Testing asymptomatic individuals for SARS-CoV-2—known unknowns

On 11 February 2021, The BMJ hosted a webinar on testing asymptomatic individuals for SARS-CoV-2. An expert panel discussed the role of asymptomatic transmission, as well as testing in a pandemic, and how to communicate and act on test results. Nikki Nabavi and Juliet Dobson report

The theme of the webinar was inspired by an editorial published in The BMJ called “Covid-19’s known unknowns.” The key message: “The more certain someone is about covid-19, the less you should trust them.” Register for future events here

Role of testing in a pandemic 

Muir Gray reminded us of the opening lines from his book: “All screening programmes do harm; some do good as well, and, of these, some do more good than harm at reasonable cost.” 

When asked by the audience whether they viewed testing asymptomatic individuals for SARS-CoV-2 as screening or case finding, Sian Taylor-Philips said: “To me, it’s definitely screening. You’re inviting people without symptoms, who don’t think they’ve got the disease, for a test to see if they have got it. The way it differs from the screening we are used to is that a lot of the benefit is not for the person who came for the test, but for transmission to others. Though all of the principles of screening apply in exactly the same way.”

Angela Raffle didn’t think that labels mattered as long as a programme is well designed. She shared some principles with the audience that helped frame the rest of the conversation on mass testing. The focus should be first on high risk groups for transmission (people with symptoms and their contacts)—“We want to find people who will transmit” the virus. For treatment, we look at the evidence before we make a policy decision, and the same must apply for testing programmes. The importance of a uniform national reference standard for what is defined as “a case,” which “we still don’t have.”  

“Part of the problem is that there have been two parallel conversations going on” added Brian McCloskey, “Some people are raising questions about the risks of testing for negatives, and others about the benefits of testing for asymptomatic positives…testing for positives and testing for negatives are fundamentally different concepts, and they require different approaches.”

“You can’t design a valuable system unless you’re really clear what you’re wanting to achieve” said Raffle. “If we want to control the pandemic the primary concern must be health outcomes, not photo opportunities for politicians, not profits for shareholders, not research empires.” 

Asymptomatic individuals often share the same motivation for wanting a test“they want to be told that they’re okay,” said Raffle. “The humans in the system behave in many ways, and how we give them clear, clean information is crucially important.”

“We are trying to detect infectious, asymptomatic people with SARS-CoV-2 and isolate them—to decrease transmission.” said Taylor-Philips. “Mass testing will stop some people from transmitting,” she added, “but it could increase transmission from some other people . . . testing negative doesn’t mean you are safe.” McCloskey added that “testing alone does not stop transmission. Testing followed by appropriate action does.”

“Maybe it’s a distraction, maybe because testing everyone is such an intuitively attractive idea, maybe for commercial reasons. The UK government is keen to take us down the route of society wide testing. This is like checking hundreds of times for a leak when we haven’t yet attended to the burst water main.” Raffle added.

Asymptomatic transmission

How common is asymptomatic SARS-CoV-2? How infectious is it? And how much does it actually contribute to overall transmission? Nicola Low spoke on behalf of herself and Muge Cevik to outline the role of asymptomatic transmission. She cited a BMJ news piece, which has been used to imply that the death rate from covid might be lower than we think that it is, because undetected people have somehow been left out of the denominator, and explained that these claims are untrue. One difficulty when identifying our picture of who is asymptomatic is the fact that everyone who tests positive is initially presymptomatic (i.e. asymptomatic until they subsequently develop symptoms): 

“At a single point of time, you can’t distinguish between someone who is presymptomatic and someone who is going to remain asymptomatic, so that means if you have a cross sectional study that at a single point in time says four fifths of people are asymptomatic as this news item in The BMJ did, that does not mean that four fifths of people are truly asymptomatic.” She added that the definition of “asymptomatic” is also challenged by the fact that the spectrum of symptoms we identify keep changing—in January 2020 we were aware of respiratory symptoms, but by March 2020 we were aware of a broader spectrum of signs and symptoms, including anosmia. 

“Types of evidence have changed over time,” concluded Low, “definitions have changed over time. Types of studies have changed over time. We can’t use cross sectional studies to assess the proportion of asymptomatic, and serological studies are difficult to interpret . . . [but] context is everything.”

Asymptomatic testing: are the tools fit for the job?

Can we identify people who are infectious or not? Jon Deeks spoke about the evidence on the relation of lateral flow tests and infectiousnessa key part of the arguments for testing asymptomatic individuals. He presented a rapid run through of existing evidence and concluded, “we can’t really be talking about tests of infectiousness. And we should be looking at stopping this language because I think it’s giving the wrong message. We really urgently need to find better tests…It’s really important to get sensitive lateral flow tests. They will be the future for us, but not the ones that we’ve got now.” 

