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AP Top Stories September 17

Here's the latest for Thursday September 17th: More flooding possible for Gulf Coast after hurricane; Trump contradicts CDC chief on vaccine; India passes 5.1 million coronavirus cases; California Observatory saved from wildfire.        
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Read full article on: usatoday.com
Navalny says he can walk and recognize people as he eyes 'clear road' to recovery from poisoning
Russian opposition politician Alexey Navalny says he is still unable to use his phone properly or pour himself a glass of water, but is on a "clear road" towards recovering from his near-fatal poisoning.
edition.cnn.com
One big reason why Biden is ahead: Seniors
Democratic presidential nominee Joe Biden's campaign is turning tradition on his head.
edition.cnn.com
Homes destroyed after winds push California fire into desert
A California fire reached a Mojave Desert community.
foxnews.com
How to delete yourself from people search sites
Face it: What you do online isn’t private. Even if you’re browsing in good ol’ incognito mode, you’re still not anonymous. 
foxnews.com
Washington’s Week 2 Preview: Defending Kyler Murray and tempering expectations on offense
As an encore to its thrilling Week 1 win, Washington faces a steep task against Arizona quarterback Kyler Murray.
washingtonpost.com
Ginsburg's Death Is A Major Cultural Moment That's About To Upend Politics Again
Senate Majority Leader Mitch McConnell is vowing a vote for a potential Trump nominee will take place on the Senate floor despite McConnell not even holding a hearing for Obama's 2016 nominee.
npr.org
Nation's Largest Business Lobby Backs Vulnerable Democrats For Reelection
The U.S. Chamber of Commerce has endorsed 30 House Democrats for reelection, the highest number of Democrats to earn the business lobby's support in at least a decade.
npr.org
Rep. Brian Mast: It's the 10th anniversary of my 'Alive Day' – here's what I know now
Ten years ago today, while serving in the Army in Afghanistan, I tried to disarm one bomb too many...
foxnews.com
11 people are arrested after a demonstration outside a federal building in Portland
Police arrested 11 people in Portland, Oregon, after a demonstration outside a federal building Friday night, authorities said
edition.cnn.com
Op-Ed: It was just a lovely morning walk with the dog — until the attack
The pit bulls' mission was not simply to knock me over. They'd come to kill my dog and were still determined to do so.
latimes.com
Happy birthday, Jimmy Fallon! The 'Tonight Show' through the years
Happy birthday, Jimmy Fallon! The TV host turns 46 on Sept. 19, 2020. To celebrate, we've rounded up photos of "The Tonight Show"'s best moments.       
usatoday.com
Bombing in Bulgaria: Turning the Tide on Hezbollah | Opinion
Justice can't be fully served unless Hezbollah, which masterminded the 2012 bombing that killed six and injured dozens more, is held accountable by Bulgaria, the European Union and the global community.
newsweek.com
What does justice for Breonna Taylor actually look like?
For this week, we think about what justice might look like in the Breonna Taylor case, discuss great performances by the music icons Patti LaBelle and Gladys Knight, and revisit the horrifying history of forced sterilizations. Plus, recommendations: Esquire's profile of Michael Kenneth Williams and Hulu's "High Fidelity."
edition.cnn.com
Aaron Judge, Giancarlo Stanton back together in Yankees’ lineup
BOSTON — For the first time since Aug. 8, the Yankees had both Aaron Judge and Giancarlo Stanton in the lineup together, with both sluggers having recovered from leg injuries. With lefty Martin Perez on the mound, manager Aaron Boone opted to put Judge in his customary No. 2 spot, with Stanton right behind him,...
nypost.com
LeBron James questions awards voters after finishing second for MVP. ‘16 out of 101!’
