COVID-19 Vagus Nerve Inflammation May Lead To Dysautonomia: New Study

  by Megan Redshaw via The Epoch Times (emphasis ours),

New data may provide answers for those experiencing persistent symptoms long after their bout with COVID-19 has ended. These may include fatigue, lightheadedness, brain fog, cognitive issues, gastrointestinal problems, heart palpitations, shortness of breath, or an inability to tolerate upright postures.

A July 15 study published in Acta Neuropathologica suggests that SARS-CoV-2 infection may damage the nerves of the autonomic nervous system (ANS), causing an inflammatory response that can later lead to dysautonomia observed in long COVID patients.

Study Findings

Using several methods, researchers at the University Medical Center Hamburg-Eppendorf in Germany performed a microscopic analysis of the vagus nerves in 27 deceased patients with COVID-19 and five controls who died of other causes, without COVID-19.

The vagus nerve is a vital component of the ANS that regulates critical functions such as digestion, respiratory and heart rate, and immune response. Vagus nerve signaling to the brainstem also controls the “sickness behavior response,” where the brain mounts flu-like symptoms including nausea, fatigue, pain, and other chronic symptoms in response to inflammation.

The researchers detected SARS-CoV-2 RNA in vagus nerve samples obtained from deceased patients with severe COVID-19 showing direct infection of the nerve was accompanied by inflammatory cell infiltration composed mostly of monocytes—a type of white blood cell that finds and destroys germs and eliminates infected cells. Their analysis revealed a “strong enrichment of genes regulating antiviral responses and interferon signaling,” supporting the idea that vagus nerve inflammation is a common phenomenon with COVID-19.

The researchers also analyzed 23 vagus nerve samples of deceased COVID-19 patients grouped into low, intermediate, and high SARS-CoV-2 RNA viral load to determine if the virus was directly detectable in the vagus nerve and if the viral load correlated with vagus nerve dysfunction. Results showed the virus was present in the vagus nerve and also determined there was a direct correlation between SARS-CoV-2 viral RNA load and dysfunction of the central nervous system.

Researchers then screened a cohort of 323 patients admitted to the emergency room between Feb. 13, 2020, and Aug. 15, 2022, categorized by whether they had mild, moderate, severe, critical, or lethal COVID-19. They found that the respiratory rate increased in survivors but decreased in non-survivors of critical COVID-19. These results suggest SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction (respiratory rate decrease), which “contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.”

Responding to the study, microbiologist Amy Proal of PolyBio Research Foundation wrote on X, “Because the vagus nerve is an essential component of the #autonomic nervous system and regulates body functions such as heart rate, digestion, and respiratory rate, direct infection of the nerve by SARS-CoV-2 may contribute to related symptoms.” She added, “The findings beg the question: Could persistent SARS-CoV-2 infection of the vagus nerve contribute to dysautonomia in #LongCovid?”

What is Dysautonomia?

Nearly 1 in 5 people in the United States continue to experience unexplained symptoms of long COVID after their infection ends, with as many as 66 percent of patients suffering from moderate to severe dysfunction of the ANS known as dysautonomia.

Dysautonomia is a disorder of the ANS, a part of the central nervous system that controls vital involuntary functions such as breathing, heart rate, blood pressure, digestion, skin and body temperature regulation, salivating, hormonal and bladder function, and sexual function. The ANS also plays a role in the acute “fight or flight” stress response and sends messages to and from internal organs.

Dysautonomia causes the ANS—which consists of the sympathetic, parasympathetic, and enteric nervous systems—to malfunction, either through an inability to perform its tasks or by causing too much activity, resulting in high blood pressure or a rapid heart rate. The condition can be confined to the arms and legs or spread throughout the entire body. It can be severe or mild, and may be reversible or worsen over time.

Postural orthostatic tachycardia syndrome (POTS) is a common form of dysautonomia that has increased since the COVID-19 pandemic began and has been reported by those with long COVID and in those following COVID-19 vaccination.

Symptoms of POTS include but are not limited to lightheadedness, difficulty thinking or concentrating, severe and long-lasting fatigue, intolerance to exercise, blurred vision, low blood pressure, heart palpitations, tremors, and nausea.

Since the rollout of COVID-19 vaccines, 801 cases of POTS were reported to the Vaccine Adverse Events Reporting System as of July 28. This includes 597 cases attributed to Pfizer and 171 cases to Moderna.

