Covid-19 vaccines may not stop people from getting sick and dying, scientist warns

Covid-19 vaccines may not prevent people from getting severely sick or dying, it was claimed today.

Trials of hundreds of thousands of volunteers are investigating whether experimental Covid-19 jabs stop a person from picking up the infection.

But Professor Peter Doshi, the associate editor of the British Medical Journal, points out scientists are not waiting to see whether volunteers are protected from severe disease or death if they do catch it — which would only be the case if the vaccine didn’t work very well — before they are rolled out. 

This is a particular concern for the elderly, who are the most at risk of severe Covid-19 outcomes, because the vaccine may not be as effective at protecting them from catching the coronavirus in the first place.

Vaccines typically do work as well  for those over the age of 60 because they have an aged immune system.  

Professor Doshi, of the University of Maryland, also revealed that the studies will not prove transmission between people can be curbed. Scientists are not measuring if those who catch it pass it on to friends and family, regardless of whether they get sick themselves. 

None of the front-runners — Moderna, Pfizer, AstraZeneca, Janssen, Sinopharm, or Sinovac — are measuring if their vaccines will save lives in their final stage trials.  

But in response to Professor Doshi’s paper, scientists say there are ‘excellent’ reasons for running the trials, the main one being to speed up finding a vaccine which could otherwise take years because so few Covid-19 patients become severely ill.  

Trials of hundreds of thousands of volunteers are investigating whether experimental Covid-19 jabs stop a person from picking up the infection. Pictured: Katelyn Evans receives a Pfizer’s experimental Covid-19 vaccine at Cincinnati Children’s Hospital Medical Center

A vaccine is considered key to ending the Covid-19 pandemic which has already killed 1.1million people worldwide. High hopes have been pinned on proving one works to cut the risk of the disease and stop it spreading. 

The goal of finding a vaccine may seem fairly obvious to the public — to stop serious disease and death, and therefore damaging lockdowns.

‘Yet the current phase III trials are not actually set up to prove either,’ Professor Doshi said in his paper, questioning what a vaccine must prove to be considered ‘effective’.

Covid-19 vaccines may not prevent people from getting severely sick or dying, Professor Peter Doshi has warned 

‘None of the trials currently underway are designed to detect a reduction in any serious outcome such as hospital admissions, use of intensive care, or deaths. 

‘Nor are the vaccines being studied to determine whether they can interrupt transmission of the virus.’

There are 44 vaccines currently in clinical trials, according to the World Health Organization. Ten are in the final stages, called phase three, which are the final hurdle scientists need to tackle before one is proven to work. 

Professor Doshi, an assistant professor of pharmaceutical health services research at the University of Maryland School of Pharmacy, Baltimore, said all ongoing phase three trials, for which details have been released, will end when a certain number of people have tested positive for coronavirus, including mild disease.

Scientists wait for a number of people to catch the coronavirus so they can compare whether the infection rates are higher in those who received the experimental Covid-19 jab, or in the placebo group.

If cases are higher in the placebo group, it would suggest that the vaccine protects against catching the coronavirus, in theory.  

None of the phase three trials are waiting for endpoints of severe disease or deaths before stopping the trial, which would confirm the vaccine is indeed ‘life-saving’. 

But Professor Doshi added: ‘A vaccine that has been proved to reduce the risk of symptomatic disease by a certain proportion should, you might think, reduce serious outcomes such as hospital admissions and deaths in equal proportion.’

Tal Zaks, the chief medical officer at Moderna, told the British Medical Journal that if the companies’ vaccine is shown to protect against mild disease, they will also be confident it protects against severe outcomes.

After all, the vaccine would have to be ineffective at preventing infection in the first place for a person to develop disease. 

But Professor Doshi said this theory breaks down if vaccines are not equally effective in all ages. 

And older people, who are most at risk of serious Covid-19, typically don’t respond to vaccines as well because their immune system takes longer to kick into action. 

Professor Doshi said: ‘Whatever reduction in cases is seen in the overall study population (most of which may be among healthy adults), this benefit may not apply to the frail elderly subpopulation, and few lives may be saved.’ 

Children, immunocompromised people, and pregnant women have also largely been excluded from studies. 

It is likely serious outcomes from Covid-19 are not being studied because it would take too long for a significant number of volunteers to actually get severely sick, given less than 10 per cent of people who catch it need hospitalisation. 

It would need a lot more trial participants, and funding, to finish the trial as quickly as planned, if scientists were hell-bent on making sure the vaccine did not cause serious disease or death, the paper explains.    

Professor Doshi said: ‘Hospital admissions and deaths from Covid-19 are simply too uncommon in the population being studied. 

‘Final efficacy analyses are planned after just 150 to 160 “events,”—that is, a positive indication of symptomatic Covid-19, regardless of severity of the illness.’

Trials will be able to report their final results once around 150 people show symptoms of the disease. 

In Pfizer and Moderna’s trials, for example, individuals with only a cough and positive lab test would bring those trials one event closer to their completion. 

Medscape’s Eric Topol has been a vocal critic of this, saying: ‘These numbers seem totally out of line with what would be considered stopping rules.

‘I mean, you’re talking about giving a vaccine with any of these programmes to tens of millions of people. And you’re going to base that on 100 events?’ 

Professor Doshi did not comment on the significance of efficacy if all 150 of the people who got symptoms were in the placebo group and none were in the vaccinated arm. 

Moderna’s Tal Zaks said ‘too many people would die’ waiting to find out if Moderna’s vaccine prevented mortality.  

Dr Andrew Preston, a reader in microbial pathogenesis who works in vaccines, University of Bath, agreed that it would cause too many delays.

He told MailOnline: ‘Covering every manifestation of Covid disease would require trials so large, that run for such long times, that they are very likely to be impossible to run and fund, and would delay the data so long that we’d be living without any vaccine-mediated intervention for years to come.’

Commenting on the BMJ editorial, Dr Preston argued there were ‘excellent and sensible reasons for running the trials as they are’. 

‘To test vaccines in the very vulnerable would require vaccinating vulnerable people and then asking them to put themselves in situations in which they might be exposed to the virus.

‘The ethics of this would be highly questionable, so it makes sense to test whether the vaccine shows any effect in people who, if they did become infected, the consequences are far less severe.’

However, he agreed that it is important for there to be clarity on what vaccine trials will and will not show.

‘I suspect many [people] are wanting them to ‘return life to normal’ and so there needs to be careful consideration of what the various effects of the vaccines might be.

‘It’s been clear for some time now that an essential component of building the trust required for interventions to be effective, is transparency. 

‘So it’s important that as we head towards the point when mass vaccination will begin, everyone is clear about what this will change in terms of restrictions, public health and disease.’  

The prospect of a Covid-19 vaccine is edging nearer, with ministers and scientists alike claiming the first roll-out could be just after Christmas.

At the end of September, the optimistic chief scientific adviser Sir Patrick Vallance said Britain could still get its hand on a coronavirus vaccine before Christmas.  

And Sir Jeremy Farrar, Sage scientific advisory group member and a director of the Wellcome Trust, has said at least one of a portfolio of UK vaccines could be ready by spring.

But other experts have waded in with a dose of realism, revealing that even if a vaccine is proven effective any time soon, it will be in limited supply. 

The head of the country’s vaccine task-force Kate Bingham has previously admitted less than half of Britain will get vaccinated against Covid-19.

Experts say it is likely people will need two doses of each vaccine to be protected against the coronavirus. And those who are most vulnerable will be front of the queue.  

Source: Daily Mail