TRANSCRIPT
Joe Elia:Ê
For the second time this week, weÕre examining the duration of protection against COVID-19 infections and reinfection afforded byÊvaccination.
YouÕre listening to clinical conversations from the NEJM Group. IÕm Joe Elia, and IÕm joined by my co-host Doctor Ali Raja who is in the department of emergency medicine at Massachusetts General Hospital and a professor of emergency medicine at Harvard MedicalÊSchool.
WeÕre about to interview Doctor Susan Hopkins on Zoom from London. Her paper with colleagues on the SIREN study Ñ on the duration of vaccine protection against COVID-19 infection and reinfection Ñ has just been published in theÊNew England Journal of Medicine. Doctor Hopkins is a clinician and an epidemiologist and chief medical advisor for the UK Health Security Agency. Welcome, DoctorÊHopkins.
Dr. SusanÊHopkins:
Thank you for invitingÊme.
Dr. Ali Raja:
Thank you, Doctor Hopkins. ItÕs great to meet you. To get us started, could you please just briefly describe the problem that you were in investigating.
Dr. SusanÊHopkins:
Well, the problem started nearly two years ago when we started to see cases of Sars CoV-2, and at that point, we really didnÕt know whether infection was going to protect you from reinfection, and then, over time, we didnÕt know whether how long the vaccination would protect you. So, we started this cohort study of health care workers in June 2020 after doing some pilot studies in the hospitals before that to see if it was feasible andÊdoable.
WeÕve been following our cohort of health care workers since June of 2020, taking bloods every month and swabs from the nose every two weeks to see how many of them get infected both symptomatically and asymptomatically. When we launched the vaccine program in December 2020, health care workers were one of the first in line. So, we were able to get really early evidence on this cohort on how they responded, and then, look at the durability of theÊresponse.
ItÕs critical that we know the durability of response because it feeds into the policy decisions about how frequently you might need boosters, whether thatÕs twice yearly, once a year, or even less frequently I think perhaps in some young, healthyÊindividuals.
Dr. AliÊRaja:
This was not a small study. This isnÕt a small single center study. How many different institutions does this encompass and how many healthcare workers were actuallyÊenrolled?
Dr. SusanÊHopkins:
So, we have over 100 sites from our hospitals and those are large hospital trusts with an average of between five and 10 thousand healthcare workers in each site and there are almost 50 thousand recruited into the study overall, but this study where we looked at those individuals who had followed up further with PCR tests in that period has more than 35 thousand individuals followed for the duration of theÊstudy.
JoeÊElia:
Could you tell us briefly, Doctor Hopkins, what were your principalÊfindings?
Dr. SusanÊHopkins:
Yes. So, our main findings are that firstly vaccines are effective and that they start to become effective after the first dose. We see a vaccine effectiveness of 85 percent after the first dose in individuals who are previously na•ve Ñ not infected. However, over time, the durability of the response declined quite substantially such that after six months, so any time between 197 and 205 days after the second dose of the vaccine, the vaccine effectiveness had reduced to about 51Êpercent.
The other big point of our study is that we were able to separate out those that had had infection before, which were 27 percent of our cohorts, and in those individuals we were able to track how well they respond to the vaccine, and we could see a single dose of vaccine was very effective, bringing their vaccine effectiveness up to close to 90 percent. Almost everyone had a second vaccine. So, weÕre unable to determine the duration or durability of a single vaccine shot, which is important because IÕve seen some comments saying you only need oneÊshot.
So, what weÕre saying is that after your second shot, you had a really durable vaccine response right out to the duration of the study to above 90 percent. My only proviso with that statement is this was pre-Omicron, and I think thatÕs quite important. We do have some early evidence that weÕve published on the Omicron data that shows that it has waned but itÕs still very effective in those that have had prior infection in theÊpast.
Joe Elia:
Now, the comparative group that you measured vaccine effectiveness against, was that the people who had were antibody positive?
Dr. SusanÊHopkins:
So, we basically divided the cohort (essentially, because itÕs so big and we can do this) into the cohort that were infected in the past, so 27 percent of the cohort are in that, and the cohort that were uninfected coming in, and then, we followed them over time. The main outcome was getting a PCR-positive infection, symptomatic or asymptomatic, in the follow upÊperiod.
