May 29, 2020 | This week saw the clinical research community make a concerted effort to continue treating patients amid the COVID-19 pandemic. Researchers have outlined recommendations for the treatment of bladder cancer during the COVID-19 pandemic. Reports also indicate that people with cancer sickened by COVID-19 have a crude death rate of 13%—more than twice that reported for all patients with the COVID-19. And in the meantime, COVID-19 related research is still in progress. Here, we round up the week’s research and industry news for COVID-19.

Literature Updates

In the journal Bladder Cancer, researchers have outlined recommendations for the treatment of bladder cancer (muscle invasive/MIBC and non-muscle invasive/NMIBC) during the COVID-19 pandemic, based on data from trials and prior studies while taking current strains on the healthcare system into account. Some patients can’t wait on treatment without compromising their oncologic outcomes. The authors propose surveillance for all patients with a history of low-risk tumors and those with non-high-grade, intermediate-risk NMIBC, reserving transurethral resection of bladder tumor for symptomatic patients. Patients with high-risk NMIBC should proceed with active treatment. For patients with the more lethal MIBC, radical cystectomy should be prioritized during the COVID-19 epidemic. DOI: 10.3233/BLC-200311

In the Journal of Clinical Investigation, researchers from Johns Hopkins University and Stanford argue for the testing alpha blockers to treat severely ill patients presenting with cytokine storm symptoms. Before COVID-19 hit, they were exploring the use of alpha blocks to ease the hyperinflammatory immune response in cancer patients treated with immunotherapy. They’re now recruiting patients ages 45 to 85 at Johns Hopkins Hospital who have COVID-19 but who aren't on a ventilator or in the ICU into a clinical trial of an alpha blocker to see if it might break the cycle of hyperinflammation before it ramps up. To gain approval for the trial, they gathered evidence from medical claims data that taking such drugs correlated to a lower risk of death from respiratory distress. Trial participants will take gradually increasing doses of prazosin, sold under the brand name Minipress, over six days and researchers will compare their outcomes (ICU admission rate or ventilator use) with patients who received the standard treatment. Preliminary data from the first patients could be available within weeks. If results suggest alpha blockers are safe and effective, the team plan to run a second trial with patients who have been diagnosed with COVID-19 but are not yet hospitalized. DOI: 10.1172/JCI139642

As reported in the New England Journal of Medicine, an international team of researchers examined seven lungs obtained during autopsy from patients who died of COVID-19 to identify vascular features during clinical course of the disease. While the lungs shared some common features with autopsied lungs obtained from patients who died of acute respiratory distress syndrome secondary to influenza A infection, there were also distinctive features related to blood vessels. Among their observations were that COVID-19 damaged the endothelial cells, causing severe endothelial injury and that patients showed widespread blood clotting as well as new vessel growth. There were also signs of a distinctive pattern of pulmonary vascular disease progression in some cases of COVID-19 compared to that of equally severe influenza virus infection. The body compensates for the thrombosis and blood vessel damage with a unique response (intussusceptive angiogenesis). Damaged blood vessels may also underlie other problems seen, such as COVID toe, children with Kawasaki, stroke, and other seemingly unrelated problems. DOI: 10.1056/NEJMoa2015432

Those who are socially isolated are over 40% more likely to have a cardiovascular event, such as a heart attack or stroke, than those who were socially integrated, according to a German study published in the Heart. They are also almost 50% more likely to die from any cause. The research further shows that a lack of financial support independently increased the risk of cardiovascular events. Findings were based on analysis of data from 4,316 individuals (average age 59.1 years) who were recruited into the large community-based study between 2000 and 2003 with no known cardiovascular disease and followed for an average of 13 years. The authors say the finding is worrisome, particularly during these times of prolonged social distancing. DOI: 10.1136/heartjnl-2019-316250

A study in Australia finds the number of children and adolescents testing positive for COVID-19 at The Royal Children’s Hospital (a tertiary pediatric hospital in Melbourne) has been low and none who contracted the virus required in-hospital treatment, in the first 30 days since seeing its first patient. Out of 434 children tested for the virus, only four had a positive result and they all recovered within two weeks after experiencing mild upper respiratory symptoms. The research published in Emergency Medicine Australasia. DOI: 10.1111/1742-6723.13550

