April 24, 2020 | As world governments continue to address the spread of SARS-CoV-2 (COVID-19), the clinical research community is looking for ways to manage and treat for the virus as well. Recent efforts include studies related to children infected with the virus, a COVID-19 convalescent plasma study, and much more.

Literature Updates

The number of children infected with the coronavirus is far more extensive than what is currently reported, according to a study by the University of South Florida and the Women's Institute for Independent Social Enquiry. Researchers estimate that for each child who requires intensive care for COVID-19, another 2,381 children are infected with the virus; that translates into a total of 176,264 children in the U.S. infected between March 18 and April 6, although only 74 of them were admitted to pediatric ICUs. Of those admissions, 30% were under 2, 24% ages 2 to 11, and 46% between 12 and 17 years old. If up to 25% of the U.S. population becomes infected with the coronavirus before the end of 2020, 50,000 children with severe illness will need to be hospitalized with 5,400 of them critically ill and requiring mechanical ventilation. Only about 5,100 PICU beds exist in the U.S. The study published in the Journal of Public Health Management and Practice. The authors recommend that state health departments and the Centers for Disease Control and Prevention begin reporting confirmed COVID-19 cases in age-specific tables and make the data publicly available. DOI: 10.1097/PHH.0000000000001190

An exploratory randomized, controlled study in China suggests that neither lopinavir/ritonavir (LPV/r) nor Arbidol improves the clinical outcome of patients hospitalized with mild-to-moderate cases of COVID-19. In some countries, LPV/r is used for HIV-1 infection and Arbidol for influenza. the antivirals had been selected as candidates for treating COVID-19 in a guidance issued in February by the National Health Commission of China, based on in vitro cell tests and previous clinical data from SARS and MERS. The findings published in Med. DOI: 10.1016/j.medj.2020.04.001

Scientists at Duke-NUS Medical School are exploring the engineering of specific virus-targeting receptors onto a patient's own immune cells as a potential therapy for controlling infectious diseases, including COVID-19—an approach classically used in treating cancer. The therapy involves extracting immune cells (T lymphocytes) from a patient's bloodstream and engineering onto them either artificially generated chimeric antigen receptors or T cell receptors that are naturally found on the surface of T lymphocytes. These receptors allow the engineered T lymphocytes to recognize cancerous or virus-infected cells. In a study published in the Journal of Experimental Medicine, researchers demonstrated that T cells can be redirected to target the coronavirus responsible for SARS. They’re now exploring the potential of CAR/TCR T cell immunotherapy for controlling SARS-CoV-2 and protecting patients from its symptomatic effects. DOI: 10.1084/jem.20191663

Researchers at the German Center for Infectious Research (DZIF) say a promising MERS coronavirus vaccine trial in humans may provide useful insights for the development of a vaccine against SARS-CoV-2. In a study just published in Lancet Infectious Diseases, they report that a vector-based vaccine, based on an attenuated virus (MVA: modified vaccinia virus Ankara), boosts immunity against MERS coronaviruses. The vaccine trial was conducted in collaboration with the Clinical Trial Center North and involved 23 healthy trial volunteers who received the experimental vaccine twice. Among the important findings were that the vaccine was well tolerated, no severe side effects occurred and after the second injection antibody formation and T cell responses occurred in 87% of trial subjects. A phase 1b trial will now be conducted with 160 trial subjects in Hamburg and Rotterdam. Results and tests from this trial will be used by DZIF researchers to start the development of a vaccine against COVID-19 where a SARS-CoV-2 spike protein, rather than a MERS-CoV-2 spike protein, gets inserted into the MVA vector. DOI: 10.1016/S1473-3099(20)30317-0

COVID-19 is unlikely to be spread through semen, unlike other emerging pathogens like Ebola and Zika, concludes an international study of 34 Chinese men who were recently diagnosed with a mild to moderate case of the novel coronavirus. No evidence of SARS-CoV-2 was found in the semen or testes of the men, researchers report in Fertility and Sterility. Genes encoding the two proteins associated with SARS-CoV-2 were only found in four of 6,500 testicular cells, suggesting the virus is unlikely to invade human testicular cells. Researchers caution that men who are critically ill with COVID-19 might have a higher viral load that could lead to a greater likelihood of infecting the semen. DOI: 10.1016/j.fertnstert.2020.04.024 [Pre-proof PDF]

Northwell Health researchers report in JAMA that hypertension (56.6%), obesity (41.7%) and diabetes (33.8%) are the most common comorbidities among 5,700 patients hospitalized with COVID-19 in the New York City area. At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/minute and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2,634 patients who were discharged or had died at the study end point. During hospitalization, 14.2% were treated in the intensive care unit care, 12.2% received invasive mechanical ventilation, 3.2% were treated with kidney replacement therapy, and 21% died. Mortality for those requiring mechanical ventilation was 88.1%. DOI: 10.1001/jama.2020.6775

