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Researchers use live virus to identify 30 existing drugs that could treat Covid-19

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Scientists at Sanford Burnham Prebys Medical Discovery Institute, the University of Hong Kong, Scripps Research, UC San Diego School of Medicine, the Icahn School of Medicine at Mount Sinai and UCLA have identified 30 existing drugs that stop the replication of SARS-CoV-2, the virus that causes Covid-19. Almost all of the drugs are entirely different from those currently being tested in clinical trials, and weren’t previously known to hold promise for Covid-19 treatment. The new candidates expand the number of “shots on goal” for a potential Covid-19 treatment and could reach patients faster than drugs that are created from scratch. The study was placed on bioRxiv – https://www.biorxiv.org/content/10.1101/2020.04.16.044016v1 – an open-access distribution service for preprints of life science research.
“We believe this is one of the first comprehensive drug screens using the live SARS-CoV-2 virus, and our hope is that one or more of these drugs will save lives while we wait for a vaccine for Covid-19,” said Sumit Chanda, Ph.D., director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys and senior author of the study. “Many drugs identified in this study – most of which are new to the Covid-19 research community – can begin clinical trials immediately or in a few months after additional testing.”
The drugs were identified by screening more than 12,000 drugs from the ReFRAME drug repurposing collection – a library of existing drugs that have been approved by the FDA for other diseases or have been tested extensively for human safety. ReFRAME was created by Scripps Research with support from the Bill & Melinda Gates Foundation to accelerate efforts to fight deadly diseases. Every compound was tested against the live SARS-CoV-2 virus, isolated from patients in Washington State and China, and the final 30 drugs were selected based on their ability to stop the virus’s growth.
“For us, the starting point for finding any new antiviral drug is to measure its ability to block viral replication in the lab,” says Chanda. “Since the drugs we identified in this study have already been tested in humans and proven safe, we can leapfrog over the more than half decade of studies normally required to get approval for human use.”
Highlights of the scientists’ discoveries follow. Each drug or experimental compound requires further evaluation in clinical trials to prove its effectiveness in treating people with Covid-19 before it can be used broadly.

  • 27 drugs that are not currently under evaluation for Covid-19 were effective at halting viral replication. 17 of these drugs have an extensive record of human safety from clinical studies in non-Covid-19 diseases, including four—clofazimine, acitretin, tretinoin and astemizole—that were previously approved by the FDA for other indications.
  • Thus far, six of the 17 were shown to be effective at concentrations, or doses, likely to be effective and tolerable in humans. Four of these six drugs – apilimod, MLN-3897, VBY-828 and ONO 5334 – have been tested clinically for diseases including rheumatoid arthritis, Crohn’s disease, osteoporosis and cancer.
  • In addition to the 27 drug candidates, three drugs currently in clinical trials for Covid-19, including remdesivir and chloroquine derivatives, were also shown to be effective at stopping the growth of SARS-CoV-2. These results reaffirm their promise as potential Covid-19 treatments and support the continuation of ongoing clinical trials to prove their effectiveness in patients.
  • Depending on regulatory guidance, the newly identified drug candidates may proceed directly to Covid-19 clinical trials or undergo further testing for efficacy in animal models.

“Based on the extensive data in this study, we believe the four drugs described above—apilimod, MLN-3897, VBY-825 and ONO 5334 – represent the best new approaches for a near-term Covid-19 treatment,” says Chanda. “However, we believe that all 30 drug candidates should be fully explored, as they were clearly active and effective at halting viral replication in our tests.”
“We have chosen to release these findings to the scientific and medical community now to help address the current global health emergency,” Chanda continues. “The data from this drug screen is a treasure trove; and we will continue to mine the data from this analysis, with a goal to find additional candidate therapies – and combinations of drugs – as they are identified.”

Can your pets get infected with the coronavirus?

