FamilyCoviDD19 Study: Lower SARS-CoV-2 transmission in children and adolescents compared to adults

doi:10.21203/rs.3.rs-1792010/v1

In the COVID-19 pandemic, children were considered to play a major role in SARS-CoV-2 transmission similar to influenza. Thus, mitigation measures have been focused on children, impacting their everyday life severely. However, infectivity in this age group regarding SARS-CoV-2 is not yet clarified. We performed a serology study in households with confirmed SARS-CoV-2 infection to evaluate virus transmission with focus on children and adolescents. Between January and July 2021, 341 minors and 650 adults from 300 households with a confirmed index case participated in the FamilyCoviDD19-study including serological assessment for SARS-CoV-2 antibodies and a questionnaire on demographics, recent and ongoing symptoms, hygiene measures and comorbidities. 45 (16.3%) of all index cases were < 18 years old. Thereof, 55.6% reported COVID-19 associated symptoms, while nearly all adult index cases were symptomatic (94.8%). There was significantly less virus transmission by children and adolescents compared to adult index cases with a secondary attack rate of 0.29 vs. 0.54. With the caveat that the results do not necessarily apply to the Delta and Omicron variants, we conclude that children and adolescents are less susceptible for SARS-CoV-2 infection, more frequently show an asymptomatic course of disease and are less infective than adults.

SARS-CoV-2 virus transmission

household

seroanalysis

secondary attack rate

children

In contrast to the assumption that children and adolescents are responsible for the majority of SARS-CoV-2 transmissions, results from this household serology study show that the secondary attack rate (SAR) from children and adolescents is significantly lower than that of adult index cases while they are less often symptomatic.

Since the emerging of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the beginning of the pandemic¹, various mitigation measures have been implemented to contain the spread of the virus. Because children often show pauci- or asymptomatic disease and therefore may have undetected infections^2,3 and because of their crucial role in influenza epidemics⁴, it is widely assumed that children are more likely to spread the coronavirus and thus strong measures e.g. school closing and frequent testing have been implemented impacting this age group specifically. With the introduction of 3G rules restricting access to many public spaces to those who are recovered, tested or vaccinated, children in particular are further deprived of participation in society. It has been shown, that the social isolation during the pandemic affects the mental health of children and adolescents, increasing the risk of anxiety and depression.^5–7 At the same time the access rules to public spaces created growing social pressure on children to get vaccinated while the benefit-risk ratio for healthy children is still under debate^8–10. However, there is little data on the infectivity of children and adolescents and thus limited evidence for the justification of the prevention strategies and the vaccination recommendations that apply for minors. In order to balance the containment of the pandemic and the children’s education and mental health, there is a need of safety measures that are maximum effective and as least restrictive as possible.

We conducted a seroprevalence study in households with at least one confirmed case of SARS-CoV-2 to determine the transmission rates within a setting of close human contact with a focus on children and adolescents. Thus, we characterized the susceptibility and infectiveness towards the novel coronavirus and defined risk factors for the virus transmission. Furthermore, we evaluated the effectiveness of specific hygiene measures implemented in the household during quarantine as well as risk factors for prolonged symptoms.

Three hundred households with a total of 1056 household members and a median household size of 4 [IQR 3-5] household members were enrolled of which 991 (94%) participated in this study. Median age of the participants was 33 [IQR 15-46], 341/991 (34.4%) were <18 years of age. In total, 950 participants consented to blood collection and were tested for antibodies against SARS-CoV-2 of which 587 (61.8%) were seropositive. An index case was defined as the person that was most probable the first one infected according to onset of symptoms, positive test or seropositivity and was identified in 276/300 (92%) households. Thereof, 244 (88.4%) reported a symptomatic infection with a significant difference between index cases <18 years old and index cases ≥18 years old (55.6% vs 94.8%; p<.0001). The ratio of index cases <18 (16.3%) and ≥18 years old (83.7%) was also clearly different. 229/276 (83.0%) index cases were seropositive in our analysis. This ratio was the same for index cases <18 and ≥18 years of age. 370 (63%) of all seropositive participants reported a previous positive SARS-CoV-2 PCR. In addition, participants with comorbidities were more likely to be seropositive (68.3% vs 55.9%, p<.001) and to have symptomatic SARS-CoV-2-infections (69.4% vs 56.4%; p<.0001) compared to those without. Further demographics of the study population are listed in Table 1.

