重症呼吸道病毒感染并发/继发侵袭性真菌感染

呼吸道病毒感染是侵袭性真菌感染的独立危险因素,包括流感、SARS-CoV、MERS-CoV等冠状病毒感染在内的重症病毒感染,因其发病机制或者治疗导致的免疫功能异常而继发侵袭性真菌感染的发病率及病死率已引起临床关注。特别是近来在全球范围内爆发的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)导致的新型冠状病毒感染(COVID-19),并发/继发侵袭性真菌感染的报道日益增多。了解重症病毒感染继发侵袭性真菌感染的危险因素、免疫反应、发病机制、临床表现及诊断治疗现状,有助于选择最适的诊断和治疗方法,从而做出及时诊断和精准治疗,以显著改善患者预后,降低患者病死率。     

对新型冠状病毒肺炎继发真菌感染的思考

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)疫情十分严重,给民众的健康带来了巨大威胁。COVID-19患者可能继发侵袭性真菌感染,会严重威胁患者的生命,因此,在诊治策略上应该给予重视。除了加强高危患者中病原真菌的常规检查外,还应加大力度支持和扶持病原真菌先进检测技术的研发;此外,还应重点支持针对医疗单位、公共场所和家庭等常温环境以及体表和器物表面灭活病毒、细菌、真菌等病原体的新型技术和方法的研发。最终为国家战胜COVID-19和继发感染疫情提供新措施和新策略。     

2019冠状病毒病(COVID-19)实验室诊断方法的应用现状

严重急性呼吸综合征冠状病毒2 (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)系通过分析鉴定2019年武汉不明原因的肺炎病例而被发现。世界卫生组织将该新型冠状病毒感染的肺炎命名为2019冠状病毒病(corona virus disease 2019, COVID-19)。COVID-19的实验室诊断方法主要有基于病毒核酸的病原学检查、通过特异性抗体检测的血清学检测以及一般检查。目前,实时逆转录PCR是COVID-19确诊的金标准,但该方法存在漏检和假阴性的问题,因此,为了更有效防控COVID-19,有必要发展高质量、高敏感的诊断方法。本文综述了COVID-19实验室诊断方法的应用现状及最新进展,以期为快速准确诊断COVID-19提供参考。     

新型冠状病毒主蛋白酶抑制剂的筛选方法研究进展

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)席卷全球,具有较高的传染性和死亡率,但目前尚缺乏安全有效的COVID-19疫苗与治疗药物。新型冠状病毒主蛋白酶(main protease,Mpro)的进化高度保守,在调控新冠病毒RNA复制中具有重要的生物学功能,已成为新型广谱抗冠状病毒药物开发的理想靶标之一。简便、快速、灵敏、经济的药物高通量筛选模型的建立是高选择性Mpro抑制剂高效筛选与开发的重要基础和关键技术。本文对Mpro分子结构及其抑制剂的筛选方法研究进展进行了综述和展望,以期为靶向Mpro广谱抗冠状病毒药物的筛选与开发提供有益的借鉴和参考。     

3例COVID-19出院后核酸复检阳性患者的检测分析

新型冠状病毒(SARS-CoV-2)核酸检测是新型冠状病毒肺炎(COVID-19)病例确诊的金标准,血清抗体检测是重要辅助手段。本文对重庆市江津区中心医院3例COVID-19出院后核酸复检阳性患者,回顾性分析在疾病初期确诊、治疗出院、转诊隔离全程诊疗过程中患者临床病例及其核酸和抗体检测结果,结合患者体内新冠病毒核酸确诊到完全转阴时间变化,初步探讨COVID-19临床治愈出院患者核酸和抗体检测与疾病传染性因素的相关性,为新冠肺炎患者治疗康复过程的病毒感染监测提供参考。     

抗新型冠状病毒单克隆中和抗体药物研发进展*

随着新型冠状病毒肺炎(COVID-19)疫情在全球的不断蔓延,开发有效的治疗药物迫在眉睫。中和抗体作为最有希望的新型冠状病毒特异性治疗药物,已经在临床研究中展现很好的治疗效果。对抗新冠病毒单克隆中和抗体药物研发的进展、涉及的主要技术和主要临床试验结果进行了总结,以期为包括COVID-19在内的新发、突发传染病中和抗体药物研发提供参考。     

