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How does the immune system mobilize in response to a COVID-19 infection or a vaccine? 5 essential reads

The COVID-19 pandemic has brought immunology terms that are typically relegated to textbooks into our everyday vernacular. These stories helped us make…

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The COVID-19 pandemic has taught most people more than they ever expected to know about immunology. Membio/iStock via Getty Images Plus

Heading into the third year of the COVID-19 pandemic, many of us have become amateur immunologists, having conversations at the dinner table and in the grocery store aisle about mRNA vaccines, variants, breakthrough infections, “waning” immunity, herd immunity, endemic viruses, booster shots and much more.

Many of the stories that we’ve published over the past two years here at The Conversation have stemmed from our own head-scratching questions that came up in our morning news meetings or were posed to us directly by curious readers. We sought out scholars who could take our readers on deep dives into immunology and virology to help demystify these sometimes confusing, conflicting and taxing science-based questions.

Here are five stories from The Conversation’s archives that highlight critical insights that we as editors and readers have gained thanks to COVID-19, and that will no doubt continue to be an important part of our pandemic lexicon.

1. COVID-19 vaccines explained

Understanding how vaccines can “trick” the body into mounting an effective immune response against a perceived or actual threat is one of the most fascinating aspects of immunology. “The most important thing to understand about vaccines is that they teach your body how to gear up to fight an infection, without your body having to deal with the infection itself,” writes Glenn J. Rapsinski, a pediatric infectious diseases fellow at the University of Pittsburgh Health Sciences. “In this way, vaccines help your body be prepared for invasions by germs that could otherwise make you very sick.”

Rapsinski explains how the COVID-19 vaccines available in the U.S. emulate the spike protein of SARS-CoV-2, the virus that causes COVID-19. “SARS-CoV-2 is a round virus, with bumps all over it – sort of like a baseball covered in golf tees. The bumps are the spike proteins.”


Read more: What happens when the COVID-19 vaccines enter the body – a road map for kids and grown-ups


How mRNA COVID-19 vaccines work.

2. And then came breakthrough infections

Soon after the relief that came with the widespread availability of vaccines in the spring of 2021, we were introduced to the idea of “breakthrough infections,” which were the rare cases in which fully vaccinated people got infected with COVID-19.

Breakthrough infections are a little more frequent than previously expected and are probably increasing because of growing dominance of the delta variant,” Sanjay Mishra, a cancer and vaccine researcher from Vanderbilt University, wrote in July 2021. “But infections in vaccinated people are still very rare and usually cause mild or no symptoms.”

Although breakthrough infections became far more common late in 2021, in part because of the emergence of the highly transmissible omicron variant – more on that down below – COVID-19 vaccines still continue to provide robust protection against the most severe forms of COVID-19 that lead to hospitalization and death.


Read more: What is a breakthrough infection? 6 questions answered about catching COVID-19 after vaccination


3. The growing list of variants

In 2020 and 2021, new strains of SARS-CoV-2 seemed to emerge faster than people could keep up with their Greek names. But by mid-2021, the highly transmissible delta variant had become the dominant strain in the U.S. and was responsible for the growing number of breakthrough infections. The continual emergence of variants was and is concerning, because it raises questions about how robust one’s immune protection will be from prior infections or from the COVID-19 vaccines, which were based on the original strain of the virus.

The delta variant was between 40% and 60% more transmissible than the alpha variant that it replaced and nearly twice as transmissible as the original SARS-CoV-2 virus, wrote Suresh V. Kuchipudi, a professor of emerging infectious diseases at Penn State.

But then, of course, came omicron, which was even more contagious than delta, thanks in part to its high number of mutations. “Omicron is very unusual in that it is by far the most heavily mutated variant yet of SARS-CoV-2, the virus that causes COVID-19,” Kuchipudi explained. “The omicron variant has 50 mutations overall, with 32 mutations on the spike protein alone. The spike protein – which forms protruding knobs on the outside of the SARS-CoV-2 virus – helps the virus adhere to cells so that it can gain entry.”


