Potential role of children in the household transmission of SARS-CoV-2 infection in Catalonia (Spain)

We analyzed the characteristics of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infected children during lock-down period in Catalonia (Spain), and their transmission role within the households. Among 295 traced household contacts of 89 pediatric patients, children were classified as final index cases in only 3.4% of the traced homes.


Introduction
Household clusters of coronavirus disease 2019 (COVID-19) may play an essential role in the community transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections, and consequently a risk for spreading the disease to the community [1]. Therefore, household contact tracing studies can be highly effective for COVID-19 prevention [2]. In South Korea, two similar studies demonstrated dissenting transmission rates within households from SARS-CoV-2 infected children [1,3]. In Europe (French Alps), a study of a cluster with twelve secondary cases included a symptomatic child who attended three schools without transmitting the virus to any of his contacts [4]. Also, in the Netherlands periodic reports from the National Institute of Public Health showed that patients under 20 years play a smaller role in the spread of the infection than adults [5]. However, studies exclusively based on SARS-CoV-2 viral load in respiratory samples suggest a possible role of children in SARS-CoV-2 transmission, even when asymptomatic [6,7].
On March 13th, as a first measure within a global lockdown, 5,492 Catalonian schools with a total of 1,565,478 students were closed in an effort to contain the spread of COVID-19 [8].

Materials and Methods
Catalonia, a northeastern region of Spain with 7.5 million inhabitants -1,581,341 below 20 years of age-with a regional-level governance public health system comprises 7 health sub-regional departments, and more than 400 Primary health-care centers.
The objectives of this project named "COVID-19 pediatric disease in Catalonia" (COPEDI-CAT) were: 1) to describe the epidemiological and clinical characteristics of all the pediatric COVID-19 cases diagnosed in Catalonia (Spain); and 2) to describe the dynamics of the SARS-CoV-2 infection within the household and 3) to assess the children's potential role in its transmission. This is a retrospective cross-sectional study, including the lock-down period, between 10th March and 31st May 2020 (study-period), to collect data from all pediatric (below 18 years of age) COVID-19 patients who were diagnosed by reverse transcription polymerase-chain-reaction (RT-PCR).
We obtained demographic, epidemiological, and diagnostic data of the pediatric cases through the Catalonian Health Quality and Assessment Agency from five different sources: primary health-care centers, hospitals, emergency departments, the Catalonian Epidemiological Surveillance Network, and the referral laboratories. Thereafter, a telephone survey was applied by expert healthcare workers to the parents or legal guardians of each confirmed SARS-CoV-2 pediatric case to obtain clinical and microbiological information from their household contacts. Finally, SARS-CoV-2 serological investigation was performed to household contacts of all the pediatric cases included in the study to better assess exposure to SARS-CoV-2. All data were registered in a web-based software platform Research Electronic Data Capture (REDCap®) database.
Index case was defined when the child was the first infected within the household considering the chronology of the symptoms and the serology results performed to the contacts as surrogates that reflects the temporality of the infection. Secondary cases were defined when another symptomatic household contact tested positive for SARS-CoV-2 RT-PCR or serology before the child. In co-primary cases we did not find any household contact other than the child testing positive for SARS-CoV-2 RT-PCR or serology, or we were unable to establish temporality within contacts testing positive for SARS-CoV-2 RT-PCR or serology.
As a project under the supervision of the Catalonian Public Health Agency to support health-policy recommendations on easing the current COVID-19 partial lockdown measures and allowing children back to school safely, ethics approval was not requested initially. However, to perform the microbiological studies to the household contacts, we finally obtained an ethical approval for this purpose and for all the study (PR (AG) 475/2020). Fever (59.6%; 50/89) and cough (49.4%; 44/89) were the most frequent symptoms while 21.3% (19/89) were asymptomatic (table 1). One death was reported (0.6%), and six patients had some, mostly minor, sequelae.

Characteristics of the household contacts
A total of 295 household contacts were linked to these 89 pediatric cases. After completing the contact-tracing study, children were defined as index cases in at 3.4%; the rest of children were classified as co-primary (40.4%) or were secondary cases to adults (56.2%) (table 2).    Secondary cases 50 56.2 (45.9-66.5) *Three final index cases were: one 17-year-old boy, one 17-year-old girl, and a 5-year-old girl.

Discussion
The clinical impact of COVID-19 on pediatric patients in Catalonia (Spain) during confinement was low compared to adults, and most presented as mild cases. The median age of the cases was 12 years, however a third of younger children were admitted to the hospital due to a possible bias for considering them at higher risk for COVID-19 complications at the beginning of the epidemic. Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 14 October 2020 doi:10.20944/preprints202010.0308.v1 Pediatric patients were classified as final index cases, and responsible for household SARS-CoV-2 transmission, in only 3.4% of the contact-traced homes which is much lower than other studies [1,9]. In contrast, in nearly 60% of the cases the final index case was an adult. To note, about 6 out of 10 household contacts were clinically and/or microbiologically diagnosed with COVID-19, most of them with mild symptoms without hospitalization, demonstrating a high transmission rate among household contacts (data not shown).
The study has some limitations, firstly because SARS-CoV-2 RT-PCR was mostly performed only to the clinically significant cases during the study-period. Secondly, the number of cases is small diminishing the ability to detect differences when comparing transmission between index and secondary children cases. Also, there is a potential memory bias regarding symptoms and the dynamics of the transmissibility of the infection. The rate of infected contacts may have been underestimated, as not all contacts were tested for RT-PCR and some serological results from them have been unable to perform. The prospective study currently ongoing will probably overcome most of these limitations, adding information in a different epidemiological context.
With the results of our study, and as other authors reported previously, children do not appear to be the responsible for household clusters of infection and are unlikely to be the main drivers of the pandemic [10][11][12]. Interventions aimed at children might have a small impact on reducing SARS-CoV-2 transmission, particularly if the transmissibility of subclinical infections is low [11]. Moreover, most children with comorbidities should be allowed to go back to school, as showed in our study where only severe cardiopathies or chronic lung diseases (excluding asthma) were associated to hospitalizations. Recent results demonstrated that child-to-child transmission in schools and childcare facilities is uncommon and not the primary cause of SARS-CoV-2 infection [13,14]. School closure seems to be an inefficient measure to contain COVID-19 disease [15]. Active surveillance is needed to confirm the safety of this approach. Funding: This research received no external funding.