scholarly journals COVID-19 Convalescent plasma

Blood ◽  
2021 ◽  
Author(s):  
Aaron Tobian ◽  
Claudia S Cohn ◽  
Beth Shaz
Keyword(s):  
Therapeutic Potential ◽  
High Titer ◽  
Severe Disease ◽  
Treatment Options ◽  
The United States ◽  
Trial Data ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Health Crisis ◽  
Viral Neutralization ◽  
Elderly Outpatients

As the coronavirus disease (COVID-19) pandemic led to a global health crisis, there were limited treatment options and no prophylactic therapies for those exposed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Convalescent plasma is quick to implement, potentially provides benefits, and has a good safety profile. The therapeutic potential of COVID-19 convalescent plasma (CCP) is likely mediated by antibodies through direct viral neutralization and Fc-dependent functions such as a phagocytosis, complement activation, and antibody-dependent cellular cytotoxicity. In the United States, CCP became one of the most common treatments with over half million units transfused despite limited efficacy data. More than a dozen randomized trials now demonstrate that CCP does not provide benefit for those with moderate to severe disease. However, similar to other passive antibody therapies, CCP is beneficial for early disease, when provided to elderly outpatients within 72 hours after symptom onset. Only high-titer CCP should be transfused. CCP should also be considered for immunosuppressed COVID-19 patients. CCP collected in proximity, by time and location, to the patient may be more beneficial due to SARS-CoV-2 variants. Additional randomized trial data are still accruing and should be incorporated with other trial data to optimize CCP indications.

scholarly journals Engineered collagen-targeting therapeutics reverse lung and kidney fibrosis in mice

2022 ◽  
Author(s):  
MICHAEL John Victor WHITE ◽  
Michal Raczy ◽  
Erica Budina ◽  
Ani Solanki ◽  
Zheng Jenny Zhang ◽  
...  
Keyword(s):  
Mouse Models ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
The United States ◽  
Kidney Fibrosis ◽  
Fibrotic Diseases ◽  
Von Willebrand ◽  
Clinical Potential ◽  
Lung And Kidney

Fibrotic diseases are involved in 45% of deaths in the United States. In particular, fibrosis of the kidney and lung are major public health concerns due to their high prevalence and lack of existing treatment options. Here, we harness the pathophysiological features of fibrotic diseases, namely leaky vasculature and aberrant extracellular matrix (ECM) protein deposition (i.e. collagen), to target an anti-fibrotic biologic and a small molecule drug to disease sites of fibrosis, thus improving their therapeutic potential in mouse models of lung and kidney fibrosis. First, we identify and validate collagen-targeting drug delivery systems that preferentially accumulate in the diseased organs: von Willebrand Factor's A3 domain (VWF-A3) and decorin-derived collagen-binding peptide-conjugated micelles (CBP-micelles). We then engineer and recombinantly express novel candidate biologic therapies based on the anti-inflammatory cytokine IL-10: A3-IL-10 and A3-Serum Albumin-IL-10 (A3-SA-IL-10). Simultaneously, we stably encapsulate the potential anti-fibrotic water-insoluble drug, rapamycin, in CBP-micelles. We show that these novel formulations of therapeutics bind to collagen in vitro and that their efficacy in mouse models of lung and kidney fibrosis is improved, compared to free, untargeted drugs. Our results demonstrate that collagen-targeted anti-fibrotic drugs may be next generation therapies of high clinical potential.

scholarly journals Androgen Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men

2020 ◽  
Author(s):  
Zaniar Ghazizadeh ◽  
Homa Majd ◽  
Mikayla Richter ◽  
Ryan Samuel ◽  
Seyedeh Maryam Zekavat ◽  
...  
Keyword(s):  
Troponin T ◽  
Severe Disease ◽  
Treatment Options ◽  
Cardiac Injury ◽  
Embryonic Stem ◽  
Screening Strategy ◽  
Cardiac Cells ◽  
Alveolar Epithelial Cells ◽  
Host Cell Membrane ◽  
Health Crisis

