Virus World

Vaccination and Household Transmission of SARS-CoV-2 In this study involving household contacts of persons with laboratory-confirmed Covid-19, the risk of household transmission was 40 to 50 lower in households of index patients who had been vaccinated 21 days or more before testing positive than in households of unvaccinated index patients.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevents infection and reduces the severity of coronavirus disease 2019 (Covid-19) in vaccinated persons.1,2 We investigated whether vaccination would reduce transmission in the household setting in the context of postvaccination infection. We analyzed data from the Household Transmission Evaluation Dataset (HOSTED), which has information on all laboratory-confirmed cases of Covid-19 in England and in which data on all persons sharing the same address are linked.3 We then linked to individual-level data on all Covid-19 vaccinations in England (see the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). We compared the risk of secondary infection (defined as a positive SARS-CoV-2 test 2 to 14 days after the positive test for the index case) among unvaccinated household contacts of persons with SARS-CoV-2 infection who had received at least one dose of the ChAdOx1 nCoV-19 or BNT162b2 vaccine 21 days or more before testing positive with the risk among unvaccinated household contacts of unvaccinated persons with infection. We fitted logistic-regression models with adjustment for the age and sex of the person with the index case of Covid-19 (index patient) and the household contact, geographic region, calendar week of the index case, deprivation (a composite score of socioeconomic and other factors), and household type and size. We also considered the timing of effects among index patients who had been vaccinated at any time up to the date of the positive test.

Between January 4 and February 28, 2021, there were 960,765 household contacts of unvaccinated index patients, and there were 96,898 secondary cases of Covid-19 (10.1%). (Descriptive data regarding the index patients and their household contacts are provided in the Summary Results section.) The numbers of secondary cases according to the vaccination status of the index patient, and the results of logistic-regression models, are shown in Table 1. Overall, the likelihood of household transmission was approximately 40 to 50% lower in households of index patients who had been vaccinated 21 days or more before testing positive than in households of unvaccinated index patients; the findings were similar for the two vaccines. Most of the vaccinated index patients in our data set (93%) had received only the first dose of vaccine. Assessment of infection risks among household contacts according to the timing of vaccination of the index patient showed protective effects when the vaccine had been administered at least 14 days before the positive test (Figs. S1 and S2 in the Supplementary Appendix)....

Published in NEJM (June 23, 2021):

https://doi.org/10.1056/NEJMc2107717 

Background: Following a single dose of BNT162b2 mRNA vaccine, higher antibody titres are observed following prior SARS-CoV-2 infection than in infection-naive individuals, but T-cell responses are less well defined.

Methods: We sampled healthcare workers (HCWs) enrolled in the UK PITCH study, before and after BNT162b2 mRNA vaccination. We measured spike-specific antibody, and quantified T-cell responses by IFNγ ELISpot assay and intracellular staining of peripheral blood mononuclear cells (PBMC), comparing SARS-CoV-2-naïve individuals to those with prior infection.

Findings: HCWs aged 22 to 71 years received one (n=216) or two (n=21) vaccine doses. After a single dose, the spike-specific T-cell response was six-fold higher in previously-infected vs. naive individuals (median 340 vs. 58 SFU/106 PBMC, p<0.0001; fresh PBMC, n=99). The T-cell response in previously-infected individuals after one vaccine dose was equivalent to naïve individuals receiving two vaccine doses (median 158 vs. 165 SFU/106 PBMCs, p=0.65; cryopreserved PBMC, n=117). Anti-spike IgG levels following a single dose in those previously infected (median 512.9 antibody units/ml (AU/ml)) were 6.8-fold higher vs. naïve individuals following one dose (median 75.0 AU/ml, p<0.0001) and 2.9-fold higher than naïve individuals given two doses three weeks apart (179.9 AU/ml, p=0.03). Following vaccination, plasma from individuals with prior infection demonstrated higher in vitro neutralisation of the B.1.351 variant of concern compared to naive individuals.

Interpretation: Following a single BNT162b2 dose, HCWs with a prior history of SARS-CoV-2 infection have significantly higher T-cell and antibody responses than naive individuals.Funding UK Department of Health and Social Care and UK Coronavirus Immunology Consortium.

