December 18, 2020 | COVID-19 deadlier than heart disease, cancer, and the flu, with in-hospital mortality rate 20.3% among inpatients, but for pediatric cancer patients, risks don’t seem to be elevated. New data on baricitinib, an anti-inflammatory drug, and remdesivir, an antiviral. Plus: NIH looks at SARS-CoV-2 infection in children, CDC uses Oracle’s EHR, Curebase launches drive-through clinical trial sites, and new vaccine trials launched.

Editor’s Note: The COVID-19 research roundups will be taking off for the upcoming holidays. We’ll return in January.

Research Updates

COVID-19 has become deadlier than heart disease and cancer, and its lethality may increase further as transmission increases with holiday travel and gatherings and with the intensified indoor exposure that winter brings, write authors from Virginia Commonwealth University in a JAMA Viewpoint. The failure of the public and its leaders to take adequate steps to prevent viral transmission has made the nation more vulnerable, allowing COVID-19 to become the leading cause of death in the United States, particularly among those aged 35 years or older. Much of this escalation was preventable, as is true for many deaths to come, they write. DOI: 10.1001/jama.2020.24865

Researchers at Washington University School of Medicine in St. Louis and Veterans Affairs St. Louis Health Care System published a deep comparison of COVID-19 to the flu, revealing a clearer distinction between the two contagious viruses: Among hospitalized patients, COVID-19 was associated with an increased need for ventilators, more admissions into intensive care units (ICUs), longer hospital stays and nearly five times the risk of death than faced by those with the flu. The work is published in The BMJ. DOI: 10.1136/bmj.m4677

Children with cancer with SARS-CoV-2 infection do not appear at increased risk of severe infection compared to the general pediatric population according to new work published in the British Journal of Cancer. The team looked at 54 cases of SARS-CoV-2 infection among pediatric cancer patients. No patients died and only three patients required intensive care support due to COVID-19. DOI: 10.1038/s41416-020-01181-0

COVID-19 patients have a 40% to 60% higher risk of ending up back in the hospital or dying in the first 10 days, compared with similar patients treated at the same hospitals during the same months for heart failure or pneumonia according to work published in JAMA. The team studied COVID-19 admissions from VA hospitals, and while longer term readmission and death rates were lower than for pneumonia and heart failure, the rates of readmission or death were higher than pneumonia or heart failure during the first 10 days after discharge following COVID-19 hospitalization, suggesting a period of heightened risk of clinical deterioration. DOI: 10.1001/jama.2020.21465

In a cohort study using the Premier Healthcare Database, outcomes were studied for 64,781 patients with COVID-19 treated in 592 US hospitals during April and May 2020. The researchers found that in-hospital mortality rate was 20.3% among inpatients, and severe complications were common. Receipt of statin, angiotensin-converting enzyme inhibitors, and calcium channel blockers were associated with decreased odds of mortality, but the combination use of hydroxychloroquine and azithromycin was associated with increased odds of mortality. The findings were published in JAMA Open Network. DOI: 10.1001/jamanetworkopen.2020.29058

Canadian researchers looked at how COVID-19 impacts infants with a retrospective study including all infants younger than 1 year with laboratory-confirmed SARS-CoV-2 infection who were diagnosed or treated at Centre Hospitalier Universitaire Sainte-Justine (CHU-SJ), Montreal, Quebec, Canada, between February 14 and May 31, 2020. Of 1,165 infants who were tested for SARS-CoV-2 infection at CHU-SJ during this 2020 study period, 25 (2%) had confirmed positive results, and 8 of those with positive results (32%) required hospitalization. The results were published in JAMA Network Open. DOI: 10.1001/jamanetworkopen.2020.30470

An epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. The epidemiology of GBS cases reported to the UK National Immunoglobulin Database was studied from 2016 to 2019 and compared to cases reported during the COVID-19 pandemic. Although it is not possible to entirely rule out the possibility of a link this study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic, which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses. The results were published in Brain. DOI: 10.1093/brain/awaa433

