With so much attention on #COVID19 in children, time for an updated #tweetorial on what we do and

[Celerity]

don't know!

Alasdair Munro

@apsmunro

Paediatric registrar | Clinical Research Fellow Paeds ID

https://twitter.com/southamptonCRF

@southamptonCRF
|
@DFTBubbles

#COVID19 review lead | Origami and Nando's | Husband and dad

Joined April 2013

Research interests: Paediatric infectious diseases, Biofilms, Antimicrobial Resistance, Sepsis, Bacteraemia

https://scholar.google.com/citations?user=2zPIy8cAAAAJ&hl=en




https://threadreaderapp.com/thread/1263493025650614279.html

We'll talk impact, risk, hyperinflammation syndrome, transmission, schools and more

Lets go!


1/21

Children remain grossly underrepresented in all case numbers, hospital admissions and deaths worldwide

See latest ISARIC report of >15,000 severe cases, or @PHE_uk UK deaths

https://media.tghn.org/medialibrary/2020/05/ISARIC_Data_Platform_COVID-19_Report_6MAY20.pdf

https://publichealthmatters.blog.gov.uk/2020/04/23/coronavirus-covid-19-using-data-to-track-the-virus/


2/21




This report from @sunilbhop and friends looks at child deaths from #COVID19 compared to other causes to put them in perspective

Of ~37,000 child deaths, 43 were from COVID19

In the words of @d_spiegel , children are "unbelievably low risk"


3/21

Link to tweet

https://threadreaderapp.com/thread/1262315964898697217.html

Are some children higher risk?

Small numbers, but children usually at risk from viral respiratory infections look equally at risk from #COVID19, including tech dependent, neurodisability, malignancy or chronic lung disease

Outcomes of Children With COVID-19 Admitted to US and Canadian Pediatric Intensive Care Units

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2766037


Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City
To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with COVID-19.

https://tinyurl.com/yaudwm9c



4/21

Important to note outcomes still pretty good for these groups, and there a number of documented cases for some (e.g. oncology, immunosuppressed) which had a predominantly mild clinical course

Even most of these children don't get very sick

COVID-19 in Children With Cancer in New York City
This cross-sectional study assesses the risk associated with Coronavirus Disease 2019 for pediatric patients with cancer.

https://jamanetwork.com/journals/jamaoncology/fullarticle/2766112


5/21

What about this hyperinflammatory syndrome?

It's called PIMS-TS (or MIS-C in the USA)

It seems to be an immune reaction after COVID19 infection (approx 2 - 4 weeks)

Usually starts with persistent fever, abdo pain and D&V, then can present similar to Kawasakis (+/- shock)


6/21



We currently have 3 published cohorts from London, Italy and France

Many kids get very sick, but most recover well

It seems to be dissipating (following trends in peaks of infection)

Read more about it here

Paediatric Multisystem Inflammatory Syndrome

It has become increasingly clear that children are less frequently affected by severe COVID-19 than adults.

https://dontforgetthebubbles.com/pims-ts/


7/21

It can be serious, but is incredibly rare

In Europe there have been about 230 cases and very few deaths. There are >80 million children

Europe CDC considers it a low risk. Be reassured

https://www.ecdc.europa.eu/sites/default/files/documents/covid-19-risk-assessment-paediatric-inflammatory-multisystem-syndrome-15-May-2020.pdf


8/21

OK - transmission. Let's go step by step.

How easily to children catch it?

5 studies have looked at transmission to children (mainly household) and 4/5 found *significantly lower* attack rates in children than adults

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

https://dontforgetthebubbles.com/the-missing-link-children-and-transmission-of-sars-cov-2/


9/21



How many children actually have/had COVID19?

<2% of known cases have been in children, but given symptoms are so mild have we just missed them all? Are they mainly asymptomatic? Are they silent assassins?

This is harder to tell, but there is some evidence...

10/21

Iceland tested those at risk and found 1/2 rate of infection in children <10y compared to adults, and 0 cases in asymptomatic screening

Spread of SARS-CoV-2 in the Icelandic Population | NEJM
Original Article from The New England Journal of Medicine — Spread of SARS-CoV-2 in the Icelandic Population

https://www.nejm.org/doi/full/10.1056/NEJMoa2006100


Vo, Italy screened >85% of the population. 2.6% had COVID19, but 0 children <10y

https://www.medrxiv.org/content/10.1101/2020.04.17.20053157v1


11/21

Some say ONS data shows there's no difference between children and adult infection rates

