June 12, 2020 | The clinical research community has made progress in the fight against COVID-19. While some organizations and universities has devoted resources to developing a vaccine, others have focused on helping our most vulnerable communities. This week’s news include reports indicating long-term care facilities are a major driver of total COVID-19 deaths, as well as the accelerated initiation of the Phase 1/2a first-in-human clinical trial of an investigational vaccine.

Literature Updates

Long-term care facilities (LTCFs) are a major driver of total COVID-19 deaths—up to 81% in some states (Minnesota and Rhode Island) and 82% in Canada—researchers from Boston Medical Center and Boston University School of Medicine report in the Journal of the American Geriatrics Society. Findings were based on case and death data reported by the Massachusetts Department of Health's COVID-19 daily Dashboard along with data provided by the Kaiser Family Foundation and other countries. Hong Kong, South Korea, Singapore and New Zealand are notably bucking the trend. Despite the lopsided figures, 11 states continue to not report the number of COVID-19 deaths occurring in LTCFs, which has contributed to a vast underestimation of the total number of COVID-19 deaths in the U.S. Other causes of under-reporting nursing home COVID-19 deaths include incomplete data collection by states and the fact that many states and the Centers for Disease Control did not accept a diagnosis of COVID-19 without substantiation by a positive test through mid-April. Officials are now going back to see if many deaths can be categorized as probable COVID-19 based on medical presentation and history of exposure. DOI: 10.1111/jgs.16669

Preliminary observations suggest a high incidence of COVID-19 in stroke patients, including younger patients who were otherwise healthy, according to a 14-patient study published in Neurosurgery. Researchers at Thomas Jefferson University and NYU Langone Medical Center in New York noted seeing patients in their 30s, 40s and 50s with massive strokes typically seen in patients in their 70s and 80s. Mortality rate for these COVID-19 stroke patients was 42.8% vs. the typical 5% to 10% for stroke. The incidence of coronavirus in this small patient sample was 31.5% and had an unusual presentation, including stroke in large vessels, in both hemispheres of the brain, and in both arteries and veins of the brain. The authors speculate that the virus may be interfering with the ACE2 receptor’s normal function, which controls blood flow in the brain, in addition to using it as an entry point to the cell. DOI: 10.1093/neuros/nyaa254

The mortality rate of mechanically ventilated COVID-19 patients is lower (about 35.7%) than previously reported (50%), reveals a study by researchers at Emory University published in Critical Care Medicine. About 60% of patients observed in the study survived to hospital discharge. The study observed 217 patients 18 years and older from six COVID-19-designated intensive care units in three Emory-affiliated hospitals in Atlanta, Georgia from March to April 2020. The authors note that the patients were admitted to pre-existing ICUs with adequate staffing ratios and equipment, which may have influenced results. DOI: 10.1097/CCM.0000000000004457

University of Melbourne (Australia) researchers have found that the newly discovered natural and “resistance resistant” antibiotic teixobactin could be effective in treating bacterial lung conditions commonly associated with COVID-19. Teixobactin was discovered in 2015 by a team at Northeastern University, spawning a company that is now developing it as a human therapeutic. The new research, which published in mSystems, is the first to explain how teixobactin works in relation to the superbug Staphylococcus aureus (MRSA). They also showed it could significantly suppress mechanisms involved in resistance to vancomycin-based antibiotics that are recommended for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and MRSA-caused meningitis. DOI: 10.1128/mSystems.00077-20

In the New England Journal of Medicine, a multi-institutional team of researchers published results from the first randomized clinical trial testing hydroxychloroquine for the post-exposure prevention of COVID-19 and found it offered no benefit over placebo. Further, 40% of trial participants taking hydroxychloroquine developed non-serious side effects—predominantly nausea, upset stomach or diarrhea. The trial enrolled 821 non-hospitalized adults from across the U.S. and Canada who were exposed to COVID-19 from someone living in the same household or as a healthcare worker or first responder. Overall, approximately 12% of those given hydroxychloroquine developed COVID-19 versus approximately 14% given the vitamin placebo (folate). DOI: 10.1056/NEJMoa2016638

