Characteristics of patients with fatal COVID-19

In a new study, researchers identified the most common characteristics of 85 COVID-19 patients who died in Wuhan, China in the early stages of the coronavirus pandemic. The study reports on commonalities of the largest group of coronavirus patient deaths to be studied to date. The paper was published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
In “Clinical Features of 85 Fatal Cases of COVID-19 From Wuhan: A Retrospective Observational Study,” researchers from China and the United States report on an analysis of the electronic health records of patients with COVID-19 who died despite treatment at two hospitals in Wuhan: Hanan Hospital and Wuhan Union Hospital between Jan. 9 and Feb. 15, 2020. Wuhan, in China’s Hubei Province, was the epicenter of the COVID-19 outbreak.
“The greatest number of deaths in our cohort were in males over 50 with non-communicable chronic diseases,” stated the authors. “We hope that this study conveys the seriousness of COVID-19 and emphasizes the risk groups of males over 50 with chronic comorbid conditions including hypertension (high blood pressure), coronary heart disease and diabetes.”
The researchers examined the medical records of 85 patients who had died, and recorded information on their medical histories, exposures to coronavirus, additional chronic diseases they had (comorbidities), symptoms, laboratory findings, CT scan results and clinical management. Statistical analyses were then done.
The median age of these patients was 65.8, and 72.9 percent were men. Their most common symptoms were fever, shortness of breath (dyspnea) and fatigue.
Hypertension, diabetes and coronary heart disease were the most common comorbidities. A little over 80 0 percent of patients had very low counts of eosinophils (cells that are reduced in severe respiratory infections) on admission. Complications included respiratory failure, shock, acute respiratory distress syndrome (ARDS) and cardiac arrhythmia, among others. Most patients received antibiotics, antivirals and glucocorticoids (types of steroids). Some were given intravenous immunoglobulin or interferon alpha-2b.
The researchers noted: “The effectiveness of medications such as antivirals or immunosuppressive agents against COVID-19 is not completely known. Perhaps our most significant observation is that while respiratory symptoms may not develop until a week after presentation, once they do there can be a rapid decline, as indicated by the short duration between time of admission and death (6.35 days on average) in our study.”
Based on their findings, eosinophilopenia – abnormally low levels of eosinophils in the blood – may indicate a poor prognosis. The scientists also noted that the early onset of shortness of breath may be used as an observational symptom for COVID-19 symptoms. In addition, they noted that a combination of antimicrobial drugs (antivirals, antibiotics) did not significantly help these patients. The majority of patients studied died from multiple organ failure.
“Our study, which investigated patients from Wuhan, China who died in the early phases of this pandemic, identified certain characteristics. As the disease has spread to other regions, the observations from these areas may be the same, or different. Genetics may play a role in the response to the infection, and the course of the pandemic may change as the virus mutates as well. Since this is a new pandemic that is constantly shifting, we think the medical community needs to keep an open mind as more and more studies are conducted.”

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The study authors are affiliated with a number of medical centers and departments of the Chinese PLA General Hospital; Wuhan Union Hospital; Renmin Hospital of Wuhan University; China’s National Clinical Research Center for Geriatric Diseases; Wuhan Hannan Hospital; Tongji Medical College, Huazhong University of Science & Technology; Joe DiMaggio Children’s Hospital, Hollywood, FL; and University of California, Davis.
https://www.eurekalert.org/pub_releases/2020-04/ats-nsi040320.php

Dealing with skin damage from face masks

DOCTORS and nurses on the COVID-19 frontline are spending many hours a day wearing face masks, and many members of the general public are doing the same. But although the devices offer invaluable protection, they can be the cause of significant skin damage through sweating and the rubbing of the masks against the nose.
Skincare experts at the University of Huddersfield are warning about the risks and are suggesting remedies.
Professor Karen Ousey is the University’s Director of the Institute of Skin Integrity and Infection Prevention and was part of a team that conducted detailed research into the pressure damage caused by a wide range of medical devices, including face masks. The findings and recommendations were published in February.
Now, the current emergency emphasises the problems that can arise with face masks, being worn for long periods by healthcare professionals.
“The wearers are sweating underneath the masks and this causes friction, leading to pressure damage on the nose and cheeks,” said Professor Ousey. “There can be tears to the skin as a result and these can lead to potential infection,” she added.
“The masks the healthcare professionals are wearing have to be fitted to the face – so if healthcare professionals add dressings to the skin under the mask after being fitted there is a chance the mask will no longer fit correctly,” continued Professor Ousey.
She suggests that people wearing masks keep their skin clean, well-hydrated and moisturised and that barrier creams should be applied at least half an hour before masks are put on.
“And we are suggesting that pressure from the mask is relieved every two hours. So you come away from the patient, relieve the pressure in a safe place and clean the skin again.”
Professor Ousey advises members of the general public – such as shop workers – who are wearing masks to keep their skin clean, dry and free of sweat.
“And if they do feel their masks rubbing, take them off as soon as they safely can.”