Lower levels of ACE2 nasal gene expression in children may explain why children have a lower risk of COVID-19 infection and mortality, according to a study by researchers at Mount Sinai that published in JAMA. The SARS-CoV-2 virus uses ACE2 to enter the host. ACE2 nasal gene expression in nasal epithelium increases with age and could potentially be used as a biomarker to evaluate COVID-19 susceptibility. Results were based on a retrospective examination of nasal epithelium from 305 individuals aged 4 to 60 years who had been recruited to study biomarkers of asthma. DOI: 10.1001/jama.2020.8707

Scientists from the U.K., Europe and the U.S. have published a consensus paper warning against high doses of vitamin D supplementation. Their study, which published in in BMJ Nutrition, Prevention & Health, finds insufficient scientific evidence to show vitamin D can be beneficial in preventing or treating COVID-19. It follows unverified reports that doses of vitamin D higher than 4000IU/d could reduce the risk of contracting COVID-19 and be used to successfully treat the virus. Further, previous studies claiming a link between vitamin D levels and respiratory tract infections were largely based on data gathered from population groups in developing countries and cannot be extrapolated to populations from more developed countries due to external factors. DOI: 10.1136/bmjnph-2020-000089

Having a faulty gene linked to dementia doubles the risk of developing severe COVID-19, according to a large-scale study conducted by researchers at the University of Exeter Medical School and the University of Connecticut School of Medicine. The study, based on an analysis of data from the UK Biobank, found high risk of severe COVID-19 infection among European ancestry participants who carry two faulty copies of the APOE e4e4 gene, which is known to increase the risk of Alzheimer's disease up to 14-fold as well as the odds of developing heart disease. The higher COVID-19 risk applies even to people who had not developed either of these diseases. The team previously found that people with dementia are three times more likely to get severe COVID-19, and the latest study indicates a genetic component may be at play. Findings published in the Journal of Gerontology: Medical Sciences. DOI: 10.1093/gerona/glaa131

Age, male sex, obesity and underlying illness have emerged as risk factors for severe COVID-19 or death in the UK, according to the largest prospective observational study to date published by The BMJ. The risk of death increases in the over-50s, as does being male, obese, or having underlying heart, lung, liver and kidney disease. The study is ongoing and has recruited over 43,000 patients. Findings were based on an analysis of data from 20,133 patients with COVID-19 admitted to 208 acute care hospitals in England, Wales and Scotland—representing about one-third of all such patients in the U.K.—between Feb. 6 and April 19, 2020. Overall, 41% of patients were discharged alive, 26% died, and 34% continued to receive care at the reporting date. Outcomes were poorer for those requiring mechanical ventilation. Other than obesity, the pattern of disease described broadly reflects the pattern reported globally. DOI: 10.1136/bmj.m1985

It's inappropriate to consider blanket do-not-resuscitate orders for COVID-19 patients because adequate data is not yet available on U.S. survival rates for in-hospital resuscitation of COVID-19 patients and data from China may not relate to U.S. patients, according to an article published in Circulation: Cardiovascular Quality and Outcomes. There is a presumption that COVID-19 patients have a low survival rate after resuscitation, based on a study from Wuhan that found an overall survival of 2.9% in 136 COVID-19 patients who underwent cardiopulmonary resuscitation for in-hospital cardiac arrest. Investigators examined data on 5,690 patients in the American Heart Association's Get With The Guidelines-Resuscitation registry who underwent CPR for in-hospital cardiac arrest while being treated in an intensive care unit for pneumonia or sepsis and were receiving mechanical ventilation at the time of cardiac arrest. Although the overall survival rate was only 12.5% in the U.S. simulation, the probability of survival without severe neurological disability ranged from less than 3% to more than 22% across key patient subgroups and the probability of mild to no disability ranged from about 1% to 17%. Survival rates were also above 20% in younger patients with an initial shockable rhythm who were not being treated with vasopressor medications prior to the cardiac arrest. DOI: 10.1161/CIRCOUTCOMES.120.006837

