Evelien Bunnik, PhD, corresponding author of the paper, said the results hint of subtle differences in the quality of immune response based on COVID-19 severity. Dr. Bunnik is an assistant professor of microbiology, immunology and molecular genetics at the health science center, also referred to as UT Health San Antonio.

The study focused on memory B cells that react against the SARS-CoV-2 spike protein. Blood samples were analyzed one month after symptom onset and five months post-onset. After one month, a significant proportion of spike-specific B cells were active.

However, samples from eight individuals who recovered from less-severe disease showed increased expression of markers associated with durable B cell memory as compared to individuals who recovered from severe disease, the authors wrote. The markers include T-bet and FcRL5.

T-bet-positive, spike-specific B cells nearly disappeared from the blood samples five months post-symptom onset, the authors noted. Overall, a more dysfunctional B cell response is seen in severe disease cases, they wrote.

Non-severe cases were defined as not requiring supplemental oxygen or invasive ventilation, while severe cases needed invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). “The definition of severe disease was made based on the need for mechanical ventilation or ECMO, because this distinguishes the most critical patients, who are the most likely to develop impaired immune responses,” said study senior author Thomas Patterson, MD, professor and chief of infectious diseases at UT Health San Antonio who leads COVID-19 care at clinical partner University Health.

Study participants were enrolled in the Adaptive COVID-19 Treatment Trial (ACTT)-1 or ACTT-2 clinical trials. Samples were from University Health patients co-enrolled in the UT Health San Antonio COVID-19 Repository.

“The increased percentage of B cells associated with long-lived immunity in non-severe COVID-19 patients may have consequences for long-term immunity against SARS-CoV-2 re-infection or severity of the resulting disease,” the authors wrote.

Acknowledgments

This work was supported by a COVID-19 pilot award from the UT Health San Antonio Joe R. and Teresa Lozano Long School of Medicine (10009547 to Dr. Evelien Bunnik). Raphael A. Reyes was supported by Translational Science Training award TL1 TR002647. Data were generated in the Flow Cytometry Shared Resource Facility, which is supported by UT Health San Antonio, NIH-NCI P30 CA054174-20 (Mays Cancer Center, home to UT Health San Antonio MD Anderson) and UL1 TR001120 (Clinical Translational Science Award grant). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The study was led by David Ho, MD, director of the Aaron Diamond AIDS Research Center and the Clyde’56 and Helen Wu Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons. The findings were published in Nature.

A striking feature of the omicron variant is the alarming number of changes in the virus’s spike protein that could pose a threat to the effectiveness of current vaccines and therapeutic antibodies.

Large drop in omicron neutralization by antibodies from vaccines

The new study tested the ability of antibodies generated by vaccination to neutralize the omicron variant in laboratory assays that pitted antibodies against live viruses and against pseudoviruses constructed in the lab to mimic omicron.

Antibodies from people double-vaccinated with any of the four most widely used vaccines — Moderna, Pfizer, AstraZeneca, Johnson & Johnson — were significantly less effective at neutralizing the omicron variant compared to the ancestral virus. Antibodies from previously infected individuals were even less likely to neutralize omicron.

Individuals who received a booster shot of either of the two mRNA vaccines are likely to be better protected, although even their antibodies exhibited diminished neutralizing activity against omicron.

“The new results suggest that previously infected individuals and fully vaccinated individuals are at risk for infection with the omicron variant,” says Ho. “Even a third booster shot may not adequately protect against omicron infection, but of course it is advisable to get one, as you’ll still benefit from some immunity.”

The results are consistent with other neutralization studies, as well as early epidemiological data from South Africa and the U.K., which show efficacy of two doses of the vaccines against symptomatic disease is significantly reduced against the omicron variant.

Most monoclonal antibodies are unable to neutralize omicron

When administered early in the course of infection, monoclonal antibodies can prevent many individuals from developing severe COVID. But the new study suggests that all of the therapies currently in use and most in development are much less effective against omicron, if they work at all.

In neutralization studies with monoclonal antibodies, only one (Brii198 approved in China) maintained notable activity against omicron. A minor form of omicron is completely resistant to all antibodies in clinical use today. The authors note that omicron is now the most complete “escapee” from neutralization that scientists have seen.

