Potential harms of chloroquine, hydroxychloroquine and azithromycin for treating COVID-19
April 8, 2020
Science Daily/Canadian Medical Association Journal
Chloroquine, hydroxychloroquine and azithromycin are being used to treat and prevent COVID-19 despite weak evidence for effectiveness, and physicians and patients should be aware of the drugs' potentially serious adverse events, states a review in CMAJ(Canadian Medical Association Journal).
"Physicians and patients should be aware of several rare but potentially life-threatening adverse effects of chloroquine and hydroxychloroquine," says Dr. David Juurlink, Division of Clinical Pharmacology and Toxicology, Sunnybrook Health Sciences Centre, and a senior scientist at ICES.
The review provides an overview of potential harms associated with these drugs as well as their management based on the best available evidence.
Potential adverse effects include:
Cardiac arrhythmias
Hypoglycemia
Neuropsychiatric effects, such as agitation, confusion, hallucinations and paranoia
Interactions with other drugs
Metabolic variability (some people metabolize chloroquine and hydroxychloroquine poorly and a small percentage metabolize them rapidly, which affects the response to treatment)
Overdose (chloroquine and hydroxychloroquine are highly toxic in overdose and can cause seizures, coma and cardiac arrest)
Drug shortages (patients with autoimmune disorders such as rheumatoid arthritis, lupus and other chronic diseases, who take hydroxychloroquine to treat these conditions could have problems accessing this drug)
The review summarizes the poor quality of evidence suggesting that these treatments might be beneficial in patients with COVID-19 and cautions that it is possible that these treatments could worsen the disease.
"Despite optimism (in some, even enthusiasm) for the potential of chloroquine or hydroxychloroquine in the treatment of COVID-19, little consideration has been given to the possibility that the drugs might negatively influence the course of disease," says Dr. Juurlink. "This is why we need a better evidence base before routinely using these drugs to treat patients with COVID-19."
"Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection" is published April 8, 2020.
https://www.sciencedaily.com/releases/2020/04/200408125521.htm
Modeling study estimates impact of relaxing control measures on possible second wave of COVID-19 in China
April 8, 2020
Science Daily/The Lancet
Use of real-time monitoring of COVID-19 transmissibility and severity to fine-tune control strategies offers the best chance to minimize second wave of infection in mainland China, outside Hubei province, researchers say in a new study.
New modelling research, published in The Lancetjournal, suggests that China's aggressive control measures appear to have halted the first wave of COVID-19 in areas outside Hubei province, the epicentre of the epidemic. However, given the substantial risk of the virus being reintroduced from abroad, and with economic activity increasing, real-time monitoring of COVID-19 transmissibility and severity is needed to protect against a possible second wave of infection, researchers say.
The study estimates that in regions outside Hubei, the instantaneous reproductive number of COVID-19 -- the average number of cases generated by a single infected individual during the outbreak -- fell substantially after lock down measures were introduced on January 23, 2020, and has remained below 1 since then -- suggesting that the epidemic has shifted from one that is expanding rapidly to one that is slowly shrinking. (The higher the reproductive number, the more transmissible the virus is and the higher the risk for rapid spread. When the reproductive number falls below one, the epidemic is likely to die out.)
However, mathematical modelling to simulate the impact of relaxing current control measures, suggests that premature lifting of these interventions will likely lead to transmissibility exceeding 1 again, resulting in a second wave of infection.
The findings are critical to countries globally that are in the early phases of lock down because they warn against premature relaxation of strict control measures, researchers say. However, the study did not specifically examine the effect of each intervention, or which one was most effective in containing the spread of the virus.
"While these control measures appear to have reduced the number of infections to very low levels, without herd immunity against COVID-19, cases could easily resurge as businesses, factory operations, and schools gradually resume and increase social mixing, particularly given the increasing risk of imported cases from overseas as COVID-19 continues to spread globally," says Professor Joseph T Wu from the University of Hong Kong who co-led the research.
He continues, "Although control policies such as physical distancing and behavioural change are likely to be maintained for some time, proactively striking a balance between resuming economic activities and keeping the reproductive number below one is likely to be the best strategy until effective vaccines become widely available.
Further analysis suggests that the confirmed case fatality risk (the probability of dying among confirmed cases of COVID-19 as officially reported) outside Hubei was 0.98% -- which is almost six times lower than in Hubei (5.91%) -- and varied substantially among different provinces, based on economic development and availability of health-care resources. Among the ten provinces with the largest number of confirmed cases, case fatality ranged from 0% in prosperous regions like Jiangsu to 1.76% in less developed provinces such as Henan.
"Even in the most prosperous and well-resourced megacities like Beijing and Shanghai, health-care resources are finite, and services will struggle with a sudden increase in demand," says senior author Professor Gabriel M Leung from the University of Hong Kong. "Our findings highlight the importance of ensuring that local health-care systems have adequate staffing and resources to minimise COVID-related deaths."