Treatments for Dysautonomia

Therapeutic treatment options for autonomic dysfunction in the medical community are aimed at symptom management and avoiding triggers using pharmaceutical drugs and nonpharmacologic measures.

https://www.zerohedge.com/political/covid-19-vagus-nerve-inflammation-may-lead-dysautonomia-new-study

Therapeutic target for Alzheimer's disease discovered

 Scientists at Université Laval and the University of Lethbridge have succeeded in reversing certain cognitive manifestations associated with Alzheimer's disease in an animal model of the disease. Their results have been published in the scientific journal Brain.

"Although this has yet to be demonstrated in humans, we believe that the mechanism we have uncovered constitutes a very interesting therapeutic target, because it not only slows down the progression of the disease but also partially restores certain cognitive functions," comments study leader Yves De Koninck, a professor in the Faculty of Medicine and researcher at Université Laval's CERVO research centre.

Previous studies have shown that even before Alzheimer's symptoms appear, brain activity is disrupted in people who go on to develop the disease. "There is neuronal hyperactivity and signal disorganization in the brain. Our hypothesis is that a mechanism that regulates neuronal activity, more specifically the one responsible for inhibiting neuronal signals, is disrupted," explains the researcher.

The main inhibitor of neuronal signals in the human brain is the neurotransmitter GABA. It works in close collaboration with a cotransporter, KCC2. This is an ion pump, located in the cell membrane, which circulates chloride and potassium ions between the inside and outside of neurons," recalls Professor De Koninck. Maintaining this ion pump in the neuron's cell membrane could slow down or reverse the pathology.

"A loss of KCC2 in the cell membrane can lead to neuronal hyperactivity. One study has already shown that KCC2 levels were reduced in the brains of deceased Alzheimer's patients. This gave us the idea of examining the role of KCC2 in an animal model of Alzheimer's disease," adds the researcher.

Promising Results in Mice

To do this, scientists used mouse lines expressing a manifestation of Alzheimer's disease. The researchers found that when these mice reached the age of four months, KCC2 levels decreased in two regions of their brains: the hippocampus and the prefrontal cortex. These two regions are also affected in people suffering from Alzheimer's disease.

In light of these results, the researchers turned to a molecule developed in their laboratory, CLP290, a KCC2 activator that prevents its depletion. In the short term, the administration of this molecule to mice that already had reduced KCC2 levels improved their spatial memory and social behaviour. In the long term, CLP290 protected them against cognitive decline and neuronal hyperactivity.

"Our results do not imply that the loss of KCC2 causes Alzheimer's disease," insists Prof. De Koninck. "On the other hand, it does appear to cause an ionic imbalance leading to neuronal hyperactivity that can lead to neuronal death. This suggests that by preventing the loss of KCC2, we could slow down and perhaps even reverse certain manifestations of the disease."

For various reasons, CLP290 cannot be used in humans. Professor De Koninck's team is searching for other KCC2-activating molecules that would be well tolerated by Alzheimer's sufferers.

"We have developed new molecules which are currently being evaluated in our laboratory. In parallel with this research, we are testing drugs that are used for purposes other than Alzheimer's in humans, in order to assess their effects on KCC2. Repositioning an existing drug would accelerate work on this new therapeutic avenue," emphasizes the researcher.

The other signatories of the study published in Brain are Iason Keramidis, Julien Bourbonnais, Feng Wang, Dominique Isabel, Marie-Eve Paquet, Romain Sansonetti, Annie Barbeau, Lionel Froux and Antoine Godin, from Université Laval, and Brendan McAllister, Edris Rezaei, Phil Degagne, Mojtaba Nazari, Samsoon Inayat, and Majid Mohajerani, from the University of Lethbridge.

Journal Reference:

1. Iason Keramidis, Brendan B McAllister, Julien Bourbonnais, Feng Wang, Dominique Isabel, Edris Rezaei, Romain Sansonetti, Phil Degagne, Justin P Hamel, Mojtaba Nazari, Samsoon Inayat, Jordan C Dudley, Annie Barbeau, Lionel Froux, Antoine G Godin, Majid H Mohajerani, Yves De Koninck. Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer’s disease mutations. Brain, 2023; DOI: 10.1093/brain/awad250

https://www.sciencedaily.com/releases/2023/08/230810110325.htm

Red blood cell particles reduce fat deposition in arteries, potentially treating atherosclerosis

 Atherosclerosis is a disease in which fat, cholesterol, and other substances build up inside artery walls. This can lead to plaque formation, which can block arteries and cause heart attacks and strokes. Immune cells play a key role in cleaning the blood, by interacting with red blood cell extracellular vesicles (RBCEVs), which are nano-sized particles released by red blood cells.

