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Sunday, October 31, 2021

Cognitive deficits in people who have recovered from COVID-19

 AdamHampshireaWilliamTrenderaSamuel RChamberlainbcAmy E.JollyaJon E.GrantdFionaPatrickeNdabaMazibukoeSteve CRWilliamseJoseph MBarnbyePeterHellyeraeMitul AMehtae





There is growing concern about possible cognitive consequences of COVID-19, with reports of ‘Long COVID’ symptoms persisting into the chronic phase and case studies revealing neurological problems in severely affected patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of disease severity.


We sought to confirm whether there was an association between cross-sectional cognitive performance data from 81,337 participants who between January and December 2020 undertook a clinically validated web-optimized assessment as part of the Great British Intelligence Test, and questionnaire items capturing self-report of suspected and confirmed COVID-19 infection and respiratory symptoms.


People who had recovered from COVID-19, including those no longer reporting symptoms, exhibited significant cognitive deficits versus controls when controlling for age, gender, education level, income, racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of substantial effect size for people who had been hospitalised (N = 192), but also for non-hospitalised cases who had biological confirmation of COVID-19 infection (N = 326). Analysing markers of premorbid intelligence did not support these differences being present prior to infection. Finer grained analysis of performance across sub-tests supported the hypothesis that COVID-19 has a multi-domain impact on human cognition.


Interpretation. These results accord with reports of ‘Long Covid’ cognitive symptoms that persist into the early-chronic phase. They should act as a clarion call for further research with longitudinal and neuroimaging cohorts to plot recovery trajectories and identify the biological basis of cognitive deficits in SARS-COV-2 survivors.


Funding. AH is supported by the UK Dementia Research Institute Care Research and Technology Centre and Biomedical Research Centre at Imperial College London. WT is supported by the EPSRC Centre for Doctoral Training in Neurotechnology. SRC is funded by a Wellcome Trust Clinical Fellowship 110,049/Z/15/Z. JMB is supported by Medical Research Council (MR/N013700/1). MAM, SCRW and PJH are, in part, supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London

Ochsner Health temporarily stopped from firing employees over COVID vax status

 A panel of three judges in Shreveport has issued a temporary restraining order preventing Ochsner Health from firing employees in north Louisiana who have not complied with a COVID-19 vaccination requirement.  

The employees, 39 of which filed a lawsuit in the 2nd Circuit Court of Appeals, would have been dismissed Friday under a policy Ochsner enacted for all 32,000 employees in August: get vaccinated or an exemption by Oct. 29 or lose your job. The ruling from the state court of appeals came Thursday, one day before the deadline.

Small groups of Ochsner employees — 39 in Shreveport, 9 in Monroe and 48 in Lafayette — have taken the matter to separate courts, where they've argued that the mandate violates employees’ reasonable right to privacy to reject medical treatments.

A lower-court judge had previously dismissed the lawsuit from the Shreveport group. But in its ruling Thursday, the appeals court said the plaintiffs should be allowed a hearing and Ochsner may not fire or discipline employees over failing to comply with vaccine requirements in the meantime.

The ruling applies to employees at hospitals listed on the lawsuit, including Ochsner LSU Health Shreveport and Ochsner LSU Health Shreveport St. Mary. The plaintiffs are 20 registered nurses, four surgical technicians, a physician, a nurse practitioner, a respiratory therapist, a licensed practical nurse, a child life specialist and several others without listed medical credentials.

Attorney Jimmy Faircloth, who was previously executive counsel to former Gov. Bobby Jindal, has filed several lawsuits on behalf of employees in Louisiana arguing that Louisiana law protects an individual’s right to choose their health care. 

Faircloth said the restraining order requiring Ochsner to halt firing unvaccinated employees in north Louisiana is encouraging because it suggests the judges think the case has merit.

“To get a temporary restraining order, you must convince the court when you file something that you have a substantial likelihood of success,” said Faircloth. “This very important issue is a resounding wake-up call to all the employers in the state that have been hoodwinked into believing that you can do this.”

But across the country and in the state, hundreds of hospital systems have enacted COVID-19 vaccine requirements, similar to requirements for the flu and hepatitis B vaccine. In September, the federal Centers for Medicare and Medicaid Services, the single largest payer of health care in the United States, said it would require the vaccine for all employees of hospitals that accept payments from the program. That would include Ochsner and all other large hospitals operating in the state.

The ruling for a hearing "just postpones the inevitable," said attorney Joel Friedman, a Tulane Law School professor who specializes in labor law. 