Available as preprint in The Lancet (March 25, 2021):

http://dx.doi.org/10.2139/ssrn.3812375 

NEW YORK: Pfizer and BioNTech's COVID-19 vaccine appeared to only lose a small bit of effectiveness against an engineered virus with three key mutations from the new variant found in South Africa, according to a laboratory study conducted by the US drugmaker. The study by Pfizer and scientists from the University of Texas Medical Branch (UTMB), which has not yet been peer-reviewed, showed a less than two-fold reduction in antibody titer levels, indicating the vaccine would likely still be effective in neutralising a virus with the so-called E484K and N501Y mutations found in the South African variant. The study was conducted on blood taken from people who had been given the vaccine. Its findings are limited, because it does not look at the full set of mutations found in the new South African variant. The scientists are currently engineering a virus with the full set of mutations and expect to have results from that in about two weeks, according to Pei-Yong Shi, an author of the study and a professor at UTMB.

The results are more encouraging than another non-peer reviewed study from scientists at Columbia University earlier on Wednesday which used a slightly different method and showed antibodies generated by the shots were significantly less effective against the South Africa variant. One possible reason for the difference could be that the Pfizer findings are based on an engineered coronavirus, and the Columbia study used a pseudovirus based on the vesicular stomatitis virus, a different type of virus, UTMB's Shi said.  He said he believes that finding in pseudoviruses should be validated using the real virus. The study also showed even better results against several key mutations from the highly transmissible UK variant of the virus. Shi said they were also working on an engineered virus with the full set of mutations from that variant as well.

Research cited available in bioRxiv (Jan. 27, 2021):

https://doi.org/10.1101/2021.01.27.427998

A single dose of the COVID-19 vaccine made by either Pfizer or AstraZeneca cuts a person’s risk of transmitting SARS-CoV-2 to their closest contacts by as much as half, according to an analysis of more than 365,000 households in the United Kingdom. Although the vaccines have been shown to reduce COVID-19 symptoms and serious illness, their ability to prevent coronavirus transmission has been unclear. Kevin Dunbar, Gavin Dabrera and their colleagues at Public Health England in London looked for cases in which someone became infected with SARS-CoV-2 after receiving a dose of either vaccine (R. J. Harris et al. Preprint at Knowledge Hub https://go.nature.com/3e3iu1i; 2021). They then assessed how often those individuals transmitted the virus to household contacts. The team found that people who had been vaccinated for at least 21 days could still test positive for the virus. But viral transmission from these individuals to others in their households was 40–50% lower than transmission in households in which the first person to test positive had not been vaccinated. Results for the two vaccines were similar. The findings have not yet been peer reviewed.

The University of Oxford will lead the first trial exploring whether different Covid-19 vaccines can be used interchangeably, the University’s vaccine group said Thursday, an effort that could make vaccination programs more flexible and even provide better protection against the disease.  The study, run by the U.K. National Immunisation Schedule Evaluation Consortium, will recruit over 800 people over the age of 50 to evaluate the feasibility of using one vaccine for the first “prime” shot and different one for the second “booster” shot. At first, the trial will use the Oxford-AstraZeneca and Pfizer-BioNTech vaccines, both already cleared for emergency use in the U.K., with others potentially being added at a later date.  Britain’s Deputy Chief Medical Officer, Jonathan Van-Tam, said the trial would offer "greater insight" into the use of vaccines against Covid-19, and provide data that could support a “more flexible immunization programme" in light of global supply chain issues. 

AstraZeneca Plc said on Sunday Britain's health regulator had started an accelerated review of its potential coronavirus vaccine. “We confirm the MHRA’s (Medicines and Healthcare Products Regulatory Agency) rolling review of our potential COVID-19 vaccine,” an AstraZeneca spokesman said. In rolling reviews, regulators are able to see clinical data in real time and have dialogue with drug makers on manufacturing processes and trials to accelerate the approval process. The approach is designed to speed up evaluations of promising drugs or vaccines during a public health emergency. AstraZeneca’s COVID-19 vaccine is being developed along with the University of Oxford. Bloomberg reported on Friday that MHRA had also begun an accelerated review for the COVID-19 vaccine candidate from Pfizer Inc. AstraZeneca and Pfizer are among the frontrunners in the race to develop a vaccine for the coronavirus, with the race also including Johnson & Johnson and Moderna Inc. Their vaccine candidates are in late-stage trials, interim data from which are expected in the coming weeks.

The British drug maker said on Monday its COVID-19 experimental vaccine produces an immune response in both old and young adults. The vaccine also triggers lower adverse responses among the elderly, it said.  The novel coronavirus has killed more than 1.19 million people globally, damaged the world economy and turned normal life upside down for billions of people. Work began on the Oxford vaccine in January. Called AZD1222 or ChAdOx1 nCoV-19, the viral vector vaccine is made from a weakened version of a common cold virus that causes infections in chimpanzees.