OpEd: 'Herd immunity will be here by April'

 COVID cases have officially fallen 77% over the last six weeks, and Johns Hopkins School of Medicine & Bloomberg School of Public Health professor Doctor Marty Makary argues in a Wall Street Journal op-ed that herd immunity is responsible for the drastic drop.

“[N]atural immunity from prior infection is far more common than can be measured by testing,” Dr. Makary writes in the Journal. “Testing has been capturing only from 10% to 25% of infections, depending on when during the pandemic someone got the virus. Applying a time-weighted case capture average of 1 in 6.5 to the cumulative 28 million confirmed cases would mean about 55% of Americans have natural immunity.”

The doomsayers are currently focused on variants, more variants and the most lethal variants known to man — Dr. Michael Osterholm from the Center for Infectious Disease Research and Policy at the University of Minnesota is calling the variants a “Cat 5 hurricane that is coming” and paints a dark picture, thanks to the B117 variant, in his latest podcast — but Makary argues the light at the end of the tunnel isn’t as far away as doomsayers believe.

“At the current trajectory, I expect Covid will be mostly gone by April, allowing Americans to resume normal life,” Makary writes.

“The consistent and rapid decline in daily cases since Jan. 8 can be explained only by natural immunity. Behavior didn’t suddenly improve over the holidays; Americans traveled more over Christmas than they had since March. Vaccines also don’t explain the steep decline in January. Vaccination rates were low and they take weeks to kick in.”

What does Dr. Makary’s COVID herd immunity stance mean for the sports world? Could we really see full stadiums — like what we saw out of Australia in November — by April? We know that fans will be allowed back to ballparks in some cities. We know the Marlins will allow 20% capacity for a ballpark that averaged just over 10,000 fans in 2019. And Spring Training cities will be allowing fans in the stands.

While the Masters will still have a limited capacity for its April 5-11 tournament since arrangements had to be made months in advance to make the event run smoothly, an event like the Pro Football Hall of Fame Game between the Steelers and Cowboys on August 5 could see full attendance.

Unless Major League Baseball beats them to the punch — which isn’t likely because it’s Major League Baseball — the Pro Football Hall of Fame in August could be your first look at life post-pandemic.

“I think there’s a very good shot that we’ll be the first full stadium for football in the United States in nearly two years,” Hall of Fame president David Baker told SiriusXM NFL Radio. “And, to me, that’s going to be good for the rest of the country and for the football season ahead. It shows that we can get our economy going and our kids educated and make even more advances on health care. But we’re going to be ready.”

“I think by the time we get to August, we’re gonna be ready to go,” Baker said. “The vaccine is picking up, obviously the trend line is in the right direction right now. I think the NFL has a wonderful study that they did with the CDC that basically said that there wasn’t one infection that could be traced to the 1.2 million people that went to a game.

“At the Pro Football Hall of Fame, we’ve got new technology that takes the temperature of as many as 70 people at a time as they go through the Hall. So there’s a lot of things we can do. We got a great operational team. We’re going to rely very heavily on the experts at the NFL.”

What’s very clear here is that a period of huge change is five miles ahead of us on the COVID highway. Either Osterholm is right and there’s yet another surge of variants coming, or Makary is right and life in the U.S. will soon get back to normal.

Stay tuned.

https://www.outkick.com/johns-hopkins-medical-professional-well-have-herd-immunity-by-april/

Deutsche Bank Downgrades EHealth to Hold From Buy

 Price Target is $63

https://www.marketscreener.com/quote/stock/EHEALTH-INC-34599/news/eHealth-Deutsche-Bank-Downgrades-EHealth-to-Hold-From-Buy-Price-Target-is-63-32480927/

Legend Biotech Announces Preliminary 2020 Results

 For the year ended December 31, 2020, Legend Biotech expects to record a loss for the year of approximately US$292.2 million to US$324.9 million and an adjusted loss for the year of approximately US$202.4 million to US$234.4 million, in each case, including research and development expenses of approximately US$220.7 million to US$255.6 million, which was mainly caused by the continuous investment into its lead product candidate, ciltacabtagene autoleucel, and other product candidates in Legend Biotech’s pipeline. See “Use of Non-IFRS Financial Measures” for a reconciliation of Loss for the year to Adjusted loss for the year.

