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This article is part of Harvard Medical Schoolscontinuing coverageof medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

What makes SARS-CoV-2, the virus behind COVID-19, such a threat?

A new study in Cell led by researchers at Harvard Medical School, Boston Children's Hospital and MIT pinpoints the likely cell types the virus infects.

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The study also unexpectedly showed that one of the bodys main defenses against viral infections may actually help the virus infect those very cells.

The study, published as a peer-reviewed pre-proof, will help focus efforts to understand what SARS-CoV-2 does in the body, why some people are more susceptible, and how best to search for treatments, the researchers say.

Multiple research models

When news broke about a new coronavirus in China, Jose Ordovas-Montanes, assistant professor of pediatrics at HMS and Boston Childrens, and colleague Alex Shalek at MIT had already been studying different cell types from throughout the human respiratory system and intestine. They also had gathered data from primates and mice.

In February, they began diving into these data.

We started to look at cells from tissues such as the lining of the nasal cavity, the lungs and gut, based on reported symptoms and where the virus has been detected, said Ordovas-Montanes, who is co-senior author of the new study along with Shalek. We wanted to provide the best information possible across our entire spectrum of research models.

COVID-19-susceptible cells

Recent research had found that SARS-CoV-2, like the closely related SARS-CoV that caused the SARS pandemic, uses a receptor called ACE2 to gain entry into human cells, aided by an enzyme called TMPRSS2.

That led Ordovas-Montanes, Shalek and colleagues to ask a simple question: Which cells in respiratory and intestinal tissue express both ACE2 and TMPRSS2?

To get the answer, the team turned to single-cell RNA sequencing. This identifies which of roughly 20,000 genes are on in individual cells.

They found that only a tiny percentage of human respiratory and intestinal cellsoften well below 10 percentmake both ACE2 and TMPRSS2.

Those cells fall into three types: goblet cells in the nose that secrete mucus; lung cells known as type II pneumocytes that help maintain the alveoli (the sacs where oxygen is taken in); and one type of so-called enterocytes that line the small intestine and are involved in nutrient absorption.

Sampling from non-human primates showed a similar pattern of susceptible cells.

Many existing respiratory cell lines may not contain the full mix of cell types, and may miss the types that are relevant, said Ordovas-Montanes. Once you understand which cells are infected, you can start to ask, How do these cells work? Is there anything within these cells that is critical for the viruss life cycle?

"With more refined cellular models, we can perform better screens to find what existing drugs target that biology, providing a stepping stone to go into mice or non-human primates.

Interferon: Helpful or harmful?

But it was the studys second finding that most intrigued the scientists.

They discovered that the ACE2 gene, which encodes the receptor SARS-CoV-2 uses to enter human cells, is stimulated by interferonone of the bodys main defenses when it detects a virus.

Interferon actually turned on the ACE2 gene at higher levels, potentially giving the virus new portals to get in.

ACE2 is also critical in protecting people during various types of lung injury, said Ordovas-Montanes. When ACE2 comes up, thats usually a productive response. But since the virus uses ACE2 as a target, we speculate that it might be exploiting that normal protective response.

Interferons, in fact, are being tested as a treatment for COVID-19. Whether they would help or do more harm than good is not yet clear.

It might be that in some patients, because of the timing or the dose, interferon can contain the virus, while in others, interferon promotes more infection, said Ordovas-Montanes. We want to better understand where the balance lies, and how we can maintain a productive antiviral response without producing more target cells for the virus to infect.

ACE inhibitors and cytokine storms

The findings may also raise new lines of inquiry around ACE inhibitors. These drugs are commonly used to treat hypertension, which has been linked to more severe COVID-19 disease. Are ACE inhibitors affecting peoples risk?

ACE and ACE2 work in the same pathway, but they actually have different biochemical properties, Ordovas-Montanes said. Its complex biology, but it will be important to understand the impact of ACE inhibitors on peoples physiological response to the virus.

Its also too soon to try to relate the study findings to the cytokine storm, a runaway inflammatory response that has been reported in very sick COVID-19 patients.

Cytokines are a family of chemicals that rally the bodys immune responses to fight infections. Interferon is part of the family.

It might be that were seeing a cytokine storm because of a failure of interferon to restrict the virus to begin with, so the lungs start calling for more help," he said. "Thats exactly what were trying to understand right now.

Future directions

In addition, the team wants to explore what SARS-CoV-2 is doing in the cells it targets and to study tissue samples from children and adults to understand why COVID-19 is typically less severe in younger people.

Carly Ziegler, Samuel Allon and Sarah Nyquist of MIT and Harvard and Ian Mbano of the Africa Health Research Institute were co-first authors on the paper. The study was done in collaboration with the Human Cell Atlas Lung Biological Network.

This has been an incredible community effort not just within Boston, but also with collaborators around the world who have shared their unpublished data to try and make potentially relevant information available as rapidly as possible, said Shalek. Its inspiring to see how much can be accomplished when everyone comes together to tackle a problem.

