GAO: A Herd Immunity For COVID-19 Primer
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Almost exactly six months ago, in UK Approves Human COVID-19 Vaccine Challenge Studies, we looked at a plan by the UK government, Imperial College London, and the Royal Free London NHS Foundation Trust to begin a controlled human challenge study on COVID-19 vaccines starting in early 2021.
While not without controversy (see Public Health Ethics Ethical Criteria for Human Challenge Studies in Infectious Diseases), human challenge studies - where volunteers are deliberately exposed to a virus in a controlled laboratory environment - can provide valuable data on vaccine effectiveness, and the human immune response, that otherwise could take months or even years to gather.
And sometimes, they yield surprising results, as we saw in a 2019 study by researchers at the NIH and NIAID (see C.I.D.: Influenza A Reinfection in Sequential Human Challenge) that unexpectedly found `. . . . that sequential infection with the identical influenza A virus can occur and suggest it may not be rare.'
Today, our primary concern is on the potential to be reinfected with COVID-19 after recovering from a natural infection, or `breakthrough' infections among fully vaccinated individuals (see CDC: COVID-19 Breakthrough Case Investigations and Reporting).
To understand better the human immune response to COVID-19, and the risks of reinfection, University oi Oxford has announced the start of a human challenge trial using young, healthy adults, to study the risks of reinfection.
Details are provided from the following press release from the University of Oxford. I'll have a bit more after the break.
Human challenge trial launches to study immune response to COVID-19RESEARCHCORONAVIRUSHEALTH
Though the COVID-19 pandemic has now been active for a year, not much is known about what happens when people who have already had COVID-19 are infected for a second time.
Researchers at the University of Oxford have launched a human challenge trial to look at what kind of immune response can stop people from becoming re-infected. They also want to see how the immune system reacts second time round. A human challenge trial in medical research is a carefully controlled study that involves purposefully infecting a subject with a pathogen or bug, in order to study the effects of that infection.he study will take place in two phases with different participants in each phase. The first phase, which will start in April 2021, will establish the lowest dose of virus which, in approximately 50% of people who have previously been naturally infected, can take hold and start replicating but produce little or no symptoms. In the second phase of the study, expected to start in summer 2021, all participants will be infected with the standardised dose of virus which was established in phase one.For phase one, up to 64 healthy participants between the ages of 18 – 30 who have previously been naturally infected with COVID-19 will be re-exposed to the virus in carefully controlled conditions. The virus used in the study will be the original strain from Wuhan, China. The participants will be quarantined in a specially designed hospital suite for a minimum of 17 days under the care of the research team. They will undergo numerous medical tests including CT scans of the lungs and MRI scans of the heart. The risks to participants will minimised by making sure that those who take part are completely fit and well and have completely recovered from their first infection with COVID.
Any participants who develop any symptoms will be given medical treatment with the Regeneron monoclonal antibody treatment. They will only be discharged from the quarantine unit when they are no longer infected and not at risk of infecting others. The full length of the study will be 12 months, including a minimum of eight follow-up appointments after discharge. Participation in the study is completely voluntary.Helen McShane, Professor of Vaccinology at the Department of Paediatrics, University of Oxford and Chief Investigator on the study said, ‘Challenge studies tell us things that other studies cannot because, unlike natural infection, they are tightly controlled. When we re-infect these participants, we will know exactly how their immune system has reacted to the first COVID infection, exactly when the second infection occurs, and exactly how much virus they got. As well as enhancing our basic understanding, this may help us to design tests that can accurately predict whether people are protected.‘In phase two, we will explore two different things. First, we will define very carefully the baseline immune response in the volunteers, before we infect them. We will then infect them with the dose of virus chosen from the first study and measure how much virus we can detect after infection. We will then be able to understand what kind of immune responses protect against re-infection. Second, we will measure the immune response at several time points after infection so we can understand what immune response is generated by the virus.‘A challenge study allows us to make these measurements very precisely because we know exactly when someone is infected. The information from this work will allow us to design better vaccines and treatments, and also to understand if people are protected after having COVID, and for how long.’
The study is funded by the Wellcome Trust. Shobana Balasingam, Vaccines Senior Research Advisor at Wellcome, said, ‘There are still many unknowns surrounding this virus and human infections studies can enable us to learn a lot about Covid-19. This study has the potential to transform our understanding by providing high-quality data on how our immune system responds to a second infection with this virus.‘The findings could have important implications for how we handle Covid-19 in the future, and inform not just vaccine development but also research into the range of effective treatments that are also urgently needed. Keeping up the pace of scientific research and development, through crucial studies such as this remain the only way we will truly get ahead of this pandemic and bring it under control.’
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The idea that we get out of this pandemic through developing `herd immunity' - either through natural infection or (preferably) through vaccination - is predicated upon the the notion that once you've been exposed, you are immune to reinfection, and that immunity is long-lasting (i.e. years not months).
While there are viral infections that leave behind that type of durable immunity - like measles and chickenpox - there are others that are not as well imprinted on the human immune system.
Infections with mild hCoV (human coronaviruses) are already known to be recurrent, and studies on MERS-CoV survivors had shown waning antibody levels (see EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors), particularly among those with mild illness.
The C.I.D.: Influenza A Reinfection in Sequential Human Challenge study, mentioned above, suggests that reinfection with the exact same flu virus (as opposed to a `drifted' virus of the same subtype) a year later is not only possible, it may be relatively common.
And of course, we've seen studies suggesting that (depending on age group) there is a poorly quantified, but non-trivial, risk of reinfection with COVID-19 within a year of recovery.
Denmark SSI: Assessment of Protection Against Reinfection with SARS-CoV-2
MMWR: Suspected SARS-CoV-2 Reinfections Among Residents Of A Skilled Nursing Facility - Kentucky, Jul.- Nov. 2020
Brazil MOH Confirms Reinfection With COVID Variant P.1 In Amazonas
The Lancet: Resurgence of COVID-19 in Manaus, Brazil, Despite High Seroprevalence
To better detect and uniformly report reinfections, 10 days ago we looked at guidance published by the ECDC Technical Rpt: Reinfection with SARS-CoV-2 (Surveillance Case Definition).
While early reports of COVID reinfection strongly suggested most second bouts were either mild, or even asymptomatic, in recent months we've seen evidence suggesting that they can also be severe, or even fatal.
The severe pandemic waves we are currently witnessing in Brazil (see Preprint: Sudden Rise In COVID-19 Case Fatality Among Young & Middle Aged Adults - Paraná, Brazil) and in India also raise serious questions about the human immune response following exposure to some of the emerging variants (as opposed to `Classic COVID').
Whether the results of these human challenge studies ultimately turn out to be reassuring, or end up raising additional concerns, we need better data in order to plot a course out of this pandemic.