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A small study published 8 April 2020 in Science by researchers in China found that cats are highly susceptible to SARS-CoV-2 and can pass the virus on to other cats via airborne transmission. However, dogs showed low susceptibility, and livestock including pigs, chickens, and ducks were not susceptible to the virus.
They did not study specifically whether cats can pass the virus to humans, although this seems likely as cats can pass the virus to other cats via airborne transmission.
From their findings, the researchers suggest that surveillance for SARS-CoV-2 in cats should be considered as an adjunct to elimination of COVID-19 in humans.>/p>
Two viruses – SARS-CoV 2/F13/environment/2020/Wuhan, isolated from an environmental sample collected in the Huanan Seafood Market in Wuhan (F13-E), and SARS-CoV-2/CTan/human/2020/Wuhan (CTan-H), isolated from a human patient – were used in the study.
The researchers first investigated the replication of SARS-CoV-2 in cats. Seven subadult cats (aged 6-9 months) were intranasally inoculated with 105 PFU of CTan-H. Two animals were scheduled to be euthanized on days 3 post infection (p.i.) and 6 p.i., respectively, to evaluate viral replication in their organs. Three subadult cats were placed in separate cages within an isolator. To monitor respiratory droplet transmission, an uninfected cat was placed in a cage adjacent to each of the infected cats.
In the transmission study, viral RNA was detected in the faeces of two virus-inoculated subadult cats on day 3 p.i., and in all three virus-inoculated subadult cats on day 5 p.i. Viral RNA was detected in the faeces of one exposed cat on day 3 p.i. The pair of subadult cats with viral RNA-positive faeces were euthanized on day 11 p.i., and viral RNA was detected in the soft palate and tonsils of the virus-inoculated animal and in the nasal turbinate, soft palate, tonsils, and trachea of the exposed animal indicating that respiratory droplet transmission had occurred in this pair of cats. Antibodies against SARS-CoV-2 were detected in all three virus-inoculated subadult cats and one exposed cat.
They replicated the study in juvenile cats and found “massive lesions in the nasal and tracheal mucosa epitheliums, and lungs”, indicating that SARS-CoV-2 can replicate efficiently in cats, with younger cats being more permissive.
Additionally, and importantly, the study showed that the virus can transmit between cats via the airborne route.
For the study in dogs, five 3-month-old beagles were intranasally inoculated with 105 PFU of CTan-H, and housed with two uninoculated beagles in a room. Oropharyngeal and rectal swabs from each beagle were collected over a series of days.
Viral RNA was detected in the rectal swabs of two virus-inoculated dogs on day 2 p.i and in the rectal swab of one dog on day 6 p.i. However, they note that “infectious virus was not detected in any swabs collected from these dogs”.
Two virus-inoculated dogs showed antibodies. The other two virus-inoculated dogs and the two contact dogs were all seronegative for SARS-CoV-2.
The dog study was repeated in pigs, chickens and ducks and viral RNA was not detected in any swabs collected from these animals or from naïve contact animals. All were seronegative for SARS-CoV-2.
doi: 10.1126/science.abb7015

New mental health programme helps frontline healthcare workers at risk from PTSD and depression

