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1.
Kidney Int ; 98(1): 232-233, 2020 07.
Article in English | MEDLINE | ID: covidwho-1382624
2.
Int J Mol Sci ; 21(9)2020 Apr 30.
Article in English | MEDLINE | ID: covidwho-1934078

ABSTRACT

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) initiates the cytokine/chemokine storm-mediated lung injury. The SARS-CoV unique domain (SUD) with three macrodomains (N, M, and C), showing the G-quadruplex binding activity, was examined the possible role in SARS pathogenesis in this study. The chemokine profile analysis indicated that SARS-CoV SUD significantly up-regulated the expression of CXCL10, CCL5 and interleukin (IL)-1ß in human lung epithelial cells and in the lung tissues of the mice intratracheally instilled with the recombinant plasmids. Among the SUD subdomains, SUD-MC substantially activated AP-1-mediated CXCL10 expression in vitro. In the wild type mice, SARS-CoV SUD-MC triggered the pulmonary infiltration of macrophages and monocytes, inducing CXCL10-mediated inflammatory responses and severe diffuse alveolar damage symptoms. Moreover, SUD-MC actuated NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-dependent pulmonary inflammation, as confirmed by the NLRP3 inflammasome inhibitor and the NLRP3-/- mouse model. This study demonstrated that SARS-CoV SUD modulated NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation, providing the potential therapeutic targets for developing the antiviral agents.


Subject(s)
Chemokine CXCL10/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , SARS Virus/metabolism , Viral Proteins/metabolism , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/immunology , Cell Line , Chemokine CXCL10/genetics , Disease Models, Animal , Humans , Lung/metabolism , Lung/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Monocytes/immunology , Monocytes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/deficiency , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Pneumonia/pathology , Pneumonia/virology , Promoter Regions, Genetic , SARS Virus/isolation & purification , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology , Up-Regulation , Viral Proteins/chemistry , Viral Proteins/genetics
3.
J Chin Med Assoc ; 2022 Jul 11.
Article in English | MEDLINE | ID: covidwho-1931931

ABSTRACT

The SARS-CoV-2 coronavirus and its variants of concern can infect people of all ages and can cause severe diseases in children, such as encephalitis, which require intensive care. Therefore, vaccines are urgently required to prevent severe disease in all age groups. We reviewed the safety and efficacy profiles of mRNA vaccines-BNT162b2 and mRNA-1273-demonstrated by clinical trials or observed in the real world. mRNA-1273 is effective in preventing SARS-CoV-2 infection in preschool children (6 months-6 years old). Both BNT162b2 and mRNA-1273 are effective in preventing SARS-CoV-2 infection in school-aged children and adolescents, thereby preventing post-COVID conditions. The common side effects of vaccination are pain at the injection site, fatigue, and headache. Myocarditis and pericarditis are uncommon. Monitoring post-vaccination troponin levels may help prevent severe cardiac events. The SARS-CoV-2 coronavirus mutates its genome to overcome the herd immunity provided by mass vaccinations; therefore, we may need to develop new generations of vaccines, such as those using viral nucleocapsid proteins as antigens. In conclusion, the mRNA vaccines are generally safe and effective in preventing severe diseases and hospitalization among children and adolescents.

4.
Scholarship of Teaching and Learning in Psychology ; : No Pagination Specified, 2022.
Article in English | APA PsycInfo | ID: covidwho-1931349