Table 1 Descriptive Statistics of the Study Population
Households, total			300
Household size, median (IQR)			4	(3-5)
Household members, total			1056
Study Participants			991
	≥ 18 years		650	(66%)
	< 18 years		341	(34%)
Age, median (IQR)			33	(15-46)
	≥ 18 years		43	(34-49)
	< 18 years		11	(7-15)
Sex, male			482	(49%)
Households with Index Case			276
	Index ≥ 18 years		231	(84%)
		seropositive	194	(84%)
		symptomatic	219	(95%)
	Index < 18 years		45	(16%)
		seropositive	35	(78%)
		symptomatic	25	(56%)
Symptomatic COVID-19
	Participants with comorbidities		197	(69%)
	Participants without comorbidities		390	(56%)

Regarding transmissions within the households, in 27/299 (9%) households none of the participants were seropositive and in 58/299 (19.4%) households only the index-case was seropositive. In 112/299 (37.5%) households all household members were seropositive. There was a lower chance that everyone in the household was seropositive with a minor index case than with an index case ≥18 years (18.2% vs 43.8%; p=.0013) (Table 2a). Accordingly, the SAR of underage index cases was significantly lower compared to ≥18 years old index cases (0.29 vs 0.54; p<.0001) (Table 3).

Table 2

Household contagion after SARS-CoV-2-infection

a. to different household characteristics

Households [%]	all households	with <18 y/o	without <18 y/o	Index <18 y/o	Index ≥18 y/o	Symptomatic Index	Asymptomatic Index	2 members	3 members	4 members	>4 members
everyone seropositive	37.6	22.2	61	18.2	43.8	43.9	0	63.9	36.4	23.3	17.6
some seropositive	34.2	47.7	14.4	29.5	30.5	33.5	10.5	5.6	36.4	50	70.6
only index seropositive	19.7	21.6	16.1	38.6	17.7	16.7	42.1	18.1	20	20	5.9
no one seropositive	8.5	8.5	8.5	13.6	8	5.9	47.4	12.5	7.27	6.7	5.9
		χ² (3, 294) = 52.18; p<.00001		χ² (3, 270) = 15.09; p=.0017		χ² (3, 258 = 51.37; p<.00001		χ² (9, 231) = 58.09; p<.00001

b. according to hygiene measures

Households [%]	no hygiene measures	unaware of infection	any hygiene measures	Index moved out	seperate rooms	seperated use of rooms	physical distance	hand hygiene	air ventilation	face mask
everyone seropositive	43.4	7.5	42.5	16.7	27	40.7	42.9	46.7	46.1	30
some seropositive	33.2	45	27.5	33.3	37.8	33.3	34.8	31.5	31.8	32
only index seropositive	16.1	40	15	33.3	24.3	16.7	13.4	15.8	14.3	24
noone seropositive	7.3	7.5	15	16.7	10.8	7.4	6.3	6.1	7.8	10
		χ²(3,80)=17.04 p<.001	χ²(3,251)=2.67 p=.45	χ²(3,46)=1.97 p=.58	χ²(3,77)=3.06 p=.38	χ²(3,94)=1.54 p=.67	χ²(3,152)=3.11 p=.37	χ²(3,209)=3.60 p=.31	χ²(3,199)=2.07 p=.56	χ²(3,90)=2.43 p=.49

Note: Chi-Square was calculated compared to households with no hygiene measures.

Table 3 SARS-CoV-2 secondary attack rates (SAR)
overall		0.53
Index case
	<12 years	0.38
	12-18 years	0.26
	<18 years	0.29 *
	18-40 years	0.44
	>40 years	0.60
	≥18 years	0.54
Index <18 years
	contacts <18 years	0.29
	contacts ≥18 years	0.29 Ⴕ
Index ≥18 years
	contacts <18 years	0.48
	contacts ≥18 years	0.59
Index case
	symptomatic	0.58
	asymptomatic	0.02 ٭
Household
	aware of infection	0.52
	unaware of infection	0.22 ˣ