Read more: Will omicron – the new coronavirus variant of concern – be more contagious than delta? A virus evolution expert explains what researchers know and what they don't


4. Putting ‘endemic’ viruses into context

At some point in 2021 – the year is one big blur – we entered a phase of the pandemic where it became clear that we were stuck with COVID-19 for the foreseeable future. For many people, there was a mental shift from the assumption that we could eradicate the coronavirus that causes COVID-19 through vaccination, into the slow realization that it just wasn’t going away. Virologists and other researchers began using the term “endemic” to describe the way that some viruses can fade away but still maintain a low level of transmission in a community.

Sara Sawyer, Arturo Barbachano-Guerrero and Cody Warren, a team of virologists and immunologists from the University of Colorado Boulder explain that SARS-CoV, the coronavirus that set off the SARS pandemic in 2003, was less contagious than SARS-CoV-2 and was brought under control relatively quickly by speedy public health measures that ultimately drove the virus extinct.

On the other hand, they wrote, “pandemic viruses may also gradually settle into a relatively stable rate of occurrence, maintaining a constant pool of infected hosts capable of spreading the virus to others.” Such viruses are said to be “endemic” – as will likely become the case with the coronavirus that causes COVID-19.


Read more: Is COVID-19 here to stay? A team of biologists explains what it means for a virus to become endemic


Epidemics, pandemics and endemic viruses explained.

5. Immune defenses shift over time

As 2021 waned, so – apparently – did protective antibodies against COVID-19. Researchers began to learn more about how the immune response shifts in the months following COVID-19 infection or vaccination. And it became clear that over time, people became more vulnerable to getting reinfected or having a breakthrough infection following vaccination – in part because of the emergence of variants.

But antibodies are only part of the immune system’s protective defense, explain Prakash Nagarkatti and Mitzi Nagarkatti, a husband-and-wife team of immunologists from the University of South Carolina.

“Throughout the COVID-19 pandemic, the public has widely and mistakenly believed that antibodies provide the bulk of protective immunity, while not recognizing the important role of killer T cells,” they write. “This is in part because antibodies are easy to detect, whereas killer T-cell detection is complex and involves advanced technology. When antibodies fail, it is the killer T cells that are responsible for preventing the more severe outcomes of COVID-19, such as hospitalization and death.”


Read more: How long does protective immunity against COVID-19 last after infection or vaccination? Two immunologists explain


Editor’s note: This story is a roundup of articles from The Conversation’s archives.

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Spread & Containment

Why Is The VIX So Low? A Surprising Answer Emerges In The Market’s Microstructure

Why Is The VIX So Low? A Surprising Answer Emerges In The Market’s Microstructure

One of the most frequent questions tossed around Wall Street…

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Why Is The VIX So Low? A Surprising Answer Emerges In The Market's Microstructure

One of the most frequent questions tossed around Wall Street trading desks (and strip clubs), and which was duly covered by Bloomberg recently in "Fear Has Gone Missing in Wall Street’s Slow-Motion Bear Market", is why despite the crushing bear market and the coming recession, does the VIX refuse to rise sustainably above 30, or in other words, why is the VIX so low?

As Goldman's Rocky Fishman wrote in a recent note "Option Markets Take the SPX Bear Market in Stride" (available to professional subs), "one of the most popular questions we have received is why the VIX hasn't surpassed its March peak (36) despite the SPX being lower than it was in March and realized vol being higher than it was in March."

Here, Fishman notes that implied volatility was unusually high in March, and the current VIX level (29) is only slightly low for the current level of realized vol. Furthermore, a VIX around 30 typically happens with the 5Y CDX HY spread above 600, and although it has risen steadily it's currently in the mid 500's.

Meanwhile, even as the VIX has fallen moderately since late April, both vol risk premium and skew have both fallen dramatically.

Picking up on this quandary, overnight JMorgan also joined the discussion with its analyst Peng Cheng laying out his own thoughts on why the VIX remains so low (note is also available to professional subs), and similar to Goldman notes that the current bear market, despite being deeper in magnitude, has produced VIX levels well below the peak observed during previous market sell-offs:

However, unlike Goldman which mostly analyzes the VIX in the context of a macro framework, JPM's Cheng offers observations based on his analysis of market microstructure in both equity and options markets.

