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FirstHealth of Carolinas Joins Mayo Clinic in Convalescent Plasma Program to Treat COVID-19

FirstHealth of the Carolinas (https://www.firsthealth.org/) has joined the convalescent plasma expanded access program (EAP) at the Mayo Clinic to provide plasma transfusion treatment for hospitalized patients with severe or life-threatening COVID-19. Patients who have recovered from COVID-19 are encouraged to donate convalescent plasma through OneBlood (https://www.oneblood.org/). The plasma is then processed and tested for antibodies that help fight against the virus. “A very old treatment is taking part of the blood of someone who recovered from a disease, someone who has the necessary antibodies to fight it, and giving it to a person with the disease,” said Gretchen Shaughnessy Arnoczy, MD, an infectious diseases physician with FirstHealth of the Carolinas. “Convalescent plasma is a promising treatment because it’s worked for other diseases.” To be eligible for donation, individuals must have recovered from coronavirus, become completely free of symptoms for 14 days, and test negative for the virus. Once all criteria are met, recovered patients can register to donate at OneBlood.org. FirstHealth has performed its first successful plasma transfusion, and Dr. Arnoczy said more will occur as long as availability allows. The Mayo Clinic program includes protocols and regulatory assistance, but does not supply the plasma. Sites are encouraged to establish local channels and to work with blood banks to identify and recruit donors. “We want to have a more robust pipeline of plasma available to us,” Dr. Arnoczy said. “We really want to encourage people who have recovered from COVID to go on the OneBlood website and register. That will help us have more supply, so we can use it in more patients.” After donation, plasma, the liquid portion of the blood, is separated and tested. On average, processing takes about 24 hours.

UK Researchers Develop Small Molecules That May Inhibit Cytokine Storm in COVID-19

A COVID-19 treatment, which could potentially also help protect cancer and organ transplant patients, is being developed at the University of Greenwich in the UK, according to a May 15, 2020 release from the University. University researchers have identified and developed compounds that can inhibit the multiple cytokine proteins that can cause death by respiratory collapse, following COVID-19 infection. Michael Leach (https://www.gre.ac.uk/people/rep/faculty-of-engineering-and-science/mike... ), PhD, has developed the compounds, known as UoG-alpha and UoG-beta. He says: “A major force that kills people who have COVID-19 is what’s known as the ‘cytokine storm.’ This is essentially a massive overload of the body’s immune system in response to the virus. Vaccination is what the government is suggesting for the future as being key to how we live ‘normally.’ That makes sense of course, but, as a complement, we need a drug therapy that can be used by someone with COVID symptoms before their ‘perfect storm.’ This would mean they don’t need to go to the hospital, although it could be used there as well. What we have identified and developed at the University are compounds that can control cytokines, which we know are contributing to COVID-19 deaths. We have been working with these small molecules for many years and they have shown themselves to control multiple target proteins linked with many disorders, such as sepsis, cancer, and various inflammatory problems. I believe a controllable drug therapy, able to prevent our immune system from disabling the body’s lung function during a cytokine storm, is what is needed.

CytoDyn Offers No-Cost Exploratory Laboratory Testing for Kawasaki-Like Childhood Inflammatory Disease Associated with COVID-19; CytoDyn Has Monoclonal Antibody Drug (Leronlimab) in Clinical Trials for Treatment of COVID-19

On May 15, 2020, CytoDyn Inc. (OTC.QB: CYDY) (http://www.cytodyn.com), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced that it is offering comprehensive cytokine profiling (including RANTES levels) (RANTES/CCL5: https://en.wikipedia.org/wiki/CCL5) through its diagnostic partner company, IncellDx (https://incelldx.com/), to help physicians understand the pathogenesis of Childhood Inflammatory Disease Related to COVID-19. These laboratory tests are exploratory in nature and not intended for clinical decision-making. Recent reports in parts of the U.S. and Europe suggest a rare and potentially fatal inflammatory disease linked to the novel coronavirus is afflicting a small number of children. The condition resembles a rare childhood illness called Kawasaki disease, which has similar signs and symptoms and can lead to enlargement of blood vessels that, in severe forms, may cause heart damage. The New York State Department of Health is currently investigating 110 reported cases and 3 deaths in children--predominantly school-aged--experiencing symptoms similar to Kawasaki disease and toxic shock-like syndrome, possibly due to COVID-19.

Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients Published; Results Suggest Treatment Is Safe for Patients; Mayo Clinic Announces Pre-Print Publication

According to a May 14, 2020 Mayo Clinic announcement, the first safety study communications overview, “Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients,” for the national Expanded Access Program (EAP) for convalescent plasma was published online on May 14, 2020 as a pre-print on the medRxiv site (https://www.medrxiv.org/content/10.1101/2020.05.12.20099879v1). The report makes the following key points. The Mayo Clinic and collaboratoring institutions, including Johns Hopkins and Michigan State University, reported safety data on the first 5,000 hospitalized patients transfused with investigational convalescent plasma as part of the U.S. Food and Drug Administration’s national EAP for COVID-19. The early indicators suggest that experimental convalescent plasma is safe in treating severely ill patients. At this time, convalescent plasma is the only antibody-based therapy available for COVID-19. Patients received plasma between April 3 and May 3. The seven-day incidence of mortality was 14.9%. Sixty-six percent of the patients were in the ICU, and nearly 20% carried the diagnosis of multi-organ dysfunction or failure. Importantly, the reports of serious adverse events related to transfusion of the plasma was small (<1%). The researchers noted that while the study was not designed to evaluate the efficacy of convalescent plasma, a seven day incidence of mortality of 14.9% in this number of patients indicates “no signal of toxicity beyond what is expected from plasma use in severely ill patients.” It is important to note that this is a first safety report and does not provide any findings on the effectiveness of convalescent plasma in the treatment of COVID-19.

New Mass Spec Technique (mePROD) Enables Discovery of Potential Targets for COVID-19 Therapy; In Cell Culture Model, Several Already-Approved Drugs Stop SARS-Cov-2 Virus; Multiple Clinical Trial Preparations Now Underway; Article Published in Nature

A team of biochemists and virologists at Goethe University Frankfurt and the Frankfurt University Hospital in Germany were able to observe how human cells change upon infection with SARS-CoV-2, the virus causing COVID-19 in people. The scientists tested a series of compounds in laboratory models and found some that slowed down or stopped virus reproduction. These results, published online on May 14, 2020 in Nature (https://www.nature.com/articles/s41586-020-2332-7_reference.pdf), have enabled the search for an active substance to be narrowed down to a small number of already approved drugs. The Nature article is titled “Proteomics of SARS-CoV-2-Infected Host Cells Reveals Therapy Targets.” Based on these findings, a US company (Moleculin Biotech) reports that it is preparing clinical trials. A Canadian company (Bausch Health Americas) is also starting a clinical study with a different substance. Since the start of February, the Medical Virology Department of the Frankfurt University Hospital has been in possession of a SARS-CoV-2 infection cell culture system. The Frankfurt scientists in Professor Sandra Ciesek's (photo) team succeeded in cultivating the virus in colon cells from swabs taken from two infected individuals returning from Wuhan (https://www.nejm.org/doi/full/10.1056/NEJMc2001899). Using a technique developed at the Institute for Biochemistry II at Goethe University Frankfurt, researchers from both institutions were, together, able to show how a SARS-CoV-2 infection changes the human host cells.