* p<.0001 compared to index cases ≥18 years

Ⴕ p=.017 compared to index ≥18 years to contacts <18 years

٭ p<.0001 compared to symptomatic index cases

ˣ p<.0001 compared to households aware of infection

Specifically, transmission from adult index cases to household contacts <18 years was more common than vice versa (SAR 0.48 vs 0.29; p=.017). Children and adolescents generally transmitted SARS-CoV-2-infections less frequently to both adult and underage household contacts (SAR 0.29). When comparing transmissions within households with PCR confirmed SARS-CoV-2-infections to those in which the SARS-CoV-2-infection was detected only retrospectively by serology, we found that SAR was significantly higher within households with a positive PCR (0.52 vs 0.22; p<.0001). Even when a household did not follow any hygiene measures during quarantine, SAR was higher than in households that were unaware of their SARS-CoV-2-infection (0.53 vs 0.22; p<.0001). Accordingly, in households with a symptomatic index person there was a higher chance that every participant from the household was seropositive (44.1% vs 0%; p<.0001). The seropositivity rate was also dependant of the household size as it decreased significantly for each additional household member. In households with more than 4 members the probability of all household members being seropositive was significantly lower compared to households with only two members (17.6% vs. 63.9%; p<.0001). To analyze the effect of hygiene measures on transmission, participants were asked if they were following specific hygiene measures e.g. distancing, wearing masks or regular room ventilation. Interestingly, the overall SAR was the same in households that implemented hygiene measures to those that did not (0.53) (Table 2b). When the index case left the household (6/211 households) as soon as the infection was confirmed, there was a 33.3% chance that no other household member was seropositive (SAR of 0.36), while this was only the case in 15% of the households without any measures (SAR 0.53). Due to the low case numbers, this was not statistically significant.

To evaluate the severity and long-term effect of the infection, participants were asked about current medical conditions at the time of blood collection. Results are displayed in Table 4 as ongoing symptoms <12 weeks and ≥12 weeks after SARS-CoV-2 infection according to specific characteristics of the participants. When the infection was <12 weeks ago 25 % of the participants suffered from ongoing symptoms while participants that were enrolled ≥12 weeks after their infection reported health restrictions in 29.7%. Seropositive participants were more likely to have persistent symptoms both <12 and ≥12 weeks after infection within their household compared to seronegative participants (12 weeks: 31.5% vs 14.5% and ≥12 weeks: 34.8% vs 20.8%; p<.001). When analysing only participants <18 years of age, differences between seronegative and seropositive participants were not significant. Individuals that reported SARS-CoV-2 related symptoms in the acute phase were more often suffering from ongoing symptoms than asymptomatic participants both <12 and ≥12 weeks after the event of SARS-CoV-2-infection within the household (< 12 weeks: 33.3% vs 5.0% and >12 weeks: 39.8% vs 3.1%; p<.0001).

Table 4

Ongoing symptoms after SARS-CoV-2-infection

time after SARS-CoV-2	ongoing symptoms	male	female	<18 years	≥18 years	<12 years	12 - 17 years	18 - 40 years	>40 years
<12 weeks	yes	19.7	30.1	8.2	32.6	6.3	10.8	21.3	40.6
<12 weeks	no	80.3	69.9	91.8	67.4	93.8	89.2	78.7	59.4
		p<.05		p<.0001		ns		p<.01
≥12 weeks	yes	17.5	40.4	3.8	41.9	0	7.3	37.8	45.5
≥12 weeks	no	82.5	59.6	96.2	58.1	100	92.7	62.2	54.5
		p<.0001		p<.0001		p<.01		p=.053

time after SARS-CoV-2	ongoing symptoms	seropositive	seronegative	symptomatic COVID-19	asymptomatic COVID-19	comorbidities	no comorbidities	BMI < 25	BMI > 25 *
<12 weeks	yes	31.5	14.5	33.3	5	42.5	17.8	8.2	0
<12 weeks	no	68.5	85.5	66.7	95	57.5	82.2	91.8	100
		p<.001		p<.0001		p<.0001		ns
≥12 weeks	yes	34.8	20.8	39.8	3.1	41	24.5	2.2	22.2
≥12 weeks	no	65.2	79.2	60.2	96.9	59	75.5	97.8	77.8
		p<.001		p<.0001		p<.01		p<.05