This work was supported in part by the National Institutes of Health (U24AI118672, AI201700104, R56AI139053, R01GM081871, T32GM007753, AI078908, HL111113, HL117945, R37AI052353, R01AI136041, R01HL136209, U19AI095219, U19HL129902, UM1AI126623, U19AI051731, R01HL095791, R33AI116184, U19AI117945, UM1AI126617), Bill and Melinda Gates Foundation, MIT Stem Cell Initiative through Foundation MIT, Aeras Foundation, Damon Runyon Cancer Research Foundation (DRG-2274-16), Richard and Susan Smith Family Foundation, UMass Center for Clinical and Translational Science Project Pilot Program, Office of the Assistant Secretary of Defense for Health Affairs (W81XWH-15-1-0317), P.B. Fondation pour la Recherche Medicale (DEQ20180339158) and Agence Nationale pour la Recherche (ANR-19-CE14-0027).

Adapted from a post in Discoveries, the Boston Children's clinical and research innovation portal.

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Into the Lungs and Beyond - Harvard Medical School

SHANGHAI, April 29, 2020 /PRNewswire/ -- Bayer and OrigiMed (Shanghai) Co., Ltd. (referred to as "OrigiMed") today announced a strategic collaboration for the development and commercialization of NGS-based companion diagnostics in vitro diagnostic (CDx-IVD) in China for detection of NTRK gene fusions. This collaboration will focus on developing a CDx-IVD for larotrectinib (Vitrakvi) for the Chinese market, the first TRK inhibitor approved in US (2018) and Europe (2019) for adult and pediatrics with TRK fusion cancer and is currently developed globally, including in China.

"Approved in various markets already, including the US and EU, larotrectinib is a first-of-its-kind treatment exclusively designed for adults and children with TRK fusion cancer. It is also the first compound that received its initial approval based on the molecular alteration (NTRK gene fusion) driving their cancer irrespective of the tumor site of origin," said Dr. Emmanuelle di Tomaso, Head of Oncology Precision Medicine, Bayer's Oncology Strategic Business Unit. "Cancer care is currently undergoing a paradigm shift, and as this new era of precision oncology treatment unfolds, we are continuing our effort of delivering innovative medicines such as larotrectinib, which can provide value to patients and their treating physicians around the world."

"As one of the first NGS companies to introduce NTRK gene fusion detection in China, we are looking forward to working with Bayer to jointly develop larotrectinib CDx-IVD, jointly support clinical trials of larotrectinib in mainland China and provide therapeutic benefits for more patients." The genomic testing and analysis of cancer patients to determine whether they are suitable for the treatment of larotrectinib is also a very urgent clinical need," said Dr. Wang Kai, CEO of OrigiMed.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2019, the Group employed around 104,000 people and had sales of 43.5 billion euros. Capital expenditures amounted to 2.9 billion euros, R&D expenses to 5.3 billion euros. For more information, go to http://www.bayer.com.

About OrigiMed

OrigiMed is a medical science and technology transforming company and a partner of biopharmaceutical companies, who focuses on developing new technologies and clinical applications to help all types of cancer patients get access to precise treatment and to help accelerate biomarker-driven drug development. By carrying out more comprehensive and high-throughput methods, leveraging wholesome bioinformatics analysis and clinical annotation, to help match patients to approved targeted therapies, immunotherapies, and clinical trials-giving physicians and patients powerful actionable insights for navigating cancer care, ultimately aiming to fortify the evolution of cancer precision medicine. More information please visit http://www.origimed.com

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Bayer and OrigiMed reached a partnership to develop a next generation sequencing (NGS) based companion diagnostic-in vitro diagnostic (CDx-IVD)...

Ethiopia pardons more than 4,000 prisoners to help prevent coronavirus spread

Los Angeles offers free testing to all county residents

The Washington Post

All residents of Los Angeles County can access free coronavirus testing at city-run sites, Mayor Eric Garcetti (D) said on Wednesday. Previously, the city had only offered testing to residents with symptoms as well as essential workers and people who lived or worked in nursing homes and other kinds of institutional facilities. In an announcement on Twitter, Garcetti said that priority would still be given to front-line workers and anyone experiencing symptoms, including cough, fever or shortness of breath. But the move, which makes Los Angeles the first major city in the country to offer such widespread testing, allows individuals without symptoms to be tested. Health experts have repeatedly said that mass testing is necessary to determine how many people have contracted the virus and in particular, those who may not have experienced symptoms and then begin to reopen the economy. Testing is by appointment only and can be arranged at one of the citys 35 sites. Read more

Global coronavirus death toll surpasses 200,000, as world leaders commit to finding vaccine

By NBC News

The global coronavirus death toll surpassed 200,000 on Saturday, according to John Hopkins University data. The grim total was reached a day after presidents and prime ministers agreed to work together to develop new vaccines, tests and treatments at a virtual meeting with both the World Health Organization (WHO) and Bill & Melinda Gates Foundation. We will only halt COVID-19 through solidarity, said Dr. Tedros Adhanom Ghebreyesus, WHO Director-General. Countries, health partners, manufacturers, and the private sector must act together and ensure that the fruits of science and research can benefit everybody. As the U.S. coronavirus death tollpassed 51,000 people, according to an NBC News tally, President Donald Trump took no questions at his White House briefing on Friday, after widespread mockery for floating the idea that light, heat and disinfectants could be used to treat coronavirus patients.

