Rogue antibodies wreak havoc in severe COVID-19 cases

 The development of antibodies to the COVID-19 virus has been the great long-term hope of ending the pandemic. However, immune system turncoats are also major culprits in severe cases of COVID-19, Yale scientists report in the journal Nature.

These autoantibodies target and react with a person's tissues or organs similar to ones that cause autoimmune diseases such as lupus or rheumatoid arthritis. In COVID-19 cases they can attack healthy tissue in brain, blood vessels, platelets, liver, and the gastrointestinal tract, researchers report. The more autoantibodies detected, the greater the disease severity experienced by patients.

And the autoantibodies paradoxically also target and interfere with many immune system proteins that are designed to fend off infections, the study found.

"It's a two-edge sword," said Aaron Ring, assistant professor of immunobiology at Yale and senior author of the paper. "Antibodies are crucial to fend off infection, but some COVID-19 patients also develop antibodies that damage their own cells and tissues."

It is clear that in many cases the presence of coronavirus drove the creation of the damaging autoantibodies, Ring said. But it is also likely that some COVID-19 patients had pre-existing autoantibodies that made them more susceptible to infection, he said. Mice with these same autoantibodies were more susceptible to infection by the COVID-19 virus and more likely to die, the authors report.

The existence of these long-lived rogue autoantibodies could also help explain why some people infected with COVID-19 can later develop lasting medical symptoms, so-called long COVID cases. "This could be the unfortunate legacy of the virus," Ring said.

"Our findings reinforce the importance of getting vaccinated," added co-corresponding author Akiko Iwasaki, the Waldemar Von Zedtwitz Professor of Immunobiology at Yale. "The fact that even mild infections are associated with autoantibody production underscores the potential for long-term health consequences of COVID-19."

For the study, Ring's lab worked with Iwasaki's lab and members of the Yale IMPACT team—a group of scientists, scholars, and physicians developing research and clinical efforts to combat COVID-19—to screen blood samples from 194 patients who had contracted the virus, with varying degrees of severity, for the presence of autoantibodies. Specifically, they used a novel technology developed by Ring's lab called Rapid Extracellular Antigen Profiling (REAP) to identify autoantibody interactions with nearly 3,000 human proteins.

Ring said the findings may lead to strategies to treat or prevent the damaging effects of autoantibodies in COVID-19 patients. In addition, the new REAP technology could be used to pinpoint important antibody responses for many other disease conditions beyond COVID-19. Ring's lab has found a host of novel autoantibodies in patients with autoimmune disease and is now searching for autoantibodies in patients with cancer and neurological illnesses.

More information: Diverse Functional Autoantibodies in Patients with COVID-19, Nature (2021). DOI: 10.1038/s41586-021-03631-y

https://medicalxpress.com/news/2021-05-rogue-antibodies-wreak-havoc-severe.html

Antibody Testing Not Useful to Prove Immunity Among Vaccinated: FDA

 The US Food and Drug Administration (FDA) is against antibody testing for SARS-CoV-2 testing to determine immunity or protection from COVID-19, especially among those who are vaccinated.

More a reminder than a new policy, the FDA advised against using the antibody test results for these indications in a Safety Communication announced today.

"The FDA is reminding the public of the limitations of COVID-19 antibody, or serology, testing and providing additional recommendations about the use of antibody tests in people who received a COVID-19 vaccination," Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA's Center for Devices and Radiological Health, said in a statement.

"Antibody tests can play an important role in identifying individuals who may have been exposed to the SARS-CoV-2 virus and may have developed an adaptive immune response," he added. "However, antibody tests should not be used at this time to determine immunity or protection against COVID-19 at any time, and especially after a person has received a COVID-19 vaccination."

Not all antibodies are created equal. The agency explained that antibodies from prior SARS-CoV-2 infection differ from antibodies induced by the COVID-19 vaccines. Therefore, testing for prior infection antibodies would not identify people with antibody protection from immunization.

SARS-CoV-2 antibody tests should be ordered only by healthcare professionals who are familiar with the use and limitations of the test, the agency notes.