LeBron James questioned whether "narrative" plays an outsized role in the NBA awards voting process after he finished second to Giannis Antetokounmpo for MVP.
washingtonpost.com
Gareth Bale looks for a fresh start as golden stay in Madrid turns sour
Since Gareth Bale joined Real Madrid for a then world record fee in 2013, only Cristiano Ronaldo and Karim Benzema have scored more goals for Los Blancos.
edition.cnn.com
Phil Mickelson looks to take ‘stress’ out of game after US Open flameout
Phil Mickelson came to this U.S. Open with a score to settle at Winged Foot, where he famously lost in 2006 with a double bogey on the 72nd hole. He failed to find redemption, quietly missing the cut on Friday. One day after opening the tournament with a 9-over 79, Mickelson shot a 4-over 74...
nypost.com
Trump’s Disrespect Endangers the Troops
If Donald Trump had been on the battlefield with me in Iraq back in November 2004, I doubt I ever would’ve made it home.In the Army, part of our soldier’s creed involves never leaving a fallen comrade behind. The only reason I am alive today is that, after a rocket-propelled grenade exploded in the Black Hawk helicopter I was co-piloting, my buddies embodied that creed. They thought I was dead but still risked their own safety to bring my body back home to my family. Only when they got me to a rescue aircraft did they realize that I was still breathing. Then they ignored their own injuries, refusing care until the medic tended to me first.[Read: ‘The military has seen the writing on the wall’]My crewmates were heroes that afternoon. Yet apparently, in Trump’s eyes, each of us in that aircraft must have been a “loser” because our helicopter got shot down by the enemy. Had we been killed, he very well might call us “suckers,” too. After all, those are the terms that, according to The Atlantic’s reporting, the commander in chief has used to describe members of the armed forces who have been killed, captured, or shot down in battle. He also told his staff that “nobody wants to see” wounded warriors like me who lost limbs fighting to keep other Americans safe.Trump might not like seeing visible proof of my injuries, but I couldn’t care less. To me, the wounds and wheelchairs of those who have worn our nation’s uniform should be considered badges of honor. I’m able to serve in the Senate today because the ethos of the United States military is the exact opposite of the craven, me-first mentality that he has shown every hour of every day of his gold-plated, privileged life.Senator Tammy Duckworth speaking with Senator Sherrod Brown in August, 2020. (Bill Clark/CQ-Roll Call, Inc via Getty)From all he’s said, from all he’s done, it’s impossible for me to believe that, like my crewmates, Trump would have risked his own life to save mine or that of any other American in that dusty field in 2004. But Trump never would have been in Iraq with us that day, because he fundamentally cannot fathom the notion of sacrificing for your nation. He can’t comprehend the true meaning of courage or the idea of fighting for something greater than himself, his bank account, or his poll numbers. The Atlantic’s story is only more evidence that he isn’t able to grasp what the military is all about. He doesn’t understand service, so he doesn’t understand America’s service members: the heroes who have allowed him to sleep soundly high up in that gilded Fifth Avenue tower.When he deploys military personnel and uses tear gas to clear his way for a crude photo op, when he talks loosely about “my generals” and “my military,” when he treats weapons of war as political props in a July Fourth parade, he’s using our nation’s armed services to boost his own ego. When Trump embraces a convicted war criminal rejected by those who served alongside him, he is undermining both the military justice system and the good order and discipline that undergird our military’s strength.A commander in chief who cares nothing about fundamental decency damages troop morale and, with it, troop readiness. When service members go into combat, they need to know that those to their left and their right will never leave them behind. That no matter what, their buddies will get them out, if only to bring their body home to rest at Arlington National Cemetery. If the nation’s so-called leader regards these heroes as “suckers” or “losers,” he endangers every man and woman in uniform—and our nation’s safety right along with them.The U.S. military is the mightiest in the world because American service members uphold its values, which, in the Army, are loyalty, duty, respect, selfless service, integrity, and personal courage. Trump has shown active disdain for each. If the person who is supposed to be commanding our military is unable—or unwilling—to understand the importance of that military’s values, those values will begin to break down. If the person charged with leading our troops questions the value of their service, the very few Americans who might be willing to defend the nation might begin to hesitate before enlisting, unsure whether their own crew would risk their life, as mine did, to carry their limp body back to safety. Yet in matters of both common decency and national security, Trump does not understand the damage that his attitudes can cause.Last week, I introduced a resolution honoring our troops, veterans, and Gold Star families and condemning Trump’s egregious comments. Republicans blocked it within moments, somehow deciding they’d rather protect Trump than affirm that the Senate will always respect the service members and military families who place the mission first time after time.In 1976, then-Army Chief of Staff General Frederick C. Weyand wrote that “the American Army really is a people’s Army in the sense that it belongs to the American people. … When the Army is committed the American people are committed … [The] Army is not so much an arm of the Executive Branch as it is an arm of the American people.” The same sentiment holds true for every military branch. Each one belongs to the American people and is made up of their mothers and fathers, siblings and spouses, all of whom have dedicated their lives to serving the nation they love on behalf of the people they love. It is my sincere hope—and my sincere belief—that other Americans understand the nature of troops’ sacrifice far better than the president does.[Timothy Kudo: Our complacent commander in chief ]The latest revelations have only strengthened my own resolve to keep honoring the heroes who saved me. I will take advantage of my second chance—using every extra moment I have, every extra breath I get to breathe—to look out for our current and former troops.When Trump mocks our service members, he’s also mocking every American in every part of this country. When he derides wounded warriors, he’s letting his own personal insecurities endanger our national security. When he makes fun of those who have fallen in battle, he’s just showing that the word sacrifice is so foreign to him, it might as well be in another language—and that service will never mean anything to him other than someone else serving him. This man is not fit to be commander in chief for another four minutes, let alone another four years.
