Generation time of the Alpha and Delta SARS-CoV-2 variants

BackgroundIn May 2021, the Delta SARS-CoV-2 variant became dominant in the UK. This variant is associated with increased transmissibility compared to the Alpha variant that was previously dominant. To understand ongoing transmission and interventions, a key question is whether the Delta variant generation time (the time between infections in infector- infectee pairs) is typically shorter-i.e., transmissions are happening more quickly-or whether infected individuals simply generate more infections. MethodsWe analysed transmission data from a UK Health Security Agency household study. By fitting a mathematical transmission model to the data, we estimated the generation times for the Alpha and Delta variants. ResultsThe mean intrinsic generation time (the generation time if there had been a constant supply of susceptibles throughout infection) was shorter for the Delta variant (4{middle dot}6 days, 95% CrI 4{middle dot}0-5{middle dot}4 days) than the Alpha variant (5{middle dot}5 days, 95% CrI 4{middle dot}6-6{middle dot}4 days), although within uncertainty ranges. However, there was a larger difference in the realised mean household generation time between the Delta (3{middle dot}2 days, 95% CrI 2{middle dot}4-4{middle dot}2 days) and Alpha (4{middle dot}5 days, 95% CrI 3{middle dot}7-5{middle dot}4 days) variants. This is because higher transmissibility led to faster susceptible depletion in households, in addition to the reduced intrinsic generation time. ConclusionsThe Delta variant transmits more quickly than previously circulating variants. This has implications for interventions such as contact tracing, testing and isolation, which are less effective if the virus is transmitted quickly. Epidemiological models of interventions should be updated to include the shorter generation time of the Delta variant.

Higher serological responses and increased vaccine effectiveness demonstrate the value of extended vaccine schedules in combatting COVID-19 in England

IntroductionIn January 2021, the UK decided to prioritise the delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval until the second dose up to 12 weeks. MethodsSerological responses were compared after BNT162b2 and AZD1222 vaccination with varying intervals in uninfected and previously-infected adults aged 50-89 years. These findings are evaluated against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. ResultsWe recruited 750 participants aged 50-89 years, including 126 (16.8%) with evidence of previous infection; 421 received BNT162b2 and 329 and AZD1222. For both vaccines, over 95% had seroconverted 35-55 days after dose one, and 100% seroconverted 7+ days after dose 2. Following a 65-84 day interval between two doses, geometric mean titres (GMTs) at 14-34 days were 6-fold higher for BNT162b2 (6703; 95%CI, 5887-7633) than AZD1222 (1093; 806-1483), which in turn were higher than those receiving BNT162b2 19-29 days apart (694; 540 - 893). For both vaccines, VE was higher across all age-groups from 14 days after dose two compared to one dose, but the magnitude varied with interval between doses. Higher two-dose VE was observed with >6 week intervals between BNT162b2 doses compared to the authorised 3-week schedule, including [≥]80 year-olds. ConclusionOur findings support the UK approach of prioritising the first dose of COVID-19 vaccines, with evidence of higher protection following extended schedules. Given global vaccine constraints, these results are relevant to policymakers, especially with highly transmissible variants and rising incidence in many countries. FundingPublic Health England

Serological surveillance of SARS-CoV-2: trends and humoral response in a cohort of public health workers

BackgroundAntibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England. MethodsClinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression. FindingsIn total, 2246 individuals attended 12,247 visits and 264 were seropositive in [≥]2 assays. Most seroconversions occurred between March and April 2020. The assays showed >85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12-16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50-68%) Euroimmun, 41% (30-52%) RBD, 10% (8-14%) Roche (N) <2% Roche (S). InterpretationTrends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies.