A noninferiority randomized open-label pilot study of 3- versus 7-day influenza postexposure prophylaxis with oseltamivir in hospitalized children.

Short influenza postexposure prophylaxis (PEP) showed high efficacy in adults, but studies in children are lacking. This randomized open-label pilot trial aimed to verify noninferiority of a 3- versus 7-day prophylaxis with oral oseltamivir in hospitalized children. Influenza contacts were randomized to the 3- or 7-day group and efficacy, relative risk of adverse events (AEs), and the cumulative costs of drugs and AEs management were compared. The intention-to-treat (ITT) analysis included 59 children (n = 28 and n = 31 in the 3- and 7-day group, respectively). The efficacy was 100% (95% CI 87.7-100%) versus 93.6% (95% CI 78.6-99.2%) in the 3- and 7-day group; the differences were statistically insignificant. A per-protocol (PP) analysis including 56 patients (n = 27 and n = 29, respectively) showed 100% (95% CI 87.2-100%) and 93.1% (95% CI 77.2-99.2%) efficacy, respectively, without statistical significance. Differences were within the predefined noninferiority margin with an efficacy difference Δ = 6.45 percentage points (p.p.) with 1-sided 95% CI (- 2.8, - 1.31, p = 0.86; ITT) and Δ = 6.9 p.p. (1-sided 95% CI - 2.83, - 1.27, p = 0.85; PP). Adverse events did not differ significantly, while the cumulative costs of the prophylaxis and AEs management were higher in the 7-day group (median 10.5 euro vs. 4.5 euro, p < 0.01). This pilot study showed the noninferiority of the 3-day versus 7-day PEP, which was associated with lower costs.Trial registration number: NCT04297462, 5th March 2020, restrospectively registered.

Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1.

Sphingolipid transporter 1 (SPNS1) is a significant differentially expressed gene (DEGs) in esophageal squamous cell carcinoma (ESCC). According to 3 pairs clinic cohorts, transcriptomic (155 pairs of ESCC samples and GSE53624, and proteomic data from PXD021701 including 124 ESCC samples) we found that SPNS1 was significantly higher in ESCC tissues compared to adjacent normal esophagus tissues. ESCC patients with high SPNS1 had a significantly poorer clinical prognosis than those with low SPNS1. Knockdown of SPNS1 significantly inhibited the proliferation, migration, and invasion abilities of ESCC cells, while promoting apoptosis. And overexpression of SPNS1 exhibited opposite functions. Furthermore, ESCC cells became more sensitive to 5-fluorouracil (5-FU) when SPNS1 was knocked down. Transcriptome sequencing revealed that NEU1 was one significant DEG affected by SPNS1 and positively correlated with SPNS1 expression. Oseltamivir phosphate (OP), one NEU1 inhibitor, markedly reversed 5-FU resistance, migration, and proliferation induced by high expression of SPNS1 both in vivo and in vitro. Our findings indicated that SPNS1 might promote the progression of ESCC by upregulating NEU1 expression and influencing chemotherapy sensitivity. These results provide new perceptions into potential therapeutic targets for ESCC treatment. The present study aimed to investigate the role and underlying mechanism of SPNS1 in ESCC.

Clinical and inflammatory response to antiviral treatments in dogs with parvoviral enteritis.

BACKGROUND: Canine parvoviral enteritis (CPE) is a fatal disease worldwide. The treatment of CPE is based mainly on supportive and symptomatic treatment. Antiviral addition to the treatment may result in a higher survival. OBJECTIVES: This study evaluated the effects of antiviral treatments with a standardized treatment (ST) on the clinical and inflammatory response of dogs with naturally occurring CPE. METHODS: Twenty-eight dogs with CPE caused by canine parvovirus type 2 were divided randomly into treatment groups. The ST group received fluid, antibiotic, antiemetic, and deworming treatments. The antiviral treatment groups received the same ST with an additional antiviral drug, recombinant feline interferon omega (rFeIFN-ω), oseltamivir (OSEL) or famciclovir (FAM). RESULTS: Compared to the healthy control, the tumor necrosis factor-α, interleukin-1ß, interferon (IFN)-α, IFN-γ, haptoglobin, and C-reactive protein values were high (p < 0.05) on day zero. At presentation, mild lymphopenia, neutropenia, and a high neutrophil to lymphocyte (LYM) ratio (NLR) were also observed. Adding rFeIFN-ω to the ST produced the best improvement in the clinical score with a decreased NLR, while leucocytes remained low and inflammatory markers stayed high on day three. The survival rates of the groups were 85.7% in ST+IFN, 71.4% in ST+OSEL, 71.4% in ST+FAM, and 57.1% in ST groups on day seven. CONCLUSIONS: Antiviral drugs may be valuable in treating CPE to improve the clinical signs and survival. In addition, the decrease in NLR in favor of LYM may be an indicator of the early prognosis before the improvement of leukocytes, cytokines, and acute phase proteins in CPE.

