September 25, 2020 | Both Johns Hopkins and Mount Sinai release patient prediction models, Mass General publishes new blood test for patient stratification, two VA studies look at COVID-19 in vet populations, study shows widespread kidney damage with 30% of patients needing dialysis, and FDA issues a guidance for assessing COVID-19 symptoms in clinical trials. Plus, NIAID launches fourth clinical trial for a SARS-CoV-2 vaccine, NIH expands trials of convalescent plasma, and screening program launches for sub-Saharan Africa.

Research Updates

In a national Veterans Affairs study of 88,747 veterans tested for SARS-CoV-2, hospitalization, mechanical ventilation, and mortality were significantly higher in patients with positive SARS-CoV-2 test results than among those with negative test results. Significant risk factors for mortality included older age, high regional coronavirus disease 2019 burden, higher Charlson Comorbidity Index score, fever, dyspnea, and abnormal results in many routine laboratory tests; however, obesity, Black race, Hispanic ethnicity, chronic obstructive pulmonary disease, hypertension, and smoking were not associated with mortality. The study is published in JAMA Network Open. DOI: 10.1001/jamanetworkopen.2020.22310

A separate study published in PLOS Medicine of around 5.8 million people who receive care from the United States Department of Veterans Affairs (VA) found that Black and Hispanic people were substantially more likely than their White counterparts to test positive for COVID-19, although no differences in 30-day mortality were observed between these groups. 91% of the participants were male. DOI: 10.1371/journal.pmed.1003379

In a cohort study of 1641 adult patients with SARS-CoV-2 infection who were hospitalized, researchers at Massachusetts General Hospital found that elevated red blood cell distribution width (RDW) at admission and increasing RDW during hospitalization were associated with statistically significant increases in mortality risk. Published in JAMA Network Open, the findings suggest that an elevated RDW measured at admission and increasing RDW during hospitalization were associated with significantly higher mortality risk for patients with SARS-CoV-2 infection; RDW may be helpful for patient risk stratification. DOI: 10.1001/jamanetworkopen.2020.22058

Patients with COVID-19 experience elevated levels of soluble urokinase receptor (suPAR), an immune-derived pathogenic protein that is strongly predictive of kidney injury, says University of Michigan researchers in the Journal of the American Society of Nephrology. Their study results show that more than a third patients with COVID-19 end up in need of dialysis and are also at much higher risk of death. DOI: 10.1681/ASN.2020060829

Using a combination of demographic and clinical data gathered from seven weeks of COVID-19 patient care early in the coronavirus pandemic, Johns Hopkins researchers have published a "prediction model" they say can help other hospitals care for COVID-19 patients—and make important decisions about planning and resource allocations. The model is based on 827 COVID-19 patients admitted to five Johns Hopkins hospitals over 52 days. The model forecasts how likely a patient's disease is to worsen while being treated in a hospital and at what point in their care that might happen. Among the risk factors researchers considered as part of the model were a patient's age, body mass index (BMI), lung health and chronic disease, as well as vital signs and the severity of a patient's COVID-19 symptoms at the time of admission. The model is published in the Annals of Internal Medicine. DOI: 10.7326/M20-3905

Mount Sinai has also published a predictive model of patient prognosis based on patients treated at the Mount Sinai Health System in New York. Their model is based on three routinely collected clinical features, namely patient's age, minimum oxygen saturation over the course of their medical encounter, and type of patient encounter (inpatient vs outpatient and telehealth visits). The model yields an additional "vital sign" that is assessed regularly during a patient's hospital course, that can be integrated into the clinical care flow of a COVID-19 patient. Clinical teams could use results from the prediction model throughout COVID-19 patients' hospital courses to flag individuals at high risk of death so that they can promptly focus treatment and attention on such individuals to prevent their mortality. The model is published in The Lancet Digital Health. DOI: 10.1016/S2589-7500(20)30217-X

FDA issued guidance for assessing COVID-19-related symptoms in outpatient adult and adolescent subjects in clinical trials of drugs and biological products for COVID-19 prevention or treatment. FDA recommends that sponsors use patient-reported outcome (PRO) instruments to assess COVID-19-related symptoms at least every 24 hours and conduct assessments at the same time each day, reminding patients to complete the PROs; include a set of common COVID-19-related symptoms for all participants regardless of which symptoms were present at baseline; and evaluate the PRO instrument’s basic comprehensibility and usability before the trial begins to mitigate risk of poor instrument performance. PDF of the guidance.

