3 Categories of Long COVID Defined and Risk Rises with Second Infection

 Long COVID, whose technical name is post-acute sequelae of SARS-CoV-2 infection (PASC), describes symptoms of COVID-19 that persist at least four weeks after infection. According to two recent studies from the Journal of the American Medical Association, 10 to 30% of people with COVID-19 reported at least one persistent symptom up to six months after infection, which qualifies as Long COVID. 

New research is revealing more about this chronic condition and potential avenues to treat it.

3 Categories of Long COVID

New research suggests there are three different forms of Long COVID, with each category having its own symptoms. One category includes neurological symptoms like fatigue, “brain fog” and headache.

This appears to occur in people who contracted the Alpha and Delta variants, according to a study out of King’s College London. These were more common during the first wave.

The second category is defined by respiratory issues, such as shortness of breath and chest pain. These are also associated with the first wave of the pandemic and suggest lung damage.

The third group comes with a wide range of symptoms, which include muscle ache and pain, changes in skin and hair and heart palpitations. These are associated with all variants.

The researchers evaluated 1,459 people living with Long COVID who were part of the Zoe Health study. They all reported symptoms at least 12 weeks after infection.

Claire Steves, Ph.D., clinical lead author from King’s College London, said, “These data show clearly that post-COVID syndrome is not just one condition, but appears to have several subtypes. Understanding the root causes of these subtypes may help in finding treatment strategies. Moreover, these data emphasize the need for Long COVID services to incorporate a personalized approach sensitive to the issues of each individual.”

New Symptoms of Long COVID

Another study out of the U.K., this one published in Nature Medicine, evaluated 500,000 adults with Long COVID. Researchers found a broader range of symptoms, including hair loss, difficulty ejaculating, reduced libido, vertigo, problems urinating, anorexia and hot flashes. These are classified as “emerging” symptoms associated with Long COVID, and there are 15 of them.

“My reaction to the study would be ‘yeah, sounds about right,’” Amy Proal, Ph.D., a microbiologist at PolyBio Research Foundation who studies chronic conditions, told Insider. “The chronic consequences of this virus are immense when you start to actually account for these symptoms.”

Catching COVID-19 Twice Increases Long-Term Health Risks

As immunity from previous infections and vaccines wanes, more people are catching COVID-19 a second time. This is exacerbated by the highly infectious Omicron subvariants, BA.4 and BA.5. Although these infections tend to be mild, data is suggesting that catching the virus a second time can increase long-term health risks, particularly due to Long COVID.

In a not yet peer-reviewed study of U.S. veterans, a second infection “contributes to additional risks of all-cause mortality, hospitalization and adverse health outcomes,” and appears to increase the risk for diabetes, fatigue and mental health disorders. In the study, people who caught COVID-19 a second time were at 2.5 times greater risk of developing heart or lung disease and having blood clotting problems.

“The additive risk is really not trivial, not insignificant,” Dr. Ziyad Al-Aly, M.D., a clinical epidemiologist at Washington University in St. Louis and chief of research and development at the Veterans Affairs St. Louis Healthcare System said. 

Axcella’s Experimental Drug Improves Mental and Physical Fatigue

Cambridge, Massachusetts-based Axcella Therapeutics reported topline results from the Phase IIa trial of AXA1125 in patients with fatigue related to Long COVID. In the study, 41 patients were enrolled and received either 67.8 grams per day of AXA1125 or a matched placebo in two divided doses for 28 days, with a one-week safety follow-up.

Endpoints included phosphocreatine recovery time following moderate exercise as assessed by 31P-magnetic resonance spectroscopy, which was used to evaluate mitochondrial function. Clinically relevant endpoints include self-reported mental and physical fatigue as evaluated by the Chalder Fatigue Questionnaire, a 6-minute walk test and serum lactate levels.