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Germany to start first coronavirus vaccine trial

By DW

German Health Minister Jens Spahn has announced the first clinical trials of a coronavirus vaccine. The Paul Ehrlich Institute (PEI), the regulatory authority which helps develop and authorizes vaccines in Germany, has given the go-ahead for the first clinical trial of BNT162b1, a vaccine against the SARS-CoV-2 virus. It was developed by cancer researcher and immunologist Ugur Sahin and his team at pharmaceutical company BioNTech, and is based on their prior research into cancer immunology. Sahin previously taught at the University of Mainz before becoming the CEO of BioNTech. In a joint conference call on Wednesday with researchers from the Paul Ehrlich Institute, Sahin said BNT162b1 constitutes a so-called RNA vaccine. He explained that innocuous genetic information of the SARS-CoV-2 virus is transferred into human cells with the help of lipid nanoparticles, a non-viral gene delivery system. The cells then transform this genetic information into a protein, which should stimulate the bodys immune reaction to the novel coronavrius.

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Webinar on COVID-19 and Mental Health: Interview with Dr. Seble Frehywot

By Liben Eabisa | TADIAS

Dr. Seble Frehywot, an Associate Professor of Global Health & Health Policy at George Washington University in Washington, D.C. and her colleague Dr. Yianna Vovides from Georgetown University will host an online forum next week on April 30th focusing on the COVID-19 pandemic and its impact on mental health. Dr. Seble who is also the Director of Global Health Equity On-Line Learning at George Washington University told Tadias that the virtual conference titled Peoples Webinar: Addressing COVID-19 By Addressing Mental Health is open to the public and available for viewing worldwide. Read more

Young and middle-aged people, barely sick with covid-19, are dying from strokes

By The Washington Post

Doctors sound alarm about patients in their 30s and 40s left debilitated or dead. Some didnt even know they were infected. Read more

CDC director warns second wave of coronavirus is likely to be even more devastating

By The Washington Post

Even as states move ahead with plans to reopen their economies, the director of the Centers for Disease Control and Prevention warned Tuesday that a second wave of the novel coronavirus will be far more dire because it is likely to coincide with the start of flu season. Theres a possibility that the assault of the virus on our nation next winter will actually be even more difficult than the one we just went through, CDC Director Robert Redfield said in an interview with The Washington Post. And when Ive said this to others, they kind of put their head back, they dont understand what I meanWere going to have the flu epidemic and the coronavirus epidemic at the same time, he said. Having two simultaneous respiratory outbreaks would put unimaginable strain on the health-care system, he said. The first wave of covid-19, the disease caused by the coronavirus, has already killed more than 42,000 people across the country. It has overwhelmed hospitals and revealed gaping shortages in test kits, ventilators and protective equipment for health-care workers.

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Americans at World Health Organization transmitted real-time information about coronavirus to Trump administration

By The Washington Post

More than a dozen U.S. researchers, physicians and public health experts, many of them from the Centers for Disease Control and Prevention, were working full time at the Geneva headquarters of the World Health Organization as the novel coronavirus emerged late last year and transmitted real-time information about its discovery and spread in China to the Trump administration, according to U.S. and international officials. A number of CDC staff members are regularly detailed to work at the WHO in Geneva as part of a rotation that has operated for years. Senior Trump-appointed health officials also consulted regularly at the highest levels with the WHO as the crisis unfolded, the officials said. The presence of so many U.S. officials undercuts President Trumps assertion that the WHOs failure to communicate the extent of the threat, born of a desire to protect China, is largely responsible for the rapid spread of the virus in the United States. Read more

In Ethiopia, Dire Dawa Emerges as Newest Coronavirus Hot Spot

By Africa News

The case count as of April 20 had reached 111 according to health minister Lia Tadesses update for today. Ethiopia crossed the 100 mark over the weekend. All three cases recorded over the last 24-hours were recorded in the chartered city of Dire Dawa with patients between the ages of 11 18. Two of them had travel history from Djibouti. Till date, Ethiopia has 90 patients in treatment centers. The death toll is still at three with 16 recoveries. A patient is in intensive care. Read more

COVID-19: Interview with Dr. Tsion Firew, an Ethiopian Doctor on the Frontline in NYC

Dr. Tsion Firew is Doctor of Emergency Medicine and Assistant Professor at Columbia University. She is also Special Advisor to the Ministry of Health in Ethiopia. (Courtesy photo)