Tim Peto highlighted the challenge of making decisions in a pandemic: “You have no time to get the right evidence. So you’ve got to go on the evidence of the balance of probability. You can’t be purist about this because people have to make decisions now about what to do for the best.

“We are trying to quarantine people we believe are infectious, and we’re doing this without much evidence. So the evidence for social distancing, face masks, all that stuff is all in the balance of probability,” he said. 

Patrick Bossuyt picked up on a point that Phil Hammond made at the start of the webinar when Hammond said that we don’t have tests for infectiousness. “That’s not entirely true…we have a range of things to use for SARS-CoV-2. The only thing is we don’t know how good they are for evaluating infectiousness because we lack a clinical reference standard…That is the most known unknown in this whole discussion about whether we have the right tools. I think we have a range of tools. The question is, we don’t know yet how good they are, and that makes decision making difficult.”

Communicating and acting on test results

Theresa Marteau discussed the behavioural responses to a negative test and asked whether we should be worried about the potential for false reassurance after negative results, which is one of the many sets of behaviours that are key to mass asymptomatic testing. “A negative result does decrease behaviours that reduce transmission, she said. “But, importantly, we don’t know the precise nature or the scale of that,” as currently the evidence to draw on is limited.

Jackie Cassell spoke about the impact that the vaccination programme will have on people’s behaviours. As the vaccination rollout continues, “We will see a growing concentration of all the remaining cases and transmissions in younger workers and in children and students,” she said. So we can expect to see a shift in people’s behaviours and their willingness to comply with testing and isolating. But we don’t yet know how that will play out. So the question is: “What changes and choices will we make about test, trace, isolate and the people on whom that burden falls and on what evidence?” 

Support for self isolation is crucial, Cassell said, “Clearly the scale of people feeling they cannot even test because they cannot afford to isolate, that is something that is an issue at whatever scale. And we need to think about that as that goes on for some people and not for others.”

Marteau underlined this point:“One of the key pieces of evidence that we’ve had is how people still do not have effective support packages. So for people to self isolate the support needs to be financial, practical, social, and clinical. And until we have that in place, we’re going to have more virus in the community.” 

Testing in different settings and contexts

The final session focused on testing in different settingsworkplaces, prisons, and the community.

Pete Buckle highlighted the impact that a loss of trust in the testing system will have, not just on testing for SARS-CoV-2 but on other public health interventions:We’re really quite concerned about the wider implications of a system where, let’s just be honest, the public think that it’s either a positive or a negative test—you’ve either got it or you haven’t. So I think the real world implementation of these things really does need to be thought about very carefully.”

Andrew Frazer spoke about the challenges of testing in prisons. One of the main risks of infection is from staff as they are more mobile. “That is maybe where we need to spend more time thinking about the risks and the appropriate tests,” he said. 

 Returning to the earlier point about support packages for self isolation, he asked: “What is the support package in prison? There are incentives and disincentives to knowing whether you’re positive or negative, but mainly drawbacks because you go from a very poor regime, and it gets even poorer if you are needing to be further isolated.”

The final speaker, Stefan Baral, spoke about his experience of community testing, and testing in homeless shelters. He emphasised that “a testing programme should integrate education and clinical services and programme management. It should be based on equity and ensure broad access to screening, and we should have an evaluation built into it.”

“I find it unethical to offer people testing without offering them an intervention in response. I find it unethical to blame individuals for the sorts of decisions that I hope to never be in a place to have to make in terms of risking not being able to feed my family versus not going to work.”

This webinar was part of The BMJ‘s series of covid-19 known, unknowns webinars. Find out more and register for future events here

Nikki Nabavi, editorial scholar, The BMJ

Juliet Dobson, editor bmj.com, The BMJ

Competing interests: none declared.

Panel and Agenda

Role of testing in a pandemic 

Chair: Muir Gray

– Angela Raffle (University of Bristol)

– Sian Taylor-Philips (University of Warwick)

– Brian McCloskey (Chatham House)

 

Role of asymptomatic transmission? 

Chair: George Davey Smith, Bristol University

– Nicola Low (University of Bern)

 

Asymptomatic testing: are the tools fit for the job?  (Covering accuracy in real world and Interpretation of results)

Chair: Sheila Bird 

– Jon Deeks (University of Birmingham)

– Tim Peto (University of Oxford)

– Patrick Bossuyt (University of Amsterdam)

 

Communicating and acting on test results 

Chair: Allyson Pollock

– Theresa Marteau (University of Cambridge) covering behavioural responses to negative tests

– Jackie Cassell (Brighton & Sussex Medical School) on the effectiveness of interventions]

 

Testing in different settings/contexts: panel 

Chair: Fiona Godlee, The BMJ

– Pete Buckle (NIHR In Vitro Diagnostics C., London) covering workplace and care home settings

– Andrew Frazer (former DCMO Scotland) covering prisons

– Stefan Baral (Johns Hopkins University) covering community settings

 

Discussion

Chair: Phil Hammond