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https://www.usatoday.com/story/sports/nfl/titans/2020/10/08/tennessee-titans-buffalo-bills-game-postponed-covid-19-coronavirus/5922306002/
Why the NFL needs to immediately end the Titans’ 2020 season
Since last week, the NFL and NFLPA have had representatives in Nashville, investigating why the Tennessee Titans have by far the most positive COVID tests of any NFL team. The organization has had …
touchdownwire.usatoday.comThe Titans’ season should be cancelled. Part of the reason guys like A’Shawn aren’t coming back is because of the positive tests. The rest of the NFL has done amazing.
Earlier this summer, the Summit supercomputer at Oak Ridge National Lab in Tennessee set about crunching data on more than 40,000 genes from 17,000 genetic samples in an effort to better understand Covid-19. Summit is the second-fastest computer in the world, but the process — which involved analyzing 2.5 billion genetic combinations — still took more than a week.
When Summit was done, researchers analyzed the results. It was, in the words of Dr. Daniel Jacobson, lead researcher and chief scientist for computational systems biology at Oak Ridge, a “eureka moment.” The computer had revealed a new theory about how Covid-19 impacts the body: the bradykinin hypothesis. The hypothesis provides a model that explains many aspects of Covid-19, including some of its most bizarre symptoms. It also suggests 10-plus potential treatments, many of which are already FDA approved. Jacobson’s group published their results in a paper in the journal eLife in early July.
According to the team’s findings, a Covid-19 infection generally begins when the virus enters the body through ACE2 receptors in the nose, (The receptors, which the virus is known to target, are abundant there.) The virus then proceeds through the body, entering cells in other places where ACE2 is also present: the intestines, kidneys, and heart. This likely accounts for at least some of the disease’s cardiac and GI symptoms.
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But once Covid-19 has established itself in the body, things start to get really interesting. According to Jacobson’s group, the data Summit analyzed shows that Covid-19 isn’t content to simply infect cells that already express lots of ACE2 receptors. Instead, it actively hijacks the body’s own systems, tricking it into upregulating ACE2 receptors in places where they’re usually expressed at low or medium levels, including the lungs.
In this sense, Covid-19 is like a burglar who slips in your unlocked second-floor window and starts to ransack your house. Once inside, though, they don’t just take your stuff — they also throw open all your doors and windows so their accomplices can rush in and help pillage more efficiently.
The renin–angiotensin system (RAS) controls many aspects of the circulatory system, including the body’s levels of a chemical called bradykinin, which normally helps to regulate blood pressure. According to the team’s analysis, when the virus tweaks the RAS, it causes the body’s mechanisms for regulating bradykinin to go haywire. Bradykinin receptors are resensitized, and the body also stops effectively breaking down bradykinin. (ACE normally degrades bradykinin, but when the virus downregulates it, it can’t do this as effectively.)
The end result, the researchers say, is to release a bradykinin storm — a massive, runaway buildup of bradykinin in the body. According to the bradykinin hypothesis, it’s this storm that is ultimately responsible for many of Covid-19’s deadly effects. Jacobson’s team says in their paper that “the pathology of Covid-19 is likely the result of Bradykinin Storms rather than cytokine storms,” which had been previously identified in Covid-19 patients, but that “the two may be intricately linked.” Other papers had previously identified bradykinin storms as a possible cause of Covid-19’s pathologies.
Covid-19 is like a burglar who slips in your unlocked second-floor window and starts to ransack your house.
As bradykinin builds up in the body, it dramatically increases vascular permeability. In short, it makes your blood vessels leaky. This aligns with recent clinical data, which increasingly views Covid-19 primarily as a vascular disease, rather than a respiratory one. But Covid-19 still has a massive effect on the lungs. As blood vessels start to leak due to a bradykinin storm, the researchers say, the lungs can fill with fluid. Immune cells also leak out into the lungs, Jacobson’s team found, causing inflammation.
Coronavirus May Be a Blood Vessel Disease, Which Explains Everything
Many of the infection’s bizarre symptoms have one thing in common
elemental.medium.comAnd Covid-19 has another especially insidious trick. Through another pathway, the team’s data shows, it increases production of hyaluronic acid (HLA) in the lungs. HLA is often used in soaps and lotions for its ability to absorb more than 1,000 times its weight in fluid. When it combines with fluid leaking into the lungs, the results are disastrous: It forms a hydrogel, which can fill the lungs in some patients. According to Jacobson, once this happens, “it’s like trying to breathe through Jell-O.”
This may explain why ventilators have proven less effective in treating advanced Covid-19 than doctors originally expected, based on experiences with other viruses. “It reaches a point where regardless of how much oxygen you pump in, it doesn’t matter, because the alveoli in the lungs are filled with this hydrogel,” Jacobson says. “The lungs become like a water balloon.” Patients can suffocate even while receiving full breathing support.
The bradykinin hypothesis also extends to many of Covid-19’s effects on the heart. About one in five hospitalized Covid-19 patients have damage to their hearts, even if they never had cardiac issues before. Some of this is likely due to the virus infecting the heart directly through its ACE2 receptors. But the RAS also controls aspects of cardiac contractions and blood pressure. According to the researchers, bradykinin storms could create arrhythmias and low blood pressure, which are often seen in Covid-19 patients.
The bradykinin hypothesis also accounts for Covid-19’s neurological effects, which are some of the most surprising and concerning elements of the disease. These symptoms (which include dizziness, seizures, delirium, and stroke) are present in as many as half of hospitalized Covid-19 patients. According to Jacobson and his team, MRI studies in France revealed that many Covid-19 patients have evidence of leaky blood vessels in their brains.
