key: cord-0859370-ampxubnl authors: Marsico, Concetta; Capretti, Maria Grazia; Aceti, Arianna; Vocale, Caterina; Carfagnini, Filomena; Serra, Carla; Campoli, Caterina; Lazzarotto, Tiziana; Corvaglia, Luigi title: Severe neonatal COVID‐19: Challenges in management and therapeutic approach date: 2021-11-29 journal: J Med Virol DOI: 10.1002/jmv.27472 sha: b81aeef63dc86f4962503c0ad171842d62a94b23 doc_id: 859370 cord_uid: ampxubnl Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the etiological agent of coronavirus disease 2019 (COVID‐19), may manifest as a life‐threatening respiratory infection with systemic complications. Clinical manifestations among children are generally less severe than those seen in adults, but critical cases have increasingly been reported in infants less than 1 year of age. We report a severe case of neonatal COVID‐19 requiring intensive care and mechanical ventilation, further complicated by a multidrug‐resistant Enterobacter asburiae super‐infection. Chest X‐rays, lung ultrasound, and chest computed tomography revealed extensive interstitial pneumonia with multiple consolidations, associated with persistent increased work of breathing and feeding difficulties. SARS‐CoV‐2 RNA was detected in respiratory specimens and stools, but not in other biological samples, with a rapid clearance in stools. Serological tests demonstrated a specific SARS‐CoV‐2 antibody response mounted by the neonate and sustained over time. The therapeutic approach included the use of enoxaparin and steroids which may have contributed to the bacterial complication, underlying the challenges in managing neonatal COVID‐19, where the balance between viral replication and immunomodulation maybe even more challenging than in older ages. On October 2020, a 10-day-old female infant presented to the Emergency Department for apnea and feeding difficulties and was admitted to the Neonatal Unit. She was born at 39 + 1 weeks of gestational age via vaginal delivery and prenatal history was un- Information. Chest-X-ray (CXR) showed slightly increased interstitial markings. All the family members were tested, including both parents, a 2-years-old sibling, and a grandmother and all had positive SARS-CoV-2 RNA PCR on the nasopharyngeal swab, all showing a mild symptomatic disease. Family members had not received SARS-CoV-2 vaccine, as it was not yet available in Italy. The clinical status of the baby further deteriorated, with recurrent episodes of apnea requiring intubation 6 h after admission. Laboratory tests performed upon admission were in the normal range for age, except for mild leucopenia (WBC 5640/mmc) with lymphopenia (800 × 10 9 /L). On the day of life (DOL) 11 the infant developed fever for 24 h (maximum 38.9°C). CXR progressively evolved to bilateral central interstitial opacities, associated with large amount of respiratory secretions ( Figure 1) . A Lung Ultrasound (LUS) with a high-frequency linear Probe (10 MHz) was performed at the bedside and showed pleural irregularities with two small subpleural consolidations and B lines, suggesting interstitial pneumonia (Figure 2 ). 11 The neonate was extubated on DOL 16 to high flow nasal cannula without supplemental oxygen. The CXR was slowly ameliorating ( Figure 1 ). She was weaned from respiratory support on DOL 19. On DOL 23 her clinical status deteriorated, with fever, Detection of SARS-CoV-2 virus was performed by RT-PCR following the CDC protocols. 12 This RT-PCR assay targets SARS-CoV-2 virus nucleocapsid N1 and N2 genes and the human RNase P gene. Three separate master mix sets for N1, N2, and RNase P were prepared. The PCR reaction was performed using 15 μL of each master mix (SuperScript™ III Literature that describes the epidemiology, clinical presentation, and prognosis of SARS-CoV-2 in neonates is scarce. As the number of neonatal cases around the globe continues to climb, there is the need F I G U R E 2 Lung ultrasound was performed scanning the lung in 14 different areas (three posteriors, two lateral, and two anterior). On day of life (DOL) 12 showing B lines and pleural irregularities, suggesting interstitial pneumonia; on DOL 26 showed a consolidation area that reached the pleura, appearing as inhomogeneous ipoechoic area, with irregular, blurred, and indistinct edges, and with lenticular echoes inside, representing air trapped. showing a rapid virological clearance in neonatal nasopharyngeal specimen, 3 this sample remained positive for 12 days after the first detection. As expected, SARS-CoV-2 RNA was also detected in stools since the fifth day after disease onset but with a high Ct and with rapid clearance. This finding is in contrast with the prolonged RNA shedding previously described in stools, up to 5-6 weeks after symptoms onset, and is even more curious considering the early use of steroids, which could have affected viral shedding. 16 This case report highlights how, more than a year after the emergence of the COVID-19 pandemic, the therapeutic approach of neonatal COVID-19 is still challenging. Neonates are known to be vulnerable to infectious diseases, but early reassuring reports on neonatal SARS-CoV-2 infection made us neonatologists feel out of the storm. Unfortunately, recent literature suggests that we are not: the balance between viral replication and immunomodulation in neonatal COVID-19 maybe even more challenging than in older age, and the clinical consequences of therapeutic approaches translated from adult medicine to neonatal age maybe unpredictable. The authors declare that there are no conflict of interests. Informed consent has been obtained by the subject's parents. and Tiziana Lazzarotto analyzed the laboratory and/or imaging data, providing substantial contribution for the interpretation of data, and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. The data that support the findings of this study are available on request from the corresponding author. 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