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to a global health crisis, and yet our understanding of the disease pathophysiology and potential treatment options remains limited. SARS-CoV-2 infection occurs through binding and internalization of the viral spike protein to angiotensin converting enzyme 2 (ACE2) on the host cell membrane. Lethal complications are caused by damage and failure of vital organs that express high levels of ACE2, including the lungs, the heart and the kidneys. Here, we established a high-throughput drug screening strategy to identify therapeutic candidates that reduce ACE2 levels in human embryonic stem cell (hESC) derived cardiac cells. Drug target analysis of validated hit compounds, including 5 alpha reductase inhibitors, revealed androgen signaling as a key modulator of ACE2 levels. Treatment with the 5 alpha reductase inhibitor dutasteride reduced ACE2 levels and internalization of recombinant spike receptor binding domain (Spike-RBD) in hESC-derived cardiac cells and human alveolar epithelial cells. Finally, clinical data on coronavirus disease 2019 (COVID-19) patients demonstrated that abnormal androgen states are significantly associated with severe disease complications and cardiac injury as measured by blood troponin T levels. These findings provide important insights on the mechanism of increased disease susceptibility in male COVID-19 patients and identify androgen receptor inhibition as a potential therapeutic strategy.

Personalized stratification of back to work risk amidst COVID-19: A machine learning approach (Preprint)

2020 ◽  
Author(s):  
Carson Lam ◽  
Jacob Calvert ◽  
Gina Barnes ◽  
Emily Pellegrini ◽  
Anna Lynn-Palevsky ◽  
...  
Keyword(s):  
Machine Learning ◽  
High Risk ◽  
Learning Algorithm ◽  
Severe Disease ◽  
High Specificity ◽  
Population Level ◽  
The United States ◽  
Health Condition ◽  
Available P ◽  
Severe Illness

BACKGROUND In the wake of COVID-19, the United States has developed a three stage plan to outline the parameters to determine when states may reopen businesses and ease travel restrictions. The guidelines also identify subpopulations of Americans that should continue to stay at home due to being at high risk for severe disease should they contract COVID-19. These guidelines were based on population level demographics, rather than individual-level risk factors. As such, they may misidentify individuals at high risk for severe illness and who should therefore not return to work until vaccination or widespread serological testing is available. OBJECTIVE This study evaluated a machine learning algorithm for the prediction of serious illness due to COVID-19 using inpatient data collected from electronic health records. METHODS The algorithm was trained to identify patients for whom a diagnosis of COVID-19 was likely to result in hospitalization, and compared against four U.S policy-based criteria: age over 65, having a serious underlying health condition, age over 65 or having a serious underlying health condition, and age over 65 and having a serious underlying health condition. RESULTS This algorithm identified 80% of patients at risk for hospitalization due to COVID-19, versus at most 62% that are identified by government guidelines. The algorithm also achieved a high specificity of 95%, outperforming government guidelines. CONCLUSIONS This algorithm may help to enable a broad reopening of the American economy while ensuring that patients at high risk for serious disease remain home until vaccination and testing become available.

scholarly journals COVID-19 in obstetrics 2020: the experience at a New York City medical center

2020 ◽  
Vol 48 (9) ◽  
pp. 892-899
Author(s):  
Ashlesha K. Dayal ◽  
Armin S. Razavi ◽  
Amir K. Jaffer ◽  
Nishant Prasad ◽  
Daniel W. Skupski
Keyword(s):  
New York ◽  
Medical Center ◽  
Severe Disease ◽  
Infection Rates ◽  
Health Crisis ◽  
The Public ◽  
Public Health Crisis ◽  
Asymptomatic Carriage ◽  
Global Spread ◽  
Workforce Flexibility

AbstractThe global spread of the SARS-CoV-2 virus during the early months of 2020 was rapid and exposed vulnerabilities in health systems throughout the world. Obstetric SARS-CoV-2 disease was discovered to be largely asymptomatic carriage but included a small rate of severe disease with rapid decompensation in otherwise healthy women. Higher rates of hospitalization, Intensive Care Unit (ICU) admission and intubation, along with higher infection rates in minority and disadvantaged populations have been documented across regions. The operational gymnastics that occurred daily during the Covid-19 emergency needed to be translated to the obstetrics realm, both inpatient and ambulatory. Resources for adaptation to the public health crisis included workforce flexibility, frequent communication of operational and protocol changes for evaluation and management, and application of innovative ideas to meet the demand.

