How to identify factors affecting COVID-19 transmission

March 26, 2020

Science Daily/Stanford University

Much remains unknown about how SARS-CoV-2, the virus that causes COVID-19, spreads through the environment. A major reason for this is that the behaviors and traits of viruses are highly variable -- some spread more easily through water, others through air; some are wrapped in layers of fatty molecules that help them avoid their host's immune system, while others are "naked."

This makes it urgent for environmental engineers and scientists to collaborate on pinpointing viral and environmental characteristics that affect transmission via surfaces, the air and fecal matter, according to Alexandria Boehm, a Stanford professor of civil and environmental engineering, and Krista Wigginton, the Shimizu Visiting Professor in Stanford's department of civil and environmental engineering and an associate professor at the University of Michigan.

Boehm and Wigginton co-authored a recently published viewpoint in Environmental Science & Technology calling for a broader, long-term and more quantitative approach to understanding viruses, such as SARS-CoV-2, that are spread through the environment. They are also principal investigators on a recently announced National Science Foundation-funded project to study the transfer of coronaviruses between skin and other materials, the effect of UV and sunlight on the coronaviruses, and the connection between disease outbreaks and virus concentrations in wastewater.

Scientists and medical experts don't have a good understanding of what virus characteristics and environmental factors control virus persistence in the environment -- for example, in aerosols and droplets, on surfaces including skin and in water including seawater, according to Boehm and Wigginton. "When a new virus emerges and poses a risk to human health, we don't have a good way of predicting how it will behave in the environment," Boehm said.

Part of the problem is historically there has been limited funding for this sort of work. The National Institutes of Health historically hasn't funded work on pathogens in the environment, and funding at the National Science Foundation for this work is limited. Also, coronaviruses and most of the emerging viruses that have caught the world's attention over the last decade are enveloped viruses that are wrapped in an outer layer of fatty lipid molecules that they've stolen from their hosts. Proteins on the surface of the envelopes can help these viruses evade the immune systems of the organisms they are infecting. "There has been much more work on the fate of non-enveloped or naked viruses because most intestinal pathogens in excrement are nonenveloped viruses -- like norovirus and rotavirus," said Wigginton.

In their paper, Boem and Wigginton address potential threats that viruses such as SARS-CoV-2 pose to water sources. We usually only worry about viruses in water if they are excreted by humans in their feces and urine. Most enveloped viruses aren't excreted in feces or urine, so they aren't usually on our minds when it comes to our water sources. There is increasing evidence that the SARS-CoV-2 viruses, or at least their genomes, are excreted in feces. If infective viruses are excreted, then fecal exposure could be a route of transmission, according to Boehm, who added, "It's unlikely this could be a major transmission route, but a person could potentially be exposed by interacting with water contaminated with untreated fecal matter."

Drinking water treatment systems have numerous treatment barriers to remove the most prevalent viruses and the most difficult-to-remove viruses, according to the engineers. Research on viruses similar to the SARS-CoV-2 virus suggests they are susceptible to these treatments. "In terms of virus concentration and persistence, this isn't a worst-case scenario," Wigginton said.

Broadly, Wigginton and Boehm write, we tend to study viruses very intensely when there is an outbreak, but the results from one virus aren't easy to extrapolate to other viruses that emerge years later. "If we took a broader approach to studying many kinds of viruses, we could better understand the characteristics driving their environmental fate," Wigginton said.

The two researchers call for experts across various fields -- including medicine and engineering and -- to work together to move methods forward faster, make discoveries and formulate strategies that wouldn't be possible independently.

https://www.sciencedaily.com/releases/2020/03/200326160759.htm

In politics and pandemics, trolls use fear, anger to drive clicks

Fake Facebook ads placed by Russians in 2016 received 9 times more clicks than typical ads

March 26, 2020

Science Daily/University of Colorado at Boulder

A new CU Boulder study shows that Facebook ads developed and shared by Russian trolls around the 2016 election were clicked on nine times more than typical social media ads. The authors say the trolls are likely at it again, as the 2020 election approaches and the COVID-19 pandemic wears on.

Facebook users flipping through their feeds in the fall of 2016 faced a minefield of targeted advertisements pitting blacks against police, southern whites against immigrants, gun owners against Obama supporters and the LGBTQ community against the conservative right.

Placed by distant Russian trolls, they didn't aim to prop up one candidate or cause, but to turn Americans against one another.

The ads were cheaply made and full of threatening, vulgar language.

And, according to a sweeping new analysis of more than 2,500 of the ads, they were remarkably effective, eliciting clickthrough rates as much as nine times higher than what is typical in digital advertising.

"We found that fear and anger appeals work really well in getting people to engage," said lead author Chris Vargo, an assistant professor of Advertising, Public Relations and Media Design at University of Colorado Boulder.

The study, published this week in Journalism and Mass Communication Quarterly, is the first to take a comprehensive look at ads placed by the infamous Russian propaganda machine known as the Internet Research Agency (IRA) and ask: How effective were they? And what makes people click on them?

While focused on ads running in 2016, the study's findings resonate in the age of COVID-19 and the run-up to the 2020 election, the authors say.

"As consumers continue to see ads that contain false claims and are intentionally designed to use their emotions to manipulate them, it's important for them to have cool heads and understand the motives behind them," said Vargo.

For the study, Vargo and assistant professor of advertising Toby Hopp scoured 2,517 Facebook and Instagram ads downloaded from the U.S. House of Representatives Permanent Select Committee On Intelligence website. The committee made the ads publicly available in 2018 after concluding that the IRA had been creating fake U.S. personas, setting up fake social media pages, and using targeted paid advertising to "sow discord" among U.S. residents.

Using computational tools and manual coding, Vargo and Hopp analyzed every ad, looking for the inflammatory, obscene or threatening words and language hostile to a particular group's ethnic, religious or sexual identity. They also looked at which groups each ad targeted, how many clicks the ad got, and how much the IRA paid.

Collectively, the IRA spent about $75,000 to generate about 40.5 million impressions with about 3.7 million users clicking on them -- a clickthrough rate of 9.2%.

That compares to between .9% and 1.8% for a typical digital ad.

While ads using blatantly racist language didn't do well, those using cuss words and inflammatory words (like "sissy," "idiot," "psychopath" and "terrorist") or posing a potential threat did. Ads that evoked fear and anger did the best.

One IRA advertisement targeting users with an interest in the Black Lives Matter movement stated: "They killed an unarmed guy again! We MUST make the cops stop thinking that they are above the law!" Another shouted: "White supremacists are planning to raise the racist flag again!" Meanwhile, ads targeting people who sympathized with white conservative groups read "Take care of our vets; not illegals" or joked "If you voted for Obama: We don't want your business because you are too stupid to own a firearm."

Only 110 out of 2,000 mentioned Donald Trump.

"This wasn't about electing one candidate or another," said Vargo. "It was essentially a make-Americans-hate-each-other campaign."

The ads were often unsophisticated, with spelling or grammatical errors and poorly photoshopped images. Yet at only a few cents to distribute, the IRA got an impressive rate of return.

"I was shocked at how effective these appeals were," said Vargo.

The authors warn that they have no doubt such troll farms are still at it.

According to some news reports, Russian trolls are already engaged in disinformation campaigns around COVID-19.

"I think with any major story, you are going to see this kind of disinformation circulated," said Hopp. "There are bad actors out there who have goals that are counter to the aspirational goals of American democracy, and there are plenty of opportunities for them to take advantage of the current structure of social media."

Ultimately, the authors believe better monitoring, via both machine algorithms and human reviewers, could help stem the tide of disinformation.

"We as a society need to start seriously talking about what role the platforms and government should play in times like the 2020 election or during COVID-19 when we have a compelling need for high-quality, accurate information to be distributed," said Hopp.

https://www.sciencedaily.com/releases/2020/03/200326155925.htm

The genetic quest to understand COVID-19

Unlocking the genetic code of the novel coronavirus will help us prevent other diseases

March 26, 2020

Science Daily/University of Sydney

How the novel coronavirus that causes COVID-19 made the leap from animals to humans is a puzzle that scientists are trying to solve as humanity comes to grip with the deadly pandemic sweeping the globe.

At the frontline of this scientific work is Professor Edward Holmes, an evolutionary virologist who holds a joint position with the School of Life and Environmental Sciences and the School of Medical Sciences at the University of Sydney.

He has been working closely with scientists in China and around the world to unlock the genetic code of SARS-CoV-2, which is the virus that causes COVID-19, to understand its origins and assist in the race other scientists are engaged in to find an effective vaccine.

