key: cord-344038-20n74z3o authors: Han, Mi Seon; Seong, Moon-Woo; Heo, Eun Young; Park, Ji Hong; Kim, Namhee; Shin, Sue; Cho, Sung Im; Park, Sung Sup; Choi, Eun Hwa title: Sequential analysis of viral load in a neonate and her mother infected with SARS-CoV-2 date: 2020-04-16 journal: Clin Infect Dis DOI: 10.1093/cid/ciaa447 sha: doc_id: 344038 cord_uid: 20n74z3o We report changes in viral load over time in a 27-day old neonate with COVID-19 who presented with fever, cough, and vomiting. SARS-CoV-2 RNA was detected in the nasopharynx, oropharynx, stool, saliva, plasma, and urine. The highest viral RNA copies in nasopharynx decreased over time while viral load in stool remained high. The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in China and rapidly spread worldwide, resulting in a pandemic [1] . As COVID-19 cases surge, the number of children with COVID-19 is also on the increase. Since the report of the first pediatric case in Korea, 619 cases aged <20 years (6.46% of the total cases) with COVID-19 have been reported, as of March 29, 2020 [2, 3] . Limited reports from China described the clinical manifestation of children with to be mild, and asymptomatic infections are not uncommon [4, 5] . However, it is difficult to infer whether neonates under 28 days of age with COVID-19 follow a similar clinical course because the immune system in early life is unique. Currently, only three descriptive studies on neonates with COVID-19 have been reported, and to our knowledge, none have investigated viral dynamics in infected neonates [6] [7] [8] . In this study, we described the clinical manifestation of COVID-19 in a neonate and her mother, and further analyzed the viral load kinetics of SARS-CoV-2 in clinical specimens from different sources. 4 A 27-day old neonate and her mother were diagnosed with COVID-19 and hospitalized at Seoul Metropolitan Government-Seoul National University (SMG-SNU) Boramae Medical Center on March 8, 2020. Their medical records including symptoms and signs, laboratory examination, results of SARS-CoV-2 tests, radiologic findings, and management were reviewed. The exposure route to SARS-CoV-2 was described based on the report by the local government and the history taken from the mother. RNA of the clinical specimens was extracted by using the MagNA Pure 96 DNA and Viral The 27-day old baby girl was born by vaginal delivery on February 11, 2020 at 38 weeks and 6 days' gestation with a birth weight of 3.73 kg. The neonate lived at her grandparents' house with her parents and two older siblings. She was directly breastfed from birth. On March 2, 2020, both of her grandparents started to cough and noticed sputum. On March 4, 2020, her mother reported sputum production and a sore throat, followed by chills and myalgia on the next day when the neonate developed nasal stuffiness. The baby's father reported chills and a sore throat on the same day and was confirmed with COVID-19 on March 7, 2020. Accordingly, the remaining family members were all tested for COVID-19, and the neonate and her mother along with her grandparents were confirmed with the diagnosis. The two older siblings tested negative. As the neonate and her mother had not left home since her birth, SARS-CoV-2 seemed to be transmitted from one of the family members, the source of whose infection remains unknown. On March 8, 2020, the neonate was hospitalized as she was too young and her mother was admitted in the same isolation room to take care of her. On admission, the neonate had mild fever of 37.6°C and nasal stuffiness. Blood pressure was 82/53 mmHg, heart rate 145/min, respiratory rate 62/min, and SpO 2 95%. Whole body jaundice was observed on physical examination. Lung sounds were clear on auscultation and the abdomen was soft with normoactive bowel sound. Her jaundice was presumed to be breast milk jaundice, which spontaneously resolved within 2-3 days. The neonate developed a fever up to 38.4°C along with tachycardia from the 2 nd hospital day and fever lasted for two days. She also had increased frequency of vomiting. From the 3 rd hospital day, she started to have a mild cough 6 yet did not show any signs of respiratory difficulty and was stable without requiring oxygen. No lung lesions were observable on her chest radiographs serially taken on the 1 st , 3 rd , and 5 th hospital days. The neonate's laboratory examination was unremarkable (see Supplementary Table) . No organisms grew on blood culture and urinalysis was normal. As the neonate remained well, no antiviral or antibacterial agents were administered. She fed well and continuously gained weight. The neonate's mother remained afebrile and the only complaint she had