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1.
Kidney Int ; 101(5): 1017-1026, 2022 05.
Article in English | MEDLINE | ID: covidwho-1700922

ABSTRACT

Collapsing glomerulopathy is a histologically distinct variant of focal and segmental glomerulosclerosis that presents with heavy proteinuria and portends a poor prognosis. Collapsing glomerulopathy can be triggered by viral infections such as HIV or SARS-CoV-2. Transcriptional profiling of collapsing glomerulopathy lesions is difficult since only a few glomeruli may exhibit this histology within a kidney biopsy and the mechanisms driving this heterogeneity are unknown. Therefore, we used recently developed digital spatial profiling (DSP) technology which permits quantification of mRNA at the level of individual glomeruli. Using DSP, we profiled 1,852 transcripts in glomeruli isolated from formalin fixed paraffin embedded sections from HIV or SARS-CoV-2-infected patients with biopsy-confirmed collapsing glomerulopathy and used normal biopsy sections as controls. Even though glomeruli with collapsing features appeared histologically similar across both groups of patients by light microscopy, the increased resolution of DSP uncovered intra- and inter-patient heterogeneity in glomerular transcriptional profiles that were missed in early laser capture microdissection studies of pooled glomeruli. Focused validation using immunohistochemistry and RNA in situ hybridization showed good concordance with DSP results. Thus, DSP represents a powerful method to dissect transcriptional programs of pathologically discernible kidney lesions.


Subject(s)
COVID-19 , Glomerulosclerosis, Focal Segmental , HIV Infections , Kidney Diseases , Female , Glomerulosclerosis, Focal Segmental/pathology , Humans , Kidney Diseases/genetics , Kidney Diseases/pathology , Kidney Glomerulus/pathology , Male , SARS-CoV-2
2.
Cell ; 184(21): 5432-5447.e16, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1454060

ABSTRACT

Understanding vaccine-elicited protection against SARS-CoV-2 variants and other sarbecoviruses is key for guiding public health policies. We show that a clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle (RBD-NP) vaccine protects mice from SARS-CoV-2 challenge after a single immunization, indicating a potential dose-sparing strategy. We benchmarked serum neutralizing activity elicited by RBD-NPs in non-human primates against a lead prefusion-stabilized SARS-CoV-2 spike (HexaPro) using a panel of circulating mutants. Polyclonal antibodies elicited by both vaccines are similarly resilient to many RBD residue substitutions tested, although mutations at and surrounding position 484 have negative consequences for neutralization. Mosaic and cocktail nanoparticle immunogens displaying multiple sarbecovirus RBDs elicit broad neutralizing activity in mice and protect mice against SARS-CoV challenge even in the absence of SARS-CoV RBD in the vaccine. This study provides proof of principle that multivalent sarbecovirus RBD-NPs induce heterotypic protection and motivates advancing such broadly protective sarbecovirus vaccines to the clinic.

3.
Arch Pathol Lab Med ; 145(4): 399-406, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1168034

ABSTRACT

CONTEXT.­: The coronavirus disease 2019 pandemic, caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2, has resulted in worldwide disruption to the delivery of patient care. The Seattle, Washington metropolitan area was one of the first in the United States affected by the pandemic. As a result, the anatomic pathology services at the University of Washington experienced significant changes in operational volumes early in the pandemic. OBJECTIVE.­: To assess the impact of coronavirus disease 2019 and both state and institutional policies implemented to mitigate viral transmission (including institutional policies on nonurgent procedures) on anatomic pathology volumes. DESIGN.­: Accessioned specimens from January to June 2020 were evaluated as coronavirus disease 2019 and institutional policies changed. The data were considered in these contexts: subspecialty, billable Current Procedural Terminology codes, and intraoperative consultation. Comparable data were retrieved from 2019 as a historical control. RESULTS.­: There was a significant reduction in overall accessioned volume (up to 79%) from prepandemic levels during bans on nonurgent procedures when compared with 2020 pre-coronavirus disease 2019 volumes and historical controls. The gastrointestinal and dermatopathology services were most impacted, and breast and combined head and neck/pulmonary services were least impacted. Current Procedural Terminology code 88305, for smaller/biopsy specimens, had a 63% reduction during nonurgent procedure bans. After all bans on procedures were lifted, the overall volume plateaued at 89% of prepandemic levels. CONCLUSIONS.­: A significant decrease in specimen volume was most strongly associated with bans on nonurgent procedures. Although all departmental areas had a decrease in volume, the extent of change varied across subspecialty and specimen types. Even with removal of all bans, service volume did not reach prepandemic levels.