In December 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan city and spread across China. Stringent restrictions on the movement of people and goods were introduced nationwide on January 23. These measures have impacted on people's livelihood and personal liberties, as well as lost economic opportunity. Since February 17, restrictions have been progressively relaxed in several provinces, and factories and offices are gradually reopening.
In the study, researchers analysed local Health Commission data of confirmed COVID-19 cases between mid-January and 29 February, 2020, to estimate the transmissibility and severity of COVID-19 in four major cities -- Beijing, Shanghai, Shenzhen, Wenzhou -- and ten provinces outside Hubei with the highest number of confirmed COVID-19 cases. The number of new daily imported and local cases were used to construct epidemic curves for each location by date of symptom onset, and reporting delays -- time lags between the onset of a disease and the reporting of cases -- were incorporated in the modelling to calculate weekly reproduction numbers. The researchers also modelled the potential impact of relaxing control measures after the first wave of infection for different scenarios with rising reproduction numbers.
The analyses suggest that in regions outside Hubei, control measures should be lifted gradually so that the resulting reproductive number does not exceed 1, or the number of cases will progressively rise over the relaxation period. Moreover, the estimates suggest that once elevated, simply tightening control interventions again would not reduce the burden back to its original level, and would require extra effort to drive the reproductive number below 1 in order to revert to the pre-relaxation level -- likely resulting in both higher health and economic loss.
"We are acutely aware that as economic activity increases across China in the coming weeks, local or imported infection could lead to a resurgence of transmission," says co-lead author Dr Kathy Leung from the University of Hong Kong. "Real-time monitoring of the effect of increased mobility and social mixing on COVID-19 transmissibility could allow policymakers to fine tune control measures to interrupt transmission and minimise the impact of a possible second wave of infections."
Despite these important findings, the study has some limitations, including that the estimated reproductive numbers were based on the reported number of confirmed cases, and the time and dates of symptom onset were unavailable for some provinces and relied on data derived from Shenzhen. Finally, a limited number of simulations for relaxing control measures were done, and did not specify which interventions or public responses to the epidemic might correspond to each of these scenarios.
Writing in a linked Comment, lead author Dr Shunqing Xu (who was not involved in the study) from Huazhong University of Science and Technology in China says: "Case fatality rate (CFR) is one of the important unknowns of COVID-19...Leung and colleagues found the confirmed CFR was correlated with provincial per capita gross domestic product and the availability of hospital beds per 10,000. In Wuhan, the CFR was up to 5.08% by March 28, 2020. The remarkable difference in the CFR between these locations and Wuhan might be attributed to the difference in the degrees of health-care capacity. Therefore, consideration should be given to the variations in health-care capacity when implementing interventions."
https://www.sciencedaily.com/releases/2020/04/200408184717.htm
Link between air pollution and coronavirus mortality in Italy could be possible
April 6, 2020
Science Daily/Aarhus University
A group of scientists has found another small piece in the puzzle of understanding COVID-19. Looking for reasons why the mortality rate is up to 12% in the northern part of Italy and only approx. 4.5% in the rest of the country, they found a probable correlation between air pollution and mortality in two of the worst affected regions in northern Italy.
The world has been hit hard by coronavirus, and health services and authorities everywhere are struggling to reduce the spread, combat the disease and protect the population. Nevertheless, the pandemic will cost lives throughout the world. An environmental researcher from Aarhus University has studied whether there could be a link between the high mortality rate seen in northern Italy, and the level of air pollution in the same region. The short answer is "yes possibly." The long answer is in the article below.
The outbreak of Severe Acute Respiratory Syndrome CoronaVirus2 had its source in the Wuhan Province in China in December 2019. Since then, the coronavirus has spread to the rest of the globe, and the world is now treating patients with the disease that follows virus infection: COVID-19. The course of the disease differs for patients the world over: many experience flu-like symptoms, while many others need hospital treatment for acute respiratory infection that, in some cases, leads to death.
However, what factors affect the course of the disease and the possibilities to combat COVID-19 remains unclear, as long as there is no medical treatment or vaccine. At the moment, there are more questions than answers, and researchers all over the world are therefore working to find new insights into the global pandemic.
At Aarhus University, the environmental scientist Dario Caro from the Department of Environmental Science, and two health researchers, prof. Bruno Frediani and Dr. Edoardo Conticini, from the University of Siena in Italy have found yet another small piece in the puzzle of understanding the deadly disease. They have focused on examining why the mortality rate is up to 12% in the northern part of Italy, while it is only approx. 4.5% in the rest of the country.
