BACKGROUND Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe, disproportionately affecting New York City. A comprehensive, integrative autopsy series that advances the mechanistic discussion surrounding this disease process is still lacking. METHODS Autopsies were performed at the Mount Sinai Hospital on 67 COVID-19 positive patients and data from the clinical records were obtained from the Mount Sinai Data Warehouse. The experimental design included a comprehensive microscopic examination carried out by a team of expert pathologists, along with transmission electron microscopy, immunohistochemistry, RNA in situ hybridization, as well as immunology and serology assays. RESULTS Laboratory results of our COVID-19 cohort show elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8 and TNFα. Autopsies revealed large pulmonary emboli in four cases. We report microthrombi in multiple organ systems including the brain, as well as conspicuous hemophagocytosis and a secondary hemophagocytic lymphohistiocytosis-like syndrome in many of our patients. We provide electron microscopic, immunofluorescent and immunohistochemical evidence of the presence of the virus and the ACE2 receptor in our samples. CONCLUSIONS We report a comprehensive autopsy series of 67 COVID-19 positive patients revealing that this disease, so far conceptualized as a primarily respiratory viral illness, also causes endothelial dysfunction, a hypercoagulable state, and an imbalance of both the innate and adaptive immune responses. Novel findings reported here include an endothelial phenotype of ACE2 in selected organs, which correlates with clotting abnormalities and thrombotic microangiopathy, addressing the prominent coagulopathy and neuropsychiatric symptoms. Another original observation is that of macrophage activation syndrome, with hemophagocytosis and a hemophagocytic lymphohistiocytosis-like disorder, underlying the microangiopathy and excessive cytokine release. We discuss the involvement of critical regulatory pathways.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted undergraduate medical education, including preclinical class-based courses, by requiring social distancing and essentially eliminating in-person teaching. The aim of this study was to compare student performance and satisfaction before and after implementation of remote instruction in a first-year introductory pathology course. Assessments (3 quizzes, 1 practical exam, and 1 final) were compared between courses given before (January 2020) and during (January 2021) the COVID-19 pandemic, in terms of mean scores, degree of difficulty, and item discrimination, both overall and across different question types. Students’ evaluations of the course (Likert scale-based) were also compared between the 2 years. Significantly higher mean scores were observed during remote instruction (compared to the prior, in-person year) on verbatim-repeated questions (94.9 ± 8.8 vs 89.4 ± 12.2; P = .002) and on questions incorporating a gross specimen image (88.4 ± 7.5 vs 84.4 ± 10.3; P = .007). The percentage of questions that were determined to be moderate/hard in degree of difficulty and good/very good in item discrimination remained similar between the 2 time periods. In the practical examination, students performed significantly better during remote instruction on questions without specimen images (96.5 ± 7.0 vs 91.2 ± 15.2; P = .004). Finally, course evaluation metrics improved, with students giving a higher mean rating value in each measured end point of course quality during the year of remote instruction. In conclusion, student performance and course satisfaction generally improved with remote instruction, suggesting that the changes implemented, and their consequences, should perhaps inform future curriculum improvements.

Human papillomavirus (HPV) is a principal driver for most oropharyngeal squamous cell carcinomas (OPSCCs), where it is strongly associated with improved survival. HPV is much less frequently detected in squamous cell carcinomas arising in nonoropharyngeal sites (non-OPSCCs), and its pathogenic role and prognostic value in these tumors is unclear. We evaluated the clinicopathologic features of 52 non-OPSCCs considered HPV-positive based upon p16 immunohistochemistry and direct HPV detection using RNA in situ hybridization (ISH), DNA ISH, or real-time DNA polymerase chain reaction. The HPV-positive non-OPSCCs were from the larynx (n=27), oral cavity (n=21), and hypopharynx (n=4). While most cases (n=34, 65%) showed classic histologic features of HPV-positive OPSCC, including endophytic growth, minimal keratinization, and hyperchromatic nuclei without koilocytic changes, a subset (n=13, 25%) were characterized by exophytic growth, exuberant surface hyperkeratosis and parakeratosis, marked nuclear pleomorphism, and prominent koilocytic atypia. These antithetical features were highly reminiscent of the warty variant of HPV-positive squamous cell carcinoma described in anogenital sites. Compared with tumors without warty features, the warty tumors presented at lower stage and were not associated with lymph node metastasis, local recurrence, or distant spread (4 y disease-free survival of 100% vs. 66%, P=0.069). The presence of transcriptionally active HPV as detected by RNA ISH suggests a pathogenic role for HPV in these nonoropharyngeal sites. While most HPV-positive non-OPSCCs are morphologically similar to their tonsillar counterparts, this study highlights a previously unrecognized warty variant that may be associated with a highly favorable clinical outcome.

Context.— Evaluation of medical curricula includes appraisal of student assessments in order to encourage deeper learning approaches. General pathology is our institution's 4-week, first-year course covering universal disease concepts (inflammation, neoplasia, etc). Objective.— To compare types of assessment questions and determine which characteristics may predict student scores, degree of difficulty, and item discrimination. Design.— Item-level analysis was employed to categorize questions along the following variables: type (multiple choice question or matching answer), presence of clinical vignette (if so, whether simple or complex), presence of specimen image, information depth (simple recall or interpretation), knowledge density (first or second order), Bloom taxonomy level (1–3), and, for the final, subject familiarity (repeated concept and, if so, whether verbatim). Results.— Assessments comprised 3 quizzes and 1 final exam (total 125 questions), scored during a 3-year period (total 417 students) for a total 52 125 graded attempts. Overall, 44 890 attempts (86.1%) were correct. In multivariate analysis, question type emerged as the most significant predictor of student performance, degree of difficulty, and item discrimination, with multiple choice questions being significantly associated with lower mean scores (P = .004) and higher degree of difficulty (P = .02), but also, paradoxically, poorer discrimination (P = .002). The presence of a specimen image was significantly associated with better discrimination (P = .04), and questions requiring data interpretation (versus simple recall) were significantly associated with lower mean scores (P = .003) and a higher degree of difficulty (P = .046). Conclusions.— Assessments in medical education should comprise combinations of questions with various characteristics in order to encourage better student performance, but also obtain optimal degrees of difficulty and levels of item discrimination.