An antibody (orange) bound to the surface spike protein of SARS-CoV-2 can block infection.
By Jon CohenMay. 5, 2020 , 6:10 PM
Sciences COVID-19 reporting is supported by the Pulitzer Center.
One of the first people to be diagnosed with COVID-19 in the United States hopes a legacy of her nightmarethe antibodies it left in her bloodwill lead to a drug that can help others infected with the novel coronavirus that has now killed more than 250,000 people worldwide.
Early this year, the woman had just learned of the outbreak in Wuhan, China, when she flew to Beijing to celebrate the Lunar New Year with her elderly parents and extended family. A brother from Wuhan joined the gathering on 23 January, catching one of the last flights out before the city went into lockdown. Days later, her father developed a fever, but the family wasnt concerned. My dad always has some fever in the winter, says the woman, a researcher who asked to be called Dr. X to protect her privacy.
On 28 January, her brother also developed a fever.
The next day, on her scheduled flight home, a nervous Dr. X wore a mask, brought disinfectant wipes and cleaned everything she touched, and didnt accept any food or drinks from flight attendants. I treated myself as a potential infectious source.
Her husband picked her up at the airport, wearing a mask. With the car windows rolled down, they drove to an emergency room to request a coronavirus test. I didnt have a fever, so they didnt really take me seriously, she says. But coincidentally, her brother texted as she waited to be seen: He had COVID-19. So she received a test. Days later, after she quarantined herself, developed mild COVID-19 symptoms, and then rebounded,, the result came back positive.
By then, her brother and father had both been hospitalized. The brother recovered after 12 days, but her father, a retired scientist in his 80s, went from a ventilator to extracorporeal membrane oxygenation, an artificial lung of sorts. The novel coronavirus, SARS-CoV-2, ultimately infected all seven family members who had gathered for the New Year celebration.
Dr. X could not help her sick family members, but her eagerness to do something grew. She knew that in China, plasma from recovered people, which contains antibodies to the virus, was showing promise as a treatment. Her doctor told her about a project, a collaboration between Vanderbilt University and AstraZeneca, to develop something safer and more powerful. It aims to go beyond the mishmash of antibodies in convalescent plasma and pull out the equivalent of a guided missile: an antibody that neutralizes the infectivity of SARS-CoV-2 by binding to the so-called spike protein that enables it to enter human cells. Once one or several neutralizing antibodies have been identified, antibody-producing B cells can be engineered to make them in quantity. These so-called monoclonal antibodies could treat or even prevent COVID-19.
The Vanderbilt-AstraZeneca team is far from the only group trying to identify or engineer monoclonals against SARS-CoV-2. Unlike the many repurposed drugs now being tested in COVID-19 patients, including the modestly effective remdesivir, the immune proteins specifically target this virus. Whereas some groups hope to sieve a neutralizing antibody (a neut) from the blood of a survivor like Dr. X, others are trying to produce a neut in mice by injecting them with the spike protein. Still others aim to re-engineer an existing antibody or even create one directly from DNA sequences.
Many researchers are optimistic that antibodies will, relatively quickly, prove their worth as a preventive or remedy that buys the world time until a vaccine arrivesif it does. Weve got at least 50and probably more we dont know aboutcompanies and academic labs that are all racing horses, says immunologist Erica Ollmann Saphire of the La Jolla Institute for Immunology, who leads an effort to coordinate and evaluate these candidates. Regeneron Pharmaceuticals, which developed a cocktail of three monoclonal antibodies that worked against the Ebola virusa notoriously difficult disease to treatmay be out of the gates first with a candidate monoclonal drug entering clinical trials as soon as next month.
The receptor-binding domain (top) at the tip of SARS-CoV-2s spike protein can be blockedby antibodies targeting several different areas (colors).
Saphire says many questions remain. We need a sense of the landscape: What are the most effective antibodies against this virus? If we need a cocktail of two, what is the most effective combination? she asks. And you might want a very different kind of antibody to prevent infection versus treating an established one.
John Mascola, an immunologist at the U.S. National Institute of Allergy and Infectious Diseases (NIAID), adds that antibodies may also have nonneutralizing, immune-boosting properties. The field doesnt know very much about protective immunity to SARS-CoV-2, Mascola says. So theres a little bit of scientific guesswork here.