As has been widely reported in the lay press, a research team led by investigators from Brigham and Women's Hospital evaluated real-world evidence related to outcomes for COVID-19 patients treated with hydroxychloroquine or chloroquine (with or without an antibiotic) and found no evidence that either drug regimen reduced the death rate. In fact, patients so treated were far more likely to experience ventricular arrhythmias (4%-8%) than their counterparts (0.3%) who had not received the drugs. Findings were based on an observational analysis of almost 100,000 hospitalized COVID-19 patients in the Surgical Outcomes Collaborative database—an international registry compromised of deidentified data from 671 hospitals across six continents—of whom nearly 15,000 received one drug or the other. Results from randomized, controlled clinical trials are not expected until the summer. The team's findings published in The Lancet. DOI: /10.1016/S0140-6736(20)31180-6

The Lancet has also published research out of China finding that the first COVID-19 vaccine to reach phase 1 clinical trial is safe, well-tolerated, and able to generate an immune response against SARS-CoV-2 in humans. This Ad5 vectored vaccine uses a weakened common cold virus to deliver genetic material that codes for the SARS-CoV-2 spike protein to the cells. It is one of more than 100 candidate COVID-19 vaccines in development worldwide. In the open-label trial, promising results were demonstrated in 108 healthy adults after 28 days with most participants across dosing groups having a four-fold increase in binding antibodies against SARS-CoV-2. The vaccine also stimulated a rapid T cell response in most volunteers, which was greater in those given the higher and middle doses. At 28 days, most recipients showed either a positive T cell response or had detectable neutralizing antibodies against SARS-CoV-2. Results will be evaluated in six months. A randomized, double-blinded, placebo-controlled phase 2 trial of the Ad5-nCoV vaccine involving 500 healthy adults (including participants over 60 years old) has been initiated in Wuhan to determine whether the results can be replicated and if there are any adverse events up to six months after vaccination. DOI: /10.1016/S0140-6736(20)31208-3

The placentas from 16 women who tested positive for COVID-19 while pregnant showed evidence of injury—specifically, abnormal blood flow between the mothers and their babies—according to pathological exams completed directly following birth by researchers at Northwestern University. Most of the babies were delivered full-term after otherwise normal pregnancies but based on the limited data validates the idea that women with COVID should be monitored more closely in the form of non-stress tests and growth ultrasounds. Previous research has found that children who were in utero during the 1918-19 flu pandemic have lifelong lower incomes and higher rates of cardiovascular disease; findings also support the clot-forming potential of the novel coronavirus. Results published in the American Journal of Clinical Pathology. DOI: 10.1093/ajcp/aqaa089

A systematic review of 21 standard, World Health Organization–specific and COVID-19–specific databases finds indirect and low-certainty evidence suggesting that use of noninvasive ventilation to respiratory failure probably reduces mortality but may increase the risk for transmission of COVID-19 to healthcare workers. Of the 123 included studies (45 on COVID-19, 70 on SARS and eight on MERS), only five were adjusted for important confounders. Direct studies in COVID-19 are limited and poorly reported. Results published in the Annals of Internal Medicine. DOI: 10.7326/M20-2306

Damage to the immune system in asymptomatic COVID-19 infections is milder compared with symptomatic infections, finds a study of patients in China that published in JAMA Network Open.  Patients with asymptomatic SARS-CoV-2 infection also have a shorter duration of viral shedding from nasopharyngeal swabs and lower risk of a recurring positive test result of SARS-CoV-2 from nasopharyngeal swabs. Included in the study were 78 patients from 26 cluster cases of exposure to the Hunan seafood market or close contact with other patients with COVID-19, who tested positive for COVID-19 between Dec. 24, 2019 and Feb. 24, 2020. DOI:10.1001/jamanetworkopen.2020.10182

The prevalence of symptomless COVID-19 infection may be much higher than thought, reveals a study charting the enforced isolation of cruise ship passengers. More than eight out of 10 of passengers and crew who tested positive for the infection had no symptoms. The researchers, all of whom were on board the vessel carrying 128 passengers and 95 crew, describe the unfolding of events in Thorax. The potentially high rate of false-negative results obtained with current swab tests suggests secondary testing is warranted. DOI: 10.1136/thorax-jnl-2020-215091

