Category Archives: Microbiology

Get Moving To Lower Your COVID Risk: Exercise Shown To Reduce Severity of Illness

New research study shows that more exercise is associated with lower rates of hospitalization or death after infection, across diverse demographic groups and chronic conditions.

Kaiser Permanente members who were more physically active prior to being diagnosed with COVID-19 had a lower risk of severe outcomes, according to research published on December 15, 2022, in the American Journal of Preventive Medicine.

The study of nearly 200,000 adults showed an association between physical activity and improved COVID-19 outcomes across major demographic groups regardless of whether patients had chronic medical conditions. Black, Hispanic, and Asian patients had a greater risk of adverse outcomes compared with white patients, in line with prior research. However, within each racial and ethnic group, more exercise was still associated with less severe COVID-19 outcomes.

“The main message is that every little bit of physical activity counts,” said the study’s lead author, Deborah Rohm Young, PhD, the director of the Division of Behavioral Research for the Kaiser Permanente Southern California Department of Research & Evaluation. “The more exercise the better, no matter a person’s race, ethnicity, age, sex, or chronic conditions.”

This research builds on earlier studies by closely examining the association between exercise and COVID-19 outcomes across demographic groups and chronic conditions.

In this study, Young and her colleagues analyzed the electronic health records of 194,191 adult patients at Kaiser Permanente in Southern California who were diagnosed with COVID-19 between January 2020 and May 2021, prior to widespread COVID-19 vaccination.

All patients had reported their physical activity levels prior to infection in a routine measure known as the Exercise Vital Sign. Each patient fell into 1 of 5 categories ranging from always inactive — 10 minutes of exercise or less per week, to always active — 150 minutes of exercise per week.

Statistical analysis showed that the more physical activity a patient reported, the lower the risk of hospitalization or death within 90 days of COVID-19 diagnosis. This trend was consistent across all activity levels, with always-active patients facing the lowest risk.

More exercise was also linked to lower rates of hospitalization or death for patients with certain underlying chronic conditions — such as hypertension, cardiovascular disease, or obesity — that are typically associated with an increased risk of poor COVID-19 outcomes.

“Our findings drive home the need for physicians to emphasize to their patients that getting vaccinated and being more physically active are 2 of the most important things you can do to prevent severe outcomes of COVID-19,” said the study’s senior author, Robert E. Sallis, MD, a family and sports medicine physician at the Kaiser Permanente Fontana Medical Center.

Young said: “This is a powerful opportunity to develop stronger policies supporting physical activity as a pandemic-mitigation strategy. Our study provides new evidence to inform appropriate interventions across demographic groups.”

Reference: “Associations of Physical Inactivity and COVID-19 Outcomes Among Subgroups” by Deborah Rohm Young, PhD; James F. Sallis, PhD; Aileen Baecker, PhD; Deborah A. Cohen, MD, MPH; Claudia L. Nau, PhD; Gary N. Smith, PhD and Robert E. Sallis, MD, 14 December 2022, American Journal of Preventive Medicine.
DOI: 10.1016/j.amepre.2022.10.007

While about 30,000 Americans are confirmed to have Lyme disease every year, the Centers for Disease Control and …

While about 30,000 Americans are confirmed to have Lyme disease every year, the Centers for Disease Control and Prevention (CDC) has estimated that the number could be as high as 476,000. Lyme disease is also becoming more common in other countries, with an estimated 200,000 cases in Western Europe every year. Ixodes tick bites transmit the bacteria that cause Lyme disease; these pathogens are varieties of Borrelia bacteria, including Borrelia burgdorferi in the US and B. afzelii and B. garinii in Europe. The disease causes rash, fever, joint pain, and can lead to nervous system and heart complications.

A digitally colorized SEM image at high magnification, depicting three Borrelia burgdorferi bacteria, derived from a pure culture. / Credit: CDC/ Claudia Molins / Photo Credit: Jamice Haney Carr

Now scientists may have learned how Borrelia bacteria migrate from the site of a bite to an infected person’s bloodstream. For this work, researchers created a specialized 3D tissue model that was meant to mimic a human blood vessel, the skin around it, and the tick bite. High-resolution optical imaging was used to monitor the bacteria. This showed that  B. burgdorferi basically uses trial and error to find an opening in spaces called junctions, which line blood vessels and can be found near the sites of bites. Once the pathogenic microbes break through, they can move into the bloodstream and on to other tissues and organs. The findings have been reported in Advanced Science.