They have just published an article entitled "Can Atmospheric pollution be considered as a co-factor in the extremely high level of SARS-CoV-2 lethality in Northern Italy?," in which they demonstrate a probable correlation between air pollution and mortality in two of the worst affected regions in northern Italy: Lombardy and Emilia Romagna.
The research project has been published in the scientific journal Environmental Pollution.
"There are several factors affecting the course of patients' illness, and all over the world we're finding links and explanations of what is important. It's very important to stress that our results are not a counter-argument to the findings already made. At the moment, all new knowledge is valuable for science and the authorities, and I consider our work as a supplement to the pool of knowledge about the factors that are important for the course of patients' illness," says environmental scientist Dario Caro, and clarifies that there are a number of other factors that could possibly play a role in the Italian situation:
"Our considerations must not let us neglect other factors responsible of the high lethality recorded: important co-factors such as the elevated medium age of the Italian population, the wide differences among Italian regional health systems, ICUs capacity and how the infects and deaths has been reported have had a paramount role in the lethality of SARS-CoV-2, presumably also more than pollution itself," he explains.
Different datasets show a link
The two northern Italian regions are among the most air-polluted regions in Europe. The recently published article took its outset in data from the NASA Aura satellite, which has demonstrated very high levels of air pollution across precisely these two regions. The group compared these data with the so-called Air Quality Index; a measurement of air quality developed by the European Environment Agency. The index gathers data from several thousand measuring stations all over Europe, providing a geographical insight into the prevalence of a number of pollutant sources in the EU.
The figures speak for themselves. The population of the northern Italian regions lives in a higher level of air pollution, and this may lead to a number of complications for patients with COVID-19 in the regions, simply because their bodies may have already been weakened by the accumulated exposure to air pollution when they contract the disease.
Dario Caro explains that the situation in the Italian regions has been a challenge for several years, with high levels of air pollution that have accumulated over a long period of time in the population. It is therefore unlikely that there is any reason to imagine that people in Denmark are exposed to the same factors or the same levels of pollution as people in northern Italy, where the authorities have been trying to reduce pollution levels for many years.
"All over the world, we're seeing different approaches from countries' authorities, in countries' general public health outset and in the standards and readiness of different countries' national healthcare systems. But this doesn't explain the prevalence and mortality rates that we're seeing in northern Italy compared with the rest of Italy. This feeds hope that we may have found yet another factor in understanding the high mortality rate of the disease in northern Italy," says Dario Caro.
https://www.sciencedaily.com/releases/2020/04/200406100824.htm
First study on the health conditions of adults one month into COVID-19 lockdown
Early evidence of people's health conditions after one-month of lockdown in China
April 8, 2020
Science Daily/University of Sydney
A new study provides some of the earliest pieces of evidence that the COVID-19 outbreak affected people mentally as well as physically.
The preliminary results reveal adults in locations more affected by COVID-19 had distress, and lower physical and mental health, and life satisfaction.
Researchers from the University of Adelaide, Tongji University and University of Sydney surveyed 369 adults living in 64 cities in China after they had lived under one-month of confinement measures in February this year.
Led by Dr Stephen Zhang from the University of Adelaide, the study identifies adults with existing health conditions and those who stopped working as most at risk of worse mental and physical health.
"As many parts of the world are only just beginning to go into lockdown, we examined the impact of the one-month long lockdown on people's health, distress and life satisfaction," said Dr Zhang.
"The study offers somewhat of a 'crystal ball' into the mental health of Australian residents once they have been in the lockdown for one month."
More than a quarter of the participants worked at the office during the lockdown period while 38 percent worked from home and 25 percent stopped work due to the outbreak.
Published in Psychiatry Research, the study suggests adults living in locations more affected by COVID-19 reported negative life satisfaction only among adults with chronic medical issues but not for those without existing health issues.
Co-author on the study, Professor Andreas Rauch from the University of Sydney said; "We weren't surprised that adults who stopped working reported worse mental and physical health conditions as well as distress. Work can provide people with a sense of purpose and routine, which is particularly important during this global pandemic."
Study participants who exercised for more than 2.5 hours per day reported worse life satisfaction in more affected locations while those who exercised for half an hour or less during the lockdown reported positive life satisfaction.
"We were really surprised by the findings around exercising hours because it appears to be counter-intuitive," said lead author Dr Zhang.
"It's possible adults who exercised less could better justify or rationalise their inactive lifestyles in more severely affected cities. More research is needed but these early findings suggest we need to pay attention to more physically active individuals, who might be more frustrated by the restrictions."
https://www.sciencedaily.com/releases/2020/04/200408102137.htm
People tune out facts and trust their guts in medical emergencies
April 3, 2020
Science Daily/University of Texas at Arlington
A study conducted by two associate professors of marketing at The University of Texas at Arlington shows that people are more likely to base decisions on anecdotal information instead of facts when they feel anxious and vulnerable.