LSU Health New Orleans pathologists performed the first series of autopsies on African Americans who died from COVID-19 in their city, revealing new cardiopulmonary findings. Researchers found that the small vessels and capillaries in the lungs were obstructed by blood clots and associated hemorrhage that significantly contributed to decompensation and death. They also found elevated levels of D-dimers (protein fragments involved in breaking down blood clots) but, notably, not myocarditis (inflammation of the heart muscle) that early reports suggested significantly contributes to death from COVID-19. Patients represented both genders, were between 40 and 70 years old and many had a history of hypertension, obesity, insulin-dependent type II diabetes and chronic kidney disease. They all presented to the hospital less than a week after developing a mild cough and fever, experiencing sudden respiratory decompensation or collapse at home; chest X-rays revealed bilateral ground-glass opacities (consistent with acute respiratory distress syndrome). Study results published in The Lancet Respiratory Medicine. DOI: 10.1016/S2213-2600(20)30243-5

Findings of the first report on mental health outcomes and associated risk factors among healthcare workers in Italy during the COVID-19 pandemic, published in JAMA Network Open, are in line with previous reports from China. The study confirms a substantial proportion of mental health issues, particularly among young women and frontline healthcare workers. Findings were based on data from 1,379 online questionnaires completed between March 27 and March 31, 2020. Nearly half of respondents reported posttraumatic stress symptoms, nearly one-quarter had symptoms of depression and about 20% had signs of anxiety and high perceived stress. DOI: 10.1001/jamanetworkopen.2020.10185

COVID-19 patients in the U.S. are enduring longer hospital stays and facing higher rates of intensive care unit admission than patients in China, according to a study led by researchers at the University of California, Berkeley and Kaiser Permanente that published in The BMJ. Conclusions were based on an analysis of the records of nearly 9.6 million Kaiser Permanente patients in Southern California, Northern California and Washington state; the focus was on 1,277 patients hospitalized with clinically- or laboratory-confirmed cases of COVID-19 between the start of the year and early April. Of those, 42% required care in the ICU and 18% died from the disease. Modeling estimates based on observations in China usually assume that only about 30% of hospitalized patients will require ICU care. Similarly, the data showed that hospital stays lasted an average of 10.7 days for survivors and 13.7 days for non-survivors, compared to an average of 7.5 days among non-survivors in China. Troublingly, 25% of patients were hospitalized for 16 days or more. A widely used modeling study projecting healthcare needs assumes an average stay of eight days. DOI: 10.1136/bmj.m1923

Montefiore Health System and the Albert Einstein College of Medicine have begun the next stage of the Adaptive COVID-19 Treatment Trial (ACTT) that will evaluate treatment options for people hospitalized with severe COVID-19 infection, and is being sponsored by the National Institute of Allergy and Infectious Diseases. Montefiore was the first New York location to join the multicenter trial that evaluated remdesivir, preliminary results of which published in the New England Journal of Medicine. Key findings of the 1,063-patient study were that COVID-19 patients treated with remdesivir recovered in 11 days on average compared to 15 days for patients in the placebo group. In ACTT 2, remdesivir is being studied in combination with rheumatoid arthritis drug baricitinib in a double-blind, placebo-controlled, randomized trial to see if the two-pronged approach can prevent or reduce the hyper-inflammatory cytokine storm that can fatally overwhelm the lungs and other parts of the body in people with COVID-19. DOI: 10.1056/NEJMoa2007764

Mortality risk factors for COVID-19 include old age, underlying health conditions, and bacterial and respiratory co-infections, according to researchers in China. The study involved 155 COVID-19 patients at Wuhan University's Zhongnan Hospital and results published in Frontiers in Medicine. While the overall mortality rate of COVID-19 is estimated to be about 2%, over 50% of critically ill COVID-19 patients at the hospital finally died due to multiple organ dysfunction and severe complications. Among the 18 non-survivors, most were men over the age of 65 with underlying conditions, and many became co-infected with other respiratory viruses, bacteria, and mycoplasma over the course of the illness. All but one developed acute respiratory distress syndrome by the time of their death, 10 had acute cardiac injury and seven had acute kidney injury. Patients also had marked decreases in T cells as well as decreases in plasma protein and albumin. The authors emphasized that early intervention was crucial; in fatal cases, the median hospital stay was just 13.5 days. DOI: 10.3389/fmed.2020.00246

