27 Nov Episode 89 How do children contribute ton the epidemic

Episode 89 Role of children in epidemic

Dear colleagues,

Triggered by some discrepant findings and by the importance of the topic, I collected some examples of transmission studies within and outside households in China, the US and Europe (1-6).  As you can see the results are variable, even within China. However, the three systematic reviews (7-9) clearly show that in most studies, children seem less susceptible than adults.  The three studies on viral load (10-12) are rather unambiguous: viral load in children is on average not lower than in adults and higher in symptomatic than non-symptomatic children.

1. Epidemiology and Transmission of COVID-19 in Shenzhen (Qifang Bi medRxiv 27 March 2020): see Table 3 and Fig 1 (in slide 1)

• Children and adults up to 50 years have a similar “attack rate” for secondary cases (4.9-7.4 %), while older adults and especially the group between 60-69 % had a much higher attack rate (15 %).
• The secondary attack rate was 15.8% among household contacts and 10.3%  overall (these drop to 11.2% and 6.6% if those with missing results are considered to be negative). 
• 80% of infections are caused by 8.9% of cases
• As could be expected, children were more likely to be asymptomatic, while elderly showed more severe symptoms.
• Clearly, the observed onwards transmission is low: less than 1 in 6 contacts were infected; and, overall, far less than one (0.4) onward transmission per primary case.

The explanation of the authors is that low transmission levels may in part be due to the impact of isolation and surveillance; but it is equally likely unobserved transmission is playing some role

2. Characteristics of Household Transmission of COVID-19 (Wei Li CID Oct 2020): This study was done in Zoayan and Chibi (250 and 150 km from Wuhan). See slide 2

Secondary transmission of SARS-CoV-2 developed in 64 of 392 household contacts (16.3%), similar to the study in Shenzen above. However:

• The secondary attack rate to children was 4% compared with 17.1% for adults.
• Self-quarantine of index totally prevented transmission 0% compared with 16.9% for contacts without quarantined index
• The secondary attack rate to contacts who were spouses of index cases was 27.8% compared with 17.3% for other adult members in the households.

3. Transmission of SARS-COV-2 Infections in Households — Tennessee and Wisconsin, April–September 2020 (Grijalva MMWR 6 Nov 2020):  Slide 3

• The secondary infection rate is very high (53 %), but apparently no clear instruction on isolation were given or followed (!!!)
•  Table 2 shows that there is no age-related difference with regard to index or secondary infected individuals: children are as likely as adults of any age to be infector (primary infected) or infectee (secondary infected).
• Tendency of slightly lower transmission in smaller as compared to larger households (!?).    

These findings suggest that transmission of SARS-CoV-2 within households is high, occurs quickly, and can originate from both children and adults. Prompt adoption of disease control measures, including self-isolating at home, appropri­ate self-quarantine of household contacts, and all household members wearing a mask in shared spaces, can reduce the probability of household transmission.

4. Contrasting results of SARS-CoV-2 Transmission Among Attendees of Overnight Camps in Georgia vs Maine (slide 4) 

These MMWR reports were already discussed in Episode 81 on Nov 4th.  

• In Georgia precautions were rather relaxed and there was an attack rate of about 45 % (with the highest figures in the youngest children).
• In Maine, precautions were strict, with almost complete prevention of transmission.

5. Children and adolescents with SARS-CoV-2 in Greece (Maltezou Pediatric infectious journal Dec 2020) :

• Transmission from a household member accounted for 132 of 178 (74.2%) of infections in children
• In 66 % the adult was the first case in the household
• Only 1 child transmitted to an adult.
• No difference in viral load according to age.

6. SARS-CoV-2 in Children of Frankfurt (Heudorf GMS Hygiene and Infection Control 2020): Slide 5

• Incidence from March to July: total population 256/100,000,

In children lower:  0–4 years 142, 5–9 years 132, and 10–14 years 178/100,000

• Excluding a cluster of 34 children from refugee accommodations and 14 children from a parish (because very intensive contacts in and outside household):  
• Of the remaining 90 children: 78% had been infected by an adult within the family, and only 4% were likely to have a reverse transmission route.  Only 5.5 % infected in school or kindergarten.

7. Spread of SARS-CoV-2 in Iceland: (Gudbjartsson NEJM June 2020): Slide 6

• In targeted surveys children under 10 were half as likely to be infected as adolescents or adults (who had equal levels of infection)
• In population screening, no infected children were found, while 0.8 % of the older population was infected.
• Males more infected than females at all ages. 