was a sore throat with mild sputum production. Laboratory findings were normal and serial chest radiographs were unremarkable. As both the neonate and her mother's viral test results were negative from two consecutive nasopharyngeal swab specimens collected ≥24 hours apart, they were discharged home on March 26, 2020. SARS-CoV-2 RNA was detected in the neonate's clinical specimens from several sources including the nasopharynx, oropharynx, plasma, urine, stool, and saliva specimens ( Figure 1A ). At the early stage of the infection, the viral load was highest in the nasopharynx (1.2 x10 10 copies/milliliter) followed by oropharyngeal swab (1.3 x10 8 copies/milliliter). The viral load in the respiratory specimens gradually decreased with time and was undetectable after 17 days from the onset of symptoms. Notably, the SARS-CoV-2 RNA in the stool sample remained high (range, 1.7 x10 6 -4.1 x10 7 copies/milliliter) until the 18 th day since the onset even though the neonate's gastrointestinal symptoms improved. The neonate also excreted the virus in urine at relatively low RNA copy numbers for more than 10 days. The viral load of the mother's respiratory and stool specimens was approximately 100-fold lower than that of the neonate's on the 10 th day from symptom onset ( Figure 1B) . The mother's plasma and urine specimens were tested negative for SARS-CoV-2. The virus was also not detected in her breast milk. 7 This study described the viral load kinetics of a neonate, the youngest COVID-19 patient in Korea as of March 29, 2020, and her mother. The neonate was febrile and SARS-CoV-2 RNA was detected in all of her clinical specimens, with high viral loads in the respiratory and stool samples. Her mother had mild symptoms with SARS-CoV-2 RNA detected in the respiratory and stool specimens at low titers. Fortunately, the neonate as well as her mother recovered well without antiviral therapies. Limited reports on neonates with COVID-19 have been published, all from Wuhan, China [6] [7] [8] . A 17-day-old neonate had mild fever, sneezing, intermittent vomiting, and diarrhea [6] . The four other neonates were diagnosed with COVID-19 shortly after the birth from mothers confirmed with COVID-19, and it remains unclear whether the cases were from intrauterine transmission or not [7, 8] . The neonates had mild symptoms and their clinical outcomes were favorable. An interesting finding in this study is that SARS-CoV-2 RNA was detected in all of the neonate's clinical specimens, including blood, urine, stool, and saliva along with the upper respiratory tract specimens. In comparison, although exposed to the same infection source, only the mother's respiratory and stool specimens were positive for SARS-CoV-2 and at a much lower viral load. These findings suggest that COVID-19 could be systemic in neonates, affecting multiple organs, including the kidney and the gastrointestinal tract. Only approximately 1-15% of the adult patients with COVID-19 had RNAemia, and no child with RNAemia has been reported so far [5, 9, 10] . To fight off virus infections in the absence of maternally transmitted IgG antibody, neonates must rely exclusively on their immature innate immune system and their own, also immature, T cells [11] . This makes them vulnerable to viral infections, including SARS-CoV-2. Although previously reported neonates with 8 COVID-19 went through favorable clinical courses, careful monitoring on this specific population at high risk is still needed until more data are available. Recent studies have reported that SARS-CoV-2 RNA could be detected in different types of clinical specimens other than respiratory tract samples [9] . Especially, stool samples could be positive for SARS-CoV-2, irrespective of the presence of gastrointestinal symptoms, and remain positive even for one month [12] . The viral load in this neonate's stool specimen World Health Organization. Coronavirus disease (COVID-19) situation report-51 First pediatric case of coronavirus disease 2019 in Korea Korea Centers for Disease Control & Prevention. The updates of COVID-19 in Republic of Korea SARS-CoV-2 infection in children A case series of children with 2019 novel coronavirus infection: clinical and epidemiological features First case of neonate infected with novel coronavirus pneumonia in China A case report of neonatal COVID-19 infection in China Neonatal early-onset infection with SARS-CoV-2 in 33 neonates born to mothers with COVID-19 in Wuhan, China Detection of SARS-CoV-2 in Different types of clinical specimens Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Development of immunity in early life Prolonged presence of SARS-CoV-2 viral RNA in faecal samples