key: cord-0770359-soybk2i2 authors: Maltezou, Helena C.; Vorou, Rengina; Papadima, Kalliopi; Kossyvakis, Athanasios; Spanakis, Nikolaos; Gioula, Georgia; Exindari, Maria; Metallidis, Symeon; Lourida, Athanasia N.; Raftopoulos, Vasilios; Froukala, Elisavet; Martinez‐Gonzalez, Beatriz; Mitsianis, Athanasios; Roilides, Emmanuel; Mentis, Andreas; Tsakris, Athanasios; Papa, Anna title: Transmission dynamics of SARS‐CoV‐2 within families with children in Greece: a study of 23 clusters date: 2020-08-07 journal: J Med Virol DOI: 10.1002/jmv.26394 sha: 8fe723115d03445f06c89faf4581480857aa6c1c doc_id: 770359 cord_uid: soybk2i2 BACKGROUND: There is limited information on SARS‐CoV‐2 infection clustering within families with children. We aimed to study the transmission dynamics of SARS‐CoV‐2 within families with children in Greece. METHODS: We studied 23 family clusters of COVID‐19. Infection was diagnosed by RT‐PCR in respiratory specimens. The level of viral load was categorized as high, moderate, or low based on the cycle threshold values. RESULTS: There were 109 household members (66 adults and 43 children). The median attack rate per cluster was 60% (range: 33.4%‐100%). An adult member with COVID‐19 was the first case in 21 (91.3%) clusters. Transmission of infection occurred from an adult to a child in 19 clusters and/or from an adult to another adult in 12 clusters. There was no evidence of child‐to‐adult or child‐to‐child transmission. In total 68 household members (62.4%) tested positive. Children were more likely to have an asymptomatic SARS‐CoV‐2 infection compared to adults (40% versus 10.5%, p‐value=0.021). In contrast, adults were more likely to develop a severe clinical course compared to children (8.8% versus 0%, p‐value=0.021). In addition, infected children were significantly more likely to have a low viral load while adults were more likely to have a moderate viral load (40.7% and 18.5% versus 13.8% and 51.7%, respectively; p‐value=0.016). CONCLUSIONS: While children become infected by SARS‐CoV‐2, they do not appear to transmit infection to others. Furthermore, children more frequently have an asymptomatic or mild course compared to adults. Further studies are needed to elucidate the role of viral load on these findings. This article is protected by copyright. All rights reserved. Following the emergence of a new coronavirus named severe acute respiratory coronavirus 2 (SARS-CoV-2) in China in late December 2019 and subsequent global spread, a pandemic was declared by the World Health Organization on March 11, 2020. 1 As of July 26, 2020, more than fifteen million cases of the new respiratory disease named Accepted Article coronavirus disease 2019 (COVID-19) and 640,016 deaths have been notified globally. 1 In Greece the first cases were diagnosed on February 26, 2020. 2 During the first weeks of the epidemic, most COVID-19 cases were travel-associated, while as the epidemic progressed, community transmission was established. 2 The first evidence that SARS-CoV-2 can be transmitted from person-to-person was set when a member of a family in China who did not travel to Wuhan, became infected by the virus after several days of contact with family members who travelled to Wuhan; all patients had radiological ground-glass lung opacities, with adults presenting respiratory symptoms, while a 10-year child remained asymptomatic. 3 Soon after, it became evident that asymptomatic infection and mild clinical illness are more prevalent in children compared to adults. 4, 5 Herein, we studied the transmission dynamics of SARS-CoV-2 infection within families with children in Greece, focusing on the comparison of disease severity, outcome, and viral load between adults and children. SARS-CoV-2 infection is notifiable disease in Greece. Surveillance of SARS-CoV-2 infection is performed by the National Public Health Organization on a case basis. Data are notified daily by all laboratories testing for SARS-CoV-2 using real-time reversetranscriptase polymerase chain reaction (RT-PCR). In addition, physicians notify all laboratory-confirmed COVID-19 cases using a standardized notification form. A passive comprehensive system for hospitalized cases is also in place, collecting data daily on admissions in intensive care unit (ICU), complications, and outcome. For every COVID-through telephone interview with the physician in charge. Contacts of SARS-CoV-2 infected cases were traced. Close contacts were instructed to stay isolated for 14 days following the last contact with the COVID-19 case. In case of onset of symptoms, contacts were advised to attend a COVID-19 referral hospital for testing. The study period extended from February 26 (first COVID-19 case diagnosed in Greece) through May 3, 2020 (last