Unpacking the lingering questions over AstraZeneca's vaccine

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In response to US government concerns over data used, AstraZeneca released updated information on its COVID-19 clinical trial, showing an effectiveness rate of 76% instead of the 79% rate it claimed earlier. Nature unpacks the “real mess” around the vaccine's rollout.

Earlier, Nature reported that shortly after the University of Oxford and the pharmaceutical firm AstraZeneca reported positive early results AstraZeneca from the largest trial so far of their COVID-19 vaccine, officials at a US government agency overseeing the trial questioned claims about the vaccine’s efficacy.

“The world, the species, depends on this vaccine. This is 2.5bn people’s worth of vaccine,” says Eric Topol, a physician-scientist and director of the Scripps Research Translational Institute in La Jolla, California. Lingering questions over the latest trial are “a real mess”, he adds.

The latest development might amount to “nothing more than a technicality”, says Stephen Griffin, a virologist at the University of Leeds, UK. But it highlights issues regarding how trial data are being communicated through press releases.

The news comes a week after countries across Europe temporarily halted roll-outs to review reports of rare blood-clotting conditions in a handful of vaccinated individuals. The vaccine has since been deemed safe by the European Medicines Agency (EMA) and continues to be recommended by the World Health Organisation (WHO).

 

For months, European countries have seesawed between craving and rebuffing AstraZeneca’s vaccine, with the shot’s fortunes rising and falling on spats over supply and on questions over the efficacy of the vaccine itself. But, reports The New York Times, few concerns have proved as disruptive to the rollout of the world’s workhorse vaccine in Europe as reports of very rare blood clots in some recipients.

Many countries responded by halting the shot’s use, only to start giving it again after an all-clear from regulators at the European Medicines Agency, and then stopped inoculations a second time in certain age groups after doctors became more concerned about the clots.

The NYT reports that on Tuesday, those concerns were reinforced yet again when a top vaccines official at the European Medicines Agency said that the vaccine was linked to extremely rare, though sometimes fatal, blood clots in a small number of recipients. It was the first indication from an international regulatory body that the clots may be a real, if very unusual, side effect of the shot.

Regulators now appear to be considering issuing their first formal warnings about the potential side effects – not only in continental Europe, which has long been wary of the shot for political and scientific reasons, but also in Britain, the birthplace of the AstraZeneca vaccine and long its biggest champion, where new data have sown concerns as well.

The University of Oxford, which developed the vaccine with AstraZeneca, said on Tuesday that it had suspended a two-month-old trial of the vaccine in children and teenagers in Britain while it waits for regulatory guidance.

The NYT reports that most scientists and health officials say that the vaccine’s benefits still far outweigh the risks in older people, who appear less susceptible to the clots. Several dozen cases of the blood clots, mostly in younger people, have been recorded among the tens of millions of people who have received the vaccine across Europe.

But more countries could restrict the vaccine’s use in younger people, setting back efforts to inoculate enough people to reopen struggling economies. The European Medicines Agency said it will meet this week to consider updating its guidance.

 

Some UK drug safety experts believe there could be a causal link between the AstraZeneca jab and rare blood clotting events including cerebral venous sinus thrombosis (CVST), reports The Guardian.

Professor Saad Shakir, the director of the drug safety research unit (DSRU) at Southampton University, said that the evidence accumulated in Europe and the UK of links between the vaccine and the rare blood clots “is consistent with causality”.

The DSRU at Southampton University looked at cases of thrombosis (blood clotting inside the arteries) linked to thrombocytopenia (a reduction in blood platelets that usually causes bleeding but in rare cases results in clotting) and concluded that they were linked to the AstraZeneca vaccine.

The events are very rare, however. In the UK, as of 24 March, 30 events had occurred resulting in seven deaths from 18.1m doses of vaccine, they said. In Germany, there was one event of cerebral venous thrombosis for every 46,512 women vaccinated and one female death associated with this condition for every 149,860 vaccine doses given to women of any age.

The Guardian reports that even for younger people, the risk of death from COVID is higher. In the UK, according to the scientists, it has been calculated that 47,000 vaccines prevent one death from COVID among all people under 50.

Shakir says that all the cases now in the public domain occurred within four to 16 days of vaccination. “So, there is what we call a close temporal relationship, and they don’t seem to be events of COVID, which you get in the first two weeks after vaccination,” he said.