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Researchers from the Department of Experimental Psychology at the University of Oxford have developed a new mental health treatment programme to provide frontline healthcare workers with one-to-one support, including fast-track access to post-traumatic stress disorder (PTSD) or depression treatment. This evidence-based programme, called SHAPE Recovery < www.shaperecovery.com >, builds on an outreach programme shown to reduce rates of PTSD and depression.
SHAPE Recovery is working with 3,300 frontline healthcare workers across England and has now been invited to work with 8,000 London Ambulance employees and staff from associated partner organisations.
Around the world, frontline healthcare workers, such as intensive care doctors, nurses, support staff and paramedics, are risking their lives daily to stem the tide of the COVID-19 pandemic. They are at an increased risk of developing mental health problems, such as PTSD as well as depression, sleep problems and anxiety. Although many hospitals offer well-being initiatives, there is little evidence to support their effectiveness and they require staff to come forward for help.
Associate Professor Jennifer Wild, Programme Lead, said: “SHAPE is based on 15 years of research to examine what predicts PTSD and depression in frontline workers. We used the findings from these studies to create a highly effective support programme to prevent the development of PTSD and depression. SHAPE is the outcome of this work. It is evidence-based, affordable, and with ongoing evaluation could, if needed, be incorporated within NHS services within 12 to 24 months. The aim is to support staff to stay well, to recover if unwell, and to continue to be able to work, providing much-valued patient care.”
Zidan Mozumder, a paramedic who has benefitted from the progamme, commented: “Work-related stress has been at an all-time high for my peers due to the current COVID-19 pandemic. Fortunately, though, my weekly calls with my well-being coach have mitigated that stress significantly. For this I am eternally grateful. I feel very lucky to have had all of this support.”
SHAPE is unique because it moves the burden of outreach for help from frontline staff to well-being coaches. This means staff don’t have to come forward for help. Instead, they can access one-to-one confidential help, independent from their employers, on their phones. In addition, SHAPE facilitates fast access to gold-standard treatment for PTSD and depression should it be indicated.
Data collected from the programme will help Oxford researchers determine:

  • the effectiveness of this evidence-based, well-being support compared with no support for reducing symptoms of PTSD, depression, anxiety and sleep problems of frontline staff
  • whether early intervention for staff who continue to work during the pandemic leads to their recovery from mental ill health
  • potential cost savings of the programme to the NHS and society

Bedside patient monitoring system

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The Nellcor Bedside SpO2 System technology continuously monitors oxygen saturation (SpO2) and pulse rate for adult, paediatric and neonatal patients. The monitoring system gives clinicians instant access to comprehensive trending respiratory information, enabling them to detect subtle yet critical variations and respiratory complications earlier. The system features enhanced digital signal processing for precise SpO2 readings during low perfusion or other challenging conditions. It also incorporates an alarm management technology to differentiate between serious and minor events and reduce clinically insignificant oxygen desaturation alarms. The monitor further offers an intuitive, multicolour screen that is easy to read in any light and from many angles. Hospital technicians can set institutional defaults, replace the battery, perform diagnostics and generally maintain the monitor within the hospital, saving time and resources.
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Patient monitoring platform with additional measurement technologies

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The IntelliVue patient monitoring platform is now available with Masimo rainbow SET technology. Philips also offers its customers the option to add rainbow SET to existing IntelliVue monitors, and the company is working to integrate the technology into its Philips SureSigns and Philips Efficia patient monitoring platforms. In conjunction with the appropriate patient monitoring platform, Masimo rainbow SET technology analyses multiple wavelengths of light to accurately measure total hemoglobin (SpHb), oxygen content (SpOC), carboxyhemoglobin (SpCO), methemoglobin (SpMet) and Pleth Variability Index (PVI) noninvasively and continuously. Continuous monitoring of rainbow SpHb on a Philips monitor at the point-of-care provides clinicians with real-time visibility to changes in hemoglobin in between invasive blood sampling. To ensure that customers have choice of SpO2 pulse oximetry measurement technology, the company continues to offer Philips FAST SpO2 pulse oximetry and Covidien’s OxiMax SpO2 pulse oximetry, depending on the patient monitoring platform.
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Hologic was due to showcase the following new products at ECR 2020, which has been postponed due to the COVID-19 pandemic