Patients receiving the drug had improvements in all measures of mental and physical fatigue. They were highly statistically significant and clinically relevant compared to the placebo cohort. The researchers noted the phosphocreatine recovery time in all patients was significantly higher and had a higher degree of variability than previously seen in the literature.

“These findings support the hypothesis that there is significant mitochondrial dysfunction in these patients but limits the utility of this parameter in a clinical trial,” the company noted.

Because Long COVID is so new and so relatively understudied, there were no standard endpoints. However, based on the results, the company plans to talk to U.K. and U.S. regulators about how to get the drug authorized for Long COVID. 

“We believe we have already demonstrated in just a month of dosing a profound effect,” Axcella CEO Bill Hinshaw said. 

The drug was originally designed to fight muscle weakness and fatigue linked to nonalcoholic steatohepatitis (NASH), a form of fatty liver disease. It appears to have a positive impact on mitochondrial function, bioenergetics and inflammation.

Persistent Loss of Smell from COVID-19 Associated with Cognitive Impairment

A research study out of Argentina analyzed 766 adults ages 55-95. Researchers followed the subjects for one year and conducted a series of physical, cognitive and neuropsychiatric tests. Of the group, 88.4% had COVID-19 infections and 11.6% were controls. Clinical evaluations found functional memory impairment in two-thirds of the people who had COVID-19 infections. They found that persistent loss of smell was a significant predictor of cognitive impairment, while severity of the initial COVID-19 infection wasn’t.

“The more insight we have into what causes or at least predicts who will experience the significant long-term cognitive impact of COVID-19 infection, the better we can track it and begin to develop methods to prevent it,” Gabriela Gonzalez-Aleman, Ph.D., professor at Pontificia Universidad Catolica Argentina, Buenos Aires said. 

https://www.biospace.com/article/long-covid-new-symptoms-risks-and-experimental-treatments/

AbbVie taps Sosei Heptares GPCR expertise with $1.2bn+ alliance

 Sosei Heptares has signed up a string of big pharma collaborators over the last few years, and one of them – AbbVie – has just expanded its partnership with a new to deal to apply the biotech’s G protein-coupled receptor (GPCR) expertise to the discovery of drugs for neurological diseases.

The collaboration adds to an earlier drug discovery agreement in the area of immunology and inflammation which dates back to June 2020, suggesting AbbVie likes what it has seen in the earlier alliance.

The new deal comes with a signing fee of $40 million, another $40 million in milestones that could accrue in the next few years, and up to $1.2 billion down the line if the partnership progresses as hoped and results in multiple drugs reaching the market.

AbbVie and Sosei Heptares will initially focus on developing up to three GPCR-modulating small-molecule drugs to the point at which they are ready to start clinical trials in humans, whereupon AbbVie has opt-in rights to take them further.

If it does so, it will have responsibility for all clinical, regulatory and commercial development thereafter.

The new agreement follows earlier alliances including one worth up to $2.6 billion with Neurocrine Biosciences in the area of schizophrenia and other neuropsychiatric disorders, a $1.2 billion deal with Takeda for gastrointestinal disease, plus partnerships with Pfizer, AstraZeneca, GSK, Biohaven, Roche/Genentech, Sanofi and others.

GPCRs are a fertile source of drug targets for the pharma industry are the target of around a third of all marketed drugs. However, the functions of many of them are poorly understood, and it is thought these so-called ‘orphan’ GPCRs could provide a rich supply of new medicines.

Matt Barnes

“We have established a highly productive working relationship with our counterparts at AbbVie over the past two years through our initial collaboration and are very pleased with how this is progressing,” said Sosei Heptares’ head of R&D Matt Barnes.

“We believe this strong foundation will enable us to get off to a quick start as we tackle the novel and challenging neurology targets under this new agreement.”

The new AbbVie deal comes shortly after Sosei Heptares signed an agreement with Cancer Research UK to start clinical trials of HTL00397322, a selective EP4 antagonist though to have potential as a treatment for a range of cancers including microsatellite stable colorectal cancer, gastroesophageal and head and neck tumours, and castration-resistant prostate cancer.

