By Clinical Research News Staff

Sept. 4, 2020 | A protease inhibitor used to cure a deadly coronavirus-causing disease in cats holds potential for testing in humans, a comparative look at current treatment approaches, proposed Fair Priority Model for vaccine distribution and needed reforms to the FDA’s Emergency Use Authorization process, concerning trends among pregnant women, rising rates of depression, promising news on steroids, and multiple trials on the launch pad—all among the explosion of COVID-19-related news over the past week. 

Research Updates 

The European Association for the Study of the Liver and the European Society of Clinical Microbiology and Infectious Diseases have published their second position paper about the impact of COVID-19 on the care of patients with liver disease in JHEP Reports. It provides a clearer picture on the evolution of the virus, how it affects liver and transplant patients, and who is most at risk. The authors note that emphasis needs to shift from an earlier focus on immune-suppressed patients or living with auto-immune liver conditions to maintaining the care of all patients, both in outpatient services and in hospitals, and looking out for specific groups at higher risk. While patients with liver disease appear not to be at increased risk of contracting SARS-CoV-2, those patients with non-alcoholic fatty liver disease, obesity, and cirrhosis seem to have poorer outcomes and fare less well. Of note, patients with auto-immune liver disease and chronic viral hepatitis are advised to continue with their treatments. DOI: 10.1016/j.jhepr.2020.100169 

Researchers at the University of Minnesota have published a study in Nature Genomic Medicine about how individualization with pharmacogenomics may improve the efficiency and safety of drugs under investigation to treat COVID-19—a strategy successfully deployed for the HIV treatment abacavir. The study looked at a variety of literature for drug therapies for COVID-19 (including hydroxychloroquine, remdesivir, tocilizumab and steroids) to find several gene variants altering how an individual's body metabolizes and processes COVID-19 therapies, potentially increasing the risk of adverse effects; the risk of taking these therapies is complex since patients with COVID-19 are usually taking multiple other medications and have underlying conditions that affect the drug; and the data for the pharmacogenomics on COVID-19 is limited due to the early stages of the clinical trials investigating treatments. While researchers didn’t find direct evidence to support use of pharmacogenomic testing for COVID-19, they did identify many actionable genetic markers that may hold promise in improving efficacy and safety. DOI: 10.1038/s41525-020-00143-y 

Older adults experienced greater depression and loneliness during the COVID-19 pandemic, according to a study by Indiana University researchers, but perceived closeness to network members had a moderating effect. Results published in The Journals of Gerontology: Series B. Researchers compared personal social networks, subjective loneliness and depression of 93 older adults in Bloomington six to nine months prior to the pandemic and from late April to late May when most people were under stay-at-home orders. Two-thirds reported spending less time than before with people they loved and 79% felt like their social life decreased or was negatively affected by COVID-19. On the other hand, 60% reported spending somewhat or much more time reconnecting or catching up with people they cared about, and 78% were using some form of internet technology to keep in touch during the pandemic. On average, older adults reported spending about 76 minutes socializing virtually or over the phone each day. DOI: 10.1093/geronb/gbaa110 

Researchers at the University of Alberta are preparing to launch clinical trials of a protease inhibitor used to cure a deadly disease caused by a coronavirus in cats that they expect will also be effective as a treatment for humans against COVID-19. Findings were published in Nature Communications after first being posted on the research website BioRxIV. The drug shows enough antiviral action against SARS-CoV-2 to proceed immediately to clinical trials, for which veterinary medicine company Anivive Life Sciences will produce the needed quality and quantity of the drug. Human testing will likely be in Alberta in combination with other promising antivirals such as remdesivir. DOI: 10.1038/s41467-020-18096-2 

People with intellectual and developmental disabilities (IDD) are disproportionately affected by COVID-19, report directors of the Intellectual and Developmental Disabilities Research Centers Network in an article that published in the American Journal of Psychiatry. In the absence of human contact, the authors call for virtual care and support of people with IDD whenever possible and prioritizing all others to receive in-person services. They also say qualified in-home surrogates should ideally be mobilized to meet the specialized educational needs of people with IDD and to support parents’ efforts. This population often cannot verbalize their symptoms during telemedicine appointments and physicians need to use their best judgement in providing in-person care, they additionally note. DOI: 10.1176/appi.ajp.2020.20060780 

