Anti-IL6 treatment of serious COVID-19 disease: A monocentric retrospective experience

COVID-19 is causing a high influx of patients suffering from serious respiratory complications leading the necessity to find effective therapies. These patients seem to present with cytokine perturbation and high levels of IL6. Tocilizumab and sarilumab could be effective in this condition.We retrospectively collected data about 112 consecutive hospitalized in a single center.Fifty (IL6 group) treated with tocilizumab (8 mg/kg intravenously [IV], 2 infusions 12 hours apart) or sarilumab 400 mg IV once and 62 treated with the standard of care but not anti-cytokine drugs (CONTROL group).To determine whether anti-IL6 drugs are effective in improving prognosis and reducing hospitalization times and mortality in COVID-19 pneumonia.To date 84% (42/50) of IL6 group patients have already been discharged and only 2/50 are still recovered and intubated in intensive care. Six/fifty patients (12%) died: 5/6 due to severe respiratory failure within a framework of severe acute respiratory distress syndrome (ARDS), 1 suffered an acute myocardial infarction, and 1 died of massive pulmonary thromboembolism. There were no adverse treatment events or infectious complications. Compared to the CONTROL group they showed a lower mortality rate (12% versus 43%), for the same number of complications and days of hospitalization.Anti-IL6 drugs seem to be effective in the treatment of medium to severe forms of COVID-19 pneumonia reducing the risk of mortality due to multi-organ failure, acting at the systemic level and reducing inflammation levels and therefore microvascular complications. However, it is essential to identify the best time for treatment, which, if delayed, is rendered useless as well as counterproductive. Further studies and ongoing clinical trials will help us to better define patients eligible as candidates for more aggressive intervention.     

Clinical and Histopathologic Features of a Feline SARS-CoV-2 Infection Model Are Analogous to Acute COVID-19 in Humans

The emergence and ensuing dominance of COVID-19 on the world stage has emphasized the urgency of efficient animal models for the development of therapeutics for and assessment of immune responses to SARS-CoV-2 infection. Shortcomings of current animal models for SARS-CoV-2 include limited lower respiratory disease, divergence from clinical COVID-19 disease, and requirements for host genetic modifications to permit infection. In this study, n = 12 specific-pathogen-free domestic cats were infected intratracheally with SARS-CoV-2 to evaluate clinical disease, histopathologic lesions, and viral infection kinetics at 4 and 8 days post-inoculation; n = 6 sham-inoculated cats served as controls. Intratracheal inoculation of SARS-CoV-2 produced a significant degree of clinical disease (lethargy, fever, dyspnea, and dry cough) consistent with that observed in the early exudative phase of COVID-19. Pulmonary lesions such as diffuse alveolar damage, hyaline membrane formation, fibrin deposition, and proteinaceous exudates were also observed with SARS-CoV-2 infection, replicating lesions identified in people hospitalized with ARDS from COVID-19. A significant correlation was observed between the degree of clinical disease identified in infected cats and pulmonary lesions. Viral loads and ACE2 expression were also quantified in nasal turbinates, distal trachea, lungs, and other organs. Results of this study validate a feline model for SARS-CoV-2 infection that results in clinical disease and histopathologic lesions consistent with acute COVID-19 in humans, thus encouraging its use for future translational studies.     

COVID-19 and Indirect Liver Injury: A Narrative Synthesis of the Evidence

The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. The most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase, with a prevalence of 16-53% among patients. Cases with severe coronavirus disease 2019 (COVID-19) seem to have higher rates of acute liver dysfunction, and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization. Patients with chronic liver diseases also have a higher risk of severe disease and mortality (mainly seen in patients with metabolic-associated fatty liver disease). Several pathways of damage have been proposed in the liver involvement of COVID-19 patients; although, the end-cause is most likely multifactorial. Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection. This enzyme is expressed widely in cholangiocytes and less in hepatocytes. Other factors attributed to liver damage include drug-induced liver injury, uncontrolled release of proinflammatory molecules (“cytokine storm”), pneumonia-associated hypoxia, and direct damage by the infection. Hepatic steatosis, vascular thrombosis, fibrosis, and inflammatory features (including Kupffer cell hyperplasia) are the most common liver histopathological findings in deceased COVID-19 patients, suggesting important indirect mechanisms of liver damage. In this translational medicine-based narrative review, we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19, the histopathological findings, and the impact of these mechanisms in patients with chronic liver disease.     