Epidemiological survey on the benefit of neuraminidase inhibitors on severe acute respiratory syndrome due to COVID-19 / Levantamento epidemiológico do benefício de inibidores de neuraminidase na síndrome respiratória aguda grave por COVID-19 / Encuesta epidemiológica del beneficio de inhibidores de neuraminidase en síndrome respiratorio agudo severo por COVID-19

Background and objectives: The COVID-19 pandemic and its consequent severe acute respiratory syndrome (SARS) have taken the lives of millions since 2020. The use of neuraminidase inhibitors is a promising alternative in treating this disease, with several studies on off-label use being conducted since the beginning of the pandemic, but none of them have a large sample size and analyze multiple risk factors. The purpose of this article is to identify possible associations between various factors and risk of hospitalization, need for ventilation and death, as well as the influence of the prescription of Zanamivir and Oseltamivir on these same indicators. Methods: In this transversal study, approximately 900,000 medical records from all regions of Brazil were collected from the Ministry of Health database, and after that, proper statistical analysis of the variables was performed. Results: Hospitalization was associated with gender, ethnicity, education, local urbanization, State, and its percentage of elderly, as well as the climate. The prescription of Zanamivir and Oseltamivir was associated with higher incidence of symptoms, lower hospitalization and death rate, and lower need for invasive and non-invasive ventilation. Medical records from146,160 patients were excluded due to SARS not caused by COVID-19. Conclusion: From this data, it is possible to draw a risk profile for hospitalization by SARS and consider the use of Zanamivir and Oseltamivir as a treatment for these patients.(AU)

Justificativa e objetivos: A pandemia de COVID-19 e sua consequente síndrome respiratória aguda grave (SRAG) levaram milhões de pessoas a óbito desde 2020. O uso de inibidores da neuraminidase é uma alternativa promissora no tratamento dessa doença, com vários estudos sobre o uso off-label sendo conduzidos desde o início da pandemia, mas nenhum que tenha um grande tamanho amostral e que analise vários fatores de risco. O objetivo deste artigo é identificar possíveis associações entre diversos fatores e risco de hospitalização, necessidade de ventilação e óbito, assim como a influência da prescrição de Zanamivir e Oseltamivir nos mesmos indicadores. Métodos: Neste estudo transversal, foi feito o levantamento de aproximadamente 900 mil prontuários de todas as regiões do Brasil, provenientes de dados do Ministério da Saúde, e em seguida foi realizado o tratamento estatístico adequado das variáveis. Resultados: A hospitalização foi associada a sexo, etnia, escolaridade, urbanização do local, Estado e porcentagem de idosos do mesmo, assim como o clima. Já a prescrição de Zanamivir e Oseltamivir foi associada a maior incidência de sintomas, menor taxa de hospitalização e óbito e menor necessidade de ventilação invasiva e não-invasiva. Foram excluídos 146.160 prontuários devido a SRAG não ocasionada pela COVID-19. Conclusão: Com esses dados, é possível traçar um perfil de risco para hospitalização por SRAG e considerar o uso de Zanamivir e Oseltamivir como tratamento para esses pacientes.(AU)

