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

New study on COVID-19 estimates 5.1 days for incubation period

Median time from exposure to symptoms affirms earlier estimates and supports CDC's current 14-day quarantine period

March 10, 2020

Science Daily/Johns Hopkins University Bloomberg School of Public Health

An analysis of publicly available data on infections from the new coronavirus, SARS-CoV-2, that causes the respiratory illness COVID-19 yielded an estimate of 5.1 days for the median disease incubation period, according to a new study led by researchers at Johns Hopkins Bloomberg School of Public Health. This median time from exposure to onset of symptoms suggests that the 14-day quarantine period used by the U.S. Centers for Disease Control and Prevention for individuals with likely exposure to the coronavirus is reasonable.

The analysis suggests that about 97.5 percent of people who develop symptoms of SARS-CoV-2 infection will do so within 11.5 days of exposure. The researchers estimated that for every 10,000 individuals quarantined for 14 days, only about 101 would develop symptoms after being released from quarantine.

The findings will be published online March 9 in the journal Annals of Internal Medicine.

For the study, the researchers analyzed 181 cases from China and other countries that were detected prior to February 24, were reported in the media, and included likely dates of exposure and symptom onset. Most of the cases involved travel to or from Wuhan, China, the city at the center of the epidemic, or exposure to individuals who had been to Hubei, the province for which Wuhan is the capital.

The CDC and many other public health authorities around the world have been using a 14-day quarantine or active-monitoring period for individuals who are known to be at high risk of infection due to contact with known cases or travel to a heavily affected area.

"Based on our analysis of publicly available data, the current recommendation of 14 days for active monitoring or quarantine is reasonable, although with that period some cases would be missed over the long-term," says study senior author Justin Lessler, an associate professor in the Bloomberg School's Department of Epidemiology.

The global outbreak of SARS-CoV-2 infection emerged in December 2019 in Wuhan, a city of 11 million in central China, and has resulted in 95,333 officially confirmed cases around the world and 3,282 deaths from pneumonia caused by the virus, according to the World Health Organization's March 5 Situation Report. The majority of the cases are from Wuhan and the surrounding Hubei province, although dozens of other countries have been affected, including the U.S., but chiefly South Korea, Iran, and Italy.

An accurate estimate of the disease incubation period for a new virus makes it easier for epidemiologists to gauge the likely dynamics of the outbreak, and allows public health officials to design effective quarantine and other control measures. Quarantines typically slow and may ultimately stop the spread of infection, even if there are some outlier cases with incubation periods that exceed the quarantine period.

Lessler notes that sequestering people in a way that prevents them from working has costs, both personal and societal, which is perhaps most obvious when health care workers and first responders like firefighters are quarantined.

The new estimate of 5.1 days for the median incubation period of SARS-CoV-2 is similar to estimates from the earliest studies of this new virus, which were based on fewer cases. This incubation period for SARS-CoV-2 is in the same range as SARS-CoV, a different human-infecting coronavirus that caused a major outbreak centered in southern China and Hong Kong from 2002-04. For MERS-CoV, a coronavirus that has caused hundreds of cases in the Middle East, with a relatively high fatality rate, the estimated mean incubation period is 5-7 days.

Human coronaviruses that cause common colds have mean illness-incubation periods of about three days.

Lessler and colleagues have published an online tool that allows public health officials and members of the public to estimate how many cases would be caught and missed under different quarantine periods.

https://www.sciencedaily.com/releases/2020/03/200310164744.htm

COVID-19 infections in U.S. may be much higher, new estimates show

But even moderate interventions can help reduce spread, according to study

March 9, 2020

Science Daily/Cedars-Sinai Medical Center

By March 1, 2020, between 1,043 and 9,484 people in the U.S. may have already been infected by the COVID-19 coronavirus, far more than the number that had been publicly reported, according to a new Cedars-Sinai study.

"This suggests that the opportunity window to contain the epidemic of COVID-19 in its early stage is closing," the researchers stated in their paper, which is posted online on a forum where physicians and researchers share information.

