Exosomes: Emerging implementation of nanotechnology for detecting and managing novel corona virus-SARS-CoV-2

The spread of SARS-CoV-2 as an emerging novel coronavirus disease (COVID-19) had progressed as a worldwide pandemic since the end of 2019. COVID-19 affects firstly lungs tissues which are known for their very slow regeneration. Afterwards, enormous cytokine stimulation occurs in the infected cells immediately after a lung infection which necessitates good management to save patients. Exosomes are extracellular vesicles of nanometric size released by reticulocytes on maturation and are known to mediate intercellular communications. The exosomal cargo serves as biomarkers in diagnosing various diseases;moreover, exosomes could be employed as nanocarriers in drug delivery systems. Exosomes look promising to combat the current pandemic since they contribute to the immune response against several viral pathogens. Many studies have proved the potential of using exosomes either as viral elements or host systems that acquire immune-stimulatory effects and could be used as a vaccine or drug delivery tool. It is essential to stop viral replication, prevent and reverse the massive storm of cytokine that worsens the infected patients’ situations for the management of COVID-19. The main benefits of exosomes could be;no cells will be introduced, no chance of mutation, lack of immunogenicity and the damaged genetic material that could negatively affect the recipient is avoided. Additionally, it was found that exosomes are static with no ability for in vivo reproduction. The current review article discusses the possibilities of using exosomes for detecting novel coronavirus and summarizes state of the art concerning the clinical trials initiated for examining the use of COVID-19 specific T cells derived exosomes and mesenchymal stem cells derived exosomes in managing COVID-19.

SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip

Coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCo V-2), has become a global pandemic. Clinical evidence suggests that the intestine is another high-risk organ for SARS-Co V-2 infection besides the lungs. However, a model that can accurately reflect the response of the human intestine to the virus is still lacking. Here, we created an intestinal infection model on a chip that allows the recapitulation of human relevant intestinal pathophysiology induced by SARSCo V-2 at organ level. This microengineered gut-on-chip reconstitutes the key features of the intestinal epithelium-vascular endothelium barrier through the three-dimensional(3 D) co-culture of human intestinal epithelial, mucin-secreting, and vascular endothelial cells under physiological fluid flow. The intestinal epithelium showed permissiveness for viral infection and obvious morphological changes with injury of intestinal villi, dispersed distribution of mucus-secreting cells, and reduced expression of tight junction(E-cadherin), indicating the destruction of the intestinal barrier integrity caused by virus.Moreover, the vascular endothelium exhibited abnormal cell morphology, with disrupted adherent junctions. Transcriptional analysis revealed abnormal RNA and protein metabolism, as well as activated immune responses in both epithelial and endothelial cells after viral infection(e.g., upregulated cytokine genes), which may contribute to the injury of the intestinal barrier associated with gastrointestinal symptoms. This human organ system can partially mirror intestinal barrier injury and the human response to viral infection, which is not possible in existing in vitro culture models. It provides a unique and rapid platform to accelerate COVID-19 research and develop novel therapies.

Inactivating SARS-CoV-2 by electrochemical oxidation

Fully inactivating SARS-Co V-2, the virus causing coronavirus disease 2019, is of key importance for interrupting virus transmission but is currently performed by using biologically or environmentally hazardous disinfectants. Herein, we report an eco-friendly and efficient electrochemical strategy for inactivating the SARS-Co V-2 using in-situ formed nickel oxide hydroxide as anode catalyst and sodium carbonate as electrolyte. At a voltage of 5 V, the SARS-Co V-2 viruses can be rapidly inactivated with disinfection efficiency reaching 95% in only 30 s and 99.99% in 5 min. Mass spectrometry analysis and theoretical calculations indicate that the reactive oxygen species generated on the anode can oxidize the peptide chains and induce cleavage of the peptide backbone of the receptor binding domain of the SARS-Co V-2 spike glycoprotein, and thereby disables the virus. This strategy provides a sustainable and highly efficient approach for the disinfection of the SARS-CoV-2 viruliferous aerosols and wastewater.

A Review of the Impact of Covid-19 on the Male Genito-Urinary Tract

Introduction and Objectives: Since its advent in 2019, Corona Virus Disease 19 (Covid-19) has changed everyday life in many unprecedented ways. With the availability of Covid-19 vaccines, clinical practice has stepped gradually towards its everyday routine. The clinician, however, needs to address such concerns as “Can Covid-19 present with urinary tract symptoms predominantly?”, “Can the urinary tract develop long-term Covid-19 symptoms?”, “Can Covid-19 vaccines/drug therapy cause male infertility?” Methods: This mini-review of the current literature has been carried out by searching the Pubmed database. Results and Conclusions: Our literature review suggests that there is insufficient evidence to conclude a significant impact on the urinary tract from Covid-19 infection. There is supporting evidence that mRNA anti-SARS-CoV-2 vaccines are safe for male gonads. Research to further support these conclusions is required.