Justificación y objetivos: la pandemia Covid-19 y su consiguiente síndrome respiratorio agudo severo (SRAS) han muerto millones de personas desde 2020. El uso de inhibidores de la neuraminidasa es una alternativa prometedora en el tratamiento de esta enfermedad, con varios estudios sobre el uso off-label que se realiza desde el principio de la pandemia, pero ninguno que tenga un tamaño de muestra grande y analice múltiples factores de riesgo. El propósito de este artículo es identificar posibles asociaciones entre varios factores y el riesgo de hospitalización, necesidad de ventilación y muerte, así como la influencia de la prescripción de Zanamivir y Oseltamivir en los mismos indicadores. Métodos: En este estudio transversal, se encuestaron a los datos del Ministerio de Salud de aproximadamente 900,000 registros de todas las regiones de Brasil, después de que se realizó un tratamiento estadístico adecuado de las variables. Resultados: La hospitalización se asoció con género, etnia, educación, urbanización del sitio, Estado y porcentaje de ancianos, así como el clima. La prescripción de zanamivir y oseltamivir se asoció con la mayor incidencia de síntomas, menor hospitalización y tasa de mortalidad y menor necesidad de ventilación invasiva y no invasiva. Se excluyeron 146,160 registros médicos debido a SRAS no causado por Covid-19. Conclusión: con estos datos, es posible dibujar un perfil de riesgo para la hospitalización por SRAS y considerar el uso de zanamivir y oseltamivir como tratamiento para estos pacientes.(AU)

Benign acute childhood myositis associated with influenza A/B in the paediatric emergency department and the efficacy of early-onset oseltamivir.

AIM: To investigate the association of benign acute childhood myositis (BACM) with respiratory viruses. Also, we aimed to assess the effect of antiviral treatment on the improvement and complications. METHODS: This study was conducted at an urban-academic emergency department during four influenza-seasons (2016-2019), retrospectively. Demographics, clinical findings, laboratories, metabolic disease analyses and serological features were extracted from the medical records. Treatments, complications and outcomes were also recorded. RESULTS: A total of 114 children were included. The median age was 7.0 (min 1.25-max 17) years and 78.9% were male. The most common symptoms were leg pain (91.2%), anorexia (54.4%), fever (45.6%), sore throat (42.1%) and walking difficulty (32.5%). On admission, the median creatine phosphokinase level was 3332 IU/L (range, 1634-50 185), median aspartate aminotransferase 107 U/L (range, 38-1798). In the multiplex polymerase chain reaction analysis, 40.4% influenza B, 36.8% influenza A, 7.8% adenovirus, 7.8% parainfluenza virus, 5.3% rhinovirus, 5.3% respiratory syncytial virus and 1.8% Mycoplasma pneumoniae were detected. Rhabdomyolysis was developed in 6.7% and acute renal failure was seen in two patients. Oseltamivir was given in 44 (38.6%) patients who had influenza A/B. Metabolic disease screening tests were performed in 33.3% of patients and metabolic diseases were detected in 4 (3.5%) patients. The median recovery time was lower in patients with oseltamivir treatment (4 (min 2-max 5) - 5 (min 3-max 10) days) (P < 0.001). CONCLUSION: Rhabdomyolysis is more common in BACM due to the influenza A virus. The early use of oseltamivir treatment was significantly associated with a shorter recovery time.

Combination of baloxavir and oseltamivir for treatment of severe influenza infection in hematopoietic cell transplant recipients: a novel treatment strategy for a high-risk population.

Baloxavir, a cap-dependent endonuclease inhibitor, was recently approved for treatment of severe influenza infections. Combining baloxavir with oseltamivir has been proposed to increase the response rate. We report 2 hematopoietic cell transplant recipients with severe influenza infections who were treated with this combination and discuss possible reasons for their different responses.

Retrospective evaluation of seven different treatment protocols in hospitalized COVID-19 patients

Background/aim: As the experience has increased regarding SARS-CoV-2 in time, treatment trends have changed since the beginning of the pandemic. This study aimed to compare the outcomes of different treatment modalities for inpatients in a tertiary pandemic hospital in Antalya, Turkey. Materials and methods: Individuals aged 18 years and above who tested positive for SARS-CoV-2 in PCR with presenting COVID-related radiological findings, hospitalized for at least 3 days, and completed follow-up between March 15, 2020 and November 30, 2020 were included in the study. Patients' data were reviewed retrospectively. Seven treatment groups based on the single or combined use of hydroxychloroquine, oseltamivir, favipiravir, and remdesivir were formed and compared in terms of mortality, survival, length of hospital stay, need for intensive care, and mechanical ventilation. Results: A total of 321 patients were included in the study. The length of hospital stay, the need for intensive care, and mechanical ventilation were lower in Group 1 (hydroxychloroquine) and Group 2 (hydroxychloroquine + oseltamivir) compared to the other groups (p < 0.05). No significant difference was determined in survival between treatment groups. Analysis of prognostic factors affecting overall survival revealed that the need for intensive care and mechanical ventilation increased mortality [11.1 times (p < 0.001) and 6.48 times (p < 0.001), respectively]. Conclusion: No significant difference was determined between different treatment protocols in terms of their impact on survival. To end the COVID-19 pandemic, there is an urgent need to develop highly efficient, rapid-acting, and orally available antiviral drugs.

