Coronary Stent Abscess in the Setting of Arteriovenous Graft Infection following COVID-19: An Autopsy Case Report.

While rare, coronary stent infections present with significant mortality-with most infections and further complications occurring within months of percutaneous coronary intervention (PCI). Here, we discuss a post-COVID-19 patient who presented approximately one year after PCI for declotting of an arteriovenous graft (AVG). Upon admission, the patient was found to be bacteremic with multilobar pneumonia and an infection of the AVG. Empiric antibiotics were started, and blood cultures were subsequently positive for MRSA. Removal of the AVG was unsuccessful, and two days after admission, the patient passed. Autopsy revealed a perivascular abscess in the RCA near the origin of the stent with a ground section of the RCA with stent revealing abundant calcific atherosclerosis and marked necrosis of the artery wall. The cause of death was determined to be sepsis complicating coronary artery disease and chronic renal failure.

Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis.

Objectives: Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics. Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear. Methods: Autopsy-derived cardiac tissue from control (n = 4) and COVID-19 (n = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling in situ with preserved anatomy and unaltered local SARS-CoV-2 expression. In so doing, we examined the paracrine effect of SARS-CoV-2 infection in cardiac tissue. Results: We observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels. Conclusion: Our results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis, and endothelial activation as key drivers of cardiovascular events during COVID-19.

A high-resolution 3D atlas of the spectrum of tuberculous and COVID-19 lung lesions.

Our current understanding of the spectrum of TB and COVID-19 lesions in the human lung is limited by a reliance on low-resolution imaging platforms that cannot provide accurate 3D representations of lesion types within the context of the whole lung. To characterize TB and COVID-19 lesions in 3D, we applied micro/nanocomputed tomography to surgically resected, postmortem, and paraffin-embedded human lung tissue. We define a spectrum of TB pathologies, including cavitary lesions, calcium deposits outside and inside necrotic granulomas and mycetomas, and vascular rearrangement. We identified an unusual spatial arrangement of vasculature within an entire COVID-19 lobe, and 3D segmentation of blood vessels revealed microangiopathy associated with hemorrhage. Notably, segmentation of pathological anomalies reveals hidden pathological structures that might otherwise be disregarded, demonstrating a powerful method to visualize pathologies in 3D in TB lung tissue and whole COVID-19 lobes. These findings provide unexpected new insight into the spatial organization of the spectrum of TB and COVID-19 lesions within the framework of the entire lung.

Perspectives of people living with HIV-1 on implementation of long-acting cabotegravir plus rilpivirine in US healthcare settings: results from the CUSTOMIZE hybrid III implementation-effectiveness study.

INTRODUCTION: The CUSTOMIZE hybrid III implementation-effectiveness study evaluated implementation of once-monthly long-acting (LA) cabotegravir + rilpivirine in diverse US healthcare settings. Here, we report patient participant perspectives after 12 months in CUSTOMIZE. METHODS: CUSTOMIZE was a phase IIIb, 12-month study conducted from July 2019 to October 2020 at eight diverse US HIV clinics that enrolled virologically suppressed people living with HIV-1 (PLHIV) on a stable oral regimen to receive monthly cabotegravir + rilpivirine LA injections after a 1-month oral lead-in. Participants were administered quantitative surveys before injections at months 1 (baseline), 4 and 12. A randomly selected subset of participants was interviewed at baseline and month 12. Data collection at month 12 was completed by October 2020 (during the COVID-19 pandemic). RESULTS: At baseline, 109 and 34 participants completed surveys and interviews, respectively; 87% were male; 35% were Black or African American. All participants who remained in the study at month 12 (n = 102) maintained HIV-1 RNA <50 copies/ml; two participants withdrew due to injection-related reasons. Mean total scores measuring acceptability and appropriateness of cabotegravir + rilpivirine LA were high at baseline (4.5-4.6 out of 5) and month 12 (4.7-4.9). At month 12, 74% of participants reported nothing interfered with receiving LA injections; injection pain or soreness was the most common concern (15%). Time spent in the clinic and coming to the clinic for monthly injections was very or extremely acceptable after 12 months for most participants (93% and 87%, respectively), with 64% reporting having spent ≤30 minutes in the clinic for injection visits. At month 12, 92% of participants preferred LA injections to daily oral tablets (3%); 97% plan to continue LA treatment going forward. In month 12 interviews, 24 (77%) of 31 participants reported the COVID-19 pandemic did not impact their ability to receive treatment. CONCLUSIONS: Once-monthly cabotegravir + rilpivirine LA was highly acceptable among PLHIV who were virologically suppressed on a stable antiretroviral regimen and interested in trying LA therapy, with few participants reporting challenges receiving LA injections. Implementation data from CUSTOMIZE suggest that monthly LA injections provide a convenient and appealing treatment option for PLHIV.

