‘In our study, we investigated which immune cells are activated in severe cases and in what way the endothelium, in other words the blood vessels, and their activation play a role in the disease progress’, explains Prof. Christine Falk, Scientist at the Hanover Medical School (MHH) and the German Center for Infection Research (DZIF). Many clinical symptoms, such as the destruction of blood vessels in the lungs and acute respiratory distress syndrome, pointed to an impact on the endothelium.

The endothelium is a thin layer of cells that line blood vessels, forming a barrier between blood flow and the surrounding tissues. Infection with SARS-CoV-2 appears to cause strong activation of immune and endothelial cells in the lungs, resulting in the release of various soluble plasma proteins. Severe COVID-19 cases are associated with a dysfunction of the endothelium, wherein the barrier between the alveoli and the surrounding vessels is no longer intact.

The scientists studied 25 patients with severe COVID-19 and 17 recovered patients in the intensive care unit (ICU). They were able to prove that the severity of the disease is linked to disruption of the endothelial barrier and can be measured by looking at inflammatory and endothelial plasma proteins. A pattern of seven plasma proteins appears to be associated with a severe form of the disease, which is characterised by strong inflammatory processes and in which the endothelium is permanently damaged. Furthermore, recovery from severe COVID-19 cases seems to be related to the regeneration of this endothelial barrier.

Which immune cells were detected in the COVID-19 ICU patients? The study showed excessive activation of T-lymphocytes and natural killer cells as well as development of memory T-cells and strong proliferation of plasmablasts, cells that can produce large amounts of antibodies. Furthermore, ICU patients infected with SARS-CoV-2 had high titres of spike- and nucleocapsid-specific antibodies. The researchers found particularly interesting that the immune cell phenotype of these patients mainly changed over time and was less related to progressive severity of the disease. The progression of COVID-19, on the other hand, was closely linked to increased levels of various soluble plasma proteins, namely certain inflammatory mediators and especially endothelial factors.

‘We were able to demonstrate that ICU patients with COVID-19 can be divided into different groups based on their plasma protein profile, which are associated with disease severity’, explains lead author Louisa Ruhl, a PhD doctoral student at MHH. This finding is of great importance for identification of potential biomarkers for severe COVID-19 courses as well as for the development and use of new therapeutic concepts.

Christine Falk’s team now wants to investigate which elements of the immune system lead to activation and damage of the endothelium and whether the strong activation of the immune system also leads to the development of virus-specific T-lymphocytes that can recognise and destroy infected cells and thus contribute to overreaction. Moreover, the study has shown that there are also shifts in the immune cell repertoire in recovered ICU patients with COVID-19. This could be related to the development of Long-COVID cases. These aspects are currently being promoted as part of the COFONI initiative of the state of Lower Saxony with a Fasttrack and a Flexfund project. In collaboration with partners from pneumology (Prof. Tobias Welte, MHH and DZL) and neurology (Prof. Günter Höglinger, MHH), they are not only investigating as to whether the endothelial inflammation with the overreaction of the T-lymphocytes and natural killer cells causes lasting damage, but also to what extent the regeneration of the lung is impaired and the nervous system is affected.

The study was conducted jointly with scientists and clinicians at the MHH, the German Center for Lung Research (DZL) and scientists at the Erlangen University Hospital.

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A multi-institutional team of researchers, including virologist Marc Johnson, a professor of molecular microbiology and immunology at the University of Missouri, has detected at least four “cryptic” variants of SARS-CoV-2, the virus that causes COVID-19, in samples of wastewater from New York City’s public sewer system. Their findings were recently published in Nature Communications, a journal of Nature.

According to the Centers for Disease Control and Prevention (CDC), viruses such as SARS-CoV-2 can continually evolve by acquiring mutations. Variants, such as delta or omicron, may contain one or more mutations within their viral sequence that help to distinguish themselves from other variants of SARS-CoV-2.

