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COVID-19 causes ‘unexpected’ cellular response in the lungs, research finds

Credit: Purdue University photo/ Rebecca McElhoe WEST LAFAYETTE, Ind. – New insights into the immune response to SARS-CoV-2 infections could bring better treatments for COVID-19 cases. An international team of researchers unexpectedly found that a biochem

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Credit: Purdue University photo/ Rebecca McElhoe

WEST LAFAYETTE, Ind. – New insights into the immune response to SARS-CoV-2 infections could bring better treatments for COVID-19 cases.

An international team of researchers unexpectedly found that a biochemical pathway, known as the immune complement system, is triggered in lung cells by the virus, which might explain why the disease is so difficult to treat. The research is published this week in the journal Science Immunology.

The researchers propose that the pairing of antiviral drugs with drugs that inhibit this process may be more effective. Using an in vitro model using human lung cells, they found that the antiviral drug Remdesivir, in combination with the drug Ruxolitinib, inhibited this complement response.

This is despite recent evidence that trials of using Ruxolitinib alone to treat COVID-19 have not been promising.

To identify possible drug targets, Majid Kazemian, assistant professor in the departments of computer science and biochemistry at Purdue University, said the research team examined more than 1,600 previously FDA-approved drugs with known targets.

“We looked at the genes that are up-regulated by COVID-19 but down-regulated by specific drugs, and Ruxolitinib was the top drug with that property,” he said.

Within the last few years, scientists have discovered that the immune complement system – a complex system of small proteins produced by the liver that aids, or complements, the body’s antibodies in the fight against blood-borne pathogens – can work inside cells and not just in the bloodstream.

Surprisingly, the study found that this response is triggered in cells of the small structures in the lungs known as alveoli, Kazemian said.

“We observed that SARS-CoV2 infection of these lung cells causes expression of an activated complement system in an unprecedented way,” Kazemian said. “This was completely unexpected to us because we were not thinking about activation of this system inside the cells, or at least not lung cells. We typically think of the complement source as the liver.”

Claudia Kemper, senior investigator and chief of the Complement and Inflammation Research Section of the National Institutes of Health, was among the first to characterize novel roles of the complement system in the immune system. She agreed these latest findings are surprising.

“The complement system is traditionally considered a liver-derived and blood-circulating sentinel system that protects the host against infections by bacteria, fungi and viruses,” she said. “It is unexpected that in the setting of a SARS-CoV2 infection, this system rather turns against the host and contributes to the detrimental tissue inflammation observed in severe COVID-19. We need to think about modulation of this intracellular, local, complement when combating COVID-19.”

Dr. Ben Afzali, an Earl Stadtman Investigator of the National Institute of Health’s National Institute of Diabetes and Digestive and Kidney Diseases, said there are now indications that this has implications for difficulties in treating COVID-19.

“These findings provide important evidence showing not only that complement-related genes are amongst the most significant pathways induced by SARS-CoV2 in infected cells, but also that activation of complement occurs inside of lung epithelial cells, i.e., locally where infection is present,” he said.

“This may explain why targeting the complement system outside of cells and in the circulation has, in general, been disappointing in COVID-19. We should probably consider using inhibitors of complement gene transcription or complement protein activation that are cell permeable and act intracellularly instead.”

Afzali cautions that appropriate clinical trials should be conducted to establish whether a combination treatment provides a survival benefit.

“The second finding that I think is important is that the data suggest potential benefit for patients with severe COVID-19 from combinatorial use of an antiviral agent together with an agent that broadly targets complement production or activation within infected cells,” he said. “These data are promising, but it is important to acknowledge that we carried out the drug treatment experiments in cell lines infected with SARS-CoV2. So, in and of themselves they should not be used to direct treatment of patients.”

Kemper added that the unexpected findings bring more questions.

“A currently unexplored and possibly therapeutically interesting aspect of our observations is also whether the virus utilizes local complement generation and activation to its benefit, for example, for the processes underlying cell infection and replication,” she said.

About Purdue University

Purdue University is a top public research institution developing practical solutions to today’s toughest challenges. Ranked the No. 5 Most Innovative University in the United States by U.S. News & World Report, Purdue delivers world-changing research and out-of-this-world discovery. Committed to hands-on and online, real-world learning, Purdue offers a transformative education to all. Committed to affordability and accessibility, Purdue has frozen tuition and most fees at 2012-13 levels, enabling more students than ever to graduate debt-free. See how Purdue never stops in the persistent pursuit of the next giant leap at https://purdue.edu/.