In this study Ho’s lab also identified four new spike mutations in omicron that help the virus evade antibodies. This information should inform the design of new approaches to combat the new variant.

Future directions

Ho suggests that scientists will need to develop vaccines and treatments that can better anticipate how the virus is evolving.

It is not too far-fetched to think that SARS-CoV-2 is now only a mutation or two away from being completely resistant to current antibodies, either the monoclonal antibodies used as therapies or the antibodies generated by vaccination or infection with previous variants,” says Ho.

More information

The paper is titled “Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization.”

The full list of contributors is available in the online version of the paper.

David Ho and some of his colleagues are inventors of certain monoclonal antibodies described in the paper.

Periodontal disease affects nearly half of Americans over age 30, and 70% of those 65 and older. It is a bacterial infection of the tissues supporting the teeth. In its early stages, periodontal disease causes redness and swelling (inflammation) of the gums. In advanced stages, called periodontitis, the underlying bone becomes damaged, leading to tooth loss. While scientists have known that periodontitis is driven in part by an exaggerated immune cell response, until now, it was unclear what triggered the response, and how it caused tissue and bone damage.

“Severe periodontal disease can lead to tooth loss and remains a barrier to productivity and quality of life for far too many Americans, especially those lacking adequate access to dental care,” said NIDCR Director Rena D’Souza, D.D.S., Ph.D. “By providing the most comprehensive picture yet of the underlying mechanisms of periodontal disease, this study brings us closer to more effective methods for prevention and treatment.”

At sites of injury or inflammation, fibrin normally plays a protective role, helping to form blood clots and activating immune cells to fight infection. But too much fibrin has been linked with health problems, including a rare form of periodontitis due to a condition called plasminogen (PLG) deficiency. In affected people, mutations in the PLG gene lead to fibrin buildup and disease at various body sites, including the mouth.

To explore the connection between abnormal fibrin buildup and periodontitis, the scientists, led by NIDCR investigators Niki Moutsopoulos, D.D.S., Ph.D., and Thomas Bugge, Ph.D., studied PLG deficiency in mice and analyzed human genetic data.

Like humans with the condition, PLG-deficient mice developed periodontitis, including periodontal bone loss and elevated levels of fibrin in the gums. The mice’s gums were crowded with immune cells called neutrophils, which are also found at high levels in common forms of periodontitis.

Neutrophils typically defend the oral cavity from harmful microbes. But an excessive neutrophil response is thought to cause tissue damage.

To find out if fibrin was driving this overactive response, the researchers impaired its ability to interact with (bind to) protein receptors on neutrophils. The weakened binding between fibrin and neutrophils completely prevented periodontal bone loss in PLG-deficient mice. Strikingly, it also reduced bone loss in normal mice with a common, age-related form of periodontitis, suggesting that similar mechanisms were at play in both forms of the disease.

“This study suggests that fibrin can cause neutrophil immunity to shift from protective to damaging in certain circumstances,” said Moutsopoulos, who credited postdoctoral fellow and study first author Lakmali Silva, Ph.D., for her research that led to the findings. “This fibrin-neutrophil engagement may be a driver of periodontitis.”

A genetic analysis of over 1,000 people seemed to support the animal findings. Even in the absence of PLG deficiency, variations in the PLG gene were linked to an increased risk of severe periodontitis, consistent with the idea that similar processes contribute to rare and common forms of the disease.

Taken together, the study suggests that excessive buildup of fibrin in the gums — whether due to changes in genes like PLG, chronic inflammation from a bacterial infection, or some combination of the two — triggers an elevated and ultimately harmful neutrophil response that causes periodontal disease.

The results are also in line with findings from other research teams, which have found that elevated fibrin may contribute to other inflammatory and autoimmune diseases such as arthritis and multiple sclerosis, and that interfering with fibrin activity could help treat these conditions.

“Our data support the idea that targeting the fibrin-neutrophil interaction could be a promising treatment avenue to explore in both rare and common forms of periodontitis,” added Silva.

This research was supported by the NIDCR Division of Intramural Research. Support also came from the intramural programs of the National Institute on Deafness and Other Communication and the National Institute of Allergy and Infectious Diseases, the extramural programs of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Fund for Scientific and Technological Development, Chile.

The researchers, from the University of Cambridge, used an organic molecule as a ‘template’ to guide perovskite films into the desired phase as they form. Their results are reported in the journal Science.

