May 22, 2020

expert reaction to systematic review preprint looking at susceptibility to SARS-CoV-2 infection in children and adolescents compared with adults

A systematic review preprint, an unpublished non-peer reviewed study,  looking at susceptibility to SARS-CoV-2 infection in children and adolescents compared with adults.

This roundup accompanied an SMC Briefing.

Prof Peter Diggle, Distinguished Professor, CHICAS (Centre for Health Informatics, Computing and Statistics), Lancaster Medical School, Lancaster University, said:

“The paper reports a standard meta-analysis – a widely accepted way to interpret the combined results of multiple studies that address the same question, based on published summaries of each.

“The work is of good quality, and supports an overall conclusion that children are less susceptible overall to infection than adults, but does not support any quantitative unpicking of this, not least because it cannot disentangle inherently biological from behavioural factors, the latter being highly variable between studies (e.g. pre-lockdown vs post-lockdown).

“The headline conclusion that “young people had 56% lower odds of catching SARS-CoV-2 from an infected person, compared with adults” mean the following:

“1. “odds” mean the ratio of the proportion who do, and the proportion who do not, catch the infection (in betting parlance, the phrase “odds against = 10 to 1” means that the probability of winning is 1/11, hence the probability of not wining is 10/11 and the ratio is 10).

“2. “56% lower odds” means that odds(children) = 0.44 * odds (adults).

“But this is only an estimate – the paper also says that the likely (95% likely – which is a convention widely used when reporting results of this kind) range of the true effect runs from 0.29 to 0.69.

“Transmission of infection is a whole different matter and the authors only claim in the paper that their study gives “weak evidence” on this issue.  In my opinion, the paper is unable to reach any conclusion regarding transmission, owing to a lack of suitable data, and restricting themselves to susceptibility would have given a clearer message.

“Low susceptibility is a necessary and important pre-condition for safe school re-opening but not a sufficient one – this needs an equal understanding of the risk of transmission within and outside the school setting, and of differences in susceptibility and transmission among important sub-groups, e.g. different ages, ethnicities, class sizes, living conditions.”

Dr Andrei Morgan, a Consultant Paediatrician and Epidemiologist working at the French National Institute for Health and Medical Research in Paris, said:

“This is a very interesting and well-done study (obviously minor criticisms are always possible with any study, but they do not detract from this one).

“The science is robust: the study has robust methods, quick turn around, and is very current, with a good discussion including of the strengths and limitations.

“Limitations are more of the included studies rather than this study itself.  The biggest limit I see with this study is that initial title/abstract screening was conducted by only one author (RV) and as there were >6000 articles he may possibly have missed some relevant for inclusion.

“I do think they put too much emphasis on the 0.44 odds ratio when heterogeneity was high (63.8%) – heterogeneity means that the studies may not be compatible and that the result should be interpreted very cautiously.  It is interesting to note that the odds ratio was slightly higher in medium (as opposed to low) quality studies at 0.51 (95% CI 0.31 – 0.84) with heterogeneity of 68.2%.  Also, bigger studies tended to be closer to 1 which is when there’s no difference between the groups.  So, I think the 56% lower odds should be taken with a pinch of salt – for a rare condition, the odds ratio tells us that there is a lower risk (of approximately half in this case) of children becoming infected, but if covid-19 is likely to become a common condition then odds and risk do not necessarily mean the same thing.

“It’s also hard to tell whether all appropriate studies were included and all inappropriate studies were excluded as there is little information on that – I wonder if there might have been important supporting information from the small case/cluster tracing studies they excluded.

“A more important point is that the majority of the included studies used PCR tests.  However, this may introduce bias, particularly in children – as the authors mention when they say: “there may be technical issues with nasopharyngeal swab samples by carers in very young children”.

“In relation to the issue of schools reopening, this study on its own can’t say much.  All the studies included in the review – as discussed by the authors – were conducted in settings with moderate to substantial public health (social distancing/’lockdown’) measures instituted, or being instituted, so it’s very hard to extrapolate this to re-opening schools.

“What this review really adds is that our knowledge is very limited!  There is a lot we do not know about children and we are still making a lot of assumptions/extrapolations from findings in adults.”

Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:

“This is a good quality systematic review, and a useful addition to the evidence base regarding the views that that children are typically less likely to be infected than adults.

“However, there is still a key question that we do not fully understand, and that is the role of children in transmission.  It’s a key topic in the UK, with some children returning to school on 1 June.  For example, many care home and domiciliary care staff will have school-age children, and it is vital that we can be sure there will be no significant chain of transmission between children and then onto parents who work close to vulnerable populations.”

Preprint (not a paper): ‘Susceptibility to SARS-CoV-2 infection amongst children and adolescents compared with adults: a systematic review and meta-analysis’ by Russell M. Viner et al.  This work is not peer-reviewed.

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Peter Diggle: “RAMP reviewer of the paper.”

None others received.