The missing link? Children and transmission of SARS-CoV-2

Cite this article as:
Roland, A. The missing link? Children and transmission of SARS-CoV-2, Don't Forget the Bubbles, 2020. Available at:
http://doi.org/10.31440/DFTB.25585

There is a huge amount of international interest currently in the role of children in the transmission chain of COVID-19, as many countries are looking to relax measures of lockdown including the possibility of school reopening. Despite significantly fewer cases of severe illness in children, and fewer detected cases in total, there are concerns about children being silent vectors of the disease and spreading it in the community.

Due to global interest, there has unsurprisingly followed a lot of hype, and some misleading claims. This post aims to outline all the evidence available so far on the potential role of children in transmission of COVID-19.

 

 

What do we need to know?

In order to understand children’s role in transmission, there are three things we need to consider:

  1. How easily children catch the disease
  2. How many children have the disease
  3. How infectious a child is once they have it

Let’s take a look at the evidence for each of these in turn

 

 

How easily children catch the disease?

On this front, we have five studies (three published and two pre-print) to help inform us. These studies all look more-or-less at the same thing, which is contact tracing. From cases that have been confirmed positive (an index case), they trace back all the people who that case has been in contact with over the recent past and test all of them for COVID-19 to see how many of them caught the illness from exposure to that index case. The proportion of people who have had contact that subsequently became infected is referred to as the Attack Rate (AR). Broadly speaking contacts can be split into two groups: household and non-household (this is important as obviously you are much more likely to transmit to someone in your house). We can also split them up according to age, and see if there is any difference in the number of children who catch the illness compared to adults.

A study from Shenzhen in China was the first to be released in pre-print in March and is now published in the Lancet ID. This study assessed 1286 contacts of 391 initial cases and showed children had a similar attack rate to the population average (7.4% vs 7.9%), but interestingly were much less likely to be symptomatic. This finding caused a lot of concern, but more data has emerged since.

A pre-print study from Japan was released shortly after. They examined 2496 contacts of 313 domestically acquired cases and found a much lower attack rate in children (7.2% males, 3.8% females) compared to adults (22% in people aged 50  -59 years).

Another pre-print study from Guangzhou in China examined 2017 close contacts of 212 confirmed cases. The overall attack rate was 12.6%, however, the attack rate in children was 5.3%. They calculated an odds ratio of acquiring infection in children of 0.27 (0.13 – 0.55) compared to adults >60 years of age.

A study published in Clinical Infectious Diseases assessed household contacts in particular. They assessed 392 contacts of 105 index cases in Wuhan, China (they had more stringent eligibility criteria to ensure they had correctly identified the index case in the household i.e. the person who brought the infection in). Of the 100 contacts under 18 years of age, only four became infected. This was compared to an attack rate of 21.9% among adult household contacts (making an overall attack rate of 16%).

A further study published in Science included some far-reaching assessments of transmission, but for our purposes, we will look at their findings regarding secondary attack rates in children. This was a contact tracing study from the Hunan CDC in China. They assessed 114 clusters (some clusters had more than one index case) and 7375 contacts.  The authors performed regression analysis to adjust for other factors that influence AR (the type of transmission, travel history, etc) to determine the odds of becoming infected at different age groups. They found an odds ratio of 0.34 (0.24–0.49) for children under 14 years, compared to the reference group of 15-64 years (consistent across models).

Below is a table summarising the findings of all these studies.

AuthorJournalNo of index casesNo. of contactsSecondary AR (children)Secondary AR (adults)OR secondary AR (children v adults)
Bi, QLancet Infect Diseases391 (32)128617/233 (7.3%)67/837 (8.0%)0.82 [0.48-1.43] †
Zhang, JScience114 (1*)737547/756* (6.2%)606/6437 (10.4%)0.34 [0.24-0.49]$
Mizumoto, KmedRxiv294 (10)249610/176 (5.6%)153/697 (21.9%)0.21 [0.11-0.41] †‡
Jing, Q-LmedRxiv335 (5)193810/244 (4.1%)127/5831 (6.2%)0.27 [0.13-0.55] ¥
Li, WClin Infect Dise105 (unknown)3924/100 (4%)60/292 (20.5%)0.16 [0.06-0.46] †

Unadjusted OR

  • Under 15 years

‡ This is based on assumption of peak rate for the 50-59 age groups applied to all adults (other data unavailable)

$ Adjusted OR in GLM for increased household exposure of children

¥ Children Vs adults age >60 years

 Thank you to Grace Leo for help compiling this table

For comparison, see this study regarding influenza where children <5yrs had the highest secondary attack rate (22.6%).

