Brazilian COVID-19 variant much more transmissible than other strains

 An international team of researchers has found evidence suggesting that the P.1 coronavirus variant that was first seen in parts of Brazil may be up to twice as transmissible as prior strains. In their paper published in the journal Science, the group describes their work involving study of the variant and what they found.

The P.1 SARS-CoV-2 variant was first seen in Manaus, the capital of the state of Amazonas in Brazil. Initial research suggested the virus arose late last year and began spreading in November. It quickly became the dominant strain, leading many in the country to believe it could infect people who had already been infected with the initial strain earlier in the year. During the initial infection period, approximately 70% of the people in the city were believed to have been infected. After variant infections rose in Manaus, the P.1 variant soon spread throughout Brazil, and then to other countries—to date, it has been found in 37 countries.

Via molecular clock analysis, the researchers determined that the virus had 17 identifiable mutations and that three spike protein mutations—N501Y, E484K and K417T—were particularly worrisome because they appeared to allow the virus to bind more tightly to human cells, and in some cases, to aid in evading antibodies. They also found evidence that the variant can evade an immune response to prior strains of the virus.

Other work involved simulating the virus to determine how its abilities have changed since it mutated. The simulations showed the variant to be from 1.7 to 2.4 times more transmissible than previous strains of the virus. The researchers were not able to determine if the increase was due to the virus persisting longer in the body or from an increase in viral load. Also, they were not able to determine if the new variant makes people sicker or if it is deadlier. They estimated that those infected in Manaus were 1.2 to 1.9 times as likely to die from a P.1 infection than prior strains, but it was not clear if that was due to changes in the virus or the health care system in the city, which has been overburdened by more demand than the city can handle.

The researchers conclude that more work is required to determine if the P.1 strain is truly able to infect people who have been infected with prior strains, or those who have been vaccinated.

More information: Nuno R. Faria et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil, Science (2021). DOI: 10.1126/science.abh2644

https://medicalxpress.com/news/2021-04-international-brazilian-covid-variant-transmissible.html

China is starting clinical trials of Covid vaccine that can be inhaled

 China’s CanSino Biologics will be starting clinical trials for a Covid-19 vaccine that is administered through inhalation next week, the company’s co-founder and Chief Executive Xuefeng Yu told CNBC on Sunday.

Efficacy rates for China’s Covid vaccines have been found to be lower than those developed by Pfizer-BioNTech and Moderna. Earlier this month, the director of the Chinese Center for Disease Control publicly acknowledged that Chinese vaccines “don’t have very high protection rates” and that they were considering giving people different Covid shots to boost vaccine efficacy.

Yu told CNBC that an inhaled vaccine could be more effective than those injected given that the coronavirus enters the human body through the airways.

CanSinoBIO is jointly developing the inhalation vaccine with the Beijing Institute of Biotechnology. To be clear, the company’s Adenovirus Type 5 Vector vaccine — or Ad5-nCoV — administered by injection was already approved for use in China and several other countries.

Speaking to CNBC’s Arjun Kharpal at the Boao Forum for Asia in the Chinese province of Hainan, Yu explained that theoretically, an inhaled vaccine could provide additional protection by activating antibodies or T cells — white blood cells that are vital to the immune system — in the airways.

If that protection layer fails and the virus travels deeper into the body, other parts of the immune system could still fight the Covid virus, added Yu.

“So you add more layers — makes sense, right? So that’s why we’re going through the mucosal route,” he said.

The CEO said the company has used the same concept to develop an inhalation vaccine for tuberculosis or TB. Trials conducted in Canada showed that the inhaled dosage for the TB vaccine needed to provide protection is “much, much less than the actual injection,” he said.

Boosting vaccine efficacy

CanSinoBIO’s single-dose injected Covid vaccine has been approved for use in several countries including China, Pakistan, Mexico and Hungary.

The company said interim data from phase three clinical trials overseas showed its vaccine was 68.83% effective at preventing symptomatic Covid-19 disease two weeks after one injection, while the rate fell to 65.28% after four weeks, reported Reuters.

In comparison, updated data showed the Pfizer-BioNTech shot was 91% effective at preventing infection, while Moderna said its vaccine was more than 90% effective six months after the second shot.

Yu said CanSinoBIO has studied adding a booster shot six months after the first injection, which managed to improve the immune response to the coronavirus. 

“That’s also indicating that our vaccine could be boosted — whether it’s being mixed with others or do it our own, I think that needs truly a scientific study. We need to actually have data to demonstrate which way could be better,” said the CEO.

Reuters reported on Monday that Chinese researchers are testing mixing Covid vaccines developed by CanSinoBIO and a unit of Chongqing Zhifei Biological Products. The trial, under way in the eastern city of Nanjing, is expected to involve 120 participants, said the report.