On a practical level, monoclonals are relatively difficult to make and administer; they have to be given by intravenous drip or injected, and they have traditionally been high-cost, niche medicines available mainly in wealthy countries. Monoclonals may well have a very important role, says Jeremy Farrar, head of the Wellcome Trust charity and an infectious disease specialist. The big questions will be the capacity to manufacture at scale, distribute, and the cost.
On 7 March, Dr. X visited the Vanderbilt lab led by James Crowe to donate blood. I couldnt really help my dad, the woman says. It was too late. So I want to make sure that fewer people have to go through what my family has gone through.
Her father died 9 days later.
Although monoclonal antibodies to treat cancer and autoimmune diseases are a booming business, few for infectious diseases have come to market so far. One prevents respiratory syncytial virus in infants, two prevent and treat anthrax, and another helps HIV-infected people whom standard drugs have failed. But Regenerons monoclonal cocktail for Ebola offers an example of their power. It proved its worth in a study conducted in the Democratic Republic of the Congo (DRC) last year and could be approved by the U.S. Food and Drug Administration within 6 months. And a single monoclonal antibody developed by an NIAID team that included Mascola thwarted Ebolavirus in the same DRC study. No other treatmentsincluding drugs and convalescent plasmahad worked against Ebola.
Treating millions of people worldwide with a monoclonal isnt far-fetched, Crowe says. In the past, fully human antibodies were difficult to isolate and expensive to produce, he notes. But its getting easier and cheaper. In the next 5 years, antibodies will become the principal tool used as a medical countermeasure in the event of an epidemic, he predicts.
First, however, Crowe and others need to find potent monoclonals against SARS-CoV-2. It generally takes several weeks before an infected persons B cells begin to pump out neuts. Because of the lag. Crowes teamone of four funded by the Pentagons Defense Advanced Research Projects Agency (DARPA) to discover monoclonals for emerging infectious threatssought out the first people in the United States to have confirmed SARS-CoV-2 infections, including Dr. X. The team isolated antibody-producing B cells from their volunteers and used the spike protein, linked to a magnetic bead, as bait for the tiny percentage that produce neuts against SARS-CoV-2.
A bioreactor like this one at AstraZeneca may soon churn out antibodies against the virus that causes COVID-19.
When they initially bled Dr. X, some 6 weeks after she became infected, those special B cells were only faintly detectable. En route to the airport on a Sunday morning to fly home from Nashville, Dr. X stopped in the lab for yet another bleed, and they finally struck gold.
A second DARPA-funded group, Canadas AbCellera Biologics, uses a version of spike that Mascola and co-workers carefully engineered as neut bait. To isolate single B cells, the AbCellera group places copies of this spike in 200,000 fluid-filled chambers in a device the size of a credit card. From the blood of an early U.S. COVID-19 case in Seattle who had severe disease, AbCellera initially found 500 candidate antibodies against spike. The company whittled them down to 24 leads, selecting those that retain their shape when mass produced and stick longest to the viral protein. (Antibodies bounce on and off their targets.)
Regeneron has also bled recovered COVID-19 patients, but it is trying an alternative strategy as well: injecting spike into mice equipped with human genes for antibody production. From a pool of human- and mouse-derived antibodies, the company plans to select two that neutralize a broad range of SARS-CoV-2 variants. Regeneron is aiming for a pair of antibodies that bind to nonoverlapping sites on the spike, too, says Christos Kyratsous, vice president of research at Regeneron. This type of antibody cocktail provides an insurance policy against the emergence of mutant strains of SARS-CoV-2 that resist the treatment. Its unlikely that both sites [on spike] are going to change at the same time, Kyratsous says.
Although Regeneron designed a three-antibody cocktail for Ebola, Kyratsous says the company decided to limit its COVID-19 cocktail for both practical and strategic reasons. The more antibodies needed, the more difficult the manufacturing issues, and the higher the price. And the likely Achilles heel of the spike, a region at its tip known as the receptor-binding domain (RBD), is so small that a third antibody might be wasted. It can accommodate about two antibodies independently of each other, Kyratsous says.