Johnson, a co-corresponding author on the study, believes the results suggest the “cryptic” mutations they identified in New York City could be linked to possible animal origins. While these origins have not been verified yet, he believes one possible source could be the rats that frequent New York City’s sewer system.

“For instance, we still don’t know where the omicron variant came from, but it had to come from somewhere,” Johnson said. “These variants are bubbling up everywhere, including omicron, which eventually spilled into the general population and wreaked havoc. We think these weird lineages could be where the next variant of concern for COVID-19 comes from.”

Hunting for virus mutations

The idea for this project started in March 2020 after John Dennehy, a virologist and professor of biology at Queens College, City University of New York, began looking for different ways to analyze the impact of the COVID-19 pandemic. Monica Trujillo, an associate professor at Queensborough Community College, City University of New York, shared with Dennehy a study from Australia that described using wastewater to track the spread of a coronavirus, and it inspired Trujillo to ask officials from the New York City Department of Environmental Protection to send her wastewater samples in order to conduct similar work.

In the summer of 2020, Dennehy and Trujillo teamed up with Davida Smyth, the lead author on the study. Smyth, now an associate professor at Texas A&M University-San Antonio, was at The New School, New York at the time. They put together a team of researchers to begin tracking the spread of coronavirus via New York City’s wastewater. Since then, Dennehy, a co-corresponding author on the study, found some interesting results. When he shared some of the more unusual results during a March 2021 episode of Vincent Racaniello’s podcast “This Week in Virology,” a popular podcast with virologists nationwide, Johnson happened to be listening.

“The mutations that we were observing in our sample weren’t typical among any of the known sequences circulating at that time,” Dennehy said.

Ironically, Johnson was simultaneously reaching out to various researchers across the United States who were doing similar work with wastewater after he observed some unusual results from his analysis of wastewater in some of his samples from the greater St. Louis area. On the podcast, he heard Dennehy describe their targeted approach, which happened to be the same method MU was using to test samples of wastewater for SARS-CoV-2 in Missouri, but with one key difference — MU was analyzing a larger region of the virus genome for possible mutations. Within a week, Johnson had samples of NYC wastewater delivered to MU for further analysis.

“When we first started with the samples from New York City, I was looking to see if they had the same virus sequences that I saw in some of my samples from St. Louis,” Johnson said. “They were different, but all of them had similar mutations in common at one particular location on the virus — Q498. What’s amazing is that in most of the samples from New York City, the Q in Q498 had turned into a Y, or glutamine into tyrosine. If you look at the database, there was not, and continues to not be, a human patient who has had that mutation.”

Dennehy believes a possible explanation could be a biological process called convergent evolution.

“An animal in Missouri is not going to mix with the same type of animal in New York City,” Dennehy said. “Therefore, the evolution of the virus in each geographic area is independent of each other, but because it’s the same animal, the virus looks the same in both places. For instance, we think conditions in South Africa that gave rise to the omicron variant are the same conditions in New York City that gave rise to our cryptic variants. As a biologist, I thought the spread of delta was menacing, but the speed in which omicron took over New York City is on another level.”

Understanding the broader impact

Smyth joined the research team in part due to her passion for taking science from inside a laboratory to showing how it can be applied through a broader, real-world impact. A proud Irish immigrant, she transitioned from studying the basics of biology early in her career to now pursuing her passion by engaging her students in real-world health issues, such as antibiotic resistance, and tracking coronavirus in wastewater.

“I’m interested in how we can take what we know and apply it to the real world where it is needed the most,” said Smyth, who is also the deputy director for the National Center for Science and Civic Engagement. “Wastewater surveillance is really important in the context of community-based, public health measures where we have the ability to communicate health information at a level where decisions, practices and interventions can be implemented. Wastewater surveillance is fast, inexpensive and unbiased, and for that reason it has the ability to be implemented depending on resource availability in a variety of contexts, especially in areas with limited resources such as low testing and vaccine availability.”

“Tracking cryptic SARS-CoV-2 lineages detected in NYC wastewater,” was published in Nature Communications. Funding was provided in part by the New York City Department of Environmental Protection, a donation from the Linda Markeloff Charitable Fund, and a grant from the National Institutes of Health (U01DA053893-01).

