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2.
Crit Care Nurs Q ; 43(4): 390-399, 2020.
Article in English | MEDLINE | ID: covidwho-729219

ABSTRACT

Coronavirus disease-2019 (COVID-19) creates severe respiratory distress and often a cascade of other systemic complications impacting several organ systems. The immune response includes a cytokine storm that creates many life-threatening problems including coagulopathies, arrhythmias, and secondary infections. This article discusses the multisystem responses to the physical insults created by this corona virus.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Cardiovascular System/virology , Gastrointestinal Tract/virology , Humans , Immune System/virology , Integumentary System/virology , Kidney/virology , Musculoskeletal System/virology , Nervous System/virology , Pandemics , Randomized Controlled Trials as Topic , Respiratory System/virology
3.
J Am Soc Nephrol ; 31(9): 2205-2221, 2020 09.
Article in English | MEDLINE | ID: covidwho-725838

ABSTRACT

BACKGROUND: The incidence, severity, and outcomes of AKI in COVID-19 varied in different reports. In patients critically ill with COVID-19, the clinicopathologic characteristics of AKI have not been described in detail. METHODS: This is a retrospective cohort study of 81 patients critically ill with COVID-19 in an intensive care unit. The incidence, etiologies, and outcomes of AKI were analyzed. Pathologic studies were performed in kidney tissues from ten deceased patients with AKI. RESULTS: A total of 41 (50.6%) patients experienced AKI in this study. The median time from illness to AKI was 21.0 (IQR, 9.5-26.0) days. The proportion of Kidney Disease Improving Global Outcomes (KDIGO) stage 1, stage 2, and stage 3 AKI were 26.8%, 31.7%, and 41.5%, respectively. The leading causes of AKI included septic shock (25 of 41, 61.0%), volume insufficiency (eight of 41, 19.5%), and adverse drug effects (five of 41, 12.2%). The risk factors for AKI included age (per 10 years) (HR, 1.83; 95% CI, 1.24 to 2.69; P=0.002) and serum IL-6 level (HR, 1.83; 95% CI, 1.23 to 2.73; P=0.003). KDIGO stage 3 AKI predicted death. Other potential risk factors for death included male sex, elevated D-dimer, serum IL-6 level, and higher Sequential Organ Failure Assessment score. The predominant pathologic finding was acute tubular injury. Nucleic acid tests and immunohistochemistry failed to detect the virus in kidney tissues. CONCLUSIONS: AKI was a common and multifactorial complication in patients critically ill with COVID-19 at the late stage of the disease course. The predominant pathologic finding was acute tubular injury. Older age and higher serum IL-6 level were risk factors of AKI, and KDIGO stage 3 AKI independently predicted death.


Subject(s)
Acute Kidney Injury/pathology , Betacoronavirus , Coronavirus Infections/complications , Kidney/pathology , Pneumonia, Viral/complications , Acute Kidney Injury/etiology , Aged , Aged, 80 and over , Coronavirus Infections/pathology , Creatinine/blood , Critical Illness , Female , Humans , Intensive Care Units , Interleukin-6/blood , Kidney/ultrastructure , Kidney/virology , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , Retrospective Studies , Risk Factors
4.
Am J Physiol Renal Physiol ; 318(6): F1454-F1462, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-714959

ABSTRACT

The new disease produced by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) represents a major pandemic event nowadays. Since its origin in China in December 2019, there is compelling evidence that novel SARS-CoV-2 is a highly transmissible virus, and it is associated to a broad clinical spectrum going from subclinical presentation to severe respiratory distress and multiorgan failure. Like other coronaviruses, SARS-CoV-2 recognizes human angiotensin-converting enzyme 2 as a cellular receptor that allows it to infect different host cells and likely disrupts renin-angiotensin-aldosterone system homeostasis. Particularly, a considerable incidence of many renal abnormalities associated to COVID-19 has been reported, including proteinuria, hematuria, and acute kidney injury. Moreover, it has been recently demonstrated that SARS-CoV-2 can infect podocytes and tubular epithelial cells, which could contribute to the development of the aforementioned renal abnormalities. In this review, we discuss the biological aspects of SARS-CoV-2 infection, how understanding current knowledge about SARS-CoV-2 infection may partly explain the involvement of the kidneys in the pathophysiology of COVID-19, and what questions have arisen and remain to be explored.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Kidney Diseases/virology , Kidney/virology , Pneumonia, Viral/complications , Coronavirus Infections/metabolism , Humans , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism
5.
Crit Care ; 24(1): 495, 2020 08 12.
Article in English | MEDLINE | ID: covidwho-714111

