key: cord-0784355-xmik7ovl authors: Yonker, Lael M.; Neilan, Anne M.; Bartsch, Yannic; Patel, Ankit B.; Regan, James; Arya, Puneeta; Gootkind, Elizabeth; Park, Grace; Hardcastle, Margot; St. John, Anita; Appleman, Lori; Chiu, Michelle L.; Fialkowski, Allison; De La Flor, Denis; Lima, Rosiane; Bordt, Evan A.; Yockey, Laura J.; D’Avino, Paolo; Fischinger, Stephanie; Shui, Jessica E.; Lerou, Paul H.; Bonventre, Joseph V.; Yu, Xu G.; Ryan, Edward T.; Bassett, Ingrid V.; Irimia, Daniel; Edlow, Andrea G.; Alter, Galit; Li, Jonathan Z.; Fasano, Alessio title: Reply date: 2020-09-21 journal: J Pediatr DOI: 10.1016/j.jpeds.2020.09.049 sha: ccd37ed537f18f2c675d9fb017ad57094a3e9078 doc_id: 784355 cord_uid: xmik7ovl nan To the Editor: COVID-19 carries significant morbidity and mortality for adults while children have been felt to be "spared". The justification for the apparent difference in clinical response remains to be J o u r n a l P r e -p r o o f understood. We provide data pertinent to viral load, ACE2 expression and SARS-CoV-2 antibody responses for SARS-CoV-2-infected children 1 . Comparisons with adults probed for factors driving the apparent dichotomous response between children and adults following infection with SARS-CoV-2. Our data show that children can, in fact, carry high viral loads despite mild symptoms, in contrast to adults who become quite ill even as viral load wanes. We do not infer that children carry a higher viral load than adults at paralleled days of symptoms, although the sample size in our adult cohort was limited for individuals with less than seven days of symptoms. Heald-Sargent et al, however, suggested that children <5 years of age had significantly lower CT values on SARS-CoV-2 RT-PCR (and therefore higher viral load) than adults >18 years of age. 2 Comparing children with adults is justified in order to ascertain factors driving disease. Our data, combined with the study by Heald-Sargent, suggest that viral load is unlikely the sole factor driving severe disease in adults as children can also carry high viral loads. We did not culture live virus in our study. However, live virus has been shown to be readily isolated from respiratory secretions during the first week of symptoms 3 Our study was conducted from April-June 2020, when schools were shut down and in-person children's extracurricular activities were cancelled. Therefore, contact tracing of infected children at that time would have been of limited value. Despite the constraints in social interactions during the time of this study, 18% of acute pediatric SAR-CoV-2 infections and 56% of children with MIS-C did not have a known household contact 1 . This suggests that they could have contracted the virus from an asymptomatic family member or an interaction with a presymptomatic individual outside of the home. Asymptomatic individuals are recognized as carrying virus and contribution to SAR-CoV-2 transmission 5, 6 . A case series in Korea found that of 91 children exposed to adults with COVID-19, only 8.5% of these children had symptoms prior to testing positive for SARS-CoV-2, and 22% never developed symptoms. 7 Contact tracing, which relies on symptom report, could miss detection of asymptomatic individuals. More research is needed to further define how children are affected by SARS-CoV-2 infection as compared to adults, and what role children will play in the COVID-19 pandemic as schools open. Based on our data, we feel safety precautions for children of all ages are justified. Maskwearing, hand washing, physical distancing, and viral testing are logical strategies for minimizing the spread of this pandemic as children return to schools and daycares. Age-Related Differences in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Levels in Patients With Mild to Moderate Coronavirus Disease Virological assessment of hospitalized patients with COVID-2019 Asymptomatic Transmission, the Achilles' Heel of Current Strategies to Control Covid-19 Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea Clinical Characteristics and Viral RNA Detection in Children With Coronavirus Disease 2019 in the Republic of Korea