Faculty Bibliography

[Figure: see text].

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)

CONTEXT/BACKGROUND:This study represents the largest compilation to date of clinical and postmortem data from decedents with coronavirus disease 2019 (COVID-19). It will augment previously published small series of autopsy case reports, refine clinicopathologic considerations, and improve the accuracy of future vital statistical reporting. OBJECTIVE:To accurately reflect the pre-existing diseases and pathologic conditions of decedents with Sars-CoV-2 infection through autopsy. DESIGN/METHODS:Comprehensive data from 135 autopsy evaluations of COVID-19-positive decedents is presented, including histologic assessment. Postmortem examinations were performed by 36 pathologists at 19 medical centers or forensic institutions in the United States and Brazil. Data from each autopsy were collected through the online submission of multiple choice and openended survey responses. RESULTS:Patients dying of or with COVID-19 had an average of 8.89 pathologic conditions documented at autopsy, spanning a combination of prior chronic disease and acute conditions acquired during hospitalization. Virtually all decedents were cited as having more than one preexisting condition, encompassing an average of 2.88 such diseases each. Clinical conditions during terminal hospitalization were cited 395 times for the 135 autopsied decedents and predominantly encompassed acute failure of multiple organ systems and/or impaired coagulation. Myocarditis was rarely cited. CONCLUSIONS:Cause-of-death statements in both autopsy reports and death certificates may not encompass the severity or spectrum of co-morbid conditions in those dying of or with COVID-19. If supported by additional research, this finding may have implications for public health decisions and reporting moving forward through the pandemic.

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.

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.

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.

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.