By Liben Eabisa

In New York City, which has now become the global epicenter of the coronavirus pandemic, working as a medical professional means literally going to a war zone, says physician Tsion Firew, a Doctor of Emergency Medicine and Assistant Professor at Columbia University, who has just recovered from COVID-19 and returned to work a few days ago. Indeed the statistics coming out of New York are simply shocking with the state recording a sharp increase in death toll this months surpassing 10,000 and growing. According to The New York Times: The numbers brought into clearer focus the staggering toll the virus has already taken on the largest city in the United States, where deserted streets are haunted by the near-constant howl of ambulance sirens. Far more people have died in New York City, on a per-capita basis, than in Italy the hardest-hit country in Europe. At the heart of the solution both in the U.S. and around the world is more testing and adhering to social distancing rules until such time as a proper treatment and vaccine is discovered, says Dr. Tsion, who is also a Special Advisor to the Ministry of Health in Ethiopia. Dr. Tsion adds that at this moment we all as humanity have one enemy: the virus. And whats going to win the fight is solidarity. Listen to the interview

Ethiopia Opens Aid Transport Hub to Fight Covid-19

By AFP

Ethiopia and the United Nations on Tuesday opened a humanitarian transport hub at Addis Ababa airport to move supplies and aid workers across Africa to fight coronavirus. The arrangement, which relies on cargo services provided by Ethiopian Airlines, could also partially offset heavy losses Africas largest carrier is sustaining because of the pandemic. An initial shipment of 3 000 cubic metres of supplies most of it personal protective equipment for health workers will be distributed within the next week, said Steven Were Omamo, Ethiopia country director for the World Food Programme (WFP). This is a really important platform in the response to Covid-19, because what it does is it allows us to move with speed and efficiency to respond to the needs as they are unfolding, Omamo said, referring to the disease caused by the coronavirus. The Addis gateway is one of eight global humanitarian hubs set up to facilitate movement of aid to fight Covid-19, according to WFP.

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Covid-19: Ethiopia to buy life insurance for health workers

By TESFA-ALEM TEKLE | AFP

The Ethiopian government is due to buy life insurance for health professionals in direct contact with Covid-19 patients. Health minister Lia Tadesse said on Tuesday that the government last week reached an agreement with the Ethiopian Insurance Corporation but did not disclose the value of the cover. The two sides are expected to sign an agreement this week to effect the insurance grant. According to the ministry, the life insurance grant is aimed at encouraging health experts who are the most vulnerable to the deadly coronavirus. Members of the Rapid Response Team will also benefit.

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U.N. says Saudi deportations of Ethiopian migrants risks spreading coronavirus

By Reuters

The United Nations said on Monday that deportations of illegal migrant workers by Saudi Arabia to Ethiopia risked spreading the coronavirus and it urged Riyadh to suspend the practice for the time being.

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Ethiopias capital launches door-to-door Covid-19 screening

Getty Images

By TESFA-ALEM TEKLE | AFP

Ethiopias capital, Addis Ababa is due to begin a door-to-door mass Covid-19 screening across the city, Addis Ababa city administration has announced. City deputy Mayor, Takele Uma, on Saturday told local journalists that the mass screening and testing programme will be started Monday (April 13) first in districts which are identified as potentially most vulnerable to the spread of the highly infectious coronavirus. The aggressive city-wide screening measure intends to identify Covid-19 infected patients and thereby to arrest a potential virus spread within communities. He said, the mass screening will eventually be carried out in all 117 districts, locally known as woredas, of the city, which is home to an estimated 7 million inhabitants. According to the Mayor, the door-to-door mass Covid-19 screening will be conducted by more than 1,200 retired health professionals, who responded to governments call on the retired to join the national fight against the coronavirus pandemic.

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Worldwide deaths from the coronavirus hit 100,000

By The Associated Press

The worldwide death toll from the coronavirus has hit 100,000, according to the running tally kept by Johns Hopkins University. The sad milestone comes as Christians around the globe mark a Good Friday unlike any other in front of computer screens instead of in church pews. Meanwhile, some countries are tiptoeing toward reopening segments of their battered economies. Public health officials are warning people against violating the social distancing rules over Easter and allowing the virus to flare up again. Authorities are using roadblocks and other means to discourage travel.

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Ethiopia COVID-19 Response Team: Interview with Mike Endale

By Liben Eabisa | TADIAS

A network of technology professionals from the Ethiopian Diaspora known as the Ethiopia COVID-19 Response Team has been assisting the Ethiopian Ministry of Health since the nations first Coronavirus case was confirmed on March 13th. The COVID-19 Response Team has since grown into an army of more than a thousand volunteers. Mike Endale, a software developer based in Washington, D.C., is the main person behind the launch of this project. Read more

Ethiopia eyes replicating Chinas successes in applying traditional medicine to contain COVID-19

By CGTN Africa

The Ethiopian government on Thursday expressed its keen interest to replicate Chinas positive experience in terms of effectively applying traditional Chinese medicine to successfully contain the spread of COVID-19 pandemic in the East African country.

This came after high-level officials from the Ethiopian Ministry of Innovation and Technology (MoIT) as well as the Ethiopian Ministry of Health (MoH) held a video conference with Traditional Chinese Medicine (TCM) practitioners and researchers on ways of applying the TCM therapy towards controlling the spread of coronavirus pandemic in the country, the MoIT disclosed in a statement issued on Thursday.

