Collagen-Specific HSP47+ Myofibroblasts and CD163+ Macrophages Identify Profibrotic Phenotypes in Deceased Hearts With SARS-CoV-2 Infections.

Background Cardiac fibrosis complicates SARS-CoV-2 infections and has been linked to arrhythmic complications in survivors. Accordingly, we sought evidence of increased HSP47 (heat shock protein 47), a stress-inducible chaperone protein that regulates biosynthesis and secretion of procollagen in heart tissue, with the goal of elucidating molecular mechanisms underlying cardiac fibrosis in subjects with this viral infection. Methods and Results Using human autopsy tissue, immunofluorescence, and immunohistochemistry, we quantified Hsp47+ cells and collagen α 1(l) in hearts from people with SARS-CoV-2 infections. Because macrophages are also linked to inflammation, we measured CD163+ cells in the same tissues. We observed irregular groups of spindle-shaped HSP47+ and CD163+ cells as well as increased collagen α 1(I) deposition, each proximate to one another in "hot spots" of ≈40% of hearts after SARS-CoV-2 infection (HSP47+ P<0.05 versus nonfibrotics and P<0.001 versus controls). Because HSP47+ cells are consistent with myofibroblasts, subjects with hot spots are termed "profibrotic." The remaining 60% of subjects dying with COVID-19 without hot spots are referred to as "nonfibrotic." No control subject exhibited hot spots. Conclusions Colocalization of myofibroblasts, M2(CD163+) macrophages, and collagen α 1(l) may be the first evidence of a COVID-19-related "profibrotic phenotype" in human hearts in situ. The potential public health and diagnostic implications of these observations require follow-up to further define mechanisms of viral-mediated cardiac fibrosis.

Emerging therapeutics in the management of COVID-19.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) pandemic has placed a tremendous burden on healthcare systems globally. Therapeutics for treatment of the virus are extremely inconsistent due to the lack of time evaluating drug efficacy in clinical trials. Currently, there is a deficiency of published literature that comprehensively discusses all therapeutics being considered for the treatment of COVID-19. A review of the literature was performed for articles related to therapeutics and clinical trials in the context of the current COVID-19 pandemic. We used PubMed, Google Scholar, and Clinicaltrials.gov to search for articles relative to the topic of interest. We used the following keywords: "COVID-19", "therapeutics", "clinical trials", "treatment", "FDA", "ICU", "mortality", and "management". In addition, searches through the references of retrieved articles was also performed. In this paper, we have elaborated on the therapeutic strategies that have been hypothesized or trialed to-date, the mechanism of action of each therapeutic, the clinical trials finished or in-process that support the use of each therapeutic, and the adverse effects associated with each therapeutic. Currently, there is no treatment that has been proven to provide significant benefit in reducing morbidity and mortality. There are many clinical trials for numerous different therapeutic agents currently underway. By looking back and measuring successful strategies from previous pandemics in addition to carrying out ongoing research, we provide ourselves with the greatest opportunity to find treatments that are beneficial.

Utilization of extracorporeal membrane oxygenation during the COVID-19 pandemic.

The ongoing outbreak of severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2, or coronavirus disease 2019 (COVID-19)] was declared a pandemic by the World Health Organization on March 11, 2020. Worldwide, more than 65 million people have been infected with this SARS-CoV-2 virus, and over 1.5 million people have died due to the viral illness. Although a tremendous amount of medical progress has been made since its inception, there continues to be ongoing research regarding the pathophysiology, treatments, and vaccines. While a vast majority of those infected develop only mild to moderate symptoms, about 5% of people have severe forms of infection resulting in respiratory failure, myocarditis, septic shock, or multi-organ failure. Despite maximal cardiopulmonary support and invasive mechanical ventilation, mortality remains high. Extracorporeal membrane oxygenation (ECMO) remains a valid treatment option when maximal conventional strategies fail. Utilization of ECMO in the pandemic is challenging from both resource allocation and ethical standpoints. This article reviews the rationale behind its use, current status of utilization, and future considerations for ECMO in critically ill COVID-19 patients.

COVID-19 and Hypercoagulability: A Review.

Thrombotic complications of the novel coronavirus (COVID-19) are a concerning aspect of the disease, due to the high incidence in critically ill patients and poor clinical outcomes. COVID-19 predisposes patients to a hypercoagulable state, however, the pathophysiology behind the thrombotic complications seen in this disease is not well understood. Several mechanisms have been proposed and the pathogenesis likely involves a host immune response contributing to vascular endothelial cell injury, inflammation, activation of the coagulation cascade via tissue factor expression, and shutdown of fibrinolysis. Treatments targeting these pathways may need to be considered to improve clinical outcomes and decrease overall mortality due to thrombotic complications. In this review, we will discuss the proposed pathophysiologic mechanisms for thrombotic complications in COVID-19, as well as treatment strategies for these complications based on the current literature available.

Telemedicine, the current COVID-19 pandemic and the future: a narrative review and perspectives moving forward in the USA.

A narrative review was conducted to examine the current state of the utilisation of telemedicine amid the current COVID-19 pandemic and to evaluate the benefits of continuing telemedicine usage in the future. A literature review was performed for articles related to telemedicine. Databases including PubMed, Google Scholar, Cochrane Library and Ovid MEDLINE were searched. Three reviewers independently performed article selection based on relevance to our topic. We included all articles between 1990 and 2020 related to telemedicine using the following keywords: 'telemedicine', 'telehealth', 'policy', 'COVID-19', 'regulation', 'rural', 'physical examination', 'future'. A total of 60 articles were identified, and through careful selection we narrowed the final number of articles to 42 based on relevance to our topic. Telemedicine has been rapidly evolving over the past several decades. Issues with regulation and reimbursement have prevented its full immersion into the healthcare system. During the current pandemic, Centers for Medicare and Medicaid services have expanded access to telemedicine services. The advantages of telemedicine moving forward include its cost-effectiveness, ability to extend access to specialty services and its potential to help mitigate the looming physician shortage. Disadvantages include lack of available technological resources in certain parts of the country, issues with security of patient data, and challenges in performing the traditional patient examination. It is critically important that changes are made to fully immerse telemedicine services into the healthcare landscape in order to be prepared for future pandemics as well as to reap the benefits of this service in the future.

Epstein-Barr Virus Versus Novel Coronavirus-Induced Hemophagocytic Lymphohistocytosis: The Uncharted Waters.

Hemophagocytic lymphohistocytosis (HLH) is a hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, and pancytopenia. It may be associated with genetic mutations or viral/bacterial infections, most commonly Epstein-Barr virus (EBV) and cytomegalovirus. As for the novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also known as COVID-19 (coronavirus disease-2019), the cytokine storm it triggers can theoretically lead to syndromes similar to HLH. In this article, we report a case of a 28-year-old female who presented with high-grade fevers, found to have both SARS-CoV-2 and EBV infections, and eventually began to show signs of early HLH. To our knowledge, this is the first case reported in literature that raises the possibility of SARS-CoV-2-related HLH development.

COVID-19 and Acute Lupus Pneumonitis: Diagnostic and Treatment Dilemma.

In this article, we present a case of a young female patient with previously diagnosed lupus pneumonitis, now with a flare and new superimposed COVID-19 infection that was treated with intravenous steroids. On computed tomography scans, she had extensive interstitial lung fibrosis in addition to a positive COVID-19 polymerase chain reaction test requiring 6 L of oxygen via nasal cannula on admission. After administration of methylprednisolone, the patient improved and was weaned off her oxygen requirements and was discharged home.