Their work will also help in the monitoring and prevention of other viruses that could potentially transfer from wildlife into humans, causing what are known as zoonotic diseases.

Already this year, Professor Holmes has co-authored four papers on the novel coronavirus, including two of the earliest descriptions of the virus (published in Nature and The Lancet).

This week he publishes two more.

Brought forward for early publication on Thursday by Nature after peer review, the first paper identifies a similar coronavirus to the one now infecting humans in the Malayan pangolin population of southern China. Professor Holmes, a co-author, is the only non-China based academic on the paper.

Understanding the evolutionary pathway by which this novel coronavirus has transferred to humans will help us not only combat the current pandemic but assist in identifying future threats from other coronaviruses in other species.

This paper is an important part of solving that puzzle.

Professor Holmes said: "The role that pangolins play in the emergence of SARS-CoV-2 (the cause of COVID-19) is still unclear. However, it is striking is that the pangolin viruses contain some genomic regions that are very closely related to the human virus. The most important of these is the receptor binding domain that dictates how the virus is able to attach and infect human cells."

The paper identifies pangolins as possible intermediate hosts for the novel human virus that has emerged. The authors call for these animals and others to be removed from wet markets in order to prevent zoonotic transmission to humans.

Professor Holmes said: "It is clear that wildlife contains many coronaviruses that could potentially emerge in humans in the future. A crucial lesson from this pandemic to help prevent the next one is that humans must reduce their exposure to wildlife, for example by banning 'wet markets' and the trade in wildlife."

Just last week Nature Medicine published research co-authored by Professor Holmes with scientists from Scripps Research Institute in La Jolla California, the University of Edinburgh, Columbia University in New York and Tulane University, New Orleans.

That paper has dispelled the fanciful idea that the novel coronavirus was a manufactured biological agent.

Using comparative analysis of genomic data, the scientists show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.

Professor Holmes said: "There is simply no evidence that SARS-CoV-2 -- the cause of COVID-19 -- came out of a lab. In reality, this is the sort of natural disease emergence event that researchers in the field like myself have been warning about for many years."

That paper has quickly become the highest ranked academic study of all time as measured by Altmetric, a company that monitors media coverage of research papers.

"The high Altmetric is a strong indication of the remarkable global interest in this topic," Professor Holmes said.

And today, Professor Holmes publishes a commentary in the journal Cell with his colleague Professor Yong-Zhen Zhang from the Shanghai Public Health Clinical Centre and the School of Life Science at Fudan University, Shanghai.

In that article they outline our current knowledge of what the genomic data reveals about the emergence of SARS-CoV-2 virus and discuss the gaps in our knowledge.

This includes taking samples from the Wuhan wet market where it is believed the virus originated. The paper says that "genome sequences of 'environmental samples' -- likely surfaces -- from the market have now been obtained and phylogenetic analysis reveals that they are very closely related to viruses sampled from the earliest Wuhan patients."

However, Professor Holmes and Professor Zhang are quick to point out that as "not all of the early [COVID-19] cases were market associated, it is possible that the emergence story is more complicated than first suspected."

The paper says that the SARS-CoV-2 virus is likely to become the fifth endemic coronavirus in the human population. It concludes that "coronaviruses clearly have the capacity to jump species boundaries and adapt to new hosts, making it straightforward to predict that more will emerge in the future."

How we respond to that will require more research to assist develop public health policy.

They point to policy and other measures to help prevent other coronaviruses becoming a health danger to humans. These include:

- Surveillance of animal coronaviruses in a variety of mammalian species. It is known that bats carry many coronaviruses, we know little about what other species carry these viruses and which has the potential to emerge in humans. 

- Increase action against the illegal wildlife trade of exotic animals

- Removal of mammalian and perhaps avian wildlife from wet markets

https://www.sciencedaily.com/releases/2020/03/200326144357.htm

A possible treatment for COVID-19 and an approach for developing others

March 26, 2020

Science Daily/American Society for Microbiology

SARS-CoV-2, the virus that causes COVID-19 disease is more transmissible, but has a lower mortality rate than its sibling, SARS-CoV, according to a review article published this week in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.

In humans, coronaviruses cause mainly respiratory infections. Individuals with SARS-CoV-2 may remain asymptomatic for 2 to 14 days post-infection and some individuals likely transmit the virus without developing disease symptoms.

So far, the most promising compound for treating COVID-19 is the antiviral, remdesivir. It is currently in clinical trials for treating Ebola virus infections.

Remdesivir was recently tested in a non-human primate model of MERS-CoV infection. Prophylactic treatment 24 hours prior to inoculation prevented MERS-CoV from causing clinical disease and inhibited viral replication in lung tissues, preventing formation of lung lesions. Initiation of treatment 12 hours after virus inoculation was similarly effective.

Remdesivir has also shown effectiveness against a wide range of coronaviruses. It has already undergone safety testing in clinical trials for Ebola, thereby reducing the time that would be necessary for conducting clinical trials for SARS-CoV-2.

Nonetheless, much work needs to be done to gain a better understanding of the mechanics of SARS-CoV-2. For example, understanding how SARS-CoV-2 interacts with the host ACE2 receptor -- by which SARS-CoV-2 gains entry into the host (whether human or animal) -- might reveal how this virus overcame the species barrier between animals and humans. This could also lead to design of new antivirals.

Although coronaviruses are common in bats, no direct animal source of the epidemic has been identified to date, according to the report. "It is critical to identify the intermediate species to stop the current spread and to prevent future human SARS-related coronavirus epidemics," the researchers write.

https://www.sciencedaily.com/releases/2020/03/200326124159.htm

Modelling study estimates impact of physical distancing measures on progression of COVID-19 epidemic in Wuhan

March 25, 2020

Science Daily/The Lancet

A new study suggests extending school and workplace closures in Wuhan until April, rather than March, would likely delay a second wave of cases until later in the year, relieving pressure on health services.

New modelling research, published in The Lancet Public Health journal, suggests that school and workplace closures in Wuhan, China have reduced the number of COVID-19 cases and substantially delayed the epidemic peak -- giving the health system the time and opportunity to expand and respond.

Using mathematical modelling to simulate the impact of either extending or relaxing current school and workplace closures, researchers estimate that by lifting these control measures in March, a second wave of cases may occur in late August, whereas maintaining these restrictions until April, would likely delay a second peak until October -- relieving pressure on the health services in the intervening months.

However, the authors caution that given the large uncertainties around estimates of the reproduction number (how many people an individual with the virus is likely to infect), and how long a person is infected on average, the true impact of relaxing physical distancing measures on the ongoing COVID-19 epidemic cannot be precisely predicted.

"The unprecedented measures the city of Wuhan has put in place to reduce social contacts in school and the workplace have helped to control the outbreak," says Dr Kiesha Prem from the London School of Hygiene & Tropical Medicine, UK, who led the research. "However, the city now needs to be really careful to avoid prematurely lifting physical distancing measures, because that could lead to an earlier secondary peak in cases. But if they relax the restrictions gradually, this is likely to both delay and flatten the peak."

In December 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China. In mid-January 2020, schools and workplace were closed as part of the Lunar New Year holidays. These closures were then extended to reduce person-to-person contact and prevent the spread of SARS-CoV-2.

In the study, researchers developed a transmission model to quantify the impact of school and workplace closures using information about how often people of different ages mix with each other in different locations, and to assess their effects on bringing the outbreak under control.

Using the latest data on the spread of COVID-19 in Wuhan and from the rest of China on the number of contacts per day by age group at school and work, they compared the effect of three scenarios: no interventions and no holidays (a hypothetical scenario); no physical distancing measures but school winter school break and Lunar New Year holidays as normal; and intense control measures with school closed and only about 10% of the workforce -- eg, health-care personnel, police, and other essential government staff -- working during the control measures (as started in Wuhan in mid-January). They also modelled the impact of lifting control measures in a staggered way, and during different stages of the outbreak (in March and April).

The analyses suggest that the normal school winter break and Lunar New Year holidays would have had little impact on the progression of the outbreak had schools and workplaces opened as usual. However, putting extreme measures in place to reduce contacts at school and workplaces, could reduce case numbers and the size of the epidemic peak, whilst also delaying the peak. The effects of these distancing measures seem to vary by age, with the greatest reductions in new cases among school children and the elderly, and lowest among working-aged adults. However, once these interventions are relaxed, case numbers are expected to rise.

Further analysis suggests that physical distancing measures are likely to be most effective if the staggered return to work commences at the beginning of April -- potentially reducing the median number of new infections by 24% up to the end of 2020, and delaying a second peak until October.

