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Insights into pathogenesis of fatal COVID-19 pneumonia from histopathology with immunohistochemical and viral RNA studies

Sauter, Jennifer L; Baine, Marina K; Butnor, Kelly J; Buonocore, Darren J; Chang, Jason C; Jungbluth, Achim A; Szabolcs, Matthias J; Morjaria, Sejal; Mount, Sharon L; Rekhtman, Natasha; Selbs, Elena; Sheng, Zong-Mei; Xiao, Yongli; Kleiner, David E; Pittaluga, Stefania; Taubenberger, Jeffery K; Rapkiewicz, Amy V; Travis, William D
INTRODUCTION/BACKGROUND:We describe postmortem pulmonary histopathologic findings of COVID-19 pneumonia in patients with a spectrum of disease course, from rapid demise to prolonged hospitalization. METHODS:Histopathologic findings in postmortem lung tissue from eight patients who died from COVID-19 pneumonia were reviewed. Immunohistochemistry (IHC) and next generation sequencing (NGS) were performed to detect virus. RESULTS:Diffuse alveolar damage (DAD) was seen in all cases with a spectrum of acute phase and/or organizing phase. IHC with monoclonal antibodies against SARS-CoV-2 viral nucleoprotein and spike protein detected virus in areas of acute but not organizing DAD, with intracellular viral antigen and RNA expression seen predominantly in patients with duration of illness less than 10 days. Major vascular findings included thrombi in medium and large caliber vessels, platelet microthrombi detected by CD61 IHC, and fibrin microthrombi. CONCLUSIONS:Presence of SARS-CoV-2 viral RNA by NGS early in the disease course and expression of viral antigen by IHC exclusively in the acute but not in the organizing phase of DAD, suggests that the virus may play a major role in initiating the acute lung injury of DAD, but when DAD progresses to the organizing phase, the virus may have been cleared from the lung by the patient's immune response. These findings suggest the possibility of a major change during the disease course of COVID-19 pneumonia that may have therapeutic implications. Frequent thrombi and microthrombi may also present potential targets for therapeutic intervention.
PMID: 32614086
ISSN: 1365-2559
CID: 4504502

Sequencing identifies multiple early introductions of SARS-CoV-2 to the New York City Region

Maurano, Matthew T; Ramaswami, Sitharam; Zappile, Paul; Dimartino, Dacia; Boytard, Ludovic; Ribeiro-Dos-Santos, André M; Vulpescu, Nicholas A; Westby, Gael; Shen, Guomiao; Feng, Xiaojun; Hogan, Megan S; Ragonnet-Cronin, Manon; Geidelberg, Lily; Marier, Christian; Meyn, Peter; Zhang, Yutong; Cadley, John A; Ordoñez, Raquel; Luther, Raven; Huang, Emily; Guzman, Emily; Arguelles-Grande, Carolina; Argyropoulos, Kimon V; Black, Margaret; Serrano, Antonio; Call, Melissa E; Kim, Min Jae; Belovarac, Brendan; Gindin, Tatyana; Lytle, Andrew; Pinnell, Jared; Vougiouklakis, Theodore; Chen, John; Lin, Lawrence H; Rapkiewicz, Amy; Raabe, Vanessa; Samanovic, Marie I; Jour, George; Osman, Iman; Aguero-Rosenfeld, Maria; Mulligan, Mark J; Volz, Erik M; Cotzia, Paolo; Snuderl, Matija; Heguy, Adriana
Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epi-demiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in Spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators.
PMID: 33093069
ISSN: 1549-5469
CID: 4642522

New York University Long Island School of Medicine

Ayala, Gladys M; Rapkiewicz, Amy V; Carsons, Steven E; Shelov, Steven P
PMID: 33626719
ISSN: 1938-808x
CID: 4794762

Sequencing identifies multiple, early introductions of SARS-CoV2 to New York City Region