Perspectives of healthcare providers on implementation of long-acting cabotegravir plus rilpivirine in US healthcare settings from a Hybrid III Implementation-effectiveness study (CUSTOMIZE).

INTRODUCTION: CUSTOMIZE evaluated the implementation of long-acting (LA) cabotegravir + rilpivirine, a novel healthcare provider-administered injectable antiretroviral therapy regimen, in diverse US healthcare settings. Findings from staff-study participants (SSPs) through 12 months of implementation are reported. METHODS: CUSTOMIZE was a phase IIIb, 12-month, single-arm, hybrid III implementation-effectiveness study conducted from July 2019 to October 2020 at eight US clinics of five clinic types: private practice (n = 2), federally qualified health centre (n = 2), university (n = 2), AIDS Healthcare Foundation (n = 2) and health maintenance organization (n = 1). Eligible patient participants received monthly cabotegravir + rilpivirine LA injections after a 1-month oral lead-in. At baseline, month 4 and month 12, SSPs (n = 3 each per clinic), including physicians, nurses or injectors, and administrators, completed quantitative surveys and semi-structured interviews to assess implementation outcomes (acceptability, appropriateness and feasibility of intervention measures), programme sustainability and SSP perceptions of, attitudes towards, and expectations for cabotegravir + rilpivirine LA. Month 12 data collection occurred during the COVID-19 pandemic. RESULTS: In surveys, SSPs reported high mean total scores for acceptability, appropriateness and feasibility of cabotegravir + rilpivirine LA implementation at baseline (4.43, 4.52 and 4.38 of 5, respectively) and month 12 (4.45, 4.61 and 4.46 of 5, respectively), regardless of clinic type. At month 12, SSPs were positive about the implementation sustainability (mean Program Sustainability Assessment Tool score, 5.83 out of 7). At baseline, SSPs' top concern was patients' ability to maintain monthly appointments (81%); at month 12, 39% had this concern. The proportion of SSPs reporting patient injection pain or soreness as a barrier was consistent at month 12 versus baseline (48% vs. 46%). Most (78%) SSPs reported optimal implementation of cabotegravir + rilpivirine LA in their clinics was achieved in 1-3 months. In interviews, SSP-reported strategies for successful implementation included teamwork, using a web-based treatment planner and having a designated person to track appointment scheduling. In month 12 interviews, SSP-reported structural changes needed for implementation included changing clinic hours and purchasing refrigerators. CONCLUSIONS: In CUSTOMIZE, cabotegravir + rilpivirine LA was successfully implemented across a range of US healthcare settings. Barriers were mitigated with minor process adjustments.

Gastrointestinal Manifestations of COVID-19 Infection: Clinicopathologic Findings in Intestinal Resections Performed at Single Institution.