"Our results won't look exactly the same in another country, because the population structure and the way people mix will be different. But we think one thing probably applies everywhere: physical distancing measures are very useful, and we need to carefully adjust their lifting to avoid subsequent waves of infection when workers and school children return to their normal routine. If those waves come too quickly, that could overwhelm health systems," says co-author Dr Yang Liu from London School of Hygiene & Tropical Medicine.

Despite these important findings, the study has some limitations, including that it assumed no difference in susceptibility between children, and that the extreme distancing measures used in Wuhan may have increased the transmission within households. Finally, the model did not capture individual-level differences in contact rates, which could be important in super-spreading events, particularly early on in an epidemic.

Writing in a linked Comment, Dr Tim Colbourn from University College London, UK (who was not involved in the study) says: "The study by Kiesha Prem and colleagues in The Lancet Public Health is crucial for policy makers everywhere, as it indicates the effects of extending or relaxing physical distancing control measures on the coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China."

He continues: "Given many countries with mounting epidemics now potentially face the first phase of lockdown, safe ways out of the situation must be identified... New COVID-19 country-specific models should incorporate testing, contract tracing, and localised quarantine of suspected cases as the main alternative intervention strategy to distancing lockdown measures, either at the start of the epidemic, if it is very small, or after the relaxation of lockdown conditions, if lockdown had to be imposed, to prevent health-care system overload in an already mounting epidemic." 

https://www.sciencedaily.com/releases/2020/03/200325212154.htm

COVID-19: Low risk of coronavirus spreading through tears

March 25, 2020

Science Daily/American Academy of Ophthalmology

A new study found no virus in tears of COVID-19 infected patients

While researchers are certain that coronavirus spreads through mucus and droplets expelled by coughing or sneezing, it is unclear if the virus is spread through other bodily fluids, such as tears. Today's just-published study offers evidence that it is unlikely that infected patients are shedding virus through their tears, with one important caveat. None of the patients in the study had conjunctivitis, also known as pink eye. However, health officials believe pink eye develops in just 1 percent to 3 percent of people with coronavirus. The study's authors conclude that their findings, coupled with the low incidence of pink eye among infected patients, suggests that the risk of virus transmission through tears is low. Their study was published online today in Ophthalmology, the journal of the American Academy of Ophthalmology.

To conduct the study, Ivan Seah, MBBS, and his colleagues at the National University Hospital in Singapore collected tear samples from 17 patients with COVID-19 from the time they showed symptoms until they recovered about 20 days later. Neither viral culture nor reverse transcription polymerase chain reaction (RT-PCR) detected the virus in their tears throughout the two-week course of the disease.

Dr. Seah also took samples from the back of the nose and throat during the same time period. While the patients' tears were clear of virus, their noses and throats were teeming with COVID-19. Dr. Seah said he hopes their work helps to guide more research into preventing virus transmission through more significant routes, such as droplets and fecal-oral spread.

Despite this reassuring news, it's important for people to understand that guarding your eyes -- as well as your hands and mouth -- can slow the spread of respiratory viruses like the coronavirus.

Here's why:

• When a sick person coughs or talks, virus particles can spray from their mouth or nose into another person's face. You're most likely to inhale these droplets through your mouth or nose, but they can also enter through your eyes.

• You can also become infected by touching something that has the virus on it -- like a table or doorknob -- and then touching your eyes.

Find other ways you can help protect yourself and others on the Academy's EyeSmart website.

 https://www.sciencedaily.com/releases/2020/03/200325143826.htm

Study shows how diligent we have to be to keep surfaces germ-free

Only half of surfaces in animal hospital disinfected

March 25, 2020

Science Daily/Ohio State University

During the COVID-19 pandemic, every frequently touched surface outside our home seems as dangerous as a hot pot right out of the oven. We won't get burned if we touch it, but we might get infected with a potentially dangerous virus.

A recent study suggests that even organized efforts to clean surfaces can fall short, a reminder for us all that keeping our surroundings clean may require some additional work.

For 5 ½ weeks, researchers tagged surfaces of a small-animal veterinary practice daily with a fluorescent dye visible only under black light. They checked tagged surfaces 24 hours later to see if the marks were showing. Surfaces were considered cleaned if the dye was completely removed.

Results showed that overall, only half of all surfaces were adequately cleaned during the study period. Human-touch surfaces -- such as medical instruments, dog run handles, and computer mice and keyboards -- were cleaned less frequently than areas touched primarily by animals. The results were similar to studies from other veterinary clinics.

The researchers recommended creating checklists of surfaces that need to be regularly cleaned and educating all staff on the importance of proper cleaning to protect animal and human health.

"The concept of infectious diseases is around us all the time, but now it's more important than ever to take steps to protect ourselves," said senior study author Jason Stull, assistant professor of veterinary preventive medicine at The Ohio State University.

"A recent study concluded the coronavirus causing COVID-19 has the ability to survive on certain types of surfaces for hours to a few days. At veterinary practices, other businesses and certainly human hospitals, surface cleaning and disinfection is extremely important. People come in and may contaminate an area and that area potentially can serve as a source of infection for other people."

The study is published in the February issue of the Journal of Small Animal Practice.

Stull specializes in veterinary infection control, including prevention of diseases that animals can share with each other or pass to humans -- such as Salmonella, E. coli and parasites.

For the current work, Stull and colleagues assessed almost 5,000 surfaces over the course of the study. On average, 50 percent of surfaces were cleaned, with broad variations by type of surface and hospital location. The human-touch surfaces were the least likely to be cleaned.

The study assessed everyday cleaning practices in a place where people spend lots of time with different animals and different people. It's not too much of a stretch to apply some lessons to what we're experiencing now with COVID-19, Stull said.

"Plenty of industries and groups outside of human health care have ramped up their efforts to clean and disinfect common-touch surfaces. The take-home messages from our study can have important parallels for others, such as other veterinary clinics, but also groups such as grocery stores.

"Our study also highlights that, despite our best efforts, 100 percent cleaning and disinfection is unlikely to occur. This is important to remember, as regardless of where you visit, it's also best to assume surfaces may be contaminated -- and before you come back into your home, you should follow the recommendations to clean your hands and clean items you've handled."

At home, Stull said, it makes sense to concentrate on cleaning common-touch surfaces like doorknobs and countertops.

"For the average person, it's thinking about your list of things in your own home and ensuring that in some way that you're actually hitting those pieces with reasonable effort," he said.

On a normal day, people who have touched commonly shared surfaces should wash their hands before eating or scratching their noses. But will we remain diligent about this level of personal cleanliness -- and community health -- once the worst of the coronavirus threat is behind us?

"People have a tendency to swing from extremes," Stull said. "Changing the innate behaviors of people is always difficult, and we've struggled in human and veterinary health care to change these everyday practices.

"The hard part is continuing these efforts. When we get to the end of this, and at some point that will happen, you will likely see people revert back to their norm. What we need is a culture shift, so people recognize that infection control through hand-washing and thorough cleaning of shared surfaces is a critically important thing we can all do all the time, and it has measurable impact."

Armando Hoet of Ohio State's College of Veterinary Medicine and Gregory Langdon of the College of Public Health also worked on the study.

https://www.sciencedaily.com/releases/2020/03/200325120849.htm

COVID-19: Stopgap measure to treat respiratory distress

March 25, 2020

Science Daily/Massachusetts Institute of Technology

Researchers at MIT and the University of Colorado at Denver have proposed a stopgap measure that they believe could help Covid-19 patients who are in acute respiratory distress. By repurposing a drug that is now used to treat blood clots, they believe they could help people in cases where a ventilator is not helping, or if a ventilator is not available.

Three hospitals in Massachusetts and Colorado are developing plans to test this approach in severely ill Covid-19 patients. The drug, a protein called tissue plasminogen activator (tPA), is commonly given to heart attack and stroke victims. The approach is based on emerging data from China and Italy that Covid-19 patients have a profound disorder of blood clotting that is contributing to their respiratory failure.

"If this were to work, which I hope it will, it could potentially be scaled up very quickly, because every hospital already has it in their pharmacy," says Michael Yaffe, a David H. Koch Professor of Science at MIT. "We don't have to make a new drug, and we don't have to do the same kind of testing that you would have to do with a new agent. This is a drug that we already use. We're just trying to repurpose it."

Yaffe, who is also a member of MIT's Koch Institute for Integrative Cancer Research and an intensive care physician at Boston's Beth Israel Deaconess Medical Center/Harvard Medical School, is the senior author of a paper describing the new approach.

The paper, which appears in the Journal of Trauma and Acute Care Surgery, was co-authored by Christopher Barrett, a surgeon at Beth Israel Deaconess and a visiting scientist at MIT; Hunter Moore, Ernest Moore, Peter Moore, and Robert McIntyre of the University of Colorado at Denver; Daniel Talmor of Beth Israel Deaconess; and Frederick Moore of the University of Florida.