Researchers in Brazil describe their clinical experience with the first 27 patients where COVID-19 was treated as a thrombotic disease, in a preprint version of a paper submitted to the Journal of Thrombosis and Haemostasis. The protocol, developed at Hospital Sírio-Libanês (São Paulo City), advocates for the use of the anti-coagulant drug heparin to treat complications caused by novel coronavirus. Researchers at University of São Paulo’s Medical School recently hypothesized that blood clotting disorders may explain some of the worst symptoms of COVID-19, including respiratory failure and pulmonary fibrosis. They now plan to conduct a randomized clinical trial in partnership with colleagues at the University of Toronto (Canada) and the University of Amsterdam (Netherlands) to demonstrate the therapeutic efficacy of heparin in COVID-19 patients. The trial will entail giving heparin to patients who come to an outpatient clinic with low oxygen saturation levels and seeing if treatment with the anti-coagulant can avoid the need for mechanical ventilation. DOI: 10.1101/2020.04.15.20067017

A team of European researchers have found the loss of smell and loss of taste to be two distinct symptoms of COVID-19, based on responses to an online questionnaire by 2,153 hospitalized and ambulatory patients in 18 hospitals with mild-to-moderate disease between March 22 and April 23, 2020. Their results suggest that anosmia may not be related to nasal obstruction or inflammation. DOI: 10.7326/M20-2428

The multinational COVID-19 and Cancer Consortium (CCC19) reports in The Lancet that people with cancer sickened by COVID-19 have a crude death rate of 13%—more than twice that reported for all patients with the COVID-19. Data on more than 900 patients in Spain, Canada and the United States in the CCC19 registry, maintained as an electronic REDCap database at Vanderbilt University Medical Center, informed the findings. The initiative also identified cancer-specific factors associated with increased mortality, notably active (measurable) cancer and impaired ECOG performance status of two or worse. Males, older patients and those with major comorbid conditions were also at substantially increased risk of dying from COVID-19. The early data showed no statistical association between 30-day mortality and cancer treatments. DOI: https://doi.org/10.1016/S0140-6736(20)31187-9

In Frontiers of Immunology, a team of researchers from the FDA provide a breakdown of key immunological factors underlying the clinical stages of COVID-19 illness that could potentially be targeted by existing therapeutic drugs. Their conclusions are based on a review all the COVID-19 clinical and research findings to date, supplemented with knowledge previously acquired from other coronaviruses. The authors underscore key immunological events that might tip the balance from a protective to a hyperinflammatory response leading to life-threatening conditions. They outline a promising list of currently available drugs that are either under study or under consideration for use in COVID-19 based on their potential to influence these key immunological events. It may be that there is no single magic bullet to resolve the disease but a combination of several interventions that target different key factors of COVID-19. DOI: 10.3389/fimmu.2020.01131

Researchers at the University of Colorado published research in the Annals of Surgery that provides guidance on treating pancreatic cancer patients during the COVID-19 pandemic. Findings are based on 337 responses to an online survey in April 2020 by members of seven international pancreatic associations and study groups across 37 countries spanning five continents. Most respondents were surgeons who work in an academic center, and the biggest takeaway was that pancreatic surgery should be prioritized for patients with non-COVID-19 pancreatic diseases during the pandemic. Other key findings were that less pancreatic surgery was being performed, most centers screened patients for symptoms of COVID-19 prior to surgery (although no consensus was reached to recommend this practice), and there was widespread agreement that patients undergoing pancreatic surgery should be informed about additional risks such as COVID-19 infection during hospitalization and possible non-optimal postoperative management (i.e., shortage of ICU beds). DOI: 10.1097/SLA.0000000000003859

Use of more than 100 off-label and experimental treatments for COVID-19 have been catalogued, thanks to the efforts of researchers at the University of Pennsylvania. The COvid19 Registry of Off-label & New Agents (aka CORONA) is an attempt to take an inventory of what's being used where, as well as to spot any evidence of treatments that warrant further investigation in a randomized clinical trial. The undertaking involved reviewing about 2,700 published papers from all over the world, and then gathering data on 9,152 patients to find doctors had tried 115 different drugs. These treatments were grouped into categories—antivirals were unsurprisingly the most common, followed by antibacterials and corticosteroids. The analysis also showed the use of immunosuppressants and blood substitutes, among other treatment options. The findings published in Infectious Diseases and Therapy. DOI: 10.1007/s40121-020-00303-8