Perovskite materials offer a cheaper alternative to silicon for producing optoelectronic devices such as solar cells and LEDs.

There are many different perovskites, resulting from different combinations of elements, but one of the most promising to emerge in recent years is the formamidinium (FA)-based FAPbI₃ crystal.

The compound is thermally stable and its inherent ‘bandgap’ — the property most closely linked to the energy output of the device — is not far off ideal for photovoltaic applications.

For these reasons, it has been the focus of efforts to develop commercially available perovskite solar cells. However, the compound can exist in two slightly different phases, with one phase leading to excellent photovoltaic performance, and the other resulting in very little energy output.

“A big problem with FAPbI₃ is that the phase that you want is only stable at temperatures above 150 degrees Celsius,” said co-author Tiarnan Doherty from Cambridge’s Cavendish Laboratory. “At room temperature, it transitions into another phase, which is really bad for photovoltaics.”

Recent solutions to keep the material in its desired phase at lower temperatures have involved adding different positive and negative ions into the compound.

“That’s been successful and has led to record photovoltaic devices but there are still local power losses that occur,” said Doherty. “You end up with local regions in the film that aren’t in the right phase.”

Little was known about why the additions of these ions improved stability overall, or even what the resulting perovskite structure looked like.

“There was this common consensus that when people stabilise these materials, they’re an ideal cubic structure,” said Doherty. “But what we’ve shown is that by adding all these other things, they’re not cubic at all, they’re very slightly distorted. There’s a very subtle structural distortion that gives some inherent stability at room temperature.”

The distortion is so minor that it had previously gone undetected, until Doherty and colleagues used sensitive structural measurement techniques that have not been widely used on perovskite materials.

The team used scanning electron diffraction, nano-X-ray diffraction and nuclear magnetic resonance to see, for the first time, what this stable phase really looked like.

“Once we figured out that it was the slight structural distortion giving this stability, we looked for ways to achieve this in the film preparation without adding any other elements into the mix.”

Co-author Satyawan Nagane used an organic molecule called Ethylenediaminetetraacetic acid (EDTA) as an additive in the perovskite precursor solution, which acts as a templating agent, guiding the perovskite into the desired phase as it forms. The EDTA binds to the FAPbI₃ surface to give a structure-directing effect, but does not incorporate into the FAPbI₃ structure itself.

“With this method, we can achieve that desired band gap because we’re not adding anything extra into the material, it’s just a template to guide the formation of a film with the distorted structure — and the resulting film is extremely stable,” said Nagane.

“In this way, you can create this slightly distorted structure in just the pristine FAPbI₃ compound, without modifying the other electronic properties of what is essentially a near-perfect compound for perovskite photovoltaics,” said co-author Dominik Kubicki from the Cavendish Laboratory, who is now based at the University of Warwick.

The researchers hope this fundamental study will help improve perovskite stability and performance. Their own future work will involve integrating this approach into prototype devices to explore how this technique may help them achieve the perfect perovskite photovoltaic cells.

“These findings change our optimisation strategy and manufacturing guidelines for these materials,” said senior author Dr Sam Stranks from Cambridge’s Department of Chemical Engineering & Biotechnology. “Even small pockets that aren’t slightly distorted will lead to performance losses, and so manufacturing lines will need to have very precise control of how and where the different components and ‘distorting’ additives are deposited. This will ensure the small distortion is uniform everywhere — with no exceptions.”

The work was a collaboration with the Diamond Light Source and the electron Physical Science Imaging Centre (ePSIC), Imperial College London, Yonsei University, Wageningen University and Research, and the University of Leeds.

While dinosaurs ruled the land, ichthyosaurs and other aquatic reptiles (that were emphatically not dinosaurs) ruled the waves, reaching similarly gargantuan sizes and species diversity. Evolving fins and hydrodynamic body-shapes seen in both fish and whales, ichthyosaurs swam the ancient oceans for nearly the entirety of the Age of Dinosaurs.

“Ichthyosaurs derive from an as yet unknown group of land-living reptiles and were air-breathing themselves,” says lead author Dr. Martin Sander, paleontologist at the University of Bonn and Research Associate with the Dinosaur Institute at the Natural History Museum of Los Angeles County (NHM). “From the first skeleton discoveries in southern England and Germany over 250 years ago, these ‘fish-saurians’ were among the first large fossil reptiles known to science, long before the dinosaurs, and they have captured the popular imagination ever since.”