从多角度分析SARS-CoV-2和SARS冠状病毒(SARS-CoV)差异

新型冠状病毒肺炎(COVID-19)在全球范围内持续肆虐,感染人数与日俱增.COVID-19的病毒SARS-CoV-2与2003年发生的严重急性呼吸系统综合症冠状病毒(SARS coronavirus,SARS-CoV)同属冠状病毒.本研究就COVID-19与SARS冠状病毒的差异以及两种冠状病毒的中间宿主进行分析和探讨,并对SARS冠状病毒中间宿主果子狸的关系进行分析,以期为从野生动物角度防控病毒疾病提供参考,也为了解冠状病毒的的传播途径提供借鉴.     

本期导读

自2019年12月以来,新型冠状病毒肺炎在全球蔓延,2020年1月30日,世界卫生组织(World Health Organization,WHO)将新型冠状病毒肺炎疫情列为"国际关注的突发公共卫生事件",我国也将该病作为急性呼吸道传染病纳入《中华人民共和国传染病防治法》规定的乙类传染病,并按照甲类传染病管理。2020年2月11日,WHO正式将新型冠状病毒肺炎命名为COVID-19(Corona Virus Disease 2019)。国际病毒分类委员会将该病毒命名为严重急性呼吸系统综合征冠状病毒(severe acute respiratory syndrome coromavirus 2,SARS-CoV-2)。截止2020年8月28日全球已累计确诊24356983人,累计死亡826791人。严重危害着人类的健康和生命安全。虽然中国政府采取了最强有力的措施,社会各界一起抗击疫情,取得了显著成效。但是由于目前COVID-19疫苗尚未上市,也无特效药物,COVID-19的全球快速蔓延势头仍没有得到有效遏制。世界各国的科学家、医学家们正在努力开发针对SARS-CoV-2和COVID-19的安全有效的预防疫苗和治疗方法。     

脐带间充质干细胞治疗新型冠状病毒肺炎2例

新型冠状病毒感染疫情,已经发展为全球公共卫生紧急事件。世界卫生组织将此病毒命名为2019新型冠状病毒(2019-nCoV),将引发的疾病命名为2019冠状病毒病(Coronavirus Disease-19,COVID-19)。COVID-19患者以发热、乏力、干咳为主要临床表现,少数患者伴有鼻塞、流涕和腹泻等症状。重症患者多在发病1周后出现呼吸困难和(或)低氧血症,严重者快速进展为急性呼吸窘迫综合征、脓毒症休克、难以纠正的代谢性酸中毒和出凝血功能障碍等。COVID-19目前尚无特效治疗手段,有学者认为,避免细胞因子风暴可能是治疗COVID-19感染患者的关键。间充质干细胞(mesenchymal stem cells,MSCs)具有强大的免疫调节能力,可能对预防或减弱细胞因子风暴、降低本病的发病率和死亡率具有一定的作用。海南医学院第二附属医院于2020年2月采用脐带间充质干细胞治疗2例新型冠状病毒肺炎患者,取得一定疗效。     

新型冠状病毒实验室检测方法研究进展

世界范围内流行的SARS-CoV-2已造成大批新型冠状病毒肺炎(COVID-19)患者,严重威胁着全人类生命健康.新型冠状病毒肺炎尚没有特效药,也没有疫苗,实验室确诊新型冠状病毒肺炎,隔离传染源,尽早治愈患者对整个疫情防控起着非常重要的作用.目前实验室检测方法有病毒分离培养、实时荧光定量PCR、环介导等温扩增技术、CRISPR/Cas技术、测序技术、基因芯片和抗原抗体检测.本文就上述几种方法做一综述,为确诊COVID-19提供参考.     

