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May 10th, 2020

Temperature & Latitude Not Associated with COVID-19 Spread, Canadian Study Finds; School Closures, Physical Distancing, and Public Health Measures Do Have Positive Effect

Temperature and latitude do not appear to be associated with the spread of coronavirus disease 2019 (COVID-19), according to a study of many countries published online on May 8, 2020 in CMAJ (Canadian Medical Association Journal) http://www.cmaj.ca/lookup/doi/10.1503/cmaj.200920, but school closures and other public health measures are having a positive effect. The article is titled “Impact of climate and public health interventions on the COVID-19 pandemic: A prospective cohort study.” "Our study provides important new evidence, using global data from the COVID-19 epidemic, that these public health interventions have reduced epidemic growth," says Dr. Peter Jüni, Institute for Health Policy, Management and Evaluation, University of Toronto, and St. Michael's Hospital, Toronto, Ontario. The Canadian study looked at 144 geopolitical areas -- states and provinces in Australia, the United States and Canada as well as various countries around the world -- and a total of more than 375,600 confirmed COVID-19 cases. China, Italy, Iran, and South Korea were excluded because the virus was either waning in the case of China or in full disease outbreak at the time of the analysis in others. To estimate epidemic growth, researchers compared the number of cases on March 27 with cases on March 20, 2020, and determined the influence of latitude, temperature, humidity, school closures, restrictions of mass gatherings and social distancing measured during the exposure period of March 7 to 13. They found little or no association between latitude or temperature with epidemic growth of COVID-19 and a weak association between humidity and reduced transmission. The results -- that hotter weather had no effect on the pandemic's progression -- surprised the authors.

Moderna (mRNA Therapeutics & Vaccines) to Present at Upcoming Investor Conferences; Live Webcasts Available: Tuesday, May 12, and Monday, May 18

On May 8, 2020, Moderna, Inc., (Nasdaq: MRNA) a clinical-stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, announced its participation in the following upcoming investor conferences: Bank of America Securities 2020 Health Care Conference on Tuesday, May 12, 2020 at 2:20 p.m. ET; and UBS Global Healthcare Conference on Monday, May 18, 2020 at 1:20 p.m. ET. A live webcast of each presentation will be available under “Events and Presentations” in the Investors section of the Moderna website at https://investors.modernatx.com/. A replay of each webcast will be archived on Moderna’s website for 30 days following the presentation. Moderna is advancing messenger RNA (mRNA) science to create a new class of transformative medicines for patients. mRNA medicines are designed to direct the body’s cells to produce intracellular, membrane or secreted proteins that can have a therapeutic or preventive benefit and have the potential to address a broad spectrum of diseases. Moderna’s platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, providing the Company the capability to pursue in parallel a robust pipeline of new development candidates. Moderna is developing therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases, and autoimmune and inflammatory diseases, independently and with strategic collaborators. Headquartered in Cambridge, Mass., Moderna currently has strategic alliances for development programs with AstraZeneca PLC and Merck & Co., Inc., as well as the Defense Advanced Research Projects Agency (DARPA), an agency of the U.S.

New York State Department of Health Partnering with New York Genome Center & Rockefeller University on Genome Study to Understand COVID-19 Related Illnesses in Children, Including Those Resembling Kawasaki Disease & Toxic Shock-Like Syndrome

On May 9, 2020, Governor Andrew M. Cuomo announced (https://www.governor.ny.gov/news/governor-cuomo-announces-state-helping-...) that the New York State Department of Health is partnering with the New York Genome Center (NYGC) and The Rockefeller University, both in New York City, to conduct a genome and RNA sequencing study to better understand COVID-19-related illnesses in children. Recently, there have been 73 reported cases with three deaths in New York in children with symptoms similar to Kawasaki disease (https://en.wikipedia.org/wiki/Kawasaki_diseas) and toxic shock-like syndrome (http://www.clinicsinsurgery.com/pdfs_folder/cis-v4-id2619.pdf). The study will involve sequencing samples collected from affected pediatric patients across hospitals in New York State, and actionable results will be shared with the patients’ clinicians. Clinical case review meetings and other multi-institutional collaborations will involve members of the COVID-19 Genomics Research Network (https://covidgenomics.org/about/) organized by the NYGC.

[NYGC press release] [New York Governor's press release] [COVID-19 Genomics Research Center] [New York Genome Center]

Nature Reviews Immunology Publishes Timely Article: “The Trinity of COVID-19: Immunity, Inflammation, and Intervention

In a review article published online on April 28, 2020, scientists from Singapore provide an overview of the pathophysiology of SARS-CoV-2 infection. The researchers describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. The open-access article was published online on April 28, 2020 in Nature Reviews Immunology and is titled “The Trinity of COVID-19: Immunity, Inflammation, and Intervention” (https://www.nature.com/articles/s41577-020-0311-8). The lead author is Matthew Zirui Tay, PhD, of the Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore; and the senior author is Lisa F. P. Ng (https://en.wikipedia.org/wiki/Lisa_Ng), PhD, of the same organization, and also with affiliations at the Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; and at the Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, UK. At the end of their review, the authors conclude that “Controlling the inflammatory response may be as important as targeting the virus. Therapies inhibiting viral infection and regulation of dysfunctional immune responses may synergize to block pathologies at multiple steps. At the same time, the association between immune dysfunction and outcome of disease severity in patients with COVID-19 should serve as a note of caution in vaccine development and evaluation. Further studies of the host immune response to SARS-CoV-2 are necessary, including a detailed investigation of the determinants of healthy versus dysfunctional outcomes.