Commonly referred to as "first responders" to infections, macrophages are immune cells which detect and clear pathogens and dead cells, and secrete molecules to activate other immune cells. To understand what happens to macrophages that are exposed to a high amount of RBCEVs and whether they prove to be beneficial in treating atherosclerosis, a multi-institutional team examined the mechanisms of how RBCEVs are internalised by macrophages and analysed the consequent changes.

Led by Assistant Professor Minh Le from the Department of Pharmacology and the Institute for Digital Medicine (WisDM), Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), the study demonstrated that the uptake of RBCEVs by macrophages was highly efficient, as the particles induced multiple changes in the macrophages. Following exposure to RBCEVs, the macrophages had decreased levels of proteins that promote inflammation, suggesting the potential use of RBCEVs to alleviate conditions associated with excessive inflammation. The macrophages also produced higher levels of an enzyme which protects cells against oxidative damage -- commonly observed in inflammatory and cardiovascular diseases. In addition, the RBCEVs led to higher resistance to lipid uptake in the macrophages, reducing fat deposition -- which characterises the condition of atherosclerosis.

Published in the Journal of Extracellular Vesicles, one of the top Cell Biology journals, the study was conducted in collaboration with the Department of Surgery, Department of Physiology, Nanomedicine Translational Research Programme, and Cardiovascular Research Institute at NUS Medicine; the School of Mechanical and Aerospace Engineering and Lee Kong Chian School of Medicine, Nanyang Technological University (NTU); and the Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR).

Asst Prof Minh Le said, "We have known for a while that RBCEVs tend to go to macrophages when they enter the body, but we did not realise some of the implications until now. The properties of RBCEVs that we have uncovered here are desirable for treating atherosclerosis and possibly other inflammatory diseases."

The team hopes to leverage their improved understanding to manipulate RBCEV uptake by macrophages and thus adjust the distribution of RBCEVs to different tissues in the body. The team also plans to further explore the therapeutic potential of RBCEVs by combining their natural beneficial properties with exogenously loaded drugs designed to treat inflammatory conditions. These plans are part of the expansion of their ongoing work on developing the RBCEV platform for the treatment of various diseases including cancer, cancer-associated muscle loss, and COVID-19.

"Atherosclerosis causes heart disease and stroke, affecting millions of people. This discovery by the team is paving the way towards exciting new therapeutic strategies that can have a real impact on healthcare. We can now start looking into the use of very tiny particles made from our own red blood cells to treat atherosclerosis and potentially other diseases," said Professor Lee Chuen Neng from the Department of Surgery, and Nanomedicine Translational Research Programme at NUS Medicine. He is also Clinical Director, Institute for Health Innovation & Technology, NUS.

Journal Reference:

1. Thach Tuan Pham, Anh Hong Le, Cong Phi Dang, Suet Yen Chong, Dang Vinh Do, Boya Peng, Migara Kavishka Jayasinghe, Hong Boon Ong, Dong Van Hoang, Roma Anne Louise, Yuin‐Han Loh, Han Wei Hou, Jiong‐Wei Wang, Minh TN Le. Endocytosis of red blood cell extracellular vesicles by macrophages leads to cytoplasmic heme release and prevents foam cell formation in atherosclerosis. Journal of Extracellular Vesicles, 2023; 12 (8) DOI: 10.1002/jev2.12354

https://www.sciencedaily.com/releases/2023/08/230810110353.htm

2 paths to autism in the developing brain

 Two distinct neurodevelopmental abnormalities that arise just weeks after the start of brain development have been associated with the emergence of autism spectrum disorder, according to a new Yale-led study in which researchers developed brain organoids from the stem cells of boys diagnosed with the disorder.

And, researchers say, the specific abnormalities seem to be dictated by the size of the child's brain, a finding that could help doctors and researchers to diagnosis and treat autism in the future.

The findings were published Aug. 10 in the journal Nature Neuroscience.

"It's amazing that children with the same symptoms end up with two distinct forms of altered neural networks," said Dr. Flora Vaccarino, the Harris Professor in the Child Study Center at Yale School of Medicine and co-senior author of the paper.

