Epidemiological burden of parents being the index cases of COVID-19 infected children

Table 1 Salient features of the reviewed studies

Ref.	Country	Continent	Study design	Study period (2020)	Inclusion criteria	COVID-19 diagnosis confirmation in children	Age of COVID-19 infected children with index case	No. of COVID-19 infected children with index case		COVID-19 infected index case/s’
								Parent	Not-parent1	Age	COVID-19 diagnosis Ascertainment	Symptoms around the time of contact with children	Death due to COVID-192
Götzinger et al[15], 2020	21 European nations except France3	Europe	Case series	1 Apr-24 Apr	≤ 18 yr SARS-CoV-2 infected individuals	RT-PCR	Median age 5·yr (IQR 5–12)	324	24 (sibling); 234 (immediate family member or unknown)	Unclear	History	Unclear	Unclear
Kim et al[16], 2020	South Korea	Asia	Cross-sectional	20 Jan- 6 Apr	≤ 18 yr SARS-CoV-2 infected individuals	RT-PCR	15 yr	0	1 (sibling)	16 yr	RT-PCR	Symptomatic	No
								0	1 [unknown (not parent or sibling)]	Unclear	Unclear	Unclear	Unclear
Luo et al[20], 2020	China	Asia	Case report	NA	NA	RT-PCR	Average 7 yr	2	0	39 yr	RT-PCR	Symptomatic	No
Merza et al[21], 2020	Iraq	Asia	Case series	18 Mar-07 April	Hospitalized conformed COVID-19 cases	RT-PCR	Average 11 yr	3	0	45 yr	RT-PCR	Symptomatic	No
Silva et al[22], 2020	Brazil	South America	Descriptive report	NA	NA	Rapid test	Average 10.5 yr	2	0	2 index cases: Male: 51 yr; female: 42 yr	RT-PCR	Symptomatic (both)	No
Song et al[23], 2020	China	Asia	Descriptive report	NA	NA	RT-PCR	Average 3.94 yr	5	0	Parents (n = 3): Average age 40.33 yr	RT-PCR	Symptomatic	No
								0	2 (grandparent)	Grandparent (n = 1): 60 yr		Symptomatic	No
Torres et al[24], 2020	Chile	South America	Cross-sectional	NA	All school staff and randomly selected students	RT-PCR	Unclear	0	7 (school staff)	Unclear	RT-PCR	Unclear	Unclear
Yang et al[25], 2020	Taiwan	Asia	Descriptive report	NA	NA	RT-PCR	11 yr	0	1 (grandparent)	85 yr	RT-PCR	Symptomatic	Yes
Yung et al[26], 2020	Singapore	Asia	Case series	5 Mar–30 Apr	Paediatric household contacts of confirmed COVID-19 cases	RT-PCR	Unclear	74	2 (grandparent or another adult except parent)5	Unclear	RT-PCR	Unclear	Unclear
Zhang et al[27], 2020	China	Asia	Research letter	28 Jan–15 Mar	Secondary COVID-19 cases	RT-PCR	Average 3 yr	2	0	Unclear	RT-PCR	One case: Mild symptoms. Other case: Moderate symptom	Unclear
Danis et al[17], 2020	France	Asia	Descriptive report	NA	NA	RT-PCR	9 yr	0	1 (a visitor/tourist)	Unclear	RT-PCR	Yes	No
James et al[18], 2020	United States	North America	Descriptive report	NA	NA	RT-PCR	≤ 18 yr	0	2 (a pastor and his wife)	Two index cases aged 56 and 57 yr	RT-PCR	During contact: Initially asymptomatic, then symptomatic	No
Jung et al[19], 2020	South Korea	Asia	Research letter	NA	NA	RT-PCR	Average 5.5 yr	1	0	The mother: 40 yr	RT-PCR	During contact asymptomatic (symptomatic after RT-PCR diagnosis)	No
								0	1 (another patient who stayed in the same room)	For 9 years old: Unclear	Unclear	Unclear	Unclear

¹In parenthesis the COVID-19 infected child/children’s relation to the index case.

²Upto the time period for which index case data reported or at the time of contact–whichever reported in the reviewed studies.

³Austria, Belgium, Bulgaria, Croatia, Denmark, Estonia, Germany, Greece, Hungary, Ireland, Italy, Lithuania, Norway, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, and the United Kingdom.

⁴Either mother or father the index case; another non-parent may be an index case for some of the children.