EP4 is though to act as an immune checkpoint much like PD-1/PD-L1, which help tumour cells to evade detection and attack by the immune system.

https://pharmaphorum.com/news/abbvie-taps-sosei-heptares-gpcr-expertise-with-1-2bn-alliance/

Positive Phase 3 for Tecentriq with ENHANZE in Lung Cancer

 Halozyme Therapeutics, Inc. (NASDAQ: HALO) ("Halozyme") today announced that Roche's Phase III IMscin001 study evaluating a subcutaneous (SC) formulation of Tecentriq® (atezolizumab) with Halozyme's ENHANZE® technology met its co-primary endpoints.

The study showed non-inferior levels of Tecentriq® in the blood (pharmacokinetics), when injected subcutaneously, compared with intravenous (IV) infusion in cancer immunotherapy-naïve patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) for whom prior platinum therapy has failed. The safety profile of the SC formulation was consistent with IV Tecentriq®.

https://www.biospace.com/article/releases/positive-results-announced-from-phase-iii-imscin001-study-evaluating-subcutaneous-formulation-of-tecentriq-with-enhanze-in-advanced-non-small-cell-lung-cancer/

A2 Milk Jumps Before Halt on FDA Nod News, Denies Report

 Shares of New Zealand's a2 Milk Co Ltd jumped more than 12% before trading in the stock was halted, after local media reported that the dairy company was close to winning an approval to sell baby formula in the United States.

A2 dismissed the report. The company had in May confirmed an application to the U.S. Food and Drug Administration (FDA) seeking permission to supply baby food to the country.

A2 Milk's stock price shot up as much as 12.2% to NZ$5.60 to hit its highest level since April 5. Australia-listed shares of the firm jumped nearly 12% to A$5.08, before eventually being halted.

The media report suggested that FDA approval could be received "as soon as this week."

"While we have been informed by the FDA that our application is under active review, at this stage there is no certainty as to the outcome of the application or the timing of any approval," the company said in a statement.

Dairy companies in Australia and New Zealand have queued up to restock empty shelves in the United States with baby food, after the country recently relaxed its import policy to mitigate one of the biggest infant formula shortages in recent history.

But barring Bubs Australia, which has already shipped baby food to the U.S. in several batches, others such as Fonterra and privately run Bellamy's Organic are yet to provide an update on the status of their respective FDA applications.

French consumer goods company Danone said recently it had shipped more than 750,000 cans of its flagship Aptamil baby formula to the United States.

https://money.usnews.com/investing/news/articles/2022-08-02/a2-milk-jumps-before-halt-on-fda-nod-news-denies-report

New Evidence: Fauci Imposed a Vaccine Delay that Cost Trump the Election

 Think back to July 2020. Trump and Fauci were at war with each other. Key leaders within the Trump administration, including Peter Navarro, wanted to fire Fauci. There were protests and sometimes riots in the streets over the murder of George Floyd. And new evidence shows that behind the scenes, Fauci was working to torpedo Trump’s chances for re-election. 

We already knew that Fauci, the FDA, CDC, and the pharmaceutical industry went to great lengths to block treatments based on repurposed pharmaceuticals, including hydroxychloroquine and ivermectin, while putting all hope and money into Covid-19 vaccines. But a new book reveals that Fauci also forced Moderna to delay their clinical trial by three weeks — which pushed the release of their preliminary results until after the presidential election. 

This key piece of information comes from The Messenger: Moderna, the Vaccine, and the Business Gamble That Changed the World published last week by Harvard Business Review Press. The author, Peter Loftus, is a reporter for the Wall Street Journal and they published his essay about the book in their Review section on Saturday. What’s astonishing is that Loftus does not even realize the enormity of the story he just stumbled upon. I will do it for him. 