Excavated from a rock unit called the Fossil Hill Member in the Augusta Mountains of Nevada, the well-preserved skull, along with part of the backbone, shoulder, and forefin, date back to the Middle Triassic (247.2-237 million years ago), representing the earliest case of an ichthyosaur reaching epic proportions. As big as a large sperm whale at more than 17 meters (55.78 feet) long, the newly named Cymbospondylus youngorum is the largest animal yet discovered from that time period, on land or in the sea. In fact, it was the first giant creature to ever inhabit the Earth that we know of.

“The importance of the find was not immediately apparent,” notes Dr. Sander, “because only a few vertebrae were exposed on the side of the canyon. However, the anatomy of the vertebrae suggested that the front end of the animal might still be hidden in the rocks. Then, one cold September day in 2011, the crew needed a warm-up and tested this suggestion by excavation, finding the skull, forelimbs, and chest region.”

The new name for the species, C. youngorum, honors a happy coincidence, the sponsoring of the fieldwork by Great Basin Brewery of Reno, owned and operated by Tom and Bonda Young, the inventors of the locally famous Icky beer which features an ichthyosaur on its label.

In other mountain ranges of Nevada, paleontologists have been recovering fossils from the Fossil Hill Member’s limestone, shale, and siltstone since 1902, opening a window into the Triassic. The mountains connect our present to ancient oceans and have produced many species of ammonites, shelled ancestors of modern cephalopods like cuttlefish and octopuses, as well as marine reptiles. All these animal specimens are collectively known as the Fossil Hill Fauna, representing many of C. youngorum‘s prey and competitors.

C. youngorum stalked the oceans some 246 million years ago, or only about three million years after the first ichthyosaurs got their fins wet, an amazingly short time to get this big. The elongated snout and conical teeth suggest that C. youngorum preyed on squid and fish, but its size meant that it could have hunted smaller and juvenile marine reptiles as well.

The giant predator probably had some hefty competition. Through sophisticated computational modeling, the authors examined the likely energy running through the Fossil Hill Fauna’s food web, recreating the ancient environment through data, finding that marine food webs were able to support a few more colossal meat-eating ichthyosaurs. Ichthyosaurs of different sizes and survival strategies proliferated, comparable to modern cetaceans’ — from relatively small dolphins to massive filter-feeding baleen whales, and giant squid-hunting sperm whales.

Co-author and ecological modeler Dr. Eva Maria Griebeler from the University of Mainz in Germany notes, “due to their large size and resulting energy demands, the densities of the largest ichthyosaurs from the Fossil Hill Fauna including C. youngourum must have been substantially lower than suggested by our field census. The ecological functioning of this food web from ecological modeling was very exciting as modern highly productive primary producers were absent in Mesozoic food webs and were an important driver in the size evolution of whales.”

Whales and ichthyosaurs share more than a size range. They have similar body plans, and both initially arose after mass extinctions. These similarities make them scientifically valuable for comparative study. The authors combined computer modeling and traditional paleontology to study how these marine animals reached record-setting sizes independently.

“One rather unique aspect of this project is the integrative nature of our approach. We first had to describe the anatomy of the giant skull in detail and determine how this animal is related to other ichthyosaurs,” says senior author Dr. Lars Schmitz, Associate Professor of Biology at Scripps College and Dinosaur Institute Research Associate. “We did not stop there, as we wanted to understand the significance of the new discovery in the context of the large-scale evolutionary pattern of ichthyosaur and whale body sizes, and how the fossil ecosystem of the Fossil Hill Fauna may have functioned. Both the evolutionary and ecological analyses required a substantial amount of computation, ultimately leading to a confluence of modeling with traditional paleontology.”

They found that while both cetaceans and ichthyosaurs evolved very large body sizes, their respective evolutionary trajectories toward gigantism were different. Ichthyosaurs had an initial boom in size, becoming giants early on in their evolutionary history, while whales took much longer to reach the outer limits of huge. They found a connection between large size and raptorial hunting — think of a sperm whale diving down to hunt giant squid — and a connection between large size and a loss of teeth — think of the giant filter-feeding whales that are the largest animals ever to live on Earth.