In a paper published in the Journal of Molecular Medicine, Russian and Iranian scientists describe currently known approaches to the treatment of SARS-CoV-2 infection and their promise. They enumerate the limitations of immunotherapy as the small number of potential donors, decreasing activity of antibodies over time and the possibility that the antibodies themselves will facilitate virus spread in the body. Another therapeutic option is to produce T-lymphocytes against the virus in vitro, based on the observation that the number of T-cells of the CD8+ subpopulation is significantly reduced in patients with COVID-19, and the more severe the disease the lower this number. A third area of research is related to the suppression of the enzymes AAK1 and GAK, which are needed for the virus to enter a cell. Some of the drugs that act as inhibitors of these enzymes have already been tested and used as a treatment for other diseases. Analogues of the ACE2 receptor have also been developed, tested and shown to slow down the spread of the virus in the body, but not stop it, which indicates the presence of other entry points into human cells. The use of antiviral drugs (remdesivir, chloroquine and HIV medications) has yielded mixed results. One more direction in the fight against COVID-19 is suppression of excessive immune system reaction, such as mesenchymal stem cells used in the treatment of inflammatory and autoimmune diseases and corticosteroids that can reduce mortality among patients with severe disease. An optimal treatment algorithm has yet to be found, they conclude. DOI: 10.1007/s00109-020-01927-6 

Nineteen global health experts from around the world have proposed a new, three-phase plan for COVID-19 vaccine distribution, called the Fair Priority Model, which aims to reduce premature deaths and other irreversible health consequences from COVID-19. In the paper, published in Science, the authors say the two main strategies that have been proposed—to immunize healthcare workers and high-risk populations (e.g., people over 65) first or, alternatively, to distribute doses proportional to the population of countries (WHO’s plan)—are both ethically flawed. Distribution of a finite resource is typically based on the severity of suffering in each place, which they argue ought to be measured in terms of the number of premature deaths that a vaccine would prevent. Benefiting people and limiting harm, prioritizing the disadvantaged, and giving equal moral concern for all individuals should be the three fundamental values considered when distributing a COVID-19 vaccine among countries, they say. The Fair Priority Model addresses these values by focusing on mitigating three types of harms caused by COVID-19: death and permanent organ damage, indirect health consequences (e.g., healthcare system strain and stress), and economic destruction. DOI: 10.1126/science.abe2803 

Pregnant women seen in hospitals with COVID-19 are less likely to show symptoms and seem to be at increased risk of needing admission to an intensive care unit than non-pregnant women of similar age, finds a study published by The BMJ. They are also more likely to experience preterm birth and their newborns are more likely to be admitted to a neonatal unit. Being older, overweight, and having pre-existing medical conditions such as hypertension and diabetes also seem to increase the risk of having severe COVID-19 in these women. Findings are based on a living systematic review conducted by an international team of researchers that analyzed 77 studies reporting rates, clinical features (symptoms, laboratory and x-ray findings), risk factors, and outcomes for 11,432 pregnant and recently pregnant women admitted to hospital and diagnosed as having suspected or confirmed COVID-19. DOI: 10.1136/bmj.m3320 

In a Viewpoint piece published in JAMA, a research team proposes reforms that the FDA could implement to improve the Emergency Use Authorization (EUA) process and drug approvals during public health crises, which could increase the FDA's credibility and the public's trust in it. The recommendations are especially timely given that FDA Commissioner Stephen Hahn has stated that the agency will consider using the EUA process to authorize a COVID-19 vaccine, as well as the potential for full approval of COVID-19 vaccines in late 2020. EUAs have typically been used for diagnostics and only rarely for therapeutics, they note. Four specific reforms are proposed for the agency, including clarifying evidentiary standards for EUAs; consulting with the external experts on its Advisory Committees before issuing EUAs; establishing extensive adverse event reporting systems, facilitate phase 4 trials to monitor post-approval safety and efficacy, and engage the National Vaccine Injury Compensation Program once COVID-19 vaccines are granted marketing authorization; and launching public education campaigns and utilizing communication tools like drug facts boxes to help explain regulatory decisions. DOI: 10.1001/jama.2020.16253 

