Study helps to identify medications which are safe to use in treatment of COVID-19

March 30, 2020

Science Daily/King's College London

A recent study has found that there is no evidence for or against the use of non-steroidal anti-inflammatory drugs such as ibuprofen for patients with COVID-19.

The study, led by researchers at King's College London, also found other types of drugs, such as TNF blockers and JAK inhibitors safe to use.

89 existing studies on other coronavirus strains such as MERS and SARS, as well as the limited literature on COVID-19, were analysed to find out if certain pain medications, steroids, and other drugs used in people already suffering from diseases should be avoided if they catch COVID-19.

Some patients, for example those with cancer, are already given immunosuppressive drugs -- therapies that can lower the body's immune system -- or immunostimulant drugs -- therapies that boost it. If these patients then catch COVID-19, doctors need to know what medication to stop.

Dr Mieke Van Hemelrijck, a cancer epidemiologist and an author on the paper, said "This pandemic has led to challenging decision-making about the treatment of COVID-19 patients who were already critically unwell. In parallel, doctors across multiple specialties are making clinical decisions about the appropriate continuation of treatments for patients with chronic illnesses requiring immune suppressive medication."

The article has been published in ecancermedicalscience, an open access oncology journal, and is authored by researchers from King's College London and Guy's and St. Thomas NHS Foundation Trust, London.

There had been some speculation that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen might make things worse for some COVID-19 patients, but the researchers did not find evidence to support this statement.

Other types of drugs such as TNF blockers and JAK inhibitors, used to treat arthritis or other forms of inflammation, were also found to be safe to use. Another class of drug known as anti-interleukin-6 agents is being investigated for helping to fight COVID-19, although there is no conclusive proof yet.

The researchers found that low amounts of prednisolone or tacrolimus therapy may be helpful in treating COVID-19. Co- author, Dr Sophie Papa, a medical oncologist and immunologist said: "Current evidence suggests that low dose prednisolone (a steroid used to treat allergies) and tacrolimus therapy (an immunosuppressive drug given to patients who have had an organ transplant) may have beneficial impact on the course of coronavirus infections. However further investigation is needed."

As more people catch the disease, researchers will continue to investigate how it interacts with commonly used medications and make further guidance recommendations.

https://www.sciencedaily.com/releases/2020/03/200330152143.htm

Experimental AI tool predicts which COVID-19 patients develop respiratory disease

March 30, 2020

Science Daily/NYU Langone Health / NYU School of Medicine

An artificial intelligence tool accurately predicted which patients newly infected with the COVID-19 virus would go on to develop severe respiratory disease, a new study found.

The work was led by NYU Grossman School of Medicine and the Courant Institute of Mathematical Sciences at New York University, in partnership with Wenzhou Central Hospital and Cangnan People's Hospital, both in Wenzhou, China.

Named "SARS-CoV-2," the new virus causes the disease called "coronavirus disease 2019" or "COVID-19." As of March 30, the virus had infected 735,560 patients worldwide. According to the World Health Organization, the illness has caused more than 34,830 deaths to date, more often among older patients with underlying health conditions. The New York State Department of Health has reported more than 33,700 cases to date in New York City.

Published online March 30 in the journal Computers, Materials & Continua, the study also revealed the best indicators of future severity, and found that they were not as expected.

"While work remains to further validate our model, it holds promise as another tool to predict the patients most vulnerable to the virus, but only in support of physicians' hard-won clinical experience in treating viral infections," says corresponding study author Megan Coffee, MD, PhD, clinical assistant professor in the Division of Infectious Disease & Immunology within the Department of Medicine at NYU Grossman School of Medicine.

"Our goal was to design and deploy a decision-support tool using AI capabilities -- mostly predictive analytics -- to flag future clinical coronavirus severity," says co-author Anasse Bari, PhD, a clinical assistant professor in Computer Science at the Courant institute. "We hope that the tool, when fully developed, will be useful to physicians as they assess which moderately ill patients really need beds, and who can safely go home, with hospital resources stretched thin."