The range of possible patients is significantly higher than the number of confirmed and presumptive U.S. cases reported by the federal Centers for Disease Control and Prevention, which stood at 164 as of March 7. Some news media on March 8 were reporting more than 500 total cases. [Editor's note: as of its March 9 update, the CDC put the total number of COVID-19 cases in the U.S. at 423, including both confirmed and presumptive positive cases.]

Cedars-Sinai investigators, who led the study, said they chose "very conservative" methods to estimate the number of coronavirus cases. "This makes our current estimation likely to be an underestimation of the true number of infected individuals in the U.S.," they wrote.

Shlomo Melmed, MB, ChB, executive vice president of Academic Affairs and dean of the medical faculty at Cedars-Sinai, added: "Cedars-Sinai is committed to the global efforts to combat COVID-19 and we believe that early dissemination of this study and the free sharing of the code that underlies the model will help in those efforts."

To arrive at infection estimates for their new study, the researchers modeled only COVID-19 coronavirus cases "imported" directly to the U.S. from the area of Wuhan, China, before Jan. 23, when the Chinese government locked down the city, and they assumed the lockdown stopped all outbound traffic. Potential cases arriving in the U.S. from other parts of China, or other heavily affected countries such as South Korea, Italy or Iran, were not included in the estimate.

The scale of the COVID-19 epidemic in the U.S. was calculated based on: air traffic data between Wuhan and the U.S., totals of confirmed cases publicly released by the CDC and transmission dynamics as estimated from previous research. The study took into account the identification and quarantine of individual domestic cases in the U.S. Among other considerations, the research team assumed the imported cases were no longer spreading infection.

Based on all these assumptions and methods, the investigators estimated the total number of people in the U.S. infected with coronavirus as of March 1 to be between 1,043 and 9,484. The first figure assumed current preventive procedures -- such as quarantines and screening international travelers at airports -- had reduced as much as 25% of the transmissibility in unidentified cases. The second figure assumed no intervention procedures had been undertaken to reduce the transmissibility.

The disparity between the lowest and highest estimates has important implications for controlling the COVID-19 epidemic, said Dermot P. McGovern, MD, PhD, professor of Medicine and Biomedical Sciences at Cedars-Sinai and senior author of the new study.

"Our model suggests that even moderately effective population interventions to reduce transmission can have a profound impact on the scale of the epidemic," McGovern explained. "This finding supports the role of public health interventions in controlling this disease."

But slowing transmission is not an easy task, given that most COVID-19 cases appear to be mild or even asymptomatic, the researchers noted, which can make it difficult to identify infected individuals who may be spreading the virus.

Despite these obstacles, McGovern said, it may still be possible to mitigate the COVID-19 outbreak through steps already suggested by public health experts.These include promoting social distancing and personal hygiene and restricting large-scale gatherings for occasions such as sporting events.

Additionally, performing mass screening for infected individuals, while expensive and logistically challenging, also would potentially help to control the epidemic, said McGovern, who also is director of Translational Research in the Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai.

Dalin Li, PhD, the new study's first author and co-corresponding author with McGovern, said the research team is releasing the just-completed study data online before the full study has been accepted in a journal due to the urgency of the COVID-19 outbreak.

"We are making the results public before peer review as it will be important for timely and informed public health decision-making. We are also making the model available to the research community so that others can build upon it." said Li, a research scientist in the Inflammatory Bowel and Immunobiology Research Institute.

The other co-authors of the study were Jonathan Braun, MD, PhD, professor of Medicine, and research operations associate Gregory Botwin from the Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai; and Jun Lv, Weihua Cao and Liming Li, all from Peking University Health Science Center in Beijing.