Surprisingly, people with less heart rate response to a stress task had more post-traumatic stress disorder (PTSD) signs after COVID-19 began, finds a study by researchers at Baylor University and their colleagues at Washington and Lee University and the University of Birmingham (U.K.) that published in Psychosomatic Medicine. The study shows that diminished biological arousal before a global pandemic may predict PTSD symptoms related to the event. The study's first phase, which ended in February 2020, involved 120 participants in Central Texas who had their resting heart rate and blood pressure measured before and during a standard acute psychological stress test. After the pandemic's onset, researchers launched a second phase between March 26 and April 5, sending participants a follow-up questionnaire about COVID-19 used to measure PTSD symptoms of intrusion, hyperarousal and avoidance. The findings are in line with a previous study of soldiers that showed a lower response of cortisol to an acute psychological stress task before deployment predicted greater PTSD symptoms post-deployment. DOI: 10.1097/PSY.0000000000000848 

Asthma may not be a significant risk factor for severe COVID-19, according to a research letter authored by researchers at the University of Colorado and Icahn School of Medicine at Mount Sinai that published in Annals of the American Thoracic Society. The findings challenge the stance of the Centers for Disease Control and Prevention that individuals with asthma are at higher risk for hospitalization and other severe effects from COVID-19. The group compared the prevalence of asthma among patients hospitalized for COVID-19, as reported in 15 peer-reviewed studies, with that of the corresponding population's asthma prevalence. They also correlated the study's asthma prevalence with the four-year average asthma prevalence in influenza hospitalizations in the U.S., as well as analyzed the medical records of 436 COVID-19 patients admitted to the University of Colorado Hospital to evaluate the likelihood that patients with asthma would be intubated more often than patients without asthma. DOI: 10.1513/AnnalsATS.202006-613RL  

In a study published in Proceedings of the National Academy of Sciences, researchers at Osaka University (Japan) identified an effective treatment for the deadly over-activation of the inflammatory response seen in many severe COVID-19 patients. The team first studied the cytokine profiles of 91 patients diagnosed with cytokine release syndrome (CRS) associated with bacterial sepsis, acute respiratory distress syndrome, or burns. Strikingly, patients from all three groups had elevated levels of proinflammatory cytokines IL-6, IL-8, IL-10, and MCP-10, as well as a protein called PAI-1 that causes small blood clots in vessels throughout the body, including the lungs. Importantly, increased PAI-1 levels are associated with more severe cases of pneumonia, a common cause of death among COVID-19 patients. Because IL-6 was positively associated with the levels of the other cytokines and PAI-1, the researchers concluded that IL-6 signaling is crucial for the development of CRS following infection or trauma, and may play a role in the pathogenesis of COVID-19. When severe COVID-19 patients were treated with a human monoclonal antibody-based drug (Actemra) that blocks IL-6 signaling, PAI-1 levels rapidly declined and severe disease symptoms were alleviated. IL-6 signaling blockade, they concluded, could therefore prove useful for the treatment of both CRS and the severe respiratory complications of COVID-19. DOI: 10.1073/pnas.2010229117 

The prevalence of depression symptoms in the U.S. was more than three-fold higher during than before the COVID-19 pandemic, report researchers in a study published in JAMA Network Open. Individuals with lower social resources, lower economic resources, and greater exposure to stressors (e.g., job loss) reported a greater burden of depression symptoms. Post-COVID-19 plans should account for the probable increase in mental illness to come, they say. Estimates were derived from the COVID-19 and Life Stressors Impact on Mental Health and Well-being study (1,441 participants), conducted from March 31 to April 13, 2020 and the National Health and Nutrition Examination Survey (5,065 participants), conducted from 2017 to 2018. DOI: 10.1001/jamanetworkopen.2020.19686 

Clinician-scientists have pooled data from 121 hospitals in eight countries to find that inexpensive, widely available steroids improve the odds that very sick COVID-19 patients will survive the illness. The findings were made through the Randomized Embedded Multifactorial Adaptive Platform-Community Acquired Pneumonia (REMAP-CAP) trial and reported in JAMA. The World Health Organization is updating its COVID-19 treatment guidance as a result. REMAP-CAP is one of seven randomized control trials to test corticosteroids for treating COVID-19 in critically ill patients. An analysis combining all the trial data reinforces the June results of the UK RECOVERY trial, which found the steroid dexamethasone reduced deaths by 29% in ventilated COVID-19 patients. Between March and June, the REMAP-CAP corticosteroid trial randomized 403 adult COVID-19 patients admitted to an intensive care unit to receive the steroid hydrocortisone or no steroids at all. The trial found a 93% probability that giving patients a seven-day intravenous course of hydrocortisone would result in better outcomes than not giving the steroid, and the results were consistent across age, race and sex. DOI: 10.1001/jama.2020.17023 