⁵May also have a parent index case. RT-PCR: Reverse transcription polymerase chain reaction; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; NA: Not applicable; COVID-19: Coronavirus disease 2019.

Table 2 Risk of bias assessment using National Heart, Lung, and Blood Institute's tool[12]

Study design: Case series
Ref.				1. Was the study question or objective clearly stated?			2. Was the study population clearly and fully described, including a case definition?		3. Were the cases consecutive?		4. Were the subjects comparable?			5. Was the intervention clearly described?	6. Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants?		7. Was the length of follow-up adequate?		8. Were the statistical methods well-described?		9. Were the results well-described?		Quality rating (Good, fair, or poor)
Götzinger et al[15], 2020				Yes			Yes		CD		Yes			NA	Yes		NA		Yes		Yes		Fair
Merza et al[21], 2020				Yes			Yes		CD		Yes			NA	Yes		NA		Yes		Yes		Fair
Yung et al[26], 2020				Yes			Yes		Yes		Yes			NA	Yes		NA		Yes		Yes		Fair
Study design: Cross-sectional study
Ref.	1. Was the research question or objective in this paper clearly stated?	2. Was the study population clearly specified and defined?	3. Was the participation rate of eligible persons at least 50%?		4. Were all the subjects selected or recruited from the same or similar populations (including the same time period)? Were inclusion and exclusion criteria for being in the study prespecified and applied uniformly to all participants?	5. Was a sample size justification, power description, or variance and effect estimates provided?		6. For the analyses in this paper, were the exposure(s) of interest measured prior to the outcome(s) being measured?	7. Was the timeframe sufficient so that one could reasonably expect to see an association between exposure and outcome if it existed?	8. For exposures that can vary in amount or level, did the study examine different levels of the exposure as related to the outcome (e.g., categories of exposure, or exposure measured as continuous variable)?		9. Were the exposure measures (independent variables) clearly defined, valid, reliable, and implemented consistently across all study participants?	10. Was the exposure(s) assessed more than once over time?			11. Were the outcome measures (dependent variables) clearly defined, valid, reliable, and implemented consistently across all study participants?	12. Were the outcome assessors blinded to the exposure status of participants?	13. Was loss to follow-up after baseline 20% or less?		14. Were key potential confounding variables measured and adjusted statistically for their impact on the relationship between exposure(s) and outcome(s)?		Quality rating (Good, fair, or poor)
Kim et al[16], 2020	Yes	Yes	NA		Yes	No		No	No	NA		Yes	NA			CD	NA	NA		No		Fair
Torres et al[24], 2020	Yes	Yes	NA		Yes	Yes		No	No	NA		Yes	NA			CD	NA	NA		No		Fair

CD: Can’t determine; NA: Not applicable.

Table 3 Subgroup wise weighted prevalence of parent being the index case in coronavirus disease 2019 infected children

Prevalence of COVID-19 infected children with parents being the index case
Subgroup	Category	Number of studies	Number of COVID-19 positive children	Number of COVID-19 positive children with parent being the index case	Weighted prevalence of COVID-19 positive children with parent being the index case		95% prediction interval	Heterogeneity measures
					%	95%CI		I2 (%)	Q (P value)
Continent	Asia	8	28	20	75.0	0.45-0.97	0.1-1.0	31.8	0.17
	Europe	2	583	324	58.0	0.52-0.63	Inestimable	-	-
	North America	1	2	0	0.0	0.00-0.84	Inestimable	-	-
	South America	2	9	2	11.0	0.00- 0.47	Inestimable	-	-
Country	21 European nations except France1	1	582	324	56.0	0.52-0.60	Inestimable	-	-
	France	1	1	0	0.0	0.00-0.98	Inestimable	-	-
	Brazil	1	2	2	100.0	0.16-1.00	Inestimable	-	-
	Chile	1	7	0	0.0	0.00-0.41	Inestimable	-	-
	China	3	11	9	87.0	0.54-1.00	Inestimable	-	-
	Iraq	1	3	3	100.0	0.29-1.00	Inestimable	-	-
	Singapore	1	9	7	78.0	0.40-0.97	Inestimable	-	-
	South Korea	2	4	1	18.0	0.00-0.77	Inestimable	-	-
	Taiwan	1	1	0	0.0	0.00-0.98	Inestimable	-	-
	United States	1	2	0	0.0	0.00-0.84	Inestimable	-	-
COVID-19 diagnosis in children	RT-PCR	12	620	344	50.0	0.24-0.76	0.0-1.0	63.4	0
	Rapid Method	1	2	2	100.0	0.16-1.00	Inestimable	-	-
COVID-19 diagnosis in the index case	RT-PCR	10	36	21	60.0	0.20-0.94	0.0-1.0	69.0	0.00
	History	1	582	324	56.0	0.52-0.60	Inestimable	-	-
	Unclear	2	4	1	18.0	0.00-0.77	Inestimable	-	-
COVID-19 index patient clinical presentation	Symptomatic	8	20	14	73.0	0.33-1.00	0.0-1.0	44.2	0.08
	Unclear	5	602	332	36.0	0.06-0.72	0.0-1.0	77.2	0.00
COVID-19 index patient mortality	Died	1	1	0	0.0	0.00-0.98	Inestimable	-	-
	Not died	6	17	12	74.0	0.29-1.00	0.0-1.0	48.5	0.08
	Unclear	6	604	334	44.0	0.13-0.78	0.0-1.0	74.1	0.00
Overall	NA	13	622	346	54.0	0.29-0.79	0.0-1.0	62.3	0.00