Bradykinin — especially at high doses — can also lead to a breakdown of the blood-brain barrier. Under normal circumstances, this barrier acts as a filter between your brain and the rest of your circulatory system. It lets in the nutrients and small molecules that the brain needs to function, while keeping out toxins and pathogens and keeping the brain’s internal environment tightly regulated.
If bradykinin storms cause the blood-brain barrier to break down, this could allow harmful cells and compounds into the brain, leading to inflammation, potential brain damage, and many of the neurological symptoms Covid-19 patients experience. Jacobson told me, “It is a reasonable hypothesis that many of the neurological symptoms in Covid-19 could be due to an excess of bradykinin. It has been reported that bradykinin would indeed be likely to increase the permeability of the blood-brain barrier. In addition, similar neurological symptoms have been observed in other diseases that result from an excess of bradykinin.”
Increased bradykinin levels could also account for other common Covid-19 symptoms. ACE inhibitors — a class of drugs used to treat high blood pressure — have a similar effect on the RAS system as Covid-19, increasing bradykinin levels. In fact, Jacobson and his team note in their paper that “the virus… acts pharmacologically as an ACE inhibitor” — almost directly mirroring the actions of these drugs.
Medium Coronavirus Blog
A real-time resource for Covid-19 news, advice, and commentary.
coronavirus.medium.comBy acting like a natural ACE inhibitor, Covid-19 may be causing the same effects that hypertensive patients sometimes get when they take blood pressure–lowering drugs. ACE inhibitors are known to cause a dry cough and fatigue, two textbook symptoms of Covid-19. And they can potentially increase blood potassium levels, which has also been observed in Covid-19 patients. The similarities between ACE inhibitor side effects and Covid-19 symptoms strengthen the bradykinin hypothesis, the researchers say.
ACE inhibitors are also known to cause a loss of taste and smell. Jacobson stresses, though, that this symptom is more likely due to the virus “affecting the cells surrounding olfactory nerve cells” than the direct effects of bradykinin.
Though still an emerging theory, the bradykinin hypothesis explains several other of Covid-19’s seemingly bizarre symptoms. Jacobson and his team speculate that leaky vasculature caused by bradykinin storms could be responsible for “Covid toes,” a condition involving swollen, bruised toes that some Covid-19 patients experience. Bradykinin can also mess with the thyroid gland, which could produce the thyroid symptoms recently observed in some patients.
The bradykinin hypothesis could also explain some of the broader demographic patterns of the disease’s spread. The researchers note that some aspects of the RAS system are sex-linked, with proteins for several receptors (such as one called TMSB4X) located on the X chromosome. This means that “women… would have twice the levels of this protein than men,” a result borne out by the researchers’ data. In their paper, Jacobson’s team concludes that this “could explain the lower incidence of Covid-19 induced mortality in women.” A genetic quirk of the RAS could be giving women extra protection against the disease.
The bradykinin hypothesis provides a model that “contributes to a better understanding of Covid-19” and “adds novelty to the existing literature,” according to scientists Frank van de Veerdonk, Jos WM van der Meer, and Roger Little, who peer-reviewed the team’s paper. It predicts nearly all the disease’s symptoms, even ones (like bruises on the toes) that at first appear random, and further suggests new treatments for the disease.
As Jacobson and team point out, several drugs target aspects of the RAS and are already FDA approved to treat other conditions. They could arguably be applied to treating Covid-19 as well. Several, like danazol, stanozolol, and ecallantide, reduce bradykinin production and could potentially stop a deadly bradykinin storm. Others, like icatibant, reduce bradykinin signaling and could blunt its effects once it’s already in the body.
Interestingly, Jacobson’s team also suggests vitamin D as a potentially useful Covid-19 drug. The vitamin is involved in the RAS system and could prove helpful by reducing levels of another compound, known as REN. Again, this could stop potentially deadly bradykinin storms from forming. The researchers note that vitamin D has already been shown to help those with Covid-19. The vitamin is readily available over the counter, and around 20% of the population is deficient. If indeed the vitamin proves effective at reducing the severity of bradykinin storms, it could be an easy, relatively safe way to reduce the severity of the virus.
Other compounds could treat symptoms associated with bradykinin storms. Hymecromone, for example, could reduce hyaluronic acid levels, potentially stopping deadly hydrogels from forming in the lungs. And timbetasin could mimic the mechanism that the researchers believe protects women from more severe Covid-19 infections. All of these potential treatments are speculative, of course, and would need to be studied in a rigorous, controlled environment before their effectiveness could be determined and they could be used more broadly.
Covid-19 stands out for both the scale of its global impact and the apparent randomness of its many symptoms. Physicians have struggled to understand the disease and come up with a unified theory for how it works. Though as of yet unproven, the bradykinin hypothesis provides such a theory. And like all good hypotheses, it also provides specific, testable predictions — in this case, actual drugs that could provide relief to real patients.
The researchers are quick to point out that “the testing of any of these pharmaceutical interventions should be done in well-designed clinical trials.” As to the next step in the process, Jacobson is clear: “We have to get this message out.” His team’s finding won’t cure Covid-19. But if the treatments it points to pan out in the clinic, interventions guided by the bradykinin hypothesis could greatly reduce patients’ suffering — and potentially save lives.
NOTE: This article is pretty dense. I’m happy to answer any questions as best I can or make the appropriate referrals.
If these findings are verified, then it proves WHY athletes who make their living being the best by fractions of a percent are in danger of losing their careers and worse for those with undiagnosed CTE. Even the idea that some player with undiagnosed CTE could get COVID from a careless Titan and have his brain devastated is beyond the pale.
