Successful combinatorial therapy of sirolimus and neuraminidase inhibitors in a patient with highly pathogenic avian influenza A (H5N6) virus: a case report

Background Highly pathogenic avian influenza A (H5N6) virus poses a continuous threat to human health since 2014. Although neuraminidase inhibitors (NAIs) are prescribed in most patients infected with the H5N6 virus, the fatality remains high, indicating the need for an improved treatment regimen. Sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), has been reported to reduce viral replication and improve clinical outcomes in severe H1N1 infections when combined with oseltamivir. Here, we report the first case of severe H5N6 pneumonia successfully treated by sirolimus and NAIs. Case Description A 22-year-old man developed high fever and chills on September 24, 2018 (Day-0) and was hospitalized on Day-3. Influenza A (H5N6) was identified on Day-6 from a throat swab specimen. Despite the administration of NAIs and other supportive measures, the patient’s clinical conditions and lung images showed continued deterioration, accompanied by persistently high viral titers. Consequently, sirolimus administration (rapamycin;2 mg per day for 14 days) was started on Day-12. His PaO2/FiO2 values and Sequential Organ Failure Assessment (SOFA) score gradually improved, and imaging outcomes revealed the resolution of bilateral lung infiltrations. The viral titer gradually decreased and turned negative on Day-25. Sirolimus and NAIs were stopped on the same day. The patient was discharged on Day-65. Based on observations from a 2-year follow-up, the patient was found to be in a good condition without complications. Conclusions In conclusion, sirolimus might be a novel and practical therapeutic approach to severe H5N6-associated pneumonia in humans.

Admission biochemical test associated with the prognosis of COVID-19: a multi-centered retrospective cohort study (preprint)

Objectives: Since December 2019, a outbreak of Corona Virus Disease-2019(COVID-19) started in Wuhan, China. Now we comprehended much more about the troublesome disease from studies than the beginning. But more details between admission laboratory test and prognosis of COVID-19 were still confusing. So we focused on the admission biochemical test, and tried to verify their influence to the prognosis of COVID-19.Method: 522 patients from 4 hospitals were enrolled in this retrospective cohort study. We collected demographic information, comorbidities and laboratory biochemical indicators, then compared them between survivors’ and nonsurvivors’ group. Logistic regression methods were used to explore the risk factors associated with in-hospital death. Linear regression and receiver operating characteristic curve(ROC-curve) was applied to assess the efficiency of risk factors and regression model.Results:Age of nonsurvivors’ group(68.9) was older than survivors group(50.0). Diabetes(68.7%) was the most common comorbidity in the nonsurvivors’ group. In univariate regression analysis, most biochemical tests were related to the mortality except lipid metabolic results. Age, fasting blood glucose and blood urea nitrogen(BUN) were with a p-value less than 0.001 in multivariate regression model.Conclusion:Age, BUN and fasting blood glucose were risk factors associated with the prognosis of COVID-19 related pneumonia.Authors Qi Long, Chen-liang Zhou, Ye-ming Wang, Bin Song, Xiao-bin Cheng, Qiu-fen Dong, and Liu-lin Wang contributed equally to this work.

Clinical findings in critical ill patients infected with SARS-Cov-2 in Guangdong Province, China: a multi-center, retrospective, observational study (preprint)

Abstract Background In December 2019, human infection with a novel coronavirus, known as SARS-CoV-2, was identified in Wuhan, China. The mortality of critical illness was high in Wuhan. Information about critically ill patients with SARS-CoV-2 infection outside of Wuhan is scarce. We aimed to provide the clinical features, treatment, and prognosis of the critically ill patients with SARS-CoV-2 infection in Guangdong Province. Methods In this multi-centered, retrospective, observational study, we enrolled critically ill patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) in Guangdong Province. Demographic data, symptoms, laboratory findings, comorbidities, treatments, and prognosis were collected. Data were compared between patients with and without intubation. Results Forty-five critically ill patients with SARS-CoV-2 pneumonia were identified in 7 ICUs in Guangdong Province. The mean age was 56.7 years, and 29 patients (64.4%) were men. The most common symptoms at the onset of illness were high fever and cough. Majority of patients presented with lymphopenia and elevated lactate dehydrogenase. Treatment with antiviral drugs was initiated in all the patients. Thirty-seven patients (82.2%) had developed acute respiratory distress syndrome, and 13 (28.9%) septic shock. A total of 20 (44.4%) patients required intubation and 9 (20%) required extracorporeal membrane oxygenation. As of February 28th 2020, only one patient (2.2%) had died and half of them had discharged of ICU. Conclusions Infection with SARS-CoV-2 in critical illness is characterized by fever, lymphopenia, acute respiratory failure and multiple organ dysfunction. Compared with critically ill patients infected with SARS-CoV-2 in Wuhan, the mortality of critically ill patients in Guangdong Province was relatively low. These data provide some general understandings and experience for the critical patients with SARS-CoV-2 outside of Wuhan.