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•Mar 17, 2021
What Alcohol Does to Your Body ____ In this video, Justin from the Institute of Human Anatomy discusses the various structures ethanol interacts with as it journey’s through the human body after consumption.
COVID-19 Virus Reinfections Rare, but Riskiest After Age 65
When researchers analyzed test results of 4 million people in Denmark, they found that less than 1% of those who tested positive experienced reinfection…Initial infection was associated with about 80% protection overall against getting SARS-CoV-2 again. However, among those older than 65, the protection plummeted to 47%.
By Damian McNamara
Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
The first large study of its kind reveals that SARS-CoV-2 reinfections remain rare, although people older than 65 are at higher risk.
When researchers analyzed test results of 4 million people in Denmark, they found that less than 1% of those who tested positive experienced reinfection.
Initial infection was associated with about 80% protection overall against getting SARS-CoV-2 again. However, among those older than 65, the protection plummeted to 47%.
Dr Daniela Michlmayr
“Not everybody is protected against reinfection after a first infection. Older people are at higher risk of catching it again,” co–lead author Daniela Michlmayr, PhD, told Medscape Medical News. “Our findings emphasize the importance of policies to protect the elderly and of adhering to infection control measures and restrictions, even if previously infected with COVID-19.”
Verifying the Need for Vaccination
“The findings also highlight the need to vaccinate people who had COVID-19 before, as natural immunity to infection ― especially among the elderly 65 and older ― cannot be relied upon,” added Michlmayr, a researcher in the Department of Bacteria, Parasites, and Fungi at the Staten Serums Institut, Copenhagen, Denmark.
The population-based observational study was published online March 17 in The Lancet.
Dr David Hirschwerk
“The findings make sense, as patients who are immunocompromised or of advanced age may not mount an immune response that is as long-lasting,” David Hirschwerk, MD, told Medscape Medical News when asked to comment. “It does underscore the importance of vaccination for people of more advanced age, even if they previously were infected with COVID.
“For those who were infected last spring and have not yet been vaccinated, this helps to support the value of still pursuing the vaccine,” added Hirschwerk, an infectious disease specialist at Northwell Health in Manhasset, New York.
Evidence on reinfection risk was limited prior to this study. “Little is known about protection against SARS-CoV-2 repeat infections, but two studies in the UK have found that immunity could last at least 5 to 6 months after infection,” the authors note.
Along with co–lead author Christian Holm Hansen, PhD, Michlmayr and colleagues found that 2.11% of 525,339 individuals tested positive for SARS-CoV-2 during the first surge in Denmark from March to May 2020. Within this group, 0.65% tested positive during a second surge from September to December.
New study points to novel drug target for treating COVID-19
The team discovered that a coronavirus enzyme called PLpro (papain-like protease) blocks the body’s immune response to the infection. More research is necessary, but the findings suggest that therapeutics that inhibit the enzyme may help treat COVID-19.
Reprinted from Medicalxpress, March 16, 2021
Researchers from Cleveland Clinic’s Florida Research and Innovation Center (FRIC) have identified a potential new target for anti-COVID-19 therapies. Their findings were published in Nature Microbiology.
Led by FRIC scientific director Michaela Gack, Ph.D., the team discovered that a coronavirus enzyme called PLpro (papain-like protease) blocks the body’s immune response to the infection. More research is necessary, but the findings suggest that therapeutics that inhibit the enzyme may help treat COVID-19.
“SARS-CoV-2—the virus that causes COVID-19—has evolved quickly against many of the body’s well-known defense mechanisms,” Gack said. “Our findings, however, offer insights into a never-before characterized mechanism of immune activation and how PLpro disrupts this response, enabling SARS-CoV-2 to freely replicate and wreak havoc throughout the host. We discovered that inhibiting PLpro may help rescue the early immune response that is key to limiting viral replication and spread.”
One of the body’s frontline immune defenses is a class of receptor proteins, including one called MDA5, that identify invaders by foreign patterns in their genetic material. When the receptors recognize a foreign pattern, they become activated and kick-start the immune system into antiviral mode. This is done in part by increasing the downstream expression of proteins encoded by interferon-stimulated genes (ISGs).
In this study, Gack and her team identified a novel mechanism that leads to MDA5 activation during virus infection. They found that ISG15 must physically bind to specific regions in the MDA5 receptor—a process termed ISGylation—in order for MDA5 to effectively activate and unleash antiviral actors against invaders. They showed that ISGylation helps to promote the formation of larger MDA5 protein complexes, which ultimately results in a more robust immune response against a range of viruses.
