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
T2 - a prospective, longitudinal, cohort study
AU - ATACCC Study Investigators
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
N1 - Funding Information:
This work is supported by the National Institute for Health Research (NIHR200927), a Department of Health and Social Care COVID-19 Fighting Fund award, and the NIHR Health Protection Research Units (HPRUs) in Respiratory Infections and in Modelling and Health Economics. NMF acknowledges funding from the MRC Centre for Global Infectious Disease Analysis and the Jameel Institute. PSF and MAC are supported by the UK Dementia Research Institute. JD is supported by the NIHR HPRU in Emerging and Zoonotic Infections. MGW is supported by the NIHR HPRU in Healthcare Associated Infections and Antimicrobial Resistance. GPT is supported by the Imperial NIHR Biomedical Research Centre. We thank all the participants who were involved in the study, Public Health England staff for facilitating recruitment into the study, the staff of the Virus Reference Department for performing PCR and sequencing assays, and the Immunisations Department for assisting with analysis of vaccination data. We also thank Kristel Timcang, Mohammed Essoussi, Holly Grey, Guilia Miserocchi, Harriet Catchpole, Charlotte Williams, Niamh Nichols, Jessica Russell, Sean Nevin, Lulu Wang, Berenice Di Biase, Alice Panes, Esther Barrow, and Lauren Edmunds for their involvement in logistics, conducting data entry, or quality control; and the Molecular Diagnostics Unit at Imperial College London, in particular Lucy Mosscrop, Carolina Rosadas de Oliveira, and Patricia Watber, for performing RNA extraction, quantitative RT-PCR, and preparing samples for sequencing.
Funding Information:
NMF reports grants from UK Medical Research Council, UK National Institute of Health Research, UK Research and Innovation, Community Jameel, Janssen Pharmaceuticals, the Bill & Melinda Gates Foundation, and Gavi, the Vaccine Alliance; consulting fees from the World Bank; payment or honoraria from the Wellcome Trust; travel expenses from WHO; advisory board participation for Takeda; and is a senior editor of the eLife journal. All other authors declare no competing interests.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/2
Y1 - 2022/2
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.
AB - 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.
KW - Adult
KW - COVID-19/epidemiology
KW - Cohort Studies
KW - England/epidemiology
KW - Female
KW - Humans
KW - Kinetics
KW - Longitudinal Studies
KW - Male
KW - Middle Aged
KW - Prospective Studies
KW - SARS-CoV-2/physiology
KW - United Kingdom/epidemiology
KW - Vaccination
KW - Vaccination Coverage
KW - Viral Load/physiology
UR - http://www.scopus.com/inward/record.url?scp=85119140177&partnerID=8YFLogxK
U2 - 10.1016/S1473-3099(21)00648-4
DO - 10.1016/S1473-3099(21)00648-4
M3 - Article
C2 - 34756186
SN - 1473-3099
VL - 22
SP - 183
EP - 195
JO - The Lancet infectious diseases
JF - The Lancet infectious diseases
IS - 2
ER -