A new study published in the open-access journal PLOS Medicine by researchers at the University of Bern, Switzerland suggests that true asymptomatic cases of SARS-CoV-2 comprise a minority of infections. The team searched a database of SARS-CoV-2 literature from PubMed, Embase, bioRxiv, and medRxiv. They included 94 studies and found that the overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 20%. Limitations of the review include that most included studies were not designed to estimate the proportion of asymptomatic SARS-CoV-2 infections and were at risk of selection biases. DOI: 10.1371/journal.pmed.1003346

Researchers from Montefiore Medical Center, Hospital of the University of Pennsylvania, Massachusetts General Hospital, Harvard Medical School, and Brigham and Women's Hospital studied scientific articles published between January and September 2020, as well as relevant articles and institutional or governmental reports, to determine the viral, host, and environmental factors that contribute to transmission of COVID-19. They found that although several experimental studies suggest that virus particles could live for hours after inoculation in aerosols or on surfaces, the real-world studies that detect viral RNA in the environment report very low levels on surfaces, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or transmission from materials or surfaces was presumed, respiratory transmission could still not be ruled out. DOI: 10.7326/M20-5008

The Korea Advanced Institute of Science and Technology (KAIST) researchers have identified biomarkers that could help pinpoint patients who are bound to get a severe reaction to COVID-19 infection. They published their findings in Frontiers in Immunology. The team re-analyzed published scRNA-seq data of COVID-19 patient bronchoalveolar lavage fluid to further classify and compare immunological features according to the patient’s disease severity. Patients with severe symptoms showed DNA damage and apoptotic features of epithelial cells, which the researchers posit is associated with neutrophil infiltration. Neutrophils were abundant in lungs of patients from the severe group. DOI: 10.3389/fimmu.2020.02145

In a perspective published in mSphere, an open-access journal of the American Society for Microbiology, a group of microbiologists in Portugal call for scientists to more closely examine the ways in which COVID-19—and our social distancing responses—interact with microbial health. The disruption in microbial sharing, as it is associated with dysbiosis (loss of bacterial diversity associated with an imbalance of the microbiota with deleterious consequences for the host), may worsen the prognosis of COVID-19 disease, they write. In addition, social detachment can also decrease the rate of transmission of antibiotic-resistant bacteria. A more thorough analysis of that relationship, they argue, is needed to prepare for long-term health consequences and to develop comprehensive control strategies. DOI: 10.1128/mSphere.00716-20

Industry Updates

A fourth Phase 3 clinical trial evaluating an investigational vaccine for coronavirus disease 2019 (COVID-19) has begun enrolling adult volunteers. The trial is designed to evaluate if the investigational Janssen COVID-19 vaccine (JNJ-78436725) can prevent symptomatic COVID-19 after a single dose regimen. Up to 60,000 volunteers will be enrolled in the trial at up to nearly 215 clinical research sites in the United States and internationally. Preclinical findings published in Nature show that the investigational Janssen COVID-19 vaccine induced neutralizing antibody responses in rhesus macaques and provided complete or near-complete protection against virus infection in the lungs and nose following SARS-CoV-2 challenge. The safety, reactogenicity and immunogenicity of the investigational vaccine are being evaluated in a Phase 1/2a trial in the United States and Belgium enrolling adult volunteers. Positive interim results from the Phase 1/2a clinical study demonstrated that the safety profile and immunogenicity after a single vaccination were supportive of further development. Press release.