According to Friedman and judges who have dismissed similar complaints, the government’s interest in public health outweighs an individual’s right to privacy, which guards against unreasonable government intrusion.

“There's no violation of any right to privacy here because the government has a compelling interest to require vaccinations under the circumstances to promote public health,” said Friedman.

Ochsner Health did not comment on the lawsuit or provide an update on how many employees were vaccinated on the day of the deadline. As of a month ago, 86% of employees had received at least one shot, according to CEO Warner Thomas. Among physicians and hospital leaders, the rate was 98%.

The new ruling is not an indication that the employees’ claim that the hospital is violating their rights has merit, nor does it have legal implications for lawsuits filed outside of the 2nd circuit, said Friedman. It means that the panel agreed that there should be a hearing to decide whether a hospital’s vaccine mandate is unconstitutional.

“They want the judge to actually rule on the merits and give these people at least the hearings,” said Friedman.

The 3rd Circuit Court of Appeal rejected a request for a similar order against Ochsner Lafayette General Health, though Faircloth said it is still moving forward with an appeal.

A lawsuit against Ochsner LSU Monroe was found to have no legal basis, according to ruling Oct. 27 by the Fourth Judicial District Court.

Anti-spike antibody response to natural SARS-CoV-2 infection in general population





Understanding the trajectory, duration, and determinants of antibody responses after SARS-CoV-2 infection can inform subsequent protection and risk of reinfection, however large-scale representative studies are limited. Here we estimated antibody response after SARS-CoV-2 infection in the general population using representative data from 7,256 United Kingdom COVID-19 infection survey participants who had positive swab SARS-CoV-2 PCR tests from 26-April-2020 to 14-June-2021. A latent class model classified 24% of participants as ‘non-responders’ not developing anti-spike antibodies, who were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms. Among those who seroconverted, using Bayesian linear mixed models, the estimated anti-spike IgG peak level was 7.3-fold higher than the level previously associated with 50% protection against reinfection, with higher peak levels in older participants and those of non-white ethnicity. The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. We estimated antibody levels associated with protection against reinfection likely last 1.5-2 years on average, with levels associated with protection from severe infection present for several years. These estimates could inform planning for vaccination booster strategies.

BioNTech founders: COVID is going to become more manageable

 Özlem Türeci and Ugur Sahin, founders of German company BioNTech, have been honored several times for developing the first COVID-19 vaccine. They spoke with DW about the future of the virus and vaccines.

DW: What's going to happen with COVID-19, and when will the pandemic be over?

Özlem Türeci: That is a difficult question, because we learn something new about the virus every day, about how it reacts to the vaccine. We need this knowledge in order to judge when the pandemic will be over. But what we can already say for sure is that gradually a new normalcy is settling in. We can already feel that. We are learning how to deal with the virus. Many of us are already vaccinated, and new degrees of freedom are being gained. There is going to be a normalcy where we can act more freely because large parts of the population are immune.

We're going to be dealing with virus for a few more years, for sure. There will also be answers to questions that are currently not clarified. The future will show whether other variants appear that are immune to the current vaccines, and whether these have to be tweaked accordingly. Over the years, the virus will acquire the status of the flu virus, for which some groups of the population are vaccinated every year or every two years. The coronavirus is going to become a more manageable virus.

Are you working on a new generation of your vaccine against other virus mutations?

Ugur Sahin: Yes, we're currently testing variant vaccines in a relatively small group of volunteers. A study on the South African beta variant is almost complete and there is an ongoing one on the delta variant, mainly to collect data. At the moment, there is no need to alter the vaccine. But we want to show that we can produce new variant vaccines and test them clinically to show they are as safe as the one that we are already using.

If a variant turns up in the next few years and the vaccine has to be adapted, we will be able to do this very quickly because we will already have set up the necessary procedure. We will, very calmly, be able to prepare for the fact that the vaccine might have to be adapted to new virus mutations every two years.

Is it necessary to vaccinate children, too?

Sahin: We cannot say whether this is necessary. We generate data and provide this to the authorities in charge. They have already approved vaccinations for children aged 12 to 15(in Germany -- Editor's note).

Türeci: We submitted data for 5- to 11-year-olds three weeks ago and the authorities now have to judge it within the whole context of the population's health.

Sahin: It's very important to us that there be availability. Once vaccines are approved, it is then up to individuals to decide whether they want it or not.

Are you disappointed that after so much research there are still people who refuse to get vaccinated?