In conclusion, we have five studies assessing the secondary attack rate of COVID-19 across age groups, in which four report a considerably lower attack rate in children and one which reports the same in children as the general population. It appears fairly convincing that children are less likely to acquire the infection than adults, by a significant amount.

 

How many children have the disease?

This is more difficult to assess. Most studies looking at case rates of COVID-19 have focused primarily on those presenting to hospital unwell with symptoms, and have tested them with PCR of nasal/oropharyngeal swabs. This risks missing out on a large population of children, if there were a large number of infected children in the community with few or no symptoms.

Where we can look for this data is in countries or populations where they have undertaken much wider community testing. South Korea for example has much more extensive community testing, and still has a minority of cases in children (5- 6%).

Iceland tested 6% of their entire population and found dramatically lower numbers of cases in children, including 6.7% children under 10 positive in “targeted testing” (symptomatic or high risk due to contacts) compared to 13.7% of those 10 and older, and found 0 children under 10 years positive in population screening (by invitation) compared to 0.8% of those over 10 years.

The Italian principality of Vo tested >85% of their population following their first death from COVID-19, and found no positive cases in children despite 2.6% of the population being positive. This finding was repeated when they tested again two weeks later – despite a number of children living in households with confirmed positive contacts.

Finally, a study in The Netherlands is undertaking community serology testing (looking for antibodies against SARS-CoV-2 as evidence of current or previous infection) and has released preliminary results. They have found 4.2% of adults are positive compared to 2% of those aged <20 years.

Whilst we cannot be certain until we have the results of widespread, high-quality sero-surveillance studies, it seems increasingly likely that there are comparatively few children with COVID-19 disease in the community, particularly younger children (<10 years).

 

How infectious a child is once they have it

This is almost impossible to tell at the moment, as we have no direct experiments comparing exposure to an infected child to exposure to an infected adult – in particular as children appear to make up a small number of index cases.

For example, in the study from Guangzhou mentioned above, only 5% of index cases were noted to be children. In the previous study from Hunan, of the 114 clusters only a single child under 14 years of age was the index case in the household. In a study of an international collection of family clusters of COVID-19, a child was found to be the index case in a household in only 10% of clusters.

An issue with this data is that given schools were closed early in the outbreak, it is possible that this had an impact on the likelihood of a child becoming infected outside of the home and therefore becoming a household index case. Children rarely mix outside of the home other than at school.

These studies cannot tell us is why this is the case. We have seen above that children appear less likely to get infection, and that fewer children seem to have the infection in the community. There could be fewer cases just because there are fewer infected children. What we don’t know is how many infected children brought an infection into their home, but didn’t give it to anybody – as these cases would never be discovered (and won’t until we have sero-surveillance). Children may be less infectious or not, but we do not have any evidence for that at present.

 

What about viral load?

A high profile study emerged in the press recently examining viral loads of children and adults from Germany. This received a lot of press for its conclusion that there was no difference in viral loads between age groups, and that this would imply children are as infectious as adults. Due to the high profile nature of this study, we will consider this in detail.

What did they do? This is hard to say as their methods section is sparse, however, in brief, they assessed the viral load of all positive samples from patients with SARS-CoV-2 at some German hospitals by comparing the ct values (a surrogate measure for viral load based on PCR) and comparing these across arbitrary age groups.

Firstly, it is important to note there is far more to how infectious an individual is than merely their viral load as determined by PCR (which also detects dead virus, as opposed to viral culture), so it is not good practice to make many assumptions past this point.

Second, there is a big issue in determining which populations these samples have come from. We do not know if these are all symptomatic cases who were unwell and presented to hospital, or if this is taken from a community setting. This is extremely important, particularly given the most striking part of their main figure:

Note how few samples from children there are compared to adults. Let’s consider who this population might be, and assume their conclusion (there is no association between viral load and age) is correct.

