scholarly journals Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

Author(s):  
Lulin Zhou ◽  
Zubiao Niu ◽  
Xiaoyi Jiang ◽  
Zhengrong Zhang ◽  
You Zheng ◽  
...  

ABSTRACTSingle-cell RNA profiling of ACE2, the SARS-CoV-2 receptor, had proposed multiple tissue cells as the potential targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic. However, most were not echoed by the patients’ clinical manifestations, largely due to the lack of protein expression information of ACE2 and co-factors. Here, we incorporated the protein information to analyse the expression of ACE2, together with TMPRSS2 and Furin, two proteases assisting SARS-CoV-2 infection, at single cell level in situ, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are lung AT2 cells and macrophages, then cardiomyocytes and adrenal gland stromal cells, followed by stromal cells in testis, ovary and thyroid. Whereas, the polarized kidney proximal tubule cells, liver cholangiocytes and intestinal enterocytes are less likely to be the primary SARS-CoV-2 targets as ACE2 localizes at the apical region of cells, where the viruses may not readily reach. Actually, the stomach may constitute a physical barrier against SARS-CoV-2 as the acidic environment in normal stomach (pH < 2.0) could completely inactivate SARS-CoV-2 pseudo-viruses. These findings are in concert with the clinical characteristics of prominent lung symptoms, frequent heart injury, and uncommon intestinal symptoms and acute kidney injury. Together, we provide a comprehensive view on the potential SARS-CoV-2 targets by pscRNA profiling, and propose that, in addition to acute respiratory distress syndrome, attentions should also be paid to the potential injuries in cardiovascular, endocrine and reproductive systems during the treatment of COVID-19 patients.

2019 ◽  
Author(s):  
Valeria Rudman-Melnick ◽  
Mike Adam ◽  
Andrew Potter ◽  
Saagar M. Chokshi ◽  
Qing Ma ◽  
...  

SummaryAcute kidney injury (AKI) is a rapid decline of renal function, with an incidence of up to 67% of intensive care unit patients. Current treatments are merely supportive, emphasizing the need for deeper understanding that could lead to improved therapies. We used single cell RNA sequencing, in situ hybridization and protein expression analyses to create comprehensive renal cell specific transcriptional profiles of multiple AKI stages. We revealed that AKI induces marked dedifferentiation, renal developmental gene activation and mixed identities in injured renal tubules. Moreover, we identified potential pathologic crosstalk between epithelial and stromal cells, and several novel genes involved in AKI. We also demonstrated the definitive effects of age on AKI outcome, and showed that renal developmental genes hold a potential as novel AKI markers. Moreover, our study provides the resource power which will aid in unraveling the molecular genetics of AKI.


2020 ◽  
Author(s):  
Qixin Yang ◽  
Xiyao Yang

ABSTRACTBackgroundThe novel coronavirus is pandemic around the world. Several researchers have given the evidence of impacts of COVID-19 on the respiratory, cardiovascular and gastrointestinal system. Studies still have debated on kidney injury of COVID-19 patients. The purpose of the meta-analysis was to evaluate the association of kidney impairment with the development of COVID-19.MethodsThe PubMed, Embase and MedRxiv databases were searched until April 1, 2020. We extracted data from eligible studies to summarize the clinical manifestations and laboratory indexes of kidney injury on COVID-19 infection patients and further compared the prevalence of acute kidney injury (AKI) and the mean differences of three biomarkers between in ICU/severe and non-ICU/non-severe cases. Heterogeneity was evaluated using the I2 method.ResultsIn the sum of 19 studies with 4375 patients were included in this analysis. The pooled prevalence of AKI, increased serum creatinine (Scr), increased blood urea nitrogen (BUN), increased D-dimer, proteinuria and hematuria in patients with COVID-19 were 7.7%, 6.6%,6.2%, 49.8%, 42% and 30.3% respectively. Moreover, the means of Scr, BUN and D-dimer were shown 6-folds, 1.8-folds and 0.68-folds, respectively, higher in ICU/severe cases than in corresponding non-ICU/non-severe patients. The prevalence of AKI was about 17 folds higher in ICU/severe patients compared with the non-ICU/non-severe cases.ConclusionsOverall, we assessed the incidences of the clinic and laboratory features of kidney injury in COVID-19 patients. And kidney dysfunction may be a risk factor for COVID-19 patients developing into the severe condition. In reverse, COVID-19 can also cause damage to the kidney.