Cheng starts with the previously noted low realized volatility: as the JPM strategist writes, YTD, the SPX realized vol, measured on a close to close basis, is only 25.5, which means that delta-hedged put options would have lost money in the gamma component. From a technical perspective, JPM believes that return volatility is dampened by a lack of intraday price momentum and increasingly frequent occurrences of intraday price reversal. As seen in the next chart, intraday reversal has only started to become noticeable in the last two years. Prior to that, intraday momentum was the dominant market behavior.

This diminishing intraday price momentum has had a non-trivial impact on realized volatility, according to JPM which estimates that if the intraday return correlation remained the same as pre-pandemic, YTD volatility would be close to 28.8, or 3.3 vol points higher than realized.

As an aside, those asking for the reason behind this change in intraday patterns in the last couple of years, Cheng notes that "this is a complex topic" but in short, his view is that it is a result of 1) crowding in intraday momentum trading strategies and 2) a potential shift in option gamma dynamics as discussed below.

Supply/demand of S&P 500 options: Although the estimation of market level option gamma profile is highly dependent on many factors, including assumptions on open interest, OTC options, and leveraged ETFs, etc., in a report published earlier this year, JPM's quants presented a more dynamic estimation of the gamma profile by using tick level data. Specifically, they assigned directions to SPX and SPY option trades based on their distance to the best bid/offer at the tick level, rather than the constant assumption of investors being outright long puts and short calls. The updated results are shown below.

Tha chart shows that starting in 2020, the put gamma imbalance has fallen meaningfully. This is the result of investors’ changing preference from buying outright puts to put spreads for protection, in JPM's view. And year to date, the decline in gamma demand has not improved. Moreover, and echoing what we have said on several recent occasions, JPM notes that judging from the outright negative put gamma imbalance in early 2022, it appears that investors have been monetizing hedges that had been held since 2021 - note the consistently positive and relatively elevated put gamma imbalance throughout 2021, which suggests that protections were put on during this period.

More in the full note available to pro subs

Tyler Durden Wed, 06/29/2022 - 15:05

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Dr. Stephen Kingsmore receives prestigious Precision Medicine World Conference 2022 Luminary Award

SAN DIEGO, Calif. – June 29, 2022 – Rady Children’s Institute for Genomic Medicine® (RCIGM) today announced that Stephen Kingsmore, MD, DSc, President…

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SAN DIEGO, Calif. – June 29, 2022 – Rady Children’s Institute for Genomic Medicine® (RCIGM) today announced that Stephen Kingsmore, MD, DSc, President and CEO, was presented with the Precision Medicine World Conference (PMWC) 2022 Luminary Award at this year’s conference in the Silicon Valley region of California for his innovation in rapid neonatal molecular diagnoses using whole-genome sequencing.

Credit: Rady Children’s Institute for Genomic Medicine

SAN DIEGO, Calif. – June 29, 2022 – Rady Children’s Institute for Genomic Medicine® (RCIGM) today announced that Stephen Kingsmore, MD, DSc, President and CEO, was presented with the Precision Medicine World Conference (PMWC) 2022 Luminary Award at this year’s conference in the Silicon Valley region of California for his innovation in rapid neonatal molecular diagnoses using whole-genome sequencing.

The Luminary Award recognizes the recent contributions of prominent figures who have accelerated precision medicine into the clinic. Additional PMWC 2022 honorees included Dr. Albert Bourla, Pfizer, for his extraordinary achievement in leading the record-time development of a vaccine and antiviral drug against the coronavirus and Dr. Stephen Hoge, Moderna, for overseeing R&D of the first antiviral synthetic mRNA vaccines ever created, including the one against COVID-19.

“I am honored to receive this award and be among this extraordinary group of past and present recipients focused on the clinical adoption of precision medicine,” said Dr. Kingsmore. “At RCIGM, we are transforming pediatric healthcare through the power of Rapid Precision Medicine™ by offering the fastest delivery of rapid Whole Genome Sequencing™ to enable prompt diagnosis and targeted treatment of critically ill newborns and children in intensive care. We know that time matters – a fast, molecular diagnosis can make the difference between improved outcomes and a lifetime of disability, or even life itself.”