The combination of baricitinib, an anti-inflammatory drug, and remdesivir, an antiviral, reduced time to recovery for people hospitalized with COVID-19, according to clinical trial results published in the New England Journal of Medicine. The clinical trial is the second iteration of the NIH Adaptive COVID-19 Treatment Trial (ACTT-2), a study protocol to evaluate therapeutics for people hospitalized with COVID-19. Remdesivir is a broad-spectrum antiviral treatment developed by Gilead Sciences. Baricitinib was discovered by Incyte and licensed to Eli Lilly and Company and marketed under the brand name Olumiant. DOI: 10.1056/NEJMoa2031994

Meanwhile, a new study by a team of UK scientists published in Nature Communications, also found that drug remdesivir is likely to be a highly effective antiviral against SARS-CoV-2. The researchers describe giving the drug to a patient with COVID-19 and a rare immune disorder and observing a dramatic improvement in his symptoms and the disappearance of the virus. DOI: 10.1038/s41467-020-19761-2

A team from the National University of Singapore used their platform known as 'IDentif.AI' (Optimising Infectious Disease Combination Therapy with Artificial Intelligence) to investigate 12 potential drug candidates for COVID-19, representing over 530,000 possible drug combinations. Their results showed that the optimal drug therapy was a combination of the drugs remdesivir, ritonavir, and lopinavir at specific doses. The study was completed within 2 weeks, with a three‐order of magnitude reduction in the number of tests needed. IDentif.AI independently mirrored clinical trial outcomes to date without any data from these trials. They published their findings in AIChE. DOI: 10.1002/btm2.10196

The majority of pregnant women who tested positive for COVID-19 on arrival to the delivery room were asymptomatic, according to a paper by Mount Sinai researchers published in PLOS One. The pregnant patients who tested positive for the coronavirus were also more likely than those who tested negative to identify as Hispanic and report their primary language as Spanish. The data were gathered at Elmhurst Hospital in Queens, NY, a 545-bed public hospital serving a diverse, largely immigrant and low-income patient population and an epicenter of the global pandemic. DOI: 10.1371/journal.pone.0238409

In an editorial published in Anaesthesia, UK researchers review available data and reveal that despite their perceived increased exposure to COVID-19 patients and high-risk procedures, anesthetists and intensive care doctors appear to be at lower risk of being infected with SARS-CoV-2 and developing COVID-19. The authors theorize that doctors undertaking aerosol‐generating procedures (and in areas where these are frequent) wear higher performing personal protective equipment and may be behaviorally attuned to infection control precautions and use of protective equipment through other aspects of their roles such as maintaining surgical sterility in operating theatres or reducing nosocomial infection in ICU. DOI: 10.1111/anae.15358

Industry Updates

NIH is launching an observational study to evaluate the short- and long-term health outcomes of SARS-CoV-2 infection in children, including multisystem inflammatory syndrome in children (MIS-C), and to characterize the immunologic pathways associated with different disease presentations and outcomes. The study, called the Pediatric Research Immune Network on SARS-CoV-2 and MIS-C (PRISM), will enroll at least 250 children and young adults ages 20 years or younger from diverse racial and ethnic backgrounds at approximately 20 sites nationwide. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is sponsoring and funding the study. Press release.

BAT's US Bio-tech arm, Kentucky BioProcessing (KBP) will commence a Phase I first-time-in-human study of its COVID-19 vaccine candidate following approval of its Investigational New Drug application by the U.S. Food and Drug Administration (FDA). The study is designed to enroll a total of 180 healthy volunteers who will be divided into two age cohorts, then subdivided into low and high dose treatment groups. The candidate vaccine has been developed using KBP's innovative fast-growing plant-based technology. This unique approach has a number of possible advantages, including the rapid production of the vaccine's active ingredients in around 6-weeks, compared to several months using conventional methods. The candidate vaccine also has the potential to be stable at room temperature. Press release.