Surprise Predictors 

For the study, demographic, laboratory, and radiological findings were collected from 53 patients as each tested positive in January 2020 for the SARS-CoV2 virus at the two Chinese hospitals. Symptoms were typically mild to begin with, including cough, fever, and stomach upset. In a minority of patients, however, severe symptoms developed with a week, including pneumonia.

The goal of the new study was to determine whether AI techniques could help to accurately predict which patients with the virus would go on to develop Acute Respiratory Distress Syndrome or ARDS, the fluid build-up in the lungs that can be fatal in the elderly.

For the new study, the researchers designed computer models that make decisions based on the data fed into them, with programs getting "smarter" the more data they consider. Specifically, the current study used decision trees that track series of decisions between options, and that model the potential consequences of choices at each step in a pathway.

The researchers were surprised to find that characteristics considered to be hallmarks of COVID-19, like certain patterns seen in lung images (e.g. ground glass opacities), fever, and strong immune responses, were not useful in predicting which of the many patients with initial, mild symptoms would go to develop severe lung disease. Neither were age and gender helpful in predicting serious disease, although past studies had found men over 60 to be at higher risk.

Instead, the new AI tool found that changes in three features -- levels of the liver enzyme alanine aminotransferase (ALT), reported myalgia, and hemoglobin levels -- were most accurately predictive of subsequent, severe disease. Together with other factors, the team reported being able to predict risk of ARDS with up to 80 percent accuracy.

ALT levels -- which rise dramatically as diseases like hepatitis damage the liver -- were only a bit higher in patients with COVID-19, researchers say, but still featured prominently in prediction of severity. In addition, deep muscle aches (myalgia) were also more commonplace, and have been linked by past research to higher general inflammation in the body.

Lastly, higher levels of hemoglobin, the iron-containing protein that enables blood cells to carry oxygen to bodily tissues, were also linked to later respiratory distress. Could this explained by other factors, like unreported smoking of tobacco, which has long been linked to increased hemoglobin levels? Of the 33 patients at Wenzhou Central Hospital interviewed on smoking status, the two who reported having smoked, also reported that they had quit.

Limitations of the study, say the authors, included the relatively small data set and the limited clinical severity of disease in the population studied. The latter may be due in part to an as yet unexplained dearth of elderly patients admitted into the hospitals during the study period. The average patient age was 43.

"I will be paying more attention in my clinical practice to our data points, watching patients closer if they for instance complain of severe myalgia," adds Coffee. "It's exciting to be able to share data with the field in real time when it can be useful. In all past epidemics, journal papers only published well after the infections had waned."

https://www.sciencedaily.com/releases/2020/03/200330152135.htm

Lessons from the Spanish flu: Early restrictions lowered disease, mortality rates

March 30, 2020

Science Daily/Loyola University Health System

A review of published data and analysis on the Spanish flu, found that cities that adopted early and broad isolation and prevention measures had disease and mortality rates that were 30% to 50% lower than other cities.

Large events are cancelled, restaurants and non-essential businesses are closed, and in many states, residents have been asked to shelter in place, all to limit the spread and impact of the COVID-19 virus. But are strict and early isolation and other preventative mandates really effective in minimizing the spread and impact of a disease outbreak?

Stefan E. Pambuccian, MD, a Loyola Medicine cytologist, surgical pathologist and professor and vice chair of the Department of Pathology and Laboratory Medicine at Loyola University Chicago Stritch School of Medicine, has reviewed published data and research from three papers dating back to the 1918-19 Spanish flu pandemic, which infected one-fifth to one-third of the world's population and killed 50 million people.

According to the data and analysis, cities that adopted early, broad isolation and prevention measures -- closing of schools and churches, banning of mass gatherings, mandated mask wearing, case isolation and disinfection/hygiene measures -- had lower disease and mortality rates. These cities included San Francisco, St. Louis, Milwaukee and Kansas City, which collectively had 30% to 50% lower disease and mortality rates than cities that enacted fewer and later restrictions. One analysis showed that these cities also had greater delays in reaching peak mortality, and the duration of these measures correlated with a reduced total mortality burden.