Maurano, Matthew T; Ramaswami, Sitharam; Westby, Gael; Zappile, Paul; Dimartino, Dacia; Shen, Guomiao; Feng, Xiaojun; Ribeiro-Dos-Santos, Andre M; Vulpescu, Nicholas A; Black, Margaret; Hogan, Megan; Marier, Christian; Meyn, Peter; Zhang, Yutong; Cadley, John; Ordonez, Raquel; Luther, Raven; Huang, Emily; Guzman, Emily; Serrano, Antonio; Belovarac, Brendan; Gindin, Tatyana; Lytle, Andrew; Pinnell, Jared; Vougiouklakis, Theodore; Boytard, Ludovic; Chen, John; Lin, Lawrence H; Rapkiewicz, Amy; Raabe, Vanessa; Samanovic-Golden, Marie I; Jour, George; Osman, Iman; Aguero-Rosenfeld, Maria; Mulligan, Mark J; Cotzia, Paolo; Snuderl, Matija; Heguy, Adriana
Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 236 SARS-CoV2 sequences from cases in the New York City metropolitan area during the initial stages of the 2020 COVID-19 outbreak. The majority of cases throughout the region had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that the majority were most related to cases from Europe. Our data are consistent with numerous seed transmissions from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of real-time genomic surveillance in addition to traditional epidemiological indicators.
PMCID:7276014
PMID: 32511587
ISSN: n/a
CID: 4477902

Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series

Rapkiewicz, Amy V; Mai, Xingchen; Carsons, Steven E; Pittaluga, Stefania; Kleiner, David E; Berger, Jeffrey S; Thomas, Sarun; Adler, Nicole M; Charytan, David M; Gasmi, Billel; Hochman, Judith S; Reynolds, Harmony R
Background/UNASSIGNED:There is increasing recognition of a prothrombotic state in COVID-19. Post-mortem examination can provide important mechanistic insights. Methods/UNASSIGNED:We present a COVID-19 autopsy series including findings in lungs, heart, kidneys, liver, and bone, from a New York academic medical center. Findings/UNASSIGNED: = 2). Platelet-rich peri‑tubular fibrin microthrombi were a prominent renal feature. Acute tubular necrosis, and red blood cell and granular casts were seen in multiple cases. Significant glomerular pathology was notably absent. Numerous platelet-fibrin microthrombi were identified in hepatic sinusoids. All lungs exhibited diffuse alveolar damage (DAD) with a spectrum of exudative and proliferative phases including hyaline membranes, and pneumocyte hyperplasia, with viral inclusions in epithelial cells and macrophages. Three cases had superimposed acute bronchopneumonia, focally necrotizing. Interpretation/UNASSIGNED:In this series of seven COVID-19 autopsies, thrombosis was a prominent feature in multiple organs, in some cases despite full anticoagulation and regardless of timing of the disease course, suggesting that thrombosis plays a role very early in the disease process. The finding of megakaryocytes and platelet-rich thrombi in the lungs, heart and kidneys suggests a role in thrombosis. Funding/UNASSIGNED:None.
PMCID:7316051
PMID: 32766543
ISSN: 2589-5370
CID: 4555682

Trends in Mortality From Human Immunodeficiency Virus Infection, 1984-2016: An Autopsy-Based Study

Nizami, Sobia; Morales, Cameron; Hu, Kelly; Holzman, Robert; Rapkiewicz, Amy
CONTEXT.—/UNASSIGNED:With increasing use and efficacy of antiretroviral therapy for human immunodeficiency virus (HIV) infection, deaths from acquired immunodeficiency syndrome (AIDS)-defining conditions have decreased. OBJECTIVE.—/UNASSIGNED:To examine trends in the cause of death of HIV-infected patients who underwent autopsy at a major New York City hospital from 1984 to 2016, a period including the major epochs of the AIDS epidemic. DESIGN.—/UNASSIGNED:Retrospective review of autopsy records and charts with modeling of trends by logistic regression using polynomial models. RESULTS.—/UNASSIGNED:< .001). CONCLUSIONS.—/UNASSIGNED:Despite limitations of autopsy studies, many trends in the evolution of the HIV/AIDS epidemic are readily discernable.
PMID: 31460770
ISSN: 1543-2165
CID: 4054442