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Breast Imaging
The 3Dimensions Mammography System is the industry’s fastest and highest resolution breast tomosynthesis system on the market. The system offers a variety of features designed to provide higher quality 3D images for radiologists, and enhanced workflow for technologists, with lowdose options, for patients. For example, the system includes Intelligent 2D imaging technology, which works with the system’s Clarity HD highresolution 3D imaging to deliver unprecedented clarity, contrast and detail at a lower dose.
Another feature available with the 3Dimensions system is the Quantra 2.2 breast density assessment software, which enables standardization in patient protocols, providing reproducible and consistent breast density assessment. Furthermore, thanks to the addition of the SmartCurve breast stabilization system, the 3Dimensions system is also clinically proven to deliver a more comfortable mammogram compared to standard compression, without compromising on speed, dose or accuracy.
Interventional
The Brevera® Breast Biopsy System with CorLumina® Imaging Technology is a real-time breast biopsy and verification system that improves the patient experience and streamlines the biopsy process from start to finish. Before the Brevera system, radiologists performing stereotactic breast biopsy procedures to diagnose breast cancer were often required to leave the patient under compression while they moved to another room to image and verify tissue samples. With the Brevera system, radiologists are able to obtain and image tissue samples in the procedure room in just a few seconds, potentially saving up to 10 minutes per patient and cutting the procedure time by up to 25%.
The Affirm® Prone Breast Biopsy System is the only dedicated prone biopsy system offering superior 2D or tomosynthesis imaging. Thanks to this high-quality 2D or tomosynthesis imaging and a field of view that’s more than 6.5 times larger than older generations of prone biopsy systems, clinicians can visualize more tissue and pinpoint subtle lesions and faint calcifications that may not be visible on older systems. Of note, more than 95% of patients reported their Affirm prone biopsy procedure was faster, more comfortable and less painful than expected. The system is designed with patients’ physical and emotional comfort in mind. Direct view of the biopsy needle is eliminated helping to reduce patient stress, and clinicians can quickly identify, target and access lesions to help reduce time spent in compression.
The Faxitron™ Core Specimen Radiography System is designed for efficiency. Within seconds this self-contained, table top unit provides highresolution imaging for immediate core sample verification in the biopsy room.
Breast Surgery
The LOCalizer™ Wireless Radio Frequency Identification (RFID) Breast Lesion Localization System is a non-radioactive, radiofrequency localization system designed for precise marking and targeting of lesions in breast-conserving surgery. It was designed to replace the traditional wire-guided localization method, which requires placement of a wire on the day of surgery. With the tag, placement can be done weeks or months prior to surgery. For patients, this means they can arrive closer to their surgery time and experience fewer interventional procedures.
The Trident® HD Specimen Radiography System delivers enhanced image quality, improved workflow and instant sample verification during breastconserving surgeries and stereotactic breast biopsies. The Trident products are the only specimen radiographs on the market to use amorphous selenium direct capture imaging – the same detector technology used in Hologic’s 3Dimensions mammography system – to generate crisp, clear, high-resolution images.
Ultrasound
The Viera™ Portable Breast Ultrasound System is a wireless, handheld ultrasound device that delivers accurate, high-resolution diagnostic images at the point of care, enabling optimization of clinical workflow and patient pathway. The system seamlessly transmits images to smart devices and communication systems (PACS) in the office, exam room or surgical suite, and allows facilities to add interventional breast ultrasound services for a fraction of the cost of comparable cart systems. Additionally, the Supersonic Mach 30 Breast Ultrasound System provides fast, high quality imaging and is the first to offer an intuitive touchpad control and large adjustable touchscreen display. The system’s enhanced ergonomics are designed to increase usability.
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Carestream increases production of mobile imaging systems in response to pandemic