8. Household transmission of COVID-19-a systematic review and meta-analysis (Lei J Infect Aug 2020): Slide 7.  The secondary attack rate

• Varied widely from  4.9 to 90 % in households (in 24 studies)
• Adults 3.7 X as likely to be infected secondarily as children (in 6 studies)
• Transmission in households was 10 X higher than with other contacts.  

9. Susceptibility to SARS-CoV-2 Infection Among Children and adolescents – a meta-analysis (Viner JAMA Pediatrics Sept 2020):   Slide 8-10

• Preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 compared with adults in contact tracing.
• Weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. 
• This study provides no information on the infectivity of children.

As you can see, however, in the slides, there is quite some heterogeneity and in some studies children and adolescent seem more susceptible than adults.

10. Review on the effect of age on the transmission of SARS-CoV-2 in households, schools and the community (Goldstein JID Oct 2020).

• Compared to younger/middle aged adults, susceptibility to infection for children aged under 10y is estimated to be significantly lower, while estimated susceptibility to infection in adults aged over 60y is higher.
• SARS-CoV-2 may spread robustly in secondary/high schools, and to a lesser degree in primary schools, if no mitigation measures are taken.

11. An analysis of SARS-CoV-2 viral load by patient age (Jones medRxiv June 2020):  Slide 11

This analysis by Christian Drosten group was amongst  the first to state children have a similar viral load than adults and that “a considerable percentage of infected people in all age groups, including those who are pre- or mild-symptomatic, carry viral loads likely to represent infectivity”  They concluded: there is little evidence from the present study to support suggestions that children may not be as infectious as adults”

Note: apparently mostly symptomatic subjects were analyzed, but there is no clear data

12. Higher nasopharyngeal viral load in children with mild to moderate COVID-19 (Heald-Sargent JAMA Paediatrics Sep 2020): slide 12 

Children younger than 5 years have high amounts of SARSCoV-2 viral RNA (lower Ct) in their nasopharynx than older children and adults.

Care was taken to exclude 7 children who required supplemental oxygen support.  7 asymptomatic patients, 29 patients with unknown duration of symptoms, and 19 patients whose symptoms started more than 1 week prior to testing.

Thus: young children potential drivers?

13. SARS-CoV-2 viral load in asymptomatic versus symptomatic children (Kociolek JCM Oct 2020): Slide 13.

Clearly, asymptomatic children have a lower, but still detectable viral load and there was no difference according to age from 0 to 17 years.  These levels were not compared to adults, but they seem to be in the same range (as already shown by Jones and Drosten).

Personal interpretation:

1. There is no doubt that children are less infected than adults in general and that is also the case in most household (HH) studies, as well as in schools, extra-school activities (camps) etc.
2. Nevertheless in some studies, in my series especially the HH study in Tennessee-Wisconsin and the Camps in Georgia (an to a lesser extent also in the HH study of Shenzen) children seem equally susceptible than (young and middle aged) adults.  At least for the American studies, the importance of implementing “non-pharmacological interventions” (quarantine, isolation, masking) is emphasized. (The Chinese did it already much earlier).
3. The studies showing similar nasopharyngeal viral load in children certainly suggest that children could be equally infectious as adults.  Then, especially young children shout, sing, sneeze, come close to hug etc….They could infect you innocently and unknowingly.    
4. It also seems evident that adults bring in the infection (from travel), it first spreads amongst (young) adults, then reaches the highly susceptible/vulnerable elderly and finally, during local or generalized “hyper-epidemic states”, the virus spreads readily amongst children as well.   We have witnessed that in Belgium especially during the last weeks of October.

As a practical conclusion, I think we should be careful in our communication to the general public.  It is true that children contribute less to the various epidemics in the world, but that is probably only true as long as they remain rather “shielded” and maybe not so much because they are biologically less susceptible to infection or less infectious (once infected).

So, we should stress the importance of the non-pharmacological interventions at a sufficiently high level to keep the virus circulation low, both in the society as a whole and in the schools and other places where children come together. Because the last thing we want is to deprive our children again from vital in-school and out-of-school education and physical/mental development.

Always interested in your opinion, especially, if you disagree or can contribute information that I overlooked.  

Have a nice WE

Guido