Relationship Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Etiology of Acute Kidney Injury (AKI)

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since it was first recognized in December 2019, it has resulted in the ongoing worldwide pandemic. Although acute hypoxic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) are the main features of the disease, the involvement of other organs needs to be explored. There has been a growing concern regarding the association between acute kidney injury (AKI) and poor outcomes in SARS-CoV-2 patients. Based on current observational data, AKI is the 2^nd most common cause of morbidity and mortality behind ARDS in SARS-CoV-2 patients. Angiotensin-converting enzyme 2 (ACE2) receptor has been shown to be the cornerstone of SARS-CoV-2 infection and possibly plays a significant role in the occurrence of renal injury. The pathogenesis of AKI is likely multifactorial that involves not only direct viral invasion but also dysregulated immune response in the form of cytokine storm, ischemia to kidneys, hypercoagulable state, and rhabdomyolysis, among others. We performed a literature search of the Pubmed and Google Scholar database from 1996 to 2020 using the following keywords: severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019, angiotensin-converting enzyme 2 receptor, and acute kidney injury to find the most pertinent and highest-quality of evidence. Any cited references were reviewed to identify relevant literature. The purpose of this review is to discuss, explore, and summarize the relationship between AKI in SARS-CoV-2 patients, with a focus on its epidemiology, association with ACE2 receptors, and pathophysiology of AKI.     

OLFM4GW112/hGC-1、GRIM19及PIN1基因在12种人肿瘤细胞株中的表达分析

目的检测OLFM4^GW112/hGC-1、GRIM19及PIN1基因在12种人肿瘤细胞株中的表达,并探讨与肿瘤细胞凋亡与周期的关系。方法利用RT-PCR半定量的方法检测GW112、GRIM19与PIN1三种基因在人12种肿瘤细胞株中转录水平。结果RT-PCR结果显示：12种人肿瘤细胞株中GW112、GRIM19与PIN1三种基因均有表达,未出现转录缺失。其中胃癌细胞SGC-7901与脑胶质瘤细胞CHG-5中的GW112表达明显强于GRIM19,而在其余十种细胞株中GW112表达却明显低于GRIM19。实验组细胞中,PIN1基因只在SGC-7901株与CHG-5株中表达较弱,其余表达均较强。结论GW112、GRIM19与PIN1在这些肿瘤细胞中的表达状况很可能与它们的周期调控和细胞凋亡有关,对三种基因的表达研究可进一步对分析三种基因的功能提供依据。     

Impact of the COVID-19 pandemic on the incidence of dengue fever in Peru

Dengue virus and severe acute respiratory syndrome coronavirus 2 coexist in dengue-endemic countries; therefore, the adoption of preventive measures is essential to control the spread of both viruses. We conducted an ecological study to compare the temporal patterns of the incidence of dengue before and during the Coronavirus disease 2019 (COVID-19) pandemic in Peru. A time-series analysis comparing the incidence of dengue using a Student's t test with variance correction was performed. Poisson regression was applied to determine the incidence rate ratio (IRR) of dengue before and during the COVID-19 pandemic. The incidence of dengue was found to be increased in all endemic regions of Peru during the COVID-19 pandemic, with the highest incidences registered in Ica (IRR = 90.14), Huánuco (IRR = 38.6), and Ucayali (IRR = 23.78), with the exception of Piura (IRR = 0.83). The highest increases in the number of dengue cases per million inhabitants were in Ucayali (393.38), Tumbes (233.19), Ica (166.08), and Loreto (129.93). The gradient of dengue cases was positive in all endemic regions during the COVID-19 pandemic. The number of dengue cases per million increased during the COVID-19 pandemic throughout Peru and in several endemic regions, with the exception of Piura.