“While discovery of a novel mechanism of immune activation is exciting on its own,” Gack said, “we also discovered a bit of bad news, which is that SARS-CoV-2 also understands how the mechanism works, considering it has already developed a strategy to block it.”
The research team shows that the coronavirus enzyme PLpro physically interacts with the receptor MDA5 and inhibits the ISGylation process.
“We’re already looking forward to the next phase of study to investigate whether blocking PLpro’s enzymatic function, or its interaction with MDA5, will help strengthen the human immune response against the virus,” Gack said. “If so, PLpro would certainly be an attractive target for future anti-COVID-19 therapeutics.”
More information: GuanQun Liu et al, ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity, Nature Microbiology (2021). DOI: 10.1038/s41564-021-00884-1
Citation: New study points to novel drug target for treating COVID-19 (2021, March 16) retrieved 17 March 2021 from https://medicalxpress.com/news/2021-03-drug-covid-.html
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Leprosy drug holds promise as at-home treatment for COVID-19
Phase 2 clinical trial could begin immediately for clofazimine, an FDA-approved drug on WHO’s List of Essential Medicines
News Release, March 16, 2021
Reprinted from EurekAlert, AAAS
LA JOLLA, CALIF. – March 16, 2021 – A Nature study authored by scientists at Sanford Burnham Prebys Medical Discovery Institute and the University of Hong Kong shows that the leprosy drug clofazimine, which is FDA approved and on the World Health Organization’s List of Essential Medicines, exhibits potent antiviral activities against SARS-CoV-2 and prevents the exaggerated inflammatory response associated with severe COVID-19. Based on these findings, a Phase 2 study evaluating clofazimine as an at-home treatment for COVID-19 could begin immediately.
“Clofazimine is an ideal candidate for a COVID-19 treatment. It is safe, affordable, easy to make, taken as a pill and can be made globally available,” says co-senior author Sumit Chanda, Ph.D., professor and director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys. “We hope to test clofazimine in a Phase 2 clinical trial as soon as possible for people who test positive for COVID-19 but are not hospitalized. Since there is currently no outpatient treatment available for these individuals, clofazimine may help reduce the impact of the disease, which is particularly important now as we see new variants of the virus emerge and against which the current vaccines appear less efficacious.”
Promising candidate revealed by screening drug library
Clofazimine was initially identified by screening one of the world’s largest collections of known drugs for their ability to block the replication of SARS-CoV-2. Chanda’s team previously reported in Nature that clofazimine was one of 21 drugs effective in vitro, or in a lab dish, at concentrations that could most likely be safely achieved in patients.
In this study, the researchers tested clofazimine in hamsters–an animal model for COVID-19–that were infected with SARS-CoV-2. The scientists found that clofazimine lowered the amount of virus in the lungs, including when given to healthy animals prior to infection (prophylactically). The drug also reduced lung damage and prevented “cytokine storm,” an overwhelming inflammatory response to SARS-CoV-2 that can be deadly.
“The animals that received clofazimine had less lung damage and lower viral load, especially when receiving the drug before infection,” says co-senior author Ren Sun, Ph.D., professor at the University of Hong Kong and distinguished professor emeritus at the University of California, Los Angeles (UCLA). “Besides inhibiting the virus, there are indications that the drug also regulates the host response to the virus, which provides better control of the infection and inflammation.”
Clofazimine also worked synergistically with remdesivir, the current standard-of-care treatment for people who are hospitalized due to COVID-19, when given to hamsters infected with SARS-CoV-2. These findings suggest a potential opportunity to stretch the availability of remdesivir, which is costly and in limited supply.
How clofazimine works
The study showed that clofazimine stops SARS-CoV-2 infection in two ways: blocking its entry into cells and disrupting RNA replication (SARS-CoV-2 uses RNA to replicate). Clofazimine was able to reduce the replication of MERS-CoV, the coronavirus that causes Middle East Respiratory Syndrome (MERS), in human lung tissue.
“Potentially most importantly, clofazimine appears to have pan-coronavirus activity, indicating it could be an important weapon against future pandemics,” says co-senior author Kwok-Yung Yuen, M.D., chair of Infectious Diseases at the University of Hong Kong, who discovered the coronavirus that causes severe acute respiratory syndrome (SARS). “Our study suggests that we should consider creating a stockpile of ready-made clofazimine that could be deployed immediately if another novel coronavirus emerges.”
