemaleHumansKineticsLongitudinal StudiesMaleMiddle AgedProspective StudiesSARS-CoV-2United KingdomVaccinationVaccination CoverageViral Load

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34756186

Citation

Singanayagam, Anika, et al. "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." The Lancet. Infectious Diseases, vol. 22, no. 2, 2022, pp. 183-195.
Singanayagam A, Hakki S, Dunning J, et al. 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. Lancet Infect Dis. 2022;22(2):183-195.
Singanayagam, A., Hakki, S., Dunning, J., Madon, K. J., Crone, M. A., Koycheva, A., Derqui-Fernandez, N., Barnett, J. L., Whitfield, M. G., Varro, R., Charlett, A., Kundu, R., Fenn, J., Cutajar, J., Quinn, V., Conibear, E., Barclay, W., Freemont, P. S., Taylor, G. P., ... Lalvani, A. (2022). 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. The Lancet. Infectious Diseases, 22(2), 183-195. https://doi.org/10.1016/S1473-3099(21)00648-4
Singanayagam A, et al. 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. Lancet Infect Dis. 2022;22(2):183-195. PubMed PMID: 34756186.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Singanayagam,Anika, AU - Hakki,Seran, AU - Dunning,Jake, AU - Madon,Kieran J, AU - Crone,Michael A, AU - Koycheva,Aleksandra, AU - Derqui-Fernandez,Nieves, AU - Barnett,Jack L, AU - Whitfield,Michael G, AU - Varro,Robert, AU - Charlett,Andre, AU - Kundu,Rhia, AU - Fenn,Joe, AU - Cutajar,Jessica, AU - Quinn,Valerie, AU - Conibear,Emily, AU - Barclay,Wendy, AU - Freemont,Paul S, AU - Taylor,Graham P, AU - Ahmad,Shazaad, AU - Zambon,Maria, AU - Ferguson,Neil M, AU - Lalvani,Ajit, AU - ,, Y1 - 2021/10/29/ PY - 2021/09/03/received PY - 2021/09/27/revised PY - 2021/10/11/accepted PY - 2021/11/11/pubmed PY - 2022/2/5/medline PY - 2021/11/10/entrez SP - 183 EP - 195 JF - The Lancet. Infectious diseases JO - Lancet Infect Dis VL - 22 IS - 2 N2 - 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. SN - 1474-4457 UR - https://www.unboundmedicine.com/medline/citation/34756186/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_ DB - PRIME DP - Unbound Medicine ER -