date of lockdown in Greece). Family clusters were identified through the national registry of SARS-CoV-2 infections. We studied family clusters diagnosed in three reference laboratories for SARS-CoV-2 (two in Athens and one in Thessaloniki) where most cases were diagnosed. Families with at least one child were included in the study. Demographic, epidemiological and clinical data were collected. An adult family member (preferably the mother) was contacted through telephone in order to collect data about the possible source of infection of the first case, symptoms of household members and in-family contacts. Patients' respiratory samples were tested by real time RT-PCR following commercial or in-house protocols. Based on the cycle threshold (Ct) value of the PCR, persons were categorized into three groups, those having high, moderate, or low viral load (Ct <25, 25- Asymptomatic SARS-CoV-2 cases were defined as those with positive SARS-CoV-2 PCR in the absence of symptoms. COVID-19 cases were defined as those with positive SARS-CoV-2 PCR and compatible signs and symptoms. COVID-19 cases were classified as mild when patients were managed in the outpatient setting, moderate when patients were admitted to hospital and had a favorable outcome, while severe were classified those admitted to intensive care unit (ICU) or had a fatal outcome. Children were defined as persons<18 years of age. A family cluster was defined as the detection of at least two cases of SARS-CoV-2 infection within a family. Index case was defined as the first laboratory-diagnosed case in the family, which brought SARS-CoV-2 infection in the family under medical attention. In contrast, first case was defined as the first COVID-19 case in a family. Household contacts were defined as persons either living in the same residence or having close contacts with a family member for >4 hours daily in the family residence. Close contact was defined as a contact of >15 minutes within a distance of <2 meters with a COVID-19 case. Categorical variables were compared by using the chi-squared test while for continuous variables t-test was used. P-values <0.05 were considered statistically significant. A logistic regression analysis was not performed due to the small sample size and the inadequate events per variable, given that small to moderate samples size such as less than 100 usually overestimate the effect measure. 6 The results are presented mainly in a This article is protected by copyright. All rights reserved. descriptive form, including total numbers, frequencies, or percentages. Analysis was performed by using IBM-SPSS 26 (IBM Corp. Released 2016). Written consent was not required, given that the data were collected within the frame of epidemiological surveillance. Data were managed in accordance with the national and European Union laws. We studied 23 family clusters with a median number of 5 (range: 3-7) household members per family. In total there were 109 household members, including 66 adults and 43 children. An adult household member with COVID-19 was the first case in 21 (91.3%) family clusters and a child in 2 (8.7%). Among adults, fathers were identified as first cases in 9 clusters, mothers in 8, both parents in 2 and other relatives in 2. In terms of source of infection of the first case, 11 were community-acquired, 6 travel-associated, 3 healthcare-associated, while in 3 the source of infection could not be identified. In six (26.1%) family clusters children constituted the index cases, including five infants <3 months (clusters 13,14,15,20,22) and one adolescent girl (cluster 9). The median number of days between the onset of symptoms and the date of sample collection for SARS-CoV-2 test was 5 days, with significant difference between children (3.67±2.35 days) and adults (5.92±3.00 days) (p-value-0.019). Table 1 shows the characteristics of household members and the timeline of transmission of infection per family cluster. There was a median of 3 (range: 1-7) infected persons per cluster. The median attack rate per family cluster was 60% (range: This article is protected by copyright. All rights reserved. in 12 clusters transmission occurred from an adult to another adult. There was no evidence of child-to-adult or child-to-child transmission, although in 14 clusters there was close contact between infected children and non-infected adult household members. (Table 1 ). We studied 23 family clusters of SARS-CoV-2 infection that occurred in Greece. We found a median attack rate of 60% (up to 100% in some clusters), which demonstrates the high transmission dynamics of SARS-CoV-2. Attack rates up to 75% have been also reported in other family clusters. 