China was the first country to report cases of Covid-19 in late 2019 and appears to have largely contained the outbreak. The country has said it aims to vaccinate 40% of its population by June.

https://www.cnbc.com/2021/04/19/china-is-starting-clinical-trials-of-a-covid-vaccine-that-can-be-inhaled.html

Brown U's Jha expects states to lift outdoor mask mandates in next few weeks

 Dr. Ashish Jha says he expects states to begin lifting outdoor mask mandates in the next few weeks.

And while Jha has generally cautioned against loosening COVID-19 restrictions too quickly, he suggests that, in this case, it may be the right move

“We’ve known for a year that outdoor infections are extremely rare,” Jha, the dean of Brown University’s School of Public Health, said Sunday on CNN.

“They only happen when you have large packed rallies for instance,” he said. “So if you are not participating in one of those, I think it is pretty safe to be out and about walking around without a mask, especially in large parts of the country where infection numbers are under reasonable control.”

Jha stressed that face covering requirements for indoor settings, where COVID-19 transmission overwhelmingly occurs, should remain in place for “a while longer,” as vaccination rollouts — in Massachusetts and across the country — race forward to combat the rise of more contagious variants of the virus. Jha also noted Sunday that, following the post-second surge decline in COVID-19 rates, infections in the United States have flatlined for roughly two months.

Most states imposed mask mandates last year requiring people to wear some form of a face covering when in public indoor places, as well as when they couldn’t consistently maintain six feet of distance from other people. An increasing number of those states have moved this spring to drop all statewide mask mandates, even for public indoor settings. That’s something that Brown’s Dr. Megan Ranney said on CNN shouldn’t be done until “around 70 percent or 80 percent” of American adults are vaccinated, citing variant-fueled spikes in places like Michigan.

Still, according to Jha, outdoor activity should be viewed “largely as a safe thing, unless you have congregations of large numbers of people together for a long periods of time.”

“I expect over the next few weeks states to start lifting outdoor mask mandates,” he said.

Jha’s comments Sunday come amid a groundswell of recent articles in Slate, The Atlantic, The New Republic, and the New England Journal of Medicine suggesting the time has come to end outdoor mask mandates, given increased vaccinations and the already-low risk of catching the disease outside. According to The Atlantic, “almost all of the documented cases of outdoor transmission have involved long conversations, or face-to-face yelling.” Additionally, Harvard Medical School epidemiologist Julia Marcus said that some mask skeptics became more amenable to wearing them indoors when they were told masking wasn’t as important outside.

In Massachusetts, Gov. Charlie Baker tightened the state’s mask mandate in November to require face coverings at all outdoor public places, with no exceptions for when individuals are not near others — a step further than other states have gone. Despite criticism that the tightened order went too far and might undermine public trust, Baker argued that it sent a simple message about the importance of wearing a mask.

During a press conference last week, Baker said that potentially relaxing the state’s mask mandate would depend on federal guidance, as well as “how fast we are able to vaccinate people and how big a deal these variants are in.”

The Centers for Disease Control and Prevention currently recommends people wear masks in “public settings, at events and gatherings, and anywhere they will be around other people.”

https://www.boston.com/news/coronavirus/2021/04/19/ashish-jha-outdoor-mask-mandates

Moderna COVID vax could get emergency authorization for ages 12 to 15 'within weeks’

 After months of clinical trials examining how Moderna’s COVID-19 vaccine affects children 12 to 15 years old, Dr. Robert Finberg of UMass Medical School in Worcester anticipates emergency authorization for the population within weeks.

UMass Medical School researchers began enrolling adolescents ages 12 through 17 in February. The trials were expected to enroll 3,000 adolescents at up to 15 sites nationwide.

They are now fully enrolled and researchers are waiting for the data to return.

“So far the clinical trials have been very successful,” Finberg said. “I think we’re confident that they will continue to be. These vaccines look like they are very safe and very efficacious.”

Last November, Moderna announced its vaccine offered a 95% efficacy rate during its phase three clinical trials, with 100% effectiveness at preventing hospitalizations as a result of the virus.

Preliminary data from the trials at UMass Medical School suggest that the vaccine could be even more effective with fewer side effects for children 12 to 15 years old. Emergency authorization by the United States’ Food and Drug Administration could be just weeks away, Finberg said.

“So far, at least, both the Pfizer and Moderna vaccine, appear to be equally effective in young people,” Finberg said. “If anything, they have fewer adverse events. There have been no big differences. We don’t expect that there will be problems with young people. If anything, they’ll do better.”

Finberg said generally speaking it’s common for young people’s immune systems to respond better to vaccines. The COVID-19 vaccines appear to be no different according to early clinical trials.