Among patients with COVID-19 and moderate or severe acute respiratory distress syndrome, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days, according to a 299-patient study in Brazil that published in JAMA. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. DOI: 10.1001/jama.2020.17021 

A third study in France, also published in JAMA, found that low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21 among critically ill patients with COVID-19 and acute respiratory failure. However, the study was stopped early and likely was underpowered (149 patients admitted to the ICU for COVID-19-related acute respiratory failure) to find a statistically and clinically important difference in the primary outcome. DOI: 10.1001/jama.2020.16761 

In a single-center, retrospective cohort study published in JAMA Open Network, likely deficient vitamin D status was associated with increased COVID-19 risk, a finding that would need to be confirmed by randomized clinical trials. In this small study involved 489 patients who had a vitamin D level measured in the year before COVID-19 testing, the relative risk of testing positive for COVID-19 was 1.77 times greater for patients with likely deficient vitamin D status compared with patients with likely sufficient vitamin D status. DOI:10.1001/jamanetworkopen.2020.19722 

Scientists at Uppsala University and the University Hospital (Sweden) have identified a protein that may trigger blood clots (thrombosis), a common complication in severe COVID-19, as reported in Thrombosis and Haemostasis. A key mechanism of clot formation, they say, may be activation of the complement system—a component of the innate immune system—which can be initiated by proteins such as mannose-binding lectin (MBL). Sixty-five patients receiving intensive care at Uppsala University Hospital had their MBL levels and activity measured and, in all those who developed thrombosis during their hospital stay, MBL activity and levels were found to be elevated. The scientists believe that when the complement system is activated by means of MBL, it contributes to a massive activation of the blood coagulation system as well, and in a way that blood-thinning drugs can't prevent. Findings might eventually lead to testing of MBL activity in COVID-19 patients to identify those who are at high risk of getting thrombosis; MBL could also be a possible target in future development of drugs to prevent the condition. DOI: 10.1055/s-0040-1715835 

Researchers from Boston Medical Center's Maxwell Finland Laboratory for Infectious Diseases have identified properties in placenta tissue that may play an important role in preventing the transmission of COVID-19 from a mother to her fetus. Their study, published in Placenta, demonstrates that the COVID-19 virus universally invades the placenta in cases with and without evidence of fetal infection, highlighting the protection that the placenta may offer against COVID-19 infection. Current data indicates a COVID-19 transmission rate of less than 5% in newborns from their mothers. Researchers also found that the placenta contains a unique pattern of cell surface proteins (TMPRSS2 and ACE2) that are important for COVID-19 viral entry. Study results underscore the importance of using placenta tissue in COVID-19 research studies aimed at developing novel ways to diagnose, treat and prevent COVID-19 virus transmission. For this study, samples were collected taken from 15 COVID-19 positive maternal-fetal dyads; five cases had evidence of fetal transmission and the placental tissue of the positive cases was analyzed and compared with ten COVID-19 negative controls. DOI: 10.1016/j.placenta.2020.08.015 

An exploratory COVID-19 outpatient study will seek to confirm a hypothesis, recently reported in Physiological Reviews, that an inexpensive, commonly used drug inhibiting the protease plasmin—tranexamic acid (TXA)—can reduce the infectivity and virulence of the virus as measured by reduced need for hospitalization within a week. The researchers noted that comorbidities (e.g., hypertension, diabetes, coronary heart disease, cerebrovascular illness, chronic obstructive pulmonary disease and kidney dysfunction) all feature elevated levels of the extracellular protease plasmin that may cleave to the furin sites (amino acid sequences) in the SARS-CoV-2 spike protein to increase the severity of illness. The double-blind study now underway is giving either TXA or a placebo pill to COVID-19 outpatients recently diagnosed with COVID-19. Patients also receive an anticoagulant. The overall goal is to assess both safety and efficacy of five days of TXA versus placebo in the COVID-19 population. Researchers are affiliated with the University of Texas Health Science Centre (Tyler), University of Alabama at Birmingham and University of California, San Francisco. DOI: 10.1152/physrev.00013.2020 