Co-authors include Devon Gregory, Maddie Graham, Yue Guan, Caitlyn Guldenpfennig, Terry Lyddon, Clayton Rushford, Reinier Suarez, Emma Teixeiro and Mark Daniels at MU; Davida Smyth and Geena Sompanya at Texas A&M University-San Antonio; Monica Trujillo at Queensborough Community College, City University of New York; Kristen Cheung, Anna Gao, Irene Hoxie, Sherin Kannoly, Nanami Kubota, Michelle Markman, and Kaung Myat San at the City University of New York; and Fabrizio Spagnolo at Long Island University.

Broadly neutralizing antibodies (bNAbs) targeting virus envelope (Env) protein have significant potential for treating HIV-1. They were initially identified in rare cases of patients whose serum was capable of inhibiting numerous HIV strains. These antibodies exhibit multiple antiviral activities. As well as neutralizing the virus, i.e. preventing it from infecting new cells, they also kill infected cells. Consequently, they are referred to as polyfunctional molecules. It is necessary to fully understand the scope of these antiviral activities in order to use existing antibodies more effectively or refine the selection criteria for new antibodies. It is moreover useful to further investigate the polyfunctionality of anti-HIV-1 antibodies in order to improve our understanding of the role played by antibodies and thus tackle other viral infections.

Initially, teams at the Institut Pasteur, CNRS, VRI and Université de Paris sought to determine whether antibodies were capable of preventing infected cells from producing viral particles. To that end, they cultured CD4 T cells (HIV’s natural target) in vitro with various antibodies for 24 hours. They subsequently measured the quantity of viral particles produced by the cells in the culture medium and the quantity of viral particles remaining in the cells. As a result of these experiments, the scientists were able to demonstrate that certain antibodies increased virus quantity in cells but reduced it in the culture medium. This intriguing finding led them to believe that certain antibodies impeded the release of viral particles without preventing their production.

To test this theory, the scientists used various microscopy techniques to observe cells’ production of viral particles. They initially examined the cells by fluorescence microscopy, a technique used to differentiate virus proteins. This enabled them to demonstrate that infected cells accumulate large quantities of mature viral protein. This finding suggests that full viral particles accumulate in cells. To determine the precise location of these viral particles, the scientists subsequently used scanning electron microscopy to observe the surface of infected cells. “Using this method, we observed that these antibodies (bNAbs) prompt an accumulation of viral particles at the surface of cells, forming clusters and highly atypical structures (see illustration),” comments Timothée Bruel, co-last author of the study and scientist in the Virus and Immunity Unit[2] at the Institut Pasteur.

Next, the scientists combined a transmission electron microscopy technique with immunogold labeling. This enabled them to demonstrate that antibodies interpose themselves between viral particles and the infected cell, forming a chain cluster. Experiments with mutant antibodies subsequently demonstrated that the antibodies’ Y shape creates this clustered structure. Their arms are capable of linking two viruses, or one virus to the infected cell membrane, and their attachment points are sufficiently strong to prompt this phenomenon.

“We have demonstrated that only the most powerful antibodies tether viral particles at the surface of infected cells. Trapped viral particles can no longer infect new cells,” concludes Olivier Schwartz, co-last author of the study and Head of the Virus and Immunity Unit at the Institut Pasteur.

This work has revealed a new antiviral activity for broadly neutralizing anti-HIV-1 antibodies. It deepens our understanding of these antibodies’ mechanism of action and explains their efficacy in clinical trials. The scientists are now examining antibodies targeting other viruses, including SARS-CoV-2, to determine whether they also inhibit viral spread through this mechanism.

[1] HIV-1 is the pandemic form of the human immunodeficiency virus. The other less common type is HIV-2.

[2] This is named the “Virology Unit” at the CNRS (CNRS/Institut Pasteur).