Funding: Research reported in this publication was supported by the National Institutes of Health, the Helmsley Charitable Trust and the F. Widjaja Foundation.

https://www.sciencedaily.com/releases/2020/03/200309110456.htm

To predict an epidemic, evolution can't be ignored

March 2, 2020

Science Daily/College of Engineering, Carnegie Mellon University

Whether it's coronavirus or misinformation, scientists can use mathematical models to predict how something will spread across populations. But what happens if a pathogen mutates, or information becomes modified, changing the speed at which it spreads? Researchers now show for the first time how important these considerations are.

When scientists try to predict the spread of something across populations -- anything from a coronavirus to misinformation -- they use complex mathematical models to do so. Typically, they'll study the first few steps in which the subject spreads, and use that rate to project how far and wide the spread will go.

But what happens if a pathogen mutates, or information becomes modified, changing the speed at which it spreads? In a new study appearing in this week's issue of Proceedings of the National Academy of Sciences (PNAS), a team of Carnegie Mellon University researchers show for the first time how important these considerations are.

"These evolutionary changes have a huge impact," says CyLab faculty member Osman Yagan, an associate research professor in Electrical and Computer Engineering (ECE) and corresponding author of the study. "If you don't consider the potential changes over time, you will be wrong in predicting the number of people that will get sick or the number of people who are exposed to a piece of information."

Most people are familiar with epidemics of disease, but information itself -- nowadays traveling at lightning speeds over social media -- can experience its own kind of epidemic and "go viral." Whether a piece of information goes viral or not can depend on how the original message is tweaked.

"Some pieces of misinformation are intentional, but some may develop organically when many people sequentially make small changes like a game of 'telephone,'" says Yagan. "A seemingly boring piece of information can evolve into a viral Tweet, and we need to be able to predict how these things spread."

In their study, the researchers developed a mathematical theory that takes these evolutionary changes into consideration. They then tested their theory against thousands of computer-simulated epidemics in real-world networks, such as Twitter for the spread of information or a hospital for the spread of disease.

In the context of spreading of infectious disease, the team ran thousands of simulations using data from two real-world networks: a contact network among students, teachers, and staff at a US high school, and a contact network among staff and patients in a hospital in Lyon, France.

These simulations served as a test bed: the theory that matches what is observed in the simulations would prove to be the more accurate one.

"We showed that our theory works over real-world networks," says the study's first author, Rashad Eletreby, who was a Carnegie Mellon Ph.D. student when he wrote the paper. "Traditional models that don't consider evolutionary adaptations fail at predicting the probability of the emergence of an epidemic."

While the study isn't a silver bullet for predicting the spread of today's coronavirus or the spread of fake news in today's volatile political environment with 100% accuracy -- one would need real-time data tracking the evolution of the pathogen or information to do that -- the authors say it's a big step.

"We're one step closer to reality," says Eletreby.

https://www.sciencedaily.com/releases/2020/03/200302153551.htm

Drug meant for Ebola may also work against coronaviruses

Drug meant for Ebola may also work against coronaviruses

Understanding how drugs work is an important step in developing new treatments for COVID-19

February 27, 2020

Science Daily/University of Alberta Faculty of Medicine & Dentistry

Researchers who have discovered why the drug remdesivir is effective in treating the coronaviruses that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) expect it might also be effective for treating patients infected with the new COVID-19 strain.

A group of University of Alberta researchers who have discovered why the drug remdesivir is effective in treating the coronaviruses that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) expect it might also be effective for treating patients infected with the new COVID-19 strain.

"Even if you know a drug works, it can be a red flag if you don't know how it works," said virologist Matthias Götte. "It is reassuring if you know exactly how it works against the target.

"We know the drug works against different coronaviruses, like MERS and SARS, and we know the novel coronavirus is very similar to SARS. So I would say I'm cautiously optimistic that the results our team found with remdesivir and MERS will be similar with COVID-19."

The study, published in the Journal of Biological Chemistry this week, is among the first in Canada to discuss the COVID-19 strain.

Until now, there has not been a published explanation of why remdesivir may work against coronaviruses, said Götte, who added his study is an important step in answering that question.