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In response to the need for critical care during the COVID-19 pandemic, Carestream Health has increased production of its portable diagnostic imaging systems.
As unlikely facilities begin to function as urgent care units, Carestream’s DRX-Revolution Mobile X-ray System and DRX-Revolution Nano Mobile X-ray System bring the X-ray exam to the patient’s bedside, delivering high-quality digital radiography images to healthcare providers in real time to aid patient diagnosis – whenever and wherever needed.
“Our manufacturing plants and warehouses are operating at full capacity with employees putting in long hours and extra days to support the healthcare professionals who are on the front line of this exhausting fight,” said Charlie Hicks, Carestream’s General Manager for Premium Tier Solutions. “Likewise, Carestream suppliers and partners are ramping up production to help support this humanitarian crisis.”
With the current physical distancing measures in place, Carestream’s mobile solutions play an instrumental role in limiting the spread of infection by providing bedside chest imaging, which is vital for patients afflicted with the coronavirus, a disease that often results in a respiratory tract infection.
The DRX-Revolution system has added features to help reduce contamination. Shelves located in each of the detector slots, within the bin, allow users to safely place protective bags on detectors. Flush-mounted displays limit fluid ingress and provide a smooth surface for easier disinfecting. Bar code scanners automatically input patient information when wristbands are scanned, allowing users to quickly start an exam with limited interaction between the patient and the equipment.
Carestream’s nonmotorized DRX-Revolution Nano Mobile X-ray System also provides chest and intensive care imaging, with a compact, lower-cost mobile unit and an ultra-lightweight design for easy manoeuvrability and arm positioning.
For more information, visit: www.carestream.com
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ndd’s new inline filters offer additional protection against COVID-19 during lung function tests

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ndd Medical Technologies (ndd), a leading provider of diagnostic technology enabling healthcare professionals in the early detection of COPD and other chronic lung diseases, has introduced new single patient-use, inline filters for its lung function testing devices, in response to the global COVID-19 pandemic. Ensuring an added level of safety, the new filters can be used with ndd’s portable EasyOne spirometry range, including the EasyOne Air, EasyOne Pro, and EasyOne Pro LAB. EasyOne spirometers are popular among pulmonologists and medical researchers as they provide sensitive, reliable, real-time lung function results and diagnosis of chronic lung diseases, even at the point of care.
The EasyOne product line was originally designed with a strong focus on infection control with easy-to-wipe surfaces, single-use parts for anything that comes into contact with a patient’s breath, and ndd’s unique spirette and flow tube design which protects the flow sensor from cross-contamination. Now, when performing spirometry and testing of the diffusing capacity of the lungs for carbon monoxide (DLCO tests), the new EasyOne inline, single patient-use filters provide “double protection” for technicians and patients by keeping the ambient environment clean, without significantly affecting the EasyOne’s sensitivity.
ndd’s rigorous sensitivity tests have shown that the new inline filters do not significantly affect the device’s sensitivity and show comparable results in 24 waveform testing, (as required by ATS/ERS) and pass testing requirements. World-renowned medical research organizations – such as Johns Hopkins University, University Hospital Zurich and University of Cape Town – are partnering with ndd to assess the long-term lung damage caused by SARS-CoV-2.
Dr Trishul Siddharthan, Assistant Professor of Pulmonary and Critical Care Medicine at Johns Hopkins University, commented: “There is a lot of research underway to investigate the long-term effects of COVID-19. Our research group has been partnering with ndd thanks to the reliability of these spirometers in global settings and the ease of cleaning these devices during the pandemic to ensure safety.”
Prof. Friedrich Thienemann, General Medicine & Global Health research group, University of Cape Town and University Hospital Zurich, also noted: “In order to measure lung functions in resource-constrained settings like South African townships, one needs a device that is portable, point-of-care, easy-to-use, low-maintenance, and reliable without complicated calibration. EasyOne Pro LAB is that device.”
Incorporating ndd’s patented TrueFlow ultrasound technology, the EasyOne translates airflow into ultrasound signals which are measured by the sensors, so the patient’s breath does not come into contact with the sensors. This helps to prevent contamination and minimizes the cleaning required for safe use, while enabling a lifetime of calibration-free accuracy for flow and volume measurements.
To learn more about ndd, visit: www.nddmed.com
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Xenios sees growing demand for ECMO devices