福建省1例输入性新型冠状病毒全基因组测序分析

目的应用高通量测序和生物信息学分析技术,从新冠肺炎病例标本中直接测定病毒基因组,并从病毒基因组水平上了解输入性新型冠状病毒(SARS-CoV-2)的全基因组特征和变异情况,追溯病毒的潜在来源。方法选取1例福建省境外输入性SARS-CoV-2无症状感染病例的咽拭子标本,采用新冠病毒全基因组靶向扩增结合Ion S5二代测序的技术进行全基因组测序。应用多种在线病毒变异分析平台,分析病毒的变异位点;根据病毒与参考株的差异,判定病毒家系及型别。应用进化分析软件构建病毒进化树,结合病例的流行病学资料,证实病毒的来源。结果成功从1例输入性无症状感染病例标本中获得SARS-oV-全基因组序列,基因组全长29 883 bp,平均测序深度达25 762×,覆盖度达98.61%;全基因组共发生18处核苷酸突变,分布于5个编码区(ORF1ab、S、ORF3a、ORF8、N);用不同方法进行病毒分型,结果显示病毒属于L基因型欧洲家系(中国分型)、B.1.1.214分支(Pangolin分型)、20B(Nextstrain分型)、GR型(GISAID分型);进化分析显示,该病毒序列与日本参考株共同处于同一分支(B.1.1.214分支),该结果与流行病学调查发现该感染者来自日本的结果一致。结论本研究构建的测序方法和分析结果可用于新冠病毒的变异分析和病例溯源,对新冠疫情防控具有重要意义。

COVID-19-associated disseminated mucormycosis:An autopsy case report

BACKGROUND Reports of mucormycosis,an infectious disease that commonly affects immunocompromised individuals,have increased during the ongoing coronavirus disease 2019(COVID-19) pandemic.Disseminated mucormycosis associated with COVID-19 is rare but fatal and is characterized by an aggressive clinical course and delayed diagnosis.Our report documents a case of disseminated mucormycosis after COVID-19 infection.This is a rare pathological autopsy report on COVID-19-associated mucormycosis.CASE SUMMARY A 58-year-old man was transferred to our hospital with severe COVID-19 pneumonia.During treatment for acute respiratory distress syndrome,he developed intra-abdominal bleeding that required a right hemicolectomy and ileostomy for hemostasis.The ileostoma and surgical wound developed necrosis followed by sepsis and multi-organ failure,which led to death.An autopsy revealed multiple thrombi associated with Rhizopus oryzae infection,which led to the necrosis of multiple infected organs.CONCLUSION Early suspicion and diagnosis followed by treatment are keys to better outcomes of mucormycosis in patients with severe COVID-19.

Link between COVID-19 vaccines and myocardial infarction

BACKGROUND Vaccines for coronavirus disease 2019(COVID-19) include Ch Ad Ox1-SARS-COV-2(Astra Zeneca),Ad26.COV2.S(Janssen),m RNA-1273(Moderna),BNT162b2(Pfizer),BBIBP-Cor V(Sinopharm),Corona Vac(Sinovac),and Bharat Biotech BBV152(Covaxin).AIM To find the association between COVID-19 vaccines and myocardial infarction(MI).METHODS This is a systematic review that involved searching databases such as MEDLINE,EMBASE,and Pak Medi Net after making a search strategy using Me SH and Emtree terms.Eligibility criteria were set,and studies having no mention of MI as a complication of COVID-19 vaccination,protocols,genetic studies,and animal studies were excluded.Data was extracted using a predesigned extraction table,and 29 studies were selected after screening and applying the eligibility criteria.RESULTS The majority of studies mentioned Astra Zeneca(18 studies) followed by Pfizer(14 studies) and Moderna(9 studies) in subjects reporting MI after vaccination.Out of all the studies,69% reported MI cases after the first COVID-19 vaccination dose and 14% after the second,44% reported ST-segment elevation MI,and 26% reported non-ST-segment elevation MI.The mortality rate was 29% after MI.CONCLUSION In conclusion,many studies linked MI to COVID-19 vaccinations,but no definitive association could be found.

Successful recovery of COVID-19-associated recurrent diarrhea and gastrointestinal hemorrhage using convalescent plasma

Background: Gastrointestinal symptoms are not rare among coronavirus disease 2019(COVID-19) patients, but there have been no reports regarding convalescent plasma therapy for the recovery of gastrointestinal problems in COVID-19 patients.Case presentation: We present two cases of patients with COVID-19-associated recurrent diarrhea and positive fecal occult blood who successfully recovered after a one-time convalescent plasma administration.Conclusion: When COVID-19 patients develop recurrent or refractory gastrointestinal symptoms and fail to respond to the available treatment, alternative therapy with convalescent plasma administration may be considered.