Breaking up clots

In one large-scale study of the Covid-19 outbreak in Wuhan, China, it was found that 5 percent of patients required intensive care and 2.3 percent required a ventilator. Many doctors and public health officials in the United States worry that there may not be enough ventilators for all Covid-19 patients who will need them. In China and Italy, a significant number of the patients who required a ventilator went on to die of respiratory failure, despite maximal support, indicating that there is a need for additional treatment approaches.

The treatment that the MIT and University of Colorado team now proposes is based on many years of research into what happens in the lungs during respiratory failure. In such patients, blood clots often form in the lungs. Very small clots called microthrombi can also form in the blood vessels of the lungs. These tiny clots prevent blood from reaching the airspaces of the lungs, where blood normally becomes oxygenated.

The researchers believe that tPA, which helps to dissolve blood clots, may help patients in acute respiratory distress. A natural protein found in our bodies, tPA converts plasminogen to an enzyme called plasmin, which breaks down clots. Larger amounts are often given to heart attack patients or stroke victims to dissolve the clot causing the heart attack or stroke.

Animal experiments, and one human trial, have shown potential benefits of this approach in treating respiratory distress. In the human trial, performed in 2001, 20 patients who were in respiratory failure following trauma or sepsis were given drugs that activate plasminogen (urokinase or streptokinase, but not tPA). All of the patients in the trial had respiratory distress so severe that they were not expected to survive, but 30 percent of them survived following treatment.

That is the only study using plasminogen activators to treat respiratory failure in humans to date, largely because improved ventilator strategies have been working well. This appears not to be the case for many patients with Covid-19, Yaffe says.

The idea to try this treatment in Covid-19 patients arose, in part, because the Colorado and MIT research team has spent the last several years studying the inflammation and abnormal bleeding that can occur in the lungs following traumatic injuries. It turns out that Covid-19 patients also suffer from inflammation-linked tissue damage, which has been seen in autopsy results from those patients and may contribute to clot formation.

"What we are hearing from our intensive care colleagues in Europe and in New York is that many of the critically ill patients with Covid-19 are hypercoagulable, meaning that they are clotting off their IVs, and having kidney and heart failure from blood clots, in addition to lung failure. There's plenty of basic science to support the idea that this concept should be beneficial," Yaffe says. "The tricky part, of course, is figuring out the right dose and route of administration. But the target we are going after is well-validated."

Potential benefits

The researchers will test tPA in patients under the FDA's "compassionate use" program, which allows experimental drugs to be used in cases where there are no other treatment options. If the drug appears to help in an initial set of patients, its use could be expanded further, Yaffe says.

"We learned that the clinical trial will be funded by BARDA [the Biomedical Advanced Research and Development Authority], and that Francis Collins, the NIH director, was briefed on the approach yesterday afternoon," he says. "Genentech, the manufacturer of tPA, has already donated the drug for the initial trial, and indicated that they will rapidly expand access if the initial patient response is encouraging."

Based on the latest data from their colleagues in Colorado, these groups plan to deliver the drug both intravenously and/or instill it directly into the airways. The intravenous route is currently used for stroke and heart attack patients. Their idea is to give one dose rapidly, over a two-hour period, followed by an equivalent dose given more slowly over 22 hours. Applied BioMath, a company spun out by former MIT researchers, is now working on computational models that may help to refine the dosing schedule.

"If it were to work, and we don't yet know if it will, it has a lot of potential for rapid expansion," Yaffe says. "The public health benefits are obvious. We might get people off ventilators quicker, and we could potentially prevent people from needing to go on a ventilator."

The hospitals planning to test this approach are Beth Israel Deaconess, the University of Colorado Anschultz Medical Campus, and Denver Health. The research that led to this proposal was funded by the National Institutes of Health and the Department of Defense Peer Reviewed Medical Research Program.

https://www.sciencedaily.com/releases/2020/03/200325120845.htm

Wuhan study shows lying face down improves breathing in severe COVID-19

March 24, 2020

Science Daily/American Thoracic Society

In a new study of patients with severe COVID-19 (SARS-CoV-2) hospitalized on ventilators, researchers found that lying face down was better for the lungs. The research letter was published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

In "Lung Recruitability in SARS -- CoV-2 Associated Acute Respiratory Distress Syndrome: A Single-Center, Observational Study," Haibo Qiu, MD, Chun Pan, MD, and co-authors report on a retrospective study of the treatment of 12 patients in Wuhan Jinyintan Hospital, China, with severe COVID-19 infection-related acute respiratory distress syndrome (ARDS) who were assisted by mechanical ventilation. Drs. Qiu and Pan were in charge of the treatment of these patients, who were transferred from other treatment centers to Jinyintan Hospital.

A majority of patients admitted to the ICU with confirmed COVID-19 developed ARDS.

The observational study took place during a six-day period the week of Feb. 18, 2020.

"This study is the first description of the behavior of the lungs in patients with severe COVID-19 requiring mechanical ventilation and receiving positive pressure," said Dr. Qiu, professor, Department of Critical Care Medicine, Zhangda Hospital, School of Medicine, Southeast University, Nanjing, China. "It indicates that some patients do not respond well to high positive pressure and respond better to prone positioning in bed (facing downward)."

The clinicians in Wuhan used an index, the Recruitment-to-Inflation ratio, that measures the response of lungs to pressure (lung recruitability). Members of the research team, Lu Chen, PhD, and Laurent Brochard, PhD, HDR, from the University of Toronto, developed this index prior to this study.

The researchers assessed the effect of body positioning. Prone positioning was performed for 24-hour periods in which patients had persistently low levels of blood oxygenation. Oxygen flow, lung volume and airway pressure were measured by devices on patients' ventilators. Other measurements were taken, including the aeration of their airway passages and calculations were done to measure recruitability.

Seven patients received at least one session of prone positioning. Three patients received both prone positioning and ECMO (life support, replacing the function of heart and lungs). Three patients died.

Patients who did not receive prone positioning had poor lung recruitability, while alternating supine (face upward) and prone positioning was associated with increased lung recruitability.

"It is only a small number of patients, but our study shows that many patients did not re-open their lungs under high positive pressure and may be exposed to more harm than benefit in trying to increase the pressure," said Chun Pan, MD, also a professor with Zhongda Hospital, School of Medicine, Southeast University. "By contrast, the lung improves when the patient is in the prone position.

Considering this can be done, it is important for the management of patients with severe COVID-19 requiring mechanical ventilation."

The team consisted of scientists and clinicians affiliated with four Chinese and two Canadian hospitals, medical schools and universities.

https://www.sciencedaily.com/releases/2020/03/200324202056.htm

Anxious about COVID-19? Stress can have lasting impacts on sperm and future offspring

Study identifies biological mechanism by which stress alters sperm and impacts brain development in next generation

March 23, 2020

Science Daily/University of Maryland School of Medicine

Prolonged fear and anxiety brought on by major stressors, like the coronavirus pandemic, can not only take a toll on a person's mental health, but may also have a lasting impact on a man's sperm composition that could affect his future offspring. That is the finding of a provocative new study published in the journal Nature Communications by researchers at the University of Maryland School of Medicine.

The research outlines a biological mechanism for how a father's experience with stress can influence fetal brain development in the womb. The effects of paternal stress can be transferred to offspring through changes in the extracellular vesicles that then interact with maturing sperm. Extracellular vesicles are small membrane-bound particles that transport proteins, lipids, and nucleic acids between cells. They are produced in large amounts in the reproductive tract and play an integral role in sperm maturation.

"There are so many reasons that reducing stress is beneficial especially now when our stress levels are chronically elevated and will remain so for the next few months," said study corresponding author Tracy Bale, PhD, Professor of Pharmacology and Director of the Center for Epigenetic Research in Child Health & Brain Development at the University of Maryland School of Medicine. "Properly managing stress can not only improve mental health and other stress-related ailments, but it can also help reduce the potential lasting impact on the reproductive system that could impact future generations."

She and her colleagues did not specifically study those who were under stress due to the coronavirus pandemic.

To examine a novel biological role for extracellular vesicles in transferring dad's stress to sperm, the researchers examined extracellular vesicles from mice following treatment with the stress hormone corticosterone. After treatment, the extracellular vesicles showed dramatic changes in their overall size as well as their protein and small RNA content.

When sperm were incubated with these previously "stressed" extracellular vesicles prior to fertilizing an egg, the resulting mouse pups showed significant changes in patterns of early brain development, and as adults these mice were also significantly different than controls for how they responded to stress themselves.

