Kidney Biopsy Findings in Patients with COVID-19 Kudose, Satoru; Batal, Ibrahim; Santoriello, Dominick ...
Journal of the American Society of Nephrology,
09/2020, Letnik:
31, Številka:
9
Journal Article
Recenzirano
Odprti dostop
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.
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,
hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
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
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.
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.
Due to the rapid emergence of antibiotic-resistant bacteria, there is a growing need to discover new antibiotics. To address this challenge, we trained a deep neural network capable of predicting ...molecules with antibacterial activity. We performed predictions on multiple chemical libraries and discovered a molecule from the Drug Repurposing Hub—halicin—that is structurally divergent from conventional antibiotics and displays bactericidal activity against a wide phylogenetic spectrum of pathogens including Mycobacterium tuberculosis and carbapenem-resistant Enterobacteriaceae. Halicin also effectively treated Clostridioides difficile and pan-resistant Acinetobacter baumannii infections in murine models. Additionally, from a discrete set of 23 empirically tested predictions from >107 million molecules curated from the ZINC15 database, our model identified eight antibacterial compounds that are structurally distant from known antibiotics. This work highlights the utility of deep learning approaches to expand our antibiotic arsenal through the discovery of structurally distinct antibacterial molecules.
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•A deep learning model is trained to predict antibiotics based on structure•Halicin is predicted as an antibacterial molecule from the Drug Repurposing Hub•Halicin shows broad-spectrum antibiotic activities in mice•More antibiotics with distinct structures are predicted from the ZINC15 database
A trained deep neural network predicts antibiotic activity in molecules that are structurally different from known antibiotics, among which Halicin exhibits efficacy against broad-spectrum bacterial infections in mice.
Precise immunofluorescence criteria for C3 glomerulopathy remain to be defined. Here we tested hierarchical immunofluorescence criteria with varying stringency for C3 glomerulopathy in a cohort with ...dense deposit disease as the gold standard and then applied these criteria to analyze the incidence of C3 glomerulopathy in membranoproliferative glomerulonephritis (MPGN) types 1 and 3. Among 319 archived cases of primary MPGN types 1–3, immunofluorescence reports were retrospectively coded as glomerular deposits of the following: C3 only; C3 dominant with trace or 1+ immunoglobulin (Ig)M only; and C3 dominant and at least two orders of intensity stronger than any combination of IgG, IgM, IgA, and C1q. The most restrictive criteria of ‘C3 only’ captured only half of the cases with dense deposit disease (compared with 8% of type 1 and 10% of type 3). Adding the most liberal definition identified 88% of those with dense deposit disease (compared with 31% of type 1 and 39% of type 3). The unaccounted 12% had stronger intensity of Ig staining, but it never exceeded the intensity of C3. Among MPGN type 3, 90% of C3 glomerulopathy cases were the Strife and Anders variant. Repeat biopsies in C3 glomerulopathy revealed a change in immunofluorescence pattern in 10 of 23 biopsies. The prevalence of low serum C3 and/or low C4 did not significantly differ among the three immunofluorescence criteria. Thus, ‘C3 only’ is an impractical definition of C3 glomerulopathy, and we propose a definition of C3 dominant and at least two orders of magnitude more intense than any other immune reactant, which requires validation by alternative pathway evaluation. These criteria provide a framework for identifying patients most likely to benefit from investigations of alternative complement pathway dysregulation.