Using stem cells collected from 13 boys diagnosed with autism -- including eight boys with macrocephaly, a condition in which the head is enlarged -- a Yale team created brain organoids (small, three-dimensional replicas of the developing brain) in a lab dish that mimic neuronal growth in the fetus. They then compared brain development of these affected children with their fathers. (Patients were recruited from clinician colleagues at the Yale Child Study Center, which conducts research, service, and training to improve understanding of health issues facing children and their families.)

The study was co-led by Alexandre Jourdon, Feinan Wu, and Jessica Mariani, all from Vaccarino's lab at the Yale School of Medicine.

About 20% of autism cases involve individuals with macrocephaly, a condition in which a child's head size is in the 90th percentile or greater at birth. Among autism cases these tend to be more severe.

Intriguingly, the researchers found that children with autism and macrocephaly exhibited excessive growth of excitatory neurons compared with their fathers while organoids of other children with autism showed a deficit of the same type of neurons.

The ability to track the growth of specific types of neurons could help doctors diagnose autism, symptoms of which generally appear 18 to 24 months after birth, the authors say.

The findings may also help identify autism cases that might benefit from existing drugs designed to ameliorate symptoms of disorders marked by excessive excitatory neuron activity, such as epilepsy, Vaccarino said. Autism patients with macrocephaly might benefit from such drugs while those without enlarged brains may not, she said.

Creating biobanks of patient-derived stem cells could be essential to tailor therapeutics to specific individuals, or personalized medicine.

Abyzov Alexej, an associate professor of biomedical informatics at the Mayo Clinic, is co-senior author of the paper.

Journal Reference:

1. Alexandre Jourdon, Feinan Wu, Jessica Mariani, Davide Capauto, Scott Norton, Livia Tomasini, Anahita Amiri, Milovan Suvakov, Jeremy D. Schreiner, Yeongjun Jang, Arijit Panda, Cindy Khanh Nguyen, Elise M. Cummings, Gloria Han, Kelly Powell, Anna Szekely, James C. McPartland, Kevin Pelphrey, Katarzyna Chawarska, Pamela Ventola, Alexej Abyzov, Flora M. Vaccarino. Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis. Nature Neuroscience, 2023; DOI: 10.1038/s41593-023-01399-0

https://www.sciencedaily.com/releases/2023/08/230810110412.htm

Long COVID symptoms can emerge months after infection

 Long COVID can persist for at least a year after the acute illness has passed, or appear months later, according to the most comprehensive look yet at how symptoms play out over a year.

The multicenter study, a collaboration between UC San Francisco, the Centers for Disease Control and Prevention (CDC) and seven other sites, expands knowledge of post-COVID-19 conditions, describing trends in more detail than previous research and highlighting significant impacts the epidemic has had on the U.S. health care system.

The study appears Aug. 10, 2023, in Morbidity and Mortality Weekly Report (MMWR), a publication of the CDC.

For about 16% of the COVID-positive people in the study, symptoms lasted for at least a year; but for others, they came and went. The study assessed symptoms every three months, enabling researchers to differentiate between symptoms that improve and those that emerge months after the initial infection.

"It was common for symptoms to resolve then re-emerge months later," said lead author Juan Carlos Montoy, MD, PhD, associate professor at UCSF's Department of Emergency Medicine. "A lot of prior research has focused on symptoms at one or two points in time, but we were able to describe symptom trajectory with greater clarity and nuance. It suggests that measurements at a single point in time could underestimate or mischaracterizes the true burden of disease."

Fluctuating Nature of Disease

Long COVID involves a range of symptoms that persist or develop about a month after initial infection. These symptoms are associated with significant morbidity or reduced quality of life.

The study involved 1,741 participants -- two-thirds of them female -- who sought COVID testing at eight major health care systems across the country. Three-quarters tested positive for COVID, but those who tested negative may also have had an infection of some type, since they were experiencing symptoms. These included fatigue, runny nose, headache, sore throat, shortness of breath, chest pain, diarrhea, forgetfulness and difficulty thinking or concentrating.

COVID positive participants were more likely to have symptoms in each of the symptom categories at baseline, but by the end of the year, there was no difference between those who were COVID positive and negative.

"We were surprised to see how similar the patterns were between the COVID positive and COVID negative groups," said Montoy. "It shows that the burden after COVID may be high, but it might also be high for other non-COVID illnesses. We have a lot to learn about post-illness processes for COVID and other conditions."