  1. Symptomatic cases presenting to hospital: Then the correct conclusion is, “among patients with COVID-19 who were unwell enough to develop symptoms and present to hospital, there appears to be no difference in viral load. As there are considerably fewer children, it is possible many children with lower symptom burden are present in the community who may have different viral loads”.
  2. Community testing: Then the correct conclusion is, “among community populations with COVID-19, of those who test positive there are similar viral loads. We note there are considerably fewer children than adults, demonstrating that although viral loads are comparable, fewer children appear to be infected”.

This all stems on their conclusions being correct, however, there is another highly significant issue with their data analysis. The study question is whether there is an association between viral load and age. Age is a continuous variable, meaning it is a number that goes up continuously and doesn’t strictly have categories. If you make categories from it, you dramatically reduce the statistical power to detect differences. This is what they have done. Not only that, but they have applied a highly punitive correction for multiplicity (making lots of comparisons, which increases the probability of finding a statistically different difference by chance) which also dramatically reduces the chances of getting a “statistically significant” result.

Of note, in their paper they actually do use something closer to a more appropriate method of analysis which is a Kruskal-Wallis test. What did they find? A statistically significant association between age and viral load (p=0.01). This is not surprising if you actually plot the means of their data (courtesy of Johannes Textor)

Even by this inappropriate method of analysis, it looks extremely likely that if children weren’t so underrepresented in their sample the result would have been statistically significant.

In summary: there are almost no meaningful conclusions which can be drawn from this study given we don’t know from which population the samples were taken. What we can say is that their conclusion about no significant difference between age and viral load is not supported by their own data, and that the opposite conclusion appears more likely – that there is a statistically significant difference between age and viral load. Even if this is the case, this does not tell us the whole story about how infectious any given individuals is.

 

What about schools?

Specific evidence in regards to transmission in schools is lacking, due to rapid shutdown at the start of the pandemic. A systematic review of the impact of school closures on the transmission of SARS and COVID-19 found only equivocal evidence for their impact in controlling transmission.

A study from an outbreak around a French secondary school has received some attention, as they found 40% of pupils and staff became infected with no difference between the two groups. What is important in this study, is that almost all the students in the study were aged 15-17 years of age, who appear to have similar disease characteristics to adults. Of the children 14 and under, a very small proportion got infected (it’s not clear how many were students and how many were family contacts). We cannot derive useful information from this study about younger children at present.

Another study from New South Wales in Australia demonstrated very low rates of infection in school children and low rates of spread, however, the absolute numbers are low (18 cases total, 12 secondary and six primary) so again it is difficult to draw firm conclusions from this study regarding spread in schools, despite the data being reassuring.

 

Conclusion

From the studies listed above we can determine:

  • Children appear significantly less likely to acquire COVID-19 than adults when exposed
  • There is reasonable evidence that there are significantly fewer children infected in the community than adults
  • Children are rarely the index case in a household cluster in the literature to date
  • It is not clear how likely an infected child is to pass on the infection compared to an infected adult, but there is no evidence that they are any more infectious

The most parsimonious explanation for all the above seems to be that children are less susceptible to becoming infected, therefore fewer of them have become infected, there are subsequently fewer infected individuals in the community, and children have therefore infrequently brought the infection into their homes.

About Alasdair Munro & Damian Roland

Alasdair is a Paediatric registrar in the UK, currently working as a Clinical Research Fellow in Paediatric Infectious Diseases. His interests include evidence based medicine and peri peri chicken.

Damian Roland is a Paediatric Emergency Medicine and Honorary Associate Professor. His research interests include scoring systems in emergency and acute care and educational evaluation. Damian also chairs PERUKI (Paediatric Emergency Research United Kingdom and Ireland), which gives him and the team an opportunity to raise awareness of the important of research and evidence based practice at scale. The list of the many things Damian hasn’t done or achieved is far longer but through these he learns and develops new ideas.

Author: Alasdair Munro & Damian Roland Alasdair is a Paediatric registrar in the UK, currently working as a Clinical Research Fellow in Paediatric Infectious Diseases. His interests include evidence based medicine and peri peri chicken. Damian Roland is a Paediatric Emergency Medicine and Honorary Associate Professor. His research interests include scoring systems in emergency and acute care and educational evaluation. Damian also chairs PERUKI (Paediatric Emergency Research United Kingdom and Ireland), which gives him and the team an opportunity to raise awareness of the important of research and evidence based practice at scale. The list of the many things Damian hasn’t done or achieved is far longer but through these he learns and develops new ideas.

