Multiple sclerosis (MS) patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, there is little data identifying clinical characteristics of MS associated with worse COVID-19 outcomes. Therefore, we conducted a multicenter prospective cohort study looking at the outcomes of 40 MS patients with confirmed COVID-19. Severity of COVID-19 infection was based on hospital course, where a mild course was defined as the patient not requiring hospital admission, moderate severity was defined as the patient requiring hospital admission to the general floor, and most severe was defined as requiring intensive care unit admission and/or death. 19/40(47.5%) had mild courses, 15/40(37.5%) had moderate courses, and 6/40(15%) had severe courses. Patients with moderate and severe courses were significantly older than those with a mild course (57[50-63] years old and 66[58.8-69.5] years old vs 48[40-51.5] years old, P = 0.0121, P = 0.0373). There was differing prevalence of progressive MS phenotype in those with more severe courses (severe:2/6[33.3%]primary-progressing and 0/6[0%]secondaryprogressing, moderate:1/14[7.14%] and 5/14[35.7%] vs mild:0/19[0%] and 1/19[5.26%], P = 0.0075, 1 unknown). Significant disability was found in 1/19(5.26%) mild course-patients, but was in 9/15(60%, P = 0.00435) of moderate course-patients and 2/6(33.3%, P = 0.200) of severe course-patients. Diseasemodifying therapy prevalence did not differ among courses (mild:17/19[89.5%], moderate:12/15[80%] and severe:3/6[50%], P = 0.123). MS patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive phenotype, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses.

SARS-CoV-2 is the virus responsible for the ongoing COVID-19 outbreak. The virus uses ACE2 receptor for viral entry. ACE2 is part of the counter-regulatory renin-angiotensin-aldosterone system and is also expressed in the lower respiratory tract along the alveolar epithelium. There is, however, significant controversy regarding the role of ACE2 expression in COVID-19 pathogenesis. Some have argued that decreasing ACE2 expression would result in decreased susceptibility to the virus by decreasing available binding sites for SARS-CoV-2 and restricting viral entry into the cells. Others have argued that, like the pathogenesis of other viral pneumonias, including those stemming from previous severe acute respiratory syndrome (SARS) viruses, once SARS-CoV-2 binds to ACE2, it downregulates ACE2 expression. Lack of the favourable effects of ACE2 might exaggerate lung injury by a variety of mechanisms. In order to help address this controversy, we conducted a literature search and review of relevant preclinical and clinical publications pertaining to SARS-CoV-2, COVID-19, ACE2, viral pneumonia, SARS, acute respiratory distress syndrome and lung injury. Our review suggests, although controversial, that patients at increased susceptibility to COVID-19 complications may have reduced baseline ACE2, and by modulating ACE2 expression one can possibly improve COVID-19 outcomes. Herein, we elucidate why and how this potential mechanism might work.

Importance: Multiple sclerosis patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, no study has identified clinical characteristics of multiple sclerosis associated with worse COVID-19 outcomes. Objective: To evaluate the clinical characteristics of multiple sclerosis, including staging, degree of disability, and disease-modifying therapy use that are associated with worse outcomes from COVID-19. Design: Prospective cohort study looking at the outcomes of multiple sclerosis patients with COVID-19 between March 1st and May 18th, 2020. Setting: This is a multicenter study of three distinct hospital systems within the U.S. Participants: The study included 40 consecutive patients with nasopharyngeal/oropharyngeal PCR-confirmed COVID-19 infection. Exposures: Multiple sclerosis staging, severe disability (based on baseline-extended disability status scale equal to or greater than 6.0) and disease-modifying therapy. Main Outcomes and Measure: Severity of COVID-19 infection was based on hospital course, where a mild course was defined as the patient not requiring hospital admission, moderate severity was defined as the patient requiring hospital admission to the general floor only, and most severe was defined as requiring intensive care unit admission and/or death. Results: For the 40 patients, the median age was 52(45.5-61) years, 16/40(40%) were male, and 21/40(52.5%) were African American. 19/40(47.5%) had mild courses, 15/40(37.5%) had moderate courses, and 6/40(15%) had severe courses. Patients with moderate and severe courses were significantly older than those with a mild course (57[50-63] years old and 66[58.8-69.5] years old vs 48[40-51.5] years old, P=0.0121, P=0.0373). There was differing prevalence of progressive multiple sclerosis staging in those with more severe courses (severe:2/6[33.3%]primary-progressing and 0/6[0%]secondary-progressing, moderate:1/14[7.14%] and 5/14[35.7%] vs mild:0/19[0%] and 1/19[5.26%], P=0.0075, 1 unknown). Significant disability was found in 1/19(5.26%) mild course-patients, but was in 9/15(60%, P=0.00435) of moderate course-patients and 2/6(33.3%, P=0.200) of severe course-patients. Disease-modifying therapy prevalence did not differ among courses (mild:17/19[89.5%], moderate:12/15[80%] and severe:3/6[50%], P=0.123). Conclusions and Relevance: Multiple sclerosis patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive staging, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses.