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Professor Ousey was a member of the global team that last year met in London to pool research on device-related pressure ulcers. It produced a 52-page document – published by the Journal of Wound Care – that examines the issues in detail.
The team was headed by Amit Gefen, who is a Professor of Biomedical Engineering at Tel Aviv University and a Visiting Professor at Huddersfield’s Institute of Skin Integrity and Infection Prevention.
Professor Gefen is recording a video session dealing with device-related pressure ulcers that will soon be available to view via the Institute’s website.
Professor Ousey also urges members of the public to visit the National Wound Care Strategy webpage, which offers wide-ranging advice on wound care and pressure ulcers.
https://www.eurekalert.org/pub_releases/2020-04/uoh-sfs040320.php

Trial drug significantly blocks early Covid-19 in engineered human tissue

An international team led by University of British Columbia researcher Dr. Josef Penninger has found a trial drug that effectively blocks the cellular door SARS-CoV-2 uses to infect its hosts.
The findings, published today in Cell, hold promise as a treatment capable of stopping early infection of the novel coronavirus that, as of April 2, has affected more than 981,000 people and claimed the lives of 50,000 people worldwide.
The study provides new insights into key aspects of SARS-CoV-2, the virus that causes COVID-19, and its interactions on a cellular level, as well as how the virus can infect blood vessels and kidneys.
“We are hopeful our results have implications for the development of a novel drug for the treatment of this unprecedented pandemic,” says Penninger, professor in UBC’s faculty of medicine, director of the Life Sciences Institute and the Canada 150 Research Chair in Functional Genetics at UBC.
“This work stems from an amazing collaboration among academic researchers and companies, including Dr. Ryan Conder’s gastrointestinal group at STEMCELL Technologies in Vancouver, Nuria Montserrat in Spain, Drs. Haibo Zhang and Art Slutsky from Toronto and especially Ali Mirazimi’s infectious biology team in Sweden, who have been working tirelessly day and night for weeks to better understand the pathology of this disease and to provide breakthrough therapeutic options.”
ACE2 — a protein on the surface of the cell membrane — is now at centre-stage in this outbreak as the key receptor for the spike glycoprotein of SARS-CoV-2. In earlier work, Penninger and colleagues at the University of Toronto and the Institute of Molecular Biology in Vienna first identified ACE2, and found that in living organisms, ACE2 is the key receptor for SARS, the viral respiratory illness recognized as a global threat in 2003. His laboratory also went on to link the protein to both cardiovascular disease and lung failure.
While the COVID-19 outbreak continues to spread around the globe, the absence of a clinically proven antiviral therapy or a treatment specifically targeting the critical SARS-CoV-2 receptor ACE2 on a molecular level has meant an empty arsenal for health care providers struggling to treat severe cases of COVID-19.
“Our new study provides very much needed direct evidence that a drug — called APN01 (human recombinant soluble angiotensin-converting enzyme 2 – hrsACE2) — soon to be tested in clinical trials by the European biotech company Apeiron Biologics, is useful as an antiviral therapy for COVID-19,” says Dr. Art Slutsky, a scientist at the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital and professor at the University of Toronto who is a collaborator on the study.
In cell cultures analyzed in the current study, hrsACE2 inhibited the coronavirus load by a factor of 1,000-5,000. In engineered replicas of human blood vessel and kidneys — organoids grown from human stem cells — the researchers demonstrated that the virus can directly infect and duplicate itself in these tissues. This provides important information on the development of the disease and the fact that severe cases of COVID-19 present with multi-organ failure and evidence of cardiovascular damage. Clinical grade hrsACE2 also reduced the SARS-CoV-2 infection in these engineered human tissues.
“Using organoids allows us to test in a very agile way treatments that are already being used for other diseases, or that are close to being validated. In these moments in which time is short, human organoids save the time that we would spend to test a new drug in the human setting,” says Núria Montserrat, ICREA professor at the Institute for Bioengineering of Catalonia in Spain.
“The virus causing COVID-19 is a close sibling to the first SARS virus,” adds Penninger. “Our previous work has helped to rapidly identify ACE2 as the entry gate for SARS-CoV-2, which explains a lot about the disease. Now we know that a soluble form of ACE2 that catches the virus away, could be indeed a very rational therapy that specifically targets the gate the virus must take to infect us. There is hope for this horrible pandemic.”

