APRIL 13, 2020

Compassionate use of remdesivir for severe COVID-19, decontaminating and reusing N95 respirators, and prolonged viral shedding in feces of children with COVID-19

By Denise Baez
NEW YORK -- April 13, 2020 -- In today’s DG Alert, we cover the use of remdesivir for patients with severe coronavirus disease 2019 (COVID-19), the feasibility of decontaminating and reusing N95 respirators, and the implications of prolonged viral shedding in the feces of paediatric patients with COVID-19. 
In a cohort of patients hospitalised for severe COVID-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 (68%) patients, according to a study published in The New England Journal of Medicine.
Specifically, improvement in oxygen-support status was observed in 68% of patients, and overall mortality was 13% over a median follow-up of 18 days. 
Of the patients administered remdesivir, 64% were receiving invasive ventilation at baseline, including 8% who were receiving extracorporeal membrane oxygenation (ECMO). The mortality in this subgroup was 18% compared with 5.3% in patients receiving non-invasive oxygen support. 
Jonathan Grein, MD, Cedars-Sinai Medical Center, Los Angeles, California, and colleagues stated that, initially, there were 61 patients enrolled in the study, but data from 8 patients could not be analysed (7 with no post-treatment data and 1 with a dosing error). The remaining 53 patients received a 10-day course of intravenous remdesivir (200 mg on day 1, followed by 100 mg/day for the remaining days) between January 25, 2020, and March 7, 2020, in the United States (n = 22), Italy (n = 12), Japan (n = 9), France (n = 4), Germany (n = 2), Austria (n = 1), the Netherlands (n = 1), Spain (n = 1), and Canada (n = 1).
At baseline, 30 (57%) patients were receiving mechanical ventilation and 4 (8%) were receiving ECMO. During a median follow-up of 18 days, 36 (68%) patients had an improvement in oxygen-support class, whereas 8 (15%) showed worsening. Improvement was observed in all 12 patients who were breathing ambient air or receiving low-flow supplemental oxygen and in 5 of 7 (71%) patients who were receiving non-invasive oxygen support (NIPPV; or high-flow supplemental oxygen). It is notable that 17 of 30 (57%) patients who were receiving invasive mechanical ventilation were extubated, and 3 of 4 (75%) patients receiving ECMO stopped receiving it -- all were alive at last follow-up. 
The majority (75%) of patients were male, were older than 60 years, and had coexisting conditions, the most common being hypertension, diabetes, hyperlipidaemia, and asthma. Among patients requiring invasive ventilation, 26% had hypertension, 24% had diabetes, 18% had hyperlipidaemia, and 15% had asthma. Among patients requiring non-invasive oxygen support, 21% had hypertension, 5% had diabetes, none had hyperlipidaemia, and 5% had asthma. 
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A total of 25 (47%) patients were discharged, and 7 (13%) died. Mortality was 18% (6/34) among patients receiving invasive ventilation and 5% (1/19) among those not receiving invasive ventilation.
“Interpretation of the results of this study is limited by the small size of the cohort, the relatively short duration of follow-up, potential missing data owing to the nature of the program, the lack of information on 8 of the patients initially treated, and the lack of a randomised control group,” the authors noted. “Although the latter precludes definitive conclusions, comparisons with contemporaneous cohorts from the literature, in whom general care is expected to be consistent with that of our cohort, suggest that remdesivir may have clinical benefit in patients with severe COVID-19.”
In another study, published in The Journal of Hospital Infection, researchers attempted to disinfect N95 respirators using a SteraMist Binary Ionization Technology. 
The main constituent contains 7.8% H2O2 solution which converts to ionized H2O2 (iHP) vapour after passing through a cold plasma arc, and moving like a gas throughout the surface of N95 respirator. The by-product of iHP is oxygen and water in form of humidity.
The experiment was conducted in a well-ventilated room with 6 air-change/per hour inside a biosafety level-2 microbiology laboratory with an operator wearing coverall protection gown. A set of 4 N95 respirators were horizontally hanged up and were inoculated with 10µL each of 3 different concentrations of influenza A virus subtype H1N1 to the outer and inner surfaces. Influenza A virus was chosen because it is an enveloped RNA virus which has similar virological characteristics of coronavirus.
The SteraMist was sprayed in a to-and-fro manner for 3 times at a distance of 24 inches for a total of appropriate 6 seconds treatment time. The influenza A virus inoculated N95 respirators without disinfection were used as positive control. One hour later, the pieces of N95 respirators with virus inoculation were cut out and neutralised. The virus was eluted from the N95 respirators for viral culture in MadinDarby Canine Kidney (MDCK) cell line. 
Cytopathic changes of MDCK cells were observed daily for 7 days by light microscopy. All treated pieces did not demonstrate cytopathic changes suggestive of presence of influenza A virus. They were sub-cultured to MDCK cell line again for another 7 days and no sign of cytopathic changes was observed after 7 days. Immunofluorescence staining confirmed the pieces were negative for the influenza A.
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The authors also stated the importance of testing for the particulate filtration efficiency of N95 respirators to determine the maximum number of disinfection cycle regardless of the method of disinfection. 
Lastly, a study published in the Journal of Microbiology, Immunology and Infectionshowed persistent shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in stools of infected children, raising the possibility that the virus might be transmitted through contaminated fomites.
Yu-Han Xing, MD, the Chinese University of Hong Kong, Hong Kong, China, and colleagues analysed data from 3 children with COVID-19 in Qingdao, Shandong Province, China. Patients were followed-up to March 10, 2020. Clearance of SARS-CoV-2 in respiratory tract occurred within 2 weeks after abatement of fever, whereas viral RNA remained detectable in stools of paediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 undetectable 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days.
“SARS-CoV-2 may exist in children’s gastrointestinal tract for a longer time than respiratory system,” the authors wrote. “Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.”
None of the children developed severe complications nor required intensive care or mechanical ventilation. All 3 children only presented with fever and mild cough or with no obvious symptom but non-typical radiological abnormalities, and all children showed increased lymphocytes. All children showed good response to anti-viral and supportive treatment including inhalation of interferon and oral ribavirin. 
SOURCE: The New England Journal of Medicine, The Journal of Hospital Infection, and Journal of Microbiology, Immunology and Infection