A nanotechnological approach in the current therapy of COVID-19: model drug oseltamivir-phosphate loaded PLGA nanoparticles targeted with spike protein binder peptide of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is today's most serious epidemic disease threatening the human race. The initial therapeutic approach of SARS-CoV-2 disease is based upon the binding the receptor-binding site of the spike protein to the host cell's ACE-2 receptor on the plasma membrane. In this study, it is aimed to develop a biocompatible and biodegradable polymeric drug delivery system that is targeted to the relevant receptor binding site and provides controlled drug release. Oseltamivir phosphate (OP) is an orally administered antiviral prodrug for primary therapy of the disease in biochemically activated carboxylate form (oseltamivir carboxylate OC). In the presented study, model drug OP loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) targeted with spike-binding peptide 1 (SBP1) of SARS-CoV-2 were designed to be used as an efficient and prolonged released antiviral drug delivery system. RY, EE, and DL values of the OP-loaded NPs produced by the solvent evaporation method were calculated to be 59.3%, 61.4%, and 26.9%, respectively. The particle size of OP-loaded NPs and OP-loaded NPs targeted with SBP1 peptide were 162.0 ± 11.0 and 226.9 ± 21.4 nm, respectively. While the zeta potential of the produced OP-loaded NPs was achieved negatively -23.9 ± 1.21 mV), the result of the modification with SBP1 peptide this value approached zero as -4.59 ± 0.728 mV. Morphological features of the OP-loaded NPs were evaluated using FEG-SEM. The further characterization and surface modification of the NPs were analyzed by FT-IR.In-vitrorelease studies of NPs showed that sustained release of OP occurred for two months that fitting the Higuchi kinetic model. By evaluating these outputs, it was reported that surface modification of OP-loaded NPs was significantly effective on characteristics such as size, zeta potential values, surface functionality, and release behavior. The therapeutic model drug-loaded polymeric formulation targeted with a specific peptide may serve as an alternative to more effective and controlled release pharmaceuticals in the treatment of COVID-19 upon an extensive investigation.

What if COVID-19 affects the child: which weapons and how to use them.

Since the reports in Wuhan (China), in December 2019, of the first cluster of cases of pneumonia caused by the new Coronavirus called 2019-nCoV or SARS-CoV-2, there has been a pandemic spread of the infection. By now, we have no specific therapy to counteract this emergency. The latest epidemiological data suggest that children are just as likely as adults to get infected by the virus. Most of them show mild clinical pictures or are completely asymptomatic, but there is an increased risk for severe disease in infancy (<12 months of age) and in children with underlying medical conditions. In this article, research achievements on the treatment of pediatric SARS-CoV-2 infection are examined.

[Scientific research in times of pandemics.] / La ricerca scientifica in tempi di pandemia.

When a pandemic occurs, scientific research moves fast in order to achieve readily results, such as effective therapies to fight the SARS-CoV-2 and vaccines. But this high-speed science, engaged by the emergency and characterized by the explosion of online publications in preprint form not subject to scrutiny by peer reviewers, carries some risks. And it represents a challenge to maintain research integrity and to comply with those globally recognized standard principles of fairness. Competition and the pressure to publish immediately - a way of encouraging rapid data sharing - can favor the dissemination of incomplete if not erroneous results obtained from partial studies, which feed false news, such as the benefits of a drug, and illusory hopes. It is commonly through press releases that "speed science" disseminates information to an audience that wants to be informed and reassured. Financial and political interests often mix with the urgency to find solutions. Covid-19 has highlighted in particular the risk of a politicization of science at the expense of transparency.

