Israeli, Canadian and UK studies showing a single dose of the Pfizer/BioNTech vaccine is 85% effective is not changing the two-dose policy of the US Food and Drug Administration, reports MedicalBrief. Presidential health adviser Dr Anthony Fauci said the US "will stick with the scientifically documented efficacy and optimal response of a prime followed by a boost".
This week, Public Health England (PHE) published the first independent analysis in the UK showing the Pfizer-BioNTech vaccine is effective against COVID-19 from the first dose. Also, an analysis by Canadian researchers suggests that a single dose of the Pfizer-BioNTech COVID-19 vaccine has 92.6 efficacy, according to a letter in the New England Journal of Medicine.
Responding to the earlier Israeli research, Fauci, who is also director of the National Institute of Allergy and Infectious Diseases, argued that one dose doesn't assure a durable immune response, and thus leaves potential for people with poorer immune responses to become incubators for escape variants. "We're not criticising the study," he added. "We do want to follow up on this."
However, a MedPage Today report says Andy Slavitt, the White House senior advisor for COVID-19 response, did not mince words in defending the US government's two-dose approach. "There are studies all the time, there are preprints all the time, there is real-world evidence all the time. One study, even though it may look attractive, it may capture a headline … it isn't always what it appears to be," he said. "It's important to understand we're not going to be persuaded by one study that happens to grab headlines."
Fauci also noted important limitations to the data, which the authors acknowledged, such as that "subjects were younger and healthier" than in other studies and the study shed no light on how long protection with one dose would last, "as most of the subjects received their second shot," he said.
When deciding on the two-dose strategy, Fauci stressed durability of immunity as a major factor. "If you look at the difference between the degree, the intensity of response after a first dose and compare it to after a second dose, the second dose has 10 times higher levels of neutralising antibodies," he said.
Even in the event of a five- to six-fold diminution of antibodies induced by an mRNA vaccine candidate against something like a COVID-19 variant, "it's still in the range of protection," he added.
"The response following the boost is so high that though (overall) efficacy is diminished to 50% (against the South African variant), it still had good efficacy against severe disease," he noted.
And if individuals have suboptimal responses, "because of immunological pressure" on the virus, they could "theoretically … be selecting for variants."
A single dose of the vaccine from Pfizer and BioNTech reduced COVID-19 infections by 85% in a study in Israel, Bloomberg reports, bolstering the UK’s decision to speed immunisations by delaying a second shot.
Among health-care workers who got the vaccine, symptomatic infections were reduced by that percentage in the 15 to 28 days after the first dose, compared with those who didn’t get a shot, according to the report in The Lancet medical journal. While most workers received a second dose on schedule – about three weeks after the first – the booster would only have just started to kick in by the end of the study, so it was essentially looking at the effects of one dose, researchers said.
Israeli researchers analysed the real-world effects of the Pfizer shot among staff at Sheba Medical Centre, the country’s largest hospital. Although it wasn’t a standard clinical trial like those used to establish the efficacy of drugs and vaccines, it gives preliminary support to health officials who recommend postponing second shots to quickly get first doses to as many people as possible.
Countries delaying second doses need to “understand the significance of the decision to give a single shot, and we show it carries quite substantial protection,” said Arnon Afek, Sheba Medical Centre’s associate director general and a co-author of the study.
“Early reductions of COVID-19 rates provide support of delaying the second dose in countries facing vaccine shortages and scarce resources,” the researchers concluded.
The Israeli researchers retrospectively analysed COVID-19 infections among more than 9,000 health-care workers who were eligible for the vaccine. The data was adjusted to reflect differing COVID exposure rates in vaccinated and non-vaccinated groups.
Case numbers were unlikely to have been affected by the second dose of vaccine, because it takes about a week to kick in, by which time the study period was over, said Sharon Amit, another study co-author and director of clinical microbiology at Sheba Medical Centre. Also, it usually takes about a week after being exposed for most people to show symptoms, so anyone who became sick toward the end of the 28-day period was likely to have been infected before their second dose.