If Borrelia could not find a junction right away, they kept searching until they found one, said senior study author Peter Searson, a professor at the Whiting School of Engineering of Johns Hopkins University. “The bacteria spend an hour or two using this behavior to find their way into the blood vessels, but once there, they are in circulation in a matter of seconds.”

Understanding how these bacterial pathogens spread could help scientists develop treatments for Lyme disease, which can cause symptoms that last for months or even years. It may be possible to prevent the pathogens from moving beyond the site of the initial bite.

The researchers have experience developing vascular models with tissue engineering, and they applied what they knew to make a dermal tissue model.

“We also believe that the kind of human tissue-engineered model we created can be broadly applied to visualize the details of dynamic processes associated with other vector-borne diseases and not just Lyme disease,” Searson added.

Sources: CDC, WHO, Johns Hopkins University, Advanced Science

Carmen Leitch

8 Ways to Improve Your Gut Health

Woman Gut Digestion Health

Gut health is an essential aspect of overall wellness. The gastrointestinal (GI) tract is home to trillions of microbes that play a major role in our overall health. These microbes are known as gut microbiota or “gut flora,” and they help digest food, synthesize vitamins and even regulate metabolism and immunity. But what does good gut health look like? And how can you improve your gut health?

There are several ways to improve your gut health:

Eating fiber-rich foods is a great way to improve your gut health. Fiber helps regulate bowel movements by absorbing water in the colon, softening stools, and making them easier to pass through the intestines. Good sources include beans, whole grains, and fresh fruits and vegetables. Foods high in fiber also make you feel full faster, so you’re less likely to overeat.

Woman Offering Drinking Water

Water helps keep things moving through your body, so you’re less prone to constipation, which can cause bloating, gas, and abdominal pain, and also less prone to kidney stones or urinary tract infections. It also keeps your skin hydrated and maintains normal body temperature by acting as a transport medium for heat exchange with the environment. Drink eight glasses (about 2 liters) of water each day to keep yourself hydrated during the day. (Note that this is a basic guideline, and your actual water needs will vary based on your body weight, activity levels, environment, etc.)

Stress can have a major impact on your digestive system because it affects the regulation of hormones and neurotransmitters that control your gastrointestinal function. This may lead to stomach problems like nausea, bloating, and diarrhea. Stress can also increase your risk of developing conditions such as irritable bowel syndrome (IBS) or Crohn’s disease due to changes in immune responses in your GI tract. If you’re feeling stressed out, try taking some time out for yourself — whether it’s meditating or exercising — so you’re less likely to develop stress-related illnesses.

Fermented foods like yogurt contain probiotics — beneficial bacteria that help improve digestion, boost immunity and prevent disease-causing pathogens from sticking around in your digestive tract for too long. You can get probiotics from food sources, or from supplements if you don’t like the taste of yogurt or other fermented foods such as pickles or sauerkraut. Talk with your doctor before taking any supplements because they may interact with the medications you’re taking or have side effects.

Regular exercise is one of the best ways to improve your gut health. It helps promote a healthy digestive system and improves your mood. Exercise can also help reduce inflammation and boost your immune system. This means that you’ll be less likely to get sick and more likely to fight off any viruses or bacteria that enter your body. So the more active you are, the healthier your gut will be.

Sugar not only contributes to weight gain but also affects how well you digest your food — especially if you eat a lot of it. Sugar feeds bad bacteria in your gut which can cause bloating, discomfort and gas. So cutting back on sugar can help promote good bacteria growth. Sugar can also cause other health issues like acne or low energy levels due to blood sugar fluctuations caused by consuming too much sugar at once.

Avoiding processed foods is one of the best ways to improve your gut health. The majority of food is processed in some way, and this can harm your gut bacteria. This is because processing food strips away many of the nutrients that your body needs to function properly. Processed foods also tend to contain additives that can cause inflammation in the body — including artificial sweeteners, refined sugars, gluten, and trans fats. Instead, opt for whole food sources such as fruits or veggies whenever possible.

Sleep is essential for maintaining a healthy gut. When you don’t get enough sleep, your immune system is weakened and cannot function properly. This can make it more difficult for your body to fight off infections and heal itself after an illness or injury. Sleep deprivation also increases inflammation in the body, which is bad news for anyone who already has inflammation issues in their gut from another cause. To get the most out of your sleep time, avoid caffeine late in the day and turn off all electronics before bedtime so you can relax.