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Excessive or inadequate weight gain during pregnancy poses numerous health risks for both pregnant individuals and children. Excessive GWG is associated with a higher risk of pregnancy complications, including pregnancy-related hypertension and greater long-term postpartum weight retention. Excessive GWG is also associated with the risk for childhood asthma and obesity. Earlier research by Columbia Mailman researchers found that GWG was linked with a three-fold increased risk of childhood obesity at age 7 and excessive maternal weight gain.

Neighborhood walkability refers to urban form characteristics that support and favor walking and is defined by criteria including population density, land-use mix, density of public transit infrastructure, and street connectivity. Residents of walkable neighborhoods have been shown to engage in more walking, greater overall physical activity, and to have lower body mass index (BMI). Walkable neighborhoods are associated with better control of blood sugar among people with Type II diabetes. The most walkable areas of New York City include Battery Park City, Greenwich Village, NoHo, SoHo, Little Italy, and the West Village (Manhattan CBs 1 and 2). The least walkable areas include neighborhoods in eastern Queens and parts of Staten Island (Queens CB13 and Staten Island CB2).

“Given the long-lasting benefits of healthy pregnancies for parental and child health, this research provides further impetus for the use of urban design and poverty reduction to support healthy weight and reduce the risk of excessive gestational weight gain and related health risks,” says the study’s first author, Eliza Kinsey, PhD, formerly a postdoctoral research scientist in the Department of Epidemiology, now an assistant professor at the University of Pennsylvania Perelman School of Medicine.

The current study was conducted in partnership with researchers at the New York City Department of Health and Mental Hygiene (DOHMH) Bureau of Vital Statistics and used de-identified birth record data for the year 2015 to examine neighborhood-level influences on GWG. Using medical record data, the DOHMH compiles data on all live births in the city, including basic health and demographic information for the pregnant individual and birth outcome statistics (e.g., birth weight, gestational age).

Among the sample of 106,285 births, 42 percent of the pregnant individuals experienced excessive GWG, and 26 percent had inadequate GWG. Pregnant people living in neighborhoods ranking among the poorest quarter of the city had an additional 17 percent greater odds of excessive GWG. Pregnant people living in the top quarter of neighborhoods ranked for walkability had 13 percent lower odds of excessive GWG. These findings align with prior studies in New York City that have found that both neighborhood poverty and walkability predict BMI in the general population.

Adjustment for pre-pregnancy BMI attenuated the association between neighborhood poverty and excessive GWG but had little impact on the association between neighborhood walkability and excessive GWG.

Senior author Andrew Rundle, DrPH, professor of epidemiology, noted: “Neighborhood walkability is likely associated with GWG due to differences in behavior during pregnancy, presumably walking for exercise and daily activities — not solely by influences on pre-pregnancy BMI. A significant amount of the exercise pregnant people get comes from low-impact activities like walking. Making neighborhoods more walkable has a host of health benefits, both for those currently living there and future generations.”

Co-authors of the current study include Elizabeth Widen, University of Texas at Austin; James Quinn, Columbia Mailman; Mary Huynh and Gretchen Van Wye, New York City Department of Health and Mental Hygiene; Gina Lovasi, Drexel University, Philadelphia; and Kathryn Neckerman, Columbia University Population Research Center.

The study was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development (grants HD101657, HD086304, HD042849)

Stretching up to 150 light years long, the one-dimensional strands (or filaments) are found in pairs and clusters, often stacked equally spaced, side by side like strings on a harp. Using observations at radio wavelengths, Northwestern University’s Farhad Yusef-Zadeh discovered the highly organized, magnetic filaments in the early 1980s. The mystifying filaments, he found, comprise cosmic ray electrons gyrating the magnetic field at close to the speed of light. But their origin has remained an unsolved mystery ever since.

Now, the new image has exposed 10 times more filaments than previously discovered, enabling Yusef-Zadeh and his team to conduct statistical studies across a broad population of filaments for the first time. This information potentially could help them finally unravel the long-standing mystery.

The study was published online today by The Astrophysical Journal Letters.