Most people already know the broad brush strokes of the Moderna story — they had never successfully brought a product to market before Operation Warp Speed. They took $25 million from the Defense Advanced Research Projects Agency (DARPA) in 2013 to develop mRNA products that never worked and another $125 million from the Biomedical Advanced Research and Development Authority (BARDA) in 2015 for a vaccine for Zika that also failed. But Fauci really liked these grifters and so when the pandemic began in 2020, BARDA directed $483 million to Moderna for Covid-19 vaccine development — and Moderna cut NIH in on the patents. That gave NIH and especially Fauci control over what came next.

The key paragraphs from Loftus’ WSJ essay are here: 

Dr. Zaks [Chief Medical Officer for Moderna] had wanted to use a private contract research organization to run the whole trial, but NIAID officials wanted their clinical-trial network involved. Eventually, Dr. Zaks backed off, and both entities participated. “I realized we were at an impasse, and I was the embodiment of the impasse,” Dr. Zaks said.

Next, when Moderna’s 30,000-person study began enrolling volunteers in July 2020, the subjects weren’t racially diverse enough. Moncef Slaoui, who led Warp Speed’s vaccine efforts, and Dr. Fauci began holding Saturday Zoom calls with Mr. Bancel and other Moderna leaders to “help coax and advise Moderna how to get the percentage of minorities up to a reasonable level,” Dr. Fauci recalled.

Drs. Fauci and Slaoui wanted Moderna to slow down overall enrollment, to give time to find more people of color. Moderna executives resisted at first. “That was very tense,” Dr. Slaoui said. “Voices went up, and emotions were very high.” Moderna ultimately agreed, and the effort worked, but it cost the trial about an extra three weeks. Later, Mr. Bancel called the decision to slow enrollment “one of the hardest decisions I made this year.”

The claim that Fauci cared about racial diversity in the clinical trial is a lie. How do we know this? Later “clinical trials” for Pfizer and Moderna in kids looked at antibodies in the blood, not actual health outcomes, in only about 300 study participants. The number of people of color enrolled in those undersized trials were in the single digits (literally two or three Black participants total) — so those results were not statistically significant. Yet this did not stop authorization. It appears that Fauci’s delay tactics were designed to accomplish a different goal. 

Let’s do the math:

Moderna released their preliminary results — claiming 94.5% effectiveness — on November 16, 2020.

The presidential election was less than two weeks earlier — on November 3, 2020. 

Trump lost by less than 1% of the vote in 4 key swing states. 

Fauci’s demand to slow down enrollment in July 2020 cost Moderna 3 weeks. 

If Moderna had released their results 3 weeks earlier – on October 25, 2020 – Trump might have scored a major win in the final week of the campaign and won the election. 

It does not matter how one feels about Trump or Biden. A massive political win in the week before the election would have convinced enough voters of Trump’s competence and thus pushed Trump’s vote total over the top.

What about Pfizer? They also could have published their preliminary results prior to the election which might have secured Trump’s re-election. According to Loftus, Pfizer “opted out of Operation Warp Speed for fear it would slow the company down.” Pfizer still took $2 billion off of the Trump administration for advance purchase orders. But Scott Gottlieb and Pfizer clearly preferred Biden and so they held their preliminary results until November 9, 2020 — just 6 days after the election. The Biden administration returned the favor by giving Pfizer a blank check and authorizing shots for additional age groups based on the worst “clinical trial” results anyone has ever seen.

The important thing to understand in all of this is that Fauci, the FDA, NIH, and CDC are political functionaries pretending to be scientists. Pandemics, vaccines, and public health are a way for the machine to direct billions of dollars to their base and reward large donors to the party. These companies and their bureaucratic enablers were happy to take money off of Trump. But they knew that they could get an even better deal from Biden. 

As you know, the results of this scheme are grim. The Covid-19 shots authorized right after the 2020 election have made no discernible impact on the course of the pandemic. Far more people have died of Covid-19 since the introduction of the shots under Biden than during the Trump administration when no Covid-19 shots existed. Even quadruple-dosed Biden and quadruple-dosed Fauci have contracted Covid-19, twice.

