Coronavirus infections may lead to delirium and potentially PTSD

May 19, 2020

Science Daily/University College London

People taken ill by coronavirus infections may experience psychiatric problems while hospitalised and potentially after they recover, suggests an analysis of past research led by the UCL Institute of Mental Health with King's College London collaborators.

The systematic review paper, published in The Lancet Psychiatry, compiled results from short- and long-term studies of people hospitalised by recent coronaviruses, namely SARS (Severe acute respiratory syndrome) in 2002-2004, MERS (Middle East respiratory syndrome) in 2012, as well as COVID-19 this year.

COVID-19 is caused by the SARS-CoV-2 virus, a type of coronavirus. Some coronaviruses only cause mild symptoms of the common cold, but SARS-CoV-2 can cause severe respiratory illness, as did SARS-CoV-1 (the virus implicated in the 2002-2004 SARS epidemic) and MERS-CoV, which caused MERS in 2012.

The analysis found that one in four people hospitalised with COVID-19 may experience delirium during their illness, a known problem among hospital patients, which can increase risk of death or extend time in hospital.

The post-recovery effects of COVID-19 are not yet known, so long-term risks such as post-traumatic stress disorder (PTSD), chronic fatigue, depression, and anxiety are based on SARS and MERS studies, which may or may not apply to COVID-19 as well.

Co-lead author Dr Jonathan Rogers (UCL Psychiatry and South London and Maudsley NHS Foundation Trust) said: "Most people with COVID-19 will not develop any mental health problems, even among those with severe cases requiring hospitalisation, but given the huge numbers of people getting sick, the global impact on mental health could be considerable.

"Our analysis focuses on potential mental health risks of being hospitalised with a coronavirus infection, and how psychiatric conditions could worsen the prognosis or hold people back from returning to their normal lives after recovering."

The authors of the new paper analysed 65 peer-reviewed studies and seven recent pre-prints that are awaiting peer review, which included data from over 3,500 people who have had one of the three related illnesses. The review only included results from people who were hospitalised, and not people with more mild cases. The findings cover both acute symptoms during the illness, and long-term outcomes from two months to 12 years.

Almost one in three people hospitalised with SARS or MERS went on to develop PTSD, at an average follow-up time of almost three years, especially if they had ongoing physical health problems. Rates of depression and anxiety were also high, at roughly 15% one year or longer after the illness, with a further 15% also experiencing some symptoms of depression and anxiety without a clinical diagnosis. More than 15% also experienced chronic fatigue, mood swings, sleep disorder or impaired concentration and memory.

While in hospital, a significant minority of people with coronavirus infections experienced delirium symptoms such as confusion, agitation and altered consciousness. Almost 28% of people hospitalised for SARS and MERS experienced confusion, and early evidence from the ongoing pandemic suggests that delirium could be similarly common in COVID-19 patients. The authors found some preliminary evidence that delirium may have been associated with raised mortality during the MERS outbreak.

Co-lead author Dr Edward Chesney (Institute of Psychiatry, Psychology & Neuroscience, King's College London and South London and Maudsley NHS Foundation Trust) said: "We need more research on how to prevent mental health problems in the long term. One possibility might be to reduce social isolation by allowing patients to communicate with their loved ones by using video links."

The body of research also identified some of the risk factors associated with worse mental health outcomes. Researchers found that worrying a lot about the illness was associated with worse mental health in the long run, and healthcare workers had worse long-term mental health outcomes than other groups, while making a good physical recovery predicted better long-term mental health.

Senior author Professor Anthony David (UCL Institute of Mental Health) said: "To avoid a large-scale mental health crisis, we hope that people who have been hospitalised with COVID-19 will be offered support, and monitored after they recover to ensure they do not develop mental illnesses, and are able to access treatment if needed.

"While most people with COVID-19 will recover without experiencing mental illness, we need to research which factors may contribute to enduring mental health problems, and develop interventions to prevent and treat them."

https://www.sciencedaily.com/releases/2020/05/200518184914.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

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

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

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

March 23, 2020

Science Daily/Louisiana State University Health Sciences Center

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

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

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

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

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

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

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

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

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

New coronavirus stable for hours on surfaces

SARS-CoV-2 stability similar to original SARS virus

March 17, 2020

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

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

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

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

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

The scientists highlighted additional observations from their study:

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

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

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

• Avoid close contact with people who are sick.

• Avoid touching your eyes, nose, and mouth.

• Stay home when you are sick.

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

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

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

COVID-19 coronavirus epidemic has a natural origin

 March 17, 2020

Science Daily/Scripps Research Institute

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

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

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

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

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

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

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

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

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

Evidence for natural evolution

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

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

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

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

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

Possible origins of the virus

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

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

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

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

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

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

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

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

COVID-19 appears less severe in children

March 13, 2020

Science Daily/Wolters Kluwer Health

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

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

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

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

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

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

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

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

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

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

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

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

Scientists identify potential targets for immune responses to novel coronavirus

Their analysis provides essential information for vaccine design and the evaluation of diagnostics and vaccine candidates

March 12, 2020

Science Daily/La Jolla Institute for Immunology

Newly published research provides the first analysis of potential targets for effective immune responses against the novel coronavirus. Researchers used existing data from known coronaviruses to predict which parts of SARS-CoV-2 are capable of activating the human immune system.