“Follow-up to assess long-term effectiveness of a single dose is needed to inform a second dose delay policy,” the researchers cautioned in their report.
Study details
Early rate reductions of SARS-CoV-2 infection and COVID-19 in BNT162b2 vaccine recipients
Sharon Amit, Gili Regev-Yochay, Arnon Afek, Yitshak Kreiss, Eyal Leshem
Published in The Lancet on 18 February 2021
Also, an analysis by Canadian researchers suggests that a single dose of the Pfizer-BioNTech COVID-19 vaccine is highly efficacious, according to a letter published in the New England Journal of Medicine. A single dose of the Pfizer/BioNTech vaccine offers 92.6% efficacy in new calculations based on data submitted to the FDA, researchers report.
Medscape reports that together with previous findings that a single Moderna vaccine dose provides 92.1% efficacy against SARS-CoV-2 infection, investigators, Dr Danuta M Skowronski, of the British Columbia Centre for Disease Control in Vancouver, Canada, and Dr Gaston De Serres of the Quebec National Institute of Health, propose it is time to defer the second dose to extend protection to more people through single-dose mRNA vaccinations.
The report says other experts disagree, however, saying more data are needed before diverting from the two-dose regimen evaluated in clinical trials. They also point out that the FDA granted emergency use authorisation based on the two-dose studies.
"One of the things we should consider here is that when these vaccines are tested in clinical trials, they are tested under specific circumstances. In this case, two doses were used to achieve the efficacy. The studies did not actually look at just giving one dose and trying to just go with that," Dr Dial Hewlett Jr, medical director of the division of disease control at the Westchester County Department of Health in White Plains, New York, said during a media briefing, sponsored by the Infectious Diseases Society of America.
Dr Matthew Zahn who also spoke during the IDSA briefing, agreed. "The CDC has worked really hard at putting a premium on adhering to what the known science is, and the trials looked at two vaccine doses separated by less than 6 weeks.
"That's really why we've maintained that recommendation. From my side, I think that makes a great deal of sense," said Zahn, medical director in the division of epidemiology and assessment, Orange County Health Care Agency, Santa Ana, California.
In their correspondence, the authors report they examined documents submitted to the FDA from 2 weeks after the first dose up to the second immunisation. They note that "even before the second dose…[the vaccine] was highly efficacious."
Even if efficacy from one dose exceeds 90% at first, how long that protection persists without a second dose remains an open question, said Hewlett, who is also a member of the National Medical Association COVID-19 Task Force on Vaccines and Therapeutics. "We don't have any trial data saying the vaccines will be just as effective if you lengthen the time between the two doses," said Zahn, who also serves as a liaison representative to the CDC's Advisory Committee on Immunisation Practices.
Other researchers reported an efficacy of 94.8% against SARS-CoV-2 after two doses of the Pfizer/BioNTech vaccine in a previous study. The same report estimated a single-dose efficacy of 52.4% between the first and second doses, "but in their calculation, they included data that were collected during the first 2 weeks after the first dose, when immunity would have still been mounting," note Skowronski and De Serres.
"There may be uncertainty about the duration of protection with a single dose, but the administration of a second dose within 1 month after the first, as recommended, provides little added benefit in the short term, while high-risk persons who could have received a first dose with that vaccine supply are left completely unprotected," they note.
"It may be true that in the short run, one dose might be effective," Hewlett conceded, "but we don't know how long that this protection will last, and is the second dose going to be adding to that?" He explained that many public health officials want to simplify vaccine administration, but "before we can support this, we are going to have to have data that looks at this."
Skowronski and De Serres conclude their letter by stating that "given the current vaccine shortage, postponement of the second dose is a matter of national security that, if ignored, will certainly result in thousands of COVID-19-related hospitalisations and deaths this winter in the US – hospitalisations and deaths that would have been prevented with a first dose of vaccine."
In its response, Pfizer said alternative dosing regimens of the vaccine had not been evaluated yet and that the decision resided with the health authorities, reports Reuters.