In July 2020 Sumit Chanda shared more about his team’s race to find a treatment for COVID-19.
Testing clofazimine in the clinic
A Phase 2 trial evaluating clofazimine in combination with interferon beta-1b as a treatment for people with COVID-19 who are hospitalized is ongoing at the University of Hong Kong. Interferon beta-1b is an immunoregulator that is given as an injection and is currently used to treat people with multiple sclerosis.
“Our data suggests that clofazimine should also be tested as a monotherapy for people with COVID-19, which would lower many barriers to treatment,” says Chanda. “People with COVID-19 would be able to simply receive a regime of low-cost pills, instead of traveling to a hospital to receive an injection.”
Old drug finds new purpose
Clofazimine was discovered in 1954 and is used to treat leprosy. Its promise for treating COVID-19 was discovered by high-throughput screening of more than 12,000 drugs from the ReFRAME drug library–one of the most comprehensive collections of compounds that have been approved by the FDA for other diseases or that have been tested extensively for human safety. ReFRAME was created by Calibr, the drug discovery division of Scripps Research, with support from the Bill & Melinda Gates Foundation, with a goal of repurposing existing drugs to meet unmet clinical needs.
A global effort
The co-senior and co-corresponding study authors are Sumit Chanda of Sanford Burnham Prebys; Ren Sun of the University of Hong Kong and the University of California Los Angeles; and Kwok-Yung Yuen of the University of Hong Kong. The first authors of the study are Shuofeng Yuan, Xiangzhi Meng, Jasper Fuk-Woo Chan and Zi-Wei Ye of the University of Hong Kong; and Xin Yin of Sanford Burnham Prebys, who contributed equally to the study.
Additional study authors include Laura Riva, Lars Pache, Naoko Matsunaga and Yuan Pu of Sanford Burnham Prebys; Chris Chun-Yiu Chan, Pok-Man Lai, Chris Chung-Sing Chan, Vincent Kwok-Man Poon, Andrew Chak-Yiu Lee, Chun-Kit Yuen, Jianli Cao, Ronghui Liang, Kaiming Tang, Wan Xu, Chit-Ying Lau, Ko-Yung Sit, Wing-Kuk Au, Runming Wang, Kong-Hung Sze, Anna Jinxia Zhang, Hin Chu, Kin-Hang Kok, Ivan Fan-Ngai Hung, Ronald Adolphus Li, Honglin Chen, Hongzhe Sun and Dong-Yan Jin of the University of Hong Kong; Yu-Yuan Zhang, Yan-Dong Tang and Xue-Hui Cai of the Chinese Academy of Agricultural Sciences; Thomas Mandel Clausen and Jessica Pihl of the University of California San Diego (UCSD) and University of Copenhagen; Juntaek Oh, Dong Wang and Jeffrey D. Esko of UCSD; Li Sheng of University of Hong Kong and University of California Los Angeles; and Yushen Du of UCLA.
The study’s DOI is 10.1038/s41586-021-03431-4.
Research reported in this press release was supported by the National Institutes of Health (NIH) (U19AI118610, U19AI135972, U19AI142733), the Department of Defense (DoD) (W81XWH-20-1-0270), Defense Advanced Research Projects Agency (HR0011-19-2-0020), the Center of Excellence for Influenza Research and Surveillance (HHSN272201400008C), JPB Foundation, the Open Philanthropy Project (2020-215611 (5384)), the University of Hong Kong, National Key R&D Programmes of China (2020YFA0707500, 2020YFA0707504), Richard Yu and Carol Yu, the Shaw Foundation Hong Kong, Michael Seak-Kan Tong, May Tam Mak Mei Yin, Hui Ming, Hui Hoy and Chow Sin, Lan Charity Fund Limited, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, the Jessie & George Ho Charitable Foundation, Perfect Shape Medical Limited, Kai Chong Tong, Foo Oi Foundation Limited, Tse Kam Ming, Laurence, the Norman & Cecilia Yip Foundation, Dinah Ruch and Susan & James Blair.
About the University of Hong Kong
The University of Hong Kong (HKU), founded in 1911, is the oldest tertiary institution in Hong Kong. HKU delivers impact through internationalisation, innovation and interdisciplinarity. It attracts and nurtures global scholars through excellence in research, teaching and learning, and knowledge exchange.