Developed by Gilead Sciences as a response to the 2014 West African Ebola virus epidemic, remdesivir was first used on a patient with the novel coronavirus earlier this year in the United States.

As reported in the New England Journal of Medicine, the patient was given the drug on the seventh day of illness, and showed marked improvement the following day, with symptoms eventually disappearing altogether. And at a recent press conference in Beijing, the assistant director-general of the World Health Organization, Bruce Alyward, said remdesivir is the only drug available that may have real efficacy against COVID-19.

"What our study showed was that remdesivir essentially mimics one of the natural building blocks for RNA synthesis necessary for genome replication of the virus. Enzymes within the virus are synthesizing the viral RNA genome with these building blocks, but they mix up the bits they need with the drug. Once the drug is incorporated into the growing RNA chain, the virus can no longer replicate,"explained Götte.

He said the next step is to wait for results from ongoing clinical trials with remdesivir, which are expected by the end of April. Even then, that won't be the end of the story, he cautioned.

"It's likely we'll need more than one drug to properly fight emerging diseases like COVID-19, as we have with HIV and hepatitis C virus infections," Götte said.

"Ideally, we will have a couple of drugs because certain strains could be resistant to certain treatments."

Götte's study was supported by grants from the Canadian Institutes of Health Research and the Alberta Ministry of Economic Development, Trade and Tourism through the Major Innovation Fund Program and Antimicrobial Resistance -- One Health Consortium.

https://www.sciencedaily.com/releases/2020/02/200227122123.htm

Novel coronavirus (COVID-19) imaging features overlap with SARS and MERS

COVID-19's imaging features are variable and nonspecific, but the imaging findings reported thus far do show

February 28, 2020

Science Daily/American Roentgen Ray Society

Although COVID-19's imaging features are variable and nonspecific, the findings thus far do show ''significant overlap'' with those of severe acute respiratory syndrome and Middle East respiratory syndrome. The early evidence suggests that initial chest imaging will show abnormality in at least 85% of patients, with 75% of patients having bilateral lung involvement initially that most often manifests as subpleural and peripheral areas of ground-glass opacity and consolidation.

COVID-19 is diagnosed on the presence of pneumonia symptoms (e.g., dry cough, fatigue, myalgia, fever, dyspnea), as well as recent travel to China or known exposure, and chest imaging plays a vital role in both assessment of disease extent and follow-up.

As per her review of the present clinical literature concerning COVID-19, Melina Hosseiny of the University of California at Los Angeles concluded: "Early evidence suggests that initial chest imaging will show abnormality in at least 85% of patients, with 75% of patients having bilateral lung involvement initially that most often manifests as subpleural and peripheral areas of ground-glass opacity and consolidation."

Furthermore, "older age and progressive consolidation" may imply an overall poorer prognosis.

Unlike SARS and MERS -- where initial chest imaging abnormalities are more frequently unilateral -- COVID-19 is more likely to involve both lungs on initial imaging.

"To our knowledge," Hosseiny et al. continued, "pleural effusion, cavitation, pulmonary nodules, and lymphadenopathy have not been reported in patients with COVID-19."

Ultimately, the authors of this AJR article recommended CT for follow-up in patients recovering from COVID-19 to evaluate long-term or even permanent pulmonary damage, including fibrosis -- as seen in SARS and MERS infections.

https://www.sciencedaily.com/releases/2020/02/200228142018.htm

COVID-19 a reminder of the challenge of emerging infectious diseases

February 28, 2020

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

The emergence and rapid increase in cases of coronavirus disease 2019 (COVID-19), a respiratory illness caused by a novel coronavirus, pose complex challenges to the global public health, research and medical communities, write federal scientists from NIH's National Institute of Allergy and Infectious Diseases (NIAID) and from the Centers for Disease Control and Prevention (CDC). Their commentary appears in The New England Journal of Medicine.