"The stricter the isolation policies, the lower the mortality rate," says Dr. Pambuccian. He studied the Spanish flu, including prevention measures and outcomes, to help develop standards for staffing and safety in the cytology lab, where infectious diseases like the COVID-19 virus are diagnosed and studied at the cellular level. His broader article appeared online this week in the Journal of the American Society of Cytopathology.

Like today, not everyone in 1918 and 1919 thought the strict measures were appropriate or effective at the time.

An estimated 675,000 people died in the U.S. from the Spanish flu, "and there was skepticism that these policies were actually working," says Dr. Pambuccian. "But they obviously did make a difference."

In 1918, the world was still at war "with overcrowded barracks," and much of the U.S. lived with "poverty, poor nutrition, poor hygiene, household/community-level crowding, and a lack of preparation of the population and decision makers due to cognitive inertia and poor medical and insufficient nursing care," says Dr. Pambuccian.

"Although the world is a much different place than it was 100 years ago, the efficacy of the measures instituted during the 1918-19 pandemic gives us hope that the current measures will also limit the impact of the COVID-19 pandemic."

https://www.sciencedaily.com/releases/2020/03/200330110344.htm

Some COVID-19 patients still have coronavirus after symptoms disappear

March 27, 2020

Science Daily/American Thoracic Society

Researchers found that half of the patients they treated for mild COVID-19 infection still had coronavirus for up to eight days after symptoms disappeared.

In a new study, researchers found that half of the patients they treated for mild COVID-19 infection still had coronavirus for up to eight days after symptoms disappeared. The research letter was published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

In "Time Kinetics of Viral Clearance and Resolution of Symptoms in Novel Coronavirus Infection," Lixin Xie, MD, Lokesh Sharma, PhD, and co-authors report on a study of 16 patients with COVID-19, who were treated and released from the Treatment Center of PLA General Hospital in Beijing between January 28 and Feb. 9, 2020. Patients studied had a median age of 35.5 years.

Researchers collected samples from throat swabs taken from all patients on alternate days and analyzed. Patients were discharged after their recovery and confirmation of negative viral status by at least two consecutive polymerase chain reaction (PCR) tests.

"The most significant finding from our study is that half of the patients kept shedding the virus even after resolution of their symptoms," said co-lead author Dr. Sharma, instructor of medicine, Section of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, Yale School of Medicine. "More severe infections may have even longer shedding times."

The primary symptoms in these patients included fever, cough, pain in the pharynx (pharyngalgia) and difficult or labored breathing (dyspnea). Patients were treated with a range of medications.

The time from infection to onset of symptoms (incubation period) was five days among all but one patient. The average duration of symptoms was eight days, while the length of time patients remained contagious after the end of their symptoms ranged from one to eight days. Two patients had diabetes and one had tuberculosis, neither of which affected the timing of the course of COVID-19 infection.

"If you had mild respiratory symptoms from COVID-19 and were staying at home so as not to infect people, extend your quarantine for another two weeks after recovery to ensure that you don't infect other people," recommended corresponding author Lixin Xie, MD, professor, College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing.

The authors had a special message for the medical community: "COVID-19 patients can be infectious even after their symptomatic recovery, so treat the asymptomatic/recently recovered patients as carefully as symptomatic patients."

The researchers emphasized that all of these patients had milder infections and recovered from the disease, and that the study looked at a small number of patients. They noted that it is unclear whether similar results would hold true for more vulnerable patients such as the elderly, those with suppressed immune systems and patients on immunosuppressive therapies.

"Further studies are needed to investigate if the real-time PCR-detected virus is capable of transmission in the later stages of COVID-19 infection," Dr. Xie added.

https://www.sciencedaily.com/releases/2020/03/200327091234.htm

New research sheds light on potentially negative effects of cannabis

March 30, 2020

Science Daily/Washington State University

Coughing fits, anxiety and paranoia are three of the most common adverse reactions to cannabis, according to a recent study by Washington State University researchers.