18 Responses to "The missing link? Children and transmission of SARS-CoV-2"

  1. Emma Blake
    Emma Blake 2 months ago .Reply

    Is there any evidence about the sensitivity of the tests in children?
    Our microbiologist says that the swans have a 50% false negative rate. So are very unreliable.
    Is there any information about how reliable they are in children? Could it be harder to get a positive swab?
    There is also some confusion about timings of swabs. Could this be an issue in children?
    Both of these would mean we are getting inaccurate data.
    I can see no information about this in the studies.

    Emma Blake
    Paediatric Consultant

  2. Alasdair Munro
    Alasdair Munro 2 months ago .Reply

    Thank you for your comment Emma.
    I am currently not aware of any studies specifically assessing test characteristics of swabbing in children. I have not seen anything to suggest 50% specificity of swabbing, including from adult literature.
    Most respiratory viral PCR tests are assumed to perform as well in children as adults (operator dependent of course).
    Alasdair

  3. Ranjith Joseph, Consultant Paediatrician
    Ranjith Joseph, Consultant Paediatrician 2 months ago .Reply

    The usual adult pick up rate of 70% likely to be lower in children as the smaller they are difficult for us to get a swab from the back of throat. In children they seem to be shedding the virus in their stools and if they are combined with nose and throat swabs should result in better pick up rates. Children are also recently presenting in toxic shock, typical and atypical Kawasaki’s with some having significant cardiac pathology.

  4. Andrea Echeverry
    Andrea Echeverry 2 months ago .Reply

    Thank you so much for putting this together. When I saw the data from the German study and realized there was at least a 2Log difference in viral load between the highest value in the under 6yr old group and highest value in the over 45yr old group (or even the over 25yr old group), I realized there was something odd with the statistics and conclusion.
    I think these data present us with an opportunity to dial in the particular innate mechanism that may be at play here. Or could it all be related to lower ACEII receptor in children? Will someone care enough to investigate this?
    We should be counting our blessing children are not as affected or symptomatic.

  5. Grzegorz Lindenberg
    Grzegorz Lindenberg 2 months ago .Reply

    In the German paper you find the following quotation:

    “To enable an estimate of infectivity in children, we analyzed viral loads observed during routine testing at a large laboratory testing centre in Berlin (Charité Institute of Virology and Labor Berlin). Charité Institute of Virology was the first laboratory qualified to test for SARS-CoV-2 in Germany and until early February 2020 was the only SARS-CoV-2 testing facility in Berlin, a city of ca. 3.8 million inhabitants. Labor Berlin is a large medical laboratory services provider in Berlin, owned by the senate of Berlin and serving Charité as well as other large hospitals in Berlin and beyond. Labor Berlin serves public testing centres that mainly see adult outpatients. It also tests out- and inpatients from several hospitals, and serves practitioners and public health agencies submitting samples taken during household-based contact tracing.”

    I understand it as saying that the samples came from all kinds of tests, both community and hospital based.

  6. Victor Pérez
    Victor Pérez 2 months ago .Reply

    Thanks a lot “mate”
    Great review

  7. Manuel Soto
    Manuel Soto 2 months ago .Reply

    Agree. Fantastic review. Cheers from Costa Rica

  8. Rob
    Rob 2 months ago .Reply

    Just a news article and a small sample, but this is concerning: https://montrealgazette.com/news/local-news/coronavirus-12-children-four-employees-infected-at-mascouche-daycare/wcm/9655f3d1-79c0-4efe-8f92-1f72883c5cf4/ . Outbreak in a daycare centre for children of health workers. Attack rate of 44% among the children.

  9. @WALangProf
    @WALangProf 2 months ago .Reply

    So in summary, despite over 3 million confirmed cases, we are really not seeing outbreaks spread by kids. In the Montreal example (quoted above) of 12/27 kids likely reflects they caught from an infected worker, not each other. This is compelling Epidemiology to say kids are not super spreader, if spreaders at all.