The Innovation Partners Institute (IPI) at Purdue University and MavenSphere have launched a personal engagement app designed to give organizations a simple tool to help people monitor their COVID symptoms, track test results, and connect to important support tools and resources. The fully-HIPAA compliant app, KeepOthersSafe, is currently being used by employees at the Purdue Research Foundation. The personal mobile engagement app is white label ready. It uses interactive questions that can be customized to help users understand community expectations and reinforce healthy behaviors based on CDC and institution-specific protocols. For a fee per user, the app can help organizations engage their employees in self-monitoring and compliance so organizations can better assess risk and facilitate consistent, clear communication with employees. It also can report symptoms seamlessly to designated healthcare professionals. More information.

The Centers for Disease Control (CDC) is using Oracle’s National Electronic Health Records Cloud plus Oracle’s Public Health Management Applications Suite to manage the COVID-19 vaccination program throughout the United States. The Oracle Public Health Management Applications Suite includes applications for managing the entire vaccination process from ordering the vaccine, tracking shipments and managing inventory—to directly communicating with vaccinated patients via smart phones to collect safety data such as side effects and adverse events. Press release.

Luminostics has used Curebase’s virtual site solution to power clinical studies for its Clip COVID Rapid Antigen Test, which was granted Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA) on December 7, 2020. For this study, Curebase was able to convert drive-through COVID-19 testing centers into clinical research sites with its unique decentralized clinical trial software platform and virtual site support model, that provided participant screening and consent in real-time while in the safety of their vehicle. Curebase’s unique web-based system allowed for potential participants to assess their eligibility for the validation study while in their cars waiting for a COVID-19 test. By accessing a specific study website on their own phones, candidates could answer screening questions and consent to participate in the Luminostics study. This high-throughput process was able to be completed without any physical interaction with patients and enabled hundreds of people to be screened in a few weeks. Press release.

Open Orphan, a CRO specializing in the testing of vaccines and antivirals, announces the first-in-human (Phase I) study of Codagenix intranasal SARS-CoV-2 (COVID-19) vaccine candidate has received approval from the UK’s independent Medicines and Healthcare Products Regulatory Agency (MHRA). The study will evaluate safety and immunogenicity of a single-dose nasal vaccine candidate in 48 healthy young adult volunteers at a state-of-the-art Quarantine Facility in Whitechapel, London. COVI-VAC is one of the few vaccines that uses the live-attenuated virus (i.e. the entire virus in a weakened form), unlike most other vaccines which only contain the viral spike. This vaccine, therefore, has the potential to induce broad antibody, cellular and mucosal immunity with a single intranasal dose and could be one of the first vaccines to provide long-term immunity from COVID-19. The trial is expected to commence in January 2021. Press release.

A new online calculator for estimating individual and community-level risk of dying from COVID-19 has been developed by researchers at the Johns Hopkins Bloomberg School of Public Health. The researchers who developed the calculator expect it to be useful to public health authorities for assessing mortality risks in different communities, and for prioritizing certain groups for vaccination as COVID-19 vaccines become available. The algorithm underlying the calculator uses information from existing large studies to estimate risk of COVID-19 mortality for individuals based on age, gender, sociodemographic factors and a variety of different health conditions. The risk estimates apply to individuals in the general population who are currently uninfected, and captures factors associated with both risk of future infection and complications after infection. Press release.

Researchers at the University of Warwick and University Hospitals Coventry and Warwickshire (UHCW) NHS Trust in the UK are investigating whether a tailored online exercise and support program would benefit those experiencing long-term symptoms of COVID-19. The results of the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) trial will help to guide recommendations for treatment of people with long COVID-19, for whom there is currently only limited advice and guidelines available. Funding of £1.19 million for the trial came from the National Institute for Health Research. Funding Announcement.