"The FDA will continue to monitor the use of authorized SARS-CoV-2 antibody tests for purposes other than identifying people with an adaptive immune response to SARS-CoV-2 from a recent or prior infection," Stenzel said.

https://www.medscape.com/viewarticle/951488

'Talents' Land U.S. Researcher in Prison

 A rheumatology professor in the U.S. has been sentenced to 37 months in prison and fined nearly $4 million for lying to federal authorities in an immunology research fraud scheme, according to the Department of Justice (DOJ).

Song Guo Zheng, MD, PhD, pleaded guilty in November 2020 after admitting he lied on applications to secure about $4.1 million in NIH grants "to develop China's expertise in the areas of rheumatology and immunology." Federal authorities suspect he planned to share research he then directed with the Chinese government, per its Thousand Talents program that seeks to steal research from other nations via embedding sympathetic allies.

"American research funding is provided by the American taxpayer for the benefit of American society -- not as an illicit gift to the Chinese government," said John C. Demers, assistant attorney general for DOJ's National Security Division.

Zheng, 58, worked as an internal medicine and rheumatology professor when he led a team at Ohio State and Pennsylvania State universities conducting autoimmune research. He was responsible for "materially false and misleading statements" on the applications, the DOJ said, and "seeking to hide his participation in Chinese Talent Plans and his affiliation and collaboration with a Chinese university controlled by the Chinese government."

Zheng was arrested in Alaska in May 2020, while trying to catch a plane to flee to China. He was carrying two laptops, three cell phones, several USB drives, some silver bars, expired Chinese passports for his family, and deeds for property in China, among other items.

Zheng is one of the latest researchers involved in Thousand Talents who have been identified publicly. In April, Yu Zhou, MD, was sentenced to 33 months in prison after pleading guilty to stealing scientific trade secrets regarding exosomes and exosome isolation from Nationwide Children's Hospital Research Institute in Ohio, according to Endpoints News. He attempted to sell that information to China.

Four other researchers resigned from Moffitt Cancer Center in Tampa last year, after hiding hundreds of thousands of dollars in research subsidies and salaries -- despite being required by Moffitt and NIH to disclose these funds because they were tied to a foreign nation (China).

In 2019, MD Anderson Cancer Center removed three scientists and Emory University removed two neuroscientists for neglecting to disclose foreign research ties or undermining the integrity of research funding.

NIH director Francis Collins, MD, had issued a letter in 2018 to more than 10,000 research institutions, asking them to make sure NIH grantees report any links with foreign governments, Endpoints News reported.

"Zheng's sentencing today is a recognition of the constant threat posed by the Chinese government to steal research funded by American taxpayers," Chris Hoffman, an agent with the FBI's Cincinnati office, said in DOJ's press release.

In addition to his prison sentence, Zheng was ordered to pay more than $3.4 million in restitution to NIH and about $413,000 to Ohio State University.

"We hope Zheng's prison sentence deters others from having anything to do with China's so-called '1000 Talents Plan' or any of its variations," said Vipal J. Patel, acting U.S. attorney for the Southern District of Ohio.

https://www.medpagetoday.com/special-reports/exclusives/92673

Peloton Shares Rise On Treadmill Software Safety Fix

 Peloton Interactive Inc 

PTON 1.43% shares traded slightly higher in a down day for the market on Wednesday after the company announced a software update for its recalled treadmills.

What Happened? Peloton has announced it is rolling out a software update for its Tread and Tread+ treadmills just two weeks after the products were recalled due to safety issues that led to dozens of injures and one death of a child. The update includes a new “Treak Lock” feature requiring a four-digit passcode to unlock the device for use and re-locks the machine automatically after 45 seconds of inactivity.

Why It’s Important: On the company’s earnings call on May 6, Peloton said it was in the process of working on both software and hardware fixes to its treadmills. For now, sales and deliveries of Tread and Tread+ machines remain halted.

Peloton also said the company will take a $165 million hit from the recall in its fiscal fourth quarter.

Peloton management also apologized for delaying the recall of its products, even after a U.S. Consumer Product Safety Commission (CPSC) report on April 19 found the products dangerous for pets and small children.