ABSTRACT

BACKGROUND: Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients. METHODS: We evaluated whether some specific post-mortem features are observed in these patients and if these changes are related to the presence of the virus in different organs. Complete macroscopic and microscopic autopsies were performed on different organs in 17 COVID-19 non-survivors. Presence of SARS-CoV-2 was evaluated with immunohistochemistry (IHC) in lung samples and with real-time reverse-transcription polymerase chain reaction (RT-PCR) test in the lung and other organs. RESULTS: Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients. Late-stage DAD, atypical pneumocytes, and/or acute pneumonia were also observed. Four lung infarcts, two acute myocardial infarctions, and one ischemic enteritis were observed. There was no evidence of myocarditis, hepatitis, or encephalitis. Kidney evaluation revealed the presence of hemosiderin in tubules or pigmented casts in most patients. Spongiosis and vascular congestion were the most frequently encountered brain lesions. No specific SARS-CoV-2 lesions were observed in any organ. IHC revealed positive cells with a heterogeneous distribution in the lungs of 11 of the 17 (65%) patients; RT-PCR yielded a wide distribution of SARS-CoV-2 in different tissues, with 8 patients showing viral presence in all tested organs (i.e., lung, heart, spleen, liver, colon, kidney, and brain). CONCLUSIONS: In conclusion, autopsies revealed a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Pneumonia, Viral/virology , Aged , Autopsy , Brain/virology , Colon/virology , Coronavirus Infections/therapy , Female , Heart/virology , Humans , Kidney/virology , Liver/virology , Lung/virology , Male , Middle Aged , Pandemics , Pneumonia, Viral/therapy , Reverse Transcriptase Polymerase Chain Reaction , Spleen/virology
6.
Dtsch Med Wochenschr ; 145(15): 1068-1073, 2020 Jul.
Article in German | MEDLINE | ID: covidwho-690651

ABSTRACT

Increasing insight into the clinical phenotype and mechanisms of SARS-CoV-2 infections and COVID-19 has identified damage of the kidneys as a key player in the course of the disease. This manuscript summarizes the current knowledge on direct viral infection of kidney tissue, proteinuria and acute kidney injury in COVID-19, and management of patients on chronic dialysis as well as after kidney transplantation. Direct infection of podocytes and proximal tubular cells by SARS-CoV-2 has been confirmed and results in proteinuria and hematuria at an early stage of COVID-19. In this context, any kidney affection is a predictor of worse outcomes among COVID-19 patients irrespective of the initial presentation and increases the risk of acute kidney injury. Specific therapies for kidney damage and acute kidney injury within COVID-19 that could be generally recommended are currently lacking. Patients on chronic hemodialysis in particular are at risk for contracting SARS-CoV-2 infections as indicated by outbreaks and super-spreading events in hemodialysis facilities. Immunosuppressive therapy after kidney transplantation needs to be adapted upon diagnosis of COVID-19 depending on the severity of the initial presentation.


Subject(s)
Acute Kidney Injury , Coronavirus Infections , Pandemics , Pneumonia, Viral , Acute Kidney Injury/physiopathology , Acute Kidney Injury/virology , Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Hematuria , Humans , Kidney/physiopathology , Kidney/virology , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Proteinuria , Renal Dialysis , Renal Insufficiency, Chronic/therapy , Risk Factors
7.
Eur Rev Med Pharmacol Sci ; 24(9): 5186-5188, 2020 05.
Article in English | MEDLINE | ID: covidwho-687446

ABSTRACT

From two COVID-19-related deaths, samples of lung, heart and kidney were collected and processed for Transmission and Scanning Electron Microscopy (TEM and SEM) with the aim of identifying the virus. Virions of SARS-CoV-2 were found in all tissues by TEM and SEM, corroborating the hypothesis that the virus enters the cells of different organs. This is the first report identifying SARS-CoV-2 in different human tissues by TEM and SEM.


Subject(s)
Betacoronavirus/isolation & purification , Betacoronavirus/ultrastructure , Coronavirus Infections/virology , Heart/virology , Kidney/virology , Lung/virology , Pneumonia, Viral/virology , Aged , Aged, 80 and over , Coronavirus Infections/pathology , Female , Humans , Kidney/pathology , Lung/pathology , Male , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Pandemics , Pneumonia, Viral/pathology
8.
J Am Soc Nephrol ; 31(9): 1959-1968, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-652873