The fluvial archive literature is dominated by research on river terraces with appropriate mention of adjacent environments such as lakes. Despite modern sedimentary basins comprising a significant ...(>88%) volume of distributive fluvial systems, of which alluvial fans (>1 km, <30 km in scale) are a significant part, interaction with these environments tends to be neglected and discussed in separate literature. This paper examines the dynamic role of alluvial fans within the fluvial landscape and their interaction with river systems, highlighting the potential value of alluvial fans to the wider fluvial archive community. Published literature is used to examine both thematic and geographical based benefits of alluvial fan research that can assist understanding of Quaternary fluvial archives. 3 regional case studies are presented that illustrate the interaction between alluvial fan and river terrace archives at Quaternary time-scales at 3 different stages of landscape evolution. These are i) continuous mountain front alluvial fans interacting with a non incising but laterally eroding axial fluvial system; ii) alluvial fans which transition into fluvial terraces as sedimentary basins shift from net aggradation to net incision and iii) tributary-junction alluvial fans that develop predominantly within incising river valley systems. A simple conceptual model is proposed to summarise the dynamic role of alluvial fans within this landscape context. The alluvial fans act as potential ‘buffers’ between hillslopes and river terrace records under ‘top down’ climate-driven high sediment supply and alluvial fan aggradation, and ‘couplers’ during periods of less sediment (in relation to water) discharge and alluvial fan incision. These dynamics will change with the addition of ‘bottom up’ controls such as main river incision, which will typically enhance the coupling effect of both systems.
•Provides the first review paper linking alluvial fan research with research into fluvial archives.•Pulls together material from across sub-disciplines.•Fans act as important ‘buffers’ or ‘couplers’ within the fluvial landscape.•Fan/river interactions change in response to top down and bottom up system drivers.•Dynamic relationships described in a conceptual model of alluvial fan/river interactions.
The oceans represent a significant global source of atmospheric aerosols. Sea spray aerosol (SSA) particles comprise sea salts and organic species in varying proportions. In addition to size, the ...overall composition of SSA particles determines how effectively they can form cloud droplets and ice crystals. Thus, understanding the factors controlling SSA composition is critical to predicting aerosol impacts on clouds and climate. It is often assumed that submicrometer SSAs are mainly formed by film drops produced from bursting bubble-cap films, which become enriched with hydrophobic organic species contained within the sea surface microlayer. In contrast, jet drops formed from the base of bursting bubbles are postulated to mainly produce larger supermicrometer particles from bulk seawater, which comprises largely salts and water-soluble organic species. However, here we demonstrate that jet drops produce up to 43% of total submicrometer SSA number concentrations, and that the fraction of SSA produced by jet drops can be modulated by marine biological activity. We show that the chemical composition, organic volume fraction, and ice nucleating ability of submicrometer particles from jet drops differ from those formed from film drops. Thus, the chemical composition of a substantial fraction of submicrometer particles will not be controlled by the composition of the sea surface microlayer, a major assumption in previous studies. This finding has significant ramifications for understanding the factors controlling the mixing state of submicrometer SSA particles and must be taken into consideration when predicting SSA impacts on clouds and climate.
Plasmid-borne colistin resistance mediated by mcr-1 may contribute to the dissemination of pan-resistant Gram-negative bacteria. Here, we show that mcr-1 confers resistance to colistin-induced lysis ...and bacterial cell death, but provides minimal protection from the ability of colistin to disrupt the Gram-negative outer membrane. Indeed, for colistin-resistant strains of Enterobacteriaceae expressing plasmid-borne mcr-1, clinically relevant concentrations of colistin potentiate the action of antibiotics that, by themselves, are not active against Gram-negative bacteria. The result is that several antibiotics, in combination with colistin, display growth-inhibition at levels below their corresponding clinical breakpoints. Furthermore, colistin and clarithromycin combination therapy displays efficacy against mcr-1-positive Klebsiella pneumoniae in murine thigh and bacteremia infection models at clinically relevant doses. Altogether, these data suggest that the use of colistin in combination with antibiotics that are typically active against Gram-positive bacteria poses a viable therapeutic alternative for highly drug-resistant Gram-negative pathogens expressing mcr-1.
Kidney allograft biopsy findings after COVID‐19 Daniel, Emily; Sekulic, Miroslav; Kudose, Satoru ...