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This research was supported in part by the Canadian federal government through emergency funding focused on accelerating the development, testing, and implementation of measures to deal with the COVID-19 outbreak.
https://www.eurekalert.org/pub_releases/2020-04/uobc-tdc040220.php

Johns Hopkins to test if virus survivors’ plasma can protect health care workers

Researchers at Johns Hopkins University now have federal approval to test if blood plasma from recovered COVID-19 patients can help protect the heroes on the front line of the battle against the coronavirus.
The hope is that transfusions of blood plasma would boost the immune systems of health care providers, first responders and others at high risk of exposure, the researchers said.
COVID-19 survivors carry antibodies generated to fight the disease and the plasma is the part of blood that contains those antibodies.
“The ability to carry out a prophylaxis trial will tell us whether plasma is effective in protecting our health care workers and first responders from COVID-19,” said Arturo Casadevall, a Johns Hopkins infectious disease expert, in a statement.
The plasma transfusions are a common treatment for patients suffering severe bleeding;  and scientists hope the same treatment can be used as both a preventative therapy and to help boost the immune systems of those already sick.
The US Food and Drug Administration issued Johns Hopkins approved for a clinical trial Friday.

Casadevall has amassed a team of physicians and scientists from around the country who are now establishing a network of hospitals and blood banks that can collect, isolate and process blood plasma from COVID-19 survivors, according to Johns Hopkins.
https://nypost.com/2020/04/03/blood-plasma-of-coronavirus-survivors-may-protect-health-care-workers/

Roche Canada crowdsources COVID-19 ideas in quick-turn innovation challenge

Roche Canada is looking for a few good ideas to fight COVID-19, and it needs them soon.
The Swiss drugmaker recently launched a Canada-specific innovation challenge, asking for entries by April 10 in a contest that promises up to $100,000 in winnings to fund development.
The Roche Canada COVID-19 Innovation Challenge hopes to uncover any and all ideas that advance the fight against the novel coronavirus, but it does offer suggestions. How to address health system capacities, enhance real-time information-sharing, and manage remote and rural populations, for three. The contest is open only to legal residents of Canada.

“We are hoping to get a broad range of interest from all facets of society, including science-based experts such as biologists, data scientists, and healthcare providers, as well as entrepreneurs and technology developers, students, patients, and anyone with an innovative mind and wants to make a difference,” said a Roche spokesperson in an email.
While innovation challenges by pharma companies have proliferated over the past few years in specific diseases and technologies, the Roche Canada contest is one of the first to crowdsource for COVID-19 ideas.
Entries will be evaluated on five equality weighted criteria: clarity, design, innovativeness, impact and outcome, and feasibility and applicability. A Roche steering committee will choose and notify winners by April 15 and grant funding up to $50,000 for individual winners and $100,000 for team submissions.