The data came from the CDC's INSPIRE project (Innovative Support for Patients with SARS-CoV-2 Infections Registry), which includes Rush University, Chicago; Thomas Jefferson University, Philadelphia; University of California, Los Angeles; University of Texas Southwestern Medical Center, Dallas; UTHealth Houston, Houston; University of Washington, Seattle; and Yale University, New Haven.

Co-authors: From UCSF, co-authors were James Ford, MD, Robert M. Rodriguez, MD, and Ralph C. Wang, MD. For co-authors from other institutions, please see the paper.

Funding: INSPIRE is a CDC-funded project (Contract 75D30120C08008).

Journal Reference:

1. Juan Carlos C. Montoy, James Ford, Huihui Yu, Michael Gottlieb, Dana Morse, Michelle Santangelo, Kelli N. O’Laughlin, Kevin Schaeffer, Pamela Logan, Kristin Rising, Mandy J. Hill, Lauren E. Wisk, Wafah Salah, Ahamed H. Idris, Ryan M. Huebinger, Erica S. Spatz, Robert M. Rodriguez, Robin E. Klabbers, Kristyn Gatling, Ralph C. Wang, Joann G. Elmore, Samuel A. McDonald, Kari A. Stephens, Robert A. Weinstein, Arjun K. Venkatesh, Sharon Saydah, Zohaib Ahmed, Michael Choi, Antonia Derden, Michael Gottlieb, Diego Guzman, Minna Hassaballa, Ryan Jerger, Marshall Kaadan, Katherine Koo, Geoffrey Yang, Jocelyn Dorney, Jeremiah Kinsman, Shu-Xia Li, Zhenqiu Lin, Imtiaz Ebna Mannan, Senyte Pierce, Xavier Puente, Andrew Ulrich, Zimo Yang, Huihui Yu, Karen Adams, Jill Anderson, Gary Chang, Nikki Gentile, Rachel E. Geyer, Zenoura Maat, Kerry Malone, Graham Nichol, Jasmine Park, Luis Ruiz, Mary Schiffgens, Tracy Stober, Michael Willis, Zihan Zhang, Grace Amadio, Alex Charlton, David Cheng, Dylan Grau, Paavali Hannikainen, Efrat Kean, Morgan Kelly, Jessica Miao, Nicole Renzi, Hailey Shughart, Lindsey Shughart, Carly Shutty, Phillip Watts, Arun Kane, Peter Nikonowicz, Sarah Sapp, David Gallegos, Riley Martin, Chris Chandler, Megan Eguchi, Michelle L’Hommedieu, Raul Moreno, Kate Diaz Roldan, Mireya Arreguin, Virginia Chan, Cecilia Lara Chavez, Robin Kemball, Angela Wong, Melissa Briggs-Hagen, Aron J. Hall, Ian D. Plumb. Prevalence of Symptoms ≤12 Months After Acute Illness, by COVID-19 Testing Status Among Adults — United States, December 2020–March 2023. MMWR. Morbidity and Mortality Weekly Report, 2023; 72 (32): 859 DOI: 10.15585/mmwr.mm7232a2

https://www.sciencedaily.com/releases/2023/08/230810141013.htm

Look to the Options Market for Signs of Stock Market Trouble

 Deep within the underbelly of the options world lies a threat to the stock-market calm that’s prevailed all year.

While benchmark indexes just limped to one of their smallest weekly changes of 2023, intraday moves tell a different story. Up-and-down swings in the S&P 500 are the widest since June and double what they were last month. Twice in the past six sessions the index’s futures erased a 0.9% gain, the first time that’s happened since February.

While uncertainty about the economy and central bank policy was one instigator, something else may be contributing to the volatility: Market makers repositioning their exposures. There’s evidence that these Wall Street dealers — with the capacity to move millions of shares to hedge their books — have shifted to a posture where their selling has the potential to exacerbate market swings.

Any turbulence is likely to be temporary and betting against price swings remains a popular trade. But this change in dealer positioning is a departure from the first seven months of the year when the cohort played a major role curbing price swings, according to a model kept by Goldman Sachs Group Inc.’s managing director Scott Rubner.

“Market moves are exacerbated, and no longer muted,” Rubner, who has studied flow of funds for two decades, wrote in a note Thursday. “This is new.”