theatlantic.com
Albert Pujols belts 661st homer to pass Willie Mays on all-time list
ANAHEIM, Calif. — Albert Pujols needed nearly five weeks to tie Willie Mays for fifth place on the career home run list. It took only five days for the Los Angeles Angels slugger to pass him. Pujols hit No. 661 in the fifth inning on Friday night against the Texas Rangers to break the tie...
nypost.com
Brodie Van Wagenen: Michael Conforto playing at ‘MVP-type’ level
Michael Conforto has performed this summer at what Brodie Van Wagenen dubbed Friday an “MVP-type” level. Eligible for free agency following the 2021 season, has Conforto established himself as someone the Mets would be interested in locking up before he hits the open market? “As a guy that was homegrown, he’s somebody that we’ve looked...
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nypost.com
Obsessed with 'Cheap Old Houses'? So are 1.3 million Instagram followers
Couple's love for old houses that need some TLC has touched a chord; their Instagram following is growing by 25K a week.       
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usatoday.com
New York City Delays School Reopening; Campus Lockdowns Grow
Our roundup of education stories looks at the turmoil following Mayor Bill de Blasio's latest delay announcement; and the continuing struggles on campus to control COVID outbreaks.
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npr.org
Wait, it's September and you still haven't received your tax refund? Here's why
Some who filed paper tax returns in February and March continued to wait for their federal income tax refunds in September after COVID-19 delays.       
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usatoday.com
Why So Many Readers Are Turning to Octavia Butler’s Apocalypse Fiction Right Now
It’s unlike anything else in the genre.
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slate.com
My New York City Kids Are Getting an Education in Failed Leadership
For weeks now, I’ve been the unpopular parent on the playground predicting with certainty for anyone who cared to listen that our children would not enter a public-school building in New York City this year. And sadly, I may be proved right. For the second time this month, Mayor Bill de Blasio has delayed the start of in-person school, largely because of a staffing shortage.New York City has done what seemed impossible in April: It flattened the coronavirus curve and now boasts a positive-test rate of about 1 percent. In theory, the low case-positivity rate might have meant that public-school principals and teachers would feel comfortable opening up this fall. Many do not, however, and the mayor has utterly failed to overcome the problem.[Katie Moylan and David Schepard: Teachers know schools aren’t safe to reopen]He could have spent the summer months convincing the stakeholders that staggered schedules—with some kids learning at home each day—smaller classes, and improvements to air-circulation systems, along with commonsense precautions such as masks and frequent hand-washing, would be sufficient for an on-time start. He could then have worked with the Department of Education to make sure that these precautions were in place and that teachers knew what to expect.Alternatively, he could have decided weeks, if not months ago to start the school year completely remote and announced that the city would gradually move toward in-person learning if conditions allowed for it.But the mayor chose neither of those paths. He set deadlines that he refused to put in the work to meet, sowing chaos and ongoing frustration for families and teachers alike. How on Earth did he not foresee a staffing shortage? De Blasio has failed our kids and is teaching them a lesson about political leadership that I hope they never forget.Our children have endured six months of hardship and fear and Zoom calls and canceled plans, and far too many have lost loved ones to this virus. The start of school, though, was a bright spot on the horizon for my family and so many others.But even as I told my children that September 10 (the first first day of school) was right around the corner, I tried to manage expectations. As many New Yorkers have discovered since the start of the pandemic, our mayor has not demonstrated the ability to manage large-scale operations or the energy to get things done. To put it bluntly, de Blasio doesn’t know how to lead New York City. Even worse, he doesn’t seem to care. At his news conference on Thursday, he did not apologize for the delay and asserted, oddly and insensitively, that because most public-school parents are low-income and live outside of Manhattan, they “understand the realities of life” and are “not shocked when something this difficult has to be adjusted from time to time.”Until last year, I was a political reporter at NY1, a local TV news station. I’ve known de Blasio since I first moved to New York in 2007 and he was a Brooklyn city councilman. I covered his long-shot campaign for City Hall in 2013 when he shocked the political establishment, coming from far behind in a crowded Democratic primary to win the general election easily.