Media Contact
Steve Tally
steve@purdue.edu

Original Source

https://www.purdue.edu/newsroom/releases/2021/Q2/covid-19-causes-unexpected-cellular-response-in-the-lungs,-research-finds.html

Related Journal Article

http://dx.doi.org/10.1126/sciimmunol.abg0833

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“Diamonds in the Rough” – Last Week’s Darlings and Dud

Each week in my DecisionPoint Diamonds reports, I give readers 10+ stock picks to consider. This week, we had 11 picks. I look for stocks that are beginning to show positive momentum, bullish chart patterns, breakouts and improving relative strength among

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Each week in my DecisionPoint Diamonds reports, I give readers 10+ stock picks to consider. This week, we had 11 picks. I look for stocks that are beginning to show positive momentum, bullish chart patterns, breakouts and improving relative strength among not only the SPX, but also against its industry group.

Today, I thought I would share three of last week's "Diamonds in the Rough." I have two "Darlings" and one "Dud." They aren't all winners and certainly are not "sure things," so I feel it is appropriate to show you the trade that didn't work out.

This week's "Darlings" come from the Biotech industry group, which really broke out this week. This week's "Dud" wasn't actually too bad. It was a timing issue, but it actually looks pretty good going forward. As part of a DP Diamonds subscription, you also get entrance into the Friday "Diamond Mine" where we review in detail the "Diamonds in the Rough" that presented for the week. I also take symbol requests and we look at BUY points for symbols with promise. An added bonus is that, at the end, we "mine" for new opportunities going into next week.

Below I have the "Diamonds in the Rough" as they were presented originally, followed by my comments on the chart today.

Darling #1:

Illumina, Inc. (ILMN) - Up +4.43% since 6/9


EARNINGS: 8/5/2021 (AMC)


Illumina, Inc. engages in the development, manufacturing, and marketing of life science tools and integrated systems for large-scale analysis of genetic variation and function. It operates through Core Illumina segment, which serves customers in the research, clinical and applied markets, and enables the adoption of a variety of genomic solutions. The firm's products include instruments, kits and reagents, selection tools, software and analysis. Its services include sequencing and microarray services; proactive instrument monitoring; and instrument services, training and consulting. The company was founded by David R. Walt, John R. Stuelpnagel, Anthony W. Czarnik, Lawrence A. Bock and Mark S. Chee in April 1998 and is headquartered in San Diego, CA.

Below is the chart and commentary from Wednesday (6/9):

"ILMN is down -0.01% in after-hours trading. I was surprised I hadn't covered this one before. It's not as volatile as many of the biotechs out there. We have a nice breakout from a trading range. The breakout occurred Monday and price has held above support today and yesterday. The RSI is on the overbought side, so we should be aware of that. The PMO is on an oversold BUY signal and has now reached positive territory. There was a recent IT Trend Model "Silver Cross" BUY signal when the 20-EMA crossed above the 50-EMA. The OBV is confirming the rally and the SCTR is almost in the "hot zone" above 75, meaning it is in the upper quartile among all large-cap stocks. Outperformance is clear. I like that you can set a reasonable 7% stop."

Here is today's chart:

The biggest flaw is the overbought RSI, which is flattening out. ILMN needs to consolidate Thursday's breakout. It began to today, I still love this Biotech and you can tighten the stop more too. The SCTR is now in the "hot zone" above 75, meaning it is in the top quartile among its peers in the large-cap "universe." Also, regarding the SCTR, the calculations are heavily based on intermediate- and long-term indicators.


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Darling #2:

Novavax, Inc. (NVAX) - Up +2.31% since yesterday


EARNINGS: 8/9/2021 (AMC)

Novavax, Inc. focuses on the discovery, development and commercialization of vaccines to prevent infectious diseases. It provides vaccines for COVID-19, seasonal flu, respiratory syncytial virus, Ebola and Middle East respiratory syndrome. The company was founded in 1987 and is headquartered in Gaithersburg, MD.

Here is the chart and commentary from Thursday (6/10):

"NVAX is up +0.16% in after hours trading. I covered NVAX as a Reader Request on July 30th, 2020. It hit its 9.2% stop when price dropped in August, so the position would be closed at this point. However, I like it today given the improvement in the Biotech space and knowing that this one is a leader based on the 98.9 SCTR. Today, price pulled back toward the breakout point. This took the RSI away from overbought territory. The PMO shows no damage and is now rising in positive territory on an oversold crossover BUY signal. Volume is coming in and, despite the pullback, the OBV didn't sustain much damage either. The stop is set below the August 2020 top."