In a systematic review of 18 studies published in JAMA Pediatrics, researchers in Italy report that most children and adolescents with SARS-CoV-2 infection present with fever, dry cough and fatigue or were asymptomatic. Only one infant presented with pneumonia, complicated by shock and kidney failure, and was successfully treated with intensive care. Most pediatric patients were hospitalized, and symptomatic children received mainly supportive care; no deaths were reported in the age range of 0 to 9 years. Recovery within one to two weeks was typical. DOI: 10.1001/jamapediatrics.2020.1467

Other News

Maccabi Healthcare Services, Israel’s leading HMO with 2.4 million members, is deploying an AI-powered algorithm developed by Medial EarlySign and the Kahn-Sagol-Maccabi Research and Innovation Institute that identifies individuals estimated to be at the highest risk of severe COVID-19 complications due to pre-existing conditions and other health factors. The new algorithm has already identified the top 2% of highest-risk patients (approximately 40,000 people), following analysis of all Maccabi patients' anonymized electronic health records (EHRs). When an individual flagged by the algorithm as high-risk contacts a nurse or doctor to report COVID-19-like symptoms, the system will automatically notify the medical professional that the patient is in the high-risk group. The patient can be sent for immediate testing. Tests are performed at designated Maccabi facilities, drive-in stations or, if necessary, in the patient’s home. The algorithm identifies high-risk patients through analysis of dozens of routine medical factors, including age; respiratory disease such as pneumonia, bronchiolitis, and influenza; hospital admission history; weight and BMI; medications prescribed for respiratory illnesses or conditions, such as asthma and cough; heart disease; smoking history; diabetes; digestive disease; immunosuppression; and more. Press release.

The Ohio State University Wexner Medical Center is the first health system in Ohio to launch a new clinical trial that uses inhaled nitric oxide to improve coronavirus outcomes and keep COVID-19 patients out of intensive care. Researchers are administering continuously pulsed inhaled nitric oxide via the Bellerophon INOpulse delivery system to prevent the progression of respiratory disease in patients with mild to moderate COVID-19-related pneumonia. The targeted treatment is given to patients who require oxygen but before a ventilator is needed to support breathing. Inhaled nitric oxide is a well-established, safe and effective treatment to dilate arteries in the lungs, improving oxygen in the blood stream. Prior studies of SARS-CoV found inhaled nitric oxide’s antiviral properties could suppress how the virus replicates. Based on the genetic similarities between the two coronaviruses, the historical data supports the potential for inhaled nitric oxide to provide meaningful benefit for patients infected with COVID-19. Press release.

The Perelman School of Medicine at the University of Pennsylvania is leading a new trial evaluating whether COVID-19 outcomes are affected if patients are taking blood pressure medications. As part of the multi-center, international REPLACE COVID trial, investigators will examine whether ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are beneficial or harmful. Hospitalized patients in the trial will by randomly assigned to either stop or continue taking their prescribed medication. Nearly half of American adults have high blood pressure and more than one-third of them are prescribed ACEIs or ARBs. Investigators plan to enroll 152 patients who are hospitalized with a suspected diagnosis of COVID-19 and already use one of the medications. Dosages will be changed, or medications discontinued, if there is a compelling clinical reason. Researchers ultimately aim to develop a global risk score that ranks patient outcomes based on four factors: time to death, number of days supported by mechanical ventilation or extracorporeal membrane oxygenation, length of time on renal replacement therapy, and a modified sequential organ failure assessment score. Press release.

Biotech CRO Novotech has released research detailing the current status of clinical trials in the Asia-Pacific region during the global COVID-19 crisis. In its situation update on Australia, for example, Novotech reports that most of the top 10 biotech sites are open for trial activity, with many sites modifying their practices to ensure continuity of operations. The country has attractive start-up times and rebates of up to 43.5% on clinical trial spend. Similar reports have been prepared on South Korea, Taiwan, Hong Kong, New Zealand, China, Thailand, Malaysia, Singapore and The Philippines. Press release.

St. Jude Children's Research Hospital, in partnership with the International Society of Paediatric Oncology, has launched a Global COVID-19 Observatory and Resource Center for Childhood Cancer. The website is a place for healthcare providers around the world to share the latest information, insights and best practices in treating pediatric cancer patients who are infected with SARS-CoV-2. The site also provides access to a pediatric cancer registry to collect de-identified data from pediatric cancer patients who have been diagnosed with COVID-19. The global pediatric hematology and oncology community will have access to the data and receive regularly updated summary information about reported cases, including the number by country and treatment. The website has already held educational sessions with physicians and infectious diseases experts from Singapore, Japan, China, and Russia. Press release.