To see if similar differences occurred in human sperm, the researchers recruited students from the University of Pennsylvania to donate sperm each month for six months, and complete questionnaires about their perceived stress state in the preceding month. They found that students who had experienced elevated stress in months prior showed significant changes in the small RNA content of their sperm, while those who had no change in stress levels experienced little or no change. These data confirm a very similar pattern found in the mouse study.

"Our study shows that the baby's brain develops differently if the father experienced a chronic period of stress before conception, but we still do not know the implications of these differences," said Dr. Bale. "Could this prolonged higher level of stress raise the risk for mental health issues in future offspring, or could experiencing stress and managing it well help to promote stress resilience? We don't really know at this point, but our data highlight why further studies are necessary."

The research team did find that stress-induced changes in the male reproductive system take place at least a month after the stress is attenuated and life has resumed its normal patterns. "It appears the body's adaptation to stress is to return to a new baseline," Dr. Bale said, "a post-stress physiological state -- termed allostasis."

This research was funded by the National Institute of Mental Health and included co-authors from the Institute for Genome Sciences at the University of Maryland School of Medicine and the Department of Pharmaceutical Science at the University of Maryland School of Pharmacy, as well as the University of Pennsylvania.

"This research represents a critical step in understanding important mechanisms that underlie the field of intergenerational epigenetics," said UMSOM Dean E. Albert Reece, MD, PhD, MBA, who is also the Executive Vice President for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor. "Such knowledge is crucial to identify early interventions to improve reproduction and early childhood development down the road."

While the study did not test stress management interventions to determine what effects they might have on attenuating the changes in sperm composition, Dr. Bale, who goes for regular runs to reduce the stress of the current COVID-19 pandemic, contends that any lifestyle habits that are good for the brain are likely good for the reproductive system.

"It is important to realize that social distancing does not have to mean social isolation, especially with modern technologies available to many of us," said Joshua Gordon, Director of the National Institute of Mental Health in his web message about coping with coronavirus. "Connecting with our friends and loved ones, whether by high tech means or through simple phone calls, can help us maintain ties during stressful days ahead and will give us strength to weather this difficult passage."

The Centers for Disease Control and Prevention has tips on "stress and coping" page on their COVID-19 site that recommends the following to "support yourself":

• Take breaks from watching, reading, or listening to news stories, including social media. Hearing about the pandemic repeatedly can be upsetting.

• Take care of your body. Take deep breaths, stretch, or meditate. Try to eat healthy, well-balanced meals, exercise regularly, get plenty of sleep, and avoid alcohol and drugs.

• Make time to unwind. Try to do some other activities you enjoy.

• Connect with others. Talk with people you trust about your concerns and how you are feeling.

https://www.sciencedaily.com/releases/2020/03/200323132410.htm

ACE inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19

March 23, 2020

Science Daily/Louisiana State University Health Sciences Center

James Diaz, MD, MHA, MPH & TM, Dr PH, Professor and Head of Environmental Health Sciences at LSU Health New Orleans School of Public Health, has proposed a possible explanation for the severe lung complications being seen in some people diagnosed with COVID-19. The manuscript was published by Oxford University Press online in the Journal of Travel Medicine.

The SARS beta coronaviruses, SARS-CoV, which caused the SARS (Severe Acute Respiratory Syndrome) outbreak in 2003 and the new SARS-CoV-2, which causes COVID-19, bind to angiotensin converting enzyme 2 (ACE2) receptors in the lower respiratory tracts of infected patients to gain entry into the lungs. Viral pneumonia and potentially fatal respiratory failure may result in susceptible persons after 10-14 days.

"Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are highly recommended medications for patients with cardiovascular diseases including heart attacks, high blood pressure, diabetes and chronic kidney disease to name a few," notes Dr. Diaz. "Many of those who develop these diseases are older adults. They are prescribed these medications and take them every day."

Research in experimental models has shown an increase in the number of ACE2 receptors in the cardiopulmonary circulation after intravenous infusions of ACE inhibitors.

"Since patients treated with ACEIs and ARBS will have increased numbers of ACE2 receptors in their lungs for coronavirus S proteins to bind to, they may be at increased risk of severe disease outcomes due to SARS-CoV-2infections," explains Diaz.

Diaz writes, this hypothesis is supported by a recent descriptive analysis of 1,099 patients with laboratory-confirmed COVID-19 infections treated in China during the reporting period, December 11, 2019, to January 29, 2020. This study reported more severe disease outcomes in patients with hypertension, coronary artery disease, diabetes and chronic renal disease. All patients with the diagnoses noted met the recommended indications for treatment with ACEIs or ARBs. Diaz says that two mechanisms may protect children from COVID-19 infections -- cross-protective antibodies from multiple upper respiratory tract infections caused by the common cold-causing alpha coronaviruses, and fewer ACE2 receptors in their lower respiratory tracts to attract the binding S proteins of the beta coronaviruses.

He recommends future case-control studies in patients with COVID-19 infections to further confirm chronic therapy with ACEIs or ARBs may raise the risk for severe outcomes.

In the meantime he cautions, "Patients treated with ACEIs and ARBs for cardiovascular diseases should not stop taking their medicine, but should avoid crowds, mass events, ocean cruises, prolonged air travel, and all persons with respiratory illnesses during the current COVID-19 outbreak in order to reduce their risks of infection."

https://www.sciencedaily.com/releases/2020/03/200323101354.htm

How to manage cancer care during COVID-19 pandemic

March 18, 2020

Science Daily/National Comprehensive Cancer Network

Experts from the Seattle Cancer Care Alliance (SCCA) -- a Member Institution of the National Comprehensive Cancer Network® (NCCN®) -- are sharing insights and advice on how to continue providing optimal cancer care during the novel coronavirus (COVID-19) pandemic. SCCA includes the Fred Hutchinson Cancer Research Center and the University of Washington, which are located in the epicenter of the COVID-19 outbreak in the United States.

"Responding quickly and confidently to the COVID-19 crisis is the health care challenge of our generation," said co-lead author F. Marc Stewart, MD, Medical Director, SCCA. "Our overarching goal is to keep our cancer patients and staff safe while continuing to provide compassionate, high-quality care under circumstances we've never had to face before. We are working around the clock to develop new guidelines and policies to address situations that we couldn't have imagined several weeks ago. When the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity."

"The COVID-19 pandemic is impacting every facet of our global and domestic societies and health care systems in unprecedented fashion," said Robert W. Carlson, MD, Chief Executive Officer, NCCN. "People with cancer appear to be at increased risk of COVID-19, and their outcomes are worse than individuals without cancer. The NCCN Member Institutions are rapidly gaining experience in preventing and managing COVID-19. As is the nature of the NCCN Member Institutions, they are sharing their experience in organizing and managing institutional and care systems responses and best practices in this rapidly evolving global effort."

The article stresses the importance of keeping channels of communication open between administrators and staff, patients, caregivers, and the general public. The authors recommend forming an Incident Command Structure (as illustrated below) to provide early coordination of institution-wide efforts and to rapidly respond to changing information. They highlight the need to remain flexible and ready for unexpected challenges.

Some of the anticipated challenges include:

• Staff shortages due to potential exposure and/or school closings

• Limitations of resources such as hospital beds, mechanical ventilation, and other equipment

• Impact on treatment from travel bans, including reduced access to international donors for allogeneic stem cell transplantation

The authors recommend mitigating some of these concerns through proactive measures that include:

• Providing patient information via handouts, signs, web-based communication, and a dedicated phone line for questions and triage

• Rescheduling "well" visits and elective surgeries, and deferring second opinion consultations (where care is already appropriately established)

• Increasing hours of general hospital operations to reduce the unnecessary use of emergency department resources

• Reinforcing a strict "stay at home when ill" policy and insuring staff have access to testing

• Restricting travel and enabling work-from-home wherever possible

• Prioritizing the use of soap and water over hand gel

• Limiting the number of team members who enter patients' rooms

• Considering lower thresholds for blood transfusions

• Moving some procedures from inpatient to outpatient

• Adopting a no visitor policy with rare exceptions such as end-of-life circumstances

• Having upfront, proactive palliative and end-of-life conversations with cancer patients who may become infected with COVID-19

The article also addresses the importance of self-care within and beyond the medical community. The authors call for the prioritization of measures to protect health and frontline staff and assure a safe work environment in order to prevent provider burnout. Those measures include compensation policies, reassignments to administrative roles for immunocompromised staff, and the creation of a back-up labor pool.