Due to the success of the trials, Finberg expects emergency authorization soon.

“It should be weeks. Everybody thinks we can get this done before the fall,” Finberg said. “That would be the goal.”

Finberg said the goal would be to immunize children ages 12 to 15 before school resumes in the fall. Children ages 3 to 11 could potentially receive the vaccine after that.

Finberg said it’s common for clinical trials to be separated into age groups. Although the trials individually aren’t all that different whether it’s for children ages 3 to 11 or adults over the age of 75.

“They’re not much different,” Finberg said. “Obviously, the parents are involved in a pediatric trial, but it’s done in very similar ways, both with close follow-up and monitoring very carefully of side effects.”

The ability to begin the vaccination of younger populations before school is critical in controlling the spread of the virus. A goal of herd immunity must include children, Finberg said.

While researchers continue to study COVID and how it spreads, Finberg said other infections spread at high volumes through school-aged children.

“It’s really important,” Finberg said. “We know influenza, for example, spreads every year and a lot of the spread appears to be in school-aged children so we definitely want to get these people vaccinated.”

Finberg believes the process of vaccinating the younger population could go quickly after emergency authorization is approved. As of Monday, everyone in Massachusetts 16 or older is eligible to receive the vaccine.

Unlike in the winter, when Pfizer and Moderna received emergency authorization, there are now large-scale vaccination sites and protocols around the country.

“That would be very quick,” Finberg said.

https://www.masslive.com/coronavirus/2021/04/moderna-covid-vaccine-could-receive-emergency-authorization-for-children-ages-12-to-15-within-weeks.html

U.S. Will Boost 'Do Not Travel' Advisories to 80% of World

 The U.S. State Department said on Monday it will boost its "Do Not Travel" guidance to about 80% of countries worldwide, citing "unprecedented risk to travelers" from the COVID-19 pandemic.

"This update will result in a significant increase in the number of countries at Level 4: Do Not Travel, to approximately 80% of countries worldwide," the department said in a statement.

The State Department already listed 34 out of about 200 countries as "Level 4: Do Not Travel," including places like Chad, Kosovo, Kenya, Brazil, Argentina, Haiti, Mozambique, Russia and Tanzania. Getting to 80% would imply adding nearly 130 countries.

Most Americans were already prevented from traveling to much of Europe because of COVID-19 restrictions. Washington has barred nearly all non-U.S. citizens who have recently been in most of Europe, China, Brazil, Iran and South Africa.

The State Department said the move does not imply a reassessment of current health situations in some countries, but rather "reflects an adjustment in the State Department's Travel Advisory system to rely more on (Centers for Disease Control and Prevention's) existing epidemiological assessments."

CDC did not immediately comment.

Earlier this month, the CDC said people who are fully vaccinated against COVID-19 can safely travel within the United States at "low risk" but CDC Director Rochelle Walensky discouraged Americans from doing so because of high coronavirus cases nationwide.

"We know that right now we have a surging number of cases. I would advocate against general travel overall," Walensky said. "We are not recommending travel at this time, especially for unvaccinated individuals."

https://www.usnews.com/news/us/articles/2021-04-19/us-to-put-more-countries-under-covid-do-not-travel-advisory-state-department

Alnylam: Positive Results from Phase 3 Neuropathy Trial

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced full positive results from the HELIOS-A Phase 3 study of vutrisiran, an investigational RNAi therapeutic in development for the treatment of transthyretin-mediated (ATTR) amyloidosis, which met its primary and both secondary endpoints at nine months in patients with hereditary ATTR (hATTR) amyloidosis with polyneuropathy. The results were presented today in an oral session at the 2021 American Academy of Neurology (AAN) Virtual Annual Meeting.

The 9-month results achieved the study’s primary endpoint, with vutrisiran showing improvement in the mean change from baseline in the modified Neuropathy Impairment Score (mNIS+7) as compared to external placebo data from the APOLLO Phase 3 study of patisiran. At 9 months vutrisiran also met all secondary endpoints, demonstrating improvement in quality of life as assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) instrument and improvement in gait speed as assessed by the timed 10-meter walk test (10-MWT), both compared to the external placebo group. The majority of patients experienced improvement in neuropathy and in quality of life, both relative to baseline, showing the potential for vutrisiran to reverse polyneuropathy manifestations of hATTR amyloidosis. Vutrisiran also demonstrated an encouraging safety profile with no drug-related discontinuations or deaths. Based on these positive data, Alnylam has submitted a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for the approval of vutrisiran for the treatment of the polyneuropathy of hATTR amyloidosis in adults.