This essay is adapted from the author’s Substack

Toby Rogers has a Ph.D. in political economy from the University of Sydney in Australia and a Master of Public Policy degree from the University of California, Berkeley. His research focus is on regulatory capture and corruption in the pharmaceutical industry. Dr. Rogers does grassroots political organizing with medical freedom groups across the country working to stop the epidemic of chronic illness in children. He writes about the political economy of public health on Substack.

https://brownstone.org/articles/new-evidence-fauci-imposed-a-vaccine-delay-that-cost-trump-the-election/

Price Controls on Meds Save Money for Feds, Not Necessarily Consumers

 While supporters of the prescription drug pricing proposal that is under consideration may position it as a benefit to consumers, the policy won’t offer meaningful savings for many and can drive up costs for the future. It encourages higher prices for new medicines and can crowd out private negotiation for lower co-pays. Furthermore, it runs counter to other policies intended to encourage investment in drugs that can improve life at a lower cost relative to other types of healthcare. While it won’t necessarily help consumers, this policy will secure savings to the government and a political victory.

First, consider how federal government price “negotiation” compares to current price negotiation between drug companies and insurers offering coverage in Medicare Part D. Drug companies give insurers discounts in formulary contracts for lower co-pays or fewer hurdles such as prior authorization. Under the price controls under consideration, the federal government sets a price according to a formula that grows bigger as the drug gets older, there is no requirement to put the drug on a favorable formulary tier.

So, consider Drug A with a list price of $600 per month and the pharmaceutical company provides a 30 percent rebate, or $180, for the preferred formulary and the consumer pays $42 per month (the average preferred co-pay for PDPs). The drug company offers this discount because more people have affordable access to the drug and sales increase. The health plan uses the rebates strategically, including to lower the co-pay and the premiums to attract more consumers to increase their business.

In the proposed policy, the federal government can set a price for Drug A of $300. If the drug company chooses not to offer the $180 rebate for the much less valuable drug, the insurer facing the loss of that contract would move Drug A to non-preferred formulary where the patient pays 40 percent (the average non preferred coinsurance for PDPs) or $120. Consider the policy also limits price increases. A new drug, drug B, that treats the same condition as A, can launch at $650 and offer a $350 rebate and get the preferred Medicare formulary placement for that big rebate with a co-pay of $42, but for the more expensive drug.

Additionally, the policy skews investment away from drugs that generate the most savings. It puts price controls on the biggest selling drugs in Medicare after nine years on the market for chemical-based pills, and thirteen years for complex biologics, which are often injectable. Because it reduces revenue for small molecule drugs after a shorter time, the policy makes complex medicines a relatively more favorable investment. Small molecule generics, which typically launch around 12 years after the original, are the biggest generator of savings in medicine, other than better health. This is a unique feature to these pills, consider that while in the not-too-distant future there will be multiple generic pills that achieve a 90 percent plus cure for Hepatitis C, there will never be a generic liver transplant.

Not only do small molecule generics create billions in savings for insurers and funders like the federal government, health insurers also often make them available for a few dollars to consumers. But this policy discourages development of small molecules relative to biologics, which have a longer period without price controls, tend to be costlier, and don’t experience the same degree of savings after patent expiration. Furthermore, by pushing the brand price down for the price-controlled drugs, this policy discourages generic entry at the end of patent life as it is difficult to compete with a low-price brand, the differential between the brand and generic price is what creates that incentive for generics to enter the market particularly right after patent expiration when there is a big financial prize for the first entrants.

Next, this policy discourages investment in new indications for existing medicines that are likely to be price controlled. While there are critics of expanding a drug’s use beyond an original intention, particularly when the drug received orphan status, it is much quicker and less expensive to develop an existing drug for a new indication rather than to develop a totally new medicine. But this policy discourages post-market study by reducing profitability near the end of the lifecycle.