Ticking Time Bomb: Malaria Plasmodium Parasite Has Its Own Inherent Clock, Takahashi-Led Study at UTSW Suggests; New Research Could Lead to ID of Targets to Fight Deadly Disease

The activity of the parasite that causes malaria is driven by the parasite’s own inherent clock, new research led by University of Texas (UT) Southwestern (UTSW) scientists suggests. The findings, published in the May 15, 2020 issue of Science (https://science.sciencemag.org/content/368/6492/746), together with those in a related article by another group also published in the same issue of Science (https://science.sciencemag.org/content/368/6492/754.full), could lead to new ways to fight this pervasive and deadly disease. More than 200 million people contract malaria worldwide each year, and over 400,000 people die annually of this disease, according to statistics from the World Health Organization (WHO). Caused by protozoa in the genus Plasmodium, malaria kills mostly children, with the majority of deaths in sub-Saharan Africa. It has long been known that malaria induces cyclical fevers, which occur every two to three days in human hosts, depending on the species of infecting organism. This is the result of all the parasites simultaneously bursting the red blood cells of the host they infect. “Together, these and other behavioral phenomena suggest that Plasmodium has a sense of time,” says study leader Joseph S. Takahashi (photo), Ph.D. Chair of Neuroscience at UTSW and a Howard Hughes Medical Institute (HHMI) Investigator (https://profiles.utsouthwestern.edu/profile/105885/joseph-takahashi.html). “But the reason for these daily rhythms has been mysterious.”

Malaria Parasite Ticks to Its Own Internal Clock, According to Duke-Led Study Published in Science; Research Could Lead to New Drugs Against Disease That Threatens Half World's Population

When a person gets malaria, a rhythmic dance takes place inside his or her body. The disease's telltale signs -- cyclical fevers and chills -- are caused by successive broods of parasites multiplying in synchrony inside red blood cells, then bursting out in unison every few days. Now, a study shows that even when grown outside the body, malaria parasites can still keep a beat. Reporting in the May 15, 2020 issue of Science, Duke researchers and collaborators have uncovered rhythms in the parasite's gene activity levels that don't rely on time cues from the host, but instead are coordinated from within the parasite itself. The Science article is titled “An Intrinsic Oscillator Drives the Blood Stage Cycle of the Malaria Parasite, Plasmodium falciparum” (https://science.sciencemag.org/content/368/6492/754). The findings indicate that the parasite that causes malaria has its own time-keeping machinery, an internal metronome that ticks of its own accord and causes thousands of parasite genes to ramp up and down at regular intervals. "Malaria has all the molecular signatures of a clock," said Duke biology professor Steven Haase, PhD, the lead author of the study. Understanding how malaria's clock works might help scientists develop new weapons against a disease that kills a child every two minutes, and has proven increasingly resistant to existing drugs, Dr. Haase said. Dr. Haase has spent years studying cell cycles in yeast to understand controls on the timing of events as one cell becomes two, but only recently has he turned to malaria. The work was prompted by a question that has vexed scientists: how do the parasites keep time?

Dynamic Electric Stimulation of Visual Cortex Via Electrodes Produces Vision of Shapes and Identification of Letters in Sighted and Blind Humans; Baylor Study Reported in Cell

For most adults who lose their vision, blindness results from damage to the eyes or optic nerve while the brain remains intact. For decades, researchers have proposed developing a device that could restore sight by bypassing damaged eyes and delivering visual information from a camera directly to the brain. In a paper published in Cell on May 14, 2020, a team of investigators at Baylor College of Medicine in Houston, Texas, report that they are one step closer to this goal. The open-access Cell article is titled "Dynamic Stimulation of Visual Cortex Produces Form Vision in Sighted and Blind Humans." The authors describe an approach in which implanted electrodes are stimulated in a dynamic sequence, essentially "tracing" shapes on the surface of the visual cortex that participants were able to "see." "When we used electrical stimulation to dynamically trace letters directly on patients' brains, they were able to 'see' the intended letter shapes and could correctly identify different letters," said senior author Daniel Yoshor (at right in photo), MD, Chairman of Neurosurgery at Baylor College of Medicine (https://www.bcm.edu/news/appointments-faculty-staff/dr-daniel-yoshor-nam...). "They described seeing glowing spots or lines forming the letters, like skywriting." Previous attempts to stimulate the visual cortex have been less successful. Earlier methods treated each electrode like a pixel in a visual display, stimulating many of them at the same time. Participants could detect spots of light, but found it hard to discern visual objects or forms. "Rather than trying to build shapes from multiple spots of light, we traced outlines," says first author Michael Beauchamp, PhD (https://www.bcm.edu/research/labs/michael-beauchamp).