ABSTRACT

COVID-19 increased problems of access for students, particularly for students who experience diverse dimensions of minoritization in the university (e.g., first generation [FG] to college, students of color, low-income). Here, access refers to institutional policies and practices that offer equitable learning and educational opportunities. To date, limited research has focused on how minoritized students grappled with challenges of access during their day-to-day experiences of pandemic-era remote learning. The present study fills this gap by documenting how minoritized undergraduate students navigated challenges related to access and how, in community with others, they leveraged strengths to expand opportunities for access. Fifteen undergraduate seniors-the majority of whom identified as FG, low-income, and/or students of color-participated in in-depth interviews during their first term of pandemic-era remote learning. The results illustrated how remote learning both limited and broadened four areas of access: learning space, learning materials, course participation, and social connections and community. We documented how flexible and collaborative practices with instructors, peers, and family provided a powerful approach to strengthening access to learning across all four areas. The results provide critical insights, as shared by students themselves, on how institutions of higher education can reduce longstanding and new inequities and invest in strategies for expanding access. Such insights are timely for continued learning in remote instruction and for consideration of long-term practices as we shift back to forms of in-person learning. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

5.
Biomedicine (Taipei) ; 12(2): 40-46, 2022.
Article in English | MEDLINE | ID: covidwho-1897355

ABSTRACT

Objectives: This study examined analytical sensitivity, specificity, and the clinical performance in detecting SARS-CoV-2 of the Cobas SARS-CoV-2 Test based on the high-throughput Cobas 6800 system and the Cobas SARS-CoV-2 & Flu A/B Test based on the point-of-care cobas Liat system. Methods: The commercial reagents containing SARS-CoV-2 RNA subgenomes were diluted for assessing the sensitivity of the RT-qPCR assay. 385 nasopharyngeal swab specimens taken from contacts of COVID-19 cases were tested for the SARS-CoV-2 detection with both Cobas SARS-CoV-2 Tests. Results: In analytical sensitivity assays, the Cobas SARS-CoV-2 & Flu A/B Test on the Liat system had a lower limit of detection (12.5-25 copies/mL) than the cobas SARS-CoV-2 Test on the cobas 6800 system (25-50 copies/mL). In clinical performance assays, the cobas SARS-CoV-2 Test demonstrated 89.36% (42 out of 47) PPA (positive percent agreement) and 98.82% (334 out of 338) NPA (negative percent agreement) compared to the results of the Cobas SARS-CoV-2 & Flu A/B test. Among five discordant specimens, four had the positive result of the cobas SARS-CoV-2 test, but the negative result of the cobas SARS-CoV-2 & Flu A/B Test. Moreover, these discordant specimens had the Ct values of greater than 33 for the cobas SARS-CoV-2 Test, implying a very small number of virions in the samples. Remarkably, four specimens with a presumptive positive result of the cobas SARS-CoV-2 test had been confirmed by the Cobas SARS-CoV-2 & Flu A/B Test. Next, the scatter plots of the Ct values showed a highly positive correlation between cobas SARS-CoV-2 & Flu A/B Test and the cobas SARS-CoV-2 Test (R-squared value = 0.954-0.962). Conclusions: Both SARS-CoV2 tests of the cobas 6800 and Liat systems produce reliable high throughput and point-of-care assays respectively for the early virus detection and the personal care decision-making during COVID-19 pandemic.

6.
Brain Sci ; 12(1)2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1613617

ABSTRACT

During the pandemic era, quarantines might potentially have negative effects and disproportionately exacerbate health condition problems. We conducted this cross-sectional, national study to ascertain the prevalence of constant pain symptoms and how quarantines impacted the pain symptoms and identify the factors associated with constant pain to further guide reducing the prevalence of chronic pain for vulnerable people under the pandemic. The sociodemographic data, quarantine conditions, mental health situations and pain symptoms of the general population were collected. After adjusting for potential confounders, long-term quarantine (≥15 days) exposures were associated with an increased risk of constant pain complaints compared to those not under a quarantine (Odds Ratio (OR): 1.26; 95% Confidence Interval (CI): 1.03, 1.54; p = 0.026). Risk factors including unemployment (OR: 1.55), chronic disease history (OR: 2.38) and infection with COVID-19 (OR: 2.15), and any of mental health symptoms including depression, anxiety, insomnia and PTSD (OR: 5.44) were identified by a multivariable logistic regression. Additionally, mediation analysis revealed that the effects of the quarantine duration on pain symptoms were mediated by mental health symptoms (indirect effects: 0.075, p < 0.001). These results advocated that long-term quarantine measures were associated with an increased risk of experiencing pain, especially for vulnerable groups with COVID-19 infection and with mental health symptoms. The findings also suggest that reducing mental distress during the pandemic might contribute to reducing the burden of pain symptoms and prioritizing interventions for those experiencing a long-term quarantine.