I agree that the Titans should be harshly dealt with up to and including going straight to ownership and letting them know that this is a forced sale level violation if they don’t take every drastic and immediate measure to get into and stay in compliance with all local, state, federal and league rules.
Wrt COVID19, the NFL needs to be the Not Fuckin-around League.
2020 has sucked enough. We don’t need losing football to be the shit cherry on the top of this giant shit sundae of a year…
Sports is the crucible of human virtue. The distillate remains are human vice.
A dummy’s guide to California 2020 ballot measures
By Eric Ting, SFGATE Updated 4:00 am PDT, Monday, September 21, 2020
You’ve seen the ads. But you’re not sure what any of these California ballot measures actually do.
Fear not! Here’s a handy, simple guide to each of the 12 propositions on the California ballot for the November general election. From affirmative action to overturning the highly controversial gig worker bill (AB-5), there are plenty of significant measures California residents will be voting on this fall. This guide is broken into three categories: 1. The big ones that interest groups are dumping millions of advertising dollars into, 2. The criminal justice ones, and 3. The rest.THE BIG ONES
Proposition 16
What it does: Allows the state and its public universities to discriminate or grant preferential treatment based on race, sex, ethnicity, or national origin in public employment, education, or contracting.
Major players for it: The University of California Board of Regents, Sens. Kamala Harris and Dianne Feinstein, and various Black Lives Matter-related advocacy groups.
Major players against it: A number of Asian American groups and Republicans in the California state Assembly.
Recent polling: 31% support, 47% oppose, 22% undecided (PPIC poll, Sept. 4-Sept 13.)
New poll finds shaky support for Proposition 16 to restore affirmative action in California (LA Times)
Proposition 16: Why some Asian Americans are on the front lines of the campaign against affirmative action (Mercury News)Proposition 15
What it does: Raises funds for schools and local governments by requiring commercial and industrial properties with more than $3 million in holdings to be taxed based on market value as opposed to purchase price. Does not impact homeowners.
Major players for it: Gov. Gavin Newsom, San Francisco Mayor London Breed, and the California Teacher’s Association.
Major players against it: California Chamber of Commerce, California Small Business Association and several taxpayers’ groups.
Recent polling: 51% support, 40% oppose, 9% undecided (PPIC poll, Sept. 4-Sept 13.)
Prop. 15 could raise billions for California, But who will pay? (NBC San Diego)
Governor’s endorsement of Proposition 15 disappoints Farm Bureau (Lassen County Times)Proposition 22
What it does: Classifies app-based drivers as independent contractors and not employees, which effectively kneecaps AB5.
Major players for it: Uber, Lyft, DoorDash and other similar services.
Major players against it: Sen. Kamala Harris, Attorney General Xavier Becerra, and several state Assembly Democrats.
Recent polling: 41% support, 26% oppose, 34% undecided (Redfield and Wilton poll, Aug. 9)
Uber and Lyft have poured millions of dollars into a November ballot measure to keep Calif. drivers paid as independent contractors (Business Insider)
Uber analyst expects California’s Prop. 22 to pass based on latest polling (Yahoo Finance)Proposition 21
What it does: Allows local governments to enact rent control on housing that was first occupied over 15 years ago.
Major players for it: Sen. Bernie Sanders, Democratic Socialists of America, Los Angeles chapter and various tenants’ groups.
Major players against it: Gov. Gavin Newsom, California Apartment Association and construction workers’ unions.
Recent polling: N/A
Bernie Sanders backs rent control, slams greedy landlords in new ‘yes on 21’ spot (Business Wire)
Opponents of rent control initiative say Prop. 21 backers violated Stolen Valor Act in ad (San Diego Union Tribune)THE CRIMINAL JUSTICE ONES
Proposition 25
What it does: Eliminates cash bail and gives judges the ability to determine whether a defendant should be released prior to a trial.
Major players for it: Gov. Gavin Newsom, several congressional Democrats and civil liberties groups.
Major players against it: Orange County Board of Supervisors and several groups affiliated with the bail bonds industry.
Recent polling: 39% support, 32% oppose, 29% undecided (UC Berkeley Institute of Government Studies poll, Sept. 13-Sept.18)
California’s cash bail system favors the rich. Would replacing it help people of color? (Fresno Bee)
Prop. 25 will replace cash bail with risk assessment, if passed (Daily Cal)Proposition 17
What it does: Restores voting rights to people with felony convictions who have been released from prison but remain on parole.
Major players for it: Sen. Kamala Harris, the ACLU of California and many state Assembly Democrats.
Major players against it: State Sen. Jim Nielsen (R-4) and the Election Integrity Project California.
Recent polling: N/A
LA County supervisors support proposition restoring voting rights to those on parole (CBS Los Angeles)
Alex Padilla: Why Prop. 17 will strengthen both voting rights and public safety (San Diego Union Tribune)Proposition 20
What it does: Adds several crimes to the list of violent felonies for which early parole is restricted. Would undo a series of reforms enacted between 2011 and 2016 aimed at reducing the state’s prison population.
Major players for it: Assemblyman Jim Cooper (D-9) and multiple law-enforcement-affiliated groups.
Major players against it: Former Gov. Jerry Brown, the ACLU of California and several criminal justice reform advocacy groups.
Recent polling: N/A
Grocery stores are pushing California to be tougher on crime (LA Times)
Opposition to Prop. 20 increases; opponents charge it’s a step backward for CA (Davis Vanguard)THE REST
Proposition 19
What it does: Allows homeowners over the age of 55, disabled or victims of a natural disaster to take existing, lower property tax rates to new homes anywhere in the state.
