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RÉSUMÉCONTEXTE:On donne de façon empirique des agents antiviraux à certains patients atteints de la maladie à coronavirus 2019 (COVID-19). Dans le but d’appuyer la rédaction de lignes directrices sur la prise en charge de la COVID-19, nous avons réalisé une revue systématique des bénéfices et des préjudices associés à 7 traitements antiviraux contre cette infection.MÉTHODES:Nous avons effectué des recherches dans MEDLINE, Embase, le Cochrane Central Register of Controlled Trials (CENTRAL), PubMed et 3 bases de données chinoises (CNKI, Wanfang Data et SinoMed) jusqu’au 19 avril 2020, dans medRxiv et ChinaXiv jusqu’au 27 avril 2020, ainsi que dans Chongqing VIP jusqu’au 30 avril 2020. Nous avons sélectionné des études sur la ribavirine, la chloroquine, l’hydroxychloroquine, l’umifénovir (Arbidol), le favipiravir, l’interféron et le lopinavir/ritonavir. Lorsqu’il n’y avait pas de données directes d’études sur la COVID-19, nous avons retenu des données indirectes d’études sur le syndrome respiratoire aigu sévère (SRAS) et le syndrome respiratoire du Moyen-Orient (SRMO) pour l’analyse de l’efficacité, et d’études sur d’autres infections respiratoires virales aiguës pour l’analyse de l’innocuité.RÉSULTATS:Le taux de décès chez les patients atteints d’une forme sans signe clinique de gravité de COVID-19 était extrêmement bas, ce qui ne permet pas de conclure à un effet important sur la mortalité. Nous n’avons obtenu que des données de très faible qualité indiquant que la plupart des traitements avaient peu ou pas de bénéfices sur les paramètres à l’étude, quelle que soit la gravité de la COVID-19. Seule exception : le traitement au lopinavir/ritonavir, pour lequel nous avons obtenu des données de faible qualité faisant état d’une réduction de la durée du séjour en unité de soins intensifs (différence des risques [DR] 5 jours de moins, intervalle de confiance [IC] de 95 % 0 à 9 jours) et de la durée d’hospitalisation (DR 1 jour de moins, IC de 95 % 0 à 2 jours). En ce qui concerne l’innocuité, les données étaient de faible ou de très faible qualité, sauf pour le traitement au lopinavir/ritonavir, où des données de qualité moyenne laissaient supposer une augmentation probable de la diarrhée, des nausées et des vomissements.INTERPRÉTATION:À l’heure actuelle, rien ne prouve de façon convaincante que les traitements antiviraux apportent des bénéfices importants dans la lutte contre la COVID-19, bien que les données propres à chaque traitement n’excluent pas cette possibilité. D’autres essais randomisés et contrôlés menés auprès de patients atteints de la COVID-19 sont nécessaires avant de pouvoir recourir à ces traitements en toute confiance.

BACKGROUND:Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19.METHODS:We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes.RESULTS:In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting.INTERPRETATION:To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.

Objective:To achieve better therapeutic results in burn wound infections and to examine alternatives to antibiotics, we designed this study to elaborate the role of myeloperoxidase (MPO) on infected burn wounds in rats.Approach:We compared chemical properties as well as bacteriostatic ability of MPO in different concentrations with NeutroPhase. Subsequently, we applied MPO (MPO group), NeutroPhase (NeutroPhase group), NaCl+H2O2(NaCl+H2O2group), or NaCl (control group) on rat dorsal burn wounds inoculated with methicillin-resistant Staphylococcus aureus(MRSA). Their effects on MRSA-colonized wounds were evaluated by microscopy, histologic section, and Western blot.Results:MPO produced more H+and HClO−, leading to a more acidic environment. Moreover, MPO inhibited the growth of MRSA more intensely after 6 h of inoculation ex vivo. In vivothe open wound rate in the MPO group was significantly lower, while the contraction rate and epithelialization rate of MPO group were higher than that of the control group, NaCl+H2O2group, and NeutroPhase group on day 20. The hematoxylin and eosin staining of MPO group showed better wound healing than other groups. More vascular endothelial growth factor (VEGF) was expressed in wound tissue of MPO group by Western blot.Innovation:This is the first study to use MPO for MRSA-colonized burn wound therapy.Conclusion:MPO displayed more effective bacteriostatic ability, possibly beneficial for MRSA-colonized wound healing.

Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants’ family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world.