The researchers surveyed more than 1,500 college students on the type and frequency of adverse reactions they had experienced while using cannabis for their study in the Journal of Cannabis Research. They also collected information on the students' demographics, personality traits, cannabis use patterns and motives for using the drug.

"There's been surprisingly little research on the prevalence or frequency of various adverse reactions to cannabis and almost no research trying to predict who is more likely to experience these types of adverse reactions," said Carrie Cuttler, assistant professor of psychology and an author on the paper. "With the legalization of cannabis in Washington and 10 other states, we thought it would be important to document some of this information so that more novice users would have a better sense of what types of adverse reactions they may experience if they use cannabis."

More than 50% of the study participants reported having experienced coughing fits, anxiety and/or paranoia while using cannabis. On the other end of the spectrum, the three least-common reported reactions were fainting/passing out, non-auditory/visual hallucinations and cold sweats.

The researchers found the most frequently occurring adverse reactions were coughing fits, chest/lung discomfort and body humming, which a subset of the study group reported occurring approximately 30-40% of the time they were using cannabis.

Panic attacks, fainting and vomiting were considered the most distressing of the 26 possible adverse reactions.

"It is worth noting even the most distressing reactions to cannabis were only rated between moderately' and quite distressing," Cuttler said. "This suggests cannabis users do not, in general, find acute adverse reactions to cannabis to be severely distressing."

The least distressing reactions were reported to be body humming, numbness and feeling off balance/unsteady, the researchers found.

The study showed less frequent users are more likely to report negative effects. Additionally, individuals who reported using cannabis to try to fit in with friends, displayed cannabis use disorder symptoms or had anxiety sensitivity -- a tendency to imagine the worse possible outcome -- were more likely to report adverse reactions as well as experiencing a greater amount of distress.

"Interestingly, we didn't find that quantity of use during a single session predicted very much in terms of whether or not a person was going to have a bad reaction," Cuttler said. "It was the people who smoke on a less frequent basis who tend to have these bad experiences more often."

Moving forward, Cuttler hopes the results of the study will be put to use by doctors, medical cannabis distributors and even bud tenders to give people a better idea of what could go wrong when they get high.

"When you get any other kind of medication, there will be a leaflet or a warning printed on the bottle about the drug's potential side effects," Cuttler said. "There really isn't very much out there on this for cannabis, and we think that it is important for people to have access to this kind of information."

https://www.sciencedaily.com/releases/2020/03/200330130543.htm

Legal marijuana products too strong for pain relief

March 26, 2020

Science Daily/Wake Forest Baptist Medical Center

More than 90% of the legal marijuana products offered in medical dispensaries are much stronger than what clinical studies have shown that doctors recommend for chronic pain relief, according to a study published in the March 26 online edition of the journal PLOS ONE.

To many that may seem like a good thing, but just the opposite is true.

"We know that high-potency products should not have a place in the medical realm because of the high risk of developing cannabis-use disorders, which are related to exposure to high THC-content products," said the study's lead author, Alfonso Edgar Romero-Sandoval, M.D., Ph.D., associate professor of anesthesiology at Wake Forest School of Medicine, part of Wake Forest Baptist Health.

"Several earlier studies showed that levels of up to 5% tetrahydrocannabinol (THC) -- the main psychoactive compound in marijuana that provides pain relief as well as intoxication -- were sufficient to reduce chronic pain with minimal side effects."

The goal of this study was to evaluate the advertised THC and CBD content of legal cannabis products to determine their suitability for medicinal use, and to compare the potency of the products offered in medical and recreational programs.

The researchers recorded the concentrations of THC and cannabidiol (CBD) -- the non-euphoric compound in marijuana -- in all plant cannabis products provided by legal dispensary websites and compared them between or within the states in the study: California, Colorado, Maine, Massachusetts, New Hampshire, New Mexico, Rhode Island, Vermont and Washington. A total of 8,505 cannabis products across 653 dispensaries were sampled.