A healthy gut can improve your quality of life in many ways. It helps your body digest food, absorb nutrients and fight off invaders. The better you take care of your gut, the healthier you’ll be.

Molecular Changes Linked to Long COVID a Year After Hospitalization

Mount Sinai researchers have published one of the first studies to associate changes in blood gene expression during COVID-19 with “long COVID” in patients more than a year after they were hospitalized with severe COVID-19. Long COVID is the common name used for what is known more technically as post-acute sequelae of SARS-CoV-2 infection.

The findings, published in the journal Nature Medicine on December 8, highlight the need for greater attention at the infection stage to better understand how the processes that begin then eventually lead to long COVID, which could help improve both prevention strategies and treatment options for COVID-19 survivors experiencing persistent symptoms after infection.

The research team identified, among other findings, two molecularly distinct subsets of long COVID symptoms with opposing gene expression patterns during acute COVID-19 in plasma cells, the immune system’s antibody-producing cells. In patients who went on to develop lung problems, antibody production genes were less abundant. However, for patients with other symptoms such as the loss of smell or taste and sleep disruptions, the same antibody production genes were more abundant instead. These opposing patterns observed in the same cells, as well as additional unique patterns observed in other cell types, point to the existence of multiple independent processes leading to different long COVID symptoms; these processes are already present during the acute infection.

“Our findings show that molecular processes leading to long COVID are already detectable during COVID-19 infection,” said co-corresponding author Noam D. Beckmann, PhD, Assistant Professor of Medicine (Data Driven and Digital Medicine) and Associate Director of Data Science Strategy at The Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai. “Furthermore, we see the start of multiple molecularly distinct paths leading to long COVID, providing a unique viewpoint into differences between long-term symptoms.”

Using the Mount Sinai COVID-19 Biobank, the researchers examined gene expression data in blood samples from more than 500 patients hospitalized with COVID-19 between April and June 2020. More than 160 of these patients provided self-reported assessments of symptoms still present six months or more after hospitalization. The team tested each gene expressed in the blood for association with each long COVID symptom, accounting for ICU admission, COVID-19 severity during hospitalization, sex, age, and other variables. The team then tested for associations specific to each of 13 different types of immune cells, including plasma cells. Finally, these associations were categorized by whether they matched up with changes in patients’ levels of antibodies specific to the virus.

“For long COVID symptoms, like smell or taste problems, connecting antibody gene expression in plasma cells with the actual levels of antibodies against the SARS-CoV-2 spike protein demonstrates a direct link to the body’s response to the virus,” said lead author Ryan C. Thompson, PhD, Data Science Analyst at The Charles Bronfman Institute for Personalized Medicine. “On the other hand, the gene expression pattern for lung problems does not match up with SARS-CoV-2-specific antibody levels, highlighting the different immune processes leading to long COVID that are triggered by COVID-19.”

The team said long COVID still remains poorly defined and future studies should take the initial stage of infection into account to more comprehensively characterize the molecular processes of long COVID and identify biomarkers that can help predict, treat, and prevent prolonged symptoms.

“Our findings show there is the potential to use data from the infection stage to predict what might happen to the patient months later,” said co-corresponding author Alexander W. Charney, MD, PhD, Associate Professor of Genetics and Genomic Sciences, and Co-Director of The Charles Bronfman Institute for Personalized Medicine. “We should not ignore the infection phase in research on long COVID—this is clearly a critical window of time where the body’s response to SARS-CoV-2 might be setting the stage for what is to come.”

Reference: “Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae” by Ryan C. Thompson, Nicole W. Simons, Lillian Wilkins, Esther Cheng, Diane Marie Del Valle, Gabriel E. Hoffman, Carlo Cervia, Brian Fennessy, Konstantinos Mouskas, Nancy J. Francoeur, Jessica S. Johnson, Lauren Lepow, Jessica Le Berichel, Christie Chang, Aviva G. Beckmann, Ying-chih Wang, Kai Nie, Nicholas Zaki, Kevin Tuballes, Vanessa Barcessat, Mario A. Cedillo, Dan Yuan, Laura Huckins, Panos Roussos, Thomas U. Marron, The Mount Sinai COVID-19 Biobank Team, Benjamin S. Glicksberg, Girish Nadkarni, James R. Heath, Edgar Gonzalez-Kozlova, Onur Boyman, Seunghee Kim-Schulze, Robert Sebra, Miriam Merad, Sacha Gnjatic, Eric E. Schadt, Alexander W. Charney and Noam D. Beckmann, 8 December 2022, Nature Medicine.
DOI: 10.1038/s41591-022-02107-4