“The second thing is that there is a clear clinical description and similarities between the cases. The thromboses, lowering of the blood platelets, and various haematological changes. All of them are consistent with an event, which occurs very, very rarely, and certainly only with a drug called heparin.”

Heparin is a blood-thinning drug. Very occasionally, it causes a syndrome called HIT – heparin-induced thrombocytopenia. A group of German scientists led by the clotting specialist Andreas Greinacher of the University of Greifswald has already pointed out that the blood clotting events reported after the AstraZeneca jab look very similar to HIT.

Shakir is quoted in The Guardian as saying the AstraZeneca vaccine was safe and effective. “It has protected millions of people from Covid-19 and will continue to do so around the world,” he said.

 

Amid the uncertainty, Nature looks at everything we do and don’t know about the AstraZeneca vaccine.

What is the vaccine’s role in the pandemic?

Unlike many of the vaccines, which are expensive and must be stored at very low temperatures, the Oxford–AstraZeneca vaccine can be kept in an ordinary fridge and costs a few dollars per dose. And, because it is expected to be produced on a huge scale, it could play a vital part in quelling the pandemic.

For the moment, “in many countries, especially on the African continent, the AstraZeneca vaccine is the only one that will be available in substantial quantities”, says Shabir Madhi, a vaccinologist at the University of the Witwatersrand in Johannesburg, South Africa.

The vaccine has received regulatory approval in more than 100 countries and should be used with confidence, Kristine Macartney, director of Australias National Centre for Immunisation Research and Surveillance in Sydney, said. But it has not yet been approved in the US.

More than 20m doses have been administered in EU countries and the UK, as have a further 27m in India of a version of the vaccine known as Covishield. The vaccine is also being delivered through the COVAX scheme to dozens of low- and middle-income countries; AstraZeneca has committed 170m doses to COVAX and plans overall to produce 3bn doses by the end of 2021.

How effective is the vaccine?

On 22 March, the company said in a press release that a preliminary analysis had found two doses to be 79% effective at preventing COVID-19 in a trial of 32,449 adults across the US, Peru and Chile. No participants who received the vaccine were hospitalised or died, even though 60% had pre-existing conditions associated with increased risk of severe disease, such as diabetes or obesity. Only 141 cases of COVID-19 were reported overall, although the breakdown of those who received the vaccine, and those who did not, has not yet been revealed.

The following day, the US National Institutes of Allergy and Infectious Diseases (NIAID) said that an independent data safety monitoring board (DSMB) overseeing the trial had concerns that AstraZeneca could have presented “outdated information” that provided an incomplete view of the vaccine’s efficacy. In a letter, the DSMB told the NIAID that it had urged the company to communicate an efficacy of 69–74%, based on more current data.

With the release of the interim trial data, AstraZeneca also said that it had not identified any safety concerns, and had found no cases of that specific disorder, which is called cerebral venous sinus thrombosis. “I hope this data is reassuring,” says Ann Falsey, an infectious-disease physician at the University of Rochester in New York, who co-led the trial. But other researchers caution that the condition could be too rare – appearing in one or two people out of a million – to crop up in a trial of tens of thousands.

In unpublished work, scientists in Norway and Germany have reported one possible mechanism by which the vaccine could have caused rare blood-clotting conditions, as well as a possible treatment.

The first studies included too few participants aged over 55 for researchers to know whether the vaccine offers the same protection for older people as for younger people. “That was a pretty big hole in the data,” says Griffin.

This lack of evidence meant that some countries, including Germany, initially didn’t approve the vaccine for those aged 65 or older. But Germany later revised its guidelines to include all adults, after reviewing studies from England and Scotland. Those studies showed “strong protection against hospitalisation, death and disease”, says Macartney.

AstraZeneca’s interim trial data suggests that the vaccine is 80% effective at preventing COVID-19 among those aged 65 or older, who made up 20% of trial participants. The press release does not state how many cases of COVID-19 were found in this cohort, but Falsey said that there were enough infections in the older age group to enable a statistically significant comparison.

What is the optimal timing of doses?

The optimal dosing schedule has been unclear since the first results were announced in November, revealing that a subset of participants who had accidentally received less vaccine in their first dose were less likely to develop COVID-19. A later analysis suggested that the increased protection resulted not from a dosing error, but from the longer time between doses.