Octapharma USA is supporting a new investigator-initiated clinical trial at Sharp Memorial Hospital in San Diego, California focused on treating COVID-19 patients experiencing respiratory failure who become ventilator-dependent. The trial—Randomized Open Label Study of Standard of Care Plus Intravenous Immunoglobulin (IVIG) Compared to Standard of Care Alone in the Treatment of COVID-19 Infection— seeks to learn if IVIG can halt coronavirus progression to respiratory failure requiring transfer into the ICU and mechanical ventilation and whether adding IVIG to the standard of care will reduce days requiring oxygen therapy and total hospital days. IVIG has traditionally been used to treat immune-mediated diseases and for prophylaxis and treatment of severe infections, especially in immunocompromised patients. It has previously demonstrated utility for COVID-19 infection in only a handful of instances, but with dramatic clinical improvement allowing hospital discharge in clinically deteriorating patients. Press release.

The University of Rochester Medical Center is launching a new study to understand how the body's immune system responds to COVID-19, including if (and when) a person could be re-infected with the virus and whether some people have pre-existing immunity. The findings could have significant implications for the public health response to the pandemic, the development of COVID-19 vaccines, and decisions related to re-opening the economy and society. The research is supported by approximately $5 million in funding from the National Institute of Allergy and Infectious Diseases, the institute headed by Anthony Fauci, M.D. Among the questions seeking answers are the durability of immunity from the virus once a person has been infected and recovered, if the virus is mutating, whether previous exposure to other seasonal coronaviruses provides a degree of protection from COVID-19, and how long potential vaccines could provide immunity. The study will recruit up to 100 COVID-19 positive individuals across all age groups from the Rochester community and follow them for 90 days. Press release.

INOVIO will be working with the International Vaccine Institute (IVI) and the Korea National Institute of Health on an early-phase trial of INOVIO's COVID-19 vaccine candidate (INO-4800) in South Korea. IVI will conduct the trial in parallel with a vaccine study currently underway in the U.S. with 40 healthy adults. Plumbline Life Sciences of South Korea will also collaborate on the project. INOVIO’s DNA vaccine platform was one of the first technologies to receive support from the Coalition for Epidemic Preparedness Innovations to accelerate a COVID-19 vaccine and is providing $6.9 million in grant funding for this trial. It comes at the heels of an announcement by the Korean Ministry of Food and Drug Safety that it will adopt a fast-track approval process for COVID-19 vaccine and treatment clinical trials, shortening the clinical trial screening period from 30 to seven days for substances with experience in use and within 15 days for new materials. INOVIO’s DNA platform also qualifies for an exemption from toxicology tests, which will minimize data submission and expedite clinical trials. Press release.

Researchers at McMaster University are taking steps to learn whether the airway microbiome can be harnessed to prevent COVID-19 infections. In one study, they’re trying to identify and isolate the microbes that protect older adults from respiratory infection in collaboration with Mount Sinai Hospital in Toronto. In a second study, they’re trying to tease out the actual infection rate in the city of Hamilton and any differences in the immune responses or airway microbiomes of those who get sick or have symptoms and those who don't. Healthcare workers who become infected with SARS-CoV-2 will be asked to provide a nasal swab of household members to measure the microbiome and a sample of nasal secretions to measure early immune responses. Both studies launched this month. Press release.

Penn Medicine plans to launch a COVID-19 convalescent plasma study, a two-part research initiative that will use the plasma from people who've recovered from the virus to investigate how the therapy works for moderately and severely ill patients. (Read more about the research behind convalescent plasma and other ongoing research projects.) Following approval from the FDA for an Investigational New Drug application, researchers will begin enrolling 50 patients into the first trial clinical trial that will take no more than four months to complete. Each patient will be given up to two units (500 milliliters) of plasma collected at Penn. Press release.

A COVID-19 registry at West Virginia University (WVU) now contains more than 7,500 negative cases and 450 positives from individuals tested through the WVU Medicine system. Updated daily, the registry includes detailed information from patients including testing method, ICU stays, ventilator use, medications, vital signs, preexisting conditions, labs, procedures and basic demographics. Researchers are provided specific datasets upon approval. Since news of the registry got out, researchers have flooded WVU’s West Virginia Clinical and Translational Science Institute with requests. Some of those projects involve convalescent plasma therapy in patients with severe COVID-19, neurological outcomes in COVID-19 patients and predictive modeling to identify high-risk patients. Press release.