Sahin: We're not disappointed at all. What we are doing is providing information in a transparent way. I think it's good that experts are expressing themselves in the media. This way, every person has the chance to understand the situation. The only thing I would recommend to everyone would be not only to look at one-sided information but to inform themselves as broadly as possible, in order to come to a good decision.

Do you understand when people say this is a new technology, and that we don't know the potential future consequences?

Sahin: We understand this, but on the other hand people generally tolerate vaccines very, very well and they are one of humanity's most important achievements. Without vaccines, our society would not have been able to develop to the extent that it has today. And our vaccine might be based on a new technology, but we understand it well because it has already been around for 30 years.

Our vaccine did not just simply appear. It is based on a biomolecule that we have in our body, in every cell. We are not introducing anything alien. We have a very good scientific basis for it because the necessary research has been conducted for over 30 years. That's why it was possible to develop our vaccine so quickly.

All over the world, governments are trying to persuade more people to get vaccinated. Could they do more?

Türeci: Every government is trying, and they have developed smart and interesting means of promoting the willingness of people to get the vaccine. All governments should be looking at others, in other regions of the world. The Cologne mayor told us that she goes out to certain districts herself when there is a vaccine rollout. That is something other decision-makers could learn from.

Dr. Özlem Türeci and Dr. Ugur Sahin are the founders of the Mainz-based company BioNTech. On October 13, 2021, they were awarded this year's Empress Theophano Prize by Greek President Katerina Sakellaropoulou in Thessaloniki, for their work developing the first COVID-19 vaccine.

The interview was conducted by Irene Anastassopoulou, and has been translated from German.

Biotech week ahead, Nov. 1

 Biotech stocks rose a third week running in the week ending Oct. 29 amid positive reaction to earnings. Big pharma earnings were mostly better than expected.

Merck & Co, Inc. 

 (Get Free Alerts for MRK) led the gains among large-cap pharma companies, with a weekly gain of over 8%, thanks to its third-quarter results that were notably above expectations. Investor optimism can also be attributed to expectations concerning its COVID-19 antiviral treatment being developed with Ridgeback.

Meanwhile, Gilead Sciences, Inc. 

 (Get Free Alerts for GILD) shares came under pressure after the biopharma tempered its forecasts for non-COVID-19 sales.

Regulatory decisions for the week were mixed. 

Eyenovia, Inc. 
's MydCombi new drug application was shot down with a complete response letter, while Clearside Biomedical, Inc. NASDAQLSD & Bausch Health Companies Inc.  received a regulatory nod for their Xipere for suprachoroidal use for the treatment of macular edema associated with uveitis, a form of eye inflammation.

On a positive vaccine-related news flow Pfizer, Inc. 

-BioNTech SE  received Food and Drug Administration authorization for their COVID-19 vaccine for use in the pediatric population.

HCW Biologics Inc. 

 was among the biggest advancers of the week after it was given the nod for proceeding with the Phase 1b trial of its pancreatic cancer treatment candidate. On the other hand, Cortexyme, Inc.  fell about 80% for the week following a failed Alzheimer's trial.

News on initial public offerings exelarated, with three biotechs pricing their offerings and listing on Wall Street.

Here are the key catalysts that are scheduled for the unfolding week:

Healthcare Conferences:

Psych Congress: Oct. 29-Nov. 1, in San Antonio (hybrid)
North American Cystic Fibrosis Conference, or NACFC: Nov. 2-5 (virtual)
International Society for Affective Disorders, or ISAD, Conference: Nov. 3-4 (virtual)
4th Inflammatory Skin Disease Summit: Nov. 3-6, in New York
American College of Rheumatology, or ACR, Convergence 2021: Nov. 3-9 (virtual)
Neuroscience Education Institute, or NEI, Congress: Nov. 4-7, in Colorado Springs, Colorado (hybrid)
The American Society of Nephrology, or ANS, Kidney Week 2021: Nov. 4-7 (virtual)


The FDA is scheduled to rule on Eton Pharmaceuticals, Inc. 

's NDA for topiramate oral solution as a treatment option for three indications – as a monotherapy for partial-onset or primary general tonic-clonic seizures in patients two years of age and older, an adjunctive treatment of partial-onset seizures, including seizures associated with Lennox-Gastaut syndrome in patients two years of age and older, and as preventative treatment of migraine in patients 12 years of age and older.