AstraZeneca, in addition to screening blood from recovered patients and spike-injected mice, is sifting through a massive library of essentially random antibodies created with a method involving viruses called phages. Most groups assume that effective antibodies must target RBD. But Mark Esser, an AstraZeneca vice president, says, We have found interesting antibodies that bind to other parts of the spike protein.. Mene Pangalos, AstraZenecas executive vice president of pharmaceutical R&D, says they, too, want to make a cocktail. And it may end up being a cocktail that includes other companies antibodies.
Research groups are also searching for clues from coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome. Vir Biotechnology, for example, has found an antibody in a recovered SARS survivor from 2003 that neutralizes SARS-CoV-2. This antibody binds to a region of the RBD that is highly conserved between the two coronaviruses, its researchers report in a preprint posted online on bioRxiv on 9 April. The company went on to modify the antibody to make it more potent. One modification slows the antibody degradation to give it a longer effective life; another improves the so-called vaccinal effect, which summons T cellsanother arm of the immune systemto help destroy infected cells.
Jacob Glanville, an immunologist and computer scientist who runs Distributed Bio, has designed neuts for SARS-CoV-2 in a computer, drawing on genetic sequences and structures of ones known to thwart the SARS virus in cells and even mice. Im basically able to get a freebie ride on [past] research in a very brief period, Glanville says.
With molecular modeling software, Glanville mutated the antibodies to the SARS virus into billions of variants. And using phages as well, Glanvilles group created a still larger library of antibodies that might work. The researchers then sorted through what Glanville calls this vast mutational space for antibodies predicted to bind to SARS-CoV-2 spike, identify 50 leads they are testing in vitro. They soon hope to select the best 13 candidates.
Glanville says the aim is to find antibodies that can potently neutralize a broad range of coronaviruses. The exercise here is to approve one drug that will protect us from this current outbreak but also will enable us to have a tool at our disposal immediately when the next coronavirus outbreak takes place. That way, he says, We dont have to play this game every time.
With so many COVID-19 monoclonals being developed, How do you know what is really best and why? Saphire asks. The Coronavirus Immunotherapy Consortium she leads, funded by $1.7 million from the Bill & Melinda Gates Foundation, is organizing a large-scale, blinded, side-by-side evaluation of candidate monoclonals in test tube studies that gauge their ability to thwart SARS-CoV-2 infection of human cells. The consortium also plans to compare lead candidates in animal models, but needs funding for that costly endeavor.
A doctor in northern Italy who recovered from COVID-19 and has, like Dr. X, contributed his own plasma to AstraZenecas antibody hunt, stresses that its far from a given that monoclonals will work. We dont know the role of neutralizing antibodies in this disease, says the doctor, who asked not to be named because of his hospitals concerns about publicity. He is also personally familiar with the cost and scarcity of existing monoclonal drugs: His hospital has already had difficulty obtaining immune-calming monoclonals for COVID-19 patients who were having dangerously strong immune reactions to the virus.
An effective COVID-19 vaccine could, in the long run, do away with the global need for SARS-CoV-2 monoclonal antibodies. But Pangalos says that prospect doesnt concern his company. That would be fantastic, he says, stressing that AstraZeneca didnt start this project for strictly business reasons. Its important for one of us to solve this pandemic so that we can all get back to some semblance of normality.
A man rides his bicycle in Gurnee, Ill., this past weekend. Officials say safe practices against the coronavirus need to continue if the state is to be successful with its phased reopening plan. Nam Y. Huh/AP hide caption
A man rides his bicycle in Gurnee, Ill., this past weekend. Officials say safe practices against the coronavirus need to continue if the state is to be successful with its phased reopening plan.
Illinois Gov. J.B. Pritzker announced Tuesday his five-phase reopening plan, while the state saw its highest daily death toll from COVID-19.
Over the previous 24 hours, 176 residents died, said Illinois Public Health Director Ngozi Ezike, who joined the governor at his daily briefing. That brings the number of deaths in the state to more than 3,800.
Ezike said the situation could have been even more dire if the governor hadn't extended his stay-at-home executive order to May 29. She also credited residents paying heed to social distancing, wearing face masks and finding other, safer ways to connect with each other. But the threat continues.