Traci Freling and Ritesh Saini, both in the College of Business, published "When poignant stories outweigh cold hard facts: A meta-analysis of the anecdotal bias" in Organizational Behavior and Human Decision Processes.
"We found that people are more likely to consider personal anecdotes than fact-based information, especially when it deals with medical emergencies," Freling said. "This has a high importance in the current environment, where everyone is concerned about the coronavirus."
Freling said people are more likely to listen to personal stories instead of facts because emotions run high during medical emergencies like the COVID-19 pandemic.
"They are especially dismissive of facts if the incident is something they personally experienced," Freling said. "Specifically, we show that when an issue is health-related, personally relevant or highly threatening, then decision-making is compromised and people tend to rely on anecdotes."
Freling pointed to the run on toilet paper buying during the COVID-19 pandemic as one example of not basing decisions on facts. This example illustrates how consumers who feel vulnerable to a particular problem may rely more heavily on subjective, anecdotal information instead of objective, statistical facts to make decisions.
Former UTA faculty member Zhiyong Yang, now a professor at the University of North Carolina-Greensboro, and two graduate students contributed to the analysis.
The research also revealed that when emotional engagement is low, statistical evidence weighs more heavily.
"Primarily, when there is low-threat severity or it's a non-health issue, people tend to take cold, hard facts into account rather than personal accounts and stories," Freling said.
Additionally, Saini noted that people make "more fact-based decisions when choosing for others, but become surprisingly irrational when choosing for self."
Elten Briggs, chair of the Department of Marketing, said Freling and Saini's analysis could have implications on decision-making processes for business and industry, especially during medical crises.
"Their research provides guidance on how to craft more influential messaging during times like these, when anxiety is heightened for so many people," Briggs said.
https://www.sciencedaily.com/releases/2020/04/200403131259.htm
Removing the novel coronavirus from the water cycle
Science Daily/University of California - Riverside
Scientists know that coronaviruses, including the SARS-CoV-19 virus responsible for the COVID-19 pandemic, can remain infectious for days -- or even longer -- in sewage and drinking water.
Two researchers, Haizhou Liu, an associate professor of chemical and environmental engineering at the University of California, Riverside; and Professor Vincenzo Naddeo, director of the Sanitary Environmental Engineering Division at the University of Salerno, have called for more testing to determine whether water treatment methods are effective in killing SARS-CoV-19 and coronaviruses in general.
The virus can be transported in microscopic water droplets, or aerosols, which enter the air through evaporation or spray, the researchers wrote in an editorial for Environmental Science: Water Research & Technology, a leading environmental journal of the Royal Society of Chemistry in the United Kingdom.
"The ongoing COVID-19 pandemic highlights the urgent need for a careful evaluation of the fate and control of this contagious virus in the environment," Liu said. "Environmental engineers like us are well positioned to apply our expertise to address these needs with international collaborations to protect public health."
During a 2003 SARS outbreak in Hong Kong, a sewage leak caused a cluster of cases through aerosolization. Though no known cases of COVID-19 have been caused by sewage leaks, the novel coronavirus is closely related to the one that causes SARS, and infection via this route could be possible.
The novel coronavirus could also colonize biofilms that line drinking water systems, making showerheads a possible source of aerosolized transmission. This transmission pathway is thought to be a major source of exposure to the bacteria that causes Legionnaire's disease, for example.
Fortunately, most water treatment routines are thought to kill or remove coronaviruses effectively in both drinking and wastewater. Oxidation with hypochlorous acid or peracetic acid, and inactivation by ultraviolet irradiation, as well as chlorine, are thought to kill coronaviruses. In wastewater treatment plants that use membrane bioreactors, the synergistic effects of beneficial microorganisms and the physical separation of suspended solids filter out viruses concentrated in the sewage sludge.
Liu and Naddeo caution, however, that most of these methods have not been studied for effectiveness specifically on SARS-CoV-19 and other coronaviruses, and they have called for additional research.
They also suggest upgrading existing water and wastewater treatment infrastructure in outbreak hot spots, which possibly receive coronavirus from places such as hospitals, community clinics, and nursing homes. For example, energy-efficient, light-emitting, diode-based, ultraviolet point-of-use systems could disinfect water before it enters the public treatment system.
Potable water-reuse systems, which purify wastewater back into tap water, also need thorough investigation for coronavirus removal, and possibly new regulatory standards for disinfection, the researchers wrote.
The extent to which viruses can colonize biofilms is also not yet known. Biofilms are thin, slimy bacterial growths that line the pipes of many aging drinking water systems. Better monitoring of coronaviruses in biofilms might be necessary to prevent outbreaks.