The original PDUFA date of Aug. 6 was extended by three months to provide the regulator time to review a recent amendment to the application by Azurity Pharma. Azurity had purchased topiramate, along with two other neurology candidates from Eton. Eton is eligible to receive a $5 million milestone payment, contingent on regulatory approval, and royalties on sales. The new PDUFA date is Nov. 6.

Clinical Readouts/Presentations

Inflammatory Skin Disease Summit Presentations

RAPT Therapeutics, Inc. 

: additional efficacy results from a Phase 1b monotherapy trial of RPT193 in patients with moderate-to-severe atopic dermatitis (Wednesday, at 5 pm – 5:30 pm)

NACFC Presentations

Calithera Biosciences, Inc. 

: data from the Phase 1b trial of CB-280, Calithera's investigational arginase inhibitor for the treatment of cystic fibrosis (poster presentation available on Monday, and poster session with presenting authors available via live video chats on Wednesday, at 1:10 pm-1:50 pm)

ANS Meeting Presentations

Talaris Therapeutics, Inc. 

: data from continued long-term follow-up of patients treated in the Phase 2 study of FCR001, as well as findings from urinary cell mRNA profiling of a subgroup of those Phase 2 patients (Thursday, at 1 pm to 3 pm)

GlaxoSmithKline plc 

: late-breaking Phase 3 data for daprodustat as a potential treatment for patients with anemia due to chronic kidney disease in both dialysis and non-dialysis populations (Friday, 1:30 pm)

Alnylam Pharmaceuticals, Inc. 

: full results from the ILLUMINATE-C Phase 3 study of lumasiran in Primary hyperoxaluria type 1

Equillium, Inc. 

: an Interim subgroup analysis from a Phase 1b study of itolizumab in systemic lupus patients with proteinuria

Chinook Therapeutics, Inc. 

: initial results of a Phase 1/2 study of BION-1301 in patients with IgA nephropathy

Vera Therapeutics, Inc. 

: data for the company's lead product candidate, atacicept, from the Phase 2a JANUS clinical trial in patients with IgA nephropathy

DiaMedica Therapeutics Inc. 

: late-breaking data from the Phase 2 REDUX trial of DM199 in chronic kidney disease (Thursday, 1 pm)

Dicerna Pharmaceuticals, Inc. 

: data from the PHYOX2 trial of nedosiran, an investigational RNAi candidate for the treatment of primary hyperoxaluria

ACR Convergence Presentations

Tonix Pharmaceuticals Holding Corp. 

: Positive results of a Phase 3 efficacy and safety trial of TNX-102 SL for the treatment of fibromyalgia (Saturday, at 11:45 am-12 pm)



Hologic, Inc. 

 (after the close)
Neurocrine Biosciences, Inc.  (after the close)


Sage Therapeutics, Inc. 

 (before the market open)
Pfizer Inc.  (before the market open)
Myriad Genetics, Inc.  (before the market open)
Incyte Corporation  (before the market open)
Integra LifeSciences Holdings Corporation  (before the market open)
Esperion Therapeutics, Inc.  (before the market open)
Catalent, Inc.  (before the market open)
Bio-Techne Corporation  (before the market open)
Avanos Medical, Inc.  (before the market open)
Pulmonx Corporation  (after the close)
Amgen Inc.  (after the close)
Deciphera Pharmaceuticals, Inc.  (after the close)
Exelixis, Inc.  (after the close)
Exact Sciences Corporation  (after the close)
Halozyme Therapeutics, Inc.  (after the close)
Inspire Medical Systems, Inc.  (after the close)
Pacific Biosciences of California, Inc.  (after the close)
MacroGenics, Inc.  (after the close)
REGENXBIO Inc.  (after the close)
Ultragenyx Pharmaceutical Inc.  (after the close)
Vertex Pharmaceuticals Incorporated  (after the close)
Related Link: Novavax Rips Higher After Completing Regulatory Filing For Authorization Of COVID-19 Vaccine In UK


Agios Pharmaceuticals, Inc. 