NIH is expanding clinical trials of convalescent plasma. One trial, called Convalescent Plasma to Limit COVID-19 Complications in Hospitalized Patients, was launched in April by NYU Langone Health in New York, with collaboration from the Albert Einstein College of Medicine and Yale University, New Haven, Connecticut, and with funding from NCATS. To increase enrollment in the trial, NYU is partnering with The University of Texas Health Science Center at Houston and the University of Miami in Florida to enroll participants at sites in these states. With these additional sites, this trial expects to enroll approximately 1,000 hospitalized patients 18 years or older with respiratory symptoms of COVID-19. The trial called Passive Immunity Trial of Our Nation for COVID-19 also is expanding to enroll about 1,000 participants. Vanderbilt University Medical Center in Nashville, Tennessee, which launched the trial in April, will have access to about 50 additional clinical trial sites across the CTSA Program. Press release.

The Boehringer Ingelheim and Eli Lilly and Company Alliance have joined the American College of Cardiology's ongoing COVID-19 response initiative to continue providing real-time clinical guidance on COVID-19. The comprehensive initiative includes a robust set of activities and events implemented by ACC to help cardiologists address critical patient needs and continue to deliver high-quality care. Press release.

Cytel has significantly widened the geographical scope of the TOGETHER trial, a unique study to identify early COVID-19 interventions in underserved low- and middle-income country (LMIC) populations. The trial, supported with seed funding from the Bill & Melinda Gates Foundation, is one of the very few studies investigating therapies at the earliest stages of COVID-19 infection, and is the only trial to explore early interventions in the Global South. The expansion consists of two new sites in South Africa to complement the study sites actively recruiting in Brazil and the United States. By leveraging its expertise in such complex trial designs, Cytel’s Global Health team is making a lasting contribution to local trial infrastructure to support future clinical investigation in these vulnerable populations. Press release.

IFC, a member of the World Bank Group, has announced a partnership with South African-listed Imperial to jointly develop a modular screening and treatment healthcare infrastructure program in sub-Saharan Africa to respond to the COVID-19 pandemic. Supported by IFC, Imperial is developing a pilot project in South Africa to manufacture and deploy modular healthcare units that will provide screening, treatment and other healthcare services to COVID-19 patients. The program’s aim is to expand services in densely populated, low-income urban areas where access to healthcare is limited. Imperial will further partner with IFC to develop additional pilots in other countries in the region, including Nigeria, Kenya and Ghana. The first pilot of the program, which launched in South Africa in September 2020, includes five modular screening and treatment centers for COVID-19 patients. These modular testing units can be deployed in less than a day and have the potential to boost healthcare options and help reduce infection risk among people and their communities. Additionally, the modular treatment facilities created under the program will contribute to primary healthcare infrastructure options beyond the COVID-19 pandemic, particularly for underserved communities. Press release.

An international group of researchers are investigating how and why the strategies implemented by countries to deal with the current pandemic succeeded or failed. The study is supported by FAPESP and coordinated by researchers at Getúlio Vargas Foundation (FGV) in São Paulo, Brazil, and the University of Michigan in the United States. A book is planned with comparative analyses of countries and regions. The project also calls for primary data collection during the pandemic, and for the creation of a repository as a basis for future studies, with news stories and data on political leaders, government communication, and public policies. Press release.

A new research consortium, Reliable Response Data Discovery (R2D2), invites clinicians, researchers, patients and the general public to submit questions that could be answered by COVID-19 patient record data from more than 200 participating hospitals. Questions are submitted and answers are provided via a new web portal: COVID19questions.org. Unlike other patient databases and registries, the R2D2 COVID-19 Questions site allows health systems to maintain control of their own data rather than pool it in a central repository. No patient-level data are ever transmitted outside of each health system, only data aggregates, and the privacy of individuals and institutions is preserved. Through advanced computational methods, complex analyses involving multiple factors can be performed. Since the system queries all patient records, not just those with COVID-19, users can ask questions about how patients with COVID-19 compare to other patients. Press release.