More than half (56%) of pregnant women recently admitted to a U.K. hospital with COVID-19 infection were from black or other ethnic minority groups, finds a national surveillance study published by The BMJ. Most women had good outcomes, and transmission of the virus to infants was uncommon, but the discrepancy is concerning. Evidence from other similar viral illnesses suggests that pregnant women and their babies are at greater risk of severe illness and death. The study looked at 427 pregnant women admitted to the hospital with COVID-19, most in the late second or third trimester; 25% were Asian, 22% were black, 70% were overweight or obese, 40% were aged 35 or over, a third had pre-existing conditions, 10% needed respiratory support in a critical care unit, and 1% women died (three as a direct result of complications of COVID-19 and two from other causes). Five percent of babies born to study mothers tested positive for COVID-19, six of them within the first 12 hours after birth. DOI: 10.1136/bmj.m2107

Analysis of Seattle emergency medical services (EMS) and hospital data from Jan. 1 to April 15, 2020 indicates bystander CPR is a lifesaving endeavor whose benefits outweigh the risks of COVID-19 infection, according to an article that published in Circulation. Experts have questioned whether chest compressions are a high-risk "aerosolizing" procedure that could increase the risk of SARS CoV-2 infection. Researchers concluded that approximately one rescuer might die in 10,000 bystander CPR events, a calculation based on the 10% incidence rate of COVID-19 among all those experiencing out-of-hospital cardiac arrests and an assumed 1% mortality for COVID-19. By comparison, bystander CPR saves more than 300 additional lives among 10,000 patients with out-of-hospital cardiac arrest. DOI: 10.1161/CIRCULATIONAHA.120.048951

Early data from a small clinical study suggests that off-label use of the blood cancer drug acalabrutinib, which blocks the Bruton tyrosine kinase (BTK) protein, was associated with reduced respiratory distress and a reduction in the overactive immune response in most of the 19 patients with severe COVID-19. The BTK protein plays an important role in the normal immune system, including in macrophages that can cause inflammation by producing cytokines (the proteins implicated in the dangerous hyperinflammatory state in some patients with severe COVID-19). Among the 19 patients, 11 had been receiving supplemental oxygen for a median of two days and eight others had been on ventilators for a median of 1.5 days. Within one to three days after they began receiving acalabrutinib, most patients in the supplemental oxygen group experienced a substantial drop in inflammation, and their breathing improved. Eight of these 11 patients were able to come off supplemental oxygen and were discharged from the hospital. Although the benefit of acalabrutinib was less dramatic in patients on ventilators, half were able to come off the machine and two of the four were eventually discharged. An additional finding was that the blood of patients with severe COVID-19 had higher activity of the BTK protein and greater production of IL-6 (a major cytokine associated with hyperinflammation) compared to that of a group of healthy volunteers. Results published in Science Immunology. DOI: 10.1126/sciimmunol.abd0110

Writing in the Annals of Internal Medicine, physicians from the Johns Hopkins University School of Medicine frame a discussion of racial health disparities through a resilience approach rather than a deficit approach and offer a blueprint for approaching the COVID-19 crisis through the lens of health equity. It comes in response to the disproportionate toll the COVID-19 pandemic is exacting on ethnic minority communities, magnifying existing disparities in healthcare access and treatment. The authors looked to history for insights, especially the 1918 influenza pandemic, to help understand the current crisis. DOI: 10.7326/M20-2223

Outdated practices may lead to psychological trauma for patients who suffer from a feeling of severe breathlessness due to ventilation strategies that protect the lungs but may cause other problems, according to a paper published in the Annals of the American Thoracic Society. Low tidal volume mechanical ventilation is an evidence-based practice but, among ICU survivors, the experience of “air hunger” is often associated with post-traumatic stress disorder. The problem is solvable, the authors say, by awareness followed by steps to ameliorate air hunger. Physicians may mistakenly believe that paralysis reduces breathlessness and treat patients with neuromuscular blocking drugs, but that can make the situation worse by preventing patients from communicating or demonstrating their discomfort. While patients are often sedated as well, most sedatives that have been studied do not relieve shortness of breath. DOI: 10.1513/AnnalsATS.202004-322VP

Researchers from Duke University and the University of North Carolina offer pediatric-specific dosing suggestions for hydroxychloroquine and remdesivir—while also raising concerns regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect. The physiologically based pharmacokinetic model analysis included 500 and 600 simulated white adult and pediatric participants, respectively, for hydroxychloroquine, where the primary outcome was average unbound plasma concentrations for five treatment days. The figures were 1,000 and 6,000 simulated participants for remdesivir, where the main outcome was plasma exposure following single-dose administration. The study published in JAMA Pediatrics. DOI: 10.1001/jamapediatrics.2020.2422

