Try a new search

Format these results:

Searched for:

person:rapkia01

in-biosketch:true

Total Results:

59


COVID-19 Infection and Placental Histopathology in Women Delivering at Term

Patberg, Elizabeth T; Adams, Tracy; Rekawek, Patricia; Vahanian, Sevan A; Akerman, Meredith; Hernandez, Andrea; Rapkiewicz, Amy V; Ragolia, Louis; Sicuranza, Genevieve; Chavez, Martin R; Vintzileos, Anthony M; Khullar, Poonam
BACKGROUND:- There is a paucity of data describing the effects of COVID-19, especially in asymptomatic patients, on placental pathology. Although the pathophysiology of COVID-19 is not completely understood, there is emerging evidence that it causes a severe systemic inflammatory response and results in a hypercoagulable state with widespread microthrombi. We hypothesized that it is plausible that a similar disease process may occur in the fetal-maternal unit. OBJECTIVE:- The aim of this study was to determine whether COVID-19 in term patients admitted to Labor and Delivery, including women without COVID-19 symptomatology, is associated with increased placental injury compared to a cohort of COVID-19 negative controls. STUDY DESIGN/METHODS:- This was a retrospective cohort study performed at NYU Winthrop Hospital between 3/31/2020 and 6/17/2020. During the study period all women admitted to Labor and Delivery were routinely tested for SARS-CoV-2 regardless of symptomatology. The placental histopathological findings of COVID-19 patients (n=77) who delivered a singleton gestation at term were compared to a control group of term patients without COVID-19 (n=56). Controls were excluded if they had obstetric or medical complications including fetal growth restriction, oligohydramnios, hypertension, diabetes, coagulopathy or thrombophilia. Multivariable logistic regression models were performed for variables that were significant in univariable analyses. A subgroup analysis was also performed comparing asymptomatic COVID-19 cases to negative controls. RESULTS:- In univariable analyses, COVID-19 cases were more likely to have evidence of fetal vascular malperfusion, i.e. presence of avascular villi and/or mural fibrin deposition (32.5% (25/77) vs. 3.6% (2/56), p<0.0001) and villitis of unknown etiology (20.8% (16/77) vs. 7.1% (4/56), p=0.030). These findings persisted in a subgroup analysis of asymptomatic COVID-19 cases compared to COVID-19 negative controls. In a multivariable model adjusting for maternal age, race/ethnicity, mode of delivery, preeclampsia, fetal growth restriction and oligohydramnios, the frequency of fetal vascular malperfusion abnormalities remained significantly higher in the COVID-19 group (OR= 12.63, 95% CI [2.40, 66.40]). While the frequency of villitis of unknown etiology was more than double in COVID-19 cases compared to controls, this did not reach statistical significance in a similar multivariable model (OR=2.11, 95% CI [0.50, 8.97]). All neonates of mothers with COVID-19 tested negative for SARS-CoV-2 by PCR. CONCLUSIONS:- Despite the fact that all neonates born to mothers with COVID-19 were negative for SARS-CoV-2 by PCR, we found that COVID-19 in term patients admitted to Labor and Delivery is associated with increased rates of placental histopathologic abnormalities, particularly fetal vascular malperfusion and villitis of unknown etiology. These findings appear to occur even among asymptomatic term patients.
PMCID:7571377
PMID: 33091406
ISSN: 1097-6868
CID: 4642442

Peripheral blood morphologic and laboratory predictors of death in hospitalized COVID-19 patients [Meeting Abstract]