Cardiovascular disease encompasses a wide range of conditions, resulting in the highest number of deaths worldwide. The underlying pathologies surrounding cardiovascular disease include a vast and complicated network of both cellular and molecular mechanisms. Unique phenotypic alterations in specific cell types, visualized as varying RNA expression-levels (both coding and non-coding), have been identified as crucial factors in the pathology underlying conditions such as heart failure and atherosclerosis. Recent advances in single-cell RNA sequencing (scRNA-seq) have elucidated a new realm of cell subpopulations and transcriptional variations that are associated with normal and pathological physiology in a wide variety of diseases. This breakthrough in the phenotypical understanding of our cells has brought novel insight into cardiovascular basic science. scRNA-seq allows for separation of widely distinct cell subpopulations which were, until recently, simply averaged together with bulk-tissue RNA-seq. scRNA-seq has been used to identify novel cell types in the heart and vasculature that could be implicated in a variety of disease pathologies. Furthermore, scRNA-seq has been able to identify significant heterogeneity of phenotypes within individual cell subtype populations. The ability to characterize single cells based on transcriptional phenotypes allows researchers the ability to map development of cells and identify changes in specific subpopulations due to diseases at a very high throughput. This review looks at recent scRNA-seq studies of various aspects of the cardiovascular system and discusses their potential value to our understanding of the cardiovascular system and pathology.

BACKGROUND Although early reperfusion is the most desirable intervention after ischemic myocardial insult, it may add to damage through oxidative stress. OBJECTIVES We investigated the cardioprotective effects of a single intravenous dose of heat shock protein (HSP72) coupled to a single-chain variable fragment (Fv) of monoclonal antibody 3E10 (3E10Fv) in a rabbit ischemia-reperfusion model. The Fv facilitates rapid transport of HSP72 into cells, even with intact membranes. METHODS A left coronary artery occlusion (40 min), reperfusion (3 h) model was employed in 31 rabbits. Of these, 12 rabbits received the fusion protein (Fv-HSP72) intravenously. The remaining 19 control rabbits received a molar equivalent of 3E10Fv alone (n = 6), HSP72 alone (n = 6), or phosphate buffered saline (n = 7). Serial echocardiographic examinations were performed to assess left ventricular (LV) function before and after reperfusion. Micro-single photon emission computed tomography imaging of 99mTc-labeled annexin-V was performed with micro-computed tomography to characterize apoptotic damage in vivo, followed by gamma counting of the excised myocardial specimens to quantify cell death. Histopathological characterization of the myocardial tissue, and sequential cardiac troponin I measurements were also undertaken. RESULTS Myocardial annexin-V uptake was 43% lower in the area at risk (p = 0.0003) in Fv-HSP72-treated rabbits compared to controls receiving HSP72 or 3E10Fv alone. During reperfusion, troponin I release was 42% lower and the echocardiographic LV ejection fraction 27% higher in the Fv-HSP72-treated group compared to controls. Histopathological analyses confirmed penetration of 3E10Fv-containing molecules into cardiomyocytes in vivo, and treatment with Fv-HSP72 showed fewer apoptotic nuclei compared to control rabbits. CONCLUSIONS A single-dose administration of Fv-HSP72 fusion protein at the time of reperfusion reduced myocardial apoptosis almost by half, and improved LV functional recovery following myocardial ischemia-reperfusion injury in rabbits. It might have a potential to serve as an adjunct to early reperfusion in the management of myocardial infarction.

Despite substantial advances in the study, treatment, and prevention of cardiovascular disease, numerous challenges relating to optimally screening, diagnosing, and managing patients remain. Simultaneous improvements in computing power, data storage, and data analytics have led to the development of new techniques to address these challenges. One powerful tool to this end is machine learning (ML), which aims to algorithmically identify and represent structure within data. Machine learning’s ability to efficiently analyze large and highly complex data sets make it a desirable investigative approach in modern biomedical research. Despite this potential and enormous public and private sector investment, few prospective studies have demonstrated improved clinical outcomes from this technology. This is particularly true in cardiology, despite its emphasis on objective, data-driven results. This threatens to stifle ML’s growth and use in mainstream medicine. We outline the current state of ML in cardiology and outline methods through which impactful and sustainable ML research can occur. Following these steps can ensure ML reaches its potential as a transformative technology in medicine.

Duramycin is similarly effective in imaging apoptotic cell death as Annexin-V with lower nontarget organ radiation. Clinical feasibility of apoptosis imaging with a PE-seeking tracer should be tested.

The use of the EC agent Definity is safe in hospitalized patients with PHT.