For vulnerable families, the pandemic's effect on mental health has been swift and harsh, according to research from the Center for Child and Family Policy at Duke University and Barnard College that published in Pediatrics. The study leveraged real-time, daily survey data collected between Feb. 20 and April 27 to examine how the crisis affected parents' and children's mental well-being. The 645 survey respondents were parents of young children working in hourly service-industry positions in retail, food service or hotel industries in a large U.S. city. Nearly half (49.5%) of the participants were Black Americans, 23% were Hispanic Americans, and 83% were women. Parents saw quick deterioration in their own mental well-being, reporting more frequent "negative moods" since March 14, the day after the first major restrictions in response to COVID-19 were announced. The majority of respondents experienced multiple hardships, including household job loss (60%), income decline (69%), caregiving burden (45%) and illness (12%). The authors suggest pediatricians screen for mental health problems among children in their practices, with particular attention to children whose families are especially vulnerable to both the economic and health aspects of the crisis. DOI: 10.1542/peds.2020-007294 

A multicentric retrospective cohort study in Paris that published in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences describes the characteristics and outcomes of 821 hospitalized older patients (ages 70 and up) with confirmed COVID-19. The mean age of patients was 86 years; 58% were female, 85% had two or more comorbidities, 29% lived in an institution, and the median (interquartile range) Activities of Daily Living (ADL) core was 4. The most common symptoms at COVID-19 onset were asthenia (63%), fever (55%), dyspnea (45%), dry cough (45%) and delirium (25%). The in-hospital mortality was 31%. At COVID-19 onset, the probability of in-hospital mortality was increased with male gender, ADL score, asthenia, quick Sequential Organ Failure Assessment score of 2 or higher and specific COVID-19 anomalies on chest computerized tomography. DOI: 10.1093/gerona/glaa210 

Another study taking a similar look at 16,942 older adults with COVID-19 in Turkey, published in the same journal, found 51% were women, with a mean age of 71.2 years, and that their mortality rate before and after curfew was statistically different (32.2% vs. 17.9%). Through multivariate analysis of the causes of death in older patients, researchers found that male gender, diabetes mellitus, heart failure, chronic kidney disease, dementia, cancer, admission to intensive care unit, and computed tomography finding compatible with COVID-19 were all significantly associated with mortality in entire cohort. Additionally, in patients aged between 60-79 years, coronary artery disease, oxygen support need, total number of drugs, and cerebrovascular disease during hospitalization were associated with increased risk of mortality, as was acute coronary syndrome during hospitalization in patients 80 years of age and older. DOI: 10.1093/gerona/glaa219 

A global COVID Impact Survey has found minimal changes in depression, anxiety, quality of life, and symptomatology affecting activities of daily living among people with progressive multiple sclerosis (MS). The surprising findings were published in the Journal of Neurology by members of the CogEx Research Team, comprised of site investigators from Canada, the U.S., Italy, the U.K., Denmark, and Belgium. The survey was administered between May and July 2020 during lockdown and the suspension of a randomized clinical trial involving 131 participants at 11 sites in the six countries. COVID infection was reported by 4% of participants. Knowing their increased risk, people with progressive MS may have been early adopters of safety precautions that helped them counter negative emotional reactions, the authors speculated.  They’re also accustomed to living with medical uncertainly and social isolation, two major factors that fueled high levels of psychological discomfort in the general population. DOI: 10.1007/s00415-020-10160-7 

The infection fatality rate (IFR) is two and a half times greater for COVID-19 than flu for patients over 60 and, regardless of age, the IFR is three times higher in non-whites, finds a brief research report appearing in the Annals of Internal Medicine. To calculate the true IFR among the community-dwelling population, researchers from Indiana University Richard M Fairbanks School of Public Health and the School of Medicine combined prevalence estimates from a statewide random sample with Indiana vital statistics data of confirmed COVID-19 deaths for all state residents aged 12 and older. They excluded deceased individuals, incarcerated persons, and nursing home residents from the random sample. Participants were tested between April 25 and April 29, 2020 for active viral infection and SARS-CoV-2 antibodies, which would indicate prior infection, and demographic information was collected. DOI: /10.7326/M20-5352 