Gene Hunt to Explain Why Some Young, Healthy People Die from COVID-19; Rockefeller Scientists Closely Examine Genetics of Outliers

Early on in its emergence, it became clear that the novel coronavirus is particularly dangerous to older people and those with pre-existing health conditions. But just as there are patterns, there are outliers. As the infection spread around the globe, reports started to pile up of young, previously healthy people whose disease suddenly turned fatal. Finding out what has made this group of people so vulnerable to the infection may be an important step in developing new ways to treat the disease or identify those at high risk. And scientists suspect the answer may be in their genes. “Infectious diseases are always an interplay between a pathogen and the host’s immunity,” says Jean-Laurent Casanova, MD, PhD, Head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University. “At least some of these patients may suffer from a genetic variation that make their host defense particularly vulnerable to SARS-CoV2.” Dr. Casanova, along with Dr. Helen Su at the National Institute of Allergy and Infectious Diseases (NIAID) are leading an international project, the COVID Human Genetic Effort (https://www.covidhge.com/), to comb through the genomes of many COVID-19 outliers in search of any rare gene variant that they may share, and that may explain their body’s insufficient response to the infection. All infections appear to come with what scientists call inter-individual clinical variability, meaning that a fraction of infected people are hit especially hard. With cytomegalovirus, for example, most cases are so mild that the infection goes unnoticed, yet it is often detrimental to fetuses and it kills one in a million infected individuals (https://www.rockefeller.edu/news/27419-unusual-patient-case-cmv-rare-imm...). Tuberculosis, on the other hand, can kill as many as five percent of infected individuals.

May 9th

Rockefeller Scientists Use “Elite” Antibodies from COVID-19 Survivors to Develop Potent Therapies; An Estimated 5% of Survivors Have Powerful Neutralizing Antibodies to COVID-19; Special Approach Allows ID, Cloning, & Subsequent Mass Production

In the few weeks since New York City came to a socially distanced halt, more than 250 COVID-19 survivors have visited Rockefeller University’s otherwise quiet campus to contribute their blood to science. Here, a group of immunologists, medical scientists, and virologists is betting that a cure for the disease can be created from the antibodies of these previously ill patients. The study is one of nearly 20 COVID-19 projects (https://www.rockefeller.edu/news/27795-rockefeller-launching-covid19-res...) that have been launched by Rockefeller researchers since early March in an effort to better understand the SARS-CoV-2 virus and speed the development of new treatments. The team’s plan is to find the so-called “elite neutralizers,” the minority of people who have conquered the infection so exceptionally that their antibodies have the potential to become drugs. “We are sifting through millions of antibodies made by each person to find which ones actually neutralize the virus,” says Michel C. Nussenzweig, MD, PhD, the Zanvil A. Cohn and Ralph M. Steinman Professor and Head of the Laboratory of Molecular Immunology at The Rockefeller. The project is being led by Dr. Nussenzweig, Dr. Paul Bieniasz, Dr. Marina Caskey, Dr. Theodora Hatziioannou, Dr. Charles M. Rice, and Dr. Davide F. Robbiani. The same approach has shown great potential against other viruses, including HIV, and there are promising signs, even as the study is still recruiting its first waves of donors (http://clinicalstudies.rucares.org/coronavirus.php): i.e., the team has already identified a number of antibodies that are able to block the virus from interacting with its receptor. Those with the best potential will be moved to the next phase of the project, where the researchers will work with industry partners to produce material for clinical testing.

Scientists Discover How Oral Secretions of Insect Pest Trigger Innate Defense Responses in Plants; Unprecedented Findings Represent Massive Step Forward Toward Developing Strategies for Pest Control In Crop Plants

In nature, every species must be equipped with a strategy to be able to survive in response to danger. Plants, too, have innate systems that are triggered in response to a particular threat, such as insects feeding on them. For example, some plants sense "herbivore-derived danger signals" (HDS), which are specific chemicals in oral secretions of insects. This activates a cascade of events in the plant's defense machinery, which leads to the plant developing "resistance" to (or "immunity" against) the predator. But despite decades of research, exactly how plants recognize these signals has remained a bit of a mystery. In a new study published in Communications Biology (https://www.nature.com/articles/s42003-020-0959-4), a research team from Tokyo University of Science, Ehime University, Okayama University, The University of Tokyo, and Iwate Biotechnology Research Center, led by Professor Gen-ichiro Arimura, PhD, attempts to shed light on exactly how plant HDS systems work. They chose to study membrane proteins called "receptor-like kinases" (RLKs), which are found in soybean leaves. They based their study on previous evidence from plants like Arabidopsis, tobacco, and cowpea, in which RLKs play a major role in HDS systems. Their results published online on May 8, 2020 in Communications Biology. The open-access article is titled” Soy and Arabidopsis receptor-like kinases respond to polysaccharide signals from Spodoptera species and mediate herbivore resistance.” Professor Arimura says, "Scientists have been trying to understand the molecular mechanism of plant resistance for years, but the 'sensors' involved in plant recognition of insect pests are still not known.