Dr. Kingsmore leads a multi-disciplinary team of scientists, physicians, genetic counselors, software engineers and bioinformaticians who are pioneering the use of rWGS® to enable precise diagnoses for critically ill newborns. In 2021, he led the RCIGM team to set a new record of 13.5 hours for achieving the fastest molecular diagnosis using rWGS, breaking his previous 2018 world record of 19.5 hours. 

PMWC is the largest and original annual conference dedicated to precision medicine. PMWC’s mission is to bring together recognized leaders, top global researchers and medical professionals, and innovators across healthcare and biotechnology sectors to showcase practical content that helps close the knowledge gap between different sectors, thereby catalyzing cross-functional fertilization and collaboration in an effort to accelerate the development and spread of precision medicine.

Rady Children’s Institute for Genomic Medicine

Rady Children’s Institute for Genomic Medicine is transforming neonatal and pediatric health care by harnessing the power of Rapid Precision Medicine™ to improve the lives of children and families facing rare genetic disease. Founded by Rady Children’s Hospital and Health Center, the Institute offers the fastest delivery of rapid Whole Genome Sequencing™ to enable prompt diagnosis and targeted treatment of critically ill newborns and children in intensive care. The Institute now provides clinical genomic diagnostic services for a growing network of more than 70 children’s hospitals. The vision is for this life-changing technology to become standard of care and enable clinicians nationwide to provide rapid, personalized care. Learn more about the non-profit Institute at RadyGenomics.org. Follow us on Twitter and LinkedIn.

Media Contact:

Ben Metcalf
bmetcalf@rchsd.org
+1 (619) 822-8593
 


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Government

Fauci Suffers “Much Worse” COVID Symptoms After ‘Paxlovid Rebound’

Fauci Suffers "Much Worse" COVID Symptoms After ‘Paxlovid Rebound’

Fully-vaxx’d and double-boosted mask-admirer Anthony Fauci is suffering.

Two…

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Fauci Suffers "Much Worse" COVID Symptoms After 'Paxlovid Rebound'

Fully-vaxx'd and double-boosted mask-admirer Anthony Fauci is suffering.

Two weeks ago, we reported that President Biden's chief medical adviser had COVID.

The 81-year-old reportedly had 'mild symptoms' and of course he 'said the words'...

Of course, Fauci followed the CDC guidelines and ingested the government-blessed treatment - Paxlovid - due to his age and possible risks from the virus.

So, that should have been it right?

But no. During an event at Foreign Policy’s Global Health Forum, Fauci admitted he had not had a good experience:

“After I finished the five days of Paxlovid, I reverted to negative on an antigen test for three days in a row,” Fauci said Tuesday .

“And then on the fourth day, just to be absolutely certain, I tested myself again. I reverted back to positive.”

Interestingly, Fauci admitted:

"...this is becoming more and more typical based on more clinical studies..."

As Bloomberg reports, large numbers of patients have reported the phenomenon, often called Covid rebound or Paxlovid rebound, of returning symptoms after taking a full course of Pfizer’s drug.

While Pfizer Chief Executive Officer Albert Bourlasaid in May that doctors could prescribe a second course of treatment to such patients, US drug regulators have said there’s no evidence that a repeat will help.

However, Fauci said he started taking a second course of Paxlovid after experiencing symptoms “much worse than in the first go around.”

Now near completion of the five-day oral treatment, he said he was still enduring symptoms but felt “reasonably good.”

Finally, as we reported less than two weeks ago, Pfizer stopped enrolling in a clinical trial for Paxlovid for standard-risk COVID-19 patients after the latest results suggested the drug did not reduce symptoms or hospitalizations and deaths to a statistically significant degree.

Watch the full interview below: (forward to around 5:26:00):

Not exactly encouraging news...

Tyler Durden Wed, 06/29/2022 - 11:45

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