In addition, Legend Biotech expects to report a one-time non-cash fair value loss of approximately US$80.0 million caused by the changes of fair value of Legend Biotech’s Series A convertible redeemable preferred shares (“Series A Preferred Shares”), which was derived from the automatic conversion of all outstanding Series A Preferred Shares (plus dividends accrued but unpaid on the Series A Preferred Shares) into ordinary shares, par value $0.0001 per share, of Legend Biotech (“Ordinary Shares”) upon Legend Biotech’s listing on the Nasdaq Global Select Market. The details of the automatic conversion of the Series A Preferred Shares into Ordinary Shares are described in Legend Biotech’s prospectus filed with the Securities and Exchange Commission on June 8, 2020. The changes in fair value led to an increase of share premium, which had no material impact on the net assets of Legend Biotech and its subsidiaries.

As of December 31, 2020, Legend Biotech had approximately US$455.7 million of cash and cash equivalents and approximately US$50.0 million in time deposits.

https://www.businesswire.com/news/home/20210219005038/en/Legend-Biotech-Announces-Preliminary-Results-for-the-Year-Ended-December-31-2020

Half of dialysis units across Texas still suffering winter storm havoc

 Widespread power outages and water supply issues have created a dialysis crisis in Texas, following an onslaught of snow, ice, and sub-freezing temperatures.

"To say we're stressed is an understatement. Almost all outpatient dialysis units closed due to power outages. Trying desperately to do as many as we can inpatient. To make matters worse some of our hospitals lost water today (so no HD [hemodialysis]). Truly a nightmare," Tessa Novick, MD, a nephrologist at the University of Texas at Austin, tweeted Wednesday evening.

Half of dialysis centers across Texas -- more than 750, serving some 54,000 patients -- are affected by power outages and water issues, according to Tiffany Jones-Smith, CEO of the Texas Kidney Foundation.

"For some of our patients, we're talking about the fourth day, the fifth day without dialysis and that's unacceptable," she said in an interview with KENS5.

Stretching those extra days puts patients at risk of potassium and fluid problems that can be life-threatening, noted Holly Kramer, MD, MPH, of Loyola University in Chicago and immediate past president of the National Kidney Foundation.

The large storm system, unofficially dubbed Winter Storm Uri, swept across much of the country but created the greatest disruptions in Texas, where it dropped snow and ice Feb. 14 and 15. Failure of the power grid has left millions across the state without electricity, and frozen pipes are causing widespread water supply problems as well.

While power has been restored for many, water remains problematic. Dialysis requires access to clean water to prepare concentrates and dialysate and to reprocess the machines for the next patient.

Most outpatient clinics don't have generators, tweeted Samaya Anumudu, MD, of Baylor College of Medicine in Houston. "Even pd [peritoneal dialysis] pts struggling without power and heat and they aren't able to warm their bags even for manuals."

Baylor and all its outpatient clinics remained closed Thursday due to "ongoing water pressure issues."

Fresenius Kidney Care said about half of its Houston area centers have been impacted by a lack of water, "with the other centers either fully operational or operating on generators." A spokesperson said that many more dialysis centers are expected to restore services today due to arrival of water trucks.

"Fresenius Kidney Care activated its disaster response team in an effort to restore service as quickly as possible to those locations impacted by the extreme weather," said Brad Puffer, spokesperson for Fresenius Kidney Care. "Our care teams are reaching out to patients to ensure their safety and evaluate those patients in need of immediate treatment."

DaVita indicated similar strategies.

Where centers closed intermittently as power and water comes and goes, "we are coordinating with other health care providers, including hospitals, to help ensure that patients have continued access to care," according to a statement from Chakilla Robinson White, DaVita's group vice president overseeing its Texas clinics. "We are also working to bring water tankers, generators and supplies to affected areas."