[Alexander Nazaryan: The mayor who can’t rise to the occasion]It didn’t seem obvious to me in the early years of his administration that we’d end up where we are today. In fact, the mayor’s initial focus was on helping parents and children, as he came into office with one big ambitious idea that he immediately executed: creating universal public prekindergarten across the city. The program was widely considered a great achievement; for my family and so many others, it meant children could get an early start on their education and parents could save money they would have otherwise spent on child care. It was one of the few local programs that I felt very tangibly made my life easier as a working parent raising children in the city.Yet de Blasio largely lost steam after he got pre-K done. And then he got distracted. He’d get driven most mornings from Gracie Mansion on the Upper East Side to his old gym in Park Slope, Brooklyn, where he’d have a leisurely workout before heading into City Hall at 10:30 or later. He decided he wanted to run for president last year and set off for South Carolina and New Hampshire and Nevada, often drawing only a handful of curious Democrats to his events, giving them his time and full attention—a striking contrast to how he dealt with constituents back home. At one point, two public-housing residents flew to Iowa to confront the mayor outside a campaign stop in Sioux City. They knew the best way to reach the mayor of New York was to go to Iowa.In the early days of the pandemic, he dithered over tough but critical decisions such as whether to shut down the school system. He gave terrible and potentially fatal advice, encouraging New Yorkers in mid-March to get one last drink at their neighborhood bar before they closed their doors. He even squeezed in a farewell trip to his gym hours before it was forced to shutter to comply with a state order.During the Black Lives Matter protests in the city this summer, de Blasio, who ran for office as a police reformer, tried to look away, claiming not to have seen the viral videos of police violently clashing with protesters. When an NYPD police vehicle drove into a crowd of demonstrators—a terrifying scene that was caught on camera—he initially defended the police. Former aides and allies of the mayor denounced him. Past and present members of his own administration staged a protest outside City Hall.For now, though, New Yorkers are stuck with the guy. We have another 15-plus months with de Blasio, who isn’t term-limited out of office until the end of 2021.There could not be a more important moment for capable and inspiring leadership from City Hall. Our city has been through hell. Yet he’s proven time and again that he’s not up to the task required. As some New Yorkers pack their bags for the suburbs or upstate, he says he’s not going to “beg anyone to live” here. His refrain throughout all of this has been that “New Yorkers are resilient.” We are. But we expect our leaders to do the work that allows us to pick ourselves up and help the city recover. We can’t do it on our own.[Kevin Baker: Affluence killed New York City, not the pandemic]City Hall has had since March to prepare for the start of the school year. For weeks, the unions have been sounding alarm bells about safety concerns and staffing shortages. The mayor says that’s what compelled him to push the start of in-person learning back yet again. But the fact that there aren’t enough teachers isn’t something that happened overnight. It’s been a clear and obvious problem on the horizon for some time. The city’s independent budget office estimates the public school system will need nearly 12,000 extra teachers to adequately staff in-person and remote learning.For some reason, I’m not optimistic that’s going to happen by September 29, the third attempt at a first day of in-person school for my children. I unfortunately predict more chaos for students and teachers and principals.As I told my children, they are going to get a real education this fall. It just won’t be the usual school curriculum. Instead, they are being taught a powerful lesson about the crucial importance of voting and having a strong, effective leader at City Hall.
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theatlantic.com
Reckoning in a small town: Civil War meets civil rights in the ‘Last Capital of the Confederacy’
Economic struggles have pushed Danville, Va., to confront its history.
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washingtonpost.com
‘Love Falls on Us’ explores the intersection of African LGBT rights and American activism
Fascinating insights and personal stories make this a compelling read.