Subject(s)
COVID-19/epidemiology , Pandemics , Pathology, Clinical , SARS-CoV-2 , Academic Medical Centers/economics , COVID-19/economics , Delivery of Health Care/economics , Delivery of Health Care/statistics & numerical data , Delivery of Health Care/trends , Humans , Pathology, Clinical/economics , Pathology, Clinical/statistics & numerical data , Pathology, Clinical/trends , Retrospective Studies , Washington/epidemiology
4.
Curr Opin Nephrol Hypertens ; 30(3): 324-331, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1153291

ABSTRACT

PURPOSE OF REVIEW: The current review summarizes the pathologic findings in kidneys from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients who have had autopsies or undergone biopsy, and the pathogenic mechanisms implicated in coronavirus disease 2019 (COVID-19)-associated kidney diseases. RECENT FINDINGS: Direct infection of the kidney by SARS-CoV-2 is not common, and convincing morphologic evidence of substantive kidney infection by SARS-CoV-2 is lacking. Severe COVID-19-associated acute kidney injury is likely multifactorial and results from the physiologic disturbances and therapies used to treat this illness. COVID-19-associated collapsing glomerulopathy (COVAN) is seen almost exclusively in patients with apolipoprotein L1 high-risk genotypes with no evidence of direct infection of the kidney by SARS-CoV-2. SUMMARY: The prevailing evidence does not support substantive or persistent infection of kidneys in COVID-19 and indirect means of tissue injury are favored, although a 'hit and run' model cannot be excluded. COVAN frequently occurs in patients with mild respiratory systems, suggesting that innate and adaptive immune responses to SARS-CoV-2 infection may provide the second hit needed for the development of collapsing glomerulopathy in susceptible individuals.


Subject(s)
Acute Kidney Injury/etiology , COVID-19/complications , SARS-CoV-2 , Humans , Kidney/pathology , Kidney/virology
5.
Am J Pathol ; 191(2): 222-227, 2021 02.
Article in English | MEDLINE | ID: covidwho-1025412

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 pandemic has infected millions of individuals in the United States and caused hundreds of thousands of deaths. Direct infection of extrapulmonary tissues has been postulated, and using sensitive techniques, viral RNA has been detected in multiple organs in the body, including the kidney. However, direct infection of tissues outside of the lung has been more challenging to demonstrate. This has been in part due to misinterpretation of electron microscopy studies. In this perspective, we will discuss what is known about coronavirus infection, some of the basic ultrastructural cell biology that has been confused for coronavirus infection of cells, and rigorous criteria that should be used when identifying pathogens by electron microscopy.


Subject(s)
COVID-19 , Coronavirus Infections/virology , Microscopy, Electron , SARS-CoV-2/pathogenicity , COVID-19/epidemiology , COVID-19/virology , Humans , Lung/ultrastructure , Lung/virology , Microscopy, Electron/methods , United States , Virus Diseases
6.
Am J Kidney Dis ; 77(1): 82-93.e1, 2021 01.
Article in English | MEDLINE | ID: covidwho-851328

ABSTRACT

RATIONALE & OBJECTIVE: Kidney biopsy data inform us about pathologic processes associated with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a multicenter evaluation of kidney biopsy findings in living patients to identify various kidney disease pathology findings in patients with coronavirus disease 2019 (COVID-19) and their association with SARS-CoV-2 infection. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We identified 14 native and 3 transplant kidney biopsies performed for cause in patients with documented recent or concurrent SARS-CoV-2 infection treated at 7 large hospital systems in the United States. OBSERVATIONS: Men and women were equally represented in this case series, with a higher proportion of Black (n=8) and Hispanic (n=5) patients. All 17 patients had SARS-CoV-2 infection confirmed by reverse transcriptase-polymerase chain reaction, but only 3 presented with severe COVID-19 symptoms. Acute kidney injury (n=15) and proteinuria (n=11) were the most common indications for biopsy and these symptoms developed concurrently or within 1 week of COVID-19 symptoms in all patients. Acute tubular injury (n=14), collapsing glomerulopathy (n=7), and endothelial injury/thrombotic microangiopathy (n=6) were the most common histologic findings. 2 of the 3 transplant recipients developed active antibody-mediated rejection weeks after COVID-19. 8 patients required dialysis, but others improved with conservative management. LIMITATIONS: Small study size and short clinical follow-up. CONCLUSIONS: Cases of even symptomatically mild COVID-19 were accompanied by acute kidney injury and/or heavy proteinuria that prompted a diagnostic kidney biopsy. Although acute tubular injury was seen among most of them, uncommon pathology such as collapsing glomerulopathy and acute endothelial injury were detected, and most of these patients progressed to irreversible kidney injury and dialysis.


Subject(s)
Acute Kidney Injury/etiology , Acute Kidney Injury/pathology , COVID-19/complications , COVID-19/pathology , Proteinuria/etiology , Proteinuria/pathology , Adult , Aged , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Kidney/pathology , Male , Middle Aged
8.
Kidney Int ; 98(2): 506-507, 2020 08.
Article in English | MEDLINE | ID: covidwho-526921
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