A study coming out of Columbia University and published in Science Advances reveals how low measles, mumps, and rubella (MMR) vaccination rates and “measles parties” designed to purposely infect children fueled a 2019 measles outbreak in New York City, which should be a wake-up call for the potential of another such outbreak as vaccination rates plummet during the COVID-19 pandemic. The outbreak subsided following extensive vaccination campaigns and a mandatory vaccination order, lowering a potential caseload of 6,500-8,100 people to 649 actual cases. Worryingly, MMR vaccination rates in New York City have dropped by 63 percent for all children and 91 percent among those over age 2 in recent weeks. As the number of unvaccinated children increases and contact resumes, the risk of disease spread will grow. DOI: 10.1126/sciadv.aaz4037

A Canadian case series of all patients with COVID-19 admitted to six intensive care units (ICUs) in Metro Vancouver found patient outcomes were substantially better than reported in other jurisdictions. Researchers looked at outcomes for 117 patients admitted to the hospital between Feb. 21 and April 14, 2020. As of May 5, 85% of patients were still alive and 61% had been discharged home. The overall mortality rate was 15%. By comparison, data from Lombardy, Italy, showed a 61% mortality rate for patients admitted to an ICU, a case study of 24 people in Seattle had a 57% mortality rate among patients in the ICU, and a case series from Wuhan, China, reported a mortality rate of 80% in patients admitted to the ICU. Fewer patients in the Canadian series received mechanical ventilation than in either Lombardy or Seattle, and very few patients received unproven treatments. The authors say the encouraging results may be due to a broader system-level response that prevented an overwhelming surge of critically ill patients with COVID-19 from presenting to their hospitals and ICUs. The paper published in the Canadian Medical Association Journal. DOI: 10.1503/cmaj.200794

Pediatric surgeons at the University of Chicago Medicine have modified an evaluation tool for use in children that allows surgeons in every pediatric specialty to prioritize elective operations during all phases of the pandemic. The Pediatric Medically Necessary Time-Sensitive (pMeNTS) scoring system is presented on the Journal of the American College of Surgeons website ahead of print. The tool is not a risk calculator. It focuses on an operation's medical necessity and time-sensitivity and assesses COVID-19 factors such as infection risk for the patient and providers as well as projected use of hospital resources. Users rate each factor on a five-point scale; a lower overall pMeNTS score indicates a more favorable surgical risk, less risk to personnel, and less resource utilization, and can be used to determine a higher priority for the procedure. Unlike the adult verson of the scoring system, pMeNTS accounts for chronic diseases of childhood and birth defects, omits chronic illnesses of adulthood that are rare in children and reflects the impact of age on a procedure. It was successfully tested on 101 pediatric patients at UChicago Comer Children's Hospital. DOI: 10.1016/j.jamcollsurg.2020.05.015

A University of Warwick (U.K.) researcher has come up with new guidelines for scientists and regulators showing how deliberate infection of volunteers for vaccine trials can be done ethically—and should be considered to speed up vaccine development. The work has been peer-reviewed and published in the Journal of Medical Ethics, and poses three key questions for those planning vaccine development studies: Has reasonable care been taken to maximize the potential benefits of the proposed study and minimize the risks of harm to participants? Is the informed consent process sufficiently robust? What do we need to do now to amend our processes to speed up the consideration and approval processes for proposed COVID-19 vaccine candidate phase II and phase III trials? DOI: 10.1136/medethics-2020-106322

A study by University of Cincinnati researchers and four Italian institutions reviewing neuroimaging and neurological symptoms in patients with COVID-19 may shed light on the virus's impact on the central nervous system. The findings, published in Radiology, reveal that altered mental status (59%) and stroke (31%) are the most common neurological symptoms in COVID-19 patients, which the authors say could help physicians notice "red flags" earlier. This is the largest and first study in the literature that characterizes the neurological symptoms and neuroimaging features in COVID-19 patients. It included images from 725 hospitalized patients in Italy with confirmed COVID-19 infection between Feb. 29 and April 4, 2020. DOI: 10.1148/radiol.2020201933