Prevalence and correlates of chronic fatigue syndrome and post-traumatic stress disorder after the outbreak of the COVID-19.

As the SARS-COV-2 becomes a global pandemic, many researchers have a concern about the long COVID-19 complications. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a persistent, debilitating, and unexplained fatigue disorder. We investigated psychological morbidities such as CFS and post-traumatic stress disorder (PTSD) among survivors of COVID-19 over 6 months. All COVID-19 survivors from the university-affiliated hospital of Tehran, Iran, were assessed 6 months after infection onset by a previously validated questionnaire based on the Fukuda guidelines for CFS/EM and DSM-5 Checklist for PTSD (The Post-traumatic Stress Disorder Checklist for DSM-5 or PCL-5) to determine the presence of stress disorder and chronic fatigue problems. A total of 120 patients were enrolled. The prevalence rate of fatigue symptoms was 17.5%. Twelve (10%) screened positive for chronic idiopathic fatigue (CIF), 6 (5%) for CFS-like with insufficient fatigue syndrome (CFSWIFS), and 3 (2.5%) for CFS. The mean total scores in PCL-5 were 9.27 ± 10.76 (range:0-44), and the prevalence rate of PTSD was 5.8%. There was no significant association after adjusting between CFS and PTSD, gender, comorbidities, and chloroquine phosphate administration. The obtained data revealed the prevalence of CFS among patients with COVID-19, which is almost similar to CFS prevalence in the general population. Moreover, PTSD in patients with COVID-19 is not associated with the increased risk of CFS. Our study suggested that medical institutions should pay attention to the psychological consequences of the COVID-19 outbreak.

Opsoclonus-myoclonus syndrome, a post-infectious neurologic complication of COVID-19: case series and review of literature.

Opsoclonus-myoclonus-ataxia syndrome is a heterogeneous constellation of symptoms ranging from full combination of these three neurological findings to varying degrees of isolated individual sign. Since the emergence of coronavirus disease 2019 (COVID-19), neurological symptoms, syndromes, and complications associated with this multi-organ viral infection have been reported and the various aspects of neurological involvement are increasingly uncovered. As a neuro-inflammatory disorder, one would expect to observe opsoclonus-myoclonus syndrome after a prevalent viral infection in a pandemic scale, as it has been the case for many other neuro-inflammatory syndromes. We report seven cases of opsoclonus-myoclonus syndrome presumably parainfectious in nature and discuss their phenomenology, their possible pathophysiological relationship to COVID-19, and diagnostic and treatment strategy in each case. Finally, we review the relevant data in the literature regarding the opsoclonus-myoclonus syndrome and possible similar cases associated with COVID-19 and its diagnostic importance for clinicians in various fields of medicine encountering COVID-19 patients and its complications.

Antiviral treatment in COVID-19: which is the most promising?-a narrative review.

The whole world is battling through coronavirus disease 2019 (COVID-19) which is a fatal pandemic. In the early 2020, the World Health Organization (WHO) declared it as a global health emergency without definitive treatments and preventive approaches. In the absence of definitive therapeutic agents, this thorough review summarizes and outlines the potency and safety of all molecules and therapeutics which may have potential antiviral effects. A number of molecules and therapeutics licensed or being tested for some other conditions were found effective in different in vitro studies as well as in many small sample-sized clinical trials and independent case studies. However, in those clinical trials, there were some limitations which need to be overcome to find the most promising antiviral against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In conclusion, many of above-mentioned antivirals seems to have some therapeutic effects but none of them have been shown to have a strong evidence for their proper recommendation and approval in the treatment of COVID-19. Constantly evolving new evidences, exclusive adult data, language barrier, and type of study (observational, retrospective, small-sized clinical trials, or independent case series) resulted to the several limitations of this review. The need for multicentered, large sample-sized, randomized, placebo-controlled trials on COVID-19 patients to reach a proper conclusion on the most promising antiviral agent is warranted.

Baloxavir treatment of oseltamivir-resistant influenza A/H1pdm09 in two immunocompromised patients.

Few treatment options are available for oseltamivir-resistant influenza. It has been proposed that baloxavir can be effective in this setting due to its distinct mechanism of action but clinical experience is lacking for immunocompromised patients. We report two such cases treated with baloxavir after failure of oseltamivir and detection of oseltamivir resistance mutations. Baloxavir/zanamivir combination therapy was effective in one patient, but persistent viral shedding was noted with baloxavir monotherapy in the other patient.