Ichthyosaurs’ initial foray into gigantism was likely thanks to the boom in ammonites and jawless eel-like conodonts filling the ecological void following the end-Permian mass extinction. While their evolutionary routes were different, both whales and ichthyosaurs relied on exploiting niches in the food chain to make it really big.

“As researchers, we often talk about similarities between ichthyosaurs and cetaceans, but rarely dive into the details. That’s one way this study stands out, as it allowed us to explore and gain some additional insight into body size evolution within these groups of marine tetrapods,” says NHM’s Associate Curator of Mammalogy (Marine Mammals), Dr. Jorge Velez-Juarbe. “Another interesting aspect is that Cymbospondylus youngorum and the rest of the Fossil Hill Fauna are a testament to the resilience of life in the oceans after the worst mass extinction in Earth’s history. You can say this is the first big splash for tetrapods in the oceans.”

C. youngorum will be permanently housed at the Natural History Museum of Los Angeles County, where it is currently on view.

In a paper published in Science today, an international team of scientists present a detailed blueprint of how plants construct phloem cells — the tissue responsible for transporting and accumulating sugars and starch in the parts of the plant that we harvest (seeds, fruits and storage tubers) to feed much of the world.

This pivotal research reveals how global signals in root meristems coordinate distinct maturation phases of the phloem tissue.

Phloem is a highly specialised vascular tissue that forms an interconnected network of continuous strands throughout a plant’s body. It transports sugars, nutrients and a range of signalling molecules between leaves, roots, flowers and fruits.

As a result, phloem is central to plant function. Understanding how the phloem network is initiated and develops is important for future applications in agriculture, forestry and biotechnology as it could reveal how to better transport this sugar energy to where it is needed.

How do plants build a sugar lane in a multi-lane highway?

Plant roots continue to grow throughout a plant’s life. This phenomenon, known as indeterminate growth, means roots continually elongate as they add new tissues to the tip of the root — like constructing a never-ending highway. A continuous file of specialised phloem cells running the length of roots (analogous to a lane on a highway) delivers the primary nutrient, sucrose, to the parts of the plant where it is needed for growth. To fulfil this vital role, phloem tissue must develop and mature rapidly so it can supply sugars to surrounding tissues — akin to building a service lane that needs to be completed in the first stage of constructing a multi-lane highway.

The problem that has long puzzled plant scientists is how a single instructive gradient of proteins are able to stage the construction phases across all the different specialised cell files (highway lanes) that are present in roots. How does one cell type read the same gradient as its neighbours, but interprets it differently to stage its own specialised development is a question that plant scientists have been working to resolve.

Over the past 15 years, researchers in Yrjö Helariutta’s teams at the University of Cambridge and University of Helsinkihave uncovered the central role of cell-to-cell communication and complex feedback-mechanisms involved in vascular patterning. This new research, undertaken with collaborators at New York University and North Carolina State University, reveals how this single lane of phloem cells is constructed independently of surrounding cells.

The Sainsbury/Helsinki group dissected each step in the construction of the phloem cell file (the sugar transport lane) in the model plant Arabidopsis thaliana using single-cell RNA-seq and live imaging. Their work showed how the proteins that control the broad maturation gradient of the root interact with the genetic machinery that specifically controls phloem development.

This is one mechanism that appears to help the phloem cell file to fast-track maturation using its own machinery to interpret the maturation cues. Dr Pawel Roszak, co-first-author of the study and researcher at the Sainsbury Laboratory Cambridge University (SLCU), explains: “We have shown how global signals in the root meristem interact with the cell type specific factors to determine distinct phases of phloem development at the cellular resolution. Using cell sorting followed by deep, high-resolution single-cell sequencing of the underlying gene regulatory network revealed a “seesaw” mechanism of reciprocal genetic repression that triggers rapid developmental transitions.”

The group also showed how phloem development is staged over time, with early genetic programs inhibiting late genetic programs and vice versa — just as the road asphalt-laying work crews’ hand over construction to lane painters in the latter stages of highway construction. In addition, they showed how early phloem regulators instructed specific genes to split the phloem cells into two different subtypes — like the construction of a fork in the road leading to two separate destinations.