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washingtonpost.com
Fantasy football: Players to start, sit for NFL Week 2
The Post’s Drew Loftis evaluates all the relevant fantasy football news ahead of Week 2 of the 2020 NFL season. Big Weeks Diontae Johnson WR, Steelers (FD $5,800/DK $4,500) A shoulder injury has cost the Broncos top cornerback A.J. Bouye. Figure Denver will shade their coverage schemes toward stopping JuJu Smith-Schuster, and that should open...
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nypost.com
Congress' inaction could leave more Americans hungry -- especially kids
Congress remains at a standstill over passing another coronavirus rescue package, but tens of millions of people still can't afford enough food for themselves and their families six months after the pandemic began upending Americans' lives.
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edition.cnn.com
Kamala Harris Agrees with Justice Ginsburg's Wish Not to Be Replaced 'Until a New President is Installed'
Democratic vice presidential candidate Kamala Harris believes Justice Ruth Bader Ginsburg's successor should be chosen by whomever holds the presidential office next.
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newsweek.com
Matt Martin reuniting with young daughter after Islanders’ ouster
In the summer of 2018 after his second season with the Maple Leafs, Matt Martin sat down to have a conversation with his future father-in-law, Boomer Esiason. The lively WFAN radio host’s phone buzzed. It was a longtime friend of his, Brendan Shanahan, the president of the Maple Leafs. He wanted to let Esiason know...
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nypost.com
Los Angeles County sheriff hits back at leaders calling for his resignation
Los Angeles County Sheriff Alex Villanueva blasted local leaders Friday as calls intensified for him to step down in the wake of an attack on two of his deputies. 
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foxnews.com
In A Tribute To Justice Ginsburg, Obama Calls On Senate Delay Naming A Successor
In his statement, Obama said Republicans should "apply rules with consistency, and not based on what's convenient or advantageous in the moment."
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npr.org
‘Marvelous Mrs. Maisel's' Caroline Aaron on what a ‘Curb Your Enthusiasm’ guest role with Larry David is like
Aaron has more than 150 acting titles to her credit and many have come in the form of guest-appearances.
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foxnews.com
University of Alabama trustees vote to rename hall that honored 'ardent white supremacist'
It is the second renaming in two months as University of Alabama trustees conduct a campus-wide review, which some have long called for.        
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usatoday.com
Dentists warning against TikTok trend that has people grinding down teeth with nail fail
Irreparable damage can be caused in the latest TikTok trend.
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foxnews.com
Battle over the replacement of Ruth Bader Ginsburg rages as tributes to late justice pour in
Senate Majority Leader Mitch McConnell (R-Ky.) said Friday that a nominee from President Trump would get a vote in his chamber, while leading Democrats, including the party’s presidential nominee, Joe Biden, said a vote should not take place until the next president takes office.
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washingtonpost.com
'My Family Is Homeless After Hurricane Laura, Our City Has Been Devastated'
I'm a doctor in Lake Charles and I was working at a hospital in the city on the night the hurricane hit. It was the worst hurricane I've ever seen, and the destruction it caused has been catastrophic.
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newsweek.com
Biden Says U.S. Should Vote Before Ginsburg Is Replaced But Trump Set to Name Candidate
The Democratic presidential contender said Ginsburg's replacement should take place after the November election.
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newsweek.com
Rochester shooting ‘like the Vietnam War’ leaves at least 2 dead, 14 wounded: reports
A manhunt was underway early Saturday in Rochester, N.Y., after a shooting at a backyard party left at least two people dead and 14 wounded, according to reports.
2 h
foxnews.com
A London coffee shop is charging $64 for its premium brew -- just don't expect milk or sugar
Coffee connoisseurs, assemble!
3 h
edition.cnn.com
San Diego Trembles Under 4.6 Magnitude Earthquake Amid Ongoing Wildfires
An earthquake briefly struck San Diego and other communities east of Los Angeles on Friday night, but the effects were minimal.
3 h
newsweek.com
2 dead, 14 wounded in mass shooting in Rochester, New York
Police said there are no suspects in custody.