Romero-Sandoval's team found that most of the products offered in the medical dispensaries in the study had more than 10% THC and that many had 15% or more, the same as what is available in products at recreational dispensaries.

This is problematic because between 60% and 80% of people who use medical marijuana use it for pain relief, Romero-Sandoval said. The higher the concentration of THC the greater risk, not only for developing dependency, but also for developing tolerance more quickly, which means higher and higher concentrations might be needed to get the same level of pain relief.

"It can become a vicious cycle," Romero-Sandoval said.

"Better regulation of the potency of medical marijuana products is critical. The FDA regulates the level of over-the-counter pain medications such as ibuprofen that have dose-specific side effects, so why don't we have policies and regulations for cannabis, something that is far more dangerous?"

This study provides the scientific evidence to help policy makers correct mistakes and to create a better framework to protect patients, he said.

https://www.sciencedaily.com/releases/2020/03/200326144354.htm

Cannabis helps fight resistant bacteria

March 24, 2020

Science Daily/University of Southern Denmark

Bacteria are increasingly becoming resistant to antibiotics. By combining antibiotics with the cannabis compound, cannabidiol, researchers have found a way to enhance the antibiotic effect

Since the discovery of penicillin in 1928 by Sir Alexander Fleming, antibiotics have saved millions of lives from fatal infections world-wide. However, with time bacteria have developed mechanisms to escape the effects of antibiotics -- they have become resistant.

With fewer antibiotics available to treat resistant bacterial infections, the possibility of entering a pre-antibiotic era is looming ahead.

Alternative strategies are being explored and helper compounds are attracting attention. Helper compounds are non-antibiotic compounds with the capability of enhancing the efficacy of antibiotics.

How to boost antibiotics

One such helper compound has been suspected to be cannabidiol (CBD); a cannabinoid from the cannabis plant. Now a research team from University of Southern Denmark, has published a scientific study proving the effect of CBD.

Janne Kudsk Klitgaard is Principal Investigator and corresponding author. First author is PhD student Claes Søndergaard Wassmann. The study is published in the journal Scientific Reports.

When we combined CBD and antibiotics, we saw a more powerful effect than when treating with antibiotics alone. So, in order to kill a certain number of bacteria, we needed less antibiotics, they say.

Bacteria clones spread globally

In the study, CBD was used to enhance the effect of the antibiotic bacitracin against Staphylococcus aureus bacteria; a major human pathogen that frequently causes community- and hospital-acquired disease.

Multidrug-resistant clones of this pathogen have spread globally. In some countries, treatment of bacterial infections with these resistant bacteria are difficult and the problem is projected to be an ever-larger problem in the future.

According to the researchers, the combination of CBD and antibiotics may be a novel treatment of infections with antibiotic resistant bacteria.

How do the bacteria die?

Three things happened with the Staphylococcus aureus bacteria, when the researchers treated them with the combination in their study:

The bacteria could no longer divide normally.

The expression of certain key genes (cell division and autolysis genes) in the bacteria was lowered.

The bacterial membrane became unstable.

Anti-resistance must be stopped

According to the researchers, overuse of antibiotics is the main cause of antibiotic resistance.

If we combine an antibiotic with a helper compound, that enhances the effect of the antibiotic, we need less antibiotic to achieve the same effect. This may contribute to the development of fewer resistant bacteria, says Janne Kudsk Klitgaard.

https://www.sciencedaily.com/releases/2020/03/200324131833.htm

'Feeling obligated' can impact relationships during social distancing

March 19, 2020

Science Daily/Michigan State University

In a time where many are practicing "social distancing" from the outside world, people are relying on their immediate social circles more than usual. Does a sense of obligation -- from checking on parents to running an errand for an elderly neighbor -- benefit or harm a relationship? A Michigan State University study found the sweet spot between keeping people together and dooming a relationship.

"We were looking to find whether obligation is all good or all bad," said William Chopik, assistant professor of psychology at MSU and co-author of the study. "When we started, we found that people were responding to types of obligations in different ways. People distinguished between requests that were massive obligations and requests that were simple. There's this point that obligation crosses over and starts to be harmful for relationships."