How “Dark Matter” Non-Coding Regions of Genome Affect Inflammatory Diseases; Deletion of Enhancer Element for GARP in Regulatory T-Cells (Tregs) Causes Uncontrolled Response to Triggered Inflammation of Colon Lining; GARP Is Promising New Drug Target

A study led by researchers at the Babraham Institute, in collaboration with scientists at the Wellcome Sanger Institute, has uncovered how variations in a non-protein-coding “dark matter” region of the genome could make patients susceptible to complex autoimmune and allergic diseases such as inflammatory bowel disease. The study in mice and human cells reveals a key genetic switch that helps immune responses remain in check. Published on May 13, 2020 in Nature, the research, involving collaborations with research institutions in the UK and worldwide, identifies a new potential therapeutic target for the treatment of inflammatory diseases. The Nature article is titled “A Distal Enhancer At Risk Locus 11q13.5 Promotes Suppression of Colitis By Treg Cells.” Over the last twenty years, the genetic basis of susceptibility to complex autoimmune and allergic diseases, such as Crohn's disease, ulcerative colitis, type 1 diabetes, and asthma, has been narrowed down to a particular region of chromosome 11. This work has involved large-scale genome-wide association studies (GWAS), a genome-wide “spot-the-difference” comparison between the genomes of individuals with or without a disease, to highlight regions of variation in the DNA code. This can identify potential genetic causes, and reveal possible drug targets. However, most of the genetic variations responsible for the susceptibility to complex immune and allergic diseases are concentrated within regions of the genome that don't encode proteins - the genome's so-called “dark matter.” This means there is not always a clear gene target for further investigation and the development of treatments.

ENHANCERS

Cats Can Infect Other Cats with Virus That Causes COVID-19: Cats In Lab Study Showed No Symptoms; Still No Evidence of Pets Spreading COVID-19 to Humans; Guidelines for Safe Pet Care Noted; UW-Madison and U of Tokyo Involved in NEJM-Published Study

Three cats infected with the virus that causes COVID-19 spread the virus to three other cats in a lab study reported in The New England Journal of Medicine (NEJM) (https://www.nejm.org/doi/full/10.1056/NEJMc2013400) by a research team working in Tokyo, Japan, and Madison, Wisconsin, USA. The open-access article was published on May 13, 2020, and is titled “Transmission of SARS-CoV-2 in Domestic Cats.” The authors included Peter J. Halfnmann, PhD, Masato Hatta, DVM, PhD, Shiho Chib, PhD, Tadashi Maemura, DVM, PhD, and Shufang Fan, PhD, at the University of Wisconsin-Madison; Makoto Takeda, MD, PhD, at the National Institutes of Infectious Diseases, Tokyo, Japan; Noriko Kinoshita, MD, and Shin-ichiro Hattori, PhD, at the National Center for Global Health and Medicine,Tokyo, Japan; and Yuko Sakai-Tagawa, PhD, Kiyoko Iwatsuki-Horimoto, DVM, PhD, Masaki Imai, DVM, PhD, and Yoshihiro Kawaoka, DVM, PhD, at the University of Tokyo, Japan. The research team emphasized that there is no evidence of the COVID-19 virus transmitting from cats to humans. The researchers stated that it is much more likely that humans are giving the virus to their pets, rather than pets causing humans to become sick. The research team infected three cats with large doses of the virus (SARS-CoV-2) that causes COVID-19, directly into both eyes, both nostrils, the mouth, and the trachea (windpipe). The infected cats were housed in pairs with uninfected cats, sharing the same space, food, water, and air. Within five days, the uninfected cats tested positive for SARS-CoV-2 in nasal swabs.

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