By the end of Thursday, all but 8% of U.S. Renal Care's dialysis units in the state, about 100, were back to normal operations, said Joseph Brunink, MBA, who oversees operations in Texas.

Houston is the main area that remains impacted as it has been slower to deliver water supply, he said. "That's changed over the last 24 hours, but there have been improvements across the state." He said he expected patients to be back to their normal dialysis schedules in the next day or so despite the disruptions.

Jones-Smith pointed to some bright spots, like the group of eight clinics in San Antonio that brought water in and have been running around the clock to dialyze patients from any closed clinic regardless of affiliation.

Other clinics too, are stepping up, she said, with some providing coupons for Lyft and Uber to get patients transportation to dialysis clinics. "We're just kind of banding together and figuring out what needs to be done."

That's not uncommon, said U.S. Renal Care Chief Operating Officer Andy Johnston, as the CMOs of the largest dialysis companies stay in close contact on disasters and it's routine for them to open up their clinics for patients from other sites in such circumstances.

"It's not just our staff; it's the whole industry -- the whole healthcare industry, but particularly the dialysis industry," he told MedPage Today. "It's really been an extraordinary 4 days. We're not out of it, there's still much to do, but it does feel like we're on the back side of it and things are getting better."

Kramer pointed to the lessons on emergency preparedness from the scramble for dialysis care when facilities closed due to loss of power and flooding from Hurricane Katrina in 2005.

"Patients receiving dialysis did not know how to adequately prepare for the storm, many hospitals and dialysis centers had insufficient disaster plans, and public health and emergency management agencies did not know how many people in their community were dialysis dependent and likely to need assistance in the wake of the storm," a paper in the American Journal of Kidney Diseases noted.

While it cited improvements in the years that followed, Jones-Smith indicated that such preparations failed in Texas. "The thought that weather could impact us in this way and that our leadership wouldn't have been prepared didn't even enter anybody's mind, obviously," she told KENS5.

Some centers said they had been told there would be water supply problems, she said, "but the way that electricity was presented to everyone was that it was going to be rolling brownouts and it wouldn't be hours. ... That is not what actually happened. It's really been catastrophic."

However, Johnston was less critical and argued it was more a problem with the utilities and governance than preparedness by the industry: "I feel like we were prepared from a process standpoint but just surprised by how long this lasted, and then the water and power issues that we had to overcome and are still overcoming."

When this crisis is over, Jones-Smith said, "We can't let this go, because we need to be prepared for the next time, not just reacting to chaos, which is what we're doing right now. ... There's no getting around we've had an epic failure."

Kramer noted that the lesson isn't just for Texas -- because global warming is intensifying and shifting the usual weather-related concerns.

"We all need to have disaster planning for dialysis moving forward," she told MedPage Today. "This just shows it's not just hurricanes. It could be disasters from severe weather in places that are not used to it. We're seeing such huge fluctuations in weather patterns across the entire United States. Disaster planning is something we should think about all the time now."

https://www.medpagetoday.com/nephrology/esrd/91258

Putting Numbers to 'Long COVID' Duration, Prevalence

 Nearly one-third of people with COVID-19 had lingering symptoms a median of 6 months after infection onset, a single-center prospective study suggested.

Among COVID-19 patients whose infections ranged from asymptomatic to severe, two problems -- fatigue and loss of smell or taste -- persisted most frequently, reported Helen Chu, MD, MPH, of University of Washington in Seattle, and co-authors, in a JAMA Network Open research letter.

"The effects of COVID-19 can linger far beyond acute infection, even in individuals who experienced mild illness," said co-author Denise McCulloch, MD, MPH, also of University of Washington.

"To our knowledge, this study presents the longest follow-up symptom assessment post-illness, with individuals surveyed out to 9 months after their COVID diagnosis," she told MedPage Today.

