• 
• 

Three Part Question

Does it make sense to [avoid contact] (Intervention) with [healthy children] (Population) to [prevent virus transmission] (Outcome)?

Clinical Scenario

The pandemic of COVID-19 affects many households. Governments install strict policies to prevent the further spread of the novel coronavirus. Schools are closed and working from home is recommended. A woman goes to her general practitioner to ask advise. Her child, who is now at home as well, had contact with a classmate who tested positive for sars-CoV 2.
Her husband, who works now at home, belongs to the risk population because of reduced immunity. The woman wants to know if her asymptomatic child should be isolated from her husband, the grandparents and/or herself. Does it make sense to avoid contact with healthy children to prevent virus transmission?

Search Strategy

MedLine, EMBASE, Cochrane: conception until 18th March 2020
Medline:
(SARS-CoV-2 OR COVID-19 OR coronavirus OR 2019-nCoV) AND (child* OR pediatr* OR boy OR girl) AND (asymptomatic OR transmis* OR epidemiolog* OR contag*)

Mesh Terms:
- "COVID-19" [Supplementary Concept] AND "Disease Transmission, Infectious"[Mesh] AND ("Child"[Mesh] OR "Child, Preschool"[Mesh])

- "COVID-19" [Supplementary Concept] AND ("Child"[Mesh] OR "Child, Preschool"[Mesh])

Embase:
(SARS-CoV-2 OR COVID-19 OR coronavirus OR 2019-nCoV) AND (child* OR pediatr* OR boy OR girl) AND (asymptomatic OR transmis* OR epidemiolog*) AND (2019:py OR 2020:py)

Cochrane:
Free search term: COVID-19

Search Outcome

Medline:
719 hits of which 706 irrelevant and 6 were excluded based on language (Chinese) Mesh termen: 11 hits, all of them were excluded based on language (Chinese)
Embase:
114 hits of which 106 irrelevant and 6 were excluded based on language (Chinese) or the full text was not available

Cochrane: 2 special collections on Coronavirus (COVID-19)

Exclusion criteria were articles not corresponding to the search query (e.g. vertical transmission) and articles in a language other than English.

Medline: 7 relevant papers

Embase: 2 (also found in Medline (Pubmed)) relevant papers

Cochrane: 1 relevant paper

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Jefferson T 2011	People of all ages	Cochrane Systematic Review	preventing respiratory virus spread	Hygienic measures, such as handwashing, especially around younger children. Benefit from reduced transmission from children to household members is broadly supported also in other study designs where the potential for confounding is greater. Multiple case-control studies suggested implementing transmission barriers, isolation and hygienic measures are effective at preventing respiratory virus epidemics.	Not specific about the transmission of COVID-19
Wang 2020	55 asymptomatic patients (aged 2 - 69 years old) were tested positive for the SARS-CoV-2 after their family member’s diagnoses of COVID-19	Observational study	clinical characteristics	Of the 55 patients, 14 turned out to be mild cases, 39 developed ordinary symptoms and 2 were severe COVID-19 cases during hospitalization. A two years old boy was diagnosed as ordinary COVID-19 after testing for three times within two weeks.	- Retrospective analysis - Potential selection bias: enrolled cases were identified from systematic screening of the family members of patients positive for COVID-19
Wei 2020	9 hospitalizedinfants (aged 1 - 11 months) diagnosed with COVID-19 infection between December 8, 2019, and February 6, 2020, in China	observational study	transmission	This study showed that infants can be infected by COVID-19. The earlier stage of the COVID-19 epidemic primarily involved adults older than 15 years. Because infants younger than 1 year cannot wear masks, they require specific protective measures. Adult caretakers should wear masks, wash hands before close contact with infants, and sterilize the infants’ toys and tableware regularly. Family clustering occurred for all infected infants.	Potential selection bias: inclusion only of infants who were hospitalized, and lack of inclusion of asymptomatic patients. Retrospective study design
Hu 2020 China	24 asymptomatic patients, aged 5 to 95 years old (5/24 aged < 15 years old), who were close contacts of COVID-19 patients in Nanjing	Observational study	Clinical characteristics	Only five cases developed typical symptoms during hospitalization. 17 patients showed typical or atypical findings on chest CT-scan. Seven patients had normal images and no symptoms during hospitalization. These seven patients were younger. Young cases (<15 years old) were prone to be asymptomatic even during hospitalization and to have a normal CT image.	Small sample size Retrospective analysis Potential selection bias: possibility of missing (other) carriers when only screening from close contacts of positive patients
			Transmission dynamics	An asymptomatic COVID-19 carrier transmitted the virus to his cohabiting family members, and 1 of the infected individuals developed severe COVID-19 pneumonia and was admitted to ICU.
Dong 2020 China	2143 pediatric patients (<18 years old) with COVID-19 were reported to the Chinese Center for Disease Control and Prevention from January 16 to February 8, 2020	Case series	Epidemiological characteristics	No statistically significant difference in the number of pediatric patients between boys and girls. Children at all ages were susceptible to COVID-19. However, young children, particularly infants, were vulnerable to 2019-nCoV infection.	Retrospective analysis No clinical features of children’s COVID-19 assessed
			Clinical characteristics	Compared with the adults’ cases, the severity of children’s COVID-19 cases was milder, and the case fatality rate was much lower.
			Transmission dynamics	Most of the children were exposed to family members and/or other children with COVID- 19 which clearly indicates person-to-person transmission.
Cai 2020 China	Between 19 January and 3 February, 2020, ten children with confirmed 2019-nCoV infection were admitted to the hospital in Shanghai, Hainan, Hefei and Qingdao	case series	Clinical characteristics	Children with COVID-19 usually presented with mild respiratory infections, as compared with adult cases.	Small sample size Case series Retrospective analysis
			Transmission dynamics	This study highly support the evidence of human-to-human transmission of COVID-19. The mean incubation period was 6.5 days. This is longer compared to adult cases in who 5.2 days was observed. The mean number of secondary symptomatic cases in household exposure setting was 2.43. Virus shedding in respiratory (mean 12 days) and stool (2 weeks - one month) specimens is long in children with a mild COVID-19 infection. Most of pediatric cases occurring outside of Wuhan were secondary cases after exposure to adult cases through household contact or travel contact. However, transmission from the infected child to adult contacts is possible.The major pattern of transmission was intrafamily transmission.
Kam 2020 China	A 6-month old boy whose parents tested positive for COVID-19	Case report	Clinical characteristics	The child was tested positive with a nasopharyngeal swab on day one of admission. He was found to be viremic with detection of SARS-CoV-2 in his blood sample on day two. Besides from a single transient temperature of 38,5° C during this viremic phase, he had no clinical signs or symptoms during hospitalization. Samples from the nasopharynx continue to remain positive up to day 16 of admission. The infant had also a positive stool sample on day 9 of admission.	Case report of only one patient Retrospective analysis
Cao 2020 China	Accumulated and daily new case numbers of children in China outside Hubei province between January 20 and February 10, 2020	Perspective (opinion based on 14 articles)	Transmission dynamics	Infection can occur by respiratory droplets containing the virus (respiratory route) or by contact with contaminated objects. Airborne or aerosol transmission can occur similar to previous SARS outbreak. In the emerging stage person-to-person transmission in the community occurs almost exclusively among adults. Afterwards, intrafamilial transmission occurs, especially transmission to the elderly and children. So aggregative onset is an important feature in pediatric cases. Children at that stage can further become the main spreader of SARS-CoV-2 because their infection is usually mild.	No statistical analysis Opinion based
			Clinical characteristics	Infected children may be asymptomatic or have fever, dry cough and fatigue; some patients experience gastrointestinal symptoms, including abdominal discomfort, nausea, vomiting, abdominal pain and diarrhea. Most infected children have mild clinical manifestations and usually have a good prognosis. Usually they recover within 1–2 weeks after the onset of the disease.