China, in particular, has agreed to provide to Ethiopia the two types of Chinese traditional medicines that the country applied to successfully treat the first two stages of the novel coronavirus, a statement from the Ethiopian Ministry of Innovation and Technology read.

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WHO Director Slams Racist Comments About COVID-19 Vaccine Testing

The Director General of the World Health Organization, Dr. Tedros Adhanom Ghebreyesus, has angrily condemned recent comments made by scientists suggesting that a vaccine for COVID-19 should be tested in Africa as racist and a hangover from the colonial mentality. (Photo: WHO)

By BBC

The head of the World Health Organization (WHO) has condemned as racist the comments by two French doctors who suggested a vaccine for the coronavirus could be tested in Africa.

Africa cant and wont be a testing ground for any vaccine, said Director General Dr Tedros Adhanom Ghebreyesus.

The doctors remarks during a TV debate sparked outrage, and they were accused of treating Africans like human guinea pigs.

One of them later issued an apology.

When asked about the doctors suggestion during the WHOs coronavirus briefing, Dr Tedros became visibly angry, calling it a hangover from the colonial mentality.

It was a disgrace, appalling, to hear during the 21st Century, to hear from scientists, that kind of remark. We condemn this in the strongest terms possible, and we assure you that this will not happen, he said.

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Ethiopia declares state of emergency to curb spread of COVID-19

By Reuters

Ethiopias prime minister, Abiy Ahmed, on Wednesday declared a state of emergency in the country to help curb the spread of the new coronavirus, his office said on Twitter. Considering the gravity of the #COVID19, the government of Ethiopia has enacted a State of Emergency, Abiys office said.

Ethiopia virus cases hit 52, 9-month-old baby infected

By TESFA-ALEM TEKLE | AFP

Ethiopia on Tuesday reported eight new Covid-19 cases, the highest number recorded so far in one day since the country confirmed its first virus case on March 12. Among the new patients that tested positive for the virus were a 9-month-old infant and his mother who had travelled to Dubai recently. During the past 24 hours, we have done laboratory tests for a total of 264 people and eight out of them have been diagnosed with coronavirus, raising the total confirmed number of Covid-19 patients in Ethiopia to 52, said Health Minister Dr Lia Tadese. According to the Minister, seven of the newly confirmed patients had travel histories to various countries. They have been under forced-quarantine in different designated hotels in the capital, Addis Ababa. Five of the new patients including the 9-month-old baby and the mother came from Dubai while the two others came from Thailand and the United Kingdom, she said

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The coronavirus is infecting and killing black Americans at an alarmingly high rate

By The Washington Post

As the novel coronavirus sweeps across the United States, it appears to be infecting and killing black Americans at a disproportionately high rate, according to a Washington Post analysis of early data from jurisdictions across the country. The emerging stark racial disparity led the surgeon general Tuesday to acknowledge in personal terms the increased risk for African Americans amid growing demands that public-health officials release more data on the race of those who are sick, hospitalized and dying of a contagion that has killed more than 12,000 people in the United States. A Post analysis of what data is available and census demographics shows that counties that are majority-black have three times the rate of infections and almost six times the rate of deaths as counties where white residents are in the majority.

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In China, Wuhans lockdown officially ends after 11 weeks

After 11 weeks or 76 days Wuhans lockdown is officially over. On Wednesday, Chinese authorities allowed residents to travel in and out of the besieged city where the coronavirus outbreak was first reported in December. Many remnants of the months-long lockdown, however, remain. Wuhans 11 million residents will be able to leave only after receiving official authorization that they are healthy and havent recently been in contact with a coronavirus patient. To do so, the Chinese government is making use of its mandatory smartphone application that, along with other government surveillance, tracks the movement and health status of every person.

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U.S. hospitals facing severe shortages of equipment and staff, watchdog says

By The Washington Post

As the official U.S. death toll approached 10,000, U.S. Surgeon General Jerome M. Adams warned that this will be the hardest and saddest week of most Americans lives.

Read more

Ethio-American Tech Company PhantomALERT Offers Free App to Track & Map COVID-19 Outbreak

By Tadias Staff

PhantomALERT, a Washington D.C.-based technology company announced, that its offering a free application service to track, report and map COVID-19 outbreak hotspots in real time. In a recent letter to the DC government as well as the Ethiopian Embassy in the U.S. the Ethiopian-American owned business, which was launched in 2007, explained that over the past few days, they have redesigned their application to be a dedicated coronavirus mapping, reporting and tracking application. The letter to the Ethiopian Embassy, shared with Tadias, noted that PhantomALERTs technology will enable the Ethiopian government (and all other countries across the world) to locate symptomatic patients, provide medical assistance and alert communities of hotspots for the purpose of slowing down the spread of the Coronavirus.

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2nd COVID-19 death confirmed in Ethiopia

By Dr. Lia Tadesse (Minister, Ministry of Health, Ethiopia)

It is with great sadness that I announce the second death of a patient from #COVID19 in Ethiopia. The patient was admitted on April 2nd and was under strict medical follow up in the Intensive Care Unit. My sincere condolences to the family and loved ones.