The University Hospital of Zurich, University of Zurich, University of Washington, and health intelligence company Sema4 contributed to this research.

mRNA COVID-19 Vaccines Less Effective Against Omicron – Booster of Limited Benefit for People With Prior SARS-CoV-2 Infection

Primary mRNA COVID-19 vaccine series and original booster provide protection against Omicron infection, but less effectively than against other variants. The additional benefit of the original booster may be limited among people with a prior SARS-CoV-2 infection.

mRNA COVID-19 vaccines are less effective against Omicron infections than other variants. A study published on December 1st in the open-access journal PLOS Medicine by Margaret L. Lind at the Yale School of Public Health, U.S. and colleagues suggests that the additional protection offered by the initial booster shot may be reduced among people with a previous COVID-19 infection.

Evidence indicates that primary (two-dose) and original booster mRNA (third dose) vaccination significantly reduces the risk of Omicron-related infection and severe outcomes in the general population. However, the benefit of mRNA COVID-19 vaccination in people who have previously experienced infection remains unclear.

In order to estimate the effectiveness of mRNA vaccination against Omicron infection among people with a prior documented infection, the researchers conducted a test-negative case control study using health records obtained through a COVID-19 study of vaccine-eligible people older than five who had at least one SARS-CoV-2 test in the Yale New Haven Health system electronic medical records.

The study group included 11,307 people who tested positive for SARS-CoV-2 between November 1, 2021 and April 30, 2022 as well as 130,041 control cases who tested negative in the same time period. The researchers then estimated vaccine effectiveness against infection and additionally whether an original booster dose was associated with increased protection beyond primary vaccination. This was achieved by comparing the odds of infection between boosted and booster-eligible people with and without a documented prior infection.

The researchers found that primary vaccination provided protection against Omicron infection among people with and without a documented prior infection. While original booster vaccination was associated with additional protection against Omicron infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection.

The researchers emphasize that while the initial booster may not provide additional benefits in preventing Omicron infection in some people, it still offers the best protection against severe illness and hospitalization, according to previous studies. This study was limited to Omicron infections and should be considered alongside other existing and future studies examining the relative benefits of booster doses against severe COVID-19 disease among people with and without prior infections. Additionally, this analysis was conducted prior to the distribution of the bivalent COVID-19 booster and the findings are limited to associations between the original vaccines and Omicron infection.

Lind adds, “In this retrospective study, we found that primary mRNA vaccination provides moderate protection against Omicron (BA.1 lineage) infection regardless of prior infection history. However, the relative benefits of an original booster dose against Omicron infection may be affected by a person’s history of prior SARS-CoV-2 infection.”

Reference: “Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case–control analysis” by Margaret L. Lind, Alexander J. Robertson, Julio Silva, Frederick Warner, Andreas C. Coppi, Nathan Price, Chelsea Duckwall, Peri Sosensky, Erendira C. Di Giuseppe, Ryan Borg, Mariam O. Fofana, Otavio T. Ranzani, Natalie E. Dean, Jason R. Andrews, Julio Croda, Akiko Iwasaki, Derek A. T. Cummings, Albert I. Ko, Matt D. T. Hitchings and Wade L. Schulz, 1 December 2022, PLoS Medicine.
DOI: 10.1371/journal.pmed.1004136

Why Colds, Flu, and COVID-19 Are More Common in Cooler Months: Biological Explanation Uncovered

A newly discovered immune response inside the nose is suppressed by colder temperatures, offering evidence for why upper respiratory infections such as colds, flu, and COVID-19 are more common in cooler months.

Scientists have discovered a previously unidentified immune response inside the nose that fights off viruses responsible for upper respiratory infections. Further testing revealed this protective response becomes inhibited in colder temperatures, making an infection more likely to occur.

The new study offers the first biological mechanism to explain why viruses like the common cold, flu, and COVID-19 are more likely to spike in colder seasons, according to the authors. The study, by researchers at Mass Eye and Ear and Northeastern University, was published on December 6 in The Journal of Allergy and Clinical Immunology.