2021 ◽  
Vol 2 (1) ◽  
pp. 8-12
Author(s):  
Angeline S. Rajakumar ◽  
Siva R. Green ◽  
S. Lokesh ◽  
Prasanna Venkatesh ◽  
V.K. Gowtham

Globally, COVID-19 is a viral disease that has become a public health challenge in 2020. COVID-19 is caused by a novel coronavirus, SARS-CoV 2, that was first discovered in the Hubei province of China and it commonly manifests as a respiratory illness but also with symptoms ranging from mild myalgia to severe pneumonia. As our primitive understanding of this novel virus has evolved, COVID-19 has been shown to present in atypical non-pulmonary clinical manifestations, such as diarrhea, acute kidney injury, hepatic and cardiovascular abnormalities, blood coagulation and stroke along with loss of some special senses. We consolidated the publicly available information to precisely summarize the knowledge about the significant non-respiratory clinical manifestations of COVID-19.


PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241953
Author(s):  
Qixin Yang ◽  
Xiyao Yang

Background The novel coronavirus is pandemic around the world. Several researchers have given the evidence of impacts of COVID-19 on the respiratory, cardiovascular and gastrointestinal system. Studies still have debated on kidney injury of COVID-19 patients. The purpose of the meta-analysis was to evaluate the association of kidney impairment with the development of COVID-19. Methods The PubMed, Embase and MedRxiv databases were searched until May 1, 2020. We extracted data from eligible studies to summarize the clinical manifestations and laboratory indexes of kidney injury on COVID-19 infection patients and further compared the prevalence of acute kidney injury (AKI) and the mean differences of three biomarkers between in ICU/severe and non-ICU/non-severe cases. Heterogeneity was evaluated using the I2 method. Results In the sum of 24 studies with 10180 patients were included in this analysis. The pooled prevalence of AKI, increased serum creatinine (Scr), increased blood urea nitrogen (BUN), increased D-dimer, proteinuria and hematuria in patients with COVID-19 were 16.2%, 8.3%, 6.2%, 49.8%, 50.1% and 30.3% respectively. Moreover, the means of Scr, BUN and D-dimer were shown 6.4-folds, 1.8-folds and 0.67-folds, respectively, higher in ICU/severe cases than in corresponding non-ICU/non-severe patients. The prevalence of AKI was about 30 folds higher in ICU/severe patients compared with the non-ICU/non-severe cases. Conclusions Overall, we assessed the incidences of the clinic and laboratory features of kidney injury in COVID-19 patients. And kidney dysfunction may be a risk factor for COVID-19 patients developing into the severe condition. In reverse, COVID-19 can also cause damage to the kidney.


2020 ◽  
Vol 10 (01) ◽  
pp. e137-e140
Author(s):  
Mosaad Abdel-Aziz ◽  
Nada M. Abdel-Aziz ◽  
Dina M. Abdel-Aziz ◽  
Noha Azab