"The truth is we are still in a significant war with an enemy," she said, adding that because the coronavirus can't be seen, some may underestimate it.
"If this was a traditional war with soldiers outside of our doors and people risking their lives to be outside of their homes," Ezike said, "no one would think about the need to go to work or get their dog groomed or their car washed."
Finding a way back to normalcy will take time, said Pritzker, adding that that can't happen until there's a vaccine, an effective treatment or widespread immunity.
Pritzker outlined his plan for slowly reopening the state, called "Restore Illinois." It divides the state into four regions, acknowledging that each section may have distinct needs and conditions. That means the areas could move through the five phases at different times if health data for that region show declines in coronavirus cases and hospitalizations.
Most of the state is already in the first two phases, with the initial shutdown of all but essential businesses and social distancing guidelines. Because the overall rate of infection is slowing, that has allowed Phase 2 to kick in. Some nonessential retail outlets can reopen, offering curbside pickup and delivery. Residents also are directed to wear face masks when outside.
Phase 3 will allow more outlets, including barbershops and salons, to reopen under certain capacity and safety limits, with groups of 10 people or fewer being able to meet.
As hospitalizations and cases continue to decline, Phase 4 kicks in. Schools, restaurants and day care centers can open with guidance from the state's health department and gatherings of 50 or fewer will be allowed.
Until there's a vaccine or widespread treatment though, Illinois will not reach Stage 5 a full resumption of its economy.
Pritzker said it brings him no joy, but that means no conventions, festivals or large events for now. He says he won't risk overwhelming the state's hospital system and opening the door to potentially tens of thousands more deaths.
As scientists learn more about COVID-19, the plan could also change, he said.
Foreign Secretary Dominic Raab said Tuesday that 29,427 people have died with Covid-19 since the outbreak began, more than in Italy and lower only than the United States. The official figure includes 693 new deaths in the most recent 24-hour period, up to 5 p.m. (12 p.m. ET) Monday.
International comparisons are not flawless because countries count deaths in different ways and with varying levels of accuracy.
Raab said at the daily UK government press briefing that a "real verdict on how countries have done" will not be fully available until after the pandemic is over.
But Italy and Spain -- previously considered Europe's two hardest-hit countries -- are also significantly further along in their outbreaks than the UK and are already tentatively lifting some lockdown restrictions.
The development comes just days before Johnson is due to address the country on Sunday.
Johnson is expected to announce the nation's next steps, with widespread reports in the UK media this week of how the country will ease its lockdown measures.
"It's now clear that the second phase will be different. We will need to adjust to a new normal," Raab said on Tuesday.
"We want to make sure that the next phase is more comfortable, is more sustainable," he added. "But we need to be under no illusions, the next stage won't be easy."
But even the most recent government figures only tell a partial story. More data, released earlier on Tuesday, indicated that the true number of deaths by late April far exceeded that which was reported daily by ministers.
England's Office of National Statistics (ONS) said there were 29,998 deaths in which Covid-19 was mentioned on the death certificate in the period ending on April 24, or two days later in Scotland. That includes suspected coronavirus-related deaths in all settings, including care homes.
Its figure far exceeds the death toll of 20,732 announced by the government at the same point. At the time, the government did not include patients who died from Covid-19 outside of hospitals.
The UK government last week started including data on deaths outside hospitals in cases where people had tested positive for Covid-19. Previously, the UK-wide figures were only for hospital deaths.
It did claim to reach its own target of conducting 100,000 tests a day by the end of April, but only for two days and with the help of thousands of tests that were mailed out to households but not completed. The number of tests carried out daily subsequently dropped to 84,000 on Monday and 85,000 the day before.
Good morning.
(Dont get California Today by email? Heres the sign-up.)
The coronavirus pandemic has left no industry and no global system unchanged.
The way we grow, harvest and distribute food has been thrown into particular disarray, as workers fall ill and big companies struggle to adapt to demand that has almost instantaneously shifted from restaurants and cafeterias to supermarkets.
He said that, although painful adjustments were underway, there were also silver linings in the pandemic, particularly for smaller growers like the Masumoto Family Farm, which has about 80 acres south of Fresno.