A study of electronic medical records from U.S. Veterans Health Administration medical centers in Med offers more evidence of no survival benefit in COVID-19 patients receiving hydroxychloroquine. The analysis was conducted by researchers from the Columbia VA Health Care System, the University of South Carolina and the University of Virginia School of Medicine, and looked at data from 807 patients, of whom 198 were treated with hydroxychloroquine and 214 with both hydroxychloroquine and azithromycin. About 86% of patients given hydroxychloroquine received it before being put on a mechanical ventilator. After adjusting for clinical characteristics, the risk of death from any cause was higher in the hydroxychloroquine group but not in the hydroxychloroquine + azithromycin group versus the no-hydroxychloroquine group. The researchers also found that the length of hospital stay was 33% longer in the hydroxychloroquine group and 38% longer in the hydroxychloroquine + azithromycin group than in the no-hydroxychloroquine group. DOI: 10.1016/j.medj.2020.06.001

In JAMA Internal Medicine, Columbia University researchers describe their emergency-department-based COVID-19 palliative care response team focused on providing high-quality goals of care conversations in time-critical situations. The 110 patients receiving this intervention ranged in age from 46 to 101, were 55.4% women and most were community-dwelling elderly persons with at least two comorbidities who lacked decision-making capacity at the time of presentation. Very few patients presented with documented advance directives or Medical Orders for Life-Sustaining Treatment and were therefore presumed to be full code (aka pursue all life-sustaining treatment). After initial palliative care intervention, the number of full code cases decreased from 91 to 20 patients. Among this group of 71 patients, 64.5% declined CPR and 55.5% turned down mechanical ventilation. On discharge, the number of full code patients further decreased to 9 patients, whereas comfort-directed care increased to 54 patients. The median length of stay was four days and 71 patients (68.2%) died in the hospital and six were discharged to hospice care. DOI: 10.1001/jamainternmed.2020.2713

Hospitalized COVID-19 patients at a New York City medical facility had higher rates of kidney complications than other COVID-19 patient groups in different areas of the U.S. and other countries, according to a study from researchers at Columbia University Irving Medical Center and New York-Presbyterian that published in the British Medical Journal. The study, using data from electronic health records, also found the need for mechanical ventilation was greatest at two different points after symptom onset. The study offers a detailed look at the clinical course of the first 1,000 COVID-19 patients treated at New York-Presbyterian/Columbia University Irving Medical Center between March 1 and April 5, 2020. Patients in the study had higher rates of underlying chronic conditions than reported in other patient populations, most commonly hypertension (60%) and diabetes (37%). More than half of patients hospitalized for COVID-19 were male, and the median age was 63. Nearly 34% of the patients developed acute kidney injury (AKI), versus 15% of patients in a recent report from China and 19% of patients in a report from Washington State. Almost 80% of patients in the ICU developed AKI. More than 95% of patients who were intubated required mechanical ventilation within the first 14 days, at either three to four days or nine days after symptom onset; intubation is much less likely to be needed after 15 days. Among patients admitted to the ICU, the median hospital stay was 23 days, compared with eight days for critically ill patients in the Chinese study; the overall mortality for those in the ICU was 43.6%. versus an overall mortality rate of around 21%. DOI: 10.1136/bmj.m1996

Researchers in France has a study published in Clinical Kidney Journal reporting on two COVID-19 patients with injury to the renal corpuscles (glomeruli) or filter membrane (podocytes), and to the renal tubules (tubular cells), as has been seen in examinations of renal tissue from deceased patients. Both patients were over 50 and known to have high blood pressure; one had cardiac insufficiency, the other hepatitis B. Both had been complaining of coughing for four days and one also had a fever. On admission, they had pulmonary CT findings typical of COVID-19 and differently elevated creatinine levels indicating AKI. Within a few days, one patient required ventilation and the other only needed oxygen; dialysis was not required in either case. Both recovered their pulmonary function within one to two weeks. Kidney function also improved, but they both had persistent, high proteinuria. Kidney biopsies were therefore performed, revealing injury to the renal structures. Although both patients had positive virus detection from the throat swab, SARS-CoV-2 was not detected in blood, urine or in kidney tissue, despite highly sensitive RT-PCR testing. Molecular genetic analysis showed variants in the APOL1 gene known to be associated with a predisposition for kidney disease. Researchers say it is probable kidney injury was caused by a SARS-CoV-2-induced inflammatory reaction. DOI: /10.1093/ckj/sfaa088