“We have studied individual filaments for a long time with a myopic view,” said Yusef-Zadeh, the paper’s lead author. “Now, we finally see the big picture — a panoramic view filled with an abundance of filaments. Just examining a few filaments makes it difficult to draw any real conclusion about what they are and where they came from. This is a watershed in furthering our understanding of these structures.”

Yusef-Zadeh is a professor of physics and astronomy at Northwestern’s Weinberg College of Arts and Sciences and a member of the Center for Interdisciplinary Exploration and Research in Astrophysics (CIERA).

Constructing the image

To construct the image with unprecedented clarity and detail, astronomers spent three years surveying the sky and analyzing data at the South African Radio Astronomy Observatory (SARAO). Using 200 hours of time on SARAO’s MeerKAT telescope, researchers pieced together a mosaic of 20 separate observations of different sections of the sky toward the center of the Milky Way galaxy, 25,000 light years from Earth.

The full image will be published in an additional, accompanying paper — led by Oxford University astrophysicist Ian Heywood and co-authored by Yusef-Zadeh — in a forthcoming issue of The Astrophysical Journal. Along with the filaments, the image captures radio emissions from numerous phenomena, including outbursting stars, stellar nurseries and new supernova remnants.

“I’ve spent a lot of time looking at this image in the process of working on it, and I never get tired of it,” Heywood said. “When I show this image to people who might be new to radio astronomy, or otherwise unfamiliar with it, I always try to emphasize that radio imaging hasn’t always been this way, and what a leap forward MeerKAT really is in terms of its capabilities. It’s been a true privilege to work over the years with colleagues from SARAO who built this fantastic telescope.”

To view the filaments at a finer scale, Yusef-Zadeh’s team used a technique to remove the background from the main image in order to isolate the filaments from the surrounding structures. The resulting picture astounded him.

“It’s like modern art,” he said. “These images are so beautiful and rich, and the mystery of it all makes it even more interesting.”

What we know

While many mysteries surrounding the filaments remain, Yusef-Zadeh has been able to piece together more of the puzzle. In their latest paper, he and his collaborators specifically explored the filaments’ magnetic fields and the role of cosmic rays in illuminating the magnetic fields.

The variation in radiation emitting from the filaments is very different from that of the newly uncovered supernova remnant, suggesting that the phenomena have different origins. It is more likely, the researchers found, that the filaments are related to past activity of the Milky Way’s central supermassive black hole rather than coordinated bursts of supernovae. The filaments also could be related to enormous, radio-emitting bubbles, which Yusef-Zadeh and collaborators discovered in 2019.

And, while Yusef-Zadeh already knew the filaments are magnetized, now he can say magnetic fields are amplified along the filaments, a primary characteristic all the filaments share.

“This is the first time we have been able to study statistical characteristics of the filaments,” he said. “By studying the statistics, we can learn more about the properties of these unusual sources.

“If you were from another planet, for example, and you encountered one very tall person on Earth, you might assume all people are tall. But if you do statistics across a population of people, you can find the average height. That’s exactly what we’re doing. We can find the strength of magnetic fields, their lengths, their orientations and the spectrum of radiation.”

What we don’t know

Among the remaining mysteries, Yusef-Zadeh is particularly puzzled by how structured the filaments appear. Filaments within clusters are separated from one another at perfectly equal distances — about the distance from Earth to the sun.

“They almost resemble the regular spacing in solar loops,” he said. “We still don’t know why they come in clusters or understand how they separate, and we don’t know how these regular spacings happen. Every time we answer one question, multiple other questions arise.”

Yusef-Zadeh and his team also still don’t know whether the filaments move or change over time or what is causing the electrons to accelerate at such incredible speeds.

“How do you accelerate electrons at close to the speed of light?” he asked. “One idea is there are some sources at the end of these filaments that are accelerating these particles.”

What’s next

Yusef-Zadeh and his team are currently identifying and cataloging each filament. The angle, curve, magnetic field, spectrum and intensity of each filament will be published in a future study. Understanding these properties will give the astrophysics community more clues into the filaments’ elusive nature.