7.
Infect Chemother ; 53(4): 730-740, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1595379

ABSTRACT

INTRODUCTION: Zika virus (ZIKV), a mosquito-borne flavivirus, causes the outbreaks of Latin America in 2015 - 2016, with the incidence of neurological complications. Sunitinib malate, an orally bioavailable malate salt of the tyrosine kinase inhibitor, is suggested as a broad-spectrum antiviral agent against emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. MATERIALS AND METHODS: This study investigated the antiviral efficacy and antiviral mechanisms of sunitinib malate against ZIKV infection using cytopathic effect reduction, virus yield, and time-of-addition assays. RESULTS: Sunitinib malate concentration-dependently reduced ZIKV-induced cytopathic effect, the expression of viral proteins, and ZIKV yield in supernatant with 50% inhibitory concentration (IC50) value of 0.015 µM, and the selectivity index of greater than 100 against ZIKV infection, respectively. Sunitinib malate had multiple antiviral actions during entry and post-entry stages of ZIKV replication. Sunitinib malate treatment at entry stage significantly reduced the levels of ZIKV RNA replication with the reduction of (+) RNA to (-) RNA ratio and the production of new intracellular infectious particles in infected cells. The treatment at post-entry stage caused a concentration-dependent increase in the levels of ZIKV (+) RNA and (-) RNA in infected cells, along with enlarging the ratio of (+) RNA to (-) RNA, but caused a pointed increase in the titer of intracellular infectious particles by 0.01 and 0.1 µM, and a substantial decrease in the titer of intracellular infectious particles by 1 µM. CONCLUSION: The study discovered the antiviral actions of sunitinib malate against ZIKV infection, demonstrating a repurposed, host-targeted approach to identify potential antiviral drugs for treating emerging and global viral diseases.

8.
Infect Genet Evol ; 97: 105164, 2022 01.
Article in English | MEDLINE | ID: covidwho-1536954

ABSTRACT

The widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuously impacts our economic and public health. The potential of emerging variants to increase transmissibility and evade vaccine-induced immunity lets us put more effort to research on viral mutations and explore the pathogenic haplotypes. In this study, we characterized the haplotype and sub-haplotype diversity of SARS-CoV-2 global variants in January-March and the areas with low and high COVID19 vaccination rates in May 2021 by analyzing viral proteome of complete genome sequences published. Phylogenetic tree analysis of the proteomes of SARS-CoV-2 variants with Neighbor-Joining and Maximum Parsimony methods indicated that haplotype 2 variant with nsp12 P323L and Spike D614G was dominant (98.81%), including new sub-haplotypes 2A_1 to 2A_3, 2B_1 to 2B_3, and 2C_1 to 2C_2 emerged post-one-year COVID-19 outbreak. In addition, the profiling of sub-haplotypes indicated that sub-haplotype 2A_1 with the mutations at N501Y, A570D, D614G, P681H, T716I, S982A, and D118H in Spike was over 58% in May 2021 in the high partly vaccinated rate group (US, Canada, and Germany). Meanwhile, the new haplotype 2C_3 bearing the mutations at EFR156-158del, T19R, A222V, L452R, T478K, and D614G in Spike occupied over 54.8% in May 2021 in the low partly vaccinated rate group (India, Malaysia, Taiwan, and Vietnam). Sub-haplotypes 2A_1 and 2C_3 had a meaningful alternation of ACE2-specific recognition site, neutralization epitopes, and furin cleavage site in SARS-CoV-2 Spike protein. The results discovered the haplotype diversity and new sub-haplotypes of SARS-CoV-2 variants post one-year pandemic in January-March 2021, showing the profiles of sub-haplotypes in the groups with low and high partly vaccinated rates in May 2021. The study reports the emergence of new SARS-CoV-2 sub-haplotypes during ongoing pandemic and vaccination in early 2021, which might help inform the response to vaccination strategies.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/epidemiology , COVID-19/prevention & control , Mutation , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Americas/epidemiology , Amino Acid Substitution , Asia/epidemiology , COVID-19/immunology , COVID-19/transmission , Epidemiological Monitoring , Europe/epidemiology , Gene Expression , Genome, Viral , Haplotypes , Humans , Immune Evasion , Models, Molecular , Phylogeny , Protein Interaction Domains and Motifs , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vaccination Coverage/statistics & numerical data
9.
Front Med (Lausanne) ; 8: 749318, 2021.
Article in English | MEDLINE | ID: covidwho-1497094