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury by a variety of mechanisms. To date, pathologic analyses have been limited to patient reports and autopsy series. METHODS: We evaluated biopsy samples of native and allograft kidneys from patients with COVID-19 at a single center in New York City between March and June of 2020. We also used immunohistochemistry, in situ hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: The study group included 17 patients with COVID-19 (12 men, 12 black; median age of 54 years). Sixteen patients had comorbidities, including hypertension, obesity, diabetes, malignancy, or a kidney or heart allograft. Nine patients developed COVID-19 pneumonia. Fifteen patients (88%) presented with AKI; nine had nephrotic-range proteinuria. Among 14 patients with a native kidney biopsy, 5 were diagnosed with collapsing glomerulopathy, 1 was diagnosed with minimal change disease, 2 were diagnosed with membranous glomerulopathy, 1 was diagnosed with crescentic transformation of lupus nephritis, 1 was diagnosed with anti-GBM nephritis, and 4 were diagnosed with isolated acute tubular injury. The three allograft specimens showed grade 2A acute T cell-mediated rejection, cortical infarction, or acute tubular injury. Genotyping of three patients with collapsing glomerulopathy and the patient with minimal change disease revealed that all four patients had APOL1 high-risk gene variants. We found no definitive evidence of SARS-CoV-2 in kidney cells. Biopsy diagnosis informed treatment and prognosis in all patients. CONCLUSIONS: Patients with COVID-19 develop a wide spectrum of glomerular and tubular diseases. Our findings provide evidence against direct viral infection of the kidneys as the major pathomechanism for COVID-19-related kidney injury and implicate cytokine-mediated effects and heightened adaptive immune responses.


Subject(s)
Betacoronavirus , Coronavirus Infections/pathology , Kidney/pathology , Pneumonia, Viral/pathology , Adult , Aged , Betacoronavirus/isolation & purification , Biopsy , Coronavirus Infections/complications , Coronavirus Infections/immunology , Female , Humans , Kidney/ultrastructure , Kidney/virology , Kidney Diseases/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/immunology
10.
Front Immunol ; 11: 1392, 2020.
Article in English | MEDLINE | ID: covidwho-628209

ABSTRACT

Since December 2019, the ongoing coronavirus disease 2019 (COVID-19) pandemic has significantly affected solid organ transplantation (SOT) worldwide and has become a threat to the lives of SOT recipients. Here, we have reviewed, condensed, and organized the available information on COVID-19 to provide recommendations to transplant healthcare workers. Our review of reported cases shows that the symptoms of SOT patients with COVID-19 are similar to those of the normal population, but their severity and outcomes are worse. Thus far, there is no evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly causes permanent damage to kidney, liver, or heart allografts.


Subject(s)
Coronavirus Infections/pathology , Heart Transplantation/adverse effects , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Pneumonia, Viral/pathology , Adult , Aged , Betacoronavirus , Coronavirus Infections/transmission , Female , Heart/virology , Humans , Kidney/pathology , Kidney/virology , Liver/pathology , Liver/virology , Male , Middle Aged , Myocardium/pathology , Pandemics , Pneumonia, Viral/transmission , Transplant Recipients/statistics & numerical data
11.
Virol Sin ; 35(3): 311-320, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-617330

ABSTRACT

The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury (AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human renal tubule cells could be the potential host cells targeted by SARS-CoV-2. Traditional cancer cell lines or immortalized cell lines are genetically and phenotypically different from host cells. Animal models are widely used, but often fail to reflect a physiological and pathogenic status because of species tropisms. There is an unmet need for normal human epithelial cells for disease modeling. In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells (KPTECs) in 2D and 3D culture systems using conditional reprogramming (CR) and organoids techniques. These cells had the ability to differentiate and repair DNA damage, and showed no transforming property. Importantly, the CR KPTECs maintained lineage function with expression of specific transporters (SLC34A3 and cubilin). They also expressed angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV and SARS-CoV-2. In contrast, cancer cell line did not express endogenous SLC34A3, cubilin and ACE2. Very interestingly, ACE2 expression was around twofold higher in 3D organoids culture compared to that in 2D CR culture condition. Pseudovirion assays demonstrated that SARS-CoV spike (S) protein was able to enter CR cells with luciferase reporter. This integrated 2D CR and 3D organoid cultures provide a physiological ex vivo model to study kidney functions, innate immune response of kidney cells to viruses, and a novel platform for drug discovery and safety evaluation.