Some countries, grappling with low supplies, are looking at dosing patterns or volumes that differ from how the vaccines were tested in clinical trials.
The report says there are differences over the merits of such strategies, with some arguing the urgency of the pandemic requires flexibility, while others oppose abandoning data-driven approaches for the sake of expediency.
In the UK, authorities have said that data supported its decision to move to a 12-week dosing schedule for Pfizer’s COVID vaccine. Both Pfizer and partner BioNTech have warned that they had no evidence to prove it.
Analysis of the data by researchers at PHE and the University of Oxford – NIHR Health Protection Research Unit shows the Pfizer-BioNTech vaccine provides high levels of protection against infection and symptomatic disease from the first dose.
Early data from PHE’s SIREN study shows a promising impact on infection in healthcare workers aged under 65. Healthcare workers in the study are tested for coronavirus (COVID-19) every 2 weeks – whether or not they have symptoms.
Data shows one dose reduces the risk of catching infection by more than 70%, rising to 85% after the second dose. This suggests the vaccine may also help to interrupt virus transmission, as you cannot spread the virus if you do not have infection.
PHE’s analysis of routine testing data also shows that one dose is 57% effective against symptomatic COVID-19 disease in those aged over 80. This effect occurs from about 3 to 4 weeks after the first dose.
Early data suggests the second dose in over 80s improves protection against symptomatic disease by a further 30%, to more than 85%.
Hospitalisation and deaths rates are falling in all age groups – but the oldest age groups are seeing the fastest decline since the peak in mid-January.
Early data suggests vaccinated people who go on to become infected are far less likely to die or be hospitalised. Overall, hospitalisation and death from COVID-19 will be reduced by over 75% in those who have received a dose of the Pfizer-BioNTech vaccine.
The risk of dying in those aged over 80 is less than half (56%) in vaccinated cases compared to unvaccinated cases, at least 14 days after receiving the first dose.
Those over 80 who develop COVID-19 infection after vaccination are around 40% less likely to be hospitalised than someone with infection who has not been vaccinated.
These high levels of protection are also seen against the variant of concern (B.1.1.7) first identified in South East England in December 2020.
While the data on infection, hospitalisation and death is promising, PHE will continue to observe these trends closely over the coming months to ensure firmer conclusions can be made.
PHE is also monitoring the real-world impact of the AstraZeneca vaccine and will publish these findings in due course – but early signals in the data suggest it’s providing good levels of protection from the first dose.
Dr Mary Ramsay, head of immunisation at PHE, said: “This is strong evidence that the Pfizer-BioNTech vaccine is stopping people from getting infected, while also protecting cases against hospitalisation and death. We will see much more data over the coming weeks and months but we should be very encouraged by these initial findings.
But protection is not complete, and we don’t yet know how much these vaccines will reduce the risk of you passing COVID-19 onto others. So even if you have been vaccinated, it is really important that you continue to act like you have the virus, practice good hand hygiene and stay at home.”
UK Health Secretary Matt Hancock said: “This crucial report shows vaccines are working – it is extremely encouraging to see evidence that the Pfizer vaccine offers a high degree of protection against coronavirus.
“Vaccines save lives, and so it is vital we roll out the vaccine programme as fast as possible, and that as many people as possible take the jab. This new evidence shows that the jab protects you, and protects those around you.
“It is important that we see as much evidence as possible on the vaccine’s impact on protection and on transmission, and we will continue to publish evidence as we gather it. As we roll out the jab, it is vital people continue to play their role in protecting the NHS by sticking with the rules.
“This data shows clear protection from the first dose, particularly against severe disease, supporting the decision to maximise the number of people vaccinated with a single dose, as advised by the Joint Committee on Vaccination and Immunisation (JCVI).
“The current dosing strategy will save more lives by ensuring more people receive protection from severe disease following the first dose.
“There is also good evidence suggesting that giving the second dose of AstraZeneca later will lead to much higher levels of protection. Offering the booster at 12 weeks will therefore help to ensure longer lasting protection beyond the current restrictions.@
The SIREN (Sarscov2 Immunity and REinfection EvaluatioN) study involves a sample of healthcare workers undertaking symptom questionnaires, respiratory swabs and serum samples.
