With Covid-19 vaccination campaigns advancing around the world, public health officials are still trying to answer the question on the lips of the newly vaccinated: could I still be a danger to people around me?
The US Centers for Disease Control and Prevention issued its first guidance for the fully vaccinated this week, saying a growing body of evidence suggests the vaccinated are less likely to have asymptomatic infection — and possibly less likely to transmit the virus.
Fully vaccinated Americans can now meet each other or people at low risk of Covid-19 in small groups, indoors without masks. The CDC argued that the benefits of reducing social isolation and relaxing measures outweighed the risks — and that more of the vaccine-hesitant might get their shots if they could enjoy these freedoms afterwards.
Elsewhere in the world, the guidance is less clear. Despite a stellar vaccination programme, the UK remains in lockdown and chief medical officer Chris Whitty warned on Monday that the situation could “turn bad” if the easing of restrictions is rushed.
“This is incredibly challenging to communicate to people,” said Angela Rasmussen, a virologist at Columbia University. “Even though it seems simple, like, ‘Can I do this or not?’ It’s not always a simple answer to that question.”
All of the Covid-19 vaccine trials focused primarily on whether the shots prevented symptomatic disease, which was seen as more important than studying transmission. But given that Covid-19 can be passed on by someone who has contracted the virus but not displayed symptoms, it is now crucial for both individuals and the economy to find out whether the vaccinated can still transmit the virus.
Logically, experts believe that because the vaccines reduce even mild disease and cut viral load, they must also reduce transmission. But scientists are still reliant on several small studies of varying value, when judging the extent to which vaccination will reduce spread.
Muge Cevik, a researcher at the University of St Andrews, said the evidence was starting to point towards a “meaningful reduction” in transmission.
“Up until now, the message was, ‘We don’t know whether it reduces transmission,’ but I think it’s wrong to say that — the message should be, ‘Yes it will reduce transmission but we don’t know the magnitude,’” she said.
The first evidence came from monkeys last year. Rhesus macaques were given shots of the BioNTech/Pfizer, Moderna and J&J vaccines and then exposed to the virus. Not only did they not develop symptoms, they showed only “limited” replication of the virus in the upper respiratory tract, which made them less likely to pass it on.
During large clinical trials, while vaccine manufacturers did not assess the impact of the shots on transmission, some did monitor asymptomatic infections among vaccinated participants.
Oxford/AstraZeneca was unusual in doing diagnostic Covid tests for all UK participants every week. Andrew Pollard, director of the Oxford Vaccine Group, said its published data was “good evidence” that the AstraZeneca vaccine reduced all positive tests — whether symptomatic or not — by about two-thirds.
“It is reasonable to infer that this will correspond to a reduction in transmission, since if there is no virus detectable infection can’t be passed on,” he said.
Other vaccine makers looked at a portion of their trial. In a subset of 3,000 J&J trial participants, the vaccine appeared to be about 74 per cent effective at stopping asymptomatic infection. Dan Barouch at Harvard’s Center for Virology and Vaccine Research, who worked on the J&J trial, said this was “very encouraging”.
But the regulator has cautioned that there is not yet enough evidence to be statistically valid. Natalie Dean, a biostatistician at the University of Florida, said the Food and Drug Administration was right to be cautious because 74 per cent was higher than the overall efficacy rate of 72 per cent in the US. “That shows the uncertainty, because biologically it has to be lower,” she said.
Now that more than 300m vaccine doses have been administered globally, researchers are publishing larger studies of “real world” evidence. In Israel, which has vaccinated by far the largest proportion of its population, the health ministry found the Pfizer vaccine was 89 per cent effective at preventing infection of any kind, and 94 per cent against symptomatic infection. The study has not yet been peer-reviewed.
Rasmussen cautions that we should take this evidence with “a pinch of salt” while vaccination programmes are still in progress, because it can often get muddied by other factors, such as lockdowns.
However, two UK studies of the Pfizer shot found similar results. A University of Cambridge study of healthcare workers who were regularly tested for Covid-19 showed the number of asymptomatic positive tests dropped by three-quarters as they began to be vaccinated. Another from Public Health England found it “effectively prevented” asymptomatic infection in working-age adults.
Michael Weekes, who co-authored the Cambridge paper, said it showed the vaccine offered “decent protection but it’s not a panacea”. “You’ve got two studies that have come to very similar conclusions. That gives it a lot of power,” he said.
The ultimate real-world evidence will come from studies of people around the vaccinated to see if they get Covid-19. In the Panther study from the University of Nottingham, researchers are looking at infection rates among the close contacts of recently vaccinated healthcare workers.
Public health experts are also eager to hear from clinical trials due to publish results in the next few months. Wafaa El-Sadr, a professor of epidemiology at Columbia, said the “most rigorous data” will come from the vaccine makers’ follow-up studies of trial participants, with a clear comparison between the vaccinated and placebo groups. Pfizer is testing a subset of its trial for antibodies that would not have been elicited by the vaccine to identify asymptomatic infection.
When the new studies land, it will make a “big difference” to the advice public health experts can give to the vaccinated about how to behave, she said. “If there is evidence of protection from asymptomatic infection, that would be fantastic news.”
The quote from Muge Cevik in an earlier version of this story has been amended for accuracy.
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