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abcnews.go.com
This theory might explain “Covid toes” and other mysteries of the disease
EMS medics with the Houston Fire Department move a patient with Covid-19 symptoms onto a stretcher before transporting him to a hospital on August 14, 2020 in Houston, Texas. | John Moore/Getty Images Bradykinin storms are the hottest new hypothesis for why Covid-19 can wreak havoc on the body. Back in March, Michigan’s Covid-19 cases exploded — leaping from zero to 3,657 in just two weeks. Detroit’s three big automakers closed factories temporarily, and the state’s largest health care system warned it was reaching capacity. In the midst of this crisis, Joseph Roche, an associate professor in the physical therapy program at Wayne State University, had an idea. From his research into muscular dystrophies, Roche understood that inflammation can do significant damage to the body. When he read that in severe Covid-19 cases, runaway inflammation was causing damage to tissues and organ failure, he dove into the data as well as older research on SARS. Initially, it appeared that the virus might cause immune cells to overproduce molecules called cytokines, causing a severe inflammatory response known as a cytokine storm. But what Roche suspected as he sifted through early case studies was that it wasn’t the immune system’s cytokines causing so much of the damage but an entirely different pathway in the circulatory system knocked off balance by the virus: bradykinin signaling. He believed that an accumulation of two peptides, des-Arg(9)-bradykinin, abbreviated to DABK, and bradykinin — both part of a system that regulates blood pressure and other functions — were starting a feedback loop of inflammation and tissue injury. By stopping this reaction, he argued in an open letter to the scientific community in April and in a May paper published in the Journal of the Federation of American Societies of Experimental Biology, doctors could prevent some of Covid-19’s worst effects. Several months later and 500 miles away, a group of researchers unaware of Roche’s work started feeding the world’s second-fastest computer data from about 17,000 genetic samples from 1,300 Covid-19 patients. The team, based at the Oak Ridge National Laboratory in Tennessee, asked the $200 million computer to look for patterns in how Covid-19 was changing genes and impacting different systems in the body. After almost a week of data crunching, the supercomputer landed on something they found surprising: bradykinins. “I was literally at home on a Sunday afternoon looking at different visualizations, and it just jumped out at me,” Daniel Jacobson, a computational systems biologist at Oak Ridge, says. He calls these haywire reactions a “bradykinin storm,” and like Roche, believes they may help researchers treat severely ill Covid-19 patients, possibly staving off damage to organ systems or even preventing deaths. Outside researchers agree: Elements of the supercomputer’s analysis have been corroborated since it was published in July, and researchers say it could help lead the way to more effective treatments. Here’s a deep dive into what has been published on bradykinin signaling since the pandemic began, and what we know about how this compound might be instigating some of the worst Covid-19 damage. ORNL and Carlos Jones The Summit supercomputer at Oak Ridge National Laboratory in Oak Ridge, Tennessee, that helped generate the “bradykinin storm” hypothesis. Why bradykinin signaling might be making Covid-19 so much worse How Covid-19 can prompt an inflammatory cascade gets complicated, but Roche and other experts now think bradykinin might be the key to the vascular changes, lung damage, and even neurological symptoms the disease can cause. The virus usually enters the body through the airways and lands on cells, where a protein called ACE2 functions as a doorway. As the virus replicates in the body, it finds other cells that have ACE2 receptors, such as those in the lungs, hearts, intestines, kidneys, and brain. “The virus not only uses ACE2 as an entryway into cells but also tells that cell’s nucleus to start reducing ACE2 expression,” Roche says. This causes an accumulation of an enzyme called DABK, which creates conditions for inflammation. This is where bradykinin might come in. When the virus binds with ACE2 receptors, DABK piles up, and bradykinin levels increase—causing an inflammatory cascade. “It creates a vicious feedback loop,” Roche says, amplifying inflammatory processes, including producing more cytokines. Scientists initially thought that Covid-19 caused the immune system to release an overwhelming flood of cytokines — as often happens in response to a viral infection. In fact, promising treatments like remdesivir lower cytokine production. But recent evidence suggests that Covid-19 patients may not have particularly elevated levels of cytokines compared to people critically ill with other respiratory conditions, and other interventions attempting to lower cytokine production failed to reduce mortality — suggesting something else is going on. That something, says Jacobson, might be a bradykinin storm instead. This hypothesis fits with a surprising number of Covid-19’s bizarre symptoms. Researchers have observed many vascular symptoms, but previously blamed cytokine storms’ inflammation or direct damage from the virus. But bradykinin can