Furthermore, the policy removes some small biopharma companies from the price controls, which means they may remain more valuable if they don’t integrate with bigger biopharma. This may increase costs for small companies who would need to develop commercialization infrastructure that typically focuses on research and discovery.

So, if this policy is implemented, consumers may see a significant change in what they spend on medicines today and tomorrow, but not in the direction they expect.

https://www.aei.org/health-care/price-controls-on-medicines-save-money-for-the-federal-government-but-not-necessarily-for-consumers/

USDA proposes new regulations to get rid of salmonella in chicken

 The federal government on Monday announced proposed new regulations that would force food processors to reduce the amount of salmonella bacteria found in some raw chicken products or risk being shut down.

The proposed U.S. Department of Agriculture rules would declare salmonella an adulterant — a contaminant that can cause food-borne illness — in breaded and stuffed raw chicken products. That includes many frozen foods found in grocery stores, including chicken cordon bleu and chicken Kyiv products that appear to be cooked through but are only heat-treated to set the batter or breading.

The agency notified producers of the proposed changes on Friday.

USDA Deputy Under Secretary for Food Safety Sandra Eskin said it marks the beginning of a broader agency effort to curtail illnesses caused by the salmonella bacteria, which sickens 1.3 million Americans each year. It sends more than 26,000 of them to hospitals and causes 420 deaths, according to Centers for Disease Control and Prevention data.

Food is the source for most of those illnesses.

The CDC says approximately one in every 25 packages of chicken sold at grocery stores contains salmonella bacteria.

Since 1998, breaded and stuffed raw chicken products have been associated with 14 salmonella outbreaks and approximately 200 illnesses, the USDA said in a statement. An outbreak last year tied to frozen breaded raw chicken products caused 36 illnesses in 11 states and sent 12 people to hospitals.

The USDA currently has performance standards that poultry processing plants have to meet to reduce contamination, but the agency cannot stop products from being sold. There is also no adequate testing system to determine levels of salmonella in meat, Eskin said.

USDA notified producers of the proposed changes on Friday.

Getty Images/iStockphoto

The proposed new rules require routine testing at chicken processing plants. Products would be considered adulterated when they exceed a very low level of salmonella contamination and would be subject to regulatory action, including shuttering plants that fail to reduce salmonella bacteria levels in their products, Eskin said.

“This action and our overall salmonella initiative underscore our view that our job is to ensure that consumers don’t get sick from meat and poultry products,” she said. “They shouldn’t be sold if they’re contaminated to the degree that people get sick.”

In 1994, the USDA’s Food Safety and Inspection Service took a similar step by declaring some strains of E. coli a contaminant in ground beef and launched a testing program for the pathogen.

Eskin said the agency met with food safety experts and poultry processors for ideas on how to reduce contamination in processing.

The National Chicken Council, the trade association for chicken producers and processors, said it is concerned about the precedent set by the abrupt shift in federal policy.

“It has the potential to shutter processing plants, cost jobs, and take safe food and convenient products off shelves. We’re equally concerned that this announcement was not science-based or data-driven,” said spokeswoman Ashley Peterson.

She said the government already has the regulatory and public health tools to work with the industry to ensure product safety, adding that companies producing chicken meat have invested millions of dollars and have worked for more than a decade to reduce salmonella in raw chicken.

A representative of Tyson Foods said the company would withhold comment until it received details of the new USDA rule.

Diana Souder, a spokeswoman for Maryland-based Perdue Farms, also declined to comment but pointed out that the company belongs to the Coalition for Poultry Safety Reform, a group formed last year to work with USDA and others to reduce foodborne illnesses from salmonella contamination.

The new rules will be published in the Federal Register this fall and the USDA’s Food Safety and Inspection Service will seek public comment before finalizing the rules and setting a date for implementation.

https://nypost.com/2022/08/01/usda-proposes-new-regulations-to-get-rid-of-salmonella-in-chicken/