May 22, 2020 | Researchers have found that COVID-19 patients have a high predisposition to developing blood clots. Elsewhere, teams develop a COVID-19 trial finder. We round up the week’s research and industry news for COVID-19.

Literature Updates

Using a combination of two specific blood-clotting tests, researchers from the University of Colorado Anschutz Medical Campus, Aurora, found COVID-19 patients are highly predisposed to developing blood clots putting them at high risk for developing renal failure, venous blood clots, and other complications associated with blood clots, such as stroke. The research team is now participating in a randomized clinical trial of a drug that breaks down blood clots in COVID-19-infected patients. Their research is published as an "article in press" on the Journal of the American College of Surgeons website ahead of print. DOI: 10.1016/j.jamcollsurg.2020.05.007

Researchers have launched a placebo-free clinical trial that the authors describe as nimble, pragmatic and rigorous. The multicenter clinical trial compared hydroxychloroquine and azithromycin as potential COVID-19 treatments and was designed to be quickly established and adopted in community and academic hospitals throughout Utah. The study design differs from that of other randomized, controlled trials in that it does not have a placebo arm, saving time and effort of placebo manufacture and making it available to hospitals that don't have research pharmacies. In place of a placebo, the investigators chose to use a comparator drug: the antibiotic azithromycin. Because the drug showed anti-inflammatory pulmonary effects and other potential benefits in some previous trials, they felt it might have efficacy, and have a very low likelihood of harm due to its established safety profile. The researchers outline the protocol in the Annals of the American Thoracic Society. DOI: 10.1513/AnnalsATS.202004-309SD.

A UK observational study of 3,802 people tested for SARS-CoV-2 (including 587 positive tests) in the UK found that older age, being male, deprivation, living in a densely populated area, ethnicity, obesity, and chronic kidney disease are all associated with a positive test for COVID-19. The study was conducted in between Jan 28 and April 4 using routine electronic health records data from GP practices across England (UK), and results are published in The Lancet Infectious Diseases. DOI: 10.1016/S1473-3099(20)30371-6.

Researchers in France and Switzerland retrospectively collected and analyzed clinical, biological, therapeutic and early outcome data for 35 children admitted to the pediatric intensive care unit with fever, cardiogenic shock or acute left ventricular dysfunction with inflammatory state. Treatment with antibodies purified from donated blood, immune globulin therapy, and steroids restored heart function in the majority of children with COVID-related multi-system inflammatory syndrome, according to research published in Circulation. DOI: 10.1161/CIRCULATIONAHA.120.048360.

According to a systematic review and meta-analysis looking at the psychiatric consequences of coronavirus infections in over 3,550 patients hospitalized with SARS, MERS, and COVID-19, most people admitted to hospital with severe COVID-19 should recover without experiencing mental illness. Nevertheless, the findings suggest that delirium (a mental state characterized by changes in consciousness, behavioral disturbance, and sometimes hallucinations) may be common in hospitalized patients in the acute stages of SARS, MERS, and COVID-19 illness. (The study looks at severe cases in which individuals have been treated in hospital and does not apply to milder cases or asymptomatic cases.) The findings were published in The Lancet Psychiatry journal. DOI: 10.1016/S2215-0366(20)30203-0.

Physicians at the Children's Hospital at Montefiore (CHAM) and Albert Einstein College of Medicine report on the clinical characteristics and outcomes of 46 children hospitalized with COVID-19. Published in the Journal of Pediatrics, this is the largest single-center study from the United States to date to describe in detail the full spectrum of COVID-19 disease in hospitalized children. DOI: 10.1016/j.jpeds.2020.05.

Some signs and symptoms of COVID-19 are similar to worsening of asthma, which can lead to a late diagnosis of COVID-19 in asthmatics. And new data suggests that asthma is associated with longer time on ventilators for hospitalized younger patients with COVID-19. Patients with COVID-19 between the ages of 20 and 59 years old who also had asthma needed a ventilator to assist with breathing for five days more on average than non-asthmatic patients with COVID-19, according to researchers at Rush University Medical Center, who published their findings today in The Journal of Allergy and Clinical Immunology: In Practice. DOI: 10.1016/j.jaip.2020.05.006.

A cohort study out of West Virginia University and published in the ASAIO Journal suggests that an extracorporeal membrane oxygenation machine can be especially useful for treating some COVID-19 patients, but less helpful for COVID-19 patients who are older, who have preexisting conditions, and whose heart function has deteriorated. An ECMO machine works by pumping someone's blood outside of their body, oxygenating it and returning it to the body. In this way, the ECMO machine gives the lungs--and sometimes the heart--time to rest and heal. DOI: 10.1097/MAT.0000000000001185.

A new paper from UVA Health highlights the serious cardiovascular complications to COVID-19 including heart failure, heart attacks and blood clots that can lead to strokes. The authors hope the study will serve as a guide for emergency-medicine doctors treating patients who may have or are known to have COVID-19. They caution that COVID-19 treatments can interact with medicines used to manage patients' existing cardiovascular conditions. DOI: 10.1016/j.ajem.2020.04.048.

Updates from Industry

Henry Ford Health System is enrolling the first patient in the Human Epidemiology and Response to SARS-CoV-2 (HEROS) study, which aims to help determine the rate of SARS-CoV-2 among U.S. children and their family members, and what percentage of children infected with SARS-CoV-2 develop symptoms of the disease. The study will also examine whether rates of SARS-CoV-2 infection differ between children who have asthma or other allergic conditions and children who do not. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), is sponsoring and funding the HEROS study. Press release.