Another study coming out of France, and published in Clinical Kidney Journal, found that acute renal Fanconi syndrome (at least two tubular abnormalities) in 75% of hospitalized COVID-19 patients. Data from 42 hospitalized COVID-19 patients with no previous kidney disease were analyzed retrospectively. Additional findings were that proteinuria (88%), phosphate loss in urine (55%), increased uric acid excretion (43%) and glycosuria (30%) were the most frequently presented features. ICU patients were more frequently affected (96% vs. 62%) and were also more severely affected by proteinuria and AKI. A noteworthy finding was that Fanconi syndrome preceded severe AKI in 88% of the patients. Five of the AKI patients required dialysis; two died (after 13 and 27 days); one patient was dialysis-free after one week and two patients were still on dialysis at the end of the follow-up. A total of 7/42 patients died (including six intensive care patients with AKI), 24/42 could be discharged (including 12 intensive care patients) and 11/42 patients were treated as in-patients for a further 34 (±4.3) days. Proximal renal tubules seem to be a specific target of SARS-CoV-2 and the significance of Fanconi syndrome as a biomarker of tubular cell infection and as a potential predictive prognostic marker deserves systematic investigation. An increased risk of subsequent kidney disease after SARS-CoV-2-associated Fanconi syndrome can also be assumed, researchers say. DOI: 10.1093/ckj/sfaa109

In a third study published in Clinical Kidney Journal, French researchers characterized COVID-19-associated AKI and acute kidney diseasein terms of its incidence, severity, clinical presentation and short-term outcomes. Findings were based on data from 71 patients with severe lung injury admitted to four ICUs at Bordeaux University Hospital in March/April 2020. On admission, basal serum creatinine was 69±21 μmol/l on average and AKI was present in 11% of patients. The median follow-up was 17; AKI developed in 80% of patients (35% Stage 1, 35% Stage 2 and 30% Stage 3) and, of those patients, 18% required dialysis. Two of the patients with AKI died within the first 72 hours. After three days, creatinine had fallen again in four of the remaining patients, indicating transient AKI, and 93% had persistent AKI with increased protein excretion, indicating predominantly tubulo-interstitial injury. Only two patients had elevated glucose excretion. Seven days after AKI development, six patients (11%) were still on dialysis, nine (16%) had serum creatinine >200 μmol/l, and a further four (7%) had died. Renal recovery occurred in 28% after seven days and in 52% after 14 days. The study verified a hypothesis that AKI is significantly higher in Western Europe than in either China (up to 15%) or the U.S. (20%). DOI: 10.1093/ckj/sfaa099

Mount Sinai researchers report in Journal of the American College of Cardiology a serious myocardial injury can triple the risk of death among patients hospitalized with COVID-19. The observational study found that 36% of patients who were hospitalized with the virus had elevated troponin levels indicative of heart injury, consistent with reports from China and Europe. Patients with milder forms of myocardial injury were associated with lower likelihood of hospital discharge and a 75% higher risk of death compared to patients with normal troponin levels. Heart injury seems to be a more important indicator in predicting risk of death than a history of heart disease. Results were based on an analysis of the electronic health records of nearly 3,000 adult patients admitted to five New York City hospitals within the Mount Sinai Health System between Feb. 27 and April 12, 2020. Their median age was 66 and roughly 60% were male. One-quarter of all patients self-identified as African American, and 27% as Hispanic or Latino. Roughly 25% of patients had a history of heart disease and roughly the same number had cardiovascular disease risk factors. DOI: 10.1016/j.jacc.2020.06.007

A study on children suffering from severe inflammatory symptoms shows the condition is new and distinct from Kawasaki disease. In a paper published in the Journal of the American Medical Association, researchers have identified the main symptoms and clinical markers of the new syndrome. The study was led by Imperial College Academic Health Science Centre and involved clinicians and academic partners at eight hospitals across England as well as the Kawasaki Disease Research Center at the University of California San Diego. The condition, which the researchers named Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS), was studied in 58 hospitalized children in England—45 of whom had evidence of current or past COVID-19 infection. PIMS-TS is extremely rare, but it can make a child very ill. It appears to be more likely to affect older children than Kawasaki disease (average nine years old versus four years old, respectively) and presents more often with abdominal pains and diarrhea alongside the common features such as persistent fever. It also appears to affect a higher proportion of black and Asian patients. Blood tests also show different results, with PIMS-TS patients showing more markers of inflammation and cardiac enzymes, which suggest the heart is under strain. DOI: 10.1001/jama.2020.10369

