July 2, 2020 | New data shed light on the potential variations in T-cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in COVID-19, and also inform vaccine design and evaluation. Meanwhile, universities are continuing to build out their telehealth capabilities in light of the pandemic. This, plus more, are included in this week’s announcements and updates from the clinical research industry.

Research Updates

In a paper published in the American Journal of Respiratory and Critical Care Medicine, a team from RCSI University of Medicine and Health Sciences describes changes in the body's normal inflammatory response in patients infected with COVID-19, in particular among those who require admission to intensive care. The team has begun a randomized double blind placebo controlled clinical trial of alpha-1-antitrypsin to treat critically ill patients mechanically ventilated in ICU with COVID-19 associated Acute Respiratory Distress Syndrome. Alpha-1-antitrypsin is a naturally occurring human protein produced by the liver and released into the bloodstream which normally acts to protect the lungs from the destructive actions of common illnesses. DOI: 10.1164/rccm.202005-1583OC

In a small study from La Jolla Institute for Immunology and published in Science Immunology, researchers studied 10 COVID-19 patients who required admission to an intensive care unit and 10 healthy controls. The team detected SARS-CoV-2-specific CD4+ and CD8+ T cells in 10 out of 10 and 8 out of 10 patients, respectively. The team also detected low levels of SARS-CoV-2-reactive T cells in 2 out of 10 healthy controls not previously exposed to SARS-CoV-2, which is indicative of cross-reactivity due to past infection with “common cold” coronaviruses. The strongest T-cell responses were directed to the spike (S) surface glycoprotein, and SARS-CoV-2-specific T cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected. Collectively, these data shed light on the potential variations in T-cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in the disease, and also inform vaccine design and evaluation. DOI: 10.1126/sciimmunol.abd2071

Researchers at Mount Sinai conducted a retrospective case-control study of 41 cases and 82 control subjects matched by age, sex, and risk factors. Cases were patients who underwent stroke alert imaging with confirmed acute stroke on imaging between March 16 and April 5, 2020, at 6 hospitals across New York City. Control subjects were those who underwent stroke alertimaging during the same timeframe without imaging evidence of acute infarction. A univariate analysis was performed to assess the covariate effect of risk factors and COVID-19 status on stroke imaging with positive findings. The team found that COVID-19 infection is significantly associated with imaging confirmation of acute ischemic stroke, and patients with COVID-19 should undergo more aggressive monitoring for stroke. The work was published in Adult Brain. DOI: 10.3174/ajnr.A6650

A case series published Radiology examines the spectrum of imaging findings in children with the post-COVID-19 inflammatory condition known in the U.S. as Multisystem Inflammatory Syndrome in Children (MIS-C). The array of findings includes airway inflammation and rapid development of pulmonary edema, coronary artery aneurysms, and extensive intra-abdominal inflammatory changes. For the study, researchers performed a retrospective review of clinical, laboratory and imaging findings of the first 35 children under age 17 who were admitted to the pediatric hospital that met the case definition for MIS-C. The study identified a pattern of imaging findings in post COVID-19 MIS-C, including airway inflammation, rapidly progressive pulmonary edema, coronary artery aneurysms and extensive abdominal inflammatory changes within the right iliac fossa. DOI: 10.1148/radiol.2020202543

Industry Updates

The University of Virginia Health System was awarded $767,139 this week to expand UVA's use of telehealth for patient care during the COVID-19 pandemic. Provided through the FCC's COVID-19 Telehealth Program, the grant will fund equipment and network upgrades to expand remote patient monitoring as patients are diagnosed with COVID-19 or are discharged from the hospital; deploy a mobile telemedicine solution to congregate care settings such as long-term care and skilled nursing facilities that include remote examination tools and monitoring tools; build a virtual urgent care platform to provide non-emergency care without an in-person visit; and support patient-care videoconferencing that reduces the potential for exposure for both patients and care providers exposure at UVA's emergency department and isolation rooms. Press release.

LabCorp’s Covance division has deployed the Xcellerate COVID-19 solution as part of its award-winning Xcellerate platform. Covance has developed a comprehensive approach to reinitiate ongoing research and start up new studies, with a focus on patient safety and study delivery. Designed in conjunction with Covance’s COVID-19 Operational Recovery Team, the Xcellerate COVID-19 solution offers integrated data collection, actionable views of critical study data, COVID-19 targeted risk management and recovery assessment. The Xcellerate COVID-19 solution combines different components of the Xcellerate informatics suite to create a tailored data collection capability, risk assessment tools, centralized monitoring and advanced metrics reporting. Its visualization dashboards provide actionable views of critical study data so that operational teams can make effective decisions, increase efficiency and reduce risk. Press release.

Noxopharm, a clinical-stage Australian drug development company, has announced commencement of its NOXCOVID clinical program with a planned Phase I trial in Europe. The trial is designed to provide important safety data and proof-of-principle of using Veyonda, a drug that blocks cGAS-STING signaling, as a potential treatment of the cytokine storm and septic shock that have emerged as major causes of morbidities and death in COVID-19 patients. In April, Noxopharm announced that laboratory studies revealed that one of the mechanisms of action of idronoxil, the active ingredient in Veyonda, is to block the cGAS-STING signaling pathway, including the overexuberant STING and cytokine response to the sort of hypoxic tissue damage associated with low body oxygen levels in COVID-19 patients suffering severe respiratory distress. Press release.