Karimkhan, A; Hossein-Zadeh, Z; Sekhon, P; Budhathoki, N; Ram, B; Rapkiewicz, A; Donovan, V; Park, C; Braunstein, M
Background: Numerous predictors of poor outcome in COVID-19 patients have been identified, including alterations in the composition of leukocytes in the peripheral blood. There nonetheless remains a need to improve predictions of patient outcomes following hospitalization in order to appropriately triage patients. We addressed this question by evaluating hematologic parameters and peripheral blood smear morphology in patients who either died or recovered following hospitalization.
Design(s): The study groups included 48 patients who died following admission ("cases") and 48 age-matched controls who recovered ("controls"). Laboratory values were collected for PCR-positive COVID-19 hospitalized patients at two time points: T1- the time of admission, and T2 - the time of discharge/death. Peripheral blood smears from two-time points for patients who died were analyzed independently by 4 pathologists.
Result(s): Study patient demographic details are shown in Table 1. Anemia and thrombocytopenia were present at the time of admission in both groups, and there was a significant decline in hemoglobin and RBC count between T1 and T2; PLT counts decreased, but not in a statistically significant manner (Table 2). WBC and absolute neutrophils increased following admission specifically in patients who died of disease (Table 2). No statistically significant differences were observed in all other hematologic parameters evaluated. Blood from patients who died showed pseudo Pelger-Huet changes 60.41% (n=29), toxic granulations 8.3% (n=4), atypical lymphocytes 91% (n=44), and giant platelets 94% (n=45) with immature myeloid forms increasing at T2. In contrast to patients who recovered , patients who died showed increased D-dimer values at admission; D-dimer values did not correlate with the presence of thrombocytopenia.
Conclusion(s): Hospitalized COVID-19 patients who died showed: 1) elevated D-dimer levels at admission; and 2) increasing WBC and neutrophil counts during their hospitalization. While several morphologic changes were observed in the blood in those who subsequently died, the changes observed were not specific to COVID-19; however, the presence of immature myeloid precursors in hospitalized patients was associated with subsequent neutrophilia and death. This finding suggests that in addition to closely monitoring the two laboratory parameters describe above, special care should be taken to asses blood films for the presence of immature myeloid precursors. Additional studies will be required to validate these findings in a larger group of hospitalized patients (Figure Presented)
EMBASE:634717280
ISSN: 1530-0307
CID: 4857082

The OSPE

Belovarac, Brendan J; Zabar, Sondra R; Warfield, Dana; Bannan, Michael A; Rapkiewicz, Amy V
OBJECTIVES/OBJECTIVE:Resident assessment tends to consist of multiple-choice examinations, even in nuanced areas, such as quality assurance. Internal medicine and many other specialties use objective structured clinical examinations, or OSCEs, to evaluate residents. We adapted the OSCE for pathology, termed the Objective Structured Pathology Examination (OSPE). METHODS:The OSPE was used to evaluate first- and second-year residents over 2 years. The simulation included an anatomic pathology sign-out session, where the resident could be evaluated on diagnostic skills and knowledge of key information for cancer staging reports, as well as simulated frozen-section analysis, where the resident could be evaluated on communication skills with a "surgeon." The OSPE also included smaller cases with challenging quality issues, such as mismatched slides or gross description irregularities. All cases were scored based on the Pathology Milestones created by the Accreditation Council for Graduate Medical Education. RESULTS:Using this OSPE, we were able to demonstrate that simulated experiences can be an appropriate tool for standardized evaluation of pathology residents. CONCLUSIONS:Yearly evaluation using the OSPE could be used to track the progress of both individual residents and the residency program as a whole, identifying problem areas for which further educational content can be developed.
PMID: 33049036
ISSN: 1943-7722
CID: 4632662

Identification of Immunohistochemical Reagents for In Situ Protein Expression Analysis of Coronavirus-associated Changes in Human Tissues