Within two months, SARS-CoV-2, a previously unknown coronavirus, has raced around globe, infecting over a 100,000 people with numbers continuing to rise quickly. Effective countermeasures require helpful tools to monitor viral spread and understand how the immune system responds to the virus.

Publishing in the March 16, 2020, online issue of Cell, Host and Microbe, a team of researchers at La Jolla Institute for Immunology, in collaboration with researchers at the J. Craig Venter Institute, provides the first analysis of potential targets for effective immune responses against the novel coronavirus. The researchers used existing data from known coronaviruses to predict which parts of SARS-CoV-2 are capable of activating the human immune system.

When the immune system encounters a bacterium or a virus, it zeroes in on tiny molecular features, so called epitopes, which allow cells of the immune system to distinguish between closely related foreign invaders and focus their attack. Having a complete map of viral epitopes and their immunogenicity is critical to researchers attempting to design new or improved vaccines to protect against COVID-19, the disease caused by SARS-CoV-2.

"Right now, we have limited information about which pieces of the virus elicit a solid human response," says the study's lead author Alessandro Sette, Dr. Biol.Sci, a professor in the Center for Infectious Disease and Vaccine Research at LJI. "Knowing the immunogenicity of certain viral regions, or in other words, which parts of the virus the immune system reacts to and how strongly, is of immediate relevance for the design of promising vaccine candidates and their evaluation."

While scientists currently know very little about how the human immune system responds to SARS-CoV-2, the immune response to other coronaviruses has been studied and a significant amount of epitope data is available.

Four other coronaviruses are currently circulating in the human population. They cause generally mild symptoms and together they are responsible for an estimated one quarter of all seasonal colds. But every few years, a new coronavirus emerges that causes severe disease as was the case with SARS-CoV in 2003 and MERS-CoV in 2008, and now SARS-CoV-2.

"SARS-CoV-2 is most closely related to SARS-CoV, which also happens to be the best characterized coronavirus in terms of epitopes," explains first author Alba Grifoni, Ph.D, a postdoctoral researcher in the Sette lab.

For their study, the authors used available data from the LJI-based Immune Epitope Database (IEDB), which contains over 600,000 known epitopes from some 3,600 different species, and the Virus Pathogen Resource (ViPR), a complementary repository of information about pathogenic viruses. The team compiled known epitopes from SARS-CoV and mapped the corresponding regions to SARS-CoV-2.

"We were able to map back 10 B cell epitopes to the new coronavirus and because of the overall high sequence similarity between SARS-CoV and SARS-CoV-2, there is a high likelihood that the same regions that are immunodominant in SARS-CoV are also dominant in SARS-CoV-2 is," says Grifoni.

Five of these regions were found in the spike glycoprotein, which forms the "crown" on the surface of the virus that gave coronaviruses their name; two in the membrane protein, which is embedded in the membrane that envelopes the protective protein shell around the viral genome and three in the nucleoprotein, which forms the shell.

In a similar analysis, T cell epitopes were also mostly associated with the spike glycoprotein and nucleoprotein.

In a completely different approach, Grifoni used the epitope prediction algorithm hosted by the IEDB to predict linear B cell epitopes. A recent study by scientists at the University of Texas Austin determined the three-dimensional structure of the spike proteins, which allowed the LJI team to take the protein's spatial architecture into account when predicting epitopes. This approach confirmed two of the likely epitope regions they had predicted earlier.

To substantiate the SARS-CoV-2 T cell epitopes identified based on their homology to SARS-CoV, Grifoni compared them with epitopes pinpointed by the Tepitool resource in the IEDB. Using this approach, she was able verify 12 out of 17 SARS-CoV-2 T cell epitopes identified based on sequence similarities to SARS-CoV.

"The fact that we found that many B and T cell epitopes are highly conserved between SARS-CoV and SARS-CoV-2 provides a great starting point for vaccine development," says Sette. "Vaccine strategies that specifically target these regions could generate immunity that's not only cross-protective but also relatively resistant to ongoing virus evolution."

The work was funded in part by the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health through contracts 75N9301900065, 75N93019C00001 and 75N93019C00076.

https://www.sciencedaily.com/releases/2020/03/200312101056.htm

COVID-19 vaccine development

February 26, 2020

Science Daily/Hong Kong University of Science and Technology

Scientists have recently identified a set of potential vaccine targets for SARS-CoV-2 coronavirus, to guide experimental efforts towards vaccine development against novel pneumonia (COVID-19).

A team of scientists at the Hong Kong University of Science and Technology (HKUST) has recently made an important discovery in identifying a set of potential vaccine targets for the SARS-CoV-2 coronavirus, providing crucial leads for guiding experimental efforts towards the vaccine development against the novel pneumonia (COVID-19) caused by the virus.