“I want to be clear, Peloton made a mistake in our initial response to the Consumer Product Safety Commission’s request that we recall the Tread+,” CEO John Foley said when the recall was issued on May 5.

Peloton shares held their ground on Monday but are now down 36.9% overall year-to-date in 2021.

Benzinga’s Take: The financial impact of the recalls on Peloton’s numbers appears to be manageable. However, the reputational damage to Peloton’s brand remains to be seen, and the company is facing extremely difficult comps in coming quarters as gyms open back up throughout the country.

https://www.benzinga.com/news/21/05/21200353/peloton-shares-rise-on-treadmill-software-safety-fix

Biopharma R&D 'surged' in 2020, but trial productivity levels mixed: IQVIA

 A major global pandemic was not enough to stop surging rates of biopharma research and development, but trial productivity still remains below the long-term average.

That is according to a new report out by CRO analytics firm IQVIA, which found that funding for early- and late-stage R&D, as well as deals, jumped last year regardless of the pandemic, while aggregate R&D spend for the top 15 companies “reached a record high.”

It also found that, overall, clinical trial activity recovered from midyear 2020 to levels above 2019–even without factoring in COVID-19 trials, which clearly didn’t exist the year before. Total trials reached 4,686, more than 300 extra than 2019 and an 8% rise, with 985 in phase 3, 1,880 in midstage testing and 1,821 in phase 1.

But there is more complexity here: There was an increase in the clinical trial productivity index, i.e., the way IQVIA measures how these trials are doing, but in 2020 it found this was mostly due to an improvement in phase 3 trials, widening the gap with phase 1 trials, “which score significantly lower with this index.”

When it comes to midstage tests, trials “have consistently been above the overall index” as success rates have been trending up and durations have been trending down, “even as complexity has been rising in phase 2 as rising numbers of endpoints and eligibility criteria are attributes of these trials.”

Overall, however, productivity “remains below historic levels,” the report found, as success rates are below the long-term average. This is because the complexity of trials is generally increasing, as are study durations in many diseases, IQVIA’s authors note.

Looking at the pipeline of pharma, IQVIA saw that growth in the late-stage pipeline continued in 2020, bringing total expansion to 43% since 2015, as cancer drugs reached record-high numbers. Growth in the early-stage pipeline, including next-generation biotherapeutics, paused in 2020, however.

The dismal lack of diversity in clinical trials also continued: African Americans or races identified as Black account for 13.4% of the U.S. population, while the clinical trials used to approve new medicines had a median participation of only 3% in the past six years and “were under-representative 79% of the time from 2015 to 2020,” IQVIA said.

Persons of Asian descent are also estimated to comprise 6.5% of the U.S. population, but again, only in 2015 was the median above this threshold, and 52% of trials in the past six years that were used by the FDA to approve medicines had under-representative participation.

“The growth in research and development driven by new oncology drugs, new funding and strategic investments is a testament to the resilience and strength of the innovative, global biopharmaceutical industry,” said Murray Aitken, executive director of the IQVIA Institute for Human Data Science, in an accompanying release.

“Faced with significant disruptions and the need to reprioritize research and development, the global life sciences industry has demonstrated its ability to meet and even exceed expectations for new and better lifesaving therapies and vaccines.”

https://www.fiercebiotech.com/biotech/biopharma-r-d-surged-2020-but-trial-productivity-levels-a-mixed-bag-report

Covid-19 Vaccine Maker Blames Problems on Producing Two Different Shots

 Emergent BioSolutions Inc. has made enough of a key ingredient to yield more than 100 million doses of Johnson & Johnson's Covid-19 vaccine, and federal health regulators are evaluating whether to release the shots, Emergent's chief executive said.

Emergent CEO Robert Kramer apologized during a congressional hearing Wednesday for the problems at the company's Baltimore plant that resulted in the contamination earlier this year of a batch of the vaccine.

Mr. Kramer said the company, which makes vaccines and drugs under contract, has been taking corrective steps to fix the manufacturing problems at the plant.