ABSTRACT

Although the pathologic investigation of liver injury was observed in a couple of cases in China, the detailed description of liver histopathologic and ultrastructural changes in a relatively larger series of liver tissues from COVID-19 patients is lacking. Samples from the liver were obtained from 24 COVID-19 cases from February 1 to April 1, 2020. Light microscopy showed that all liver sections had different degrees of liver injury manifested as swelling of the hepatocytes, hepatocellular necrosis, steatosis, lobular inflammation, portal inflammation, dilatation of sinusoids, and so on. SARS-CoV-2 induced liver injury might be independent of pre-existing Schistosoma infection or obstructive cholestasis. Patients combined with respiratory failure had more severe hepatocellular necrosis and male patients were more susceptible to liver injury. Although coronavirus particles or viral inclusions were not detected in the liver tissues for all cases, vacuolar degenerations in hepatocytes, edematous of mitochondria with the disruption of cristae, and expansions of the endoplasmic reticulum were observed. In conclusion, pathologic changes of liver tissues provide us a further understanding of liver injury in COVID-19 patients. Changes in the liver seem to be related to the underlying diseases/conditions.

11.
Infect Genet Evol ; 91: 104800, 2021 07.
Article in English | MEDLINE | ID: covidwho-1116814

ABSTRACT

The pandemic spread of Coronavirus Disease 2019 (COVID-19) is still ongoing since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is identified as the etiologic pathogen late December 2019. After over six-month spread of COVID-19, SARS-CoV-2 causes critical threats to global public health and economy. The investigations on evolution and genotyping on genetic variations are of great importance, therefore, the present study characterized the molecular variation of SARS-CoV-2 by analyzing 4230 complete genome sequences from the worldwide samples collected during the first 6-month pandemic. Phylogenetic tree analysis with Neighbor-Joining and Maximum-Parsimony methods indicated that the haplotypes of SARS-CoV-2 genome sequences were classified into four clades with the unique nucleotide and amino acid changes: T27879C (ORF8 L84S) in clade 1 (25.34%), A23138G (spike D614G) in clade 2 (63.54%), G10818T (nsp6 L37F), C14540T (nsp12 T442I), and G25879T (ORF3a V251F) in clade 3 (2.58%), and miscellaneous changes in clade 4 (8.54%). Interestingly, subclade 2B with the amino acid changes at nsp2 T85I, Spike D614G, and ORF3a Q57H was firstly reported on March 4, 2020 in United States of America, becoming the most frequent sub-haplogroup in the world (36.21%) and America (45.81%). Subclade 1C with the amino acid changes at nsp13 P504L and ORF8 L84S was becoming the second most frequent sub-haplogroup in the world (19.91%) and America (26.29%). Subclade 2A with the amino acid changes in Spike D614G and Nucleocapsid R203K and G204R was highly prevalent in Asia (18.82%) and Europe (29.72%). The study highlights the notable clades and sub-clades with unique mutations, revealing the genetic and geographical relevant post the six-month outbreak of COVID-19. This study thoroughly observed the genetic feature of SARS-CoV-2 haplotyping, providing an epidemiological trend of COVID-19.