scholarly journals Letter on Rocket's et al., manuscript: Fatal self-injury in the United States, 1999–2018: Unmasking a national mental health crisis

2021 ◽  
Vol 34 ◽  
pp. 100820
Author(s):  
Julian Santaella-Tenorio ◽  
Tarlise Townsend ◽  
Noa Krawczyk ◽  
David Frank ◽  
Samuel R. Friedman
Keyword(s):  
Mental Health ◽  
United States ◽  
The United States ◽  
Mental Health Crisis ◽  
Health Crisis ◽  
Self Injury ◽  
National Mental Health

scholarly journals Use of monoclonal antibody therapy for nosocomial SARS-CoV-2 infection in patients at high risk for severe COVID-19: experience from a tertiary-care hospital in Germany

Infection ◽  
2021 ◽  
Author(s):  
Johanna Koehler ◽  
Barbara Ritzer ◽  
Simon Weidlich ◽  
Friedemann Gebhardt ◽  
Chlodwig Kirchhoff ◽  
...  
Keyword(s):  
High Risk ◽  
Tertiary Care Hospital ◽  
Severe Disease ◽  
Treatment Options ◽  
Tertiary Care ◽  
Antibody Therapy ◽  
Additional Treatment ◽  
Care Hospital ◽  
Cross Sectional ◽  
Asymptomatic Patients

AbstractAdditional treatment options for coronavirus disease (COVID-19) are urgently needed, particularly for populations at high risk of severe disease. This cross-sectional, retrospective study characterized the outcomes of 43 patients with nosocomial severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with and without treatment using monoclonal SARS-CoV-2 spike antibodies (bamlanivimab or casirivimab/imdevimab). Our results indicate that treatment with monoclonal antibodies results in a significant decrease in disease progression and mortality when used for asymptomatic patients with early SARS-CoV-2 infection.

scholarly journals 549. Clinical Characteristics and Outcomes of Patients with COVID-19 treated with Convalescent Plasma in Miami, Florida

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S340-S341
Author(s):  
Shweta Anjan ◽  
Dimitra Skiada ◽  
Miriam Andrea Duque Cuartas ◽  
Douglas Salguero ◽  
David P Serota ◽  
...  
Keyword(s):  
Treatment Options ◽  
Disease Outbreaks ◽  
Nasopharyngeal Swab ◽  
Rt Pcr ◽  
Health Crisis ◽  
Infectious Disease Outbreaks ◽  
Reactive Protein ◽  
High Acuity ◽  
Us Fda ◽  
Oxygen Requirements

Abstract Background The Coronavirus disease of 2019 (COVID-19) global health crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in unprecedented mortality, impacted society, and strained healthcare systems, yet sufficient data regarding treatment options are lacking. Convalescent plasma, used since 1895 for infectious disease outbreaks, offers promise as a treatment option for COVID-19. Methods This is a retrospective study of patients diagnosed by a nasopharyngeal swab SARS-CoV-2 reverse transcriptase–polymerase chain reaction (RT-PCR), who received convalescent plasma between April to June 2020 at two large hospitals in Miami, Florida, as part of the US FDA Expanded Access Program for COVID-19 convalescent plasma (CCP). Results A total of 23 patients received CCP, 13 (57%) had severe COVID-19 disease, while 8 (35%) had critical or critical with multiorgan dysfunction. Median time of follow up was 26 (range, 7–79) days. Overall, 11 (48%) survived to discharge, 6 (26%) died, while 6 (26%) are currently hospitalized. All deaths reported were due to septic shock from secondary infections. 15 (65%) showed improvement in oxygen requirements 7 days post CCP transfusion. Measured inflammatory markers, c-reactive protein, lactate dehydrogenase, ferritin and d-dimer improved 7 days post transfusion in 13 (57%) patients. No adverse events due to the transfusion were reported. 10 (43.4%) patients had a negative SARS-CoV-2 RT-PCR at a median of 14.5 (range, 4–31) days after receiving convalescent plasma. Conclusion Administration of convalescent plasma was found to be safe, with favorable outcomes in this small cohort of relatively high acuity patients. Larger studies including control arms are needed to establish the efficacy of convalescent plasma on clinical and virologic outcomes for patients with COVID-19. Table Disclosures All Authors: No reported disclosures

scholarly journals Neutralizing antibodies against SARS-CoV-2: current understanding, challenge and perspective

