The most detailed studies to date have just been published in the journal Lancet Infectious Diseases that reveal how the virus – notably the more contagious mutated form known as the Delta variant – spreads through vaccinated households.
The work was conducted by Science Museum Group Trustee Prof Ajit Lalvani, Chair of Infectious Diseases, and Director of the National Institute for Health Research’s Health Protection Research Unit in Respiratory Infections, Imperial College London, working with the UK’s Health Security Agency.
His team is also trying to find early tell-tale signs of an individual’s risk of developing serious disease and further details, such as whether the virus is more effectively transmitted by air or by touch. His edited responses to my questions are shown in italics.
Our paper, which had a global impact within 24 hours of publication, provides important support for the following crucial public health actions: vaccinate the unvaccinated ASAP; give boosters to all those who are eligible ASAP; maintain social and public health measures despite vaccination.
No study has been done like this before.
The context of our work is that highly vaccinated populations in the UK, Israel and the US all seem to have surging Delta virus epidemics and we set out to understand what is happening in households.
It is in the home where, globally, the vast majority of transmission occurs and spread of the Delta variant in highly vaccinated populations is a major public health concern.
We found that even the double vaccinated population tend to transmit the illness (though they tend to have mild symptoms or be symptom free.)
Prof Lalvani’s team launched these detailed studies last year to understand the proportion of infections that are symptom-free, the risk factors that promote or impede transmission of COVID-19 within households and the early immune responses that predict whether a given recently exposed person will have a symptom-free infection or instead develop symptomatic or severe illness.
Early in the pandemic he launched the Integrated Network for Surveillance, Trials and Investigations into COVID-19 Transmission (INSTINCT) study of newly diagnosed cases and their contacts in their homes.
In addition, there was ATACCC (Assessment of Transmission And Contagiousness of Covid19 Contacts) and ATACCC 2 in May 2021, which investigated how the virus spread in households infected with the Delta variant. The museum’s COVID-19 collecting project has acquired objects from his pathfinding research.
‘It is a very valuable study’, commented his Imperial colleague Anika Singanayagam, Honorary Clinical Research Fellow, adding it was ‘highly labour intensive.’
Another collaborator, Prof Maria Zambon, Head of Influenza and Respiratory Virology at the UK’s Health Security Agency, and Co-Director of NIHR Respiratory Health Protection Unit at Imperial College London, added that it was designed to close the ‘evidence gaps.’
HOW WAS THE STUDY CONDUCTED?
We have now recruited over 1000 contacts overall. The median time of recruitment of a contact after exposure is three to four days after exposure, that is when one person in the household develops symptoms.
So, we have a system where we are getting into COVID infected households and studying contacts earlier than any other team in the world.
We are in a globally unique position in that we have a platform where we can enrol and intensively sample contacts very early after exposure.
This allows us to ask questions about the early events in the immune system that predict the outcomes.
In particular, those which correlate with – and presumably mediate – the best clinical outcomes, where you have the lowest viral load and the least symptom burden. We have all the data, and we are analysing it like mad.
We are also looking at how the virus spreads in household. While furiously writing all these manuscripts, we talked through all these aspects with our advisor Ben Cowley, an epidemiologist at the University of Hong Kong.
WHAT DID YOUR STUDY REVEAL?
This work, published in the journal Lancet Infectious Diseases, found substantial ongoing transmission in households.
We had to weigh up scenarios where the index (original) case was vaccinated or unvaccinated, and where the contact may or may not be vaccinated and may or may not acquire infection.
We found that among unvaccinated contacts in these households the secondary attack rate was 38%, that is the proportion of unvaccinated contacts who are infected in households where there is an infectious index (first) case.
In doubly vaccinated households, the figure was still 25%. This is very alarming, a very high secondary attack rate given these are doubly vaccinated contacts.
IN OTHER WORDS, BEING VACCINATED DID NOT DO MUCH TO CURB DISEASE SPREAD?
That’s right. We looked at the infectiousness of index cases who were vaccinated, and had a so-called breakthrough infection, and unvaccinated and it was around 22-24% either way, and not very different. This is quite concerning.
We went a step further and in households where we had throat swabs from the index cases and contacts, which was in around four households that were doubly vaccinated in three cases, we used genetic sequencing to show the same strain was being transmitted from index to contact.
We could track the viral load and see the index case peak earlier than the contacts, so we could infer who infected whom.