The surge in household use of bactericides, virucides and disinfectants will probably cause an increase of antibiotic-resistant bacteria in the environment. Treated wastewater discharged into natural waterways demands careful monitoring through the entire water cycle. Liu and Naddeo call on chemists, environmental engineers, microbiologists, and public health specialists to develop multidisciplinary and practical solutions for safe drinking water and healthy aquatic environments.
Lastly, developing countries and some regions within highly developed nations, such as rural and impoverished communities, which lack the basic infrastructure to remove other common contaminants might not be able to remove SARS-CoV-19 either. These places might experience frequent COVID-19 outbreaks that spread easily through globalized trade and travel. Liu and Naddeo suggest governments of developed countries must support and finance water and sanitation systems wherever they are needed.
"It is now clear to all that globalization also introduces new health risks. Where water and sanitation systems are not adequate, the risk of finding novel viruses is very high," Naddeo said. "In a responsible and ideal scenario, the governments of developed countries must support and finance water and sanitation systems in developing countries, in order to also protect the citizens of their own countries."
https://www.sciencedaily.com/releases/2020/04/200403132347.htm
Wearing surgical masks in public could help slow COVID-19 pandemic's advance
Masks may limit the spread diseases including influenza, rhinoviruses and coronaviruses
April 3, 2020
Science Daily/University of Maryland
Surgical masks may help prevent infected people from making others sick with seasonal viruses, including coronaviruses, according to new research that could help settle a fierce debate spanning clinical and cultural norms.
In laboratory experiments, the masks significantly reduced the amounts of various airborne viruses coming from infected patients, measured using the breath-capturing "Gesundheit II machine" developed by Dr. Don Milton, a professor of applied environmental health and a senior author of the study published April 3 in the journal Nature Medicine.
Milton has already conferred with federal and White House health officials on the findings, which closely follow statements this week from the head of the Centers for Disease Control and Prevention saying the agency was reconsidering oft-stated advice that surgical masks aren't a useful precaution outside of medical settings. (The debate takes place at a time when clinicians themselves face dangerously inadequate supplies of masks -- a shortfall other UMD researchers are scrambling to help solve.)
The question of masks has roiled society as well, with some retailers refusing to let employees wear them for fear of sending negative signals to customers, and cases of slurs and even physical attacks in the United States and elsewhere against Asians or Asian Americans who were wearing masks, a measure some consider a necessity during a disease outbreak.
The study, conducted prior to the current pandemic with a student of Milton's colleagues on the Faculty of Medicine at the University of Hong Kong, does not address the question of whether surgical masks protect wearers from infection. It does suggest that masks may limit how much the infected -- who in the case of the novel coronavirus often don't have symptoms -- spread diseases including influenza, rhinoviruses and coronaviruses.
Milton, who runs the Public Health Aerobiology, Virology, and Exhaled Biomarker Laboratory in the School of Public Health, demonstrated in a 2013 study that surgical masks could help limit flu transmission. However, he cautions that the effect may not be as great outside of controlled settings.
Nevertheless, he said, the chance they could help justifies taking a new look at whether all people should be encouraged to wear them when they venture out of their houses to stores or other populated locations during the current COVID-19 lockdown.
"In normal times we'd say that if it wasn't shown statistically significant or the effective in real-world studies, we don't recommend it," he said. "But in the middle of a pandemic, we're desperate. The thinking is that even if it cuts down transmission a little bit, it's worth trying."
Previous studies have shown that coronavirus and other respiratory infections are mostly spread during close contact, which has been interpreted by some infectious disease specialists to mean that the disease could spread only through contact and large droplets, such as from a cough or sneeze -- a message that has often been shared with the public.
"What they don't understand is that is merely a hypothesis," Milton said. The current study (along with earlier ones) shows, by contrast, that tiny, aerosolized droplets can indeed diffuse through the air. That means it may be possible to contract COVID-19 not only by being coughed on, but by simply inhaling the breath of someone nearby who has it, whether they have symptoms or not. Surgical masks, however, catch a lot of the aerosolized virus as it's exhaled, he said.
The study was conducted at the University of Hong Kong as part of the dissertation research of the lead author, Dr. Nancy Leung, who, under the supervision of the co-senior authors Drs. Cowling and Milton, recruited 246 people with suspected respiratory viral infections. Milton's Gesundheit machine compared how much virus they exhaled with and without a surgical mask.
"In 111 people infected by either coronavirus, influenza virus or rhinovirus, masks reduced detectable virus in respiratory droplets and aerosols for seasonal coronaviruses, and in respiratory droplets for influenza virus," Leung said. "In contrast, masks did not reduce the emission of rhinoviruses."