Co-leader of the work, Professor Yrjö Helariutta, said his teams’ reconstruction of the steps from birth to terminal differentiation of protophloem in the Arabidopsis root exposed the steps. Helariutta said: “Broad maturation gradients interfacing with cell-type specific transcriptional regulators to stage cellular differentiation is required for phloem development.”

“By combining single-cell transcriptomics with live imaging, here we have mapped the cellular events from the birth of the phloem cell to its terminal differentiation into phloem sieve element cells. This allowed us to uncover genetic mechanisms that coordinate cellular maturation and connect the timing of the genetic cascade to broadly expressed master regulators of meristem maturation. The precise timing of developmental mechanisms was critical for proper phloem development, with apparent “fail safe” mechanisms to ensure transitions.”

The researchers plan to further explore the evolution of these mechanisms and whether these steps are replicated in other regions of plants and other plant species.

Published today in Science, the study led by the University of Texas and the National Institutes of Health is a promising development in the fight against multiple types of cancer including melanoma, the most deadly form of skin cancer, the researchers said.

Nationwide, melanoma is the fifth-most common cancer. Roughly 100,000 new melanoma cases will be diagnosed in the United States in the coming year, and more than 7,000 of those patients are expected to die, according to the American Cancer Society.

One of the most aggressive cancers, melanoma kills by metastasizing, or spreading, to other organs such as the liver, lungs and brain.

The new study focuses on a therapeutic technique called immune checkpoint blockade, often referred to by its initials of ICB, which has revolutionized treatment of melanoma, and cancer in general.

ICB therapy relies on inhibitor drugs that block proteins called checkpoints that are produced by certain immune system cells — T cells, for example — and also by some cancer cells.

Checkpoints help prevent immune responses from being too strong, but sometimes that means keeping T cells from killing cancer cells. Thus, when the checkpoints are blocked, T cells can do a better job of killing cancer cells.

“ICB has been a game-changer in cancer therapy, and the influence of the gut microbiome on therapeutic response has been demonstrated in numerous studies, in preclinical models and also in research involving human cohorts,” Morgun said. “A person’s microbiome is shaped by a wide range of environmental factors including food and medications, while human genetics accounts for a much smaller proportion of the microbiome variation from person to person.”

The human gut microbiome is a complicated community of more than 10 trillion microbial cells from about 1,000 different bacterial species. It has remained unclear whether dietary fiber intake and the use of commercially available probiotics affect immunotherapy response in cancer patients, Morgun said.

Morgun and collaborators on this study looked at hundreds of melanoma patients, analyzing their gut microbiomes, dietary habits, use of probiotics, disease features and treatment outcomes. Most of the patients were being treated via ICB, typically a type known as anti-programmed cell death protein therapy, abbreviated to anti-PD-1.

A parallel study involving mice implanted with tumors was also part of the research.

In the human, observational cohort portion of the study, higher dietary fiber intake was associated with disease non-progression among patients on ICB; the most pronounced benefits were found in patients with strong dietary fiber intake and no probiotic use.

The mouse model generated similar results.

“We showed that dietary fiber and probiotic use, both known to impact the gut microbiome, are associated with differing ICB outcomes,” Morgun said. “From the human cohort results we can’t assign causality — there may have been other things going on with those patients that we didn’t measure in this study.”

But Morgun said the results in the mice support the idea that anti-tumor immunity is strongest with a high-fiber diet and no probiotics.

To help make sense of microbiome complexity, Morgun and Natalia Shulzhenko of Oregon State’s Carlson College of Veterinary Medicine earlier invented a computer modeling technique known as transkingdom network analysis.

The model, used in this latest work, integrates multiple types of “omics” data — metagenomic, metabolomic, lipidomic, proteomic, etc. — in determining how interactions among specific types of gut microbes help or hinder biological functions in the host. In this case, the microbial interactions involved how well the host responds to immune checkpoint blockade.

It’s important to note, Morgun said, that transkingdom network analysis in mice showed a family of bacteria, Ruminococcaceae, among the organisms increased by the high-fiber diet; the same bacteria were found in the current study involving humans and in previous, related research with people.

Double-blind, randomized dietary intervention studies will be critical for establishing whether a targeted, achievable diet change at the start of ICB therapy can improve patient outcomes, he said.