This is the first evidence globally of doubly vaccinated cases with breakthrough infections transmitting virus to doubly vaccinated contacts and it is not rare.
In India, where the Delta variant originated, doctors have observed widespread transmission among double vaccinated people but have not hitherto investigated or documented it.
So, their clinical impressions are now supported by the evidence we provided which in turn in may lead to public health actions.
DID IT MAKE ANY DIFFERENCE IF PEOPLE IN INFECTED HOUSEHOLDS HAD BEEN VACCINATED WITH OXFORD-ASTRAZENECA OR PFIZER-BIONTECH?
Our numbers were too small to say.
HOW LONG DOES VACCINE IMMUNITY LAST?
Surprisingly, we found vaccine induced protection is already waning around three months after the second dose.
Doubly vaccinated contacts who tested were positive, had an average time from the second dose of three months, while the doubly vaccinated people who stayed negative had a median time from the second dose of two months.
What this tells us is that at three months post vaccination, compared with two, the risk of acquiring Delta if you are exposed to it is higher.
That it was happening early was surprising to me, that you could see a decline from two to three months after the second vaccination.
We already know from a Public Health England paper in the journal Lancet Infectious Diseases that the risk of hospitalisation with Delta is twice that of Alpha (the original COVID-19 strain), and that risk of serious illness is doubled in both vaccinated and unvaccinated people.
However, it is important to stress that the risk of ending up in hospital when you are vaccinated is still low, even with Delta.
The message of our paper is NOT that the vaccines are not working – they are – but it is probably that they are a lot less effective at preventing secondary transmission than anticipated.
HOW INFECTIOUS ARE VACCINATED PEOPLE WHO ARE INFECTED?
We measured daily viral load in throat swabs taken from 133 people and – here’s the other concerning thing – you’d think that if you were doubly vaccinated and got a breakthrough infection the viral load in your throat would be lower, but we were surprised to find no difference in peak viral load over 14 days compared with unvaccinated people.
That may explain why the transmission is ongoing despite so many people being vaccinated.
We did find a faster rate of decline in viral load in vaccinated people, which is nice, but the problem is that most transmission occurs before or at the peak viral load.
YOU WOULD THINK THAT THE VACCINE, WHICH GENERATES IMMUNITY, WOULD REDUCE THE VIRAL LOAD SO WHAT IS THE EXPLANATION?
We think that if you are vaccinated your immune response to the virus is not quick enough to delay or reduce the rate of growth of the virus in the first few days, so it does not blunt the peak amount of virus in the body.
A few days into your illness the rate of decline is faster, suggesting the immune response prompted by vaccination is only kicking in by around five days, when the virus has already peaked.
By then the immune system is kicking the virus harder due to the priming of vaccination – and something in the immune response by then is preventing them developing severe disease.
WHAT DOES YOUR STUDY MEAN FOR UNVACCINATED PEOPLE?
Unvaccinated people cannot rely on the immunity of the vaccinated population for protection. It is yet another reminder of the risks they take in remaining unvaccinated.
HAS THE UK REACHED PEAK COVID YET?
‘It is too early to say whether we have reached a peak…we need to wait three weeks to be sure but there are some encouraging signs, such as a dip in case numbers’, commented Prof Neil Ferguson, Director of the MRC Centre for Global Infectious Disease Analysis, Imperial College London.
He added: ‘we are seeing virus evolving to higher levels of infectiousness over time’.
CAN WE DO MORE TO CONTROL COVID-19 TRANSMISSION USING VACCINES?
We have seen evidence of waning immunity by three months, and it is important that we get the Government’s plan to offer boosters six months after the second vaccination working at the same level of efficiency as the first vaccination campaign.
As for how long that booster protection will last, we don’t know for sure but from our knowledge of immune system we would expect boosters to longer and longer immune memory – well over six months to a year.
Prof Zambon added that these are ‘first generation’ vaccines and another 300 COVID-19 vaccines are currently in development globally. ‘It will be interesting to see how the next generation of improved vaccines will help with prevention of infection as well as prevention of severe disease.’
HOW CAN I FIND OUR MORE?
There is more information in my earlier blog posts (including some in German by focusTerra, ETH Zürich, with additional information on Switzerland), from the UK Research and Innovation, UKRI, the EU, US Centers for Disease Control, WHO, on this COVID-19 portal and Our World in Data.