Earlier studies focused largely on long-term effects in hospitalized COVID patients, McCulloch noted. "Our study is unique in characterizing a group consisting of mostly outpatients: 90% of our cohort experienced only a mild COVID-19 illness, yet one-third continue to have lingering effects," she said.

"Many of these individuals are young and have no pre-existing medical conditions, indicating that even relatively healthy individuals may face long-term impacts from their illness."

There's very little data about people who have long-term COVID symptoms, observed Allison Navis, MD, of Icahn School of Medicine at Mount Sinai in New York City, who wasn't involved with the study.

Early in 2021, researchers in Wuhan, China, reported that 76% of hospitalized COVID-19 patients had at least one symptom that persisted 6 months after acute infection, mostly fatigue or muscle weakness. "Studies of non-hospitalized patients have shown that anywhere from 35% to 50% of non-hospitalized patients had symptoms 2 to 4 months later," Navis noted.

Fatigue, breathing issues, and cardiac concerns like chest pain are common findings, as are neurologic symptoms, she pointed out. Of patients at the Center for Post-COVID Care at Mount Sinai with neurology referrals, "about 65% come in with cognitive complaints or brain fog," Navis said.

"Brain fog means different things to different people, but usually it's some combination of short-term memory issues, attention issues, and word-finding difficulty." It's a little different for every patient, she added: "A clear phenotype hasn't really emerged yet."

The University of Washington study followed 177 people with laboratory-confirmed SARS-CoV-2 infection who completed questionnaires from August to November 2020, 3 to 9 months after their COVID-19 onset (median 169 days). Mean age was 48 and 57% were women. Hypertension was the most common comorbidity (13%).

Across the cohort, 6.2% of participants were asymptomatic, 84.7% were outpatients with mild illness, and 9.0% were hospitalized with moderate or severe disease. Patients completed followup questionnaires a median of 169 days after COVID-19 onset.

Overall, 32.7% of outpatients and 31.3% of inpatients reported at least one persistent symptom, most commonly fatigue (13.6%) and loss of sense of smell or taste (13.6%). In addition, 13.0% reported other symptoms, including brain fog (2.3%).

Among outpatients and hospitalized patients, 30.7% reported worse health-related quality of life compared with baseline; this figure was 12.5% for patients who never had overt COVID symptoms. About 8% of all participants said at least one activity of daily living suffered long-term consequences, most commonly household chores.

Study limitations include small sample size, single study location, and potential bias from self-reported symptoms, the researchers acknowledged. "We plan to continue to survey our cohort every 6 months for 2 years to continue to assess changes in long-term symptoms over time," McCulloch said. "With over 28 million cases of COVID-19 in the U.S. alone, if even a small percentage of people experience long-term debility, this could have significant and lasting health and economic consequences."

More research is needed to understand why some COVID-19 patients have lingering symptoms, Navis noted. "We don't know what's causing this. There might be different etiologies for different people; it might not be just one thing," she suggested. "Is it vascular? Is it metabolic? Is it inflammatory? It's hard to say."

Disclosures

This research was funded by grants from the Bill and Melinda Gates Foundation.

Chu reported receiving personal fees from Merck, Ellume, the Bill and Melinda Gates Foundation, GlaxoSmithKline, and Pfizer; receiving grants from Sanofi-Pasteur; and receiving reagents from Cepheid Research outside the submitted work. No other disclosures were reported.

Primary Source

JAMA Network Open

Source Reference: Logue JK, et al "Sequelae in Adults at 6 Months After COVID-19 Infection" JAMA Netw Open 2021; DOI: 0.1001/jamanetworkopen.2021.0830.

https://www.medpagetoday.com/infectiousdisease/covid19/91270

AbbVie, Evolus, Medytox Resolve Intellectual Property Litigation

 AbbVie (NYSE: ABBV), Evolus (NASDAQ: EOLS) and Medytox announce settlement agreements to fully resolve all outstanding litigation, including the United States International Trade Commission (ITC) case regarding the sale of Jeuveau®, between the companies. A California court case filed by Medytox against Evolus will be dismissed.