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The Next Coronavirus Test Will Tell You If You Are Now Immune. And Its Fast.

People line up in their cars at the COVID-19 testing area at Roseland Community Hospital on April 3, 2020, in Chicago. (E. Jason Wambsgans / Chicago Tribune)

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LA Becomes First City in US to Offers Free COVID-19 Testing to All Residents at Tadias Magazine - Tadias Magazine

April 28, 2020

Rochester research into RNA structure and function provides key information for developing coronavirus treatments.

Viruses like the coronavirus that causes COVID-19 are able to unleash their fury because of a devious weapon: ribonucleic acid, also known as RNA.

A contingent of researchers at the University of Rochester study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. As COVID-19 continues to spread around the globe, RNA research provides an important foundation for developing antiviral drugs, vaccines, and other therapeutics to disrupt the virus and stop infections.

The Universitys website is a way to find guidance and critical information during a rapidly changing situation.

Find out what to do if you or a close contact have symptoms or think you may have been exposed.

Understanding RNA structure and function helps us understand how to throw a therapeutic wrench into what the COVID-19 RNA doesmake new virus that can infect more of our cells and also the cells of other human beings, says Lynne Maquat, professor of biochemistry and biophysics at the University of Rochester Medical Center and the director of Rochesters Center for RNA Biology.

In the past few decades, as scientists came to realize that genetic material is largely regulated by the RNA it encodes, that most of our DNA produces RNA, and that RNA is not only a target but also a tool for disease therapies, the RNA research world has exploded, Maquat says. The University of Rochester understood this.

In 2007, Maquat founded the Center for RNA Biology as a means of conducting interdisciplinary research in the function, structure, and processing of RNAs. The center involves researchers from both the River Campus and the Medical Center, combining expertise in biology, chemistry, engineering, neurology, and pharmacology.

While much of the research across the University has been put on pause, labs that are involved in coronavirus research remain active.

Our strength as a university is our diversity of research expertise, combined with our highly collaborative nature, says Dragony Fu, an assistant professor of biology on the River Campus and a member of the Center for RNA Biology. We are surrounded by outstanding researchers who enhance our understanding of RNA biology, and a medical center that provides a translational aspect where the knowledge gained from RNA biology can be applied for therapeutics.

In mammals, such as humans, DNA contains genetic instructions that are transcribedor copiedinto RNA. While DNA remains in the cells nucleus, RNA carries the copies of genetic information to the rest of the cell by way of various combinations of amino acids, which it delivers to ribosomes. The ribosomes link the amino acids together to form proteins that then carry out functions within the human body.

Many diseases occur when these gene expressions go awry.

COVID-19, short for coronavirus disease 2019, is caused by the novel coronavirus SARS-CoV-2. Like many other viruses, SARS-CoV-2 is an RNA virus. This means that, unlike in humans and other mammals, the genetic material for SARS-CoV-2 is encoded in RNA. The viral RNA is sneaky: its features cause the protein synthesis machinery of our cells to mistake it for RNA produced by our own DNA.

While SARS-CoV-2 is a new coronavirus, it likely replicates and functions similar to related coronaviruses that infect animals and humans, says Douglas Anderson, an assistant professor of medicine in the Aab Cardiovascular Research Institute and a member of the Center for RNA Biology, who studies how RNA mutations can give rise to human disease.

A graphic created by the New York Times illustrates how the coronavirus that causes COVID-19 enters the body through the nose, mouth, or eyes and attaches to our cells. Once the virus is inside our cells, it releases its RNA. Our hijacked cells serve as virus factories, reading the viruss RNA and making long viral proteins to compromise the immune system. The virus assembles new copies of itself and spreads to more parts of the body andby way of saliva, sweat, and other bodily fluidsto other humans.

Once the virus is in our cells, the entire process of infection and re-infection depends on the viral RNA, Maquat says.

Researchers Douglas Anderson, Dragony Fu, and Lynne Maquat are among the scientists at the University of Rochester who study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. (University of Rochester photos / Matt Wittmeyer / J. Adam Fenster)

Maquat has been studying RNA since 1972 and was part of the earliest wave of scientists to realize the important role RNA plays in human health and disease.

Our cells have a number of ways to combat viruses in what can be viewed as an arms race between host and virus. One of the weapons in our cells arsenal is an RNA surveillance mechanism Maquat discovered called nonsense-mediated mRNA decay (NMD).

Nonsense-mediated mRNA decay protects us from many genetic mutations that could cause disease if NMD was not active to destroy the RNA harboring the mutation, she says.

Maquats discovery has contributed to the development of drug therapies for genetic disorders such as cystic fibrosis, and may be useful in developing treatments for coronavirus.

NMD also helps us combat viral infections, which is why many viruses either inhibit or evade NMD, she adds. The genome of the virus COVID-19 is a positive-sense, single-stranded RNA. It is well known that other positive-sense, single-stranded RNA viruses evade NMD by having RNA structures that prevent NMD from degrading viral RNAs.