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Xenios AG, a company of the Fresenius Medical Care Group, reports that it has seen a significant growth in demand for its extracorporeal membrane oxygenation (ECMO) devices, which can be used for the treatment of patients who develop severe pneumonia and acute respiratory distress syndrome (ARDS) due to COVID-19 infection.
Jürgen Böhm, CMO of Xenios, explained that for critically ill COVID-19 patients with acute lung failure and refractory hypoxemia – despite use of standard therapy – “our treatment often remains the last therapeutic option and has been a lifesaver for many patients”.
Xenios’s ECMO therapy bypasses the function of the lungs. The patient’s blood is freed from carbon dioxide outside the body and enriched with oxygen. The lungs are thus given time to heal. Because of the increase of critically ill COVID-19 patients, more physicians are opting for ECMO therapy, and thus the increase in demand for Xenios’s ECMO devices.
To meet the demand, the company has increased production of its ECMO devices. “We have put many measures in place to maximize the utilization of our capacity to manufacture ECMO devices as well as patient kits. Our biggest challenge right now is the availability of specific components for our products,” said Andreas Terpin, CEO of Xenios.
For more information, visit: www.xenios-ag.com
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Fujifilm’s Synapse 3D provides clinical decision support, speeds up workflow during COVID-19 emergency at Pisa University Hospital

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Pisa University Hospital has received support from Fujifilm Italia to improve and speed up the analysis of lung CT images which are important for the diagnosis of COVID-19. This has been possible thanks to an update by Fujifilm of the configuration of the Synapse 3D software used by emergency room radiologists.
The hospital says this new technological development has been useful to improving management of patients affected by COVID-19, during the emergency.
Synapse3D is a 3D medical image analysis system that uses Fujifilm’s image recognition technology to construct and analyze highprecision 3D images, compiled from tomographic images from CT and MRI. It delivers 3D visualization of medical images and has applications in image-based diagnosis and surgery simulation.
Synapse 3D delivers clinical value through fast, accurate, efficient and robust image processing for radiology, cardiology and surgical preoperation simulation.
It was developed in Japan (where it is named Synapse VINCENT) and it consists of more than 50 different processing modules.
The Synapse3D Lung Analysis/Airway module enables the analysis of density ranges in the lung in a quick, easy, objective and reproducible way.
At Pisa University Hospital the configuration of Synapse 3D was completed quickly, with the study of density ranges and a feasibility analysis carried out in a few days, meaning that this updated integrated workflow has been possible to use in the hospital since April 1.
The Pisa University Hospital had already set up three levels of assessing Coronavirus patients, and with the support of Synapse 3D software, doctors have had the ability to quickly and easily identify the stage of pneumonia, and therefore hospitalise patients accordingly:

  • normal hospitalisation for patients with mild pneumonia not requiring respiratory support
  • assessment by a pulmonologist or intensive care doctor for patients with moderate pneumonia to plan suitable respiratory support
  • intensive care assessment for patients with severe pneumonia with a view to transferring them to the intensive care unit

The density analysis provided by Synapse 3D has made it is possible to analyse the lung according to the different pixel densities of the CT images. Three groups were therefore defined based on different density ranges that allow the radiologist to evaluate the percentage of lung with lower density (emphysema), higher density (interstitial effort) and normal lung.
Dr. Chiara Romei, MD, PhD, Radiologist at the Pisa University Hospital, explained: “In a time of emergency such as this, it is crucial for us radiologists to detect accurate data as quickly as possible. Synapse 3D has enabled a quantitative analysis that is much faster and more objective than the visual analysis of the radiologist; in a couple of minutes it is possible to obtain data relating to the percentage of lung with greater and lesser density and to have a precise and objective, reproducible and shareable value.”
It is important to note that the data obtained by Synapse 3D does not replace the molecular diagnoses made through the nasopharyngeal swab (RT-PCR) and does not replace the analysis and diagnostic work by the radiologist, but instead it supports the reporting of daily exams to monitor and study the evolution of the disease, thus optimising workflow.
For medical professionals – download the take-away: https://synapse.fujifilm.eu/fujifilm-takeaway/
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