Below is today's chart & commentary:

The trade still looks good and it isn't too late for entry. The RSI is positive and not overbought. The PMO is rising strongly on a BUY signal. Most interesting is the nearing of an IT Trend Model "Silver Cross" BUY signal, which will be triggered when the 20-EMA crossover above the 50-EMA. Join me in the free Trading Room on Monday and we'll explore the best BUY points! Register HERE if you haven't already.



Dud:


Dycom Industries, Inc. (DY) - Down -2.91% Since 6/8


EARNINGS: 8/25/2021 (BMO)


Dycom Industries, Inc. provides contracting services throughout the United States. Its services include engineering, construction, maintenance and installation services to telecommunications providers, underground facility locating services to various utilities, including other construction and maintenance services to electric and gas utilities, and others. The company was founded in 1969 and is headquartered in Palm Beach Gardens, FL.

Below is the chart and commentary from Tuesday (6/8):

"DY is up +0.72% in after hours trading. I covered DY in the October 14th 2020 Diamonds Report. I didn't put a stop on the chart, but an 8% stop wouldn't have triggered even on the big gap down in November. This means that the position is up +26.7%. The end of May was killer for DY, but it is retracing the decline rapidly. The first of two gaps has now been covered. Today's rally pushed DY above the 20-EMA. The PMO had already begun to curl upward. The RSI isn't positive yet, but it is on its way. The industry group is outperforming the SPX and DY is outperforming both. The stop is set below the gap, right around the 200-EMA at $77.28."

Below is today's chart:

While a lot of things went wrong on this chart, everything still looks bullish, especially after today's strong rally. A short-term flag has formed. The PMO had a positive crossover today. The RSI is still negative, but it is rising again. The timing was just off for it to look good this week. However, if we revisit this chart later, I expect that flag will have resolved upward and we'll be challenging the highs from April and May.

 Happy Charting! - Erin


Technical Analysis is a windsock, not a crystal ball.


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DecisionPoint is not a registered investment advisor. Investment and trading decisions are solely your responsibility. DecisionPoint newsletters, blogs or website materials should NOT be interpreted as a recommendation or solicitation to buy or sell any security or to take any specific action.

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EU adds another rare blood condition as side effect of AstraZeneca shot

Europe’s drug regulator on June 11 identified another rare blood condition as a potential side effect of AstraZeneca’s Covid-19 vaccine and said it was looking into cases of heart inflammation after inoculation with all coronavirus shots.

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EU adds another rare blood condition as side effect of AstraZeneca shot

(Reuters; )

Europe’s drug regulator on Friday identified another rare blood condition as a potential side effect of AstraZeneca’s (AZN.L) COVID-19 vaccine and said it was looking into cases of heart inflammation after inoculation with all coronavirus shots.

The European Medicines Agency’s (EMA) safety committee said that capillary leak syndrome must be added as a new side effect to labelling on AstraZeneca’s vaccine, known as Vaxzevria.

People who had previously sustained the condition, where fluids leak from the smallest blood vessels causing swelling and a drop in blood pressure, should not receive the shot, the EMA added.

The regulator first began looking into these cases in April and the recommendation adds to AstraZeneca’s woes after its vaccine was associated with very rare and potentially lethal cases of blood clotting that come with a low platelet count.

Last month, the EMA had advised against using the second AstraZeneca shot for people with that clotting condition, known as thrombosis with thrombocytopenia syndrome (TTS).

The committee reviewed six validated cases of capillary leak syndrome in people, mostly women, who had received Vaxzevria, including one death. Three had had a history of the condition.

A vial of AstraZeneca coronavirus vaccine is seen at a vaccination centre in Westfield Stratford City shopping centre, amid the outbreak of coronavirus disease (COVID-19), in London, Britain, February 18, 2021. REUTERS/Henry Nicholls/File Photo

AstraZeneca declined to immediately comment.

More than 78 million Vaxzevria doses have been administered in the European Union, Liechtenstein, Iceland & Norway and Britain.

Britain’s regulator, the MHRA said on Thursday it had received 8 reports of capillary leak syndrome in the context of more than 40 million doses of the AstraZeneca vaccine given, and currently does not see a causal link.