impact how your blood coagulates — possibly explaining the strange clotting problems reported in Covid-19 patients and the high percentage of Covid-19 deaths from heart attacks, strokes, and deep vein thrombosis. As the virus causes bradykinin to accumulate in the cells it has hijacked, it makes your blood vessels permeable, letting your blood leak out. This could also explain the “Covid toes,” that have been linked to blood circulation. In the lungs, increasing gaps in the cells of blood vessels can spell further damage. Lungs are covered in capillaries, so these gaps start leaking blood and immune cells into the interior surface of the lungs, potentially providing the reason for Covid-19 patients’ respiratory distress. To make things worse, according to the supercomputer analysis, the virus might also increase the natural production of hyaluronic acid—a biopolymer familiar to skincare aficionados, as it can absorb more than 1,000 times its weight in water. As bradykinin causes blood vessels to leak water into your lungs, it hits the hyaluronic acid in your lungs and forms a hydrogel. “It’s like trying to breathe through Jell-O,” Jacobson says. “At that point, unfortunately no matter how much oxygen you’re pumping through a ventilator, you can’t get a gas exchange through the hydrogel.” Bradykinin dysregulation may also be behind the thyroid problems some Covid-19 patients are reporting. Previous research has found that, in addition to influencing the circulatory system, bradykinin is an important regulator of thyroid hormones. Ilaria Muller, an endocrinologist at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, and colleagues recently found that many patients who were hospitalized had abnormally low levels of thyroid-stimulating hormones, suggesting thyrotoxicosis and at least temporary thyroid damage. She says this damage could come from direct damage from the virus through the thyroid’s ACE2 receptors or from systemic inflammation. More surprisingly, bradykinin storms also help offer an explanation for some of Covid-19’s neurological symptoms — from headaches to long-term nerve damage — which in one study afflicted 57 percent of Covid-19 patients. High levels of bradykinin in particular can cause the blood-brain barrier to break down, potentially allowing the virus into the brain and causing inflammation and damage. Finally, as Elemental reports, the theory may even explain why men seem to be more likely to have worse cases of Covid-19. Some aspects of the RAS systems have receptors on the X chromosome, meaning that women have twice the levels of these stop-gap proteins, possibly giving them extra protection against the virus. The supercomputer model also found different gene expression patterns in the lavage fluid from the lungs of COVID-19 patients. This is rare data, in part because getting that fluid can be dangerous to healthcare professionals, who may get infected while taking the samples, so this procedure is no longer carried out. A clinical trial measuring actual bradykinin levels in samples from Covid-19 patients’ lungs would provide a lot of valuable information but is unlikely to happen because of the transmission risk. When something like a virus tweaks part of the body’s intertwined systems, you often end up with rippling consequences—in this case, a dire trend toward inflammation, possibly through both bradykinin pathways and cytokine production. Essentially, the bradykinin pathway gets off the track—and then it’s like a runaway train, potentially causing damage in many locations around your body. Zac Freeland/Vox Treatment targeting bradykinin signaling wouldn’t have to be perfect to improve lung damage and long-term Covid-19 outcomes. What do bradykinin storms mean for possible Covid-19 treatments? After finding the potential role of bradykinins in severe Covid-19 in March, Roche went looking for a way to halt this inflammatory cascade. “It’s like a set of gear wheels—inflammation, injury, inflammation—and you’re trying to jam up the wheels,” he says. Along with his wife, Renuka Roche, an assistant professor in occupational therapy at Eastern Michigan University, he started to explore potential treatments that were ready to use. As clinicians trained to pay a lot of attention to recovery through rehabilitation, he says, “We know that health care does not end with just saving a person’s life.” Roche says life quality is important too, meaning any intervention that could minimize damage would be a true advancement in the fight against Covid-19’s ravages. Treatment targeting bradykinin signaling wouldn’t have to be perfect to improve lung damage and long-term outcomes. “If you’re able to even dampen the cycle by 50 percent, that means that much tissue may be spared,” Roche says. In the medical literature, the Roches found a medication called icatibant that is both known to be safe and inhibits bradykinin signaling. It was already approved by the FDA, with the added benefit of an expired patent, meaning generic versions could be made much more affordably. They reached out to the Canadian and Indian governments about starting rapid research on icatibant in late March, wrote an open letter to the scientific community in April, and published a paper on their hypothesis in May. At the same time, Frank van de Veerdonk, an infectious disease specialist at Radboud University Medical Center in the Netherlands, was reaching similar conclusions. He