Subject(s)
Betacoronavirus/metabolism , Cell Culture Techniques/methods , Coronavirus Infections/virology , Coronavirus/metabolism , Epithelial Cells/virology , Kidney/virology , Pneumonia, Viral/virology , Animals , Betacoronavirus/pathogenicity , Cell Line , Coronavirus/pathogenicity , DNA Damage , Disease Models, Animal , Humans , Organoids , Pandemics , Peptidyl-Dipeptidase A/metabolism , Receptors, Cell Surface/metabolism , SARS Virus/metabolism , SARS Virus/pathogenicity , Sodium-Phosphate Cotransporter Proteins, Type IIc/metabolism , Spike Glycoprotein, Coronavirus/metabolism
12.
Intensive Care Med ; 46(7): 1339-1348, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-597960

ABSTRACT

Acute kidney injury (AKI) has been reported in up to 25% of critically-ill patients with SARS-CoV-2 infection, especially in those with underlying comorbidities. AKI is associated with high mortality rates in this setting, especially when renal replacement therapy is required. Several studies have highlighted changes in urinary sediment, including proteinuria and hematuria, and evidence of urinary SARS-CoV-2 excretion, suggesting the presence of a renal reservoir for the virus. The pathophysiology of COVID-19 associated AKI could be related to unspecific mechanisms but also to COVID-specific mechanisms such as direct cellular injury resulting from viral entry through the receptor (ACE2) which is highly expressed in the kidney, an imbalanced renin-angotensin-aldosteron system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. Non-specific mechanisms include haemodynamic alterations, right heart failure, high levels of PEEP in patients requiring mechanical ventilation, hypovolemia, administration of nephrotoxic drugs and nosocomial sepsis. To date, there is no specific treatment for COVID-19 induced AKI. A number of investigational agents are being explored for antiviral/immunomodulatory treatment of COVID-19 and their impact on AKI is still unknown. Indications, timing and modalities of renal replacement therapy currently rely on non-specific data focusing on patients with sepsis. Further studies focusing on AKI in COVID-19 patients are urgently warranted in order to predict the risk of AKI, to identify the exact mechanisms of renal injury and to suggest targeted interventions.


Subject(s)
Acute Kidney Injury/virology , Betacoronavirus/isolation & purification , Coronavirus Infections/complications , Pneumonia, Viral/complications , Renin-Angiotensin System/physiology , Acute Kidney Injury/drug therapy , Acute Kidney Injury/physiopathology , Acute Kidney Injury/therapy , Betacoronavirus/physiology , Blood Coagulation Disorders/virology , Coronavirus Infections/metabolism , Coronavirus Infections/urine , Creatinine/blood , Critical Illness , Hematuria/etiology , Humans , Kidney/physiopathology , Kidney/virology , Pandemics , Pneumonia, Viral/metabolism , Pneumonia, Viral/urine , Proteinuria/etiology , Urinalysis , Urine/chemistry , Urine/virology
13.
Virus Res ; 286: 198034, 2020 09.
Article in English | MEDLINE | ID: covidwho-348559

ABSTRACT

The angiotensin-converting enzyme 2 receptor (ACE2) is expressed in epithelial cells of many tissues including the kidney, and has been identified to interact with human pathogenic coronaviruses, including SARS-CoV-2. Although diffuse alveolar damage and acute respiratory failure are the main features of COVID-19 infection, two recent studies demonstrate that kidney impairment in hospitalized COVID-19 patients is common, and that kidney involvement is associated with high risk of in-hospital death. Interestingly, studies in rats have demonstrated that high dietary sodium intake results in down-regulation of the ACE2 expression in kidney tissue. We hypothesize that low sodium status makes kidney involvement during the course of COVID-19 infection more likely due to upregulation of membrane bound ACE2 in the kidneys. We propose that sodium intake and status should be monitored carefully during severe COVID-19 infections, and that low sodium intake be corrected early in its course, despite a potential conflict regarding common dietary recommendations to restrict dietary sodium intake in patients with hypertension, diabetes, and kidney disease.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/genetics , Kidney/drug effects , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Sodium, Dietary/pharmacology , Spike Glycoprotein, Coronavirus/genetics , Animals , Betacoronavirus/metabolism , Betacoronavirus/pathogenicity , Coronavirus Infections/metabolism , Coronavirus Infections/pathology , Coronavirus Infections/virology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Epithelial Cells/virology , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Humans , Hypertension/genetics , Hypertension/metabolism , Hypertension/pathology , Hypertension/virology , Kidney/metabolism , Kidney/pathology , Kidney/virology , Lung/metabolism , Lung/pathology , Lung/virology , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Protein Binding , Rats , Rats, Inbred SHR , Severity of Illness Index , Sodium, Dietary/metabolism , Spike Glycoprotein, Coronavirus/metabolism
15.
Nature ; 583(7818): 834-838, 2020 07.
Article in English | MEDLINE | ID: covidwho-261141