Subject(s)
COVID-19/epidemiology , Genetic Variation , Genome, Viral , Nucleocapsid Proteins/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Americas/epidemiology , Amino Acid Substitution , Asia/epidemiology , COVID-19/transmission , COVID-19/virology , Europe/epidemiology , Evolution, Molecular , Gene Expression Regulation, Viral , Haplotypes , Humans , Mutation Rate , Open Reading Frames , Phylogeny , SARS-CoV-2/classification , Selection, Genetic
12.
Cell ; 184(3): 775-791.e14, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-1014394

ABSTRACT

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.


Subject(s)
COVID-19/metabolism , Gene Expression Regulation , Proteome/biosynthesis , Proteomics , SARS-CoV-2/metabolism , Autopsy , COVID-19/pathology , COVID-19/therapy , Female , Humans , Male , Organ Specificity
13.
J Am Soc Nephrol ; 31(2): 297-307, 2020 02.
Article in English | MEDLINE | ID: covidwho-992922

ABSTRACT

BACKGROUND: Myeloperoxidase-specific ANCA (MPO-ANCA) are implicated in the pathogenesis of vasculitis and GN. Kinins play a major role during acute inflammation by regulating vasodilatation and vascular permeability and by modulating adhesion and migration of leukocytes. Kinin system activation occurs in patients with ANCA vasculitis. Previous studies in animal models of GN and sclerosing kidney diseases have demonstrated protective effects of bradykinin receptor 1 (B1R) blockade via interference with myeloid cell trafficking. METHODS: To investigate the role of B1R in a murine model of MPO-ANCA GN, we evaluated effects of B1R genetic ablation and pharmacologic blockade. We used bone marrow chimeric mice to determine the role of B1R in bone marrow-derived cells (leukocytes) versus nonbone marrow-derived cells. We elucidated mechanisms of B1R effects using in vitro assays for MPO-ANCA-induced neutrophil activation, endothelial adherence, endothelial transmigration, and neutrophil adhesion molecule surface display. RESULTS: B1R deficiency or blockade prevented or markedly reduced ANCA-induced glomerular crescents, necrosis, and leukocyte influx in mice. B1R was not required for in vitro MPO-ANCA-induced neutrophil activation. Leukocyte B1R deficiency, but not endothelial B1R deficiency, decreased glomerular neutrophil infiltration induced by MPO-ANCA in vivo. B1R enhanced ANCA-induced neutrophil endothelial adhesion and transmigration in vitro. ANCA-activated neutrophils exhibited changes in Mac-1 and LFA-1, important regulators of neutrophil endothelial adhesion and transmigration: ANCA-activated neutrophils increased surface expression of Mac-1 and increased shedding of LFA-1, whereas B1R blockade reduced these effects. CONCLUSIONS: The leukocyte B1R plays a critical role in the pathogenesis of MPO-ANCA-induced GN in a mouse model by modulating neutrophil-endothelial interaction. B1R blockade may have potential as a therapy for ANCA GN and vasculitis.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/immunology , Glomerulonephritis/etiology , Peroxidase/immunology , Receptor, Bradykinin B1/physiology , Animals , Bradykinin B1 Receptor Antagonists/therapeutic use , Cell Adhesion , Disease Models, Animal , Endothelial Cells/physiology , Glomerulonephritis/drug therapy , Mice , Mice, Inbred C57BL , Neutrophils/physiology
15.
Am J Kidney Dis ; 76(4): 490-499.e1, 2020 10.
Article in English | MEDLINE | ID: covidwho-730121