Alnylam management will discuss the full 9-month results from the HELIOS-A Phase 3 clinical trial via conference call on Monday, April 19th at 4:00 pm ET. A webcast presentation will also be available on the Investors page of the Company’s website, www.alnylam.com. To access the call, please dial 877-312-7507 (domestic) or +1-631-813-4828 (international) five minutes prior to the start time and refer to conference ID 9580096. A replay of the call will be available beginning at 7:00 pm ET on the day of the call. To access the replay, please dial 855-859-2056 (domestic) or +1-404-537-3406 (international) and refer to conference ID 9580096.

https://finance.yahoo.com/news/alnylam-presents-positive-results-helios-180000221.html

3 Things to Look For When Intuitive Surgical Reports Q1 2021

 Intuitive Surgical (NASDAQ:ISRG), the undisputed leader of robot-assisted surgery, will report earnings from the first three months of 2021 after the market closes on Tuesday, April 20, 2021. The COVID-19 pandemic has been an enormous challenge for hospitals that use the company's surgical systems and shareholders are probably right to be nervous about the company's performance. Here are the three most important topics investors want to listen for when Intuitive Surgical discusses reports first-quarter results. 

1. A U.S. rebound

Instead of double-digit percentages investors are used to seeing year after year from Intuitive Surgical's domestic market, total procedures performed with the company's da Vinci systems actually fell 1% in 2020 from the previous year. That's a very big problem because more than two-thirds of all surgical procedures performed with consumable instruments and accessories clients purchase from Intuitive Surgical occur in the United States.

Procedure volumes and new system sales were humming along in the U.S. at the beginning of the first quarter last year. By the end of March, though, COVID-19 related restrictions hammered weekly procedure volumes around 65% lower. As the pandemic progressed, hospital operators began deferring new da Vinci system placements, and millions of doctor visits that eventually lead to a da Vinci-assisted surgical procedure have also been rescheduled. Demand for the company's da Vinci surgical systems has been depressed all over the globe since the pandemic started, but clear signs of a rebound in the company's most important region could push the stock higher.

America's relatively rapid COVID-19 vaccine rollout should lead to a rebound for Intuitive's U.S. market months before we see a similar return to normal in Europe and other established markets, but the timing is still uncertain. During Medtronic's (NYSE:MDT) fiscal third quarter that ended Jan. 31, the medical-device giant's surgical innovations segment reported a year-over-year revenue loss of 5.3% because of resurging COVID-19 outbreaks.

2. East Asia

With the first SARS outbreak from 2003 lingering in their memories, rapidly modernizing hospitals across the Pacific ocean from Intuitive Surgical's headquarters haven't been as severely affected as their counterparts in the U.S. Before the end of 2020, China had already become the company's second-largest market by procedure count and analysts will be watching for signs of continuing growth in this crucial geographic segment. 

In 2020, all procedures performed with da Vinci outside the U.S. reached just 346,000 compared to 876,000 domestic procedures. In the relatively limited U.S. market, procedure growth in recent years has been driven by increased demand for gynecology, general surgery, and other operating segments that are still coming online in China and neighboring countries.

3. New avenues

More procedures are performed with Intuitive Surgical machines in China than in any other country outside of the U.S., even though a big joint venture with Fosun Pharma to directly market equipment in China isn't expected to report any revenue this year. The Joint Venture is built around lung tumor biopsy technology that the company's still rolling out in the U.S. following a green light from the FDA in 2019. An estimated 787,000 people in China were diagnosed with a new case of lung cancer in 2015, and nearly all of them would benefit from a clear look at samples of their tumors. 

Getting a surgical tool into a position where it can retrieve a lung tumor sample isn't easy, but Intuitive Surgical's Ion endoluminal system is a tiny, flexible catheter-shaped device that could be used to perform biopsies that would be too dangerous with traditional methods. At the end of 2020, Intuitive Surgical had placed just 36 of its Ion endoluminal devices and they're all in the U.S. If this number doesn't start rising soon, investors might have to assume the joint venture with Fosun Pharma isn't going anywhere fast either.

Prostate and kidney surgeries accounted for just 15% of total procedures performed in the mature U.S. market last year, but urology was still the largest growth driver outside of the U.S. Investors will want to keep an eye open for signs of expansion abroad beyond the limited urology field.

Hang on tight

While there's a lot to look out for when Intuitive Surgical posts first-quarter results, shareholders should remember not to overreact if things aren't going as smoothly as hoped. Intuitive Surgical isn't the only device maker dealing with hospitals that have to make some tough choices. This means any would-be competitors attempting to get the attention of purchasing departments don't have a chance right now. With plenty of real-world data that proves da Vinci machines can pay for themselves, though, Intuitive Surgical's dominance of the surgical robotics industry looks unbreakable.

https://www.fool.com/investing/2021/04/19/things-to-look-for-when-intuitive-surgical-reports/