Maquats lab is currently collaborating with a lab at Harvard University to test how viral proteins can inhibit the NMD machinery.

Like Maquat, Fu studies fundamental aspects of RNAand has found that his research on proteins may, too, be applicable to coronavirus research.

Fus lab analyzes enzymes and proteins that modify the chemical structure of RNA and how these chemical modifications impact the function of RNA. A research group at the University of California, San Francisco, recently identified an interaction between a protein made by the SARS-CoV-9 virus and a protein Fu studies.

This is an intriguing result, and we are currently thinking of ways this interaction could affect the host cell, Fu says. There is emerging evidence that RNA-based viruses undergo RNA modification, so we could use this knowledge to identify key links between the host and pathogen for development of a coronavirus vaccine or treatment.

One of the reasons viruses are such a challenge is that they change and mutate in response to drugs.

Targeting viral RNA, or the proteins it produces, is key for treating this disease.

That means novel virus treatments and vaccines have to be created each time a new strain of virus presents itself. Armed with innovative research on the fundamentals of RNA, scientists are better able to develop and test therapeutics that directly target the RNAs and processes critical to a viruss life cycle.

The University of Rochester Medical Center, for instance, is currently participating in a clinical trial to evaluate the safety and efficacy of a potential coronavirus treatment called remdesivir, an antiviral drug particularly tailored to attack RNA viruses. The drug inhibits RNA polymerase, an enzyme responsible for copying a DNA sequence into an RNA sequence.

Anderson has found that alternative therapeutics, such as the gene-editing technology CRISPR, may additionally usher in a new approach to how we target and combat infectious diseases, he says.

For the past few years, Andersons lab has developed tools and delivery systems that use the RNA-targeting CRISPR-Cas13 to treat human genetic diseases that affect muscle function. CRISPR-Cas13 is like a molecular pair of scissors that can target specific RNAs for degradation, using small, programmable guide RNAs.

When the health crisis first became apparent in Wuhan, China, researchers in Andersons lab turned their focus toward developing a CRISPR-Cas13 therapeutic aimed at SARS-CoV-2. Applying the knowledge already available about coronavirus RNA replication, they designed single CRISPR guide RNAs capable of targeting every viral RNA that is made within a SARS-CoV-2 infected cell. Using a novel cloning method developed in Andersons lab, multiple CRISPR guide-RNAs could be packaged into a single therapeutic vector (a genetically engineered carrier) to target numerous viral RNA sites simultaneously. The multi-pronged targeting strategy could be used as a therapy to safeguard against virus-induced cell toxicity and prevent escape of viruses which may have undergone mutation.

Infectious viruses and pandemics seemingly come out of nowhere, which has made it hard to rapidly develop and screen traditional small molecule therapeutics or vaccines, Anderson says. There is a clear need to develop alternative targeted therapeutics, such as CRISPR-Cas13, which have the ability to be rapidly reprogrammed to target new emerging pandemics.

While many new treatments for the novel coronavirus are being considered, there is one thing that is certain, Maquat says: Targeting viral RNA, or the proteins it produces, is key for treating this disease.

Tags: Arts and Sciences, Center for RNA Biology, COVID-19, Department of Biochemistry and Biophysics, Department of Biology, Douglas Anderson, Dragony Fu, featured-post, Lynne Maquat, medical center

Category: Featured

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COVID-19: What's RNA research got to do with it? - University of Rochester

Cryopreservation has become an indispensable step in the daily routine of scientific research as well as in a number of medical applications, ranging from assisted reproduction and transplantations to cell-based therapies and biomarker identification. It is hardly possible to picture todays scientific and medical advancements without this technique.The successful development and implementation of all the therapeutic and scientific discoveries involving cryopreservation relies on the correct and safe translation of the method from the laboratory to the clinical and manufacturing scale.

With the need to correctly use this technique, more research is focusing on optimizing cryopreservation methods and investigating what the long-term effects and consequences are on the physiology of the cryopreserved material.

An important part of cell therapy research is focused on adult stem cells (ASCs). ASCs can be derived from different sources such as peripheral blood, bone marrow or adipose tissue and display strong promises because of their capacity to differentiate into any cell type of the human body.In recent work3, the team of Michael Pepper at the Institute for Cellular and Molecular Medicine in Pretoria, South Africa, explored the effects of cryopreservation on the differentiation ability of adipose tissue-derived stem cells (ADSCs). After analyzing gene expression of key adipogenic genes and the degree of differentiating cells, characterized with high levels of CD36 and intracellular lipid droplets, the scientists reported that slow freeze cryopreservation of cells shortly after their isolation causes no alterations on their ability to differentiate. Pepper is convinced of the necessity to perform such analysis when cryopreserving important cell pools: It is critical to do a post-thaw analysis of cell function to determine how the cryopreservation may have affected the cells.His team is analyzing the effects of cryopreservation on other cell types largely used in cell-based therapies such as hematological stem cells and peripheral blood mononuclear cells (PBMCs). Although they didnt observe major alterations in terms of immunophenotyping or the post-thaw proliferation of the cells, Pepper expresses his concern that more subtle characteristics might be affected.