ABSTRACT

RATIONALE & OBJECTIVE: Patients receiving maintenance hemodialysis (MHD) are highly vulnerable to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current study was designed to evaluate the prevalence of SARS-CoV-2 infection based on both nucleic acid testing (NAT) and antibody testing in Chinese patients receiving MHD. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: From December 1, 2019, to March 31, 2020, a total of 1,027 MHD patients in 5 large hemodialysis centers in Wuhan, China, were enrolled. Patients were screened for SARS-CoV-2 infection by symptoms and initial computed tomography (CT) of the chest. If patients developed symptoms after the initial screening was negative, repeat CT was performed. Patients suspected of being infected with SARS-CoV-2 were tested with 2 consecutive throat swabs for viral RNA. In mid-March 2020, antibody testing for SARS-CoV-2 was obtained for all MHD patients. EXPOSURE: NAT and antibody testing results for SARS-CoV-2. OUTCOMES: Morbidity, clinical features, and laboratory and radiologic findings. ANALYTICAL APPROACH: Differences between groups were examined using t test or Mann-Whitney U test, comparing those not infected with those infected and comparing those with infection detected using NAT with those with infection detected by positive serology test results. RESULTS: Among 1,027 patients receiving MHD, 99 were identified as having SARS-CoV-2 infection, for a prevalence of 9.6%. Among the 99 cases, 52 (53%) were initially diagnosed with SARS-CoV-2 infection by positive NAT; 47 (47%) were identified later by positive immunoglobulin G (IgG) or IgM antibodies against SARS-CoV-2. There was a spectrum of antibody profiles in these 47 patients: IgM antibodies in 5 (11%), IgG antibodies in 35 (74%), and both IgM and IgG antibodies in 7 (15%). Of the 99 cases, 51% were asymptomatic during the epidemic; 61% had ground-glass or patchy opacities on CT of the chest compared with 11.6% among uninfected patients (P<0.001). Patients with hypertensive kidney disease were more often found to have SARS-CoV-2 infection and were more likely to be symptomatic than patients with another primary cause of kidney failure. LIMITATIONS: Possible false-positive and false-negative results for both NAT and antibody testing; possible lack of generalizability to other dialysis populations. CONCLUSIONS: Half the SARS-CoV-2 infections in patients receiving MHD were subclinical and were not identified by universal CT of the chest and selective NAT. Serologic testing may help evaluate the overall prevalence and understand the diversity of clinical courses among patients receiving MHD who are infected with SARS-CoV-2.


Subject(s)
Antibodies, Viral/analysis , Betacoronavirus/immunology , Coronavirus Infections/diagnosis , Kidney Failure, Chronic/therapy , Pneumonia, Viral/diagnosis , Renal Dialysis , COVID-19 , China/epidemiology , Comorbidity , Coronavirus Infections/epidemiology , Cross-Sectional Studies , Female , Humans , Kidney Failure, Chronic/epidemiology , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Prevalence , Retrospective Studies , SARS-CoV-2 , Serologic Tests/methods , Tomography, X-Ray Computed
16.
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 , COVID-19 , 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 , SARS-CoV-2
17.
Kidney International ; 98(1):219-227, 2020.
Article | WHO COVID | ID: covidwho-680431

ABSTRACT

Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help de fine this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new -onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non -isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identi fied. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial in flammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus-like particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation -relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection.

