Neurologic Care of COVID-19 in Children

Abstract Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. Results A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). Conclusions Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)

The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations.

To the Editor: As of March 10, 2020, the 2019 novel coronavirus (SARS-CoV-2) has been responsible for more than 110,000 infections and 4000 deaths worldwide, but data regarding the epidemiologic characteristics and clinical features of infected children are limited. 1-3 A recent review of 72,314 cases by the Chinese Center for Disease Control and Prevention showed that less than 1% of the cases were in children younger than 10 years of age. 2 In order to determine the spectrum of disease in children, we evaluated children infected with SARS-CoV-2 and treated at the Wuhan Children’s Hospital, the only center assigned by the central government for treating infected children under 16 years of age in Wuhan. Both symptomatic and asymptomatic children with known contact with persons having confirmed or suspected SARS-CoV-2 infection were evaluated. Nasopharyngeal or throat swabs were obtained for detection of SARS-CoV-2 RNA by established methods. 4 The clinical outcomes were monitored up to March 8, 2020. Of the 1391 children assessed and tested from January 28 through February 26, 2020, a total of 171 (12.3%) were confirmed to have SARS-CoV-2 infection. Demographic data and clinical features are summarized in Table 1. (Details of the laboratory and radiologic findings are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.) The median age of the infected children was 6.7 years. Fever was present in 41.5% of the children at any time during the illness. Other common signs and symptoms included cough and pharyngeal erythema. A total of 27 patients (15.8%) did not have any symptoms of infection or radiologic features of pneumonia. A total of 12 patients had radiologic features of pneumonia but did not have any symptoms of infection. During the course of hospitalization, 3 patients required intensive care support and invasive mechanical ventilation; all had coexisting conditions (hydronephrosis, leukemia [for which the patient was receiving maintenance chemotherapy], and intussusception). Lymphopenia (lymphocyte count, <1.2×109 per liter) was present in 6 patients (3.5%). The most common radiologic finding was bilateral ground-glass opacity (32.7%). As of March 8, 2020, there was one death. A 10-month-old child with intussusception had multiorgan failure and died 4 weeks after admission. A total of 21 patients were in stable condition in the general wards, and 149 have been discharged from the hospital. This report describes a spectrum of illness from SARS-CoV-2 infection in children. In contrast with infected adults, most infected children appear to have a milder clinical course. Asymptomatic infections were not uncommon. 2 Determination of the transmission potential of these asymptomatic patients is important for guiding the development of measures to control the ongoing pandemic.