Note: table shows fraction of participants with and without ongoing symptoms [%], p-values refer to Fisher’s exact test results, * BMI analysis for participants <18 years old, n=178

Generally, adults were more likely to develop ongoing symptoms compared to children and teenagers <18 years (<12 weeks: 32.6% vs 8.2%; p<.0001 and ≥12 weeks: 41.9% vs 3.8%; p<.0001). Furthermore, participants >40 years of age were more likely to have ongoing symptoms up to 12 weeks after infection than young adults (46.9% vs 21.3%; p<.01). When participants ≥18 years were enrolled ≥12 weeks after the infection, they more often reported medical issues than those seen within 12 weeks after infection (41.9% vs 32.6%) while the rate of persisting symptoms in minor participants decreased over time (<12 weeks 8.2% vs >12weeks 3.8%). The probability of ongoing symptoms did not only correlate with age but with gender. Female participants had a higher prevalence of ongoing symptoms ≥12 weeks after the infection compared to male participants (40.4 % vs 17.5 %; p<.0001). Consistent with higher infection rates and seroprevalence, participants with comorbidities were more likely to experience persisting symptoms after the infection (< 12 weeks: 42.5% vs 17.8%; p<.0001 and >12 weeks: 41.0% vs 24.5%; p<.01). Here, seropositive participants were significantly more affected than seronegative subjects (47.5% vs 21.6%; p<.005). BMI did not have any influence on the rate of ongoing symptoms in participants ≥18 years old, but children and adolescents with a BMI >25 were more likely to report ongoing symptoms ≥12 weeks after the infection than those of lower BMI (22,2% vs 2.2%, p<.05).

In this prospective seroprevalence study, we analyzed SARS-CoV-2-transmission in 300 households with confirmed index-cases to evaluate infectivity and susceptibility in a setting of close contact. We found that 587/950 (61.8%) household members were seropositive after an event of SARS-CoV-2-infection within their household. This rate is higher than in a previous analysis from January 2021¹¹ and most other studies.^12,13 While the incident rate was the same in children and adults in the household setting, only 16.3% of the index cases were < 18 years old, indicating that SARS-CoV-2-infections were mostly introduced into the household by an adult household member. Additionally, the SAR was much lower for underage index cases compared to that of adult index cases. Children and adolescents were less likely to infect both household contacts of the same age and adult household contacts (SAR 0.29), which indicates a lower infectivity in this age group. This is in line with several previous studies ^14–16 while some others found children to be more likely than adults to transmit the virus.¹⁷ However, overall, SARS-CoV-2 transmission rates from children seem to be lower in contrast to other respiratory viruses, for which children were found responsible for most of transmission clusters.¹⁸ Additionally to the lower SAR in children and adolescents in our study, participants in this age group showed fewer symptoms during infection and were more often asymptomatic compared to adults which is described very consistently in literature.^2,19,20 This indicates that an asymptomatic SARS-CoV-2-infection is associated with a reduced infectivity and contradicts the assumption that children quickly spread the virus because of asymptomatic and therefore undetected infections. This evidence is in line with observations in other studies.²¹ In households, that were enrolled only after positive seroanalysis of a child or adolescents within the SchoolCoviDD19-study and did not know of any event of SARS-CoV-2-infection within their household, the SAR was the lowest of all (SAR 0.22), which supports this theory.

In contrast to other studies, we did not identify any hygiene measures that were associated with a reduced seropositivity rate within the household. This seems logical considering that the infectivity is highest even before and until shortly after the first symptoms^22,23 while hygiene measures are implemented only when the infection is PCR-confirmed a few days later. Wang et al. found combined hygiene measures to only be effective when implemented before the beginning of symptoms.²⁴ Otherwise the lack of effect of the hygiene measures might also indicate a higher contagiousness of the first virus variants since earlier similar studies during the alpha variant could detect an effect.

Sometime after the beginning of the pandemic, discussions emerged about ongoing or recurring symptoms after the initial SARS-CoV-2-infection, the so-called Long-COVID-syndrome.