Industry Updates 

FSD Pharma Inc. has announced that it has submitted an Investigational New Drug application with the FDA for the use of FSD201 (ultramicronized palmitoylethanolamide, or ultramicronized PEA) to treat COVID-19. The company is focused on developing FSD201 for its anti-inflammatory properties to avoid the cytokine storm associated with acute lung injury in hospitalized COVID-19 patients. The trial will be a randomized, controlled, double-blind, multicenter study, conducted at 25-30 sites in North America to assess the efficacy and safety of FSD201 dosed at 600mg or 1200mg twice-daily, together with standard of care (SOC) compared to SOC alone in hospitalized patients with documented COVID-19 disease. Press release. 

U.K.-based AstraZeneca is leading a multi-site, phase 3 clinical trial evaluating an investigational COVID-19 vaccine known as AZD1222. The newly launched trial will enroll approximately 30,000 adult volunteers at 80 sites in the U.S. to evaluate if the candidate vaccine can prevent symptomatic COVID-19. Funding support is being provided by the National Institute of Allergy and Infectious Diseases and the Biomedical Advanced Research and Development Authority. The public-private partnership Accelerating COVID-19 Therapeutic Interventions and Vaccines guided the development of the trial protocol to ensure a coordinated approach across multiple vaccine efficacy trials. Oxford University’s Jenner Institute and Oxford Vaccine Group developed AZD1222, which uses a non-replicating chimpanzee adenovirus to deliver a SARS-CoV-2 spike protein to induce an immune response. Press release. 

Data presented by a University of Lille (France) researcher at the recent European and International Congress on Obesity show a clear relationship between obesity and the severity of COVID-19 disease. The session presented data from the earlier part of the epidemic that quickly revealed patients with obesity were facing more serious disease and a higher mortality risk than patients without obesity. It also discussed how areas of France with higher prevalence of obesity appeared to take longer to release their lockdown restrictions (because the virus was still circulating more in those areas), by showing a map comparing the two situations. Perhaps most strikingly, the data show the chances of increasing to more severe disease increases with BMI to the point where almost all intensive care COVID-19 patients with severe obesity will end up on a ventilator. The session included discussion about an ongoing multicenter trial including more than 1,500 patients taking place at two centers in the U.S. 18 in Europe, and one in Israel, to gather more data on the how increasing BMI and having obesity relates to the increased risk of mechanical ventilation. Press release. 

Experts at the University of Cincinnati (UC) are investigating how treatments for patients with cancer and COVID-19 could cause other health complications. Their year-long study will attempt to understand how treatments for cancer, specifically hormonal therapy and certain immunotherapies, could impact artery and vein blood clots in patients who have also been diagnosed with COVID-19. The research is being supported by a $25,000 grant from the North American Thrombosis Forum and will use a database called COVID-19 and Cancer Consortium, the largest registry-based dataset to date recording outcomes of patients with the two diseases. In May, UC joined cancer centers like Vanderbilt-Ingram Cancer Center, Moffitt Cancer Center, Mayo Clinic Cancer Center as well as national organizations like the American Society of Clinical Oncology to participate in this database. Press release. 

Aegis Life has announced that a phase 1 clinical trial of its first SARS-CoV-2 DNA vaccine is planned for this fall. The company was founded with a goal of developing a novel DNA vaccine using the Entos Pharmaceuticals breakthrough Fusogenix gene delivery technology that has previously been leveraged for other diseases such as cancer. The technology enables Aegis Life’s investigational DNA vaccine to target and deliver simultaneously the spike and nucleocapsid proteins intracellularly to maximize the potential of inducing a potent, durable and balanced T cell response against COVID-19, in addition to having a strong neutralizing antibody response. Since DNA is inherently more stable than RNA, the vaccine has simpler requirements for shipping and storage. Press release. 