Efficacy of oseltamivir compared with zanamivir in COPD patients with seasonal influenza virus infection: a randomized controlled trial

Influenza viruses exacerbate chronic obstructive pulmonary disease (COPD) with considerable morbidity and mortality. Zanamivir and oseltamivir are effective in treating influenza. However, their efficacy in relieving influenza symptoms in COPD patients remains unknown, with the lack of controlled trials in this subject. Therefore, we conducted this randomized controlled trial to investigate the clinical efficacy of both interventions in this population. Patients were allocated to two groups (80 patients each): oseltamivir (OSELTA) and zanamivir (ZANA) groups. Oseltamivir (75 mg) was orally administered twice daily for 5 days, while zanamivir (10 mg) was inhaled twice daily for 5 days. Clinical parameters including body temperature, influenza symptoms (i.e., sore throat, cough, etc.), and serial blood tests were recorded on days 1, 3, and 7. We analyzed primary (changes in body temperature) and secondary outcomes (changes in non-specific symptoms) using the pre-protocol and intention-to-treat analyses. Differences between groups were assessed using t-test. Oseltamivir and zanamivir significantly reduced body temperature on the 3rd day after treatment; however, the number of patients who reported clinical improvement in influenza-like symptoms was significantly higher in the OSELTA group compared to the ZANA group on days 3 (85 vs 68.8%, P=0.015) and 7 (97.5 vs 83.8%, P=0.003). However, no significant changes in hematological (white blood cells and its subtypes) and inflammatory (C-reactive protein) parameters were noted (P>0.05). Our results suggested that oseltamivir and zanamivir are effective in reducing body temperature, while oseltamivir led to better clinical improvement regarding influenza-like symptoms in patients with COPD.

Diagnostic difficulties of AH1N1 influenza infection in children with acute lymphoblastic leukemia: Two case reports.

INTRODUCTION: Children with acute lymphoblastic leukemia (ALL) are at a risk of developing influenza-related complications. Approximately 10% of influenza-infected children with ALL or other types of cancer need intensive care, and 5% of them eventually die. PATIENTS' CONCERNS: We report 2 children with ALL and the swine-origin influenza A virus infection. Diagnosing influenza in them was a challenge. Medical records of these children were reviewed for demographic, clinical, and laboratory data. Patients were hospitalized in the Department of Pediatric Hematology, Oncology, and Transplantology of the Medical University of Lublin, Poland. Case 1 involved a 2-year-old girl who, according to acute lymphoblastic leukemia intercontinental Berlin-Frankfürt-Münster protocol 2009, started chemotherapy in July 2015. She was categorized in the intermediate risk group and received the induction and consolidation phase of the therapy without severe complications. The reinduction therapy was administered in the outpatient department till the 15 day. On the 20 day of this phase, she was admitted to our department with fever, mucositis, tachypnea, abdominal pain, and diarrhea. In September 2009, a 14-year-old boy (case 2) who, according to acute lymphoblastic leukemia intercontinental Berlin-Frankfürt-Münster protocol 2002, was categorized in the high-risk (HR) group, received the induction (Protocol I) phase of therapy without severe complications. On the 7 day of the HR-1 course, he manifested fever and strong, tiring cough, followed by strong mucositis. Chemotherapy had to be interrupted in both children. DIAGNOSIS: Respiratory viral infections, causing pneumonia, occurred in both patients during anticancer treatment. Initially, the real-time polymerase chain reaction test for the swine-origin influenza A was negative in both patients, which delayed the diagnosis. Additionally, bacterial, and fungal complications were also observed. INTERVENTIONS: Both patients received oseltamivir twice a day, a broad-spectrum antibiotic, antifungal drug, and granulocyte colony growth factor. OUTCOMES: The disease progressed quickly, and our patients subsequently died. CONCLUSION: We speculated that early antiviral treatment can help in the better management of patients in the HR group. It is also important to minimize influenza morbidity and mortality by vaccinating family members, using empiric therapy, providing immediate antiviral therapy, and educating parents about hygiene measures.

Is oseltamivir suitable for fighting against COVID-19: In silico assessment, in vitro and retrospective study.