But they found ~30 positive cases in 10,000 people

The CIs are too wide for inference about relative infection rates (compatible with 10x rates in any group)

https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/coronaviruscovid19infectionsurveypilot/england14may2020?WT.mc_id=9e5557c21c93a6f19d36bf985082f4de&WT.sn_type=TWITTER&hoot.message=There%20is%20currently%20no%20evidence%20that%20age%20affects%20the%20likelihood%20of%20being%20infected%20with%20COVID-19%20%5BLINK%5D&hoot.send_date=2020-05-14%2013%3A15%3A14&hoot.username=ONS&hoot.send_dayofweek=Thursday&hoot.send_hour=13&hootPostID=602e6bfaca6d5de6b869e70e6e9a7230#main-points


12/21



The same principle applies for 2 sero-epi studies from Switzerland & Germany

Despite lower rates of infection in children, numbers too small to be statistically significant

This is not evidence for equal rates of infection

https://www.medrxiv.org/content/10.1101/2020.05.02.20088898v1

https://www.medrxiv.org/content/10.1101/2020.05.04.20090076v1


13/21




What do we find if we do proper sized sero-epi?

Infection rates of 1-3% in children compared to 5% in adults in a Spanish study of >60,000 people

https://www.ciencia.gob.es/stfls/MICINN/Ministerio/FICHEROS/ENECOVID_Informe_preliminar_cierre_primera_ronda_13Mayo2020.pdf



14/21



How infectious are children when infected?

Hard to say. Some examples of children not spreading at all despite multiple exposures (>100 other children) but spreading other respiratory viruses

Cluster of coronavirus disease 2019 (Covid-19) in the French Alps, 2020

Abstract Background. On 07/02/2020, French Health authorities were informed of a confirmed case of SARS-CoV-2 coronavirus in an Englishman infected in Singapore

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa424/5819060


15/21


A German study claimed to find similar viral loads in children as adults, stating they're "just as infectious"

https://zoonosen.charite.de/fileadmin/user_upload/microsites/m_cc05/virologie-ccm/dateien_upload/Weitere_Dateien/analysis-of-SARS-CoV-2-viral-load-by-patient-age.pdf

Amongst other issues, if analysed properly the data actually showed significantly lower viral loads in children

https://osf.io/bkuar/


16/21



National reports from Netherlands

https://www.rivm.nl/en/novel-coronavirus-covid-19/children-and-covid-19

Iceland

https://www.eapaediatrics.eu/eap-blog-covid-19-series-5-icelands-data-on-the-infectivity-of-children-cross-infection-risk/

Norway

https://www.fhi.no/contentassets/c9e459cd7cc24991810a0d28d7803bd0/notat-om-risiko-og-respons-2020-05-05.pdf

Australia

http://ncirs.org.au/sites/default/files/2020-04/NCIRS%20NSW%20Schools%20COVID_Summary_FINAL%20public_26%20April%202020.pdf

Have found limited evidence of children contributing to spread of COVID19. Most transmission is adult to adult.

17/21




What does it mean for schools?


Children are not COVID-19 super spreaders: time to go back to school

https://adc.bmj.com/content/early/2020/05/19/archdischild-2020-319474


Children can get COVID19 so can almost certainly spread it

But, they are barely affected by infection, and appear less likely to catch or spread it than adults

Schools seem lower risk than adult work environments



18/21

Will outbreaks happen? Of course.

But this is our new reality for the foreseeable future. We need to mitigate against the risks and ensure mechanisms for quick response (track/trace/isolate) are in place

Children suffer harm from lockdown

https://bmjpaedsopen.bmj.com/content/4/1/e000701


19/21

Now for WHY children seem so much less affected...

Still no clear answers. Possible differences in ACE2 expression, but they seem small

Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults

This study compares angiotensin-converting enzyme 2 (ACE2) gene expression, which has been associated with SARS-CoV-2 cell entry, in the nasal epithelium of children vs adults.

https://jamanetwork.com/journals/jama/fullarticle/2766524?utm_source=twitter&utm_campaign=content-shareicons&utm_content=article_engagement&utm_medium=social&utm_term=052020#.XsVklEVpvmF.twitter


Some suggest immune differences. Need to be proven.

The immune system of children: the key to understanding SARS-CoV-2 susceptibility?



https://tinyurl.com/ybzfdfuq


More research needed...!


20/21



Thanks for making it to the end!

For our comprehensive review of all paediatric #COVID19 literature (cited by @UKRI_News and @WHO ) check it out here on @DFTBubbles


21/21

AN EVIDENCE SUMMARY OF PAEDIATRIC COVID-19 LITERATURE

https://dontforgetthebubbles.com/evidence-summary-paediatric-covid-19-literature/