Stocks fell for a second week as a mixed bag of inflation data added to an already heated debate about whether the Federal Reserve is finished hiking rates and how long the economy can avoid a recession. The S&P 500 slipped 0.3%, while the Nasdaq 100 capped a two-week retreat in which it has fallen 4.6%.

For the five sessions through Thursday, the S&P 500 posted an average intraday swing of 1.1% — the widest gyration since June, data compiled by Bloomberg show. While the oscillation pales in comparison to 2022’s bear market, it’s almost double the average daily move from just two weeks ago.

“There’s still the potential for soft landing and there’s still a potential for like a consumer retraction, which leads to a corporate profit contraction,” said Tom Hainlin, national investment strategist at US Bank Wealth Management. “People are trading on the two range of outcomes, so you’ve just got this push and pull.”

A potential accelerant in the process is captured by the concept known in derivatives parlance as gamma, or the theoretical value of stock that option dealers must sell or buy to hedge against the directional risk resulting from price changes in the underlying assets.

To be sure, getting a clear read on the interplay between the vast derivatives universe and the underlying shares isn’t easy. Oftentimes, models built on subjective assumptions spit out different numbers on how much market-maker hedging is required in a given scenario. While not an exact science, such analysis offers a lens into the potential impact from the complex derivatives world on the cash market.

And right now, two widely followed Wall Street trading desks are sounding alarms over potential turbulence on the horizon as option dealers move away from their “long gamma” position — a status that previously obliged them to go against the prevailing market trend, selling stocks when they go up, or vice versa.

By Goldman’s model, the group’s exposure to S&P 500 options flipped this week to negative for the first time this year, while that for all index contracts was the most short since last October.

The shift was also detected by a Morgan Stanley team led by Christopher Metli, who flagged dealers’ exposure plunged more than 80% from a few weeks ago. The pullback, the team observed, coincided with a slowdown in volatility selling — the kind of activity increasingly driven by exchange-traded funds that sell call contracts for income.

That, combined with the activity of leveraged ETFs right now — those employing derivatives to generate performance that’s multiple times that of the underlying asset — means the market is susceptible to larger moves, according to the Morgan Stanley team.

“The Street will sell into a down tape and buy into an up tape,” they wrote. “This is likely temporary – but for now, it leaves the market free to move.”

There are signs that traders are hesitant to bid up stocks after a 10-month, 28% rally pushed the S&P 500’s price-earnings ratio to elevated levels that were reached only twice in the past three decades. Funds focusing on US stocks just had their first outflow in three weeks, according to Bank of America Corp., citing data from EPFR Global.

Down almost 3% into August, the S&P 500 is off to its worst start of a month since March. The retreat, if it continues, could prompt an exodus from systematic money managers that make asset allocation based on volatility and momentum signals, according to Goldman’s Rubner.

Thanks to a steady advance in equities this year, these rules-based funds have rushed to buy stocks, with positioning among volatility-targeting strategies hovering near a decade high.

Commodity trading advisers, or CTAs that surf the momentum of asset prices through long and short bets in the futures market, have loaded up so much stock that Rubner says even a small pullback would set off a violent unwinding. One number to watch, he says, is the S&P 500’s 50-day moving average. That trend line, currently near 4,438, hasn’t been breached since the banking crisis in March.

A dip below 4,278 could turn the medium-term momentum to negative for CTAs, his model shows. That level is near the index’s 100-day average.

“This is the theme here, if we start rolling downhill, there is an accelerant based on positioning and rules based trading,” Rubner wrote. “Volatility is a player on the field and no longer the coach.”

For much of 2023, US stocks have spent the time grinding higher with subdued volatility. Even after the recent increase, the Cboe Volatility Index, a gauge of cost in S&P 500 options known as VIX, hovers below its long-term average, poised for its calmest year since 2019.

A further pickup in volatility could ignite a rush for risk-off, just as it happened during the banking turmoil in March, according to Bob Elliott, chief investment officer at Unlimited. Many investors came into the year defensively positioned only to find themselves getting dragged into a resilient market.

“A big part of what has driven the rally, particularly in stocks, is low volatility in aggregate has led to people willing to take on more risk in the system,” Elliott said. “But if we transition to a period where there is more volatility, as we’ve seen in the last few weeks, that’s likely to constrain the leverage that investors are willing to apply to their positions and cause a drag on asset prices and eventually the economy.”

https://finance.yahoo.com/news/look-options-market-signs-stock-200536548.html

Old antibiotic may get new life as an STI prevention pill

 The United States is set to roll out a powerful new weapon in the long fight against sexually transmitted infections: a decades-old antibiotic repurposed as a preventative pill.