Major players for it: California Realtors Association, California Professional Firefighters and several local real estate groups.
Major players against it: Howard Jarvis Taxpayers Association.Recent polling: N/A
Links to learn more:
Prop. 19 debate: Funding for fighting wildfires or attack on Prop 13 tax protections? (CBS San Francisco)
Worried about fires? California ballot initiative could help you move to a new city (Sacramento Bee)Proposition 24
What it does: Expands the state’s consumer data privacy laws by creating a new state agency to enforce privacy laws, empowering consumers to order that businesses not sell their personal information, and increasing financial penalties on those who violate privacy laws.
Major players for it: Former Democratic presidential candidate Andrew Yang and several online privacy groups.
Major players against it: ACLU of California and the Consumer Federation of California.
Recent polling: N/A
Links to learn more:
Andrew Yang takes lead role in California data privacy campaign (Politico)
Prop. 24 seemingly seeks to expand internet privacy, critics say it won’t (Salinas Californian)Proposition 18
What it does: Allows 17-year-old Californians who will be 18 by the following general election to vote in primaries and special elections.
Major players for it: California Secretary of State Alex Padilla and Assembyman Kevin Mullin (D-22).
Major players against it: The Election Integrity Project California.
Recent polling: N/A
Links to learn more:
Alex Padilla: Vote yes on Prop. 18 to engage, energize and empower the next generation of voters (San Diego Union Tribune)
Thousands of 17-year-olds could vote in California primaries if initiative passes, study says (Sacramento Bee)Proposition 14
What it does: Issues $5.5 billion in general obligation bonds for the state’s stem cell research institute.
Major players for it: Californians for Stem Cell Research, Treatments & Cures and the University of California Board of Regents.
Major players against it: The Center for Genetics and Society
Recent polling: N/A
Link to learn more:
Prop. 14: There’s much, much more than meets the eye (Capitol Weekly)Proposition 23
What it does: Places several new regulations on dialysis clinics, including requiring an on-site physician, mandating increased reporting of dialysis-related infections, and not allowing clinics to close before obtaining consent from the state health department.
Major players for it: Californians for Kidney Dialysis Patient Protection
Major players against it: American Legion, California Medical Association and several veterans’ and health groups.
Link to learn more:
Prop. 23: Kidney dialysis clinic rules (Cal Matters)A Supercomputer Analyzed Covid-19 — and an Interesting New Theory Has Emerged
A closer look at the Bradykinin hypothesis[/b]Earlier this summer, the Summit supercomputer at Oak Ridge National Lab in Tennessee set about crunching data on more than 40,000 genes from 17,000 genetic samples in an effort to better understand Covid-19. Summit is the second-fastest computer in the world, but the process — which involved analyzing 2.5 billion genetic combinations — still took more than a week.
When Summit was done, researchers analyzed the results. It was, in the words of Dr. Daniel Jacobson, lead researcher and chief scientist for computational systems biology at Oak Ridge, a “eureka moment.” The computer had revealed a new theory about how Covid-19 impacts the body: the bradykinin hypothesis. The hypothesis provides a model that explains many aspects of Covid-19, including some of its most bizarre symptoms. It also suggests 10-plus potential treatments, many of which are already FDA approved. Jacobson’s group published their results in a paper in the journal eLife in early July.
According to the team’s findings, a Covid-19 infection generally begins when the virus enters the body through ACE2 receptors in the nose, (The receptors, which the virus is known to target, are abundant there.) The virus then proceeds through the body, entering cells in other places where ACE2 is also present: the intestines, kidneys, and heart. This likely accounts for at least some of the disease’s cardiac and GI symptoms.But once Covid-19 has established itself in the body, things start to get really interesting. According to Jacobson’s group, the data Summit analyzed shows that Covid-19 isn’t content to simply infect cells that already express lots of ACE2 receptors. Instead, it actively hijacks the body’s own systems, tricking it into upregulating ACE2 receptors in places where they’re usually expressed at low or medium levels, including the lungs.
In this sense, Covid-19 is like a burglar who slips in your unlocked second-floor window and starts to ransack your house. Once inside, though, they don’t just take your stuff — they also throw open all your doors and windows so their accomplices can rush in and help pillage more efficiently.
The renin–angiotensin system (RAS) controls many aspects of the circulatory system, including the body’s levels of a chemical called bradykinin, which normally helps to regulate blood pressure. According to the team’s analysis, when the virus tweaks the RAS, it causes the body’s mechanisms for regulating bradykinin to go haywire. Bradykinin receptors are resensitized, and the body also stops effectively breaking down bradykinin. (ACE normally degrades bradykinin, but when the virus downregulates it, it can’t do this as effectively.)
The end result, the researchers say, is to release a bradykinin storm — a massive, runaway buildup of bradykinin in the body. According to the bradykinin hypothesis, it’s this storm that is ultimately responsible for many of Covid-19’s deadly effects. Jacobson’s team says in their paper that “the pathology of Covid-19 is likely the result of Bradykinin Storms rather than cytokine storms,” which had been previously identified in Covid-19 patients, but that “the two may be intricately linked.” Other papers had previously identified bradykinin storms as a possible cause of Covid-19’s pathologies.
As bradykinin builds up in the body, it dramatically increases vascular permeability. In short, it makes your blood vessels leaky. This aligns with recent clinical data, which increasingly views Covid-19 primarily as a vascular disease, rather than a respiratory one. But Covid-19 still has a massive effect on the lungs. As blood vessels start to leak due to a bradykinin storm, the researchers say, the lungs can fill with fluid. Immune cells also leak out into the lungs, Jacobson’s team found, causing inflammation.