It is now known that COVID-19 not only involves the lungs, but other organs as well including the gastrointestinal tract. Although clinic-pathological features are well-described in lungs, the histopathologic features of gastrointestinal involvement in resection specimens are not well characterized. Herein, we describe in detail the clinicopathologic features of intestinal resection specimens in four patients with COVID-19 infection. COVID-19 viral particles by in situ hybridization and immunofluorescence studies are also demonstrated. All four patients were males, aged 28-46 years, with comorbidities. They initially presented with a severe form of pulmonary COVID-19 and showed gastrointestinal symptoms, requiring surgical intervention. Histopathologic examination of resected GI specimens, mostly right colectomies, revealed a spectrum of disease, from superficial mucosal ischemic colitis to frank transmural ischemic colitis and associated changes consistent with pneumatosis cystoides intestinalis. Three patients were African American (75%), and one was Caucasian (25%); three patients died due to complications of their COVID-19 infection (75%), while one ultimately recovered from their GI complications (25%), but experienced prolonged sequela of COVID-19 infection including erectile dysfunction. In conclusion, COVID-19 infection, directly or indirectly, can cause ischemic gastrointestinal complications, with predilection for the right colon.

THE IMPACT OF OLDER ADULTS' LIVING ENVIRONMENT ON THEIR HEALTHY AGING IN PLACE DURING THE COVID-19 PANDEMIC

Keywords: older adults, private home, cohousing, assisted living, healthy aging, COVID-19 pandemic THE IMPACT OF OLDER ADULTS' LIVING ENVIRONMENT ON THEIR HEALTHY AGING IN PLACE DURING THE COVID-19 PANDEMIC The World Health Organization (WHO) declared the novel Coronavirus [SARS-CoV-2], which causes COVID-19, a respiratory disease, a public health emergency on March 11, 2020 (Government of Canada, 2021;Nascimento, 2020). The research question was, "how does older adults' living environment promote their healthy aging in place during the COVID-19 pandemic?" LITERATURE REVIEW Multiple factors, including an individual's composition, physical environment, social interaction, independence, cognitive/mental health, mobility, transportation, services such as recreational opportunities, healthcare and information work together to impact older adults' healthy aging (Bigonnesse, 201 7;Puplampu, Matthews, et al., 2020). Healthy aging is a multidimensional construct that indicates the older adult is doing well;it can be defined as promoting and optimizing the health of an older adult by managing chronic diseases, ensuring cognitive, physical, and mental health, facilitating social engagement and resilience, independence, safety, support and services from the community (Batsis et al., 2021;Government of Canada, 201 6;Lock & Belza, 201 6;Pac et al., 2019). Housing for older adults plays a key role in their healthy aging, which became apparent during the COVID-19 pandemic as long-term care facilities in Canada became high-risk settings and sources of outbreaks and deaths (Public Health Agency of Canada, 2020).

Use of Telepathology to Facilitate COVID-19 Research and Education through an Online COVID-19 Autopsy Biorepository.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has increased the use of technology for communication including departmental conferences, working remotely, and distance teaching. Methods to enable these activities should be developed and promulgated. OBJECTIVE: To repurpose a preexisting educational website to enable the development of a COVID-19 autopsy biorepository to support distance teaching and COVID-19 research. METHODS: After consent was obtained, autopsies were performed on patients with a confirmed positive severe acute respiratory syndrome coronavirus-2 reverse-transcriptase-polymerase-chain reaction test. Autopsies were performed according to a COVID-19 protocol, and all patients underwent both gross and microscopic examination. The H and E histology slides were scanned using a Leica Biosystems Aperio CS ScanScope whole slide scanner and the digital slide files were converted to deep zoom images that could be uploaded to the University of Alabama at Birmingham (UAB) Pathology Educational Instructional Resource website where virtual microscopy of the slides is available. RESULTS: A total of 551 autopsy slides from 24 UAB COVID-19 cases, 1 influenza H1N1 case and 1 tuberculosis case were scanned and uploaded. Five separate COVID-19 research teams used the digital slides remotely with or without a pathologist on a Zoom call. The scanned slides were used to produce one published case report and one published research project. The digital COVID-19 autopsy biorepository was routinely used for educational conferences and research meetings locally, nationally and internationally. CONCLUSION: The repurposing of a pre-existing website enabled telepathology consultation for research and education purposes. Combined with other communication technology (Zoom) this achievement highlights what is possible using pre-existing technologies during a global pandemic.