DoxyPEP, or doxycycline used as a post-exposure prophylaxis, has been found to significantly cut the risk of chlamydia, gonorrhea and syphilis when used after condomless sex.

The Center for Disease Control and Prevention (CDC), which is developing national guidance for clinicians, will need to weigh the need to contain record high rates of STIs impacting millions of Americans against potentially giving rise to more antibiotic-resistant strains.

"Innovation and creativity matter in public health, and more tools are desperately needed," senior CDC official Jonathan Mermin told AFP.

But the recommendations, set for publication this summer, will remain narrow in scope.

They will likely target only the most at-risk groups of gay men and transgender women with histories of prior infection.

As word spreads, some clinics are already prescribing DoxyPEP.

Malik, a 37-year-old man in Washington, said his doctor recently told him he could start using doxycycline as a "morning-after pill" following risky sex, something he's had to do twice—including after a partner did not warn him he had removed his condom.

Two-thirds reduction

Reported cases of the three bacterial infections grew to 2.5 million in the United States in 2021, following about a decade of growth.

Several issues are behind the rise: fewer people are using condoms since the advent of PrEP—daily pills that significantly reduce chances of contracting HIV.

And people who are on PrEP are recommended to undergo screening every three months, likely increasing the identification of infections.

Then there is the basic epidemiological fact that the greater the number of people infected, the more they can further infect.

Researchers have found DoxyPEP efficacious in three of four trials.

"What we found was there was about a two-thirds reduction in sexually transmitted infection every three months," Annie Luetkemeyer, who co-led a US trial, told AFP.

The physician-scientist at the University of California, San Francisco recruited some 500 people in San Francisco and Seattle among communities of men who have sex with men and transgender women.

Efficacy was greatest for chlamydia and syphilis, both of which were reduced by about 80 percent, while for gonorrhea it was about 55 percent. There were few side effects.

Antibiotic resistance

Broadening access to doxycycline has prompted concerns about causing antibiotic resistance, particularly in gonorrhea, which is fast mutating.

But early research hasn't shown cause for alarm.

Connie Celum of the University of Washington, who co-led the US study, told AFP researchers tested gonorrhea samples from breakthrough infections in the DoxyPEP group and compared them to the group who didn't receive the pill.

Though they found the rate of resistant gonorrhea slightly higher in the DoxyPEP group, she says the finding could simply mean the pill is less effective against already resistant strains, rather than causing that resistance.

DoxyPEP could even boost responsible antibiotic stewardship—cutting the incidence of infections, thus also cutting need for antibiotic treatment.

If it slashed gonorrhea cases by some 50 percent, it could reduce the number of people requiring antibiotic treatment with the current frontline treatment drug, ceftriaxone, which doctors are eager to preserve.

Longer term study is required, on both impacts on STIs but also "bystander" bacteria such as Staphylococcus aureus, which live inside people's noses but sometimes cause serious infections.

'Additional tool'

Malik said that while he is glad he could use DoxyPEP as a last resort, he wishes more men were willing to use condoms. Since moving to America from South Asia, he gets relatively little interest on dating app Grindr when he says he's not willing to have condomless sex.

But Stephen Abbott—a doctor at Washington's Whitman-Walker clinic who prescribes and uses DoxyPEP—said it's crucial to meet people where they are.

"From speaking with patients, and being part of the community that's now on PrEP... I think the age of prevention through condoms is fading," he told AFP.

A 42-year-old man in London who runs a cultural organization told AFP that word had spread about DoxyPEP through the international gay party circuit and he had procured a supply on the black market and through a partner who buys in bulk in Mexico.

It had largely worked for him, though he did have one breakthrough infection of throat gonorrhea. He said he was looking forward to the United Kingdom adopting similar guidance so that people have the right information and aren't left to guess at the right dosage.

For Luetkemeyer, DoxyPEP won't be "the answer" to the STI epidemic, and there is considerable interest in the development of a gonorrhea vaccine.

"But I'm optimistic... I think this is an additional tool," she said.

https://medicalxpress.com/news/2023-08-antibiotic-life-sti-pill.html