Comment(s)

Main results: Multiple studies provide evidence for the human-to-human transmission of COVID-19. The virus transmission occurs through respiratory droplets and contact with contaminated objects. Positive stool samples suggest that indirect transmission might also be possible via faeces. The most seen pattern of transmission is intra-family transmission. Children of all ages are susceptible for COVID-19 infection and younger children, particularly infants (<1y), are most vulnerable. Infected children are often asymptomatic or have a mild disease course with symptoms as fever, mild cough or sore throat. One case even describes a high viral load with a viremia in a 6-month old boy with a single temperature increase to 38,5°C. The case fatality rate in children is much lower as compared with adults. Children might have a longer incubation time compared to adults with a mean of 6,5 days. Prolonged virus shedding is observed in respiratory tract and faeces at the convalescent stage. As a consequence of their mild and unnoticed coronavirus infection, children can become the main spreader of the virus. Hygienic measures in children are very effective in preventing the spread of respiratory viruses. Risks of bias: Most of the included studies have a low grade of evidence. In our research we were confronted with bias due to small sample sizes and retrospective study designs. Most studies originate from the first epidemic region in China and may be prone to selection bias. The recent onset of this new disease and therefore scarce data on this topic, is the main driver for these biases.

Clinical Bottom Line

Even healthy children may play an important role in the transmission of COVID-19 because they could be asymptomatic or have only mild symptoms of infection. Due to the mild course of the disease and the prolonged viral shedding, children can easily spread the virus without parents realizing it. Persons in close contact with these healthy children, especially risk populations, should be aware of this. We advise them to avoid unnecessary contact with children. Adult caretakers should wash hands before and after close contact with infants and sterilize their toys and tableware regularly.

References

1. Jefferson T Cochrane special collection on coronavirus (COVID-19): infection control and prevention measures, section physical interventions to interrupt or reduce the spread of respiratory viruses Cochrane Collaboration 2011
2. Wang Clinical outcome of 55 asymptomatic cases at the time of hospital admission infected with SARS-Coronavi rus-2 in Shenzhen, China The Journal of Infectious Diseases 2020
3. Wei Novel coronavirus infection in hospitalized infants under 1 year of age in China JAMA 2020
4. Hu Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China Science China Life Sciences 2020
5. Dong Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus Disease in China Pediatrics 2020
6. Cai A case series of children with 2019 novel coronavirus infection: clinical and epidemiological features Clinical Infectious Diseases 2020
7. Kam A well infant with coronavirus disease 2019 (COVID-19) with high viral load. Clinical Infectious Diseases 2020
8. Cao SARS-CoV-2 infection in children: Transmission dynamics and clinical characteristics Journal of the Formosan Medical Association 2020