NCCN is also gathering documents and links from the leading cancer centers that comprise the nonprofit alliance, and sharing them all online at NCCN.org/covid-19. These include print outs for patient information, screening tools, visitation policies, and other essential forms. Hospitals worldwide are free to use or adapt these resources immediately. The site will be continuously updated as new resources become available.

Article link at NCCN.org/covid-19.

https://www.sciencedaily.com/releases/2020/03/200318143632.htm

Study reveals how long COVID-19 remains infectious on cardboard, metal and plastic

People may acquire coronavirus through air and by touching contaminated surfaces

March 20, 2020

Science Daily/University of California - Los Angeles

The virus that causes COVID-19 remains for several hours to days on surfaces and in aerosols, a new study published in the New England Journal of Medicine found.

The study suggests that people may acquire the coronavirus through the air and after touching contaminated objects. Scientists discovered the virus is detectable for up to three hours in aerosols, up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel.

"This virus is quite transmissible through relatively casual contact, making this pathogen very hard to contain," said James Lloyd-Smith, a co-author of the study and a UCLA professor of ecology and evolutionary biology. "If you're touching items that someone else has recently handled, be aware they could be contaminated and wash your hands."

The study attempted to mimic the virus being deposited onto everyday surfaces in a household or hospital setting by an infected person through coughing or touching objects, for example. The scientists then investigated how long the virus remained infectious on these surfaces.

The study's authors are from UCLA, the National Institutes of Health's National Institute of Allergy and Infectious Diseases, the Centers for Disease Control and Prevention, and Princeton University. They include Amandine Gamble, a UCLA postdoctoral researcher in Lloyd-Smith's laboratory.

In February, Lloyd-Smith and colleagues reported in the journal eLife that screening travelers for COVID-19 is not very effective. People infected with the virus -- officially named SARS-CoV-2 -- may be spreading the virus without knowing they have it or before symptoms appear. Lloyd-Smith said the biology and epidemiology of the virus make infection extremely difficult to detect in its early stages because the majority of cases show no symptoms for five days or longer after exposure.

"Many people won't have developed symptoms yet," Lloyd-Smith said. "Based on our earlier analysis of flu pandemic data, many people may not choose to disclose if they do know."

The new study supports guidance from public health professionals to slow the spread of COVID-19:

• Avoid close contact with people who are sick.

• Avoid touching your eyes, nose and mouth.

• Stay home when you are sick.

• Cover coughs or sneezes with a tissue, and dispose of the tissue in the trash.

• Clean and disinfect frequently touched objects and surfaces using a household cleaning spray or wipe.

https://www.sciencedaily.com/releases/2020/03/200320192755.htm

New coronavirus stable for hours on surfaces

SARS-CoV-2 stability similar to original SARS virus

March 17, 2020

Science Daily/NIH/National Institute of Allergy and Infectious Diseases

The virus that causes coronavirus disease 2019 (COVID-19) is stable for several hours to days in aerosols and on surfaces, according to a new study from National Institutes of Health, CDC, UCLA and Princeton University scientists in The New England Journal of Medicine.

The scientists found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detectable in aerosols for up to three hours, up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel. The results provide key information about the stability of SARS-CoV-2, which causes COVID-19 disease, and suggests that people may acquire the virus through the air and after touching contaminated objects. The study information was widely shared during the past two weeks after the researchers placed the contents on a preprint server to quickly share their data with colleagues.

The NIH scientists, from the National Institute of Allergy and Infectious Diseases' Montana facility at Rocky Mountain Laboratories, compared how the environment affects SARS-CoV-2 and SARS-CoV-1, which causes SARS. SARS-CoV-1, like its successor now circulating across the globe, emerged from China and infected more than 8,000 people in 2002 and 2003. SARS-CoV-1 was eradicated by intensive contact tracing and case isolation measures and no cases have been detected since 2004. SARS-CoV-1 is the human coronavirus most closely related to SARS-CoV-2. In the stability study the two viruses behaved similarly, which unfortunately fails to explain why COVID-19 has become a much larger outbreak.

The NIH study attempted to mimic virus being deposited from an infected person onto everyday surfaces in a household or hospital setting, such as through coughing or touching objects. The scientists then investigated how long the virus remained infectious on these surfaces.

The scientists highlighted additional observations from their study:

• If the viability of the two coronaviruses is similar, why is SARS-CoV-2 resulting in more cases? Emerging evidence suggests that people infected with SARS-CoV-2 might be spreading virus without recognizing, or prior to recognizing, symptoms. This would make disease control measures that were effective against SARS-CoV-1 less effective against its successor.

• In contrast to SARS-CoV-1, most secondary cases of virus transmission of SARS-CoV-2 appear to be occurring in community settings rather than healthcare settings. However, healthcare settings are also vulnerable to the introduction and spread of SARS-CoV-2, and the stability of SARS-CoV-2 in aerosols and on surfaces likely contributes to transmission of the virus in healthcare settings.

The findings affirm the guidance from public health professionals to use precautions similar to those for influenza and other respiratory viruses to prevent the spread of SARS-CoV-2:

• Avoid close contact with people who are sick.

• Avoid touching your eyes, nose, and mouth.

• Stay home when you are sick.

• Cover your cough or sneeze with a tissue, then throw the tissue in the trash.

• Clean and disinfect frequently touched objects and surfaces using a regular household cleaning spray or wipe. 

  https://www.sciencedaily.com/releases/2020/03/200317150116.htm

Understanding how COVID-19 affects children vital to slowing pandemic

March 19, 2020

Science Daily/University of Virginia Health System

Though COVID-19 so far appears to be largely sparing children, researchers are cautioning that it is critical to understand how the virus affects kids to model the pandemic accurately, limit the disease's spread and ensure the youngest patients get the care they need.The warning comes from Steven L. Zeichner, MD, PhD, the head of UVA Health's Division of Pediatric Infectious Diseases, and Andrea T. Cruz, MD, MPH, a pediatric emergency medicine physician at Houston's Baylor College of Medicine. They have authored a commentary in the journal Pediatrics accompanying a new article that reveals a small percentage of infected children become seriously ill. Those at greatest risk include babies and preschoolers.

"Many infectious diseases affect children differently than adults and understanding those differences can yield important insights," the commentary authors write. "This will likely be true for COVID-19, just as it was for older infectious diseases."

Assessing COVID-19 Risks

Zeichner and Cruz note that there are subgroups of children who appear to be at greater risk of COVID-19 complications, particularly those who are younger, immunocompromised or have other pulmonary health problems.

However, the presence of other viral infections in up to two-thirds of childhood coronavirus cases makes it very difficult to assess the true effect of COVID-19 on children, they state. (This figure is based on prior studies of children with coronaviruses detectable in the respiratory tract.)

While much remains unknown, Cruz and Zeichner caution that children, even asymptomatic children, could play a "major role" in disease transmission. For example, they cite a study that found the virus remained in children's stool for several weeks after diagnosis. That, combined with other routes of transmission such as nasal secretions, could pose a major challenge for schools, day care centers and the children's families, they note.

"Since many children infected with COVID-19 appear to have have mild symptoms, or even no symptoms at all, it is important to practice all the social distancing, hygiene and other precautions being recommended by public health authorities to minimize transmission from children to others, including family members who may be at greater risk from the infection, such as grandparents or family members with chronic medical conditions," said Zeichner, who is working on innovative potential COVID-19 vaccines in his lab. "In addition, studies of the reasons why children are affected differently than adults by the infection may yield insights that can be helpful in understanding the disease and ways to treat or prevent it."

https://www.sciencedaily.com/releases/2020/03/200319125201.htm

COVID-19 coronavirus epidemic has a natural origin

 March 17, 2020

Science Daily/Scripps Research Institute

An analysis of public genome sequence data from SARS-CoV-2 and related viruses found no evidence that the virus was made in a laboratory or otherwise engineered.

The novel SARS-CoV-2 coronavirus that emerged in the city of Wuhan, China, last year and has since caused a large scale COVID-19 epidemic and spread to more than 70 other countries is the product of natural evolution, according to findings published today in the journal Nature Medicine.

The analysis of public genome sequence data from SARS-CoV-2 and related viruses found no evidence that the virus was made in a laboratory or otherwise engineered.

"By comparing the available genome sequence data for known coronavirus strains, we can firmly determine that SARS-CoV-2 originated through natural processes," said Kristian Andersen, PhD, an associate professor of immunology and microbiology at Scripps Research and corresponding author on the paper.

In addition to Andersen, authors on the paper, "The proximal origin of SARS-CoV-2," include Robert F. Garry, of Tulane University; Edward Holmes, of the University of Sydney; Andrew Rambaut, of University of Edinburgh; W. Ian Lipkin, of Columbia University.