And Covid-19 has another especially insidious trick. Through another pathway, the team’s data shows, it increases production of hyaluronic acid (HLA) in the lungs. HLA is often used in soaps and lotions for its ability to absorb more than 1,000 times its weight in fluid. When it combines with fluid leaking into the lungs, the results are disastrous: It forms a hydrogel, which can fill the lungs in some patients. According to Jacobson, once this happens, “it’s like trying to breathe through Jell-O.”
This may explain why ventilators have proven less effective in treating advanced Covid-19 than doctors originally expected, based on experiences with other viruses. “It reaches a point where regardless of how much oxygen you pump in, it doesn’t matter, because the alveoli in the lungs are filled with this hydrogel,” Jacobson says. “The lungs become like a water balloon.” Patients can suffocate even while receiving full breathing support.
The bradykinin hypothesis also extends to many of Covid-19’s effects on the heart. About one in five hospitalized Covid-19 patients have damage to their hearts, even if they never had cardiac issues before. Some of this is likely due to the virus infecting the heart directly through its ACE2 receptors. But the RAS also controls aspects of cardiac contractions and blood pressure. According to the researchers, bradykinin storms could create arrhythmias and low blood pressure, which are often seen in Covid-19 patients.
The bradykinin hypothesis also accounts for Covid-19’s neurological effects, which are some of the most surprising and concerning elements of the disease. These symptoms (which include dizziness, seizures, delirium, and stroke) are present in as many as half of hospitalized Covid-19 patients. According to Jacobson and his team, MRI studies in France revealed that many Covid-19 patients have evidence of leaky blood vessels in their brains.
Bradykinin — especially at high doses — can also lead to a breakdown of the blood-brain barrier. Under normal circumstances, this barrier acts as a filter between your brain and the rest of your circulatory system. It lets in the nutrients and small molecules that the brain needs to function, while keeping out toxins and pathogens and keeping the brain’s internal environment tightly regulated.
If bradykinin storms cause the blood-brain barrier to break down, this could allow harmful cells and compounds into the brain, leading to inflammation, potential brain damage, and many of the neurological symptoms Covid-19 patients experience. Jacobson told me, “It is a reasonable hypothesis that many of the neurological symptoms in Covid-19 could be due to an excess of bradykinin. It has been reported that bradykinin would indeed be likely to increase the permeability of the blood-brain barrier. In addition, similar neurological symptoms have been observed in other diseases that result from an excess of bradykinin.”
Increased bradykinin levels could also account for other common Covid-19 symptoms. ACE inhibitors — a class of drugs used to treat high blood pressure — have a similar effect on the RAS system as Covid-19, increasing bradykinin levels. In fact, Jacobson and his team note in their paper that “the virus… acts pharmacologically as an ACE inhibitor” — almost directly mirroring the actions of these drugs.By acting like a natural ACE inhibitor, Covid-19 may be causing the same effects that hypertensive patients sometimes get when they take blood pressure–lowering drugs. ACE inhibitors are known to cause a dry cough and fatigue, two textbook symptoms of Covid-19. And they can potentially increase blood potassium levels, which has also been observed in Covid-19 patients. The similarities between ACE inhibitor side effects and Covid-19 symptoms strengthen the bradykinin hypothesis, the researchers say.
ACE inhibitors are also known to cause a loss of taste and smell. Jacobson stresses, though, that this symptom is more likely due to the virus “affecting the cells surrounding olfactory nerve cells” than the direct effects of bradykinin.
Though still an emerging theory, the bradykinin hypothesis explains several other of Covid-19’s seemingly bizarre symptoms. Jacobson and his team speculate that leaky vasculature caused by bradykinin storms could be responsible for “Covid toes,” a condition involving swollen, bruised toes that some Covid-19 patients experience. Bradykinin can also mess with the thyroid gland, which could produce the thyroid symptoms recently observed in some patients.
The bradykinin hypothesis could also explain some of the broader demographic patterns of the disease’s spread. The researchers note that some aspects of the RAS system are sex-linked, with proteins for several receptors (such as one called TMSB4X) located on the X chromosome. This means that “women… would have twice the levels of this protein than men,” a result borne out by the researchers’ data. In their paper, Jacobson’s team concludes that this “could explain the lower incidence of Covid-19 induced mortality in women.” A genetic quirk of the RAS could be giving women extra protection against the disease.
The bradykinin hypothesis provides a model that “contributes to a better understanding of Covid-19” and “adds novelty to the existing literature,” according to scientists Frank van de Veerdonk, Jos WM van der Meer, and Roger Little, who peer-reviewed the team’s paper. It predicts nearly all the disease’s symptoms, even ones (like bruises on the toes) that at first appear random, and further suggests new treatments for the disease.
As Jacobson and team point out, several drugs target aspects of the RAS and are already FDA approved to treat other conditions. They could arguably be applied to treating Covid-19 as well. Several, like danazol, stanozolol, and ecallantide, reduce bradykinin production and could potentially stop a deadly bradykinin storm. Others, like icatibant, reduce bradykinin signaling and could blunt its effects once it’s already in the body.
Interestingly, Jacobson’s team also suggests vitamin D as a potentially useful Covid-19 drug. The vitamin is involved in the RAS system and could prove helpful by reducing levels of another compound, known as REN. Again, this could stop potentially deadly bradykinin storms from forming. The researchers note that vitamin D has already been shown to help those with Covid-19. The vitamin is readily available over the counter, and around 20% of the population is deficient. If indeed the vitamin proves effective at reducing the severity of bradykinin storms, it could be an easy, relatively safe way to reduce the severity of the virus.