Emergent has blamed some of the problems on having to produce two Covid-19 vaccines at large scale, which the company said strained the capacity of its equipment. The plant also was making AstraZeneca PLC's Covid-19 vaccine.

Emergent described some of the problems and its plan to fix them in a letter to the U.S. Food and Drug Administration, responding to the agency's finding of various deficiencies during an April inspection.

A subcommittee of the U.S. House Committee on Oversight and Reform released the April 30 letter ahead of its hearing about Emergent.

Emergent was producing a bulk key vaccine ingredient for Johnson & Johnson's Covid-19 vaccine, but a mishap led to the contamination of material that could have yielded up to 15 million doses during January and February.

The contamination came from viral material similar to what was used in the production of the AstraZeneca vaccine at the same plant, according to a memo from the Democratic staff of the House committee to members.

The incident ruined the batch of J&J's vaccine ingredient and led to a halt in production of the J&J vaccine, as well as a decision to relocate production of AstraZeneca's vaccine elsewhere. In addition, J&J took over manufacturing at the Emergent plant.

At the hearing, Mr. Kramer said the company agreed last year with the federal government to manufacture both J&J's and AstraZeneca's vaccines, though the plant hadn't previously produced vaccines at full capacity.

"Ramping up production of two novel vaccines on a very large scale in the same facility is unprecedented," he said in remote online testimony.

The FDA's inspection of the Emergent plant found it didn't maintain clean, sanitary conditions and didn't take proper steps to prevent contamination. The inspection found the building and equipment, including refrigerators, weren't big enough to support large-scale manufacturing in a way that would ensure clean conditions.

Emergent, in its April 30 response, said: "The sudden scale-up to full-scale manufacturing activities for two different Covid-19 vaccine drug substances strained the capacity of Emergent's" refrigerators.

The company said it has cleaned and organized them and will purchase additional refrigerators.

The company also said its plant "experienced a dramatic increase in storage and staging demands as the facility operated at full capacity for the first time." The company said it has changed procedures to mitigate the risk of contamination.

At the hearing, Democratic members of the committee generally criticized Emergent for the contamination problem. Rep. James Clyburn (D., S.C.), who is chair of the House Select Committee on the Coronavirus Crisis, said the destruction of millions of J&J vaccine doses was "due to Emergent's failure to properly maintain its facilities, adequately train its staff and ensure that proper protocols were followed."

Several Republican members of the committee, however, defended Emergent. Rep. Mark Green (R., Tenn.) said Emergent had successfully delivered drugs and vaccines for other diseases including an overdose treatment. Addressing Mr. Kramer, he said "you are a reputable company that has done yeoman's work to protect this nation in biodefense."

Emergent, based in Gaithersburg, Md., said in a statement Wednesday that its role in responding to the Covid-19 pandemic is "unlike any we have confronted before." The company said it is focused on releasing a vaccine ingredient that is currently under evaluation and on resuming vaccine production.

The House committee also released documents showing that Emergent has charged the federal government $27 million a month in reservation fees to be ready to manufacture vaccines.

The government has paid Emergent $271 million of these fees to date, but has partially stopped payment since learning of the contamination, the committee's Democratic staff said in the memo to members.

https://www.marketscreener.com/quote/stock/EMERGENT-BIOSOLUTIONS-INC-36547/news/Covid-19-Vaccine-Maker-Blames-Problems-on-Producing-Two-Different-Shots-2nd-Update-33303867/

Experts Still Unclear on the Timing of Potential COVID-19 Vaccine Boosters

 An open question is whether booster shots against COVID-19 will be necessary. The predominant vaccines in the Western world are Moderna, Pfizer-BioNTech, AstraZeneca-Oxford, and Johnson & Johnson. All but the J&J vaccines require two shots, 21 to 28 days apart. The J&J vaccine requires only a single dose. 

The director of the U.S. Food and Drug Administration (FDA)’s Center for Biologics Evaluation and Research, Peter Marks, noted that it is possible booster shots would be necessary for fully vaccinated individuals within a year even though the Pfizer-BioNTech and Moderna vaccines are highly effective at COVID-19 prevention. Also, they seem to protect against the variants identified so far in the U.S.