Although the experiment took place before the current pandemic, COVID-19 and seasonal coronaviruses are closely related and may be of similar particle size. The report's other senior author, Professor Benjamin Cowling, division head of epidemiology and biostatistics, School of Public Health, HKUMed, and co-director of the World Health Organization Collaborating Centre for Infectious Disease Epidemiology and Control, said, "The ability of surgical masks to reduce seasonal coronavirus in respiratory droplets and aerosols implies that such masks can contribute to slowing the spread of (COVID-19) when worn by infected people."
Milton pointed to other measures his research has found is even more effective than masks, such as improving ventilation in public places like grocery stores, or installing UV-C lights near the ceiling that works in conjunction with ceiling fans to pull air upwards and destroy viruses and bacteria.
"Personal protective equipment like N95 masks are not our first line of defense," Milton said. "They are our last desperate thing that we do."
Hong Kong University contributed to this report.
https://www.sciencedaily.com/releases/2020/04/200403132345.htm
Rapid infectious disease shifts in Chinese children and adolescents prior to COVID-19
Science Daily/Murdoch Children’s Research Institute
Deaths of children and adolescents in China due to infectious diseases were becoming rare prior to the covid-19 pandemic, according to a new study.
Quarantinable conditions with high death rates such as cholera and plague had effectively disappeared and many traditional and vaccine-preventable infectious diseases of childhood including diarrhea, measles and rubella became uncommon.
The research, led by the Murdoch Children's Research Institute (MCRI) and Peking University and published in the British Medical Journal, found the leading causes of death from infectious diseases in China had shifted markedly over a 10 year period from rabies and tuberculosis to HIV/AIDS.
But overall deaths from infectious diseases decreased steadily between 2008-2018 from 0.21 per 100,000 population in 2008 to 0.07 per 100,000 in 2017.
MCRI Professor George Patton said until now no study had reported on recent trends in infectious diseases among children and adolescents in China.
The new research analysed national surveillance data across 31 mainland Chinese provinces. It involved 5 million students aged six to 22 years, and involved 44 notifiable infectious diseases.
Study author Yanhui Dong, from Peking University, said China had made 'remarkable progress' in infectious disease control in this age group.
But Dr Dong said while animal-to-human infections like bird flu remained low, the potential for major outbreaks like SARS-CoV-2 remained a very real possibility.
After the SARS outbreak in 2003, China made substantial investments in laboratory testing, surveillance system enhancement, national intervention programs for specific diseases, and collaboration with international partners.
Professor Patton said despite the progress, China faced new challenges in responding to seasonal and unpredictable new infectious diseases in children and adolescents.
Comprehensive national surveillance systems and rapid proactive government responses would be an integral part of future infectious disease control in China and around the world, he said.
"China will need to continue its successful efforts against older infectious diseases of children and adolescents, including measles, tuberculosis, rabies, and scarlet fever and now scale-up vaccination for mumps, seasonal influenza, and hepatitis B," Professor Patton said.
"Along with the rest of the world, China will also need greater vigilance around the highly transmissible seasonal and unpredictable diseases that we have seen in the past two decades including SARS, MERS, novel influenzas, Zika, Ebola and now the new SARS-CoV-2 virus."
Despite expanding the national childhood immunisation program in 2008, the most common infections in early childhood in China were still vaccine preventable diseases and gastrointestinal and enterovirus diseases, such as hand, foot and mouth disease.
Sexually transmitted diseases and bloodborne infections largely affected older adolescents.
Dr Dong said the significant increase of HIV/AIDs and STI's among 15-24 year olds seemed related to high risk sexual behaviours and poor awareness of infection risks.
"There is a pressing need for more school and university-based sex education programs as well as peer education, and access to rapid testing for sexually transmitted infections," Dr Dong said.
Dr Dong said the data especially highlighted the need for prevention programs to pivot towards a different set of risks, which would also require different interventions.
Researchers from the Chinese Centre for Disease Control and Prevention, the University of Melbourne and The Royal Children's Hospital also contributed to the study.
Key findings for the six to 22 year age group in China included:
Deaths from infectious diseases has decreased between 2008-2018 from 0.21 per 100,000 population in 2008 to 0.07 per 100,000 in 2017
Quarantinable conditions with high death rates have effectively disappeared
Zoonotic infections like bird flu remained low but there is potential for major outbreaks
Notifiable infectious diseases decreased from 280 per 100,000 in 2008 to 162 per 100,000 in 2015, but rose again to 242 per 100,000 in 2017, largely related to mumps and seasonal influenza
Most vaccine preventable diseases were at low levels, but seasonal variation in mumps, rubella, measles, and influenza suggested these diseases should remain a priority for public policy
Vectorborne diseases, such as those transmitted by mosquitoes and fleas, have declined
Gastrointestinal and enterovirus diseases remained constant, but typhoid, paratyphoid, and dysentery continued to decline
Tuberculosis remained the most common bacterial infection, although cases of scarlet fever doubled between 2008 and 2017
Sexually transmitted diseases and bloodborne infections increased significantly. By the end of 2018, 149,000 people with newly diagnosed HIV/AIDS had been reported, 95 per cent of which were sexually transmitted. Of these, 16,000 new HIV/AIDS cases were reported among 15-24 year olds
Children and adolescents in western China continued to carry a disproportionate burden from infectious diseases
https://www.sciencedaily.com/releases/2020/04/200403103957.htm
COVID-19 vaccine candidate shows promise
Medical research concept (stock image). Credit: © tilialucida / Adobe Stock
April 2, 2020
Science Daily/University of Pittsburgh
University of Pittsburgh School of Medicine scientists today announced a potential vaccine against SARS-CoV-2, the new coronavirus causing the COVID-19 pandemic. When tested in mice, the vaccine, delivered through a fingertip-sized patch, produces antibodies specific to SARS-CoV-2 at quantities thought to be sufficient for neutralizing the virus.