“Conventionally, it was thought that cold and flu season occurred in cooler months because people are stuck indoors more where airborne viruses could spread more easily,” said Benjamin S. Bleier, MD, FACS, director of Otolaryngology Translational Research at Mass Eye and Ear and senior author of the study. “Our study however points to a biological root cause for the seasonal variation in upper respiratory viral infections we see each year, most recently demonstrated throughout the COVID-19 pandemic.”

The nose is one of the first points of contact between the outside environment and inside the body and, as such, a likely entry point for disease-causing pathogens. Pathogens are inhaled or directly deposited (such as by the hands) into the front of the nose where they work their way backward through the airway and into the body infecting cells, which can lead to an upper respiratory infection. How the airway protects itself against these pathogens has long been poorly understood.

That is until a 2018 study led by Dr. Bleier and Mansoor Amiji, PhD, Distinguished Professor of Pharmaceutical Sciences at Northeastern University, uncovered an innate immune response triggered when bacteria is inhaled through the nose: Cells in the front of the nose detected the bacteria and then released billions of tiny fluid-filled sacs called extracellular vesicles (or EVs, known previously as exosomes) into the mucus to surround and attack the bacteria. Dr. Bleier compares the release of this EV swarm to “kicking a hornets’ nest.”

The 2018 study also showed that the EVs shuttle protective antibacterial proteins through the mucus from the front of the nose to the back of it along the airway, which then protects other cells against the bacteria before it gets too far into the body.

For the new study, the researchers sought to determine if this immune response was also triggered by viruses inhaled through the nose, which are the source of some of the most common upper respiratory infections.

Led by first study author Di Huang, PhD, a research fellow at Mass Eye and Ear and Northeastern, the researchers analyzed how cells and nasal tissue samples collected from the noses of patients undergoing surgery and healthy volunteers responded to three viruses: a single coronavirus and two rhinoviruses that cause the common cold.

They found each virus triggered an EV swarm response from nasal cells, albeit using a signaling pathway different from the one used to fight off bacteria. The researchers also discovered a mechanism at play in the response against the viruses: Upon their release, the EVs acted as decoys, carrying receptors that the virus would bind itself to instead of the nasal cells.

“The more decoys, the more the EVs can mop up the viruses in the mucus before the viruses have a chance to bind to the nasal cells, which suppresses the infection,” said Dr. Huang.

The researchers then tested how colder temperatures affected this response, which is especially relevant in nasal immunity given the internal temperature of the nose is highly dependent on the temperature of the outside air it inhales. They took healthy volunteers from a room temperature environment and exposed them to 4.4°C (39.9°F) temperatures for 15 minutes and found that the temperature inside the nose fell about 5°C (9°F). They then applied this reduction in temperature to the nasal tissue samples and observed a blunted immune response. The quantity of EVs secreted by the nasal cells decreased by nearly 42 percent and the antiviral proteins in the EVs were also impaired.

“Combined, these findings provide a mechanistic explanation for the seasonal variation in upper respiratory infections,” said Dr. Huang.

Future studies will aim to replicate the findings with other pathogens. The studies could take place as challenge studies, where an animal model or human is exposed to a virus and their nasal immune response is measured.

From their recent findings, the researchers can also imagine ways in which therapeutics can induce and strengthen the nose’s innate immune response. For example, a drug therapy, such as a nasal spray, could be designed to increase the number of EVs in the nose or binding receptors within the vesicles.

“We’ve uncovered a new immune mechanism in the nose that is constantly being bombarded, and have shown what compromises this protection,” said Dr. Amiji. “The question now changes to, ‘How can we exploit this natural phenomenon and recreate a defensive mechanism in the nose and boost this protection, especially in colder months?’”

Reference: “Cold exposure impairs extracellular vesicle swarm–mediated nasal antiviral immunity” by Di Huang, PhD; Maie S. Taha, PhD; Angela L. Nocera, PhD; Alan D. Workman, MD; Mansoor M. Amiji, PhD and Benjamin S. Bleier, MD, 6 December 2022, Journal of Allergy and Clinical Immunology.
DOI: 10.1016/j.jaci.2022.09.037

In addition to Drs. Bleier, Amiji and Huang, co-authors of the study were Maie S. Taha, PhD, Angela L. Nocera, PhD and Alan D. Workman, MD of Mass Eye and Ear. The study was supported by funding from Northeastern University and National Eye Institute of the National Institutes of Health (P30EY003790).