Most of the registered clinical trials of potential treatments for COVID-19 underway as of late March were designed in ways that will greatly limit their value in understanding potential treatments, according to a study from researchers at Johns Hopkins Bloomberg School of Public Health. Findings appeared in BMJ Open and were based on an analysis of 201 clinical trials for drugs or plasma registered in the U.S. (ClinicalTrials.gov) and internationally (World Health Organization) as of March 26. Of these, 49.8% were registered in China and 37.8% in the U.S. Most of the trials registered in the U.S. were from international researchers. Among the 201 trials analyzed, 126 were recruiting participants from China, 31 from Europe and 14 from the U.S. Many lacked control groups and patient and clinician blinding, one-third had no clinical endpoints to clearly define success or failure, nearly a half were designed to enroll fewer than 100 patients, and two-thirds were open label—meaning they’re likely to yield only preliminary evidence. DOI: 10.1136/bmjopen-2020-039978

Patients recovering from COVID-19 could suffer significant long-term effects, according to research into the experiences of people hospitalized by previous coronavirus outbreaks. Researchers at the universities of Leeds, Manchester and Hull in the U.K. collated evidence on the physical, psychological and social impacts among patients who fell victim to severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These previous outbreaks resulted in respiratory and exercise capacity problems in the first six months after hospitalization; mental health problems, including post-traumatic stress disorder, anxiety and depression in up to a third of survivors at six months and beyond; and impaired quality of life for one-third of survivors even 12 months after hospital discharge. The authors carried out a systematic review of 28 international studies into the harmful long-term clinical outcomes for survivors of SARS and MERS coronavirus infections after hospitalization or intensive care unit admission, 23 of which were included in their meta-analysis. Findings published in the Journal of Rehabilitation Medicine. DOI: 10.2340/16501977-2694

Despite immunosuppression, the clinical presentation and laboratory markers of disease severity among heart transplant patients who contracted COVID-19 showed similarities to what has been observed in the general population, report University of Michigan researchers in an article in press with the Journal of Cardiac Failure. However, almost half were critically ill and there was a higher rate of mortality than described among non-heart transplant recipients. Findings were based on the experience of 13 patients, all black males, who had a previous heart transplant and were admitted to one of two hospitals in southeast Michigan in March or April for COVID-19 symptoms. Researchers recommend further research with a focus on racial and gender disparities in COVID-19 and on the identification of prognostic markers, treatments and appropriate immunosuppression management for patients with heart transplant with COVID-19. DOI: 10.1016/j.cardfail.2020.05.008

A study from researchers at Sun Yat-sen University (China) and University of Birmingham (U.K.) and published in The BMJ underlines the importance of adequate personal protective equipment (PPE) and training for frontline health professionals to prevent COVID-19 infection. Researchers found that, when appropriately protected, clinical staff on the front lines did not contract infection or develop protective immunity against the virus. Findings were based on 420 healthcare professionals (116 doctors and 304 nurses) with an average age of 36 years, who were deployed to Wuhan for 6-8 weeks from Jan. 24 to April 7, 2020 to care for patients with COVID-19. Participants worked four- to six-hour shifts for an average of 5.4 days a week, and an average of 16.2 hours each week in intensive care units. DOI: 10.1136/bmj.m2195

If clinical trials are not designed with equity considerations consciously in mind, the response to the COVID-19 pandemic may further exacerbate disparities in health status between population groups, according to a law professor at Seton Hall University. He identified the following key issues: (a) providing study support in low‐ and middle‐income countries without taking needed resources away from other critical clinical and public health needs; (b) designing recruitment strategies likely to generate sufficient enrollment from groups that have been disproportionately burdened by the virus, such as African Americans; (c) supporting studies designed to improve outcomes in high‐risk environments, such as nursing homes and group homes for the developmentally disabled; and (d) ensuring that the medical products resulting from research are made available throughout the world at an affordable price. Findings published in Ethics & Human Research. DOI: 10.1002/eahr.500055