Study details
Effectiveness of BNT162b2 mRNA Vaccine Against Infection and COVID-19 Vaccine Coverage in Healthcare Workers in England, Multicentre Prospective Cohort Study (the SIREN Study)
Victoria Jane Hall, Sarah Foulkes, Ayoub Saei, Nick Andrews, Blanche Oguti, Andre Charlett, Edgar Wellington, Julia Stowe, Natalie Gillson, Ana Atti, Jasmin Islam, Ioannis Karagiannis, Katie Munro, Jameel Khawam, The SIREN Study Group, Meera A Chand, Colin Brown, Mary E Ramsay, Jamie Lopez Bernal, Susan Hopkins
Published in The Lancet pre-print on 22 Feb 2021
Abstract
Background
BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK. We determined the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in our healthcare worker (HCW) cohort study of staff undergoing regular asymptomatic testing.
Methods
The SIREN study is a prospective cohort study among staff working in publicly funded hospitals. Baseline risk factors, vaccination status (from 8/12/2020-5/2/2021), and symptoms are recorded at 2 weekly intervals and all SARS-CoV-2 polymerase chain reaction (PCR) and antibody test results documented. A mixed effect proportional hazards frailty model using a Poisson distribution was used to calculate hazard ratios to compare time to infection in unvaccinated and vaccinated participants to estimate the impact of the BNT162b2 vaccine on all (asymptomatic and symptomatic) infection.
Findings
Vaccine coverage was 89% on 5/2/2021. Significantly lower coverage was associated with prior infection (aOR 0.59 95% confidence interval [CI] 0.54-0.64), female (aOR 0.72, 95% CI 0.63-0.82), aged under 35 years, being from minority ethnic groups (especially Black, aOR 0.26, 95% CI 0.21-0.32), porters/security guards (aOR 0.61, 95% CI 0.42-0.90),or midwife (aOR 0.74, 95% CI 0.57-0.97), and living in more deprived neighbourhoods (IMD 1 (most) vs. 5 (least) (aOR 0.75, 95% CI 0.65-0.87). A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort.
Conclusion
Our study demonstrates that the BNT162b2 vaccine effectively prevents both symptomatic and asymptomatic infection in working age adults; this cohort was vaccinated when the dominant variant in circulation was B1.1.7 and demonstrates effectiveness against this variant.
[link url="https://www.medpagetoday.com/infectiousdisease/covid19/91288?xid=nl_mpt_DHE_2021-02-20&eun=g1788811d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%20Top%20Cat%20HeC%20%202021-02-20&utm_term=NL_Daily_DHE_dual-gmail-definition"]Full MedPageToday report (Restricted access)[/link]
[link url="https://www.bloomberg.com/news/articles/2021-02-18/single-pfizer-shot-reduced-illness-in-israeli-health-workers?utm_source=google&utm_medium=bd&cmpId=google"]Full Bloomberg report (Restricted access)[/link]
[link url="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00448-7/fulltext"]The Lancet correspondence (Open access)[/link]
[link url="https://www.medscape.com/viewarticle/946102"]Full Medscape report (Restricted access)[/link]
[link url="https://www.nejm.org/doi/full/10.1056/NEJMc2036242"]New England Journal of Medicine letter[/link]
[link url="https://www.reuters.com/article/us-health-coronavirus-pfizer-idUSKBN2AI0EC"]Full Reuters report (Open access)[/link]
[link url="https://www.gov.uk/government/news/first-real-world-uk-data-shows-pfizer-biontech-vaccine-provides-high-levels-of-protection-from-the-first-dose"]PHE material[/link]
[link url="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3790399"]The Lancet study pre-print (Open access)[/link]
See also MedicalBrief archives:
[link url="https://www.medicalbrief.co.za/archives/israeli-data-shows-pfizer-vaccine-94-effective-against-covid-19/"]Israeli data shows Pfizer vaccine 94% effective against COVID-19[/link]