Experimental Biology 2020 Meeting Abstracts

Oh, So-Young; Dorsainville, Gregory A; Harnik, Victoria; Rapkiewicz, Amy; Shearer, Brian; Ramirez, Kristen; Alfaro, Veronica; Rosenfeld, Mel
NYU School of Medicine recently embarked on a re-design of its anatomy curriculum that decreased the use of cadavers with plastinated specimens. Plastinated models provide an authentic learning experience of the human body, but lack necessary labels outlining important structures. Due to the fragile nature of the specimens, we endeavored to solve the challenge of labeling by developing a digitized supplement and archive of plastinated and pathology specimens. An interdisciplinary team of faculty and multimedia designers at NYU School of Medicine designed and developed electronic resources related to the artistic models and plastinated specimens. Over the course of three months, 60 artistic and plastinated models of different sizes were captured from dozens of angles using a digital camera or an Artec Leo Scanner. The numerous image captures of the plastinated specimens were processed in Agisoft Metashape, a stand-alone software product, that performs photogrammetric processing of digital images and generates 3D spatial data. After Agisoft Metashape exported a complex 3D mesh with a high-resolution texture, anatomy faculty added labels to the digitized 3D anatomy specimens using the Sketchfab web platform. The labeled 3D anatomy models were then uploaded into the Living Anatomy site on NYU School of Medicine's learning management system for students to explore before, during, and after their anatomy lab sessions. Quizzes using these models also were created to help students identify the structures and link them to physiology and clinical scenarios. The digitized 3D models allow students to zoom in, rotate and explore the specimens in a more interactive way, thereby enhancing the process of just observing fragile plastination models. When asked, 84% of students reported that the 3D models of plastinated specimens contributed "very much so" to their learning of anatomical relationships. We will continue to find opportunities for the meaningful integration of these 3D models within the anatomy curriculum as well as into other pre-clerkship and clerkship modules. We will also assess the educational outcomes of the 3D models and, by doing so, will incorporate instructional design into the process.
PMID: 35134270
ISSN: 1530-6860
CID: 5156752

Analysis: Intravascular Devices with a Higher Risk of Polymer Emboli: The Need for Particulate Generation Testing

Chopra, Amitabh Madhukumar; Rapkiewicz, Amy; Daggubati, Ramesh; Sequeira, Adrian; Hu, Yin C; Bhatt, Deepak L; Sharma, Samin K; Cruz, Juan Pablo; Tzafriri, Abraham R; Edelman, Elazer R
Hydrophilic polymer coatings on intravascular devices lower friction between the device and vasculature, thereby reducing trauma during interventional procedures. Polymer coating embolism-the detachment and downstream embolism of polymer particles-has been reported as an iatrogenic complication of coated interventional devices affecting the vasculature and various organs. The Food and Drug Administration (FDA) acknowledges this complication and continues to work with stakeholders to close gaps in performance testing and standards related to polymer coating integrity. Recent innovations within interventional technologies have led to development of new hydrophilic-coated devices with expanded indications for use. The 2018 FDA draft guidance for intravascular guidewires expands the application of particulate generation testing to most devices and recommends labeling changes to increase industry awareness. This article highlights current procedural trends where the phenomenon of polymer coating embolism may be more prevalent. It describes the mechanisms of polymer separation, reported clinical sequelae, and risk factors for relevant indications. These procedural trends and associated risk factors articulate the need for particulate testing and support the FDA's draft guidance recommendations for performance testing of applied coatings. If standardized, particulate assessments may allow characterization and comparisons of coating integrity among devices from various manufacturers, and are an important foundation for setting particulate limits. As hydrophilic coatings enable endovascular treatment for a range of patient populations, setting particulate limits or finding alternative solutions without compromise to device function may be essential. Particulate testing is relevant to physicians, regulators, and manufacturers for the purposes of product development and quality improvement of interventional devices.
PMID: 31961742
ISSN: 0899-8205
CID: 4379462

Educational Case: Babesiosis and Transfusion-Transmitted Infections

Miller, Maureen J; McVoy, Lauren; Rapkiewicz, Amy
The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.
PMCID:7370331
PMID: 32733991
ISSN: 2374-2895
CID: 4552652

Photogrammetric Digitization and labeling of Plastinated Models for Pre-Clerkship Education [Meeting Abstract]

Dorsainville, Gregory; Harnik, Victoria; Rapkiewicz, Amy; Shearer, Brian; Ramirez, Kristen; Alfaro, Veronica; Rosenfeld, Mel
ISI:000546023100020
ISSN: 0892-6638
CID: 4873492