The MeerKAT telescope, which launched in July 2018, will continue to unveil new secrets.

“We’re certainly one step closer to a fuller understanding,” Yusef-Zadeh said. “But science is a series of progress on different levels. We’re hoping to get to the bottom of it, but more observations and theoretical analyses are needed. A full understanding of complex objects takes time.”

The study, “Statistical properties of the population of the galactic center filaments: The spectral index and equipartition magnetic field,” was supported by NASA and the National Science Foundation.

The scientists used the NOEMA (Northern Extended Millimeter Array) observatory in the French Alps, the most powerful radio telescope in the Northern Hemisphere, to observe HFLS3, a massive starburst galaxy at a distance corresponding to an age of only 880 million years after the Big Bang. They discovered a screen of cold water gas that casts a shadow on the cosmic microwave background radiation. The shadow appears because the colder water absorbs the warmer microwave radiation on its path towards Earth, and its darkness reveals the temperature difference. As the temperature of the water can be determined from other observed properties of the starburst, the difference indicates the temperature of the Big Bang’s relic radiation, which at that time was about seven times higher than in the Universe today.

‘Besides proof of cooling, this discovery also shows us that the Universe in its infancy had some quite specific physical characteristics that no longer exist today,’ said lead author Professor Dr Dominik Riechers from the University of Cologne’s Institute of Astrophysics. ‘Quite early, about 1.5 billion years after the Big Bang, the cosmic microwave background was already too cold for this effect to be observable. We have therefore a unique observing window that opens up to a very young Universe only,’ he continued. In other words, if a galaxy with otherwise identical properties as HFLS3 were to exist today, the water shadow would not be observable because the required contrast in temperatures would no longer exist.

‘This important milestone not only confirms the expected cooling trend for a much earlier epoch than has previously been possible to measure, but could also have direct implications for the nature of the elusive dark energy,’ said co-author Dr Axel Weiss from the Max Planck Institute for Radio Astronomy (MPIfR) in Bonn. Dark energy is thought to be responsible for the accelerated expansion of the Universe over the past few billion years, but its properties remain poorly understood because it cannot be directly observed with the currently available facilities and instruments. However, its properties influence the evolution of cosmic expansion, and hence the cooling rate of the Universe over cosmic time. Based on this experiment, the properties of dark energy remain — for now — consistent with those of Einstein’s ‘cosmological constant’. ‘That is to say, an expanding Universe in which the density of dark energy does not change,’ explained Weiss.

Having discovered one such cold water cloud in a starburst galaxy in the early Universe, the team is now setting out to find many more across the sky. Their aim is to map out the cooling of the Big Bang echo within the first 1.5 billion years of cosmic history. ‘This new technique provides important new insights into the evolution of the Universe, which are very difficult to constrain otherwise at such early epochs,’ Riechers said.

‘Our team is already following this up with NOEMA by studying the surroundings of other galaxies,’ said co-author and NOEMA project scientist Dr Roberto Neri. ‘With the expected improvements in precision from studies of larger samples of water clouds, it remains to be seen if our current, basic understanding of the expansion of the Universe holds.’

Dominik Riechers (University of Cologne) conducted the study together with his colleagues Axel Weiss (Max Planck Institute for Radio Astronomy, MPIfR), Fabian Walter (Max Planck Institute for Astronomy, MPIA), Christopher L. Carilli (National Radio Astronomy Observatory, NRAO), Pierre Cox (Institut d’Astrophysique de Paris, IAP, and Sorbonne Université), Roberto Decarli (INAF — Osservatorio di Astrofisica e Scienza dello Spazio), and Roberto Neri (Institut de RadioAstronomie Millimétrique, IRAM).

The study was funded by the US National Science Foundation, the Alexander von Humboldt Foundation, the Max Planck Society, Institut National des Sciences de l’Univers/Centre National de la Recherche Scientifique, and Instituto Geográfico Nacional.

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