The paper appeared today in EBioMedicine, which is published by The Lancet, and is the first study to be published after critique from fellow scientists at outside institutions that describes a candidate vaccine for COVID-19. The researchers were able to act quickly because they had already laid the groundwork during earlier coronavirus epidemics.
"We had previous experience on SARS-CoV in 2003 and MERS-CoV in 2014. These two viruses, which are closely related to SARS-CoV-2, teach us that a particular protein, called a spike protein, is important for inducing immunity against the virus. We knew exactly where to fight this new virus," said co-senior author Andrea Gambotto, M.D., associate professor of surgery at the Pitt School of Medicine. "That's why it's important to fund vaccine research. You never know where the next pandemic will come from."
"Our ability to rapidly develop this vaccine was a result of scientists with expertise in diverse areas of research working together with a common goal," said co-senior author Louis Falo, M.D., Ph.D., professor and chair of dermatology at Pitt's School of Medicine and UPMC.
Compared to the experimental mRNA vaccine candidate that just entered clinical trials, the vaccine described in this paper -- which the authors are calling PittCoVacc, short for Pittsburgh Coronavirus Vaccine -- follows a more established approach, using lab-made pieces of viral protein to build immunity. It's the same way the current flu shots work.
The researchers also used a novel approach to deliver the drug, called a microneedle array, to increase potency. This array is a fingertip-sized patch of 400 tiny needles that delivers the spike protein pieces into the skin, where the immune reaction is strongest. The patch goes on like a Band-Aid and then the needles -- which are made entirely of sugar and the protein pieces -- simply dissolve into the skin.
"We developed this to build on the original scratch method used to deliver the smallpox vaccine to the skin, but as a high-tech version that is more efficient and reproducible patient to patient," Falo said. "And it's actually pretty painless -- it feels kind of like Velcro."
The system also is highly scalable. The protein pieces are manufactured by a "cell factory" -- layers upon layers of cultured cells engineered to express the SARS-CoV-2 spike protein -- that can be stacked further to multiply yield. Purifying the protein also can be done at industrial scale. Mass-producing the microneedle array involves spinning down the protein-sugar mixture into a mold using a centrifuge. Once manufactured, the vaccine can sit at room temperature until it's needed, eliminating the need for refrigeration during transport or storage.
"For most vaccines, you don't need to address scalability to begin with," Gambotto said. "But when you try to develop a vaccine quickly against a pandemic that's the first requirement."
When tested in mice, PittCoVacc generated a surge of antibodies against SARS-CoV-2 within two weeks of the microneedle prick.
Those animals haven't been tracked long term yet, but the researchers point out that mice who got their MERS-CoV vaccine produced a sufficient level of antibodies to neutralize the virus for at least a year, and so far the antibody levels of the SARS-CoV-2 vaccinated animals seem to be following the same trend.
Importantly, the SARS-CoV-2 microneedle vaccine maintains its potency even after being thoroughly sterilized with gamma radiation -- a key step toward making a product that's suitable for use in humans.
The authors are now in the process of applying for an investigational new drug approval from the U.S. Food and Drug Administration in anticipation of starting a phase I human clinical trial in the next few months.
"Testing in patients would typically require at least a year and probably longer," Falo said. "This particular situation is different from anything we've ever seen, so we don't know how long the clinical development process will take. Recently announced revisions to the normal processes suggest we may be able to advance this faster."
https://www.sciencedaily.com/releases/2020/04/200402144508.htm
China's control measures may have prevented 700,000 COVID-19 cases
March 31, 2020
Science Daily/Penn State
China's control measures during the first 50 days of the COVID-19 epidemic may have delayed the spread of the virus to cities outside of Wuhan by several days and, by interrupting transmission nationwide, prevented more than 700,000 infections across the country, according to an international team of researchers. The findings, published March 31 in the journal Science, could be useful to countries that are still in early phases of the COVID-19 outbreak.