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus with high nucleotide identity to SARS-CoV and to SARS-related coronaviruses that have been detected in horseshoe bats, has spread across the world and had a global effect on healthcare systems and economies1,2. A suitable small animal model is needed to support the development of vaccines and therapies. Here we report the pathogenesis and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters (Mesocricetus auratus). Immunohistochemistry assay demonstrated the presence of viral antigens in nasal mucosa, bronchial epithelial cells and areas of lung consolidation on days 2 and 5 after inoculation with SARS-CoV-2, followed by rapid viral clearance and pneumocyte hyperplasia at 7 days after inoculation. We also found viral antigens in epithelial cells of the duodenum, and detected viral RNA in faeces. Notably, SARS-CoV-2 was transmitted efficiently from inoculated hamsters to naive hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was not as efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally infected hamsters showed apparent weight loss on days 6-7 post-inoculation or post-contact; all hamsters returned to their original weight within 14 days and developed neutralizing antibodies. Our results suggest that features associated with SARS-CoV-2 infection in golden hamsters resemble those found in humans with mild SARS-CoV-2 infections.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/transmission , Coronavirus Infections/virology , Disease Models, Animal , Lung/pathology , Lung/virology , Mesocricetus/virology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Aerosols , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/virology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antigens, Viral/immunology , Antigens, Viral/isolation & purification , Antigens, Viral/metabolism , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , Betacoronavirus/metabolism , Bronchi/pathology , Bronchi/virology , Coronavirus Infections/immunology , Duodenum/virology , Fomites/virology , Housing, Animal , Kidney/virology , Male , Mesocricetus/immunology , Nasal Mucosa/virology , Pandemics , Pneumonia, Viral/immunology , RNA, Viral/analysis , Viral Load , Weight Loss
16.
Mol Biol Rep ; 47(6): 4383-4392, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-260333

ABSTRACT

The ACE2 gene is a receptor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) for COVID-19 (coronavirus disease 2019). To analyze the expression profiles and clinical significances for this gene in humans, RNA-seq data representing 27 different tissues were analyzed using NCBI; total RNA was extracted from different tissues of mouse and semi-quantitative reverse transcriptional-polymerase chain reaction (Q-RT-PCR) was carried out. Immunohistochemistry expression profiles in normal tissues and cancer tissues and TCGA survival analysis in renal and liver cancer were conducted. ACE2 was highly conserved in different species. In normal tissues, ACE2 expression distributions were organ-specific, mainly in the kidney, male testis and female breast, and cardiovascular and gastrointestinal systems. High level of expression in testis, cardiovascular and gastrointestinal system indicated that SARS-CoV-2 might not only attack the lungs, but also affect other organs, particularly the testes, thus it may severely damage male sexual development for younger male and lead to infertility in an adult male, if he contracted COVID-19. On the other side, high expression of ACE2 was correlated with increased survival rate in renal and liver cancer, indicating that ACE2 is a prognostic marker in both renal cancer and liver cancers. Thus, the ACE2 is a functional receptor for SARS-CoV-2 and has a potential anti-tumor role in cancer. Taken together, this study may not only provide potential clues for further medical pathogenesis of COVID-19 and male fertility, but also indicate the clinical significance of the role of the ACE2 gene in cancer.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Kidney Neoplasms/genetics , Liver Neoplasms/genetics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/epidemiology , Receptors, Virus/genetics , Spike Glycoprotein, Coronavirus/genetics , Adult , Animals , Betacoronavirus/drug effects , Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/genetics , Databases, Genetic , Female , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Humans , Kidney/metabolism , Kidney/pathology , Kidney/virology , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Kidney Neoplasms/virology , Liver/metabolism , Liver/pathology , Liver/virology , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/virology , Lung/metabolism , Lung/pathology , Lung/virology , Male , Mammary Glands, Human/metabolism , Mammary Glands, Human/pathology , Mammary Glands, Human/virology , Mice , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/genetics , Protein Binding , Receptors, Virus/metabolism , Sequence Analysis, RNA , Signal Transduction , Spike Glycoprotein, Coronavirus/metabolism , Survival Analysis , Testis/metabolism , Testis/pathology , Testis/virology
19.
Cell ; 181(4): 905-913.e7, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-30638

ABSTRACT

We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000-5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Peptidyl-Dipeptidase A/pharmacology , Pneumonia, Viral/drug therapy , Recombinant Proteins/pharmacology , Animals , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Betacoronavirus/ultrastructure , Blood Vessels/virology , Chlorocebus aethiops , Humans , Kidney/cytology , Kidney/virology , Mice , Organoids/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Receptors, Virus/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
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