New Discoveries Could Improve Cheese Production and Lead to Novel Cheeses

New Discoveries Could Improve Cheese Production and Lead to Novel Cheeses

Washington, D.C. – November 15, 2022 – New research shows that the flavoring of various soft cheeses is due in part to the bacteria that colonize them during the ripening process. The research is published in Microbiology Spectrum, a journal of the American Society for Microbiology.
As cheese ages, beneficial bacteria degrade proteins and lipids (from milk fat) and produce the molecules responsible for characteristic aromas of ripening cheeses. (1) The diversity of “non-starter” bacteria, which spontaneously develop during ripening and form flavor compounds, is the key factor for developing the characteristics of cheese.
The role of microorganisms in flavor formation had not been fully understood, “due to the diversity of cheese varieties and the complexity of cheese microbial consortia,” said corresponding author Morio Ishikawa, Ph.D., a professor at the Department of Fermentation Science, Faculty of Applied Bioscience at the Tokyo University of Agriculture in Japan.
In the study, the investigators presented an approach to identifying and examining certain bacteria known to be involved in cheese production, including 3 phyla of bacteria, Firmicutes, which are lactic acid bacteria, and Actinobacteria and Proteobacteria, which produce characteristic flavors in certain cheeses. By comparing bacteria from across the 3 phyla to other known flavor-producing bacteria in a cheese ripening test, the researchers showed a relationship between specific microbes and flavor.
Ishikawa and his collaborators had used statistical analysis to reveal relationships between bacterial types and the various volatile flavor-producing organic compounds that each produces in surface-mold ripened cheeses. To test that relationship of specific microbes to flavor, they then selected non-starter bacteria of taxa that were strongly correlated with specific volatile compounds and flavors, and performed cheese-ripening tests. These tests showed that the bacteria from the correlational research were in fact responsible for the flavors of the cheeses.
Additionally, this research could provide a scientific basis for improving the safety and quality of cheese. “By isolating and investigating microorganisms involved in flavor formation as targets, rather than blindly examining them, we will be able to scientifically evaluate the safety of these microorganisms. At the same time, it may be possible to construct a cheese production method that uses only those microorganisms that play a major role in flavor production,” said Ishikawa.
“The comprehensive insights into the complex associations between microbiota and flavor improve our systematic understanding of mechanism of cheese flavor production,” said Ishikawa. The new research will not only provide a scientific basis for the traditional method of cheese production, but might also enable the creation of novel cheeses.
1. per Ishikawa, little or no lactose remains in cheese during ripening.



The American Society for Microbiology is the largest single life science society, composed of more than 30,000 scientists and health professionals. ASM’s mission is to promote and advance the microbial sciences.  

ASM advances the microbial sciences through conferences, publications, certifications, educational opportunities and advocacy efforts. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences.  

Boosting Accuracy, Reducing False Positives of PCR COVID-19 Tests

Boosting Accuracy, Reducing False Positives of PCR COVID-19 Tests


  • PCR tests are the gold standard for COVID-19 diagnosis, but they’re not always accurate. 

  • False positives and false negatives both have negative repercussions and risks for patients. 

  • New research suggests adding a test for the genetic response of the infected individual (the host) could improve accuracy. 

  • Researchers have derived and tested a classifier, based on 2 host genes, that could readily be added to existing PCR assays. 

Washington, D.C. – Dec. 12, 2022 – PCR swab tests that look for viral RNA have become the gold standard for identifying infection with the SARS-CoV-2 virus, but their results aren’t 100% accurate. This week in  mSystems,  researchers report that testing for levels of certain immune-related genes in an infected individual, in addition to looking for genetic material of the virus itself, could increase diagnostic accuracy. 

Researchers compared gene expression data from people diagnosed with COVID-19 to those of people diagnosed with other viral respiratory illnesses and people with non-viral conditions. The analysis revealed that expression of a combination of 2 host genes is strongly associated with SARS-CoV-2 infection. Furthermore, a test for that genetic response could be readily incorporated into existing PCR assays and retain its accuracy for existing and future variants of the virus. 

“We envision this as an add-on to a PCR test that still looks for direct evidence of the virus and uses the host genes as a fallback to make sure we catch situations where there might be false positive or false negative results from the viral PCR,” said computational biologist Eran Mick, Ph.D., at the University of California, San Francisco. 