Using electronic health record (EHR) data to simulate randomized, controlled drug trials for pregnant patients could one day offer a solution to the current practice of delivering babies pre-term if an expectant mother contracts COVID-19, according to a position paper published in Nature Medicine. The practice could significantly harm fetuses and recent case reports have shown that COVID-19 transmission occurs in utero if not treated in the mother. A team of drug safety researchers from Vanderbilt, Northwestern, Harvard and the National Institutes of Health propose that high-powered algorithms like machine be used to identify therapeutics that are safe for use in pregnant patients with COVID-19, based on prior cases in which pregnant patients have been exposed to current therapeutic candidates. These “target trials” are the only ethical way to gather human drug exposure data for pregnant people on a significant scale and across all classes of drugs, they argue. DOI: 10.1038/s41591-020-0925-1

Updates from Industry

Janssen Pharmaceutical Companies has accelerated the initiation of the Phase 1/2a first-in-human clinical trial of its investigational SARS-CoV-2 vaccine, Ad26.COV2-S, recombinant. Initially scheduled to begin in September, the trial is now expected to commence in the second half of July. The randomized, double-blind, placebo-controlled Phase 1/2a study will evaluate the safety, reactogenicity (response to vaccination), and immunogenicity (immune response) of the investigational SARS-CoV-2 vaccine, Ad26.COV2-S, recombinant in 1045 healthy adults aged 18 to 55 years, as well as adults aged 65 years and older. The study will take place in the U.S. and Belgium. Press release.

ConvergeHEALTH by Deloitte is waiving all licensing fees for MyPath for Clinical for current COVID-19 related clinical trials, as well as any current clinical trial impacted by COVID-19. MyPath for Clinical is a cloud-based digital platform designed to enhance the patient experience as well as the success and efficiency of global clinical trials. Any biopharmaceutical manufacturer, academic research organization, or other organization with a COVID-19 clinical trial or a clinical trial impacted by COVID-19 can take advantage of the offer. License fees will be waived for organizations that sign up for MyPath for Clinical through August 31, 2020. Fees also will be waived for the duration of the clinical trial in process through its completion. Press release.

The European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) reports that ERACODA, the database it established to investigate COVID-19 outcomes in patients with kidney failure, has information on 1,073 patients as of June 1. Complete follow-up data has been entered by physicians from 98 centers in 26 countries, mainly in Europe. Of patients included in the database, 305 were kidney transplant recipients, 21% of whom had died by 28 days—a case fatality rate only slightly lower than that seen (25%) in dialysis patients. In patients managed outside the hospital, mortality was low at 3% of kidney transplant patients compared to 5% of dialysis patients. Following admission to hospital, 24% of transplant patients died compared to 33% of dialysis patients. Of those treated in the intensive care unit, 45% of kidney transplant patients died compared with 53% of dialysis patients. As in the general population, age over 75 years was the most important risk factor for death in transplant patients (male sex, diabetes and cardiovascular disease were not). Press release.

At the recent Opening Conference of the ERA-EDTA Congress, data gathered from the Hospital Vall d'Hebron in Barcelona, Spain was presented showing an alarmingly high (24%) COVID-19 mortality rate among 21 dialysis patients. The death rate was verified in an analysis of the Spanish COVID-19 Dialysis/Transplantation Registry, which included 1,572 end-stage renal disease patients (523 of them kidney transplant recipients). Across Spain, the mortality rate is more than 27% for hemodialysis patients, over 23% for kidney transplant patients and 15% for peritoneal dialysis patients. The high mortality rate among dialysis patients was also verified in a study (DOI: 10.1016/j.kint.2020.04.031) that monitored the course of disease in 36 hemodialysis patients between March 12 and April 10 in Hospital Gregorio Marañón in Madrid. The death rate here was as high as 30.5%, and three factors beyond older age and pneumonia that were found to be significant influencers were the number of years on dialysis, lymphopenia and elevated LDH levels. Press release.

ERA-EDTA additionally reports that a registry created in Germany to investigate the prevalence and outcome of SARS-CoV-2 infected dialysis patients reports the mortality rate at around 20%. Phase 2 of the registry will also include patients with acute kidney injury (AKI) and chronic kidney disease and will investigate outcomes and prognostic factors. Data also suggest that the kidneys might be a target organ of COVID-19. Based on early data from China on COVID-19 (DOI: 10.1101/2020.02.18.20023242), kidney involvement seems to be frequent in people who have tested positive and developed symptoms. Another study in the U.S. (DOI: 10.1016/j.kint.2020.05.006) shows that the incidence of AKI is significantly increased among hospitalized patients. An autopsy study conducted in Hamburg (DOI: 10.1056/NEJMc2011400) also shows the kidneys are particularly hard hit by the virus. Press release.