Other compounds could treat symptoms associated with bradykinin storms. Hymecromone, for example, could reduce hyaluronic acid levels, potentially stopping deadly hydrogels from forming in the lungs. And timbetasin could mimic the mechanism that the researchers believe protects women from more severe Covid-19 infections. All of these potential treatments are speculative, of course, and would need to be studied in a rigorous, controlled environment before their effectiveness could be determined and they could be used more broadly.
Covid-19 stands out for both the scale of its global impact and the apparent randomness of its many symptoms. Physicians have struggled to understand the disease and come up with a unified theory for how it works. Though as of yet unproven, the bradykinin hypothesis provides such a theory. And like all good hypotheses, it also provides specific, testable predictions — in this case, actual drugs that could provide relief to real patients.
The researchers are quick to point out that “the testing of any of these pharmaceutical interventions should be done in well-designed clinical trials.” As to the next step in the process, Jacobson is clear: “We have to get this message out.” His team’s finding won’t cure Covid-19. But if the treatments it points to pan out in the clinic, interventions guided by the bradykinin hypothesis could greatly reduce patients’ suffering — and potentially save lives.Topic: McVay … 8/9 … transcript
Rams Head Coach Sean McVay – August 9, 2020
(Opening remarks)
“We had a really good first week, guys have done a great job. Since we’ve spoken last, have placed (DL) A’Shawn Robinson on the NFI (Non-Football Injury List) and really it was a condition that he had. He’s doing really well, he’s going to be able to partake in meetings, get treatments, be around his teammates and then we’ll look forward to being able to get him back at some point this season. When that is – don’t know specifically. I think a lot of positives came out of this, we we’re able to identify something and most importantly, look out for the players best interest, but he’s going to be around and I know that he’ll be excited about when he can return to action. But in the meantime, he’ll take part in meetings and all those good things. I have (OLB) Terrell Lewis back in the building today. I’m looking forward to him getting back into a routine and a rhythm, and if he stays asymptomatic with the next few days, he will be able to return back to everything football related in three days. So, that’s a good thing.”(On any A’Shawn Robinson’s timeline to return and if it will be this season)
“No, when you place them on the NFI, you’re restricted in terms of the length and longevity that he has to remain off of that. That was what we felt like was the best decision – No. 1 for him and for us. It was a situation where (Vice President, Football and Business Administration) Tony Pastoors and A’Shawn (Robinson’s) agent were able to work something out that was, I think, favorable to both parties – both A’Shawn and our club and that’s a good thing.”(On the most optimistic return for Robinson)
“I don’t want to place any specifics on it, just because we’ve still have some time to be able to work through that and it was such a recent decision. I think most importantly, he’s in a great place. He’s looking forward to just getting around the guys and partaking in the meetings and in the above-the-neck information that he can do and then we’ll be excited about when he can return to the physical part of it as well.”(On if Lewis is still on the Reserve/ COVID-19 list)
“Basically, the way that this works, and this is something that is a flexible thing as you guys have seen. Some of the protocols have changed, even since the last week. Where we’re at with him, is that he’s back in the building. If he remains asymptomatic for the next three days with all things that he will be doing, then he’ll be able to return back to full action and be in good shape.”(On how he will utilize WR Van Jefferson in his offense)
“He’s a really impressive guy. I’ve really been impressed with his maturity just in the week that we’ve been around one another in person. He’s wired the right way, really like his attention to detail in the meetings. And then when you see the guys ready to go out in their strength and conditioning phase of this part of the training camp acclimation period, you can see all the things that we loved so much about him at Florida even going back to some of the stuff that he did at Ole Miss. He is a guy that’s wired to separate, he’s got great body control. You can see his football pedigree. A guy that’s been around the game his entire life with his dad being a coach and then being a baller as a receiver for a long time in the NFL. He just has a natural feel for how to work edges on people, double people up, got good aggressive hands. So, he’s got all those traits and characteristics that you’re looking for. As far as what his role will be, I think that’s really up to the way he continues to compete throughout training camp. We’ve got some guys that will be a great example of epitomizing how you handle yourself in that receiver room. When you look at (WR Robert) Woods, (WR Cooper) Kupp and (WR) Josh Reynolds, and guys that have been in this system for the last three years, with them going into their fourth year and I think he’s done a great job absorbing the information from them and from (Wide Receiver coach) Coach (Eric) Yarber and from (Assistant Wide Receivers Coach) Zac Robinson.”(On how he classifies A’Shawn Robinson’s injury)
This is just being precautionary with some things that we discovered. He was able really communicate clearly to us, so it was something that recently came about. It’s really not anything that’s too concerning, it’s more just really glad that we were able to get a hold of it early on. I’ve really been pleased with the way that its been handled over the last couple of days. But it was something that kind of surprised us. This wasn’t something that we expected, but based on the on-boarding physical process and all that it entailed we were able to come to some conclusions and learn some things that made this decision come about.”(On conducting meetings outside under the big tent)
“Yeah, that’s pretty much where everything goes on. A lot of that is due to the things that we’ve learned as far as risk-mitigation. You know, we’ve got a lot of space. That tent is huge, as you can see. We’re cycling guys in and out. We make sure that we have enough time in between transitional meetings to get the cleaning crew and the sanitation (crew) in there. You can social distance, guys can wear their mask and just the airflow in general. You see this building that we’re in, it can be really congested and we want to try and avoid that at all costs. We’ve fortunately had the luxury of being in a great climate, it’s got a nice cool breeze throughout the course of the day. It’s really been a great thing for us this last week and couldn’t have anticipated it going any better thus far. Our indoor facility is basically non-existent, if that’s really what you’re asking. But hey, you know what? All we need is our film and a field.”(On how deep the team scouted RB Cam Akers)