knew that ACE2 is an important part of the RAS, and in April, hypothesized that a dysregulated bradykinin system was causing blood vessels to leak into Covid-19 patients’ lungs. More recently, “We published data in patients with icatibant targeting bradykinin in Covid-19 as a treatment,” van de Veerdonk wrote Vox in an email. While not a controlled clinical trial, van de Veerdonk published a study where nine hospitalized patients were treated with icatibant and matched to similar Covid-19 patients who were not; the patients who’d received icatibant needed less supplemental oxygen and experienced no adverse effects from the drug. In the US, Quantum Leap Healthcare Collaborative has started a clinical trial of five potential treatments, including icatibant. (They are still currently enrolling patients.) “The safety of the drug is well understood, and it’s fast-acting,” says Paul Henderson, director of collaboration at Quantum Leap. In general, he says bradykinin receptors are interesting because they are upstream of most of the inflammatory response, including cytokines. If proven effective, he says, these treatments will probably also be useful for influenza and other diseases that cause acute respiratory distress. Henderson doesn’t discount cytokines’ inflammatory impact altogether but suggests that interventions targeting cytokines may have been “taking out too little of all the processes going on to have much impact.” Imagine how much easier it is to dam a river at its headwater than closer to its mouth—similarly, interventions further “upstream” in biological pathways could have a larger impact. In some ways, this work could be as important as finding a vaccine. “Reducing the burden on the health care system and preventing the very sickest from dying is really important,” Henderson says. Lo and behold, at the end of August, a clinical trial in Spain on vitamin D found that it significantly reduced the need for ICU treatment in Covid-19 patients. But he also cautions that, like with cancer, there is unlikely to be one “magic bullet drug.” Instead, it’s more likely a combination therapy, including anti-inflammatory medications and antivirals, will be necessary. “You’ll likely need different interventions in different stages of infection,” he says. “It is extremely complicated.” Nevertheless, since Jacobson’s paper came out, his hypotheses have been supported by other research. For example, vitamin D is known to regulate RAS, and vitamin D deficiencies have been associated with severe cases of Covid-19. This fits with a part of the supercomputer analysis that suggested the virus activates genes that break down more vitamin D. Lo and behold, at the end of August, a clinical trial in Spain on vitamin D found that it significantly reduced the need for ICU treatment in Covid-19 patients. Similarly, another analysis, run by the World Health Organization, which incorporates seven different clinical trials, found that corticosteroids, which inhibit a protein activated by the bradykinin receptor, reduced the risk of Covid-19 death — fitting the computer model’s prediction neatly. Bradykinin storms may also have implications for long-haul Covid-19 patients. Jacobson is now collaborating with Covid patient groups to gather data. “We’re looking at the top 100 symptoms and trying to map them to this mechanism,” he says, adding that several of his fellow researchers are long-haulers. He says one of the next questions they hope to address is whether bradykinin dysfunction continues even after the virus has cleared, if the virus itself is persisting in different organ systems or some combination of both. When new information raises more questions The notion of bradykinin storms are appealing because they offer a tantalizingly unified theory that would explain so many of Covid-19’s inscrutable impacts. Joshua Zimmerberg, a biophysical virologist at the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health, who was not involved in any of the bradykinin research, says the evidence is now compelling. “When you have independent confirmation, when people come to the same conclusion for different reasons—that’s very good evidence.” But he warns against raising hopes for immediate treatments. “We all crave simple pathways and simple ideas, but inflammation is really complicated. There are still a lot of inflammatory diseases without good treatments.” Dampening bradykinin production too much, or at the wrong time—for example, early in the infection, when the natural inflammation cycle is needed to fight the virus—might actually be harmful. Roche says the next steps are for large-scale randomized placebo-controlled clinical trials on potential drugs that inhibit bradykinin. “The hypothesis, [Jacobson’s] gene expression data, [van de Veerdonk’s] small-scale case series—these won’t move the needle,” he says. Data is needed to add drugs to doctors’ arsenal against the pandemic. But he’s gracious about more widespread attention only being directed toward bradykinin now, after he’s spent months trying to raise its profile. “The pandemic has exposed key weaknesses in health care itself,” he says. “We need to empower ourselves with as much knowledge as we can, so we can serve our patients and protect ourselves.” Lois Parshley is a freelance investigative journalist. Follow her Covid-19 reporting on Twitter @loisparshley.
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