“We are establishing this initiative in the hope that it can foster much needed solutions and create opportunities for people to get involved,” Michael Duong, head of personalized healthcare at Roche Canada, said in a news release. “Every Canadian is touched by this situation and it’s going to take the whole community coming together to get through it.”
https://www.fiercepharma.com/marketing/roche-canada-crowdsources-covid-19-ideas-new-quick-turn-innovation-challenge

UK seeks to end coronavirus lockdown with ‘immunity passports’

The UK is facing fresh questions over its coronavirus testing plan, as it emerged that the government is hoping to exit the lockdown through controversial “immunity passports” and antibody tests that are still not proven to work.
In the face of intense criticism, the health secretary, Matt Hancock, on Thursday admitted for the first time that mistakes had been made. “There will be criticisms made, and some of them will be justified,” he told the daily press briefing.
Hancock revealed that certificates to prove someone is immune to the virus could allow some of the population to go back to work, as he made a new pledge to complete 100,000 tests a day in England by the end of the month.
He attempted to relaunch the government’s strategy while Boris Johnson remains unwell in self-isolation, after a week of pressure about why so few tests are being carried out, especially on NHS workers.
Hancock promised that tests would be expanded from hospital patients and medics to more NHS staff, key workers and finally more people in the community. These will be a combination of tests for live cases of the virus and antibody tests to determine whether someone has previously been infected. Germany is carrying out around 70,000 tests a day, all for live cases of Covid-19.
However, the government was also forced to acknowledge it was not likely to have the capacity to embark on a programme of mass testing for live cases in the general public, as advocated by the World Health Organization and public experts.

Instead, No 10 and health department sources confirmed the general public would primarily have to rely on the potential for an antibody test – but these are “ideally” done 28 days after an infection, to give the clearest indication of whether someone has already had the virus, according to Prof John Newton, a senior Public Health England official.

Newton said the idea of testing all those that have symptoms in the country was “unrealistic” and the as yet unproven antibody test was more likely to be used by people at home.
Hancock said work was progressing with the antibody tests but that the results of many of the early tests had been “poor” and he was more hopeful about later ones that have been acquired. The government has bought options on up to 17.5m antibody tests of different types that are currently being tested, but cannot say definitively when they will be safe to use.
When the antibody tests are available, Hancock said, the government was looking at the possibility of issuing immunity certificates, so that some of the population “can get back to work as much as possible”.

However, some critics fear that this could lead to resentment in the population who have not had the virus, and that people might even deliberately try to get infected in order to obtain an immunity certificate.
Paul Hunter, professor in medicine at the University of East Anglia, told the Guardian that immunity certificates for frontline medical workers would be crucial for allowing staff to return to work and allowing personal protective equipment to be rationed in the safest way.
However, in the wider population, fraud could be an issue, which could rule out home-based testing, and there were concerns about unintended consequences. “People going out to deliberately get infected so they could get back to work is a concern and I don’t know how you’d avoid that,” he said. “Those are big issues.”
After a week spent in isolation with coronavirus himself, Hancock was forced to defend the government on numerous fronts. He told the press briefing:

• Johnson’s ultimate target of 250,000 tests a day – first made on March 18 – was still valid.
• Premiership footballers should take a pay cut in solidarity with NHS workers who are putting their lives on the line.
• Shortages of swabs had been rectified, but the UK was “still tackling the reagents issue, which is a global challenge”.
• The UK was having to build its capacity from a “lower base” than the likes of Germany, which is testing around 70,000 people per day.
• More commercial laboratories, including universities and private businesses, would be used to accelerate testing after criticism that this “Dunkirk” approach had initially been ignored.
• The NHS will have £13.4bn of debt written off, as previously confirmed.

Tensions have bubbled in Whitehall over who is to blame for low testing numbers in the UK, with some political sources blaming Public Health England (PHE) for not placing enough emphasis on the issue in recent weeks.
However, PHE rejected criticism that it had been trying to do all the testing itself and was too inflexible in which chemicals were allowed to be used, suggesting that it was the responsibility of ministers to find private capacity for more tests.
Prof Paul Cosford, emeritus medical director of the public health body, said PHE’s role was to “make sure our labs are doing what they need to do” in terms of testing hospital patients with a clinical need, with NHS staff a second priority.
Conservative backbenchers voiced concern in private about the government’s failure to roll out testing faster, saying there was anxiety that the public mood could turn against the government if it appeared there was no end to the lockdown as a result.
A former supporter Johnson in the leadership contest said they were worried sentiment could turn rapidly: “I think the government could get blown away if people are still inside after Easter and there is no progress on testing.”
Concerns were voiced that Johnson and other ministers had appeared to allow PHE to lead on testing, without asking the independent researchers and the private sector to get involved until Hancock’s announcement. “The fact that there’s not mass testing now is inexcusable,” another Conservative MP complained.
One senior MP said the party would be watching the polls closely and that he was “frankly amazed” that Johnson’s popularity was holding up. A bit like the virus, there might be a two-week lag before the public comes to fully realise that the government is failing to get the testing issue under control, they said.
“There are some in my party who are trying to blame PHE, but ultimately, it will be the politicians who get the blame if the economy collapses because we can’t test NHS workers.
“The death toll will become totemic. If we get thousands of people dying every day for several days, who knows where this will go. It is frightening, and the prime minister looks like he doesn’t know what to do.”
Jeremy Corbyn, the outgoing Labour leader, said: “The fact that we are not yet even testing 10,000 people a day is very, very serious indeed. There are almost half a million [frontline] people working in the NHS and the care sector. Even they have not yet been tested. It is ludicrous. We have got to get on top of testing.”
https://www.theguardian.com/politics/2020/apr/02/no-10-seeks-to-end-covid-19-lockdown-with-immunity-passports