According to Jeewon Oh, MSU doctoral student and co-author of the study, obligation is sometimes the "glue that holds relationships together," but it often carries negative connotations.

"We found that some obligations were linked with greater depressive symptoms and slower increases in support from friends over time," Oh said. "However, other obligations were linked with both greater support and less strain from family and friends initially."

Chopik and Oh's findings suggest that there's a distinct point at which obligation pushes individuals to the brink of feeling burdened, which can start to harm their relationships.

"The line in our study is when it crosses over and starts to be either a massive financial burden or something that disrupts your day-to-day life," Chopik said. "While engaging in substantive obligation can benefit others and make someone feel helpful, it is still costly to a person's time, energy and money."

Until now, similar research showed inconsistencies in how obligation impacts relationships, which Chopik attributes to the spectrum of obligation. This spectrum ranges from light obligation, like keeping in touch with a friend, to substantive obligation, like lending that friend a considerable amount of money.

"In a way, major obligations violate the norms of friendships," Chopik said. "Interestingly, you don't see that violation as much in relationships with parents or spouses."

Chopik explained that friendships are viewed as low-investment, fun relationships that make people feel good.

"Our longest lasting friendships continue because we enjoy them. But if obligations pile up, it might compromise how close we feel to our friends," Chopik said. "Because friendships are a relationship of choice, people can distance themselves from friends more easily than other types of relationships when faced with burdensome obligations."

Additionally, substantive obligations may create strain in a friendship as we try to encourage our friends to do the same even when they might not be able to do so, Oh said.

"Although we may feel good when we do things for our friends, and our friends are grateful to us, we may start to feel like we are investing too much in that relationship," Oh said.

On the other end of the spectrum, light obligation creates what Chopik calls a "norm of reciprocity."

"Those light obligations make us feel better, make us happier and make our relationships stronger," Chopik said. "There's a sense that 'we're both in this together and that we've both invested something in the relationship.'"

That's why, among the best relationships, low-level acts of obligation don't feel like obligations at all. Small acts of kindness, which strengthen the bonds of our relationships, are done without any fuss or burden.

Still, some types of relationships can make even minor obligations seem daunting. If someone doesn't have a great relationship with a parent, a quick phone call to check in isn't enjoyable, it's an encumbrance.

"Even for things we would expect family members to do, some in the study did them begrudgingly," Chopik said.

Chopik and Oh's findings reveal a spectrum of obligations as diverse as the relationships one has in life.

"It's the little things you do that can really enhance a friendship, but asking too much of a friend can damage your relationship," Chopik said.

https://www.sciencedaily.com/releases/2020/03/200319125132.htm

How to boost immune response to vaccines in older people

Apply immune expertise and some genital wart cream!

March 27, 2020

Science Daily/Babraham Institute

Identifying interventions that improve vaccine efficacy in older persons is vital to deliver healthy aging for an aging population. Immunologists have identified a route for counteracting the age-related loss of two key immune cell types by using genital wart cream to boost immune response to vaccination in aged mice. After this validation in mice, the findings offer an attractive intervention to tailor the make-up of vaccines for older people.

Research just published by the Linterman lab shows that the immune system of older mice can be given a helping hand by applying immunology expertise and some genital wart treatment (don't try this at home just yet)!

Mice and humans show similar age-dependent changes in their immune system so this finding offers hope for easily increasing the robustness of vaccination response in the older population.

As we age, the function of our immune system declines, rendering us more susceptible to infections, and making us less able to generate protective immunity after vaccination. By understanding the cellular and molecular mechanisms that underpin this poor response in older individuals, researchers in the Linterman lab were able to repurpose an existing treatment for genital warts, and demonstrate that this was effective in overcoming the age-related effects on two of the many cell types making up our immune system. The research is published online in the journal eLife.