Under the terms of the settlement agreements, AbbVie and Medytox will release all claims against Evolus related to the alleged misappropriation of Medytox's trade secrets and grant a license to Evolus to continue to commercialize Jeuveau® in the United States and Nuceiva™ in all other territories in which Evolus has licensing rights. AbbVie and Medytox will receive milestone and royalty payments from Evolus. In addition, Evolus will issue common stock to Medytox.

This agreement follows the final determination of the ITC on December 16, 2020 which found a misappropriation of Medytox's manufacturing trade secrets and strain of C. botulinum and concluded that a violation of Section 337 of the Tariff Act of 1930 had occurred. As Daewoong Pharmaceutical Co. Ltd. is not a party to the settlement agreements, this settlement does not affect any legal rights, positions, or proceedings between Medytox and Daewoong in Korea and other countries.

https://finance.yahoo.com/news/abbvie-evolus-medytox-announce-resolution-141500404.html

Bluebird’s Zynteglo safety snag could spell trouble for other gene therapies

 Cancer cases that cropped up in a clinical trial definitely set back Bluebird Bio’s one-time blood disorder gene therapy Zynteglo. But the incident could ripple beyond the company's specific products, analysts argued.

Bluebird has already hit pause on selling Zynteglo as a beta-thalassemia therapy in Europe, even though the two cases—acute myeloid leukemia and myelodysplastic syndrome—happened in the drug’s sickle cell disease trial. It’s not approved in the U.S. for either use.

The company launched an investigation into the cancer cases to determine whether there’s a causal link, and the European Medicines Agency said Wednesday that it would examine the evidence and decide on future regulatory moves for Zynteglo “or any similar medicines under evaluation.”

The question focuses on whether Zynteglo’s lentivirus vector inserted itself into the human genome to cause cancer. Even though no other approved medicines use the same viral vector—as the EMA noted—analysts at Jefferies and J.P. Morgan figure the problem could reach beyond Bluebird.

“[I]t is hard to see how this news doesn’t have some clinical, regulatory, and eventually commercial implications...regardless of what further investigation uncovers,” JPM’s Cory Kasimov wrote in a Wednesday note.

Jefferies analysts listed three ways the Bluebird problem could affect the company itself and other gene therapies.

First, the team figures it would be difficult for Bluebird to completely rule out a causal relationship between Zynteglo and the blood cancers, given the small number of patients involved and the large number of potential generic culprits.

So far, 47 patients with sickle cell disease have been treated with the drug in clinical trials, and none of the 63 beta-thalassemia patients who've received it has developed cancer so far, Bluebird chief Nick Leschly said on a call Tuesday.

Bluebird’s approach is to investigate whether the vector is inserted into regions of the genome close to cancer-driving genes and whether the vector triggers any change in gene expression, Bluebird’s chief scientific officer, Phil Gregory, told investors on the call.

Even if evidence later proves that Zynteglo isn’t to blame for the two cancer cases among sickle cell disease patients, the drag on the drug’s commercial rollout could last for a while, the Jefferies team said, adding that physicians and the FDA may want to see longer-term follow-up data—possibly up to five years.

Besides the vector and each patient’s own underlying risk factors, Bluebird also fingered the chemotherapy busulfan as a possible culprit. Zynteglo patients first take a busulfan preconditioning regimen to prepare their bodies for the gene therapy.

If that’s the case, the Jefferies team expects safety scrutiny across all gene therapy programs that use busulfan as a conditioning regimen. One example would be CRISPR Therapeutics and Vertex’s investigational CRISPR gene-edited therapy CTX001, a potential treatment for sickle cell disease and beta-thalassemia.

“The bigger issue is how to administer ex vivo cells with a non-chemo regimen that can successfully engraft cells and ensure patient safety, and we believe this is the long-term challenge for the field,” the Jefferies team said.

https://www.fiercepharma.com/marketing/bluebird-s-zynteglo-safety-snag-may-have-broader-implications-for-gene-therapy-analysts