Szabolcs, Matthias; Sauter, Jennifer L; Frosina, Denise; Geronimo, Jerica A; Hernandez, Enmily; Selbs, Elena; Rapkiewicz, Amy V; Rekhtman, Natasha; Baine, Marina K; Jäger, Elke; Travis, William D; Jungbluth, Achim A
We studied the suitability of commercially available monoclonal antibodies (mAbs) for the immunohistochemical (IHC) detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in standard archival specimens. Antibodies were screened on HEK293 cells transfected with viral nucleoprotein, S1 subunit and S2 subunit of spike protein and on untransfected cells, as well as a panel of normal tissue. Lung tissue with presence of SARS-CoV2 confirmed by in situ hybridization (ISH) was also used. A total of 7 mAbs were tested: (1) mAb 001 (Sino Biological, 40143-R001), (2) mAb 007 (Sino Biological, 40150-R007), (3) mAb 019 (Sino Biological, 40143-R019), (4) mAb 1A9 (GeneTex, GTX632604), (5) mAb ABM19C9 (Abeomics, 10-10007), (6) FIPV3-70 (Santa Cruz, SC-65653), and (7) mAb 6F10 (BioVision, A2060). Only 2 mAbs, clone 001 to the nucleoprotein and clone 1A9 to the S2 subunit spike protein displayed specific immunoreactivity. Both clones showed strong staining in the acute phase of COVID-19 pneumonia, mostly in areas of acute diffuse alveolar damage, but were not completely congruent. Viral protein was also found in kidney tubules, endothelia of multiple organs and a nasal swab of a patient with persistent SARS-CoV2 infection. The other tested reagents were either poorly reactive or demonstrated nonspecific staining in tissues and lesions not infected by SARS-CoV2. Our study demonstrates that rigid specificity testing is mandatory for the evaluation of mAbs to SARS-CoV2 and that clones 001 to nucleoprotein and 1A9 to S2 subunit spike protein are useful for the in situ detection of SARS-CoV2.
PMID: 33086222
ISSN: 1533-4058
CID: 4642322

Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID-19)

Zhao, Chaohui Lisa; Rapkiewicz, Amy; Maghsoodi-Deerwester, Mona; Gupta, Mala; Cao, Wenqing; Palaia, Thomas; Zhou, Jianhong; Ram, Bebu; Vo, Duc; Rafiee, Behnam; Hossein-Zadeh, Zarrin; Dabiri, Bahram; Hanna, Iman
Although coronavirus disease 2019 (COVID-19) is transmitted via respiratory droplets, there are multiple gastrointestinal and hepatic manifestations of the disease, including abnormal liver-associated enzymes. However, there are not many published articles on the pathological findings in the liver of patients with COVID-19. We collected the clinical data from 17 autopsy cases of patients with COVID-19 including age, sex, Body mass index (BMI), liver function test (alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), direct bilirubin, and total bilirubin), D-dimer, and anticoagulation treatment. We examined histopathologic findings in postmortem hepatic tissue, immunohistochemical (IHC) staining with antibody against COVID-19 spike protein, CD68 and CD61, and electron microscopy. We counted the number of megakaryocytes in liver sections from these COVID-19-positive cases. Abnormal liver-associated enzymes were observed in 12 of 17 cases of COVID-19 infection. With the exception of three cases that had not been tested for D-dimer, all 14 patients' D-dimer levels were increased, including the cases that received varied doses of anticoagulation treatment. Microscopically, the major findings were widespread platelet-fibrin microthrombi, steatosis, histiocytic hyperplasia in the portal tract, mild lobular inflammation, ischemic-type hepatic necrosis, and zone 3 hemorrhage. Rare megakaryocytes were found in sinusoids. COVID-19 IHC demonstrates positive staining of the histiocytes in the portal tract. Under electron microscopy, histiocyte proliferation is present in the portal tract containing lipid droplets, lysosomes, dilated ribosomal endoplasmic reticulum, microvesicular bodies, and coronavirus. The characteristic findings in the liver of patients with COVID-19 include numerous amounts of platelet-fibrin microthrombi, as well as various degrees of steatosis and histiocytic hyperplasia in the portal tract. Possible mechanisms are also discussed.
PMCID:7722493
PMID: 33307078
ISSN: 1532-8392
CID: 4770842

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