Dr Michelle Linterman, a group leader in the Institute's Immunology research programme, said: "The current coronavirus pandemic highlights that older members of our families and communities are more susceptible to the morbidity and mortality associated with infectious diseases. Therefore, it is imperative that we understand how the immune system in older people works, and to explore how we might be able to boost their immune responses to vaccines to ensure they work well in this vulnerable part of our society."

Vaccines work by generating antibodies that are able to block the ability of pathogens to infect us. Antibody secreting cells are produced in the germinal centre, immune reaction hubs that forms after infection or vaccination. With age, the magnitude and quality of the germinal centre reaction declines.

Immune cells called T follicular helper cells are essential to the germinal centre response. In this study the team used mice and humans to investigate why T follicular helper cell numbers decline with age, and if there is a way to boost them upon vaccination.

"The germinal centre response is a highly collaborative process that requires multiple cell types to interact at the right place and the right time. Therefore, it made sense to us that defects in one or more of these cell types could explain the poor germinal centre response observed in older individuals after vaccination," explains Dr Linterman.

The researchers found that older mice and humans form fewer T follicular helper cells after vaccination, which is linked with a poor germinal centre response and antibody response. By developing our understanding of the cellular and molecular events occurring in the germinal centre after vaccination, the researchers identified that T follicular helper cells in older mice and people received less stimulatory interactions from their immune system co-workers. By using a cream (imiquimod, currently used to treat genital warts in humans) on the site of immunisation to boost the number of stimulatory cells, they were able to restore the formation of T follicular helper cells in older mice and also rescue the age-dependent defects in another immune cell type (dendritic cells). Encouragingly, this demonstrates that the age-related defects in T follicular helper cell formation in ageing are not irreversible, and can be overcome therapeutically.

The full picture and evaluation of whether this approach will work as an intervention in humans requires more research into why the germinal centre response changes with age, and what can be done to overcome this. Once achieved, it could be that clinical trials are established to incorporate this knowledge into new vaccine formulations for older people.

https://www.sciencedaily.com/releases/2020/03/200327113752.htm

Standardizing COVID-19 data analysis to aid international research efforts

March 27, 2020

Science Daily/Center for Genomic Regulation

Researchers from the Centre for Genomic Regulation (CRG) have launched a new database to advance the international research efforts studying COVID-19.

The publicly-available, free-to-use resource (https://covid.crg.eu) can be used by researchers from around the world to study how different variations of the virus grow, mutate and make proteins.

"Scientists are working round the clock to understand SARS-CoV-2, the virus causing COVID-19, so that we can find its weak spots and beat it. A huge amount of scientific data is being published around the world," says Eva Novoa, a researcher at the CRG in Barcelona.

"However, some of the technologies we use to study SARS-CoV-2, such as nanopore RNA sequencing, are so new that the results of one paper aren't comparable to another due to the patchwork of different standards and methodologies used. We are taking all this data and analyzing it so that it meets a more universally comparable standard. This will help researchers more quickly and accurately spot the strengths and weaknesses of the coronavirus."

To understand how the coronavirus grows, mutates and replicates, scientists have to sequence the RNA of COVID-19. The RNA sequence reveals crucial information about the proteins the virus makes to invade human cells and replicate, which in turn informs governments on the infectiousness and severity of the pandemic.

Traditional sequencing tools can take a long time to provide results. In recent years, sequencing data in real time has become a reality thanks to the use of nanopore sequencing technologies, revolutionizing genomics research and disease outbreak monitoring. Nanopore sequencing provides scientists and clinicians with immediate access to the DNA and RNA sequence information of any living cell in real-time, enabling a rapid response against the threat of a pandemic.

However, the raw data produced by nanopore sequencing is highly complex. Scientists and clinicians currently lack systematic guidelines for the reproducible analysis of the data, limiting the vast potential of the nascent technology.

To standardize the analysis of publicly available SARS-CoV-2 nanopore sequencing data, researchers at the Centre for Genomic Regulation (CRG) in Barcelona are using MasterOfPores, a computer program developed by the group of Eva Novoa and CRG Bioinformatics Unit. The software was first described last week in Frontiers in Genetics.