In an article published in Chemical & Engineering News, researchers from the Emory Institute for Drug Development report on an emerging antiviral called EIDD-2801 that might turn the tide for this pandemic and the next. It has shown promise against several RNA viruses, including Ebola, influenza and SARS-CoV-1, in cell and animal studies. EIDD-2801 targets the same viral enzyme as remdesivir, but is an oral medication. If shown to be safe and effective, it could be taken at home rather than in the hospital, allowing treatment earlier in the course of the disease. Phase I human trials of EIDD-2801 are now underway in the U.K., and a U.S. trial is slated to begin in the next few weeks. To have an impact, EIDD-2801 will most likely need to be given before the virus has time to ravage the body—ideally, soon after a person is exposed to SARS-CoV-2 or at the initial onset of symptoms. The potential drug's ability to target an array of viruses bodes well for future outbreaks, the authors say. Article.

Updates from Industry

Airway Therapeutics, Inc. and Celonic Group are collaborating to produce the novel human recombinant protein AT-100 as a therapeutic candidate against COVID-19. Based on the agreement, Celonic will be responsible for process optimization and GMP manufacturing of AT-100 for clinical study. AT-100 is an engineered version of an endogenous protein and has shown potential in addressing the inflammation and injury caused by serious, infection-driven respiratory diseases in preclinical studies but has never been produced for larger-scale clinical trial indications. Airway has previously filed a pre-IND submission with the U.S. Food and Drug Administration for AT-100 as a preventive treatment of the serious respiratory disease bronchopulmonary dysplasia in very preterm infants, with an IND filing expected in Q3 and plans to enter the clinic in late 2020. Celonic expects to begin production of AT-100 in June 2020. Press release.

Data scientists and cancer doctors from the University of Michigan Rogel Cancer Center and the U-M School of Public Health have developed a free, web-based application to compare the long-term risk to a patient from a months-long postponement of care to the additional risk posed by potential COVID-19 infection if they undergo surgery, chemotherapy and/or radiation. The OncCOVID app draws on large, national cancer data sets (National Cancer Institute's Surveillance, Epidemiology, and End Results registry and the National Cancer Database) combined with county-level COVID infection data from Johns Hopkins University to help assess the risk from of immediate treatment versus delayed treatment, depending on patients’ individual characteristics, as well as on COVID's impact on their local community. Up to now, hospitals have essentially been using a three-tiered system during the pandemic—treat, delay a little or delay a lot. The app allows doctors to enter more than 45 characteristics about patients and then calculates their likely five-year survival following immediate treatment and delayed treatment. In some cases, the personalized risk assessments run counter to the generic, three-tiered approach. Press release.

A nationwide collaboration of clinicians, informaticians and other biomedical researchers plan to turn data from hundreds of thousands of medical records from COVID-19 patients into effective treatments and predictive analytical tools that could help lessen or end the global pandemic. Through the National COVID Cohort Collaborative, about 60 clinical institutions affiliated with the National Institutes of Health-supported Clinical and Translational Science Awards Program are invited to partner with U.S. Department of Health & Human Services agencies and clinical organizations. Together, Collaborative members will support the analysis of electronic health records (EHRs) on a new, secure database. The collaborative platform will be based at Oregon Health & Science University. Individuals granted access to the database will be able to run algorithms on this first-of-its-kind patient data set without seeing actual patient records. A safe derivative of the patient data (synthetic data) also will be available. Fifteen institutions that have agreed to contribute data thus far, and the first sampling of EHRs was transferred to the database on May 12. Press release.

A string of government-supported studies is launching in Ontario investigating a range of important COVID-19 questions, including three led by teams from Lawson Health Research Institute and Western University. These include the world’s first study of the human protein annexin A5 as a potential therapy for COVID-19 patients with sepsis. The randomized controlled trial will enroll up to 60 critically ill patients from London Health Sciences Centre, and its goal is to determine whether the drug reduces hyperinflammation associated with sepsis in order to prevent respiratory and multi-organ failure. The team also believes the drug will prevent cell death and blood clots associated with COVID-19 through annexin A5's anti-apoptotic and anti-coagulant properties. Press release