Coronaviruses are a large family of viruses that can cause illnesses ranging widely in severity. The first known severe illness caused by a coronavirus emerged with the 2003 Severe Acute Respiratory Syndrome (SARS) epidemic in China. A second outbreak of severe illness began in 2012 in Saudi Arabia with the Middle East Respiratory Syndrome (MERS).

On December 31 of last year, Chinese authorities alerted the World Health Organization of an outbreak of a novel strain of coronavirus causing severe illness, which was subsequently named SARS-CoV-2. As of February 20, 2020, nearly 167,500 COVID-19 cases have been documented, although many more mild cases have likely gone undiagnosed. The virus has killed over 6,600 people.

Shortly after the epidemic began, Chinese scientists sequenced the genome of SARS-CoV-2 and made the data available to researchers worldwide. The resulting genomic sequence data has shown that Chinese authorities rapidly detected the epidemic and that the number of COVID-19 cases have been increasing because of human to human transmission after a single introduction into the human population. Andersen and collaborators at several other research institutions used this sequencing data to explore the origins and evolution of SARS-CoV-2 by focusing in on several tell-tale features of the virus.

The scientists analyzed the genetic template for spike proteins, armatures on the outside of the virus that it uses to grab and penetrate the outer walls of human and animal cells. More specifically, they focused on two important features of the spike protein: the receptor-binding domain (RBD), a kind of grappling hook that grips onto host cells, and the cleavage site, a molecular can opener that allows the virus to crack open and enter host cells.

Evidence for natural evolution

The scientists found that the RBD portion of the SARS-CoV-2 spike proteins had evolved to effectively target a molecular feature on the outside of human cells called ACE2, a receptor involved in regulating blood pressure. The SARS-CoV-2 spike protein was so effective at binding the human cells, in fact, that the scientists concluded it was the result of natural selection and not the product of genetic engineering.

This evidence for natural evolution was supported by data on SARS-CoV-2's backbone -- its overall molecular structure. If someone were seeking to engineer a new coronavirus as a pathogen, they would have constructed it from the backbone of a virus known to cause illness. But the scientists found that the SARS-CoV-2 backbone differed substantially from those of already known coronaviruses and mostly resembled related viruses found in bats and pangolins.

"These two features of the virus, the mutations in the RBD portion of the spike protein and its distinct backbone, rules out laboratory manipulation as a potential origin for SARS-CoV-2" said Andersen.

Josie Golding, PhD, epidemics lead at UK-based Wellcome Trust, said the findings by Andersen and his colleagues are "crucially important to bring an evidence-based view to the rumors that have been circulating about the origins of the virus (SARS-CoV-2) causing COVID-19."

"They conclude that the virus is the product of natural evolution," Goulding adds, "ending any speculation about deliberate genetic engineering."

Possible origins of the virus

Based on their genomic sequencing analysis, Andersen and his collaborators concluded that the most likely origins for SARS-CoV-2 followed one of two possible scenarios.

In one scenario, the virus evolved to its current pathogenic state through natural selection in a non-human host and then jumped to humans. This is how previous coronavirus outbreaks have emerged, with humans contracting the virus after direct exposure to civets (SARS) and camels (MERS). The researchers proposed bats as the most likely reservoir for SARS-CoV-2 as it is very similar to a bat coronavirus. There are no documented cases of direct bat-human transmission, however, suggesting that an intermediate host was likely involved between bats and humans.

In this scenario, both of the distinctive features of SARS-CoV-2's spike protein -- the RBD portion that binds to cells and the cleavage site that opens the virus up -- would have evolved to their current state prior to entering humans. In this case, the current epidemic would probably have emerged rapidly as soon as humans were infected, as the virus would have already evolved the features that make it pathogenic and able to spread between people.

In the other proposed scenario, a non-pathogenic version of the virus jumped from an animal host into humans and then evolved to its current pathogenic state within the human population. For instance, some coronaviruses from pangolins, armadillo-like mammals found in Asia and Africa, have an RBD structure very similar to that of SARS-CoV-2. A coronavirus from a pangolin could possibly have been transmitted to a human, either directly or through an intermediary host such as civets or ferrets.

Then the other distinct spike protein characteristic of SARS-CoV-2, the cleavage site, could have evolved within a human host, possibly via limited undetected circulation in the human population prior to the beginning of the epidemic. The researchers found that the SARS-CoV-2 cleavage site, appears similar to the cleavage sites of strains of bird flu that has been shown to transmit easily between people. SARS-CoV-2 could have evolved such a virulent cleavage site in human cells and soon kicked off the current epidemic, as the coronavirus would possibly have become far more capable of spreading between people.

Study co-author Andrew Rambaut cautioned that it is difficult if not impossible to know at this point which of the scenarios is most likely. If the SARS-CoV-2 entered humans in its current pathogenic form from an animal source, it raises the probability of future outbreaks, as the illness-causing strain of the virus could still be circulating in the animal population and might once again jump into humans. The chances are lower of a non-pathogenic coronavirus entering the human population and then evolving properties similar to SARS-CoV-2.

Funding for the research was provided by the US National Institutes of Health, the Pew Charitable Trusts, the Wellcome Trust, the European Research Council, and an ARC Australian Laureate Fellowship.

https://www.sciencedaily.com/releases/2020/03/200317175442.htm

Median incubation period for COVID-19

March 17, 2020

Science Daily/University of Massachusetts Amherst

A new study calculates that the median incubation period for COVID-19 is just over 5 days and that 97.5% of people who develop symptoms will do so within 11.5 days of infection.

A University of Massachusetts Amherst biostatistician who directs the UMass-based Flu Forecasting Center of Excellence was invited by the White House Coronavirus Task Force to participate Wednesday morning in a coronavirus modeling webinar.

The four-hour, virtual gathering will include 20 of the world's leading infectious disease and pandemic forecasting modelers, from researchers at Harvard, Johns Hopkins and the Centers for Disease Control and Prevention (CDC) in the U.S. to those based at institutions in England, Hong Kong, South Africa and the Netherlands.

According to the White House Coronavirus Task Force coordinator Dr. Charles Vitek, "This webinar is designed to highlight for the Task Force what modeling can tell us regarding the potential effects of mitigation measures on the coronavirus outbreak. The unprecedented speed and impact of the nCoV-19 epidemic requires the best-informed public health decision-making we can produce."

Nicholas Reich, associate professor in the School of Public Health and Health Sciences, heads a flu forecasting collaborative that has produced some of the world's most accurate models in recent years. He and postdoctoral researcher Thomas McAndrew have been conducting weekly surveys of more than 20 infectious disease modeling researchers to assess their collective expert opinion on the trajectory of the COVID-19 outbreak in the U.S. The researchers and modeling experts design, build and interpret models to explain and understand infectious disease dynamics and the associated policy implications in human populations.

Reich is co-author of a new study in the Annals of Internal Medicine that calculates that the median incubation period for COVID-19 is just over five days and that 97.5 percent of people who develop symptoms will do so within 11.5 days of infection. The incubation period refers to the time between exposure to the virus and the appearance of the first symptoms.

The study's lead author is UMass Amherst biostatistics doctoral alumnus Stephen Lauer, a former member of the Reich Lab and current postdoctoral researcher at the Johns Hopkins Bloomberg School of Public Health.

The researchers examined 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. They conclude that "the current period of active monitoring recommended by the U.S. Centers for Disease Control and Prevention [14 days] is well supported by the evidence."

https://www.sciencedaily.com/releases/2020/03/200317175438.htm

COVID-19: The immune system can fight back

March 17, 2020

Science Daily/University of Melbourne

Melbourne researchers have mapped immune responses from one of Australia's first novel coronavirus (COVID-19) patients, showing the body's ability to fight the virus and recover from the infection.

Researchers at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) -- a joint venture between the University of Melbourne and the Royal Melbourne hospital -- were able to test blood samples at four different time points in an otherwise healthy woman in her 40s, who presented with COVID-19 and had mild-to-moderate symptoms requiring hospital admission.

Published today in Nature Medicine is a detailed report of how the patient's immune system responded to the virus. One of the authors on the paper, research fellow Dr Oanh Nguyen said this was the first time that broad immune responses to COVID-19 have been reported.

"We looked at the whole breadth of the immune response in this patient using the knowledge we have built over many years of looking at immune responses in patients hospitalised with influenza," Dr Nguyen said.

"Three days after the patient was admitted, we saw large populations of several immune cells, which are often a tell-tale sign of recovery during seasonal influenza infection, so we predicted that the patient would recover in three days, which is what happened."