American journal of transplantation,
December 2021, Letnik:
21, Številka:
12
Journal Article
Recenzirano
Odprti dostop
COVID‐19 has been associated with acute kidney injury and published reports of native kidney biopsies have reported diverse pathologies. Case series directed specifically to kidney allograft biopsy ...findings in the setting of COVID‐19 are lacking. We evaluated 18 kidney transplant recipients who were infected with SARS‐CoV‐2 and underwent allograft biopsy. Patients had a median age of 55 years, six were female, and five were Black. Fifteen patients developed COVID‐19 pneumonia, of which five required mechanical ventilation. Notably, five of 11 (45%) biopsies obtained within 1 month of positive SARS‐CoV‐2 PCR showed acute rejection (four with arteritis, three of which were not associated with reduced immunosuppression). The remaining six biopsies revealed podocytopathy (n = 2, collapsing glomerulopathy and lupus podocytopathy), acute tubular injury (n = 2), infarction (n = 1), and transplant glomerulopathy (n = 1). Biopsies performed >1 month after positive SARS‐CoV‐2 PCR revealed collapsing glomerulopathy (n = 1), acute tubular injury (n = 1), and nonspecific histologic findings (n = 5). No direct viral infection of the kidney allograft was detected by immunohistochemistry, in situ hybridization, or electron microscopy. On follow‐up, two patients died and most patients showed persistent allograft dysfunction. In conclusion, we demonstrate diverse causes of kidney allograft dysfunction after COVID‐19, the most common being acute rejection with arteritis.
Allograft biopsies from kidney transplant recipients with COVID‐19 with acute kidney injury or proteinuria shows a high incidence of acute rejection with arteritis that is not always associated with decreased immunosuppression.
Magnetic resonance imaging (MRI) based diffusion tensor imaging (DTI) can assess white matter (WM) integrity through several metrics, such as fractional anisotropy (FA), axial/radial diffusivities ...(AxD/RD), and mode of anisotropy (MA). Standard DTI is susceptible to the effects of extracellular free water (FW), which can be removed using an advanced free-water DTI (FW-DTI) model. The purpose of this study was to compare standard and FW-DTI metrics in the context of Alzheimer's disease (AD). Data were obtained from the Open Access Series of Imaging Studies (OASIS-3) database and included both healthy controls (HC) and mild-to-moderate AD. With both standard and FW-DTI, decreased FA was found in AD, mainly in the corpus callosum and fornix, consistent with neurodegenerative mechanisms. Widespread higher AxD and RD were observed with standard DTI; however, the FW index, indicative of AD-associated neurodegeneration, was significantly elevated in these regions in AD, highlighting the potential impact of free water contributions on standard DTI in neurodegenerative pathologies. Using FW-DTI, improved consistency was observed in FA, AxD, and RD, and the complementary FW index was higher in the AD group as expected. With both standard and FW-DTI, higher values of MA coupled with higher values of FA in AD were found in the anterior thalamic radiation and cortico-spinal tract, most likely arising from a loss of crossing fibers. In conclusion, FW-DTI better reflects the underlying pathology of AD and improves the accuracy of DTI metrics related to WM integrity in Alzheimer's disease.
Among the many questions unanswered for the COVID-19 pandemic are the origin of SARS-CoV-2 and the potential role of intermediate animal host(s) in the early animal-to-human transmission. The ...discovery of RaTG13 bat coronavirus in China suggested a high probability of a bat origin. Here we report molecular and serological evidence of SARS-CoV-2 related coronaviruses (SC2r-CoVs) actively circulating in bats in Southeast Asia. Whole genome sequences were obtained from five independent bats (Rhinolophus acuminatus) in a Thai cave yielding a single isolate (named RacCS203) which is most related to the RmYN02 isolate found in Rhinolophus malayanus in Yunnan, China. SARS-CoV-2 neutralizing antibodies were also detected in bats of the same colony and in a pangolin at a wildlife checkpoint in Southern Thailand. Antisera raised against the receptor binding domain (RBD) of RmYN02 was able to cross-neutralize SARS-CoV-2 despite the fact that the RBD of RacCS203 or RmYN02 failed to bind ACE2. Although the origin of the virus remains unresolved, our study extended the geographic distribution of genetically diverse SC2r-CoVs from Japan and China to Thailand over a 4800-km range. Cross-border surveillance is urgently needed to find the immediate progenitor virus of SARS-CoV-2.
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