Early trials were originally designed for a one-dose regimen, but researchers decided to add a booster after data showed that a single dose didn’t produce a strong enough immune response. They tried a range of intervals between doses, from 4 to 12 weeks. The interim results from AstraZeneca do not add more clarity on how to optimise dosing, because all participants were given two doses four weeks apart. Falsey says that a longer gap would probably induce a stronger immune response, but a briefer interval is more practical in the middle of a pandemic. The WHO recommends an interval of 8 to 12 weeks.

What will be the impact of this latest confusion on the US roll-out?

Falsey said that AstraZeneca planned to file for emergency-use authorisation with the US Food and Drug Administration (FDA) in the coming weeks, and hopes to gain approval in April.

Stephen Evans, a biostatistician at the London School of Hygiene & Tropical Medicine, hopes that the FDA will put the vaccine’s reputation back on track. In contrast to other regulators, the FDA uses raw trial data to conduct its own analysis. “I think the way that the ship will be righted is by having the FDA’s scrutiny,” says Evans, who expects it to eventually authorise the vaccine.

It is unclear whether the vaccine will be widely rolled out in the US, which is flush with doses of vaccine from Pfizer, Moderna and Johnson & Johnson. But researchers worry that confusion over the AstraZeneca vaccine’s efficacy will dent global uptake. “What I’m most distressed about is the effect in low- and middle-income countries – that they will lose confidence,” says Evans.

This uncertainty only adds to any fallout from the pauses in Europe last week. “Decisions made in the global north can have substantial consequences,” warns Madhi.

How does the Oxford–AstraZeneca vaccine perform against variants?
A big question facing all vaccines since new virus variants started emerging last year – some more transmissible than earlier variants – is how well vaccines work against them. Preliminary analysis in one UK trial of the AstraZeneca vaccine found that it provided a similar level of protection against the B.1.1.7 variant, first detected in the UK, as it did against pre-existing variants.

But the situation with B.1.351, first detected in South Africa, is more complicated. A small study there, of some 2,000 adults aged under 65, found that it didn’t protect against mild-to-moderate COVID-19 from that variant. South Africa has suspended roll-out of the AstraZeneca vaccine, but the WHO still recommends its use in regions where variants of concern are circulating.

Soon, AstraZeneca will start trials on next-generation vaccines that will work against all current SARS-CoV-2 variants, said Mene Pangalos, the company’s executive vice-president of biopharmaceuticals research and development, at a virtual press briefing on 23 March. He added that he hopes they will become available for use in late 2021.

 

AstraZeneca's updated information on its COVID-19 clinical trial only marginally changed the picture, USA Today reports.

As of 17 February, 141 people in the trial had come down with COVID-19, the vast majority in the group that received a saltwater placebo rather than the active vaccine. Among those people, the vaccine was shown to be 79% effective in preventing any symptoms of COVID-19, and 100% effective in preventing severe disease and hospitalisations.

The updated information, which included 190 symptomatic cases, showed only a slightly different picture.

The vaccine prevented 76% of cases of symptomatic disease two weeks after the second dose, as well as all severe disease and hospitalizations, according to the updated data. It was 85% effective against symptomatic COVID-19 in trial volunteers aged 65 and over, according to the new data, instead of the 80% reported earlier.

Eight trial participants developed severe COVID-19, all of whom received a saline shot instead of active vaccine, the company said.

Fourteen more cases of possible or probable infection have yet to be fully examined, so the figures may change slightly, the company said.

The updated figures show the vaccine remains effective enough to meet the FDA's standards.

The trial also showed the vaccine to be safe, despite concerns raised in Europe over about a dozen incidents of rare blood clots among the 20m people vaccinated there. European and British drug regulators and the WHO have determined the AstraZeneca-Oxford vaccine to be safe, though they could not completely rule out the possibility that the shot played a role in the unusual blood clots.

Regulators will continue to follow vaccine recipients to make sure the blood clots are not a problem. There were none seen in the US trial.

USA Today reports that it is not clear why AstraZeneca presented dated information to the public, knowing it would have to provide the remaining figures a few weeks later, particularly because the findings were so similar.

 

Further cases of a rare blood clotting syndrome including seven deaths have been reported among recipients of the Oxford/AstraZeneca jab in the UK, although experts say the numbers remain low and the benefits of the vaccine far outweigh any risks, reports The Guardian.