About Sanford Burnham Prebys Medical Discovery Institute
Sanford Burnham Prebys is a preeminent, independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. For more than 40 years, our research has produced breakthroughs in cancer, neuroscience, immunology and children’s diseases, and is anchored by our NCI-designated Cancer Center and advanced drug discovery capabilities. For more information, visit us at SBPdiscovery.org or on Facebook at facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.
2,000-year-old biblical texts found in Israel, 1st since Dead Sea Scrolls
6,000-year-old child skeleton found together with world’s oldest woven basket in Judean Desert cave • First discovery of this kind since Dead Sea Scrolls.
By ROSSELLA TERCATIN MARCH 16, 2021
A 2,000-year-old biblical scroll has been unearthed in the Judean desert, the Israel Antiquities Authority announced Tuesday. The groundbreaking discovery marks the first time that such an artifact has been uncovered in decades, since the time of the Dead Sea Scrolls.
The two dozen fragments were found in a cave in the Judean Desert, as a result of a several-year-long breathtaking rescue operation with the purpose of surveying all the caves of the area, carried out by the IAA in cooperation with the Archaeology Department of the Civil Administration.
The scroll was written in Greek, but God’s name appears in paleo-Hebrew. It contains passages from the Minor Prophets, including Nahum.
Besides the manuscript, the cave harbored several other unique findings, including a trove of coins from the time of the Bar Kochba Revolt, the skeleton of a child dating back to some 6,000 years, and a 10,000-year-old exceptionally well-preserved basket which experts say might be the earliest item of this kind ever uncovered.
The excavation of the caves was conducted in difficult conditions Photo: Yoli Schwartz, Israel Antiquities Authority
“These are the things you are to do: Speak the truth to one another, render true and perfect justice in your gates. And do not contrive evil against one another, and do not love perjury, because all those are things that I hate – declares the Lord,” one of the fragments reads, featuring an excerpt of the biblical book of Zechariah.
“The aim of this national initiative is to rescue these rare and important heritage assets from the robbers’ clutches,” IAA director Israel Hasson said in a press release. “The newly discovered scroll fragments are a wake-up call to the state. Resources must be allocated for the completion of this historically important operation. We must ensure that we recover all the data that has not yet been discovered in the caves, before the robbers do. Some things are beyond value.”
The cave, known as “the Cave of Horror” in the Judean Desert reserve’s Nahal Hever, stands some 80 meters below the clifftop and can be accessed only by clinging to ropes.
Rappelling to the Cave of Horror. Photo: Eitan Klein, Israel Antiquities Authority
“This is definitely an exciting moment, as we present and reveal to the public an important and significant piece in the history and culture of the Land of Israel,” said Hananya Hizmi, Head Staff Officer of the Civil Administration’s Archaeology Department in Judea and Samaria.
“In as early as the late 1940s, we became aware of the cultural heritage remains of the ancient population of the Land of Israel with the first discoveries of the Dead Sea Scrolls,” he said. “Now, in this national operation, which continues the work of previous projects, new finds and evidence have been discovered and unearthed that shed even more light on the different periods and cultures of the region.
“The finds attest to a rich, diverse and complex way of life, as well as to the harsh climatic conditions that prevailed in the region hundreds and thousands of years ago.”
The basket as found in Muraba‘at Cave. (Yoli Schwartz, Israel Antiquities Authority)
The conditions of the region remain challenging to this day. Some 80 kilometers of caves have been surveyed within the operation, including very remote and inaccessible hollows. Drones and mountain equipment have been employed; about half of the area is still to be explored.
A rare cache from the Bar Kokhba period. Photo: Dafna Gazit, Israel Antiquities Authority
The skeleton, which probably belonged to a child aged 6-12, was wrapped in a cloth and mummified.
6,000-year-old skeleton of a girl or a boy who was buried wrapped in cloth. (Emil Aladjem, Israel Antiquities Authority)
“On moving two flat stones, we discovered a shallow pit intentionally dug beneath them, containing a skeleton of a child placed in a fetal position,” IAA prehistorian Ronit Lupu explained.
“It was obvious that whoever buried the child had wrapped him up and pushed the edges of the cloth beneath him, just as a parent covers his child in a blanket,” she said. “A small bundle of cloth was clutched in the child’s hands. The child’s skeleton and the cloth wrapping were remarkably well preserved, and because of the climatic conditions in the cave, a process of natural mummification had taken place; the skin, tendons, and even the hair were partially preserved, despite the passage of time.”