The research team was able to do this research so rapidly thanks to SETREP-ID (Sentinel Travellers and Research Preparedness for Emerging Infectious Disease), led by Royal Melbourne Hospital Infectious Diseases Physician Dr Irani Thevarajan at the Doherty Institute.

SETREP-ID is a platform that enables a broad range of biological sampling to take place in returned travellers in the event of a new and unexpected infectious disease outbreak, which is exactly how COVID-19 started in Australia.

"When COVID-19 emerged, we already had ethics and protocols in place so we could rapidly start looking at the virus and immune system in great detail," Dr Thevarajan said.

"Already established at a number of Melbourne hospitals, we now plan to roll out SETREP-ID as a national study."

Working together with University of Melbourne Professor Katherine Kedzierska, a laboratory head at the Doherty Institute and a world-leading influenza immunology researcher, the team were able to dissect the immune response leading to successful recovery from COVID-19, which might be the secret to finding an effective vaccine.

"We showed that even though COVID-19 is caused by a new virus, in an otherwise healthy person, a robust immune response across different cell types was associated with clinical recovery, similar to what we see in influenza," Professor Kedzierska said.

"This is an incredible step forward in understanding what drives recovery of COVID-19. People can use our methods to understand the immune responses in larger COVID-19 cohorts, and also understand what's lacking in those who have fatal outcomes."

Dr Thevarajan said that current estimates show more than 80 per cent of COVID-19 cases are mild-to-moderate, and understanding the immune response in these mild cases is very important research.

"We hope to now expand our work nationally and internationally to understand why some people die from COVID-19, and build further knowledge to assist in the rapid response of COVID-19 and future emerging viruses," she said.

https://www.sciencedaily.com/releases/2020/03/200317103815.htm

New Yorkers and Coronavirus -- Support for school closures, while most feel not at risk

Most people changing their behavior because of Coronavirus

March 16, 2020

Science Daily/CUNY Graduate School of Public Health and Health Policy

A new CUNY Graduate School of Public Health and Health Policy (CUNY SPH) survey released today found that 60% of New York State residents believe their chances of contracting the novel Coronavirus are low or very low. The survey of 1000 New York households, conducted between March 13-15, 2020 and considered accurate within a range of 3%, also found that more than half (55%) of all respondents live in households with one or more members over age 60, the highest risk age group for Coronavirus infection. However, just more than one-fourth (27%) of them believed that they were living with someone who has a high chance of becoming sick. In general, a bare majority of New Yorkers (51%) said they have some knowledge of Coronavirus, while 34% believed they know a lot about it.

A substantial majority of New York residents believe that current policies help in containing the virus, including closing schools and universities (68%), limiting travel to and from certain countries (69%), and two weeks of quarantine for people exposed to the virus (71%).

Messages about ways to prevent the spread of the virus have led many residents to change their plans and routines in the past week. Almost one-fourth (24%) of respondents reported they did not attend an event they had paid for due to concerns about the virus, and almost two in five respondents (39%) decided to stay home instead of going to work or changed existing travel plans (40%). Almost three in five (57%) said they had stayed at home instead of going to a restaurant or movie, and almost two-thirds (64%) say they have avoided shaking hands or hugging. The single recommendation that most respondents reported following regarded handwashing. Nine out of ten (88%) of New Yorkers reporting they increased the frequency of which they wash their hands or used hand sanitizer.

Almost three New Yorkers in ten (29%) rated television news ranked as the most trusted source of information about Coronavirus, followed by the CDC at 26%, and the WHO at 15%. Only 7% of respondents reported that President Trump was their most trusted source of information.

While an equally low percentage of respondents said social media were their most trusted information source, most people (51%) reported that they do share information on Coronavirus on these platforms at least once a day. Three in ten (30%) said they have passed along information on social media about Coronavirus without knowing it was accurate. The most frequently used online media sources respondents reported using were news media posts (36%), followed by friends (27%) and the government (20%).

"We conducted this survey and will update it regularly over the course of this public health crisis as a part of our unique mission within the City's largest public university," said CUNY SPH Dean Ayman El Mohandes. "Working together promoting evidence-based communication with innovative approaches for individual and community action, we can and will help address the threat of COVID-19."

The CUNY SPH survey was conducted by Emerson College Polling from March 13-15, 2020. The sample for the NY Statewide results, n=1,000, with a Credibility Interval (CI) similar to a poll's margin of error (MOE) of +/- 3 percentage points. The data sets were weighted by gender, age, ethnicity, education and region based on the 2018 1-year American Community Survey model. It is important to remember that subsets based on gender, age, ethnicity and region carry with them higher margins of error, as the sample size is reduced. Data was collected using an Interactive Voice Response (IVR) system of landlines (n=477), SMS-to-online (n=360) and an online panel provided by MTurk and Survey Monkey (n=166).

The CUNY Graduate School of Public Health and Health Policy (CUNY SPH) is committed to teaching, research and service that creates a healthier New York City and helps promote equitable, efficient and evidence-based solutions to pressing health problems facing cities around the world.

https://www.sciencedaily.com/releases/2020/03/200316141550.htm

COVID-19 appears less severe in children

March 13, 2020

Science Daily/Wolters Kluwer Health

As outbreaks of COVID-19 disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue worldwide, there's reassuring evidence that children have fewer symptoms and less severe disease. That's among the insights provided by an expert review in The Pediatric Infectious Disease Journal, the official journal of The European Society for Paediatric Infectious Diseases. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Like previous epidemic coronaviruses, "SARS-CoV-2 [seems] to cause fewer symptoms and less severe disease in children compared with adults," according to the review by Petra Zimmerman, MD, PhD, of the University of Fribourg, Switzerland and Nigel Curtis, FRCPCH, PhD, of The University of Melbourne, Australia. They summarize available evidence on coronavirus infections in children, including COVID-19.

"There is some suggestion that children are just as likely as adults to become infected with the virus but are less likely to be unwell or develop severe symptoms," Drs. Zimmerman and Curtis write. "However, the importance of children in transmitting the virus remains uncertain."

The Evidence on SARS-CoV-2 -- Focusing on Risks to Children

Coronaviruses are a large family of viruses that can cause infection and disease in animals. "Coronaviruses are capable of rapid mutation and recombination, leading to novel coronaviruses that can spread from animals to humans," Drs. Zimmerman and Curtis write. There are four coronaviruses that circulate in humans, mostly causing respiratory and gastrointestinal symptoms -- ranging from the common cold to severe disease.

Over the past two decades, there have been three major disease outbreaks due to novel coronaviruses: SARS-CoV in 2002, MERS-CoV in 2012, and now SARS-CoV-2 in 2019. Arising in the Chinese city of Wuhan, SARS-Cov-2 spread rapidly around the world and has been declared a pandemic by the World Health Organization. "The term COVID-19 is used for the clinical disease caused by SARS-CoV-2," according to the authors. Transmission of SARS-CoV-2 appears similar to that of the related SARS and MERS coronaviruses, but with a lower fatality rate. SARS-CoV-2 can still cause serious and life-threatening infections -- particularly in older people and those with pre-existing health conditions.

What are the risks for children from SARS-CoV-2? It's a pressing question for pediatric infectious disease specialists and concerned parents alike. Children appear to have milder clinical symptoms than adults and to be at substantially lower risk of severe disease -- which was also true in the SARS and MERS epidemics.

In Chinese data from February 2020, children and adolescents accounted for only two percent of SARS-CoV-2 hospitalizations, Drs. Zimmerman and Curtis write. However, as children are less frequently symptomatic and have less severe symptoms they are less often tested, which might lead to an underestimate of the true numbers infected. Also, children are less frequently exposed to the main sources of transmission.

Again based on Chinese data, "Most infected children recover one to two weeks after the onset of symptoms, and no deaths had been reported by February 2020," the researchers add. Most reported infections with SARS-CoV-2 have occurred in children with a documented household contact. Children with COVID-19 may be more likely to develop gastrointestinal symptoms.

The experts also review the diagnostic findings (laboratory tests and imaging studies) of children with COVID-19 laboratory and imaging findings in children. Whole genome sequencing approaches have enabled rapid development of molecular diagnostic tests for SARS-CoV-2. For now, treatment is supportive; no specific antiviral medications are available.

Several approaches are being considered for development of new drugs and vaccines -- some targeting a "spike glycoprotein" involved in interactions between coronaviruses and cells. Until such treatment and preventive measures are available, the researchers emphasize the importance of the full range of strategies for controlling SARS-CoV-2 -- as for the "highly effective global public health response" that led to containment of the SARS epidemic.

https://www.sciencedaily.com/releases/2020/03/200313112145.htm