In this study we screened for ongoing symptoms with a questionnaire and found that nearly every third participant reported any ongoing symptom at the time of blood collection. These symptoms were clearly associated with a symptomatic SARS-CoV-2-infection and with a positive serostatus. In line with the milder course of disease in children and adolescents, they were least often suffering from ongoing symptoms while the rate of prolonged disease increased with age. Furthermore, comorbidity was a risk factor for ongoing symptoms and this was specifically associated with the SARS-CoV-2-infection as seronegative participants with comorbidities suffered significantly less often from ongoing symptoms. Previous studies showed that common medical conditions e.g. diabetes or hypertension are risk factors for severe COVID-19 and increased mortality.²⁵

In line with previous studies and clinical reports, we could show that children and teenagers of < 18 years of age did not only have a milder course of disease²⁶, but they were less prone to be infected with SARS-CoV-2 and most importantly less likely to transmit it to their household members. Several other studies found that children and adolescents have a similar seroprevalence for SARS-CoV-2 as adults²⁷ and some even reported that the infectivity seems to be reduced²⁸, but still most conclude that because of the same susceptibility as adults plus the undetected cases, strict hygiene measures and surveillance should be implemented to prevent SARS-CoV-2-spreading in day cares and schools. However, our study could not confirm an overrepresentation of children in adolescents in SARS-CoV-2 cases²⁹ but also show that their probability to transmit the virus is much lower than that of adult index cases. Consequently, the focus of pandemic control should be directed more towards adults than children and adolescents.

To investigate SARS-CoV-2 seroprevalence within households and define possible risk factors for infection, transmission and prolonged symptoms, households with a confirmed SARS-CoV-2-infection were contacted by the local Health Department and invited to participate in the FamilyCoviDD19-study. The study was approved by the ethics committee of the Technical University of Dresden (BO-EK-342072020) and performed according to the declaration of Helsinki. Upon informed consent, a blood sample was taken from the participants and information was obtained about demographics, past episodes of illness, PCR-testing for SARS-CoV-2, hygiene measures during quarantine as well as their current state of health. Between 18th January and 20th July 2021, 394 households were enrolled into the seroprevalence study FamilyCoviDD19 of which 254 households were enrolled upon a positive SARS-CoV-2-PCR and 46 were additionally enrolled after positive antibody testing in our seroprevalence SchoolCoviDD19- and KiTaCoviDD19-study. Eventually, 21 households were excluded because they did not meet the inclusion criteria (no other household member of the index person participated, household members did not have any contact during the infection period) and 73 households were excluded in this analysis because of at least one household member with vaccination for SARS-CoV-2. The detection of antibodies against SARS-CoV-2 was done with the Diasorin LIASON SARS-CoV-2 S1/S2 IgG Assay and if equivocal or positive confirmed with a second assay, either the Abbott Diagnostics ARCHITECT SARS-CoV-2 or the Euroimmun Anti-SARS-CoV-2 ELISA (a positive result was considered if at least 2 of 3 tests were positive). Transmission within the household was assessed based on the secondary attack rate (SAR) as a function of seropositive contacts out of all contacts of the index person within the household. Statistical analysis was done by Fisher’s exact test in GraphPad Prism v9.

Acknowledgement

We like to thank the whole CoViDD19-study team of the University Clinic Dresden for their support and coordination of this project. Furthermore, we are grateful for the good cooperation with the Health Department of Dresden who helped to recruit participants for this study. Finally, we like to thank all participants for their essential contribution to this work.

Author contributions

L.S. acquired participants, collected participants data, performed statistical analysis, wrote the manuscript and prepared Tables 1-4. J.B. acquired participants, collected participants data and helped to write the manuscript. E.K. acquired participants and collected participants data. J.A. designed and supervised the study, acquired funding, helped with statistical analysis, helped with interpretation of the data and helped to write the manuscript. A.H.D. helped to design the study, supervised serological analysis, helped with interpretation of the data and helped to write the manuscript. C.L. supervised serological analysis and helped with interpretation of the data. R.B. designed and supervised the study, acquired funding and helped to write the manuscript. P.C. supervised the study, acquired participants and collected participants data. All authors reviewed and approved the manuscript before submission.

Competing interests

The authors declare no competing interests.

Funding

This work was supported by the State Ministry for Higher Education, Research and the Arts of the Federal State of Saxony.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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No competing interests reported.

FamilyCoviDD19 Study: Lower SARS-CoV-2 transmission in children and adolescents compared to adults

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Abstract

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