“He was the top high school recruit as a quarterback coming out. So, his stats are, when you look at them, it’s almost like a ‘Madden’ stat-line when you see the stuff he was doing in high school. We knew about it. I know our personnel staff did a great job of vetting him and going real deep in terms of the background with (Southeastern Area Scout) Michael Pierce and all of those guys. Then when you really start to study him, it shows up, and then they use him. I mean, there are some trick plays where he’s catching a swing pass to his left and flipping his hips and making 50-yard throws down the field. He did some impressive stuff. You never know, we might have a wildcat package coming to a theater near you.”(On the rapport of WR Robert Woods and WR Cooper Kupp)
“I think it’s vital. We want to make sure that we’re making the defense defend all five eligible (receivers) on every play. We have to be mindful from as a self-scout of getting different guys involved, but understanding that (WR) Robert (Woods) and (WR) Cooper (Kupp) are going to be big parts of our offense. You want to get them their touches. But when you talk about selfless receivers, I’ve just appreciated working with these guys over the last couple of years so much. I think that’s a great reflection of them as human beings, but also (Wide Receivers Coach) Eric Yarber leading that room. I think they also understand, (being) they are such smart football players, that they know if our offense is hitting on all cylinders, they’ll find a way to get their touches as well. I think it’s been reflected in the last couple of years. They just need to continue to grow together. Watching those two and their communication amongst one another or with (QB) Jared (Goff), it’s really impressive. In some instances, it’s good as a coach where you can just step back and let them take that autonomy and ownership, because it’s certainly earned. I know I’ve learned a lot from them as well, just listening to the way they approach the game. You just watch them and that’s what it looks like to do right.”(On the anticipation level to start the next phase of training camp)
“I think with probably the coaches, we’re sitting there and we can do any coaching. (The players) are able to get a bunch of strength and conditioning work. Get their field work. Get out there in the walk-thru and that’s really the only time we can get out there on the field with them. So, I think the guys have done a great job. One of the things we’ve talked about is just being totally present. Being completely present mentally and physically, and that’s what they’ve done. I think that’s enabled us to really maximize each day. We’ve got eight days in this acclimation period, today represents the sixth day. So, we’ve got three more days in this schedule format, if you will. Then we’ll get into the ‘Ramp Up’ phase. What we’ve really just had guys focus on is maximizing the moment, capitalize on things we can do today. I’ve really been pleased that the way our players have handled that, but we’re certainly excited about when that time will come to be able to practice and do some of these things in a full speed setting once you get to Day 3 of the ‘Ramp Up Phase.’”(On thoughts about the ‘iron sharpens iron’ relationship between WRs Cooper Kupp and Robert Woods)
“Yeah. I think you (KABC-TV Reporter Curt Sandoval) just said it. I think it’s two guys that are incredible football players, that are incredible people. They have such an appreciation for one another. Their friendship enables them to really push one another in a positive way. I mean they’re pushing each other, don’t get me wrong, but it’s a nice competitiveness, where they are really sharpening one another, as you said. It’s a joy to be around those guys. I think it also takes great security on both their parts to be that way. I mean, they’re truly secure men in themselves. They’re really genuinely happy for one another and especially at that receiver position, where there’s only so many touches to go around, sometimes somebody else’s success means somebody else isn’t getting the most touches and I’ve never felt anything but real, genuine, happiness for one another. I think their success has been reflective of that, because they’ve both equally been extremely productive for us and I think that’s been a huge part of the success of the Rams’ offense each of the last few years, both those two.”(On if he thought of a contingency plan if he tested positive for COVID-19 or needed to quarantine)
“Well first of all, why would you bring such a scenario up? That sound’s awful (laughs). No, it really is. It is absolutely something we’ve talked about. And you know, the natural kind of trajectory with the offense and the defense, because you have more numbers, where we’ve really had to be intentional, God forbid, if (Special Teams Coordinator) Coach (John) Bonamego or (Assistant Special Teams Coach) Tory Woodbury ended up getting sick, because you only have two guys allocated to your special teams. So, we’ve kind of had some guys that are allocated to each phase. You know you look at (Offensive Coordinator) Kevin O’Connell and (Assistant Quarterbacks Coach) Liam Coen, that are working closely with the quarterbacks, making sure those two are never too close to one another. So, it is a very real thing, but I think the most important thing is, for us, to make sure that in the building, out of the building, we’re making sure that our actions are in alignment to risk mitigate as much as possible. Certain things come up, but those are scenarios. Now, what are the parameters around if that does come up? What can you do? I think we’ll try to make sure that we avoid it, but if it does come up, I would certainly like to stay engaged in any way possible, but I’m not going down that negative route right now. But if we had to get on this Zoom and I’m yelling through an iPhone and somebody is holding it up, you know, maybe that’ll happen. We’ve learned a lot more about technology these last couple months then I think we would of ever learned otherwise. So, I think we’d have to demonstrate some agility. No doubt about it.”(On feedback from the strength and conditioning coaches during the acclimation period)