"The number of confirmed cases in China by day 50 (February 19) of the epidemic, was around 30,000," said Christopher Dye, visiting professor of zoology and visiting fellow at the Oxford Martin School, University of Oxford. "Our analysis suggests that without the Wuhan travel ban and the national emergency response there would have been more than 700,000 confirmed COVID-19 cases outside of Wuhan by that date. China's control measures appear to have worked by successfully breaking the chain of transmission -- preventing contact between infectious and susceptible people."
The researchers used a unique combination of case reports, human movement data and public health intervention information to investigate the spread and control of COVID-19. They examined the movements of 4.3 million people out of Wuhan before the travel ban, the types and timing of control measures implemented across the cities of China and the numbers of COVID-19 cases reported each day in every city.
"One fascinating aspect of our work is that it shows the power of novel data streams such as cell phone mobility data," said Ottar Bjornstad, distinguished professor of entomology and biology, Penn State. "Since the time period we studied included the Spring Festival holiday and Chinese Lunar New Year, we were able to compare patterns of travel into and out of Wuhan during the outbreak with cell phone data from two previous spring festivals. The analysis revealed an extraordinary reduction in movement following the travel ban of January 23, 2020. Based on this data, we could also calculate the likely reduction in Wuhan-associated cases in other cities across China."
The team's model also analyzed the specific effects of the Wuhan shutdown and found that it delayed the arrival of COVID-19 in other cities by several days. "This delay provided extra time to prepare for the arrival of COVID-19 in more than 130 cities," said Huaiyu Tian, associate professor of epidemiology, Beijing Normal University.
These cities banned public gatherings, closed entertainment venues and suspended public transport, among other actions. As a result, they reported 33% fewer confirmed cases during the first week of their outbreaks than cities that did not implement a Level 1 Response.
While the control measures taken thus far have reduced the number of COVID-19 infections to very low levels, China, is by no means out of the woods.
"Given the small fraction of the Chinese population that has been infected, a much larger number of people remains at risk of COVID-19," said Tian. "We are acutely aware that resident or imported infections could lead to a resurgence of transmission."
Bjornstad noted that SARS-CoV-2 may establish as a human endemic globally in the years to come.
"It is critical to keep in mind that this virgin epidemic likely will affect people of different ages and susceptibilities, and therefore have different fatality levels, than possible subsequent seasonal epidemics," he said.
https://www.sciencedaily.com/releases/2020/03/200331130012.htm
Wastewater test could provide early warning of COVID-19
March 31, 2020
Science Daily/Cranfield University
Researchers at Cranfield University are working on a new test to detect SARS-CoV-2 in the wastewater of communities infected with the virus.
The wastewater-based epidemiology (WBE) approach could provide an effective and rapid way to predict the potential spread of novel coronavirus pneumonia (COVID-19) by picking up on biomarkers in faeces and urine from disease carriers that enter the sewer system.
Rapid testing kits using paper-based devices could be used on-site at wastewater treatment plants to trace sources and determine whether there are potential COVID-19 carriers in local areas.
Dr Zhugen Yang, Lecturer in Sensor Technology at Cranfield Water Science Institute, said: "In the case of asymptomatic infections in the community or when people are not sure whether they are infected or not, real-time community sewage detection through paper analytical devices could determine whether there are COVID-19 carriers in an area to enable rapid screening, quarantine and prevention.
"If COVID-19 can be monitored in a community at an early stage through WBE, effective intervention can be taken as early as possible to restrict the movements of that local population, working to minimise the pathogen spread and threat to public health."
Recent studies have shown that live SARS-CoV-2 can be isolated from the faeces and urine of infected people and the virus can typically survive for up to several days in an appropriate environment after exiting the human body.
The paper device is folded and unfolded in steps to filter the nucleic acids of pathogens from wastewater samples, then a biochemical reaction with preloaded reagents detects whether the nucleic acid of SARS-CoV-2 infection is present. Results are visible to the naked eye: a green circle indicating positive and a blue circle negative.
"We have already developed a paper device for testing genetic material in wastewater for proof-of-concept, and this provides clear potential to test for infection with adaption," added Dr Yang. "This device is cheap (costing less than £1) and will be easy to use for non-experts after further improvement.
"We foresee that the device will be able to offer a complete and immediate picture of population health once this sensor can be deployed in the near future."
WBE is already recognised as an effective way to trace illicit drugs and obtain information on health, disease, and pathogens. Dr Yang has developed a similar paper-based device to successfully conduct tests for rapid veterinary diagnosis in India and for malaria in blood among rural populations in Uganda.
Paper analytical devices are easy to stack, store and transport because they are thin and lightweight, and can also be incinerated after use, reducing the risk of further contamination.
https://www.sciencedaily.com/releases/2020/03/200331092713.htm
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
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