"The internet and an increasing culture of open science, data sharing and preprints have transformed the research landscape. Infrastructure that would take months to set up to research an emerging virus can now be done in just a few days owing to novel scientific computing approaches," says Julia Ponomarenko, Head of the Bioinformatics Unit at the CRG.

MasterOfPores can be executed on any Unix-compatible OS on a computer, cluster or cloud without the need of installing any additional software or dependencies, and is freely available in Github. The publicly-available, free-to-use resource has currently analysed 3TB of SARS-CoV-2 nanopore RNA sequencing data. The CRG researchers will continue to update the resource with new data as soon as it becomes available.

https://www.sciencedaily.com/releases/2020/03/200327122315.htm

COVID-19 linked to cardiac injury, worse outcomes for patients with heart conditions

March 27, 2020

Science Daily/University of Texas Health Science Center at Houston

COVID-19 can have fatal consequences for people with underlying cardiovascular disease and cause cardiac injury even in patients without underlying heart conditions, according to a review published today in JAMA Cardiology by experts at The University of Texas Health Science Center at Houston (UTHealth).

Experts have known that viral illnesses such as COVID-19 can cause respiratory infections that may lead to lung damage and even death in severe cases. Less is known about the effects on the cardiovascular system.

"It is likely that even in the absence of previous heart disease, the heart muscle can be affected by coronavirus disease," said Mohammad Madjid, MD, MS, the study's lead author and an assistant professor of cardiology at McGovern Medical School at UTHealth. "Overall, injury to heart muscle can happen in any patient with or without heart disease, but the risk is higher in those who already have heart disease."

The study authors explained that research from previous coronavirus and influenza epidemics suggest that viral infections can cause acute coronary syndromes, arrhythmias, and the development of, or exacerbation of, heart failure.

In a clinical bulletin issued by the American College of Cardiology, it was revealed that the case fatality rate of COVID-19 for patients with cardiovascular disease was 10.5%. Data also points to a greater likelihood that individuals over the age of 65 with coronary heart disease or hypertension can contract the illness, as well experience more severe symptoms that will require critical care.

According to the study authors, critical cases are those that reported respiratory failure, septic shock, and/or multiple organ dysfunction or failure that resulted in death. "It is reasonable to expect that significant cardiovascular complications linked to COVID-19 will occur in severe symptomatic patients because of the high inflammatory response associated with this illness," said Madjid, who also sees patients at the UT Physicians Multispecialty -- Bayshore clinic.

The novel virus that causes COVID-19 was first identified in January 2020. This novel virus originated in Wuhan, China, and by March 11, 2020, the World Health Organization had declared it a global pandemic. The three most common symptoms of COVID-19 include fever, cough, and shortness of breath. Other less common symptoms are muscle pain, sore throat, nasal congestion, and headache. Symptoms can appear as soon as two days after exposure to the virus to up to14 days after. There is a high viral load in both symptomatic and asymptomatic patients, meaning asymptomatic spread between person to person is likely.

Previously identified coronaviruses known to cause severe illness in humans include Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV). SARS-CoV was first identified in southern China in 2002, and by 2003 it had killed over 8,000 individuals in 29 countries. Data suggests that SARS-CoV may have resulted in cardiovascular complications, such as acute coronary syndrome and myocardial infarction. MERS-CoV was first discovered in 2012 in Saudi Arabia. As of 2019, 2,494 cases have been confirmed along with 858 deaths in 26 countries.

Current COVID-19 treatment options are being researched, and there is a large effort to develop vaccines for prevention and to test antivirals for the treatment of the disease. In the meantime, the study authors encourage all individuals to consult with their health care providers about being vaccinated against influenza and that at-risk patients seek advice on receiving a pneumonia vaccine from their primary care physician. While these vaccines will not provide specific protection against COVID-19, they can help prevent superimposed infections alongside COVID-19.

https://www.sciencedaily.com/releases/2020/03/200327113743.htm

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