“And though the findings suggest that some commercially available probiotics may be harmful for patients on ICB, more research is needed to determine which probiotics could actually be beneficial,” Morgun said.

Leading the study were Jennifer Wargo, Lorenzo Cohen and Carrie Daniel of the University of Texas and Giorgio Trinchieri of the National Institutes of Health. Approximately 80 scientists took part in the research.

Funders included the NIH and the U.S. Department of State.

Previous research led by the U.S. Department of Agriculture had shown evidence of antibodies in wild deer. This study, published today (Dec. 23, 2021) in Nature, details the first report of active COVID-19 infection in white-tailed deer supported by the growth of viral isolates in the lab, indicating researchers had recovered viable samples of the SARS-CoV-2 virus and not only its genetic traces.

Based on genomic sequencing of the samples collected between January and March 2021, researchers determined that variants infecting wild deer matched strains of the SARS-CoV-2 virus that had been prevalent in Ohio COVID-19 patients at the time. Sample collection occurred before the Delta variant was widespread, and that variant was not detected in these deer. The team is testing more samples to check for new variants as well as older variants, whose continued presence would suggest the virus can set up shop and survive in this species.

The fact that wild deer can become infected “leads toward the idea that we might actually have established a new maintenance host outside humans,” said Andrew Bowman, associate professor of veterinary preventive medicine at The Ohio State University and senior author of the paper.

“Based on evidence from other studies, we knew they were being exposed in the wild and that in the lab we could infect them and the virus could transmit from deer to deer. Here, we’re saying that in the wild, they are infected,” Bowman said. “And if they can maintain it, we have a new potential source of SARS-CoV-2 coming in to humans. That would mean that beyond tracking what’s in people, we’ll need to know what’s in the deer, too.

“It could complicate future mitigation and control plans for COVID-19.”

A lot of unknowns remain: how the deer got infected, whether they can infect humans and other species, how the virus behaves in the animals’ body, and whether it’s a transient or long-term infection.

The research team took nasal swabs from 360 white-tailed deer in nine northeast Ohio locations. Using PCR testing methods, the scientists detected genetic material from at least three different strains of the virus in 129 (35.8%) of the deer sampled.

The analysis showed that B.1.2 viruses dominant in Ohio in the early months of 2021 spilled over multiple times into deer populations in different locations.

“The working theory based on our sequences is that humans are giving it to deer, and apparently we gave it to them several times,” Bowman said. “We have evidence of six different viral introductions into those deer populations. It’s not that a single population got it once and it spread.”

Each site was sampled between one and three times, adding up to a total of 18 sample collection dates. Based on the findings, researchers estimated the prevalence of infection varied from 13.5% to 70% across the nine sites, with the highest prevalence observed in four sites that were surrounded by more densely populated neighborhoods.

White-tailed deer functioning as a viral reservoir of SARS-CoV-2 would likely result in one of two outcomes, Bowman said. The virus could mutate in deer, potentially facilitating transmission of new strains to other species, including humans, or the virus could survive in deer unmutated while it simultaneously continues to evolve in humans, and at some point when humans don’t have immunity to the strains infecting deer, those variants could come spilling back to humans.

How transmission happened initially in these deer, and how it could happen across species, are among the pending questions related to these findings. The research team speculated that white-tailed deer were infected through an environmental pathway — possibly by drinking contaminated water. Research has shown that the virus is shed in human stool and detectable in wastewater.

The white-tailed deer tested for this study were part of a population control initiative, so they are not a transmission threat.

Though there are an estimated 600,000 white-tailed deer in Ohio and 30 million in the United States, Bowman said this sampling focused on locations close to dense human populations and is not representative of all free-ranging deer.

This work was supported by the Ohio State Infectious Diseases Institute and the National Institute of Allergy and Infectious Diseases. In addition to USDA, NIAID, Ohio Wildlife Center and Cleveland Metroparks contributors, Ohio State co-authors include Vanessa Hale, Patricia Dennis, Dillon McBride, Jacqueline Nolting, Christopher Madden, Devra Huey, Margot Ehrlich, Jenessa Winston, Dubraska Diaz-Campos, Page Yaxley, Alexis McLaine, Risa Pesapane, Mark Flint, Jaylene Flint, Anastasia Vlasova, Scott Kenney, Qiuhong Wang, Linda Saif and Seth Faith.