Chinese Medicine in Fighting against Covid-19: Role and Inspiration

Covid-19 pandemic has caused hundreds of thousands deaths and millions of infections and continued spreading violently.Although researchers are racing to find or develop effective drugs or vaccines,no drugs from modern medical system have been proven effective and the high mutant rates of the virus may lead it resistant to whatever drugs or vaccines developed following modern drug development procedure.Current evidence has demonstrated impressive healing effects of several Chinese medicines(CMs)for Covid-19,which urges us to reflect on the role of CM in the era of modern medicine.Undoubtedly,CM could be promising resources for developing drug candidates for the treatment of Covid-19 in a way similar to the development of artemisinin.But the theory that builds CM,like the emphasis of driving away exogenous pathogen(virus,etc.)by restoring self-healing capacity rather than killing the pathogen directly from the inside and the'black-box'mode of diagnosing and treating patients,is as important,yet often ignored,an treasure as CM herbs and should be incorporated into modern medicine for future advancement and innovation of medical science.

Severe acute respiratory syndrome coronavirus protein 6 mediates ubiquitin-dependent proteosomal degradation of N-Myc(and STAT) interactor

Severe acute respiratory syndrome coronavirus(SARS-Co V) encodes eight accessory proteins, the functions of which are not yet fully understood. SARS-Co V protein 6(P6) is one of the previously studied accessory proteins that have been documented to enhance viral replication and suppress host interferon(IFN) signaling pathways. Through yeast two-hybrid screening, we identified eight potential cellular P6-interacting proteins from a human spleen c DNA library. For further investigation, we targeted the IFN signaling pathway-mediating protein, N-Myc(and STAT) interactor(Nmi). Its interaction with P6 was confirmed within cells. The results showed that P6 can promote the ubiquitin-dependent proteosomal degradation of Nmi. This study revealed a new mechanism of SARS-Co V P6 in limiting the IFN signaling to promote SARS-Co V survival in host cells.

新型冠状病毒肺炎(COVID-19)相关临床试验注册信息特征分析

目的对COVID-19相关的临床试验注册信息进行特征分析,探讨相关临床研究的特点和不足。方法检索中国临床试验注册中心(Chi CTR)网站有关COVID-19的临床研究注册信息,检索时间为2020年3月1日。对注册信息特征进行描述性分析。结果(1)共纳入有效研究282项,平均每天增长(8.3±4.8)项。(2)注册信息填写存在漏填错填现象。干预性研究中仅7.7%设置了盲法,33.0%采用多中心合作研究。研究样本量普遍偏低,少于100人的研究数占总研究数的47.5%。(3)干预措施方面,有151项为药品干预研究,共涉及75种药品。西药干预主要涉及的药品种类有抗病毒药,抗疟药和激素;研究数最多的药品是洛匹那韦/利托那韦,共有20项。有37.7%的临床研究涉及中药或中成药,还有27.8%的研究涉及生物制剂。结论COVID-19相关的临床研究数量多,增长速度快,临床研究人员科研和临床试验注册意识强。但整体临床试验设计方案质量不高,主要体现在盲法的设置和样本量设定等方面。从总体情况来看,相似的研究过多,缺乏管理部门有效的统筹安排。

Tongue and pulse features of 668 asymptomatic patients infected with the severe acute respiratory syndrome coronavirus 2 omicron variant in Shanghai

OBJECTIVE: To characterize the tongue and pulse manifestations in asymptomatic coronavirus disease 2019(COVID-19) cases in Shanghai. METHODS: We conducted a clinical study of 668 patients with asymptomatic infections in which we analyzed the tongue and pulse features in the Shanghai New International Expo Center mobile cabin hospital. The medical records of the patients, including tongue color, tongue coating, and pulse manifestations, were reviewed by healthcare workers. RESULTS: In total, 668 COVID-19 cases were included in the study. Patient age ranged from 5 to 96 years, with a median of 44.0(IQR 33.0-53.0) years. Among the patients, 6.14% had comorbidities. The most common comorbid condition was diabetes(1.65%), followed by hypertension(0.89%), coronary heart disease(0.89%), thrombotic diseases(0.89%), congestive heart failure(0.60%), and stroke(0.45%). Pink-red(75.4%) was the most common tongue color, followed by red(23.4%) and pale red(1.2%). Tongue coating color and thickness were classified as white fur(9.28%), thin and yellow fur(48.65%), white greasy fur(8.98%), yellow greasy fur(24.70%), and less coating(8.39%). In addition, a large number of patients(n = 300, 44.91%) presented superficial and rapid pulses, and 250 patients(37.4%) exhibited a slippery pulse. CONCLUSION: Our preliminary results showed that wind, heat, and dampness were the main etiologies of the severe acute respiratory syndrome coronavirus 2 Omicron(B.1.1.529) variant infection in traditional Chinese medicine. Furthermore, the main symptoms of the disease may be wind-heat invading the lung syndrome or damp-heat with the exuberance of virulence syndrome, which is of most significance in COVID-19 treatment.