 (before the market open)
Amneal Pharmaceuticals, Inc.  (before the market open)
Horizon Therapeutics Public Limited Company  (before the market open)
Amarin Corporation plc  (before the market open)
Intercept Pharmaceuticals, Inc.  (before the market open)
Ionis Pharmaceuticals, Inc.  (before the market open)
Pacira BioSciences, Inc.  (before the market open)
Syneos Health, Inc.  (before the market open)
United Therapeutics Corporation  (before the market open)
Praxis Precision Medicines, Inc.  (before the market open)
Viking Therapeutics, Inc.  (after the close)
Outset Medical, Inc.  (after the close)
Zymergen Inc.  (after the close)
Heron Therapeutics, Inc.  (after the close)
Ortho Clinical Diagnostics Holdings plc  (after the close)
Supernus Pharmaceuticals, Inc.  (after the close)
Sarepta Therapeutics, Inc.  (after the close)
QIAGEN N.V.  (after the close)
Penumbra, Inc.  (after the close)
ICU Medical, Inc.  (after the close)
Corcept Therapeutics Incorporated  (after the close)
AtriCure, Inc.  (after the close)
Adaptive Biotechnologies Corporation  (after the close)
10x Genomics, Inc.  (after the close)


Zimmer Biomet Holdings, Inc. 

 (before the market open)
Regeneron Pharmaceuticals, Inc.  (before the market open)
NeoGenomics, Inc.  (before the market open)
Moderna, Inc.  (before the market open)
Lantheus Holdings, Inc.  (before the market open)
Ironwood Pharmaceuticals, Inc.  (before the market open)
Intellia Therapeutics, Inc.  (before the market open)
Sangamo Therapeutics, Inc.  (before the market open)
Jounce Therapeutics, Inc.  (before the market open)
Fulcrum Therapeutics, Inc.  (before the market open)
Chimerix, Inc.  (before the market open)
Provention Bio, Inc.  (before the market open)
Aerie Pharmaceuticals, Inc.  (after the close)
Aligos Therapeutics, Inc.  (after the close)
Allogene Therapeutics, Inc.  (after the close)
Global Blood Therapeutics, Inc.  (after the close)
Caladrius Biosciences, Inc.  (after the close)
Bionano Genomics, Inc.  (after the close)
Kura Oncology, Inc.  (after the close)
Y-mAbs Therapeutics, Inc.  (after the close)
Zogenix, Inc.  (after the close)
Vir Biotechnology, Inc.  (after the close)
Quidel Corporation  (after the close)
Puma Biotechnology, Inc.  (after the close)
Novavax, Inc.  (after the close)
Nektar Therapeutics  (after the close)
Natera, Inc.  (after the close)
Insulet Corporation  (after the close)
Illumina, Inc.  (after the close)
Guardant Health, Inc.  (after the close)
Iovance Biotherapeutics, Inc.  (after the close)
Collegium Pharmaceutical, Inc.  (after the close)
Globus Medical, Inc.  (after the close)
Glaukos Corporation  (after the close)
Fate Therapeutics, Inc.  (after the close)
Endo International plc  (after the close)
Emergent BioSolutions Inc.  (after the close)
Axonics, Inc.  (after the close)
Arena Pharmaceuticals, Inc.  (after the close)


Elanco Animal Health Incorporated 

 (before the market open)

IPO Calendar

IPO Pricing

Hamburg, Germany-based Evotec SE NASDAQEVO has filed a preliminary prospectus with the SEC for a 22-million ADS initial public offering at a price of $26.16 per ADS. Each ADS represents one-half of one ordinary share. The per-ADS pricing is based on the closing price of the company's ordinary shares on the Frankfurt Stock Exchange Friday and assuming an exchange rate of $1.163 per euro. The company is a drug discovery and development partner for the pharmaceutical and biotechnology industry. The shares are expected to be listed on the Nasdaq under the ticker symbol "EVO."

Mainz Biomed B.V. NASDAQMYNZ is planning to offer 2 million ordinary shares in an IPO, with the offering expected to be priced between $4 and $6. The molecular genetics cancer diagnostic company has applied for listing its shares on the Nasdaq under the ticker symbol "MYNZ."

Belgium-based MDxHealth SA NASDAQMDXH is offering 3.75 million ADSs in an IPO, assuming an offer price of $13.46 per ADS. Each ADS represents ten ordinary shares. The commercial-stage precision diagnostics company has applied to list the ADSs on the Nasdaq under the ticker symbol "MDXH."

Nuvectis Pharma, Inc. NASDAQNVCT, a New Jersey-based biopharma focused on the development of precision medicines for the treatment of serious unmet medical needs in oncology, is planning a 2.3-million share IPO. The company expects the offering to be priced between $12 and $14 and has applied for listing its shares on the Nasdaq under the ticker symbol "NVCT."

IPO Quiet Period Expiry

Theseus Pharmaceuticals, Inc. 

Cognition Therapeutics, Inc. 
IsoPlexis Corporation 
Pyxis Oncology, Inc.