New Study Shines Light on Mysterious Giant Viruses

In recent years, giant viruses have been unearthed in several of the world's most mysterious locations, from the thawing permafrost of Siberia to locations unknown beneath the Antarctic ice. In a new study, a team of Michigan State University (MSU) scientists shed light on these enigmatic, yet captivating, giant microbes and key aspects of the process by which they infect cells. The study results were published online on May 8, 2020 in Cell. The article is titled "Structural and Proteomic Characterization of the Initiation of Giant Virus Infections." With the help of cutting-edge imaging technologies, this study developed a reliable model for studying giant viruses and is the first to identify and characterize several key proteins responsible for orchestrating infection. Giant viruses are bigger than 300 nanometers in diameter and can survive for many millennia. For comparison, the rhinovirus -- responsible for the common cold -- is roughly 30 nanometers in diameter. "Giant viruses are gargantuan in size and complexity," said principal investigator Kristin Parent, PhD, Associate Professor of Biochemistry and Molecular Biology at MSU. "The giant viruses recently discovered in Siberia retained the ability to infect after 30,000 years in permafrost." The outer shells -- or capsids -- are rugged and able to withstand harsh environments, protecting the viral genome inside. The capsids of the species analyzed in this study -- mimivirus, Antarctica virus, Samba virus, and the newly discovered Tupan viruses -- are icosahedral, or shaped like a twenty-sided die. These species have a unique mechanism for releasing their viral genome. A starfish-shaped seal sits atop one of the outer shell vertices.

Newly Discovered Dendritic Cell Plays Crucial Role in Immune Response to Respiratory Infections

With a discovery that could prompt a rewrite of immunology textbooks, an international group of scientists, including the research teams of Bart Lambrecht, PhD; Martin Guilliams, PhD; Hamida Hammad, PhD; and Charlotte Scott, PhD (all from the VIB-UGent Center for Inflammation Research) identified a new type of antigen-presenting immune cell. These cells, which are part of an expanding family of dendritic cells, play a crucial role in presenting antigens to other immune cells during respiratory virus infections, and could explain how convalescent plasma helps to boost immune responses in virus-infected patients. When our body faces an infection, it responds with inflammation and fever. This is a sign that the immune system is doing its work, and leads to the activation of many cells, like soldiers in an army. Dendritic cells (DCs) are the generals of that army. They can precisely activate and instruct the soldiers to kill infected cells by presenting antigens derived from the “invaders” to cells of the immune system. There are several types of DCs that perform antigen-presenting functions in the body. A first type of conventional DCs continuously scans the body for dangerous invaders, even when there is no infection. When there is inflammation triggered by infection, another subset of DCs emerges from inflammatory monocytes. Because monocyte-derived DCs are easily prepared in vitro from monocytes isolated form human blood, it was always assumed these cells were very important antigen-presenting cells. Clinical trials using monocyte-derived DCs in cancer therapy have, however, been disappointing.

AstraZeneca & Oxford University Announce Landmark Agreement for COVID-19 Vaccine (Weakened Adenovirus Containing mRNA for Viral Spike Protein); Collaboration Will Enable Global Development, Manufacturing, and Distribution of Vaccine

On April 30, 2020, AstraZeneca and the University of Oxford announced an agreement for the global development and distribution of the University’s potential recombinant adenovirus vaccine aimed at preventing COVID-19 infection from SARS-CoV-2. The collaboration aims to bring to patients the potential vaccine known as ChAdOx1 nCoV-19, being developed by the Jenner Institute and Oxford Vaccine Group, at the University of Oxford. Under the agreement, AstraZeneca would be responsible for development and worldwide manufacturing and distribution of the vaccine. Pascal Soriot, Chief Executive Officer, AstraZeneca, said: “As COVID-19 continues its grip on the world, the need for a vaccine to defeat the virus is urgent. This collaboration brings together the University of Oxford’s world-class expertise in vaccinology and AstraZeneca’s global development, manufacturing, and distribution capabilities. Our hope is that, by joining forces, we can accelerate the globalization of a vaccine to combat the virus and protect people from the deadliest pandemic in a generation.” Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “The University of Oxford and AstraZeneca have a longstanding relationship to advance basic research and we are hugely excited to be working with them on advancing a vaccine to prevent COVID-19 around the world. We are looking forward to working with the University of Oxford and innovative companies such as Vaccitech (https://www.vaccitech.co.uk/), as part of our new partnership.” Alok Sharma, UK Business Secretary, said: “This collaboration between Oxford University and AstraZeneca is a vital step that could help rapidly advance the manufacture of a coronavirus vaccine.