Heres our conversation, lightly edited and condensed:
How are things going?
All in all, good, in that were not in the middle of harvest. But its that cloud of uncertainty. Farmers are used to that, because of nature, but this is totally different.
Were reading the tea leaves about how consumer tastes are changing.
For example, we make organic raisins and a lot go into raisin bran. Cereal sales are going fantastic after they were declining for some time.
So after we lift the shelter in place, are people going back to skipping breakfast? How do peaches fit into this? Are peaches a luxury item or part of a new, healthy diet?
[Read more about growing peaches as the climate changes in this Opinion piece.]
Were in a good position because weve always diversified some small farmers are hurting because their main buyers were restaurants. We sell some to restaurants, but some to wholesale and direct sales.
Each of those are starting to shift. Were getting word that people may buy produce like peaches packaged in clamshells because they dont want to touch the fruit so how does packaging affect how we do things? Does that change the kind of fruit we want? Medium or big? I dont know!
This is one time where small is beautiful. When youre small you can make these shifts much more easily.
Do you supply to community-supported agriculture boxes? And is that something youre shifting toward more?
Absolutely. Our friends are small farmers who do C.S.A. boxes.
People are paying attention to food theyre paying attention to what they make, and so small-scale C.S.A.s have been booming.
We sell into some C.S.A.s, but we dont have a system set up to do our own. If we were a little closer to the Bay Area we probably would have set up something much more direct.
How do you see sustainability fitting into all these changes?
The broader question has to do with living with nature. People draw the comparison with World War II and victory gardens this is working with nature, and the key with that is knowing there are unknowns.
[Read more about the re-emergence of victory gardens.]
Do you think this will change how you actually grow the peaches?
When I got here, the huge shift was me keeping heirloom varieties we grow, as opposed to breeding for shelf life. Were very fortunate the market grew with us and we found an audience for that when the whole food revolution took over in the 1980s and 1990s.
I wonder now, is it one of those pivot moments, where were in the middle of another food revolution?
I think this whole crisis has accentuated the middlemen: the distributors, the packers, the shippers theyre the ones at the heart of all this and they have tended to be ignored.
A static example is toilet paper. There are truckers and shippers, then the local store gets their Tuesday shipment of toilet paper. No one used to pay attention to when toilet paper arrived.
The same thing is happening with the food chain. I always had a little struggle when people used the term farm to fork. It leaves out the middle thats so critical.
Another thing that were in the middle of accentuating is labor.
I was just going to ask about that.
What is the safety of farmworkers? We need sick-leave policies. But I think this could be a shift to people paying attention.
For us, we did a lot of the work ourselves and initially just had seasonal employees at pruning, trimming and harvest time. But about 10 years ago, the labor supply was getting very inconsistent and so we got one full-time employee and a few seasonal employees. At the height, were talking about only about a dozen and they tend to be the same.
[Read about how the pandemic has essentially halted migration to the U.S.]
And about five to 10 years ago, we started transitioning so the farm fits the labor. Usually in business, its the opposite. Im not faulting big agriculture for doing that, but we have efficiencies on a small scale that work to our advantage.
Are you worried right now about finding even the labor you do need?
Were definitely concerned. All these hands that feed us what happens with politics and immigration. All those factors come butting into what we do. I always think that were in Fresno, which is hundreds of miles from the border but were actually on the border because it affects us directly.
I think thats true with a lot of people in the industry and the food world.
[See every coronavirus case in California by county.]
We often link to sites that limit access for nonsubscribers. We appreciate your reading Times coverage, but we also encourage you to support local news if you can.
Jill Cowan grew up in Orange County, graduated from U.C. Berkeley and has reported all over the state, including the Bay Area, Bakersfield and Los Angeles but she always wants to see more. Follow along here or on Twitter.
California Today is edited by Julie Bloom, who grew up in Los Angeles and graduated from U.C. Berkeley.
WASHINGTON A federal scientist who says he was ousted from his job amid a dispute over an unproven coronavirus treatment pushed by President Trump said Tuesday that top administration officials repeatedly pressured him to steer millions of dollars in contracts to the clients of a well-connected consultant.
Rick Bright, who was director of the Department of Health and Human Services Biomedical Advanced Research