Sequential Analysis of Viral Load in a Neonate and Her Mother Infected With Severe Acute Respiratory Syndrome Coronavirus 2

Abstract

We report changes in viral load over time in a 27-day-old neonate with coronavirus disease 2019 who presented with fever, cough, and vomiting. Severe acute respiratory syndrome coronavirus 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 29 March 2020 [2, 3]. Limited reports from China have described the clinical manifestation of children with COVID-19 to be mild, and asymptomatic infections are not uncommon [4, 5].

However, it is difficult to infer whether neonates < 28 days of age with COVID-19 follow a similar clinical course, because the immune system in early life is unique. Currently, only 3 descriptive studies on neonates with COVID-19 have been reported, and to our knowledge, none has investigated viral dynamics in infected neonates [6–8]. 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.

METHODS

Clinical Analysis

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 8 March 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.

Quantitation of SARS-CoV-2

RNA of the clinical specimens was extracted by using the MagNA Pure 96 DNA and Viral NA small volume kit (Roche, Germany) according to the manufacturer’s instructions. Viral RNA was detected by using the PowerChek 2019-nCoV real-time polymerase chain reaction kit (Kogene Biotech, Seoul, Korea) for amplification of the E gene and the RNA-dependent RNA polymerase region of the ORF1b gene, and quantified with a standard curve that was constructed using in vitro transcribed RNA provided from the European Virus Archive (https://www.european-virus-archive.com). This study was approved by the Institutional Review Board at SMG-SNU Boramae Medical Center and written consent was waived.

RESULTS

Diagnosis of COVID-19

The 27-day-old baby girl was born by vaginal delivery on 11 February 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 2 older siblings. She was directly breastfed from birth. On 2 March 2020, both of her grandparents started to cough and noticed sputum. On 4 March 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 7 March 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 2 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.

Clinical Manifestation

On 8 March 2020, the neonate was hospitalized for close monitoring, 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 mm Hg, heart rate 145 beats per minute, respiratory rate 62 breaths per minute, and oxygen saturation 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 second hospital day, and fever lasted for 2 days. She also had increased frequency of vomiting. From the third hospital day, she started to have a mild cough 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 first, third, and fifth hospital days. The neonate’s laboratory examination was unremarkable (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 her only complaint 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 2 consecutive nasopharyngeal swab specimens collected ≥ 24 hours apart, they were discharged home on 26 March 2020.

Analysis of SARS-CoV-2 RNA

SARS-CoV-2 RNA was detected in the neonate’s clinical specimens from several sources including the nasopharynx, oropharynx, plasma, urine, stool, and saliva (Figure 1A). At the early stage of the infection, the viral load was highest in the nasopharynx (1.2 × 10¹⁰ copies/mL) followed by oropharyngeal swab (1.3 × 10⁸ copies/mL). 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 × 10⁶–4.1 × 10⁷ copies/mL) until the 18th 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 > 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 10th day from symptom onset (Figure 1B). The mother’s plasma and urine specimens tested negative for SARS-CoV-2. The virus was also not detected in her breast milk.

DISCUSSION

This study described the viral load kinetics of a neonate, the youngest COVID-19 patient in Korea as of 29 March 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 [6–8]. A 17-day-old neonate had mild fever, sneezing, intermittent vomiting, and diarrhea [6]. The 4 other neonates were diagnosed with COVID-19 shortly after birth from mothers confirmed with COVID-19, and it remains unclear whether the cases were from intrauterine transmission [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 immunoglobulin (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 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]. In particular, stool samples could be positive for SARS-CoV-2, irrespective of the presence of gastrointestinal symptoms, and remain positive even for 1 month [12]. The viral load in this neonate’s stool specimen remained high even after the respiratory specimens became negative. Of note, the neonate also excreted the virus in urine at low levels. Although respiratory transmission is the primary route for SARS-CoV-2, presence of SARS-CoV-2 RNA in both urine and stool in the baby is an important finding because these specimens could serve as additional vehicles for virus transmission. Whether the virus detected in urine and stool is viable and infective needs further research. Nevertheless, caregivers need to be educated to practice proper handwashing, especially when changing diapers of neonates and young infants, to prevent the spread of SARS-CoV-2 among household contacts.

This report highlights the different clinical manifestations and viral load kinetics of a neonate and her mother with COVID-19. As neonates could have systemic complications and SARS-CoV-2 could be shed for a long time in their urine and stool, close monitoring of neonates with COVID-19 and good hygiene practices by caregivers are essential.

Supplementary Data

Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

Notes

Acknowledgments. The authors greatly appreciate the tireless efforts of all the staff at the isolation unit and the department of Infection Prevention and Control at Seoul Metropolitan Government–Seoul National University Boramae Medical Center. The authors also thank all of the members of the Seoul Metropolitan Government and the Korean Centers for Disease Control and Prevention for their efforts and dedication during this outbreak.

Financial support. This research was supported by the Research Program 2020 funded by the Department of Pediatrics, Seoul National University College of Medicine Research Foundation.

Potential conflicts of interest. M. S. H. reports grants from the Research Program 2020 funded by the Department of Pediatrics, Seoul National University College of Medicine Research Foundation, during the conduct of the study. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

References

Author notes