Mick was one of 3 lead authors on the paper. The other 2 were UCSF microbiologist Estella Sanchez-Guerrero, Ph.D., and Jack Albright, an undergraduate student at Stanford University, who began working on the project as a high school intern at the Chan Zuckerberg (CZ) Biohub. Infectious disease researcher Charles Langelier, M.D., Ph.D., also at UCSF and CZ Biohub, was senior author on the study. 

The U.S. Food and Drug Administration approved the first PCR test for COVID-19 in the spring of 2020. However, during widespread use the test is vulnerable to false negatives—especially as the virus evolves into new variants that might escape detection—and false positives as through contamination by other samples in a testing lab. A person who received a false negative result might get sick without treatment and continue to spread the virus. A false positive result could cause a person to endure unnecessary isolation or have planned medical procedures canceled. 

“There are a lot of repercussions,” said Langelier. 

In November 2020, Mick and Langelier led a study that demonstrated COVID-19 causes a unique gene expression pattern in infected individuals. The observation prompted them to investigate whether those genes might have some diagnostic utility. In previously published work, the team used RNA sequencing data from nasopharyngeal swabs to identify combinations of multiple genes that could serve as diagnostic classifiers for COVID-19. 

However, according to Langelier, testing for the response of a large number of genes isn’t feasible on a routine basis and is incompatible with existing clinical PCR tests. For the new work, the researchers tested a range of 2-gene combinations to find a pair that could accurately diagnose COVID-19. They found that the optimal signature included  IFI6, a gene stimulated by interferon and strongly induced in COVID-19 compared to non-viral conditions, and  GBP5,  which is strongly induced in other viral infections. 

“It’s really a combination of 1 gene that does a good job at separating those with no viral infections from those with [an infection], and another gene that separates out the COVID-19 cases from other respiratory viral infections,” said Albright. 

“So many different biological processes change in the setting of an infection,” said Langelier. “It was surprising that all of that complex biology could be distilled down to these 2 genes with predictive value.” 

Once they identified the gene pair, the team showed that the classifier could be included in a PCR assay, is unaffected by cross-contamination (because it measures the host response) and works for all common variants of the virus.  

“To bring it down to such a small number of genes is a game changer,” said Mick. 

Mick noted that this 2-gene host signature is designed to be used in combination with a viral PCR test to diagnose COVID-19 because there is still significant overlap between the response to SARS-CoV-2 and the response to other viral infections. However, a purely host-based classifier could be used as a broad-range surveillance tool to identify people infected with any respiratory virus. Even before the pandemic, Mick noted that viral infections were a major public health issue, and many went undetected. A diagnostic tool that flags viral infections could be useful for screening vulnerable populations in nursing homes or hospitals.  

# # # 

The American Society for Microbiology is one of the largest single life science societies, composed of more than 30,000 scientists and health professionals. ASM’s mission is to promote and advance the microbial sciences.   

ASM advances the microbial sciences through conferences, publications, certifications, educational opportunities and advocacy efforts. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences. 

Antibody treatment improves chronic food allergy symptoms in young adults, study finds

A weekly dose of dupilumab, a monoclonal antibody, led to a reduction of symptoms and tissue improvement in young adults and adolescents with eosinophilic esophagitis (EoE), according to a new study published in the New England Journal of Medicine. The study analyzed data from two phase 3 clinical trials and involved an international group of researchers, including those from Children’s Hospital of Philadelphia (CHOP).

EoE is a chronic food allergy that affects the esophagus, the tube that connects the mouth to the stomach. Triggered by certain foods, the disease occurs when eosinophils, a type of white blood cell, accumulate in the esophagus causing pain and injury. If untreated, the in the esophagus can become stiff and scarred, leading to narrowing of the esophagus, as well as other medical complications including food impaction and choking.

Current treatments for EoE involve food elimination diets, proton-pump inhibitors (PPIs), swallowed topical glucocorticoids, and, in some cases, esophageal dilation. However, anywhere from 30 to 40% of patients may not respond to first-line treatments, and some of the treatments have unwanted side effects.

Given that growing evidence suggests that type 2 cytokines play key roles in EoE, researchers have investigated using dupilumab to treat the condition. Dupilumab is a monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, two cytokines that are key and central drivers of type 2 inflammation.