“Our guys have come in great shape. I think, really, (Head Strength Coach) Justin Lovett, (Vice President, Sports Medicine and Performance) Reggie (Scott), (Director, Sports Science) Tyler (Williams), (Assistant Director, Strength and Conditioning) Dustin Woods, and Nando (Assistant Strength and Conditioning Fernando Noriega), I mean so many of those guys have done a great job. We’ve really pushed those guys in the weight room. I know guys are good sore right now. So, they’ve been working, they’re getting great work on the field, that are in a lot of instances, some football related drills that are just in the absence of coaches. So, been getting a lot of good, positive feedback, I’ve really been impressed with the way that our players have handled the above-the-neck information when we’ve gone out and done walk-thrus. Really, it’s been a really good thing. I think these first five days and today, we’re in the middle of our sixth day, it’s been a great start and I want to keep it rolling.”(On if Akers is the emergency QB)
“It’s been Cooper Kupp in the past, but watching Cam whip it around and some of the things he can do, I think we’ll let those guys duke it out if the worst-case scenario comes up. But he certainly is very capable and he hasn’t been shy about telling me he can still spin it either (laughs).”(On COVID protocols and if they are becoming second nature)
“I think you want to continue to remind them and really, for me too. I mentioned to the players this morning, ‘Hey, let’s not forget,’ because you get into an atmosphere where you get a little bit comfortable, things have gone well and then you tend to say, ‘Okay, in situations where we need to make sure our mask is on, we’re socially distanced, it kind of just falls by the wayside if you’re not mindful of it,’ but I think a lot of the normal, daily rhythm things – filling out our questionnaire, daily COVID testing, all that stuff, that has become a little bit more normalized. I think the key message for us, and it’s as much for everybody that’s involved, it’s not just our players, it’s myself, it’s all of our coaches, our staff, is just continuing to not lose sight. As well as things have gone for us through this point to not lose side of the things that have enabled it to go smoothly with all the things that we’ve kind of been educated on – the social distancing, wearing the mask, washing your hands, all of that stuff and what that entails. Then when you set out onto the field, as long as everybody’s doing everything they can to protect this ecosystem, then you can focus on playing football and you certainly don’t want to minimize the seriousness of what this virus is, but I do think as long as you’re doing all of the right things to put yourself in a position to be keeping that ecosystem clear, if you will, then guys can go out and play with a quieted mind and focus on being the best football players that they can possibly be and not worry too much about some of the things that can be a distraction if you’re not careful and you have to acknowledge that.”(On if there is anything that he could learn from the slow build up to the season and implement into next season)
“We’ve been able to be a little bit more patient based on the parameters, but then also not having preseason games. That would definitely dictate and determine a different approach if that was the case. It’s been really good because I think for the players when you talk about how to onboard them the right way physically and mentally, this has been a great trajectory up to this point, where you can really get a lot of mental reps, you can slow things down. You’re not rushing to get the amount of volume that you typically would need to get ready for a first preseason game. I go back to last year for us, that was planning practice against the Raiders or a practice against the Chargers, where you want to be able to do a bunch of different situations and you want to have enough volume to be able to have guys go compete and do well in those settings. I think this has been something that we definitely have enjoyed, but a lot of the times the parameters will dictate our availability or ability really in general to be able to do it this way. I think it’s been a really good smooth process and something that we’ve definitely enjoyed, and I think the players would share the same feelings.”(On the importance of retaining DL Michael Brockers with Robinson on the NFI)
“Thank the Lord. I am so thankful that we got him back in general. In a lot of instances, when you look at it, before we knew we were going to be fortunate enough to get (DL) Michael (Brockers) back, we really liked A’Shawn Robinson but he was kind of the vision before we got Michael back on board that he was going to be able to try to hopefully fill some of those voids left by Brockers. To be able to still have him is huge and it’s not just his production on the field either. I think you guys, from being around each of the last couple of years, watching his growth as a leader and the way guys follow him, the way he goes about his business and everything that the day encompasses, he’s a real joy to be around and I’m very thankful to have Michael back without a doubt.”(On if Robinson requires a procedure or is in recovery mode)
“He’s in recovery mode. It’s not going to be anything like that, so that’s a good positive thing there.”(On if the team will withhold payment from Robinson)
“No. That’s not something that we want to be able to do. We wanted to be able to get something worked out where it was good for him, it was good for us and I think that was what it ended up being. Finding out some of that information, we wanted to make sure – No. 1 the concern is with the player, making sure he feels comfortable about it and I think like I mentioned earlier, it’s a great representation of the collaboration between Tony and A’Shawn’s agent to be able to get this worked out and I think A’Shawn feels good about it with all the circumstances as well so we are excited about that.”(On if OL Andrew Whitworth and OL Brian Allen were impacted or restricted in any way from having COVID-19 in the offseason)
“They aren’t. They aren’t having anything that’s holding them back. They’re in good shape. (OL Andrew) Whitworth is 38 going on 30. He looks good. This guy’s unbelievable. I still can’t believe he’s playing tackle with all these snaps he’s taken. Another one of those guys you feel fortunate to be around.”
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A New York Times investigation found that surviving the coronavirus in New York had a lot to do with which hospital a person went to.
Our investigative reporter Brian M. Rosenthal pulls back the curtain on inequality and the pandemic in the city.
podcast: https://itunes.apple.com/us/podcast/the-daily/id1200361736?mt=2
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Reading:
At the peak of New York’s pandemic, patients at some community hospitals were three times more likely to die than were patients at medical centers in the wealthiest parts of the city. Read here: https://www.nytimes.com/2020/07/01/nyregion/Coronavirus-hospitals.html
The story of a $52 million temporary care facility in New York illustrates the missteps made at every level of government in the race to create more hospital capacity. Read here: https://www.nytimes.com/2020/07/21/nyregion/coronavirus-hospital-usta-queens.html