2020 ◽  
Vol 3 (4) ◽  
pp. 285-299
Author(s):  
Yang Huang ◽  
Hui Sun ◽  
Hai Yu ◽  
Shaowei Li ◽  
Qingbing Zheng ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Therapeutic Potential ◽  
Therapeutic Interventions ◽  
Viral Escape ◽  
Global Burden ◽  
Health Crisis ◽  
The Us ◽  
Preclinical And Clinical Studies ◽  
Insight Into ◽  
Rapid Emergence

Abstract The rapid emergence of Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2) as a pandemic that presents an urgent human health crisis. Many SARS-CoV-2 neutralizing antibodies (NAbs) were developed with efficient therapeutic potential. NAbs-based therapeutics against SARS-CoV-2 are being expedited to preclinical and clinical studies with two antibody drugs, LY3819253 (LY-CoV555) and REGN-COV2 (REGN10933 and REGN10987), approved by the US Food and Drug Administration for emergency use authorization for treating COVID-19. In this review, we provide a systemic overview of SARS-CoV-2 specific or cross-reactive NAbs and discuss their structures, functions and neutralization mechanisms. We provide insight into how these NAbs specific recognize the spike protein of SARS-CoV-2 or cross-react to other CoVs. We also summarize the challenges of NAbs therapeutics such as antibody-dependent enhancement and viral escape mutations. Such evidence is urgently needed to the development of antibody therapeutic interventions that are likely required to reduce the global burden of COVID-19.

scholarly journals Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

2021 ◽  
Vol 10 (4) ◽  
pp. 711
Author(s):  
Byung-Chul Lee ◽  
Insung Kang ◽  
Kyung-Rok Yu
Keyword(s):  
Clinical Trials ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Genetic Material ◽  
Experimental Models ◽  
Attractive Alternative ◽  
Cell Based Therapy ◽  
Cellular Rejection

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

scholarly journals The Public’s Perception of Interventions for Migraine Headache Disorders: A Crowdsourcing Population-Based Study

2019 ◽  
Vol 1 (2) ◽  
Author(s):  
Orr Shauly ◽  
Daniel J Gould ◽  
Ketan M Patel
Keyword(s):  
Migraine Headache ◽  
Treatment Options ◽  
The United States ◽  
Cost Of Care ◽  
Adverse Outcomes ◽  
Amazon Mechanical Turk ◽  
Cross Sectional ◽  
Economic Productivity ◽  
Migraine Headaches ◽  
Patient Reported

Abstract Background Migraine disorders are a leading cause of morbidity and decreased economic productivity in the United States among both men and women. As such, it is important to consider patient opinions, and have an accurate representation of the burden and sentiment toward currently available interventions among those suffering from migraines. Objectives The aim of the study was to assess patient options regarding adverse outcomes of the various treatment options available for migraine headaches. Methods A prospective cross-sectional study of volunteers recruited through an internet crowdsourcing service, Amazon Mechanical Turk©, was conducted. Surveys were administered to collect patient-reported opinions regarding adverse outcomes of both surgical and nonsurgical treatment options for migraine headaches. Results The prevalence of migraine headache across all study participants was 15.6% and varied slightly across participant demographics. Individuals ages 35–44 (2.73 migraines per month) experienced the fewest migraine and with the lowest severity. Those individuals ages 45+ experienced the most severe headaches (Visual Analog Scale = 44.23 mm). Additionally, the greatest migraine frequency and severity existed among those households with yearly income of $75,000–$100,000. The lowest injection therapy utility scores were obtained for adverse outcomes of hematoma (47.60 mm) and vertigo (54.40 mm). Conclusions Migraine headaches remains a significant problem among the US population, with an overall prevalence of 15.6% (approximately 50 million Americans). Additionally, physicians interesting in offering minimally invasive or surgical treatment for migraine headaches should focus on mitigating patient fears regarding clinical outcomes and cost of care.

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