18.
Eur Urol Focus ; 6(5): 1124-1129, 2020 Sep 15.
Article in English | MEDLINE | ID: covidwho-437089

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), involves multiple organs. Testicular involvement is largely unknown. OBJECTIVE: To determine the pathological changes and whether SARS-CoV-2 can be detected in the testes of deceased COVID-19 patients. DESIGN, SETTING, AND PARTICIPANTS: Postmortem examination of the testes from 12 COVID-19 patients was performed using light and electron microscopy, and immunohistochemistry for lymphocytic and histiocytic markers. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the virus in testicular tissue. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Seminiferous tubular injury was assessed as none, mild, moderate, or severe according to the extent of tubular damage. Leydig cells in the interstitium were counted in ten 400× microscopy fields. RESULTS AND LIMITATIONS: Microscopically, Sertoli cells showed swelling, vacuolation and cytoplasmic rarefaction, detachment from tubular basement membranes, and loss and sloughing into lumens of the intratubular cell mass. Two, five, and four of 11 cases showed mild, moderate, and severe injury, respectively. The mean number of Leydig cells in COVID-19 testes was significantly lower than in the control group (2.2 vs 7.8, p < 0.001). In the interstitium there was edema and mild inflammatory infiltrates composed of T lymphocytes and histiocytes. Transmission EM did not identify viral particles in three cases. RT-PCR detected the virus in one of 12 cases. CONCLUSIONS: Testes from COVID-19 patients exhibited significant seminiferous tubular injury, reduced Leydig cells, and mild lymphocytic inflammation. We found no evidence of SARS-CoV-2 virus in the testes in the majority (90%) of the cases by RT-PCR, and in none by electron microscopy. These findings can provide evidence-based guidance for sperm donation and inform management strategies to mitigate the risk of testicular injury during the COVID-19 disease course. PATIENT SUMMARY: We examined the testes of deceased COVID-19 patients. We found significant damage to the testicular parenchyma. However, virus was not detected in testes in the majority of cases.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Seminiferous Tubules/pathology , Testis/pathology , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2 , Betacoronavirus , COVID-19 , Cell Count , Coronavirus Infections/metabolism , Coronavirus Infections/physiopathology , Humans , Inflammation , Leydig Cells/pathology , Leydig Cells/ultrastructure , Male , Microscopy, Electron , Middle Aged , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Pneumonia, Viral/physiopathology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Seminiferous Tubules/ultrastructure , Sertoli Cells/pathology , Sertoli Cells/ultrastructure , Spermatogenesis/physiology , Testis/metabolism , Testis/ultrastructure , Testis/virology
19.
Kidney Int ; 98(1): 219-227, 2020 07.
Article in English | MEDLINE | ID: covidwho-115633

ABSTRACT

Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new-onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non-isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identified. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial inflammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus-like particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation-relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection.


Subject(s)
Coronavirus Infections/pathology , Kidney/ultrastructure , Pneumonia, Viral/pathology , Adult , Aged , Aged, 80 and over , COVID-19 , China , Female , Humans , Male , Middle Aged , Pandemics
20.
Eur Urol ; 77(6): 742-747, 2020 06.
Article in English | MEDLINE | ID: covidwho-27850

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a novel and lethal infectious disease, posing a threat to global health security. The number of cases has increased rapidly, but no data concerning kidney transplant (KTx) recipients infected with COVID-19 are available. To present the epidemiological, clinical, and therapeutic characteristics of KTx recipients infected with COVID-19, we report on a case series of five patients who were confirmed as having COVID-19 through nucleic acid testing (NAT) from January 1, 2020 to February 28, 2020. The most common symptoms on admission to hospital were fever (five patients, 100%), cough (five patients, 100%), myalgia or fatigue (three patients, 60%), and sputum production (three patients, 60%); serum creatinine or urea nitrogen levels were slightly higher than those before symptom onset. Four patients received a reduced dose of maintenance immunosuppressive therapy during hospitalization. As of March 4, 2020 NAT was negative for COVID-19 in three patients twice in succession, and their computed tomography scans showed improved images. Although greater patient numbers and long-term follow-up data are needed, our series demonstrates that mild COVID-19 infection in KTx recipients can be managed using symptomatic support therapy combined with adjusted maintenance immunosuppressive therapy.


Subject(s)
Betacoronavirus/isolation & purification , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Opportunistic Infections/diagnosis , Pneumonia, Viral/diagnosis , Transplant Recipients , Adult , Betacoronavirus/genetics , Betacoronavirus/immunology , COVID-19 , COVID-19 Testing , China , Coronavirus Infections/therapy , Coronavirus Infections/virology , Female , Humans , Immunocompromised Host , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Opportunistic Infections/therapy , Opportunistic Infections/virology , Pandemics , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Predictive Value of Tests , SARS-CoV-2 , Severity of Illness Index , Time Factors , Treatment Outcome
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