  10. Alasdair Munro
    Alasdair Munro 2 months ago .Reply

    Thanks for your comment Rob. Yes I have seen the article. Many details are unclear at the moment, but we should not be surprised to see examples where significant numbers of children become infected. If anyone is exposed for prolonged periods of time, they will become infected. It is best to consider the evidence as a whole rather than to focus on individual anecdotes to help keep perspective. Thanks again!

  11. Andy oliver
    Andy oliver 2 months ago .Reply

    children run around lick thinks hug each other suck fingers pick noses , shout and scream cry share crayons share seats and desks spit food when they eat ,,dont wash hands correctly , cant even look after PE kit let alone a mask , share food drinks sweets , snog , only 2 % i think are at school at this time in England , stand by your beds when that is even 20%, Talking about receptors and studies etc, forgets that kids are kids you try changing that , they get ill quick and recover quick try testing for that let alone trying to protect a teacher from a vomiting child without a military grade NBC suit,, and the effects of the disease may not present as they do in adults could be a multi organ inflammatory response , not a clue ,, last time i checked is not that ethical to test on children and the approach in England seems like that ..
    anyone with kids know they have many viral infections recover in 12 mins are back eating ice cream and you get “it” and are buggered for 3 weeks , i have no idea take care all

  12. Andy oliver
    Andy oliver 2 months ago .Reply

    comorbidity children has to be less no ? type 2 diabetic etc

  13. Maryza Graham
    Maryza Graham 2 months ago .Reply

    Hi Alasdair, thank you for a great summary. Regarding “How easily children catch the disease?” it seems that all contacts in the Shenzen study were tested by PCR at start and end of quarantine period, contacts in CID paper tested at start and midway through quarantine and in Science paper were tested once but it’s not clear when. For the other two studies it’s not clear to me if all contacts had PCR done irrespective of symptoms or if the attack rate is a clinical attack rate. So this may explain why the attack rates in children vary in these studies? Thanks

  14. Alasdair Munro
    Alasdair Munro 2 months ago .Reply

    Thanks for your reply Maryza. Whilst the issues you mentioned might influence the absolute attack rates in the studies, they shouldn’t influence the attack rate of children relative to adults, as the same testing procedures were performed on all cohorts. Therefore the OR should be uninfluenced. Hope that makes sense!

  15. Maryza Graham
    Maryza Graham 2 months ago .Reply

    Thanks Alasdair. If children are more likely than adults to have asymptomatic infection then it seems possible that testing only symptomatic people may make it appear that the attack rate in children is less than in adults. It would be good to see more studies that indicate whether the testing was on asymptomatic children but as you say the data so far looks good for children.

  16. Katrin
    Katrin 2 months ago .Reply

    I think that the above discussed high profile study by Jones and collegues has far more concerns and limitations than mentioned and I strongy agree that it actually provides evidence in favour for the notion, that the viral load differs between children and adults (for many reasons). I just want to add one of these reasons: As mentioned above in this study a significant Kruskal-Wallis test was obtained, indicating differences regarding viral load between age groups. Dunn‘s post hoc test indicates significant differences between age groups „Kindergarten“ and „Mature“ as well. This result is simply ignored by their conclusion (it is not even discussed in the results or discussion section). Their conclusion seems to be based primarly on the non-significant Tukey HSD post hoc analysis for which the requirements (e.g. homogeneity of variance) ist not met and therefore should not have been conducted at all. I‘m stunned, that these (obviously wrong) conclusion of this study is cited so many times (at least in Germany) without beeing criticized for all its methodological errors and limitations.

  17. Kai Schulze
    Kai Schulze 2 weeks ago .Reply

    Hi Alisdair / Damien,

    thanks for the good work. What is your thought on this study?
    https://www.medrxiv.org/content/10.1101/2020.04.27.20076778v1

    All the best
    Kai

  18. Kai Schulze
    Kai Schulze 2 weeks ago .Reply

    Our data show that initial VLs at diagnosis in symptomatic children is comparable to those in adults, and that symptomatic children of all ages shed infectious virus in early acute illness. Infectious virus isolation success was largely comparable to that of adults, although two specimens yielded an isolate at a lower VL (1.2×104 and 1.4×105 copies/ml) than what was observed in adults. SARS-CoV-2 shedding patterns of culture competent virus in symptomatic children resemble those observed in adults. Therefore, transmission of SARS-CoV-2 from children is plausible.

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