The Medicines and Healthcare products Regulatory Agency (MHRA) runs a “yellow card” scheme to pick up suspected side-effects or other concerns for medicines and medical devices.

The Guardian reports that according to the latest figures from the MHRA, there have been 22 reports of a blood clot in the brain called cerebral venous sinus thrombosis (CVST) that was accompanied by a low platelet count as well as eight reports of other blood clotting problems with low platelets, among recipients of the Oxford/AstraZeneca jab up to and including 24 March. Platelets are fragments in the blood that help it to clot.

Of these 30 reports, the MHRA said seven people had died.

However, such cases remain rare: the MHRA notes that by 24 March, 18.1m doses of the COVID-19 Oxford vaccine had been given. There have also been two cases of CVST among people who received the Pfizer/BioNTech jab, neither of them accompanied by a low platelet count.

The Guardian reports that concerns over rare blood clotting events have dogged the Oxford jab in recent weeks. The MHRA and the European Medicines Agency (EMA) have said it has not been proven that the events were caused by the jab, and the benefits of vaccination far outweigh the risks, given the danger posed by COVID. But the EMA said a warning about such events would be included in the vaccine information while investigations continued.

Estimates of CVST in an unvaccinated population vary, but, The Guardian reports, it is rare, with upper estimates of 15 to 16 cases per million people per year.

At present, most of these rare clotting events appear to be occurring in women under the age of 65 – but quite why this is remains unclear.

 

 

A CIDRAP report notes that a handful of countries are investigating more reports of blood clots in people who received the AstraZeneca-Oxford COVID-19 vaccine, including the Netherlands, which has suspended use in people younger than 60.

The report notes that health groups continue to maintain that the benefits from the AstraZeneca vaccine greatly outweigh the risks, but reports of rare blood clotting problems in those who received the vaccine continue to trickle in.

In the Netherlands, the health ministry announced a pause in vaccinating people younger than 60 as a precaution over possible side effects. It said the move was prompted by new reports of thrombosis and low platelet counts after vaccination, which involved five women ages 25 to 65. So far, about 400,000 doses of the vaccine have been administered in the Netherlands.

CIDRAP reports that a panel from the British Society of Haematology has released interim guidance on diagnosing and managing the rare conditions, which they say have not been definitively linked to vaccination. However, they say the cases are unusual, because despite thrombocytopenia, patients experience progressive thrombosis, mainly venous, with a high preponderance of CVST.

Meanwhile, Australia's vaccine advisory group said that officials are investigating one probable case of a rare clotting event after vaccination. Media reports said the blood clots occurred in a 44-year-old man who was admitted to a Melbourne hospital with serious thrombosis and low platelet count.

So far, more than 400,000 doses of the AstraZeneca vaccine have been given in the country. Officials said they have not changed their recommendations and will meet again on 7 April.

In Germany, ongoing questions about the side effects led to another policy change about the use of the vaccine, following an announcement earlier this week of a pause in people younger than 60.

In the latest development, officials said people under 60 who got their first dose of AstraZeneca vaccine should receive a different product for their second dose. The country's vaccine commission acknowledges that there is no scientific evidence of safety on mixed vaccine use.

 

 

Authors ask the question in The Lancet: Thromboembolism and the Oxford-AstraZeneca COVID-19 vaccine – side-effect or coincidence?
Søren Dinesen Østergaard, Morten Schmidt, Erzsébet Horváth-Puhó, Reimar Wernich Thomsen and Henrik Toft Sørensen write:
By mid March, 2021, vaccination against COVID-19 using the ChAdOx1 nCoV-19 (AZD1222) vaccine from Oxford–AstraZeneca was paused in a number of European countries due to reports of thromboembolic events in vaccinated individuals.

According to the European Medicines Agency (EMA), 30 cases of thromboembolic events (predominantly venous) had been reported by 10 March, 2021, among the approximately 5m recipients of the Oxford–AstraZeneca COVID-19 vaccine in the European Economic Area.

The EMA subsequently stated that “The number of thromboembolic events in vaccinated people is no higher than the number seen in the general population”.

To inform the ongoing discussion on the safety of the Oxford–AstraZeneca COVID-19 vaccine, we analysed nationwide population-based data from Denmark to estimate the natural incidence of venous thromboembolism.

