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Historically SARS-CoV-2 secondary attack rates (SAR) have been based on PCR positivity on screening symptomatic contacts; this misses transmission events and identifies only symptomatic contacts who are PCR positive at the time of sampling. We used serology to detect the relative transmissibility of Alpha Variant of Concern (VOC) to non-VOC SARS-CoV-2 to calculate household secondary attack rates. We identified index patients diagnosed with Alpha and non-VOC SARS-CoV-2 across two London Hospitals between November 2020 and January 2021 during a prolonged and well adhered national lockdown. We completed a household seroprevalence survey and found that 61.8% of non-VOC exposed household contacts were seropositive compared to 82.1% of Alpha exposed household contacts. The odds of infection doubled with exposure to an index diagnosed with Alpha. There was evidence of transmission events in almost all households. Our data strongly support that estimates of SAR should include serological data to improve accuracy and understanding.

Historically SARS-CoV-2 secondary attack rates (SAR) have been based on PCR positivity on screening symptomatic contacts; this misses transmission events and identifies only symptomatic contacts who are PCR positive at the time of sampling. We used serology to detect the relative transmissibility of Alpha Variant of Concern (VOC) to non-VOC SARS-CoV-2 to calculate household secondary attack rates. We identified index patients diagnosed with Alpha and non-VOC SARS-CoV-2 across two London Hospitals between November 2020 and January 2021 during a prolonged and well adhered national lockdown. We completed a household seroprevalence survey and found that 61.8% of non-VOC exposed household contacts were seropositive compared to 82.1% of Alpha exposed household contacts. The odds of infection doubled with exposure to an index diagnosed with Alpha. There was evidence of transmission events in almost all households. Our data strongly support that estimates of SAR should include serological data to improve accuracy and understanding.

BackgroundHeterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified Vaccinia Virus Ankara (MVA) vectored vaccines is a strategy previously shown to provide substantial protective efficacy against P. falciparum infection in United Kingdom adult Phase IIa sporozoite challenge studies (approximately 20-25% sterile protection with similar numbers showing clear delay in time to patency), and greater point efficacy in a trial in Kenyan adults.MethodologyWe conducted the first Phase IIb clinical trial assessing the safety, immunogenicity and efficacy of ChAd63 MVA ME-TRAP in 700 healthy malaria exposed children aged 5-17 months in a highly endemic malaria transmission area of Burkina Faso.ResultsChAd63 MVA ME-TRAP was shown to be safe and immunogenic but induced only moderate T cell responses (median 326 SFU/106 PBMC (95% CI 290-387)) many fold lower than in previous trials. No significant efficacy was observed against clinical malaria during the follow up period, with efficacy against the primary endpoint estimate by proportional analysis being 13.8% (95%CI -42.4 to 47.9) at sixth month post MVA ME-TRAP and 3.1% (95%CI -15.0 to 18.3; p = 0.72) by Cox regression.ConclusionsThis study has confirmed ChAd63 MVA ME-TRAP is a safe and immunogenic vaccine regimen in children and infants with prior exposure to malaria. But no significant protective efficacy was observed in this very highly malaria-endemic setting.Trial registrationClinicalTrials.gov NCT01635647. Pactr.org PACTR201208000404131.