COVID-19–associated mucormycosis: Evidence-based critical review of an emerging infection burden during the pandemic’s second wave in India

Coronavirus Disease 2019 (COVID-19), during the second wave in early 2021, has caused devastating chaos in India. As daily infection rates rise alarmingly, the number of severe cases has increased dramatically. The country has encountered health infrastructure inadequacy and excessive demand for hospital beds, drugs, vaccines, and oxygen. Adding more burden to such a challenging situation, mucormycosis, an invasive fungal infection, has seen a sudden surge in patients with COVID-19. The rhino-orbital-cerebral form is the most common type observed. In particular, approximately three-fourths of them had diabetes as predisposing comorbidity and received corticosteroids to treat COVID-19. Possible mechanisms may involve immune and inflammatory processes. Diabetes, when coupled with COVID-19–induced systemic immune change, tends to cause decreased immunity and an increased risk of secondary infections. Since comprehensive data on this fatal opportunistic infection are evolving against the backdrop of a major pandemic, prevention strategies primarily involve managing comorbid conditions in high-risk groups. The recommended treatment strategies primarily included surgical debridement and antifungal therapy using Amphotericin B and selected azoles. Several India-centric clinical guidelines have emerged to rightly diagnose the infection, characterise the clinical presentation, understand the pathogenesis involved, and track the disease course. Code Mucor is the most comprehensive one, which proposes a simple but reliable staging system for the rhino-orbital-cerebral form. A staging system has recently been proposed, and a dedicated registry has been started. In this critical review, we extensively analyse recent evidence and guidance on COVID-19–associated mucormycosis in India.     

COVID-19 and Fungal infections: a double debacle

Fungal infections remain hardly treatable because of unstandardized diagnostic tests, limited antifungal armamentarium, and more specifically, potential toxic interactions between antifungals and immunosuppressants used during anti-inflammatory therapies, such as those set up in critically ill COVID-19 patients. Taking into account pre-existing difficulties in treating vulnerable COVID-19 patients, any co-occurrence of infectious diseases like fungal infections constitutes a double debacle for patients, healthcare experts, and the public economy. Since the first appearance of SARS-CoV-2, a significant rise in threatening fungal co-infections in COVID-19 patients has been testified in the scientific literature. Better management of fungal infections in COVID-19 patients is, therefore, a priority and requires highlighting common risk factors, relationships with immunosuppression, as well as challenges in fungal diagnosis and treatment. The present review attempts to highlight these aspects in the three most identified causative agents of fungal co-infections in COVID-19 patients: Aspergillus, Candida, and Mucorales species.     

Possible Trichosporon asahii urinary tract infection in a critically ill COVID-19 patient

BackgroundTrichosporon asahii, an emerging fungal pathogen, has been frequently associated with invasive infections in critically ill patients.Case reportA 74-year-old male patient diagnosed with COVID-19 was admitted to an Intensive Care Unit (ICU). During hospitalization, the patient displayed episodes of bacteremia by Staphylococcus haemolyticus and a possible urinary tract infection by T. asahii. While the bacterial infection was successfully treated using broad-spectrum antibiotics, the fungal infection in the urinary tract was unsuccessfully treated with anidulafungin and persisted until the patient died.ConclusionsWith the evolving COVID-19 pandemic, invasive fungal infections have been increasingly reported, mainly after taking immunosuppressant drugs associated with long-term broad-spectrum antibiotic therapy. Although Candida and Aspergillus are still the most prevalent invasive fungi, T. asahii and other agents have emerged in critically ill patients. Therefore, a proper surveillance and diagnosing any fungal infection are paramount, particularly in COVID-19 immunocompromised populations.     