Separately, the EMA said it was continuing its probe into cases of heart inflammation known as myocarditis and pericarditis, primarily following inoculation with the Pfizer/BioNTech (PFE.N), (22UAy.DE) and Moderna mRNA shots, but also after the J&J (JNJ.N) and AstraZeneca vaccines.

U.S. health officials said on Thursday they had registered a higher-than-expected number of heart inflammation cases in young men who received a second dose of the mRNA shots, though a causal relationship could not be established. read more

Israel’s Health Ministry said this month it had found a likely link to the condition in young men who received the Pfizer/BioNTech shot. read more

Both Pfizer and Moderna have acknowldged the observations but said a causal association with their vaccines has not been established.

BioNTech said adverse events, including myocarditis and pericarditis, are being regularly and thoroughly reviewed by the companies and regulatory authorities.

“More than 300 million doses of the Pfizer-BioNTech COVID-19 vaccine have been administered globally and the benefit risk profile of our vaccine remains positive.”

The United States and Israel have been months ahead of the EU in vaccinating men below 30, who are particularly prone to heart inflammation, giving them potentially more cases to analyse.

Our Standards: The Thomson Reuters Trust Principles.

 

Reuters source:

https://www.reuters.com/business/healthcare-pharmaceuticals/eu-advises-against-astrazeneca-shot-people-with-rare-blood-condition-2021-06-11

 

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G7 Leaders Pledge 1 Billion Covid-19 Vaccines For Nations in Need

The summit of the Group of Seven industrialized nations in southwest England saw global leaders pledging at least 1 billion Covid-19 vaccines for underdeveloped countries and struggling nations.

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G7 Leaders Pledge One Billion COVID-19 Vaccines For Nations in Need

 

A most recent summit of the Group of Seven industrialized nations in southwest England saw global leaders pledging at least one billion COVID-19 vaccines for underdeveloped countries and struggling nations. Half of these doses will be shared by the U.S., while the U.K. has committed another 100 million shots.

The commitment to share these shots was announced during the session “Building Back Better From COVID-19.” During this session, President Joe Biden discussed with the G7 leaders – hailing from Canada, France, Germany, Italy, U.K. and Japan – that the U.S. will work alongside global partners to meet its goal of getting vaccines to those who need them most.

As reported by CTV News, pressure has been placed on the G7 leaders in recent months to develop a clear and workable vaccine-sharing strategy for poorer countries. The U.S., for instance, has reportedly accumulated a large stock of COVID-19 vaccines as the demand for inoculation has declined in the country.

In response, Biden said at the meeting that the U.S. plans to give up to 500 million vaccine doses to less privileged nations that currently lack widescale access. This is in addition to the 80 million doses the U.S. already committed to sharing with these countries by the end of this month. Biden also outlined a coordinated effort by each of the G7 countries to improve vaccine availability. 

British Prime Minister Boris Johnson reportedly said that 5 million does from the U.K. will be shared in the next few weeks, while the remaining vaccines will be disseminated over the next year. Johnson added that he expects the G7 leaders to commit up to 1 billion when all is said and done.

“At the G7 Summit I hope my fellow leaders will make similar pledges so that, together, we can vaccinate the world by the end of next year and build back better from coronavirus,” said Johnson in a statement, as reported by AP News.

Source: BioSpace

Likewise, French President Emmanuel Macron noted that France would share at least 30 million of its COVID-19 vaccines by the end of 2021.

For its part in the global vaccine-sharing effort, the U.S. plans to purchase and distribute 500 million doses of Pfizer/BioNTech’s mRNA COVID-19 vaccine. The distribution will be accomplished through the global COVAX alliance and will go toward 92 lower-income nations as well as the African Union. 

According to Biden, the vaccine doses will be shipped to these countries in August, with up to 200 million distributed across the globe by 2021’s end. The other 300 million vaccine doses will be distributed in the first half of next year. As such, the U.S. represents COVAX’s largest vaccine donor and single largest funder set at a $4 billion pledge.

The vaccine-sharing commitment by the G7 leaders is welcome news, considering the global COVAX alliance experienced a slow start to its inoculation campaign. 

To date, the alliance has distributed approximately 81 million vaccine doses across the world, but parts of Africa and other regions have largely been unable to gain access to these doses. Only France has so far started shipping its vaccines through the COVAX alliance. 

On Thursday, Biden said that a part of the 80 million doses the country had committed to donation were already being distributed. Additionally, the U.S. has provided Mexico and Canada a few million COVID-19 vaccines.

 
BioSpace source:
 
 
 

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