Denmark has a tax-supported universal health-care system, in which all hospital contacts are registered in the Danish National Patient Registry.

We first used the Danish Civil Registration System to identify all Danes who were at least 18 years old between Jan 1, 2010, and Nov 30, 2018. Using data from the Danish National Patient Registry, we then identified all first-time cases of venous thromboembolism in the general adult population in this period (corresponding to the available data period). We focused on venous thromboembolism because the thromboembolic events reported in relation to the Oxford–AstraZeneca COVID-19 vaccine by March 10, 2021, were predominantly venous, according to publicly available data on EudraVigilance.

We followed all individuals from 1 January, 2010, or their 18th birthday (whichever came first), until their first incident venous thromboembolism, death, emigration, or 30 November, 2018. Individuals with a diagnosis of venous thromboembolism before 1 January, 2010, or their 18th birthday were not included in the analyses. Incident venous thromboembolism was defined as the first primary or secondary inpatient hospital diagnosis or outpatient clinic diagnosis of venous thromboembolism.

Specifically, the following diagnoses were included in the outcome definition: deep vein thrombosis (International Classification of Diseases version 10[ICD-10]: I80.1–3), pulmonary embolism (ICD-10: I26), portal vein thrombosis (ICD-10: I81), hepatic vein thrombosis (ICD-10: I82.0), thrombophlebitis migrans (ICD-10: I82.1), embolism or thrombosis of vena cava (ICD-10: I82.2), embolism or thrombosis of renal vein (ICD-10: I82.3), mesenteric thrombosis (ICD-10: K55.0H), cerebral infarction due to non-pyogenic cerebral venous thrombosis (ICD-10: I63.6), and non-pyogenic thrombosis of intracranial venous system (ICD-10: I67.6).

The diagnoses of venous thromboembolism in the Danish National Patient Registry have a documented high positive predictive value.

We then calculated incidence rates for venous thromboembolism (any of the diagnoses listed above) for all Danish adults (aged 18 years or older censored at the 100th birthday) as well as for Danes aged 18–64 years. The 18–64-year age group represents the age group in which the Oxford–AstraZeneca COVID-19 vaccine, due to initial perceptions of limited evidence on its efficacy among those aged 65 years and older, has predominantly been used in most European countries – with the exception of the UK, where the vaccine has also been administered among those aged 65 years and older from the outset.

We repeated the analysis restricting outcomes to deep vein thrombosis or pulmonary embolism, as they account for more than 95% of all diagnoses and stratified by sex. All incidence rates were calculated by dividing the number of incident venous thromboembolisms during follow-up by the sum of person-years during follow-up and reported per 1000 person-years. Subsequently, using these incidence rates for venous thromboembolism, we estimated the number of cases that would be expected over the course of 1 week and 1 month, respectively, in a population with the same size as that having received the Oxford–AstraZeneca COVID-19 vaccine in Europe by 10 March, 2021. This was done by rescaling the incidence rates to the weekly (7 days) and monthly level (30·5 days) per individual, and multiplying them by 5 million. An example of the calculation carried out for this estimation is provided in the appendix.

The study population aged 18–99 years included 4 915 426 individuals, with a total follow-up time of 38 449 703 person-years. The study population aged 18–64 years included 3 963 153 individuals, with a total follow-up time of 29 537 310 person-years. Equivalent sex-stratified numbers are provided in the appendix.

The number of venous thromboembolic events, as well as the incidence rates in the Danish population in the period from 2010 to November, 2018 are also provided in the appendix. The incidence rate per 1000 person-years was 1·76 (95% CI 1·75–1·78) for venous thromboembolism among Danes aged 18–99 years, and 0·95 (0·94–0·96) among Danes aged 18–64 years. When restricting to deep vein thrombosis or pulmonary embolism, the incidence rate per 1000 person-years was 1·70 (95% CI 1·68–1·71) among Danes aged 18–99 years and 0·91 (0·89–0·92) for those aged 18–64 years. The results were consistent for women and men.

In a population of 5m people (size matching the approximate number of people having received the Oxford–AstraZeneca COVID-19 vaccine in Europe by 10 March, 2021), this incidence would correspond to approximately 169 expected cases of venous thromboembolism per week, or 736 expected cases per month (if based on the incidence rate among the 18–99-year-old Danes). Similarly, if estimated based on the incidence rate among 18–64-year-old Danes, one would expect 91 cases of venous thromboembolism per week, or 398 cases per month.