BioNTech, CureVac urge lower clinical trial bar for quick COVID-19 vaccine

Two German biotech companies at the start of a race to create new vaccines against the COVID-19 pandemic are warning the European Medicines Agency and the FDA they will need traditional clinical trial hurdles removed if governments want the inoculations as quickly as possible.
Speaking to the Financial Times, both companies said some of the bigger clinical trial regulations will need to be cut in order for hundreds of millions of doses to be available by the end of the year.
Both BioNTech and CureVac, the former now partnered with Pfizer and the latter recently embroiled in a weird tale that allegedly saw the U.S. government try to lure it over the pond, are in preclinical trials for potential vaccines and are set to start testing on humans within the coming weeks.

In any normal time, and we’re far from that now, this would kick-start a long and laborious process that can take years to complete.
This is to accurately and thoroughly assess safety and efficacy. But given the ongoing spread of the pandemic, which at the start of April had infected at least 1 million people and killed more than 35,000, the pair said it wants to “abbreviate” these rules to speed up development.
This would include not having to do the final phase large-scale test, an expensive and time-consuming element, as well as making changes to how data are gathered.

Speaking to the FT, a spokesman for CureVac, which intends to start trials on humans in June, said that, if the company were forced to go through all three clinical stages, “It would take too much time to get a vaccine to market to fight against the current pandemic on time.” He added, “To speed this process up, authorities would have to allow us to abbreviate the approval process.”
Ugur Sahin, the founder of BioNTech, also told the financial newspaper: “Governmental organizations, experts and regulators need to work together to identify potential ways of accelerating the approval and availability of the vaccine.” BioNTech intends to begin testing its prototype on 150 healthy volunteers this month.
Other ways companies want to cut down on time are by sidelining on-site visits for side effects data gathering, using phone interviews instead, and perhaps lowering the level on just how comprehensive clinical reports will have to be.
It’s not clear whether they will or can be granted these “abbreviations” nor whether a regulator would be happy passing vaccines that had foregone the normal path to approval.(Although they will likely be under major political pressure to do so.) It also opens the door to potentially unsafe or nonefficacious medicines flooding a global market, with billions of people being inoculated with medicines that had not been tested to the same rigorous standards as all other vaccines have been.
But in a pandemic, which is also turning into an economic crisis, risk-benefit analysis starts to become a much harder proposition. The EMA, FDA and the U.K.’s MHRA have all already said they are willing to help speed up COVID-19 trials using a variety of methods.
Alongside U.S. biotech Moderna, the pair are using messenger RNA to develop these vaccines, which has the potential to speed up normal R&D lead times. There are, however, no mRNA vaccines on the market, making it more of an unknown. Both will also massively need to ramp up manufacturing capabilities.
CureVac told the FT it could produce 1 billion vaccines in one run, depending on the dose, once it completed its fourth manufacturing facility, which is being built.
BioNTech will manufacture BNT162 at its European mRNA manufacturing facilities with the support of its CDMO partner Polymun. However, global demand for an authorized SARS-CoV-2 vaccine could be huge, necessitating the coordination of other facilities to ensure fast access to the product.
https://www.fiercebiotech.com/biotech/biontech-curevac-tell-regulators-to-lower-clinical-trial-bar-if-they-want-a-covid-19