NIAID Director Anthony S. Fauci, M.D., NIAID Deputy Director for Clinical Research and Special Projects H. Clifford Lane, M.D., and CDC Director Robert R. Redfield, M.D., shared their observations in the context of a recently published report on the early transmission dynamics of COVID-19. The report provided detailed clinical and epidemiological information about the first 425 cases to arise in Wuhan, Hubei Province, China.

In response to the outbreak, the United States and other countries instituted temporary travel restrictions, which may have slowed the spread of COVID-19 somewhat, the authors note. However, given the apparent efficiency of virus transmission, everyone should be prepared for COVID-19 to gain a foothold throughout the world, including in the United States, they add. If the disease begins to spread in U.S. communities, containment may no longer be a realistic goal and response efforts likely will need to transition to various mitigation strategies, which could include isolating ill people at home, closing schools and encouraging telework, the officials write.

Drs. Fauci, Lane and Redfield point to the many research efforts now underway to address COVID-19. These include numerous vaccine candidates proceeding toward early-stage clinical trials as well as clinical trials already underway to test candidate therapeutics, including an NIAID-sponsored trial of the experimental antiviral drug remdesivir that began enrolling participants on February 21, 2020.

"The COVID-19 outbreak is a stark reminder of the ongoing challenge of emerging and re-emerging infectious pathogens and the need for constant surveillance, prompt diagnosis and robust research to understand the basic biology of new organisms and our susceptibilities to them, as well as to develop effective countermeasures," the authors conclude.

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Materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2020/02/200228142016.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

Remdesivir prevents MERS coronavirus disease in monkeys

February 13, 2020

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

The experimental antiviral remdesivir successfully prevented disease in rhesus macaques infected with Middle East respiratory syndrome coronavirus (MERS-CoV), according to a new study from National Institutes of Health scientists. Remdesivir prevented disease when administered before infection and improved the condition of macaques when given after the animals already were infected.

The new report from NIH's National Institute of Allergy and Infectious Diseases (NIAID) appears in the Proceedings of the National Academy of Sciences.

MERS-CoV is closely related to the 2019 novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV) that has grown to be a global public health emergency since cases were first detected in Wuhan, China, in December.

Remdesivir has previously protected animals against a variety of viruses in lab experiments. The drug has been shown experimentally to effectively treat monkeys infected with Ebola and Nipah viruses. Remdesivir also has been investigated as a treatment for Ebola virus disease in people.

The current study was conducted at NIAID's Rocky Mountain Laboratories in Hamilton, Montana. The work involved three groups of animals: those treated with remdesivir 24 hours before infection with MERS-CoV; those treated 12 hours after infection (close to the peak time for MERS-CoV replication in these animals); and untreated control animals.

The scientists observed the animals for six days. All control animals showed signs of respiratory disease. Animals treated before infection fared well: no signs of respiratory disease, significantly lower levels of virus replication in the lungs compared to control animals, and no lung damage. Animals treated after infection fared significantly better than the control animals: disease was less severe than in control animals, their lungs had lower levels of virus than the control animals, and the damage to the lungs was less severe.

The scientists indicate that the promising study results support additional clinical trials of remdesivir for MERS-CoV and COVID-19, the disease that SARS-CoV-2 causes. Several clinical trials of remdesivir for COVID-19 are under way in China, and other patients with COVID-19 have received the drug under a compassionate use protocol.

The Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, also provided support for this study. Gilead Sciences, Inc., developed remdesivir, also known as GS-5734, and collaborated in the research.

MERS-CoV emerged in Saudi Arabia in 2012. Through December 2019, the World Health Organization had confirmed 2,499 MERS-CoV cases and 861 deaths (or about 1 in 3). Because about one-third of MERS-CoV cases spread from infected people being treated in healthcare settings, the scientists suggest that remdesivir could effectively prevent disease in other patients, contacts of patients, and healthcare workers. They also note the drug might help patients who are diagnosed with MERS or COVID-19 if given soon after symptoms start.

https://www.sciencedaily.com/releases/2020/02/200213160128.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