The National Institutes of Health has launched a study to track the prevalence and impact of SARS-CoV-2 infection among approximately 16,000 pregnant women in seven low- and middle-income countries. The study will follow women through pregnancy and 12 months after childbirth to compare maternal, fetal and newborn outcomes of participants who have been infected with the virus to those of pregnant women who have not been infected. At delivery, women enrolled in the study will receive an antibody test to determine if they have been exposed to SARS-CoV-2. Researchers hope to determine if infection increases the risk of complications such as preterm birth, fetal growth restriction, stillbirth, newborn death and birth defects. The study is being conducted by the NIH-funded Global Network for Women’s and Children’s Health Research. Participating countries are Guatemala, Bangladesh, India, Pakistan, Kenya, Democratic Republic of Congo and Zambia. Press release. 

Heart patients hospitalized with COVID-19 can safely continue taking angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), according to trial results presented in a Hot Line session at European Society of Cardiology Congress 2020. There is conflicting observational evidence about the potential clinical impact of ACE inhibitors and ARBs (commonly taken by heart patients to reduce blood pressure and treat heart failure) on patients with COVID-19. The phase 4 randomized BRACE CORONA study found that in patients hospitalized with COVID-19, suspending ACE inhibitors and ARBs for 30 days did not impact the number of days alive and out of hospital. Since there is no clinical benefit from routinely interrupting these medications in patients with mild to moderate COVID-19, they should generally be continued for those with an indication, they conclude. The trial enrolled 659 patients from 29 sites in Brazil. Press release. 

Atlanta-based Florence Healthcare has announced a collaboration with Pfizer to support a global phase 2/3 COVID-19 vaccine study. Florence is the largest site and sponsor connectivity platform in the industry, in use by more than 7,200 research sites and 18,000 research professionals across 27 countries. This extensive network of connectivity supports the COVID-19 trial by ensuring research can continue and thrive in a digital capacity, as on-site visits and collaboration are restricted due to the pandemic. With support from Florence’s Remote Site Monitoring Module, coupled with the use of eBinders, Pfizer was able to accelerate remote site access as it commenced a global safety and efficacy clinical trial of an mRNA-based vaccine candidate against SARS-CoV-2 in July 2020. Press release.  

Vanderbilt University Medical Center (VUMC) is launching a clinical trial of promising treatments for COVID-19 in the outpatient setting. The trial is part of the national ACTIV-2 protocol to evaluate the safety and efficacy of new potential therapeutics in adult patients who have COVID-19 illness but are not hospitalized. VUMC is one of 25 trial sites nationwide conducting ACTIV-2, sponsored by the National Institute of Allergy and Infectious Diseases, which includes both phase 2 and phase 3 evaluations of multiple potential therapeutics for COVID-19 in a single trial. The first investigational drug being evaluated is LY3819253, a monoclonal antibody produced by Eli Lilly and Company in partnership with AbCellera Biologics. In the first stage, 220 volunteers will be randomly assigned to receive the study drug or placebo. If the study advances to phase 3, another 1,780 volunteers will be enrolled to test whether the drug can prevent hospitalization and death in non-hospitalized adults with COVID-19. Press release. 

In the U.K., a new study has launched to assess the impact of COVID-19 on people with cancer who are at heightened risk of complications. The Clinical Characterization Protocol (CCP) CANCER-UK project will run over 12 months and will examine questions that are important for the care of patients with cancer as well as determine COVID-19 infection and mortality rates in people with different types of cancer and receiving different treatments. With almost 7,000 patients with both confirmed cancer and COVID-19 diagnoses already enrolled, it will be one of the largest and most detailed studies in the world. The study is a companion to the highly successful U.K. arm of the International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterization Consortium that has collected data from 79,000 patients in the U.K. with COVID-19, around 9% of whom also have cancer. CCP CANCER-UK is being led by researchers at the University of Liverpool. Press release. 

In a Viewpoint that published in JAMA Oncology, researchers from Princess Margaret Cancer Centre (Ontario, Canada) make the case for applying lessons learned from the pandemic to make clinical research leaner and more efficient. Specifically, they call for the scientific community to share its collective wisdom and nonclinical and clinical protocols, methods, and results; greater use of adaptive trial designs; applying emerging technologies such as ultrasensitive liquid biopsies to research challenging value-unproven practices; abandoning bureaucratic practices once thought to be compulsory; and embracing opportunities for decentralization. DOI: 10.1001/jamaoncol.2020.4240