Dupilumab is approved for the treatment of several type 2 , including , asthma, and EoE, and a phase 2 trial involving adults with active EoE showed that a weekly 300mg dose of dupilumab reduced symptoms and improved esophageal tissue.

In the phase 3 trial described in the study, researchers assessed the efficacy and safety of dupilumab in patients 12 years and older, with the treatment administered weekly or every two weeks, compared to placebo. They found that 300mg of dupilumab given subcutaneously every week reduced symptoms and improved histologic outcomes, whereas a dose every other week improved histologic outcomes but did not improve symptoms.

“The results of this phase 3 trial give hope to patients and families who have historically had limited options to treat EoE,” said study co-author Jonathan Spergel, MD, Ph.D., Chief of the Allergy Program at Children’s Hospital of Philadelphia and the Stuart E Starr Chair of Pediatrics. “This study shows that dupilumab is a good treatment option for patients with EoE and not only reduces symptoms but also targets the root cause of the disease.”

More information:
Evan S. Dellon et al, Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis, New England Journal of Medicine (2022). DOI: 10.1056/NEJMoa2205982

Journal information:
New England Journal of Medicine

Science X Network

COVID-19 booster increases durability of antibody response, research shows

New research from the University of Virginia School of Medicine speaks to the benefits of a COVID-19 booster.

The new findings shed light on how mRNA boosters—both Pfizer and Moderna—affect the durability of our antibodies to COVID-19. A , the researchers report, made for longer-lasting antibodies for all recipients, even those who have recovered from a COVID-19 infection.

“These results fit with other and indicate that booster shots enhance the durability of vaccine-elicited antibodies,” said senior researcher Jeffrey Wilson, MD, Ph.D., of UVA Health’s Division of Asthma, Allergy and Immunology.

Tracking COVID-19 antibodies

Wilson and his collaborators looked at following a booster in 117 UVA employee volunteers and compared those results with the levels seen in 228 volunteers after their primary vaccination series. Antibody levels one week to 31 days after the primary series and booster were similar, but the boosted antibodies stuck around longer regardless of whether the person had had COVID-19.

“Our initial thought was that that boosters would lead to higher antibody levels than the primary vaccine series, but that was not what we found,” said researcher Samuel Ailsworth, the first author of a new scientific paper outlining the findings. “Instead, we found that the booster led to longer lasting antibodies.”

Antibody levels naturally decline over time after an infection or after vaccination, but higher levels are thought to be more protective. Thus, longer-lasting antibodies would be expected to provide more sustained immunity against severe COVID-19.

The researchers found that the antibodies generated by the Moderna booster proved longer lasting than those generated by the Pfizer booster. Moderna’s antibody levels exceeded Pfizer’s out to five months, the end of the study period. Although the findings were statistically significant, Wilson notes that both mRNA vaccine boosters provide enhanced and fairly similar levels of protection against COVID-19 in recently published large epidemiologic studies.

Because the frequency of COVID-19 infections in the community was relatively high when the boosters were being given, the authors also studied the effect of COVID-19 infection on antibody levels. The findings suggest that the “enhanced antibody durability observed after booster vaccination was not explained by hybrid immunity,” the researchers report in their paper.

The new results are the latest from Wilson’s team tracking the antibody response to the COVID-19 vaccines over time. The researchers previously found that after the primary vaccination series the antibodies generated by Pfizer’s COVID-19 vaccine rose more slowly and declined more quickly than those generated by the Moderna vaccine. That study also found that older recipients of the Pfizer generated fewer antibodies than did younger recipients—but this wasn’t the case for Moderna, where age did not appear to be a factor.

In the latest results, younger booster recipients initially generated more antibodies than did older recipients, but this difference disappeared with time.

Wilson notes that this study adds to the accumulating evidence that boosters are an important of protecting the community from COVID-19. “Although only about half of the U.S. population that is eligible for a booster has received one, it is increasingly clear that boosters enhance the protection that is conferred by the primary series mRNA vaccines alone,” he said.

The researchers have published their latest findings in the journal Annals of Allergy, Asthma & Immunology.

More information:
Samuel M. Ailsworth et al, Enhanced SARS-CoV-2 IgG durability following COVID-19 mRNA booster vaccination and comparison of BNT162b2 with mRNA-1273, Annals of Allergy, Asthma & Immunology (2022). DOI: 10.1016/j.anai.2022.10.003

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