Cardiac pathology in COVID-19: a single center autopsy experience.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is commonly associated with myocardial injury and heart failure. The pathophysiology behind this phenomenon remains unclear, with many diverse and multifaceted hypotheses. To contribute to this understanding, we describe the underlying cardiac findings in fifty patients who died with coronavirus disease 2019 (COVID-19). METHODS: Included were autopsies performed on patients with a positive SARS-CoV-2 reverse-transcriptase-polymerase-chain reaction test from the index hospitalization. In the case of out-of-hospital death, patients were included if post-mortem testing was positive. Complete autopsies were performed according to a COVID-19 safety protocol, and all patients underwent both macroscopic and microscopic examination. If available, laboratory findings and echocardiograms were reported. RESULTS: The median age of the decedents was 63.5 years. The most common comorbidities included hypertension (90.0%), diabetes (56.0%) and obesity (50.0%). Lymphocytic inflammatory infiltrates in the heart were present in eight (16.0%) patients, with focal myocarditis present in two (4.0%) patients. Acute myocardial ischemia was observed in eight (16.0%) patients. The most common findings were myocardial fibrosis (80.0%), hypertrophy (72.0%), and microthrombi (66.0%). The most common causes of death were COVID-19 pneumonia in 18 (36.0%), COVID-19 pneumonia with bacterial superinfection in 12 (24.0%), and COVID-19 pneumonia with pulmonary embolism in 10 (20.0%) patients. CONCLUSIONS: Cardiovascular comorbidities were prevalent, and pathologic changes associated with hypertensive and atherosclerotic cardiovascular disease were the most common findings. Despite markedly elevated inflammatory markers and cardiac enzymes, few patients exhibited inflammatory infiltrates or necrosis within cardiac myocytes. A unifying pathophysiologic mechanism behind myocardial injury in COVID-19 remains elusive, and additional autopsy studies are needed.

A Postmortem Portrait of the Coronavirus Disease 2019 (COVID-19) Pandemic: A Large Multi-institutional Autopsy Survey Study.

CONTEXT.­: 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 preexisting diseases and pathologic conditions of decedents with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection through autopsy. DESIGN.­: 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 open-ended 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 1 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 comorbid 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.

Spatial mapping of SARS-CoV-2 and H1N1 lung injury identifies differential transcriptional signatures.

Severe SARS-CoV-2 infection often leads to the development of acute respiratory distress syndrome (ARDS), with profound pulmonary patho-histological changes post-mortem. It is not clear whether ARDS from SARS-CoV-2 is similar to that observed in influenza H1N1, another common viral cause of lung injury. Here, we analyze specific ARDS regions of interest utilizing a spatial transcriptomic platform on autopsy-derived lung tissue from patients with SARS-CoV-2 (n = 3), H1N1 (n = 3), and a dual infected individual (n = 1). Enhanced gene signatures in alveolar epithelium, vascular tissue, and lung macrophages identify not only increased regional coagulopathy but also increased extracellular remodeling, alternative macrophage activation, and squamous metaplasia of type II pneumocytes in SARS-CoV-2. Both the H1N1 and dual-infected transcriptome demonstrated an enhanced antiviral response compared to SARS-CoV-2. Our results uncover regional transcriptional changes related to tissue damage/remodeling, altered cellular phenotype, and vascular injury active in SARS-CoV-2 and present therapeutic targets for COVID-19-related ARDS.

Stress-Induced Cardiomyopathy Precipitated by COVID-19 and Influenza A Coinfection.

Myocardial injury is associated with excess mortality in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections, but the mechanisms of injury are diverse. We describe a case of stress-induced cardiomyopathy in the setting of SARS-CoV-2 and influenza A coinfection. (Level of Difficulty: Intermediate.).