Rafael Bardaji on Why Europe “Will Remain Hostile to Israel”
Bardaji discussed several factors that give rise to these and other clashes of interests between the EU and Israel. Culturally, there is a clash of values between a “pacifist continent … [where] nobody wants to kill or die for anything,” and Israel, “defined as a Jewish state for the Jewish people” committed to defending its borders and people.
By Marilyn Stern
Rafael Bardaji, executive director of the Friends of Israel Initiative and Spain’s former national security advisor, spoke to participants in a February 15 Middle East Forum webinar (video) about the persistent “clash of interests … between the European Union (EU) and the Israeli government” likely to endure for the foreseeable future.
According to Bardaji, three points of friction between the EU and Israel are prominent this year. The first is the decision by the International Criminal Court (ICC) and its former prosecutor, Gambian lawyer Fatou Bensouda, to “accept the Palestinians as a national state … able to ask for investigation, prosecution and indictment of a non-state-member of the ICC,” namely Israel. “The Europeans are very well attached, by heart, to the ICC despite all violations of international law regarding this decision.” Bardaji said the most effective way to counter the ICC’s illegal action is to approach those European powers opposed to Bensouda’s decision and persuade them to defund the ICC.
The second point of friction concerns Iran. Despite Tehran’s violations of the Joint Comprehensive Plan of Action (JCPOA), the EU is eager to “keep it afloat” and press the U.S. to lift its sanctions imposed under Trump in order to resume their own trade with Tehran. The Biden administration’s clear desire to reach out to Iran for a new agreement will encourage the Europeans to “offer even more concessions to Iran” to hasten a deal.
The third point of conflict is European eagerness to “pull the Palestinians back into the center stage” of the Middle East peace process, despite the fact that their longstanding belief that “without them, nothing can be done in the region” has been proven wrong. The Abraham Accords established as a result of Trump’s “thinking out of the box” bore results, but the Biden administration has expressed “doubts about nurturing new countries” to join the accords, which will cause the Europeans to stiffen their own resistance.
An anti-Israel, anti-Semitic demonstration in Berlin, Germany, on July 21, 2014. (AP)
Bardaji discussed several factors that give rise to these and other clashes of interests between the EU and Israel. Culturally, there is a clash of values between a “pacifist continent … [where] nobody wants to kill or die for anything,” and Israel, “defined as a Jewish state for the Jewish people” committed to defending its borders and people. Europeans “reject defense as a tool of the state,” and perceive Israel as a framework foreign to its embrace of a multicultural European identity. “We [Europeans] despise ourselves and we embrace everyone else coming from every country in the world, even if they don’t want to integrate, like Muslim radicals.”
Furthermore, “a state that is defined by religious belief – the state of the Jewish people” is seen as an “anachronism” given the “radical secularization of Europe.” The average European, ascribing to a “post-modern world,” cannot comprehend a people defined by a religion other than Islam surviving in the hostile environs of the Middle East. Further contributing to Europe’s hostility towards Israel is that it has evolved from its beginnings as a socialist experiment, which appealed to the left in Europe, to become the “pro-capitalist … start-up nation,” where the European left “cannot see itself … represented.”
Israel is no longer the “smiling socialism on earth” admired by European leftists, said Bardaji.
The irony is that the Europeans, in their embrace of secular values while exhibiting hostility toward the Jewish state, see no contradiction between these sentiments and their tolerance of Muslim migrants who ascribe to “a religion that is hostile to our values and our way of life,” and who are becoming more radicalized. Indeed, the “new left” in Europe has established a “symbiotic relationship” with Muslims that is “making [the continent] more fertile for anti-Semitism … [and] anti-Israeli criticism.”
Bardaji questioned whether the emergence of the new right in Europe is an antidote to the hostility towards Israel because, excluding “what Daniel Pipes calls civilizationist parties,” there are elements of anti-Semitism there as well. With the far left and far right “emerging as the only two poles determining the political dynamics in the EU and the European continent,” Bardaji is pessimistic about the future of EU-Israel relations.
Marilyn Stern is communications coordinator at the Middle East Forum.
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Katz COVID Reality Check 27: Demystifying Pandemic Mortality Differentials
•Mar 12, 2021
Much in the news of late has been the large variations in COVID mortality around the globe. What accounts for this “mystery”? It hides in plain sight… My print column on demystifying COVID mortality differentials: https://www.linkedin.com/pulse/demyst…
On cardiometabolic risk factors and COVID outcomes: https://www.ahajournals.org/doi/10.11…
On obesity and COVID outcomes in various countries: https://www.medrxiv.org/content/10.11…