¹Austria, Belgium, Bulgaria, Croatia, Denmark, Estonia, Germany, Greece, Hungary, Ireland, Italy, Lithuania, Norway, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, and the United Kingdom. RT-PCR: Reverse transcription polymerase chain reaction; NA: Not applicable; COVID-19: Coronavirus disease 2019.

Table 4 Subgroup wise weighted prevalence of parent not being the index case in coronavirus disease 2019 infected children

Prevalence of COVID-19 infected children with parents not being the index case
Subgroup	Category	Number of studies	Number of COVID-19 positive children	Number of COVID-19 positive children with parent not being the index case	Weighted prevalence of COVID-19 positive children with parent not being the index case		95% prediction interval	Heterogeneity measures
					%	95% CI		I2 (%)	Q (P value)
Continent	Asia	8	28	8	25.0	0.03-0.55	0.0-0.9	31.8	0.17
	Europe	2	583	259	42.0	0.37-0.48	Inestimable	-	-
	North America	1	2	2	100.0	0.16-1.00	Inestimable	-	-
	South America	2	9	7	89.0	0.53-1.00	Inestimable	-	-
Country	21 European nations except France1	1	582	258	44.0	0.40-0.48	Inestimable	-	-
	France	1	1	1	100.0	0.03-1.00	Inestimable	-	-
	Brazil	1	2	0	0.0	0.00-0.84	Inestimable	-	-
	Chile	1	7	7	100.0	0.59-1.00	Inestimable	-	-
	China	3	11	2	13.0	0.00-0.46	Inestimable	-	-
	Iraq	1	3	0	0.0	0.00-0.71	Inestimable	-	-
	Singapore	1	9	2	22.0	0.03-0.60	Inestimable	-	-
	South Korea	2	4	3	82.0	0.23-1.00	Inestimable	-	-
	Taiwan	1	1	1	100.0	0.03-1.00	Inestimable	-	-
	United States	1	2	2	100.0	0.16-1.00	Inestimable	-	-
COVID-19 diagnosis in children	RT-PCR	12	620	276	50.0	0.24-0.76	0..0-1.0	63.4	0.00
	Rapid method	1	2	0	0.0	0.00-0.84	Inestimable	-	-
COVID-19 diagnosis in the index case	RT-PCR	10	36	15	40.0	0.06-0.80	0.0-1.0	68.9	0.00
	History	1	582	258	44.0	0.40-0.48	Inestimable	-	-
	Unclear	2	4	3	82.0	0.23-1.00	Inestimable	-	-
COVID-19 index patient clinical presentation	Symptomatic	8	20	6	27.0	0.00-0.67	0.0-1.0	44.3	0.08
	Unclear	5	602	270	64.0	0.28-0.94	0.0-1.0	77.2	0.00
Overall	NA	13	622	276	46.0	0.21-0.71	0.0-1.0	62.3	0.00

¹Austria, Belgium, Bulgaria, Croatia, Denmark, Estonia, Germany, Greece, Hungary, Ireland, Italy, Lithuania, Norway, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, and the United Kingdom. RT-PCR: Reverse transcription polymerase chain reaction; NA: Not applicable; COVID-19: Coronavirus disease 2019.