Like SARS-CoV, which caused the SARS (Severe Acute Respiratory Syndrome) outbreak in 2003, SARS-CoV-2 belongs to the same Betacoronavirus genus. By considering the genetic similarity between SARS-CoV-2 and SARS-CoV, the team leveraged experimentally-determined immunological data to identify a set of SARS-CoV- derived B cell and T cell epitopes that exactly match to SARS-CoV-2. Epitopes are biomarkers recognized by the immune system to trigger actions against the virus. As no mutation has been observed in the identified epitopes among the available SARS-CoV-2 genetic sequences, immune targeting of these epitopes may potentially offer protection against the novel pneumonia COVID-19.

The team, led by data scientists Prof. Matthew McKay and Dr. Ahmed Abdul Quadeer, expected that their work can assist in guiding experimental research towards the development of effective vaccines against SARS- CoV-2.

Prof. McKay highlighted that "Despite similarities between SARS-CoV and SARS-CoV-2, there is genetic variation between the two, and it is not obvious if epitopes that elicit an immune response against SARS-CoV will likely be effective against SARS-CoV-2. We found that only roughly 20% of the SARS-CoV epitopes map identically to SARS-CoV-2, and believe these are promising candidates."

"For the identified T cell epitopes, we also performed a population coverage analysis and determined a set of epitopes that is estimated to provide broad coverage globally as well as in China" said Dr. Quadeer. The estimated population coverage represents the percentage of individuals within the selected population that are likely to elicit an immune response to at least one epitope from the identified set.

Prof. McKay is a Professor in the Departments of Electronic & Computer Engineering and Chemical & Biological Engineering; Dr. Quadeer is a post-doctoral fellow in the Department of Electronic & Computer Engineering. Their findings were recently published in the scientific journal Viruses this month.

"Our objective was to try to assist with the initial phase of vaccine development, by providing recommendations of specific epitopes that may potentially be considered for incorporation in vaccine designs" Prof. McKay added. "More generally, our work is part of a global effort seeking to capitalize on data for COVID-19, made available and rapidly shared by the scientific community, to understand this new virus and come up with effective interventions."

The beginning of 2020 has seen the emergence of SARS-CoV-2 outbreak in mainland China, which has quickly spread to over 30 countries around the world, infecting over 80,000 people and causing over 2,600 deaths as of late February 2020.

https://www.sciencedaily.com/releases/2020/02/200226091227.htm

Effectiveness of travel bans -- readily used during infectious disease outbreaks -- mostly unknown

February 13, 2020

Science Daily/University of Washington

While travel bans are frequently used to stop the spread of an emerging infectious disease, a new study of published research found that the effectiveness of travel bans is mostly unknown.

Because of the quick and deadly outbreak in late December of a novel coronavirus in Wuhan, China, now known as COVID-19 -- infecting tens of thousands and killing hundreds within weeks, while spreading to at least 24 other countries -- many governments, including the United States, have banned or significantly restricted travel to and from China.

And while travel bans are frequently used to stop the spread of an emerging infectious disease, a new University of Washington and Johns Hopkins University study of published research found that the effectiveness of travel bans is mostly unknown.

However, said lead author Nicole Errett, a lecturer in the UW Department of Environmental & Occupational Health Sciences in the School of Public Health, that's largely due to the fact that very little research into the effectiveness of travel bans exists.

"Some of the evidence suggests that a travel ban may delay the arrival of an infectious disease in a country by days or weeks. However, there is very little evidence to suggest that a travel ban eliminates the risk of the disease crossing borders in the long term," said Errett, co-director of the ColLABorative on Extreme Event Resilience, a research lab focused on addressing real-world issues relevant to community resilience.

The researchers combed through thousands of published articles in an effort to identify those that directly addressed travel bans used to reduce the geographic impact of the Ebola virus, SARS (Severe Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome) and the Zika virus. They did not include studies of influenza viruses, for which travel bans have already been shown to be ineffective in the long term.

In the end, the researchers were able to identify just six studies that fit their criteria. Those six were based on models or simulations, not data from actual bans after they were implemented, to assess the effectiveness of travel bans in controlling outbreaks. Consequently, to improve research in this area, the study authors recommend that research questions, partnerships and study protocols be established ahead of the next outbreak so empirical data can be collected and assessed quickly.

"Travel bans are one of several legal options that governments have drawn on to mitigate a pandemic," said co-author Lainie Rutkow, a professor of health policy and management at Johns Hopkins Bloomberg School of Public Health. "As coronavirus spreads, our study raises the importance of understanding the effectiveness of legal and policy responses intended to protect and promote the public's health."

"When assessing the need for, and validity of, a travel ban, given the limited evidence, it's important to ask if it is the least restrictive measure that still protects the public's health, and even if it is, we should be asking that question repeatedly, and often," said co-author Lauren Sauer, an assistant professor of emergency medicine at Johns Hopkins University's School of Medicine and director of operations with the university's Office of Critical Event Preparedness and Response.

Consequently, the authors write, additional research is "urgently needed" to inform policy decisions, especially in light of the tremendous social, economic and political impacts of their implementation.

https://www.sciencedaily.com/releases/2020/02/200213175923.htm