So, the main unvaccinated cohorts are those that are unvaccinated and uninfected were predominantly in that cohort prior to vaccination Ñ so prior to December 2020 when the vaccination campaign started. So, they were individuals who had been followed up for the previous six or seven months and had not yet got an infection at that point, and that infection was determined by the serological response and also any PCR tests that theyÕd hadÊdone.
JoeÊElia:
Now, your analysis then was mostly among those who were at risk for the Delta variant. Is thatÊright?
Dr. Susan Hopkins:Ê
Exactly. Exactly. So, we have individuals who are at risk in the alpha periods because we were in the middle of the alpha wave from the vaccination program started. So, from the individuals who were infected between December and April were predominantly alpha variant, and then, individuals who were infected after May were predominantly Delta-period. So, this really gives you strong evidence for the Delta period and that durability of response in thatÊperiod.
Dr. AliÊRaja:
Doctor Hopkins, you mentioned very correctly the caveat that this was pre-Omicron. I hate to ask a scientist of your caliber to speculate but what do you think you will find as you continue to look at theseÊfindings?
Dr. SusanÊHopkins:
We have done some very early provisional analysis. The analysis is getting more and more complicated because the time-variant exposures are more complicated as we follow the cohort and they become positive over time, and theyÕre exposed to differentÊvariants.
So, the time-variant exposures means that we have looked at this and weÕve started to look at this of the cohort from December 2021 and we are seeing that those whoÕve only had two doses of the vaccine have significant immune waning, which is at about nine months post their second dose of vaccine but that a third dose really substantially adds to that, and those that have had an infection and at least two doses have a substantially better response. It has waned as well, so the early evidence suggests that it is reducing by 25 to 30 percent, which is consistent with what weÕve seen in some of the other studies with Omicron asÊwell.
Dr. AliÊRaja:
So, IÕm like you, a clinician, and I see patients in an emergency department. What do I take away from this as somebody who talks to patients, many of whom are vaccinated but some of whom areÊnot?
Dr. Susan Hopkins:
This is a study looking at the outcome from infection, so thatÕs important, but what weÕre really seeing is that if we have an effective vaccine then that reduces both symptomatic and asymptomatic disease. People will know that they are now increasing meta-analysis in reviews looking at long COVID, and clearly, thatÕs if you prevent the infection that helps prevent long COVID as well, but also early evidence that even people whoÕve been vaccinated after the symptoms of long COVID then thatÕs reduced too.
So, I think thatÕs a really big positive that we should be telling people about who are not so much worried about hospital admissions but are worried about consequences. The second is that, you know, we have population level studies in the UK that weÕve been doing where we are seeing that the reduction in severity after vaccination is quite marked. WeÕre seeing very sustained reductions in hospital admissions post vaccination and with Omicron post a booster dose inÊparticular.
So, I mean, IÕm offer strong encouragement for vaccine. I believe that people whoÕve had an infection in the past get additional benefit from vaccine. I think thatÕs an important point to make, and itÕs probably a sustained and broad immune response that lasts longer and better and that would be really important for them in the future as well, and to reduce the infections spread in theÊcommunity.
JoeÊElia:
It sounds like youÕve got a lot of work ahead of you to do and we want to wish you luck with that, Doctor Hopkins. Is there a question that we have not asked you that you wished that weÊhad?
Dr. SusanÊHopkins:
So, I think the things that weÕre really interested inÉand weÕll be hopefully submitting some late-breakers for ECCMID this year if people who are traveling to the European Conference on Clinical Microbiology & Infectious Diseases. Things looking out: what are the predictors of people who are likely to get reinfected? So, we have started to analyze utilizing antibodies to various variants due to various pseudo virus and liveÊvirus.
WeÕre looking at the titers and how they fall over time. And so, within this cohort, weÕve started to do nested case-control analysis to try and see if we can define predictors in all of this that makes people more likely immunologically, both from their antibody responses and their t cell responses, to developÊsubsequences.
JoeÊElia:
Well, we want to thank you very much, Doctor Hopkins for your time with usÊtoday.
Dr. SusanÊHopkins:
Thank you for havingÊme.
JoeÊElia:
That was our 283rdÊClinical Conversation. We come to you from the NEJM Group and the writers and editors of NEJM Journal Watch. Kristin Kelley is our executive producer. IÕm JoeÊElia.
Dr. AliÊRaja:
And IÕm Ali Raja. Thanks forÊlistening.