Parexel has launched the #KeepingPatientsFirst integrated Real-World Evidence (RWE) research platform collating critical evidence and accelerating patient and physician access to insights on treatment and outcomes in COVID-19. The platform is powered by Microsoft Azure. #KeepingPatientsFirst is focused on aggregating, analyzing, and predicting real-world COVID-19-related disease progression and outcomes using machine learning, artificial intelligence and analytics. This epidemiological approach will also help to characterize and define an unprecedented worldwide event, including documenting the real-world patient journey from awareness to diagnosis to disease resolution, speeding the evaluation of potential COVID-19 therapies. More information.

Meanwhile, Aetion has signed a research collaboration agreement with the U.S. Food and Drug Administration (FDA) to use real-world data to advance the understanding of and response to coronavirus disease (COVID-19). The research will support FDA objectives to explore the natural history of the disease, as well as treatment and diagnostic patterns, by facilitating the use of relevant, novel data sources and analyzing these data according to well-established principles. Aetion and the FDA will identify and analyze fit-for-purpose data sources to characterize COVID-19 patient populations and their medication use, identify risk factors for COVID-19-related complications, and contribute to the scientific evaluation of potential interventions. The collaboration will make use of the Aetion Evidence Platform, which includes structured workflows and transparent reporting to facilitate efficient sharing, examination, and reproduction of findings. Press release.

eClinical Solutions has released a list of core recommendations to sustain clinical research based on its recent joint study with the Tufts Center for the Study of Drug Development (Tufts CSDD). To continue advancing clinical research during the pandemic, the company suggests the following steps: 1. Define an enterprise data strategy, centralize data and automate the data pipeline, and build data sciences and analytics competencies. Blog post.

The National Institutes of Health (NIH) has launched a Phase IIb clinical trial to evaluate whether the malaria drug hydroxychloroquine in combination with the antibiotic azithromycin can prevent hospitalization and death from COVID-19, the disease caused by the novel coronavirus 2019 or SARS-CoV-2. There are numerous clinical trials planned or underway to assess hydroxychloroquine as a safe, effective treatment of adults hospitalized with COVID-19. The new NIH trial is the largest and highest profile to date: a randomized, double-blind interventional trial that will recruit 2,000 participants at 30 sites across the United States. Press release.

Researchers at the Walter And Eliza Hall Institute in Australia, in partnership with human data science company IQVIA, have launched a multi-center, randomized, double-blind study to test hydroxychloroquine’s effectiveness as prophylactic COVID-19 prevention. The trial—COVID SHIELD—will enroll 2250 participants through participating hospitals and healthcare providers. Half of the participants will be given hydroxychloroquine, while the other half will receive a placebo tablet, both for the duration of four months. Press release.

UCLA researchers have launched a phase 2 clinical trial to test if temporarily using a hormone suppresser commonly used to treat men with prostate cancer may help COVID-19 patients get out of the hospital faster, decrease the need for intubation, and improve mortality. Recent data from New York show that men are infected in greater numbers and are dying at nearly twice the rate of women. The convergence between prostate cancer research and COVID-19 research begins with a protein receptor called TMPRSS2, which is abnormal in about half of all prostate cancer patients and plays a role in the development and progression of prostate cancer. This is the same receptor that researchers believe the virus uses to enter the lungs and attack lung tissue. The receptor is regulated by male hormones in prostate cancer, and researchers believe it may also be regulated in lung tissue by male hormones. In the clinical trial, researchers will suppress male hormones using the FDA-approved medication known as degarelix, to temporarily shut down the production of TMPRSS2 and block the virus from entering lung tissue. The UCLA-led study is being conducted at the Veterans Affairs Greater Los Angeles Healthcare System and other VA sites across the country. Press release.

Researchers at Columbia University have developed COVID-19 Trial Finder, a simplified method for patients, clinicians and healthy volunteers to search for appropriate COVID-related clinical trials in their general location. There are currently more than 1500 COVID-related trials ongoing, including more than 300 in the United States, according to ClinicalTrials.gov. COVID-19 Trial Finder, based on a dynamic questionnaire system detailed in JAMIA last November, eases the burden for trial seekers by generating user-specific questionnaires dynamically to filter out trials. The development team created a version of the system to focus solely on COVID-related trials, which can reduce a large set of potential trials to only a handful within 5-6 survey questions. This publicly facing site opens with questions related to a person's location, age, gender and COVID status (diagnosed with, high risk for contracting, hospitalized, etc.) to come up with a first set of related trials, and then allows the user to answer a minimal number of questions tailored to a patient's clinical characteristics to filter out even more trials. Press release.

SWORD Health, a digital therapy provider, today launched a remote pulmonary rehabilitation program to meet the urgent need for and significant shortage of rehabilitation programs for COVID-19 patients. The program is the first of its kind in the US, pairing physical therapists with medical-grade and wearable technology so patients can make a full recovery from the comfort and safety of their homes. To help COVID-19 survivors breathe easily again, SWORD Health accelerated development of its fully-remote pulmonary rehabilitation program and made it immediately available to businesses whose employees need it. The program extends SWORD’s highly effective musculoskeletal therapy solution for back, joint and muscle pain, which was 30% more effective, and had higher retention rates (54% more) than in-person therapy. It includes an AI-enabled backend and a wearable-based biofeedback system that can track even the slightest errors in movements and ensure patients do exercises correctly from home. More information.

Prellis Biologics has generated 300 human IgG antibodies that bind to either the S1 or S2 spike protein of the SARS-CoV2-Wuhan strain of the novel coronavirus. Using the Prellis Externalized Human Immune System technology, the team produced 960 synthetic human lymph nodes that were challenged with a SARS-CoV2 vaccine-like cocktail, leading to virus-specific antibody generation. Prellis expects refinement of its lead candidates to take about one month, after which the company will pursue development of a multi-antibody cocktail therapeutic. Press release.