- Allyson M Pollock, professor of public health1,
- James Lancaster, independent researcher2
- 1Newcastle University, Newcastle upon Tyne, UK
- 2Newcastle upon Tyne, United Kingdom
- Correspondence to: AM Pollock Allyson.Pollock {at} newcastle.ac.uk
The £ 100bn “Operation Moonshot” in the UK for launching mass tests for covid-19 in cities and universities across the country raises two key questions. How infectious are people who are positive but have no symptoms? And, what is their contribution to the transmission of the living virus?
Unusually in the management of the disease, a positive test result is the only criterion for a covid-19 case. Normally, a test is a support for clinical diagnosis, not a substitute. This lack of clinical surveillance means that we know very little about the proportions of people with positive results who are truly asymptomatic during their infection and about the proportions that are asymptomatic (subclinical), presymptomatic (continues to develop symptoms later) or post-infection (with viral RNA fragments still detectable from a previous infection).
Previous estimates that 80% of infections are asymptomatic were too high and have since been revised to 17% and 20% of people with infections.12 Studies estimating this proportion are limited by heterogeneity in case definitions, incomplete assessment of symptoms, and inadequate retrospective. and prospective follow-up of symptoms. However, approximately 49% of people initially defined as asymptomatic continue to develop symptoms45.
It is also unclear to what extent asymptomatic people transmit SARS-CoV-2. The only test for the live virus is the viral culture. PCR tests and lateral flow do not distinguish the live virus. No test of infection or infectivity is currently available for routine use.678 Currently, a person who tests positive for any test may or may not have an active live virus infection and may or may not be infectious. 9
The relationships between viral load, viral shedding, infection, infectivity and duration of infectivity are not well understood. In a recent systematic review, no study was able to cultivate the live virus from symptomatic participants after the ninth day of illness, despite persistent high viral loads in quantitative PCR diagnostic tests. However, the cycle threshold (Ct) the values in the PCR tests are not direct measurements of the viral load and are subject to errors
While the viral load appears to be similar in people with and without symptoms, the presence of RNA does not necessarily represent the living transmissible virus. The duration of viral RNA clearance (the interval between the first and last positive PCR result for any sample) is shorter in people who remain asymptomatic, so they are probably less infectious than people who develop symptoms.11
Viral culture studies suggest that people with SARS-CoV-2 may become infectious one to two days before the onset of symptoms and may continue to be infectious for up to seven days thereafter; the viable virus has a relatively short duration.7 Symptomatic and presymptomatic transmission has a greater role in the spread of SARS-CoV-2 than truly asymptomatic transmission.121213
Transmission rates to contacts in a particular group (secondary attack rate) can be 3-25 times lower for asymptomatic people than for those with symptoms.1121415 A city-wide prevalence study of nearly 10 million people from Wuhan found no evidence of asymptomatic transmission.16 Cough, which is a prominent symptom of covid-19, can lead to the elimination of many more viral particles than speech and respiration, so people with symptomatic infections are more contagious, regardless of contact. close.17 On the other hand, asymptomatic and pre-symptomatic people may have more contacts than symptomatic (isolating) people, emphasizing the importance of hand washing and social distancing measures for everyone.
Missed opportunity
By failing to integrate tests into clinical care, we missed an important opportunity to better understand the role of asymptomatic infection in transmission. Given the variation of prevalence and testing strategies by region, the proportions of people with positive and negative test results should be published together with the purpose of the testing strategy and the population tested (screening of healthy populations in schools, universities and healthcare and or testing people with symptoms). Government regulations regarding the registration of the age, ethnicity, sex and place of residence of people with positive results must also be observed.
The search for asymptomatic but infectious people is like looking for those that appear and reappear temporarily in hay, especially when rates are falling.19 Mass testing risks damaging diversion of scarce resources. Another concern is the use of inadequate tests evaluated as screening tools in healthy populations
The UK testing strategy needs to be reset in line with the recommendation of the Scientific Advisory Group on Emergencies that “Prioritizing rapid testing of symptomatic people has a greater impact on identifying positive cases and reducing transmission than frequent testing of asymptomatic people an area focus. “21
Testing should be reintegrated into clinical care with clinical and public health surveillance and case definitions based on clinical diagnosis. Carefully designed prospective case and contact studies are needed to estimate the transmission rates of people with or without symptoms. These should include thorough investigations of outbreaks – for example, testing all contacts of people with a clear history of exposure, especially in high-risk environments such as nursing homes, prisons and other institutional institutions.
Coronavirus infection surveys conducted by the Bureau of National Statistics22 and the REACT23 survey could be extended to include clinical follow-up of participants combined with viral load and viral culture tests. The lack of strong evidence that asymptomatic people are a transmission factor is another good reason to stop conducting mass tests in schools, universities and communities.
Footnotes
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Concurrent interests: I have read and understood the BMJ’s policy on declaring interests. AP was a member of the independent SAGE.
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Provenance and peer review: Not recommended; externally evaluated by colleagues.
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