AbstractThe clinical manifestations of novel coronavirus disease 2019 (COVID-19) vary from mild flu-like symptoms to severe fatal pneumonia. However, children with COVID-19 may be asymptomatic or may have mild clinical symptoms. The aim of this study was to investigate clinical features of pediatric COVID-19 and to search for the factors that may mitigate the disease course. We reviewed the literature to realize the clinical features, laboratory, and radiographic data that may be diagnostic for COVID-19 among children. Also, we studied the factors that may affect the clinical course of the disease. Fever, dry cough, and fatigue are the main symptoms of pediatric COVID-19, sometimes flu-like symptoms and/or gastrointestinal symptoms may be present. Although some infected children may be asymptomatic, a recent unusual hyperinflammatory reaction with overlapping features of Kawasaki's disease and toxic shock syndrome in pediatric COVID-19 has been occasionally reported. Severe acute respiratory syndrome-coronvirus-2 (SARS-CoV-2) nucleic acid testing is the corner-stone method for the diagnosis of COVID-19. Lymphocyte count and other inflammatory markers are not essentially diagnostic; however, chest computed tomography is highly specific. Factors that may mitigate the severity of pediatric COVID-19 are home confinement with limited children activity, trained immunity caused by compulsory vaccination, the response of the angiotensin-converting enzyme 2 receptors in children is not the same as in adults, and that children are less likely to have comorbidities. As infected children may be asymptomatic or may have only mild respiratory and/or gastrointestinal symptoms that might be missed, all children for families who have a member diagnosed with COVID-19 should be investigated.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Md Anzar Alam ◽  
Mohd Abdul Gani ◽  
G. Shama ◽  
Ghulamuddin Sofi ◽  
Mohd Aleemuddin Quamri

AbstractAccording to the World Health Organization (WHO), viral diseases continue to rise, and pose a significant public health problem. Novel coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2. The pathogenesis and clinical manifestations of COVID-19 is close to Amraz-e-Wabai (epidemic diseases) which was described by Hippocrates, Galen, Aristotle, Razes, Haly Abbas, Avicenna, Jurjani etc. Presently, there is no specific or challenging treatment available for COVID-19. Renowned Unani Scholars recommended during epidemic situation to stay at home, and fumigate the shelters with aromatics herbs like Ood kham (Aquilaria agallocha Roxb.), Kundur (Boswellia serrata Roxb), Kafoor (Cinnamomum camphora L.), Sandal (Santalum album L), Hing (Ferula foetida L.) etc. Use of specific Unani formulations are claimed effective for the management of such epidemic or pandemic situation like antidotes (Tiryaqe Wabai, Tiryaqe Arba, Tiryaqe Azam, Gile Armani), Herbal Decoction (Joshandah), along with Sharbate Khaksi, Habbe Bukhar, Sharbate Zanjabeel, Khamira Marwareed, Jawarish Jalinus, and Sirka (vinegar). Such drugs are claimed for use as antioxidant, immunomodulatory, cardiotonic, and general tonic actions. The study enumerates the literature regarding management of epidemics in Unani medicine and attempts to look the same in the perspective of COVID-19 prevention and management.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanping Long ◽  
Zhijian Liu ◽  
Jinbu Jia ◽  
Weipeng Mo ◽  
Liang Fang ◽  
...  

AbstractThe broad application of single-cell RNA profiling in plants has been hindered by the prerequisite of protoplasting that requires digesting the cell walls from different types of plant tissues. Here, we present a protoplasting-free approach, flsnRNA-seq, for large-scale full-length RNA profiling at a single-nucleus level in plants using isolated nuclei. Combined with 10x Genomics and Nanopore long-read sequencing, we validate the robustness of this approach in Arabidopsis root cells and the developing endosperm. Sequencing results demonstrate that it allows for uncovering alternative splicing and polyadenylation-related RNA isoform information at the single-cell level, which facilitates characterizing cell identities.


Author(s):  
Yu Zhao ◽  
Ulf Panzer ◽  
Stefan Bonn ◽  
Christian F. Krebs

AbstractSingle-cell biology is transforming the ability of researchers to understand cellular signaling and identity across medical and biological disciplines. Especially for immune-mediated diseases, a single-cell look at immune cell subtypes, signaling, and activity might yield fundamental insights into the disease etiology, mechanisms, and potential therapeutic interventions. In this review, we highlight recent advances in the field of single-cell RNA profiling and their application to understand renal function in health and disease. With a focus on the immune system, in particular on T cells, we propose some key directions of understanding renal inflammation using single-cell approaches. We detail the benefits and shortcomings of the various technological approaches outlined and give advice on potential pitfalls and challenges in experimental setup and computational analysis. Finally, we conclude with a brief outlook into a promising future for single-cell technologies to elucidate kidney function.


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