“So, hopefully, you know, it would be nice if it’ll turn out that it’ll be a year before anyone might need a booster,” Marks said. “But we still don’t know. It could be more, it could be a little less but … this is just something we’re going to have to figure out as we go.”

The Moderna and Pfizer-BioNTech vaccines have very high efficacy in clinical trials, around 95%. That is not true of all vaccines in use around the world. For example, China’s Sinovac Biotech reported efficacy in a late-stage trial in Brazil of only 50.38%. 

However, it’s important to note that the FDA initially set the bar for vaccine authorization at 50%. The extremely high efficacy of the Pfizer and Pfizer-BioNTech mRNA vaccines has been an unexpected benefit.

The United Arab Emirates reported yesterday that it is offering a third booster shot for people who received the Chinese-developed Sinopharma COVID-19 vaccine. Expressly, the country indicated that the vaccine did not create enough antibodies in some people. But in March, a researcher at G42, an Abu Dhabi-based company that conducted late-stage trials of the Sinopharm vaccine, indicated few people would likely need the booster.

The UAE Emergency Crisis and Disaster Management Authority said the booster shots were part of the UAE’s “proactive strategy to provide maximum protection for society.” The booster will be offered to seniors and people with chronic illness. 

The country has been very effective in getting its citizens vaccinated, with more than 73% of adults in the country having been vaccinated. 

The Sinopharm vaccine in clinical trials has demonstrated an efficacy level of 79% against symptomatic infection. However, there has been mixed data on the vaccine, particularly about much lower rates under real-world conditions.

For example, Seychelles, the most vaccinated country globally, has recently seen a surge of new COVID-19 cases in people who are vaccinated. And about 60% of those vaccinated received the Sinopharm vaccine.

Bahrain has also begun offering third booster shots of the Sinopharm vaccine. The country’s National Medical Taskforce for Combatting the Coronavirus announced “the opening of registration for a booster COVID-19 vaccine dose for the most vulnerable groups in Bahrain, at least six months after taking the second dose of the Sinopharm vaccine, for first responders, as well as citizens and residents above the age of 50, as well as those suffering from obesity, low immunity, or other underlying health conditions.”

In related news, there have been reports that the AstraZeneca-Oxford vaccine is effective as a third booster, regardless of the original vaccines. There are also suggestions that the Sanofi and GSK vaccine, which is still in mid and late-stage trials, might have “strong potential for development as a booster vaccine.”

Broadly, however, it’s not yet known whether a third booster shot will be necessary. Janet Woodcock, acting FDA Commissioner, recently said that U.S. regulators and researchers don’t know how long immunity lasts or how far it should drop in vaccinated people to make them vulnerable to re-infection.

“As far as variants go,” she said, “we’re just going to have to determine that currently the immune response to these vaccines is being tested against all the variants to see how strong it is against each of the variants. And we just hope a variant doesn’t arise that can elude our vaccines.”

Ugur Sahin, chief executive officer of BioNTech, recently told CNBC that scientists are observing a drop in antibody responses against the virus after eight months.

“If we provide a boost we could really amplify the antibody response even above the levels that we had at the beginning and that could give us real comfort for protection for at least 12 months, maybe 18 months,” Sahin said. “And this is really important in a time where all the variants are coming in.”

The CDC recently indicated that it is preparing for the possible use of booster shots “just in case.”

That said, investigators at the World Health Organization (WHO) and Tom Frieden, former director of the U.S. Centers for Disease Control and Prevention (CDC), are more skeptical about the demand for booster shots, with some concern that the pharmaceutical companies’ emphasis on their need might be a bit biased in their own self-interest.

“It’s not going to be a decision that’s going to be made by a pharmaceutical company,” said Anthony Fauci at NBC’s “Meet the Press” in April. Fauci is the director of the U.S. National Institute of Allergy and Infectious Disease (NIAID) and chief medical advisor to President Biden. He also pointed out that it wouldn’t be clear if booster shots would be needed until at least late summer.

https://www.biospace.com/article/covid-19-vaccine-boosters-an-update/