Fungal Infections in COVID-19 Intensive Care Patients

Opportunistic fungal infections increase morbidity and mortality in COVID-19 patients monitored in intensive care units (ICU). As patients’ hospitalization days in the ICU and intubation period increase, opportunistic infections also increase, which prolongs hospital stay days and elevates costs. The study aimed to describe the profile of fungal infections and identify the risk factors associated with mortality in COVID-19 intensive care patients. The records of 627 patients hospitalized in ICU with the diagnosis of COVID-19 were investigated from electronic health records and hospitalization files. The demographic characteristics (age, gender), the number of ICU hospitalization days and mortality rates, APACHE II scores, accompanying diseases, antibiotic-steroid treatments taken during hospitalization, and microbiological results (blood, urine, tracheal aspirate samples) of the patients were recorded. Opportunistic fungal infection was detected in 32 patients (5.10%) of 627 patients monitored in ICU with a COVID-19 diagnosis. The average APACHE II score of the patients was 28 ± 6. While 25 of the patients (78.12%) died, seven (21.87%) were discharged from the ICU. Candida parapsilosis (43.7%) was the opportunistic fungal agent isolated from most blood samples taken from COVID-19 positive patients. The mortality rate of COVID-19 positive patients with candidemia was 80%. While two out of the three patients (66.6%) for whom fungi were grown from their tracheal aspirate died, one patient (33.3%) was transferred to the ward. Opportunistic fungal infections increase the mortality rate of COVID-19-positive patients. In addition to the risk factors that we cannot change, invasive procedures should be avoided, constant blood sugar regulation should be applied, and unnecessary antibiotics use should be avoided.     

Secondary hemophagocytic lymphohistiocytosis versus cytokine release syndrome in severe COVID-19 patients

COVID-19 or SARS-CoV-2 infection can lead to severe acute respiratory distress syndrome/pneumonia with features of cytokine storm reminiscent of secondary hemophagocytic lymphohistiocytosis (HLH), which can be diagnosed by the calculated HScore. Recent reports have suggested favorable responses to the interleukin-1 receptor antagonist, anakinra in patients with COVID-19 associated secondary HLH. In our single institution study, we compared 14 COVID-19 cytokine storm patients with 10 secondary HLH patients seen immediately prior to the pandemic (non-COVID-19), to determine whether diagnostic features of secondary HLH were typically seen in COVID-19 patients presenting with cytokine storm. Although most of our COVID-19 patients did not fulfill diagnostic criteria for HLH, we hypothesize that identification of HLH may relate to the severity or timing of cytokine release. Based on our observations, we would suggest distinguishing between cytokine release syndrome and secondary HLH, reserving the latter term for cases fulfilling diagnostic criteria.Impact statementSevere COVID-19 associated pneumonia and acute respiratory distress syndrome has recently been described with life-threatening features of cytokine storm and loosely referred to as hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS). Although a recent report indicated favorable responses to the interleukin-1 receptor antagonist, anakinra in eight patients with COVID-19 secondary HLH diagnosed using the HScore calculation, others have suggested that the diagnosis of secondary HLH is uncommon and that the use of the HScore has limited value in guiding immunomodulatory therapy for COVID-19. Here, we provide additional perspective on this important controversy based upon comparisons between 14 COVID-19 cytokine storm patients and 10 secondary HLH patients seen immediately prior to the pandemic. We hypothesize that identification of HLH may relate to the severity or timing of cytokine release and suggest distinguishing between cytokine release syndrome and secondary HLH, reserving the latter term for cases fulfilling diagnostic criteria.     

Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): Case Report and Systematic Review of Literature

Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients. While COVID-19 associated pulmonary aspergillosis is increasingly recognized, mucormycosis is rare. We describe a case of probable pulmonary mucormycosis in a 55-year-old man with diabetes, end-stage kidney disease, and COVID-19. The index case was diagnosed with pulmonary mucormycosis 21 days following admission for severe COVID-19. He received 5 g of liposomal amphotericin B and was discharged after 54 days from the hospital. We also performed a systematic review of the literature and identified seven additional cases of COVID-19 associated mucormycosis (CAM). Of the eight cases included in our review, diabetes mellitus was the most common risk factor. Three subjects had no risk factor other than glucocorticoids for COVID-19. Mucormycosis usually developed 10–14 days after hospitalization. All except the index case died. In two subjects, CAM was diagnosed postmortem. Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. A high index of suspicion and aggressive management is required to improve outcomes.