The National Science Foundation's Rapid Response Research (RAPID) program has awarded a $200,000 grant to scientists at the Erik Jonsson School of Engineering and Computer Science at The University of Texas at Dallas and Vanderbilt University Medical Center to create an open-source software tool to help policymakers and healthcare providers decide how much information can be disclosed to researchers without violating patient privacy. Much of the data used for research comes in the form of aggregate statistics, which show the number of cases without any identifying information about individual patients. For COVID-19, however, person-level data is critical to understanding how various health factors might affect the virus's spread and impact individuals. The usefulness of information about COVID-19 patients also changes quickly and might differ from day to day. The decision tool being developed could evaluate whether releasing data about patients' locations or medical histories increases the risk of identification. Potentially, certain data could only be shared with researchers with restricted access. Press release.

Another RAPID grant has gone to a multidisciplinary group of researchers at the University of Missouri, who hope to uncover what the 1918 flu pandemic in Missouri can teach people about the current COVID-19 pandemic. Their findings could help inform overall strategies for mitigating the spread of the current virus in the U.S. The project will use Missouri death certificate data between 1918-1920 from people who died from influenza and pneumonia to develop a detailed analysis of the 1918 pandemic—including geographical spread, underlying socioeconomic conditions and any differences between rural and urban areas in the state. The ability to analyze racial and ethnic disparities will be limited due to the amount of information that is available from that time. Press release.

The Government of the Russian Federation gave fast-track approval to levilimab, whose mechanism of action is associated with the control of cytokine storm—an often-deadly manifestation of COVID-19. The drug is developed and produced by biotech company BIOCAD, which reports that results of clinical trials initiated on April 24 demonstrate that levilimab therapy can significantly reduce mortality among patients with COVID-19. Levilimab is the original inhibitor of the interleukin 6 receptor, originally being developed for treatment of rheumatoid arthritis. Article.

Research being overseen by the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is evaluating drugs prescribed to treat COVID-19 in infants, children and adolescents across the country. The study—called Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care—leverages an existing clinical trial that examines drugs that are prescribed off-label to children for a variety of medical conditions. Researchers will investigate several drugs currently given to children diagnosed with COVID-19, including antiviral and anti-inflammatory drugs, and add and remove products from the list as they learn more about the treatment needs of patients. Healthcare providers who are already treating patients with drugs on the list may enroll patients whose parents or guardians have given their consent. The study is being conducted in approximately 40 sites of the NICHD-funded Pediatric Trials Network, many of which are located near diverse communities. Researchers will analyze blood samples collected from routine medical procedures to understand how drugs move through the bodies of children and collect information on potential side effects and patient outcomes. Its intent is to gather information to refine dosing and improve safety, not evaluate which drug is best. Press release.

The African Academy of Sciences has launched the first iteration of the Clinical Trials Community (CTC) online platform with features that will increase visibility of African clinical trial sites and investigators with potential to participate in COVID-19 clinical trials. The idea is to promote and enhance intra-Africa collaboration around trials and reduce duplication of work across the region, accelerating the fight against the virus. It also seeks to strengthen all aspects of clinical trials and translational sciences capacity continent-wide. The launch marked the release of the Minimum Viable Product (MVP), a process for attracting early-adopter users and validating a product idea early in the development cycle. Early release to the public is necessitated by the need to share information on ongoing COVID-19 clinical trials in Africa, profile the researchers leading these studies and provide insight on the regulatory requirements of different countries on the continent to guide expedited review of clinical trial protocols. An additional feature on the MVP platform is a community forum section for the public to discuss the nature of the COVID-19 disease, the role of clinical trials to advance understanding of the safety and efficacy for drugs and treatment and general information on participating in a clinical trial. Currently, only 35 (3%) of COVID-19 clinical trials are in Africa, according to ClinicalTrials.gov, the Pan African Clinical Trials Registry and COVID-19 Trial Tracker. Press release.

The Data Co-creation Working Group at the University of Tokyo has joined the COVID-19 Data Exchange pro bono initiative launched by Dawex to provide researchers and organizations with a free and globally connected information system to share and exchange data. The platform, which recently went live, allows those with information to share it securely and to specify who can access that data and under which terms and conditions. Shared information can also be tracked so users can always trace its sources. Press release.