7, 8 In line with studies from Switzerland and China 7,9 , in This article is protected by copyright. All rights reserved. our study adults accounted for almost all virus importations within families. Of note, five clusters were brought under attention because a young infant became ill and hospitalization was required. In terms of timing, the complete lockdown had an exceptional impact on the onset of family clusters, given that less than one-fifth of identified clusters occurred after that date. We found no case of transmission of SARS-CoV-2 infection from an infected child to another child or an adult. In a cluster of COVID-19 that occurred in the French Alps, one infected, symptomatic child had many close contacts within three different schools, yet no case of transmission was identified despite an exhaustive epidemiologic and virologic investigation. 10 This may be attributed to the fact that children with SARS-CoV-2 infection more often have an asymptomatic infection or a mild course compared to adults. 5, [7] [8] [9] 11 In our study infected children were significantly more likely to have an asymptomatic infection or a mild disease and a favorable outcome, compared to adults. The shorter time period that elapsed between the onset of symptoms and testing in children compared to adults, may be attributed to the increased awareness and high rate of healthcare seeking for ill children. It has been reported that patients with severe COVID-19 tend to have a higher viral load than those with mild disease. 12 Although the number of children in the present study was low, it was found that one third (4/12) of asymptomatic children presented high viral load. High viral load has been detected in children with no severe symptoms. 9 In our study, children were either asymptomatic or presented mild symptoms, and only infants presented a moderate form of the disease, and none presented a severe form of the disease. Most probably these findings are related with the immune response in the various age groups rather than the viral load. This article is protected by copyright. All rights reserved. Limitations of the study were the relatively low number of clusters tested and the fact that the clinical samples were taken from different sites and on different days after symptoms' onset in each patient; thus any conclusion on association of the viral load and severity of the disease cannot be drawn. In conclusion, the present study provides an insight into transmission dynamics of SARS-CoV-2 within families with children indicating that the prevalent direction of transmission is adult-to-child than child-to-adult. Contact tracing showed that in most cases the adults had contact with a confirmed COVID-19 case, thus, they were the primary source of the family infection. However, since the tracing was based on the dates of the PCR test and given that adults present symptoms in a higher proportion than children, it may happen that more adults have been identified first and the positive children were assessed as secondary cases. Therefore, a conclusion about the index case cannot be drawn with certainty and the role of children in virus transmission needs further investigation. World Health Organization, Coronavirus disease (COVID-19) pandemic National Public Health Organization, Daily report of epidemiological surveillance of COVID-19, available at: www.eody.gov.gr (accessed 27 A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-toperson transmission: a study of a family cluster Clinical characteristics of COVID-19 in children compared with adults in Shandong Province Clinical and transmission dynamics characteristics of 406 children with coronavirus disease 2019 in China: a review Sample size guidelines for logistic regression from observational studies with large population: emphasis on the accuracy between statistics and parameters based on real life clinical data Transmission potential of asymptomatic and paucisymptomatic SARS-CoV-2 infections: a three-family cluster study in China Clinical and epidemiological features of a family cluster of symptomatic and asymptomatic SARS-CoV-2 infection COVID-19 in children and the dynamics of infection in families Cluster of coronavirus disease 2019 (Covid-19) in the French Alps Clinical and epidemiological features of COVID-19 family clusters in Beijing Viral dynamics in mild and severe cases of COVID-19 We thank all patients and healthcare personnel for their assistance in data collection. We also thank Anastasia Tentoma for technical assistance. The opinions are those of the authors and do not necessarily represent those of their institutions. The data that support the findings of this study are available from the corresponding author upon reasonable request. This article is protected by copyright. All rights reserved.