     

Off-the-shelf mesenchymal stem cells from human umbilical cord tissue can significantly improve symptoms in COVID-19 patients: An analysis of evidential relations

Coronavirus disease-2019 (COVID-19) has affected more than 200 countries worldwide. This disease has hugely affected healthcare systems as well as the economy to an extent never seen before. To date, COVID-19 infection has led to about 165000 deaths in 150 countries. At present, there is no specific drug or efficient treatment for this disease. In this analysis based on evidential relationships of the biological characteristics of MSCs, especially umbilical cord (UC)-derived MSCs as well as the first clinical trial using MSCs for COVID-19 treatment, we discuss the use of UC-MSCs to improve the symptoms of COVID-19 in patients.     

COVID-19 Outcomes of Patients With Differentiated Thyroid Cancer: A Multicenter Los Angeles Cohort Study

ObjectiveCancer may be a risk factor for worse outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections. However, there is a significant variability across cancer types in the extent of disease burden and modalities of cancer treatment that may impact morbidity and mortality from coronavirus disease-19 (COVID-19). Therefore, we evaluated COVID-19 outcomes in patients with a differentiated thyroid cancer (DTC) history.MethodsThis is a retrospective cohort study of patients with a history of DTC and SARS-CoV2 infection from 2 academic Los Angeles healthcare systems. Demographic, thyroid cancer, and treatment data were analyzed for associations with COVID-19 outcomes.ResultsOf 21 patients with DTC and COVID-19, 8 (38.1%) were hospitalized and 2 (9.5%) died from COVID-19. Thyroid cancer initial disease burden and extent, treatment, or current response to therapy (eg, excellent vs incomplete) were not associated with COVID-19 severity in DTC patients. However, older age and the presence of a comorbidity other than DTC were significantly associated with COVID-19 hospitalization (P = .047 and P = .024, respectively). COVID-19–attributed hospitalization and mortality in DTC patients was lower than that previously reported in cancer patients, although similar to patients with nonthyroid malignancies in these centers.ConclusionThese data suggest that among patients with DTC, advanced age and comorbid conditions are significant contributors to the risk of hospitalization from SARS-CoV2 infection, rather than factors associated with thyroid cancer diagnosis, treatment, or disease burden. This multicenter report of clinical outcomes provides additional data to providers to inform DTC patients regarding their risk of COVID-19.     

COVID-19-Associated Histoplasmosis in an AIDS Patient

Mycopathologia - Most reports associating fungal infections with COVID-19 have been cases of invasive aspergillosis. Here, we report a case of severe histoplasmosis and COVID-19 infections in an...     

The rise in cases of mucormycosis,candidiasis and aspergillosis amidst COVID19

The Coronavirus outbreak globally has changed the medical system and also led to a shortage of medical facilities in both developing and underdeveloped countries. The COVID19 disease, being novel in nature along with high infectivity and frequent mutational rate, has been termed to be fatal across the globe. The advent of infection by SARS-CoV-2 has brought a myriad of secondary complications and comorbidities resulting in additional challenges to the health care system induced by novel therapeutic procedures. The emerging variant with respect to the Indian subcontinent and the associated genetic mutations have worsened the situation at hand. Proper clinical management along with epidemiological studies and clinical presentations in scientific studies and trials is necessary in order to combat the simultaneous waves of emerging strains. This article summarizes three of the major fungal outbreaks in India namely mucormycosis, candidiasis and aspergillosis, and elaborates their subtypes, pathogenesis, symptoms and treatment and detection techniques. A detail of future therapeutics under consideration are also elaborated along with a general hypothesis on how COVID19 is related to immunological advances leading to major widespread fungal infection in the country. The factors that contribute in promoting virus proliferation and invasive fungal infections include cell-mediated immunity, associated immunocompromised conditions and treatment protocols that slows down immune mechanisms. To better comprehend a fungal or bacterial outbreak, it is very important to conduct audits mediated through multicenter national and state research teams for recognizing patterns and studying current cases of fungal infection in both healthy and comorbid groups of COVID19 patients.