The Danish data provided here cannot rule out the possibility that some venous thromboembolic events reported in relation to the use of the Oxford–AstraZeneca COVID-19 vaccine are caused by the vaccine. However, although affected by several limitations, these data suggest that the reported number of thromboembolic events among Europeans who have received the Oxford–AstraZeneca COVID-19 vaccine (at least those reported as deriving from the venous system) does not seem to be increased relative to the expected number estimated from incidence rates from the entire Danish population before the introduction of the vaccination programme.

Our findings should be interpreted in the context of their limitations. The number of cases of thromboembolism reported in relation to the Oxford–AstraZeneca COVID-19 vaccine cannot be directly compared to the numbers estimated based on the incidence rates from the Danish population for several reasons.

First, data on the sex and age distribution from those who received the Oxford–AstraZeneca COVID-19 vaccine are not yet publicly available. In Denmark, about 99% of those having receiving the Oxford–AstraZeneca COVID-19 vaccine are health-care workers (Valentiner-Branth P, Statens Serum Institut, Denmark, personal communication). The median age of all COVID-19 vaccinated health-care workers in Denmark is 47 years (IQR 36–57), and 82·2% of health-care workers are women.

Second, data on the duration of the period during which the Oxford–AstraZeneca COVID-19 vaccinated population developed the reported thromboembolic events are also not publicly available, making it impossible to estimate incidence rates for this population. Third, detailed clinical descriptions of the thromboembolic events reported in relation to Oxford–AstraZeneca COVID-19 vaccinations are still lacking.

We are, however, aware that although a substantial fraction of the thromboembolisms seem to be venous, reports are emerging of rare types of multiple thrombosis, bleeding, and thrombocytopenia, apparently similar to disseminated intravascular coagulation, occurring in otherwise healthy individuals shortly after receiving the Oxford–AstraZeneca COVID-19 vaccine.

These outcomes are not included in the present analysis. Fourth, as even the most efficient spontaneous reporting of adverse events is unlikely to capture all cases, the true incidence rate of thromboembolic events in relation to the Oxford–AstraZeneca COVID-19 vaccine is unknown, and the 30 reported cases by 10 March, 2021, is probably an underestimate.

Finally, our estimated weekly and monthly venous thromboembolism case numbers in the population of 5m individuals are based entirely on incidence rates from Denmark and might not be representative of the other countries where the Oxford–AstraZeneca COVID-19 vaccine has been used.

However, previous studies of the incidence rate of venous thromboembolism in other countries have found numbers within range of the Danish rates.

When making decisions on the use of drugs based on pharmacovigilance, it is important to take into account the natural incidence of illnesses, such as venous thromboembolisms, that might be interpreted as serious adverse events.

Here, based on pre-pandemic incidence rates from the entire Danish population, we report that the number of venous thromboembolisms reported in relation to the Oxford–AstraZeneca COVID-19 vaccine does not seem to be increased beyond the expected incidence rate.

Nevertheless, recent reports of thrombocytopenia-associated cerebral venous sinus thrombosis, multiple thrombosis, and bleeding within a short timeframe after receipt of the vaccine are concerning and are receiving due attention from health authorities.

On 18 March 2021, with reference to the Oxford–AstraZeneca COVID-19 vaccine, the EMA concluded that “benefits still outweigh the risks despite possible link to rare blood clots with low blood platelets”.

 

Full report in The New York Times (Restricted access)

Full report in The Guardian (Open access)

Nature material

Full USA Today report (Open access)

Full report in The Guardian (Open access)

MHRA figures

CIDRAP material

The Lancet article (Open access)

 

 

See also MedicalBrief archives:

 

AstraZeneca shoots itself in the foot, again

 

Political blows to AstraZeneca vaccine may boost vax hesitancy

 

Updated pooled analysis of 3 Oxford/AstraZeneca vaccine trials

 

Debate continues over SA’s ditching of the AstraZeneca vaccine

 

SA plans AstraZeneca trial to assess effect on severe COVID-19

 

Oxford vaccine shows sustained protection of 76% during 3-month interval to second dose

 

Oxford University’s COVID-19 vaccine trial resumes but only in the UK

 

AstraZeneca/Oxford COVID-19 vaccine trial paused over an illness


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