Correct cryopreservation of cells intended for therapeutic use is crucial. This is very important particularly as cells may persist for a long time in the recipient. This area of cell therapy research definitely requires more attention, Pepper says. Moreover, his words reflect on the need to evaluate not only the direct post-thaw recovery, but to look deeper into the late-onset effects cryopreservation might have and ensure that transplanted cells have preserved their therapeutic properties.

In contrast to slow freezing, vitrification relies on the fast freezing of the material by putting it in high concentration of cryoprotectant and in contact with liquid nitrogen. This method allows the direct transition of water from liquid to solid state without crystal formation. The highly concentrated cryoprotectant prevents ice formation and therefore there is no need for slow cooling.

Although vitrification has a great potential, there are a couple of parameters that are a point of concern. The quick and drastic freeze is possible thanks to the high concentration of cryoprotectant, but the latter is also associated with higher toxicity. In some cases, an additional limitation is the direct contact of the sample with liquid nitrogen which is a predisposition for viral or bacterial contamination.The team of Christiani Amorim at the Institute for Experimental and Clinical Research in Louvain, Belgium, is approaching the challenges of vitrification in the context of ovarian auto-transplantation. Ovarian auto-transplantation consists of preserving a piece of ovarian tissue with active follicles from the pre-therapeutic ovary of a cancer patient, as chemotherapy often has damaging effects on the reproductive organs. This tissue sample will be conserved and auto-transplanted onto the patients ovary when she has recovered and wishes to become pregnant.In their recent research4, the authors used stepped vitrification, in which the concentration of the cryoprotectant is gradually increased while simultaneously temperature decreases. This avoids ice crystal formation and also prevents cryoprotectant toxicity.Although stepped vitrification has previously given good results in bovine ovarian tissue5, this was not the case for human ovarian tissue. The scientists didnt detect normal follicles following thawing and linked this to high cryoprotectant toxicity. Indeed, they observed all signs of dimethyl sulfoxide (DMSO)-related cell membrane damage: significant organelle damage, cell membrane disintegration and apoptosis. These observations imply on the variability of outcomes that the method could give when applied to the same type of tissue but from a different organism.Amorim is positive about the future of their method and recognizes the need for further research on the topic: I can see a great potential in the stepped vitrification approach, but I also believe that there is a lot we still need to learn before thinking about using it as method of choice for human ovarian tissue cryopreservation. The high cryoprotectant concentration that should be applied in this approach is my first concern. () Our study clearly showed that 50% DMSO is too high, so we need to try lower concentrations or combine it with other cryoprotectants.

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Freezing Life: The Current Trends in Cryopreservation - Technology Networks

The Albany Medical Center in New York and University of Wisconsin researchers are collaborating to find a way to better allocate medical resources to COVID-19 patients using mass spectrometry techniques.

According to a UW press release, Dr. Ariel Jaitovich, a pulmonary and critical care physician at the Albany Medical Center, reached out to UW researchers for improving treatment and care for COVID-19 patients.

Its a new disease. Two months ago, we knew nothing about it, Dr. Jaitovich said in the release. What we are trying to do now is do systematic work to better understand what this disease is about.

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The team is comprised of the Albany Medical Center in New York, Morgridge Institute for Research and the Department of Biomolecular Chemistry at the UW School of Medicine and Public Health, according to the release.

SMPH professor Josh Coon, who specializes in mass spectrometry research, is working together with the research group to contrast samples from COVID-19 patients with control samples of those who have tested negative for the virus. The team will analyze about 150 samples from the Albany Medical Center to understand the molecular profile of COVID-19, according to the press release.

UW professionals discussed transmission of, responses to COVID-19 through online panelAs part of the Crossroads of Ideas lecture series, UW professionals discussed transmission of and responses to COVID-19 on Tuesday, Read

This is extremely important for many reasons, because you can, for example, intervene early with people who are more likely to do worse over time based on these early identified markers, Coon said inthe release. You can better allocate resources in a moment in which there is a shortage of resources to deal with this pandemic.

Coon said mass spectrometry can provide molecular signals that can then help in distinguishing between mild and severe cases. Coon also said some possible indicators of the severity of the disease could be blood clotting factors in lung vessels and cytokine storms that trigger the immune systems inflammatory response to skyrocket and result in acute respiratory distress syndrome, according to the release.

UW research team analyzes travel, social media data to monitor COVID-19 spreadA multidisciplinary research team, headed by University of Wisconsin professor Song Gao, started analyzing travel and social media data to Read

The Coon Laboratory is investigating the molecular signals of the disease and Jaitovichs team in New York is examining the potential genetic influences on COVID-19 through RNA sequencing by collaborating with Associate Director of Bioinformatics Ron Stewart and computational biologist Scott Swanson at the Morgridge Institute for Research.

We should be able to get an idea about what genes or gene sets are involved in things like inflammation, and how that might differ between COVID-19 and other ARDS cases, Stewart said in the release.

Excerpt from:
UW researchers collaborate with New York doctors for improved COVID-19 treatments - The Badger Herald