BACKGROUND: Oseltamivir is a first-line antiviral drug, especially in primary hospitals. During the ongoing outbreak of coronavirus disease 2019 (COVID-19), most patients with COVID-19 who are symptomatic have used oseltamivir. Considering its popular and important role as an antiviral drug, it is necessary to evaluate oseltamivir in the treatment of COVID-19. OBJECTIVE: To evaluate the effect of oseltamivir against COVID-19. METHODS: Swiss-model was used to construct the structure of the N-terminal RNA-binding domain (NRBD) of the nucleoprotein (NC), papain-like protease (PLpro), and RNA-directed RNA polymerase (RdRp) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). TM-align program was performed to compare the structure of the viral proteins with the structure of the neuraminidase of influenza A. Molecular docking was used to analyze the theoretical possibility of effective binding of oseltamivir with the active centers of the viral proteins. In vitro study was used to evaluate the antiviral efficiency of oseltamivir against SARS-CoV-2. By clinical case analysis, we statistically evaluated whether the history of oseltamivir use influenced the progression of the disease. RESULTS: The structures of NRBD, PLpro, and RdRp were built successfully. The results from TM-align suggested that the S protein, NRBD, 3C-like protease (3CLpro), PLPrO, and RdRp were structurally similar to the influenza A neuraminidase, with TM-scores of 0.30077, 0.19254, 0.28766, 0.30666, and 0.34047, respectively. Interestingly, the active center of 3CL pro was found to be similar to the active center from the neuraminidase of influenza A. Through an analysis of molecular docking, we discovered that oseltamivir carboxylic acid was more favorable to bind to the active site of 3CLpro effectively, but its inhibitory effect was not strong compared with the positive group. Finally, we used in vitro study and retrospective case analysis to verify our speculations. We found that oseltamivir is ineffective against SARS-CoV-2 in vitro study and the clinical use of oseltamivir did not improve the patients' symptoms and signs and did not slow the disease progression. CONCLUSIONS: We consider that oseltamivir isn't suitable for the treatment of COVID-19. During the outbreak of novel coronavirus, when oseltamivir is not effective for the patients after they take it, health workers should be highly vigilant about the possibility of COVID-19.

Informe diário de evidências COVID-19: Busca realizada em 5 de agosto de 2020 / Daily evidence report COVID-19: Search conducted on August 5, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 11 artigos e 6 protocolos.

Informe diário de evidências COVID-19: busca realizada em 6 de agosto de 2020 / Daily evidence report COVID-19: Search conducted on August 6, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 11 artigos e 10 protocolos.

Successful treatment with baloxavir marboxil of a patient with peramivir-resistant influenza A/H3N2 with a dual E119D/R292K substitution after allogeneic hematopoietic cell transplantation: a case report.

BACKGROUND: Extended use of oseltamivir in an immunocompromised host could reportedly induce neuraminidase gene mutation possibly leading to oseltamivir-resistant influenza A/H3N2 virus. To our knowledge, no report is available on the clinical course of a severely immunocompromised patient with a dual E119D/R292K neuraminidase mutated-influenza A/H3N2 during the administration of peramivir. CASE PRESENTATION: A 49-year-old male patient was admitted for second allogeneic hematopoietic cell transplantation for active acute leukemia. The patient received 5 mg prednisolone and 75 mg cyclosporine and had severe lymphopenia (70/µL). At the time of hospitalization, the patient was diagnosed with upper tract influenza A virus infection, and oseltamivir treatment was initiated immediately. However, the patient was intolerant to oseltamivir. The following day, treatment was changed to peramivir. Despite a total period of neuraminidase-inhibitor administration of 16 days, the symptoms and viral shedding continued. Changing to baloxavir marboxil resolved the symptoms, and the influenza diagnostic test became negative. Subsequently, sequence analysis of the nasopharyngeal specimen revealed the dual E119D/R292K neuraminidase mutant influenza A/H3N2. CONCLUSIONS: In a highly immunocompromised host, clinicians should take care when peramivir is used for extended periods to treat influenza virus A/H3N2 infection as this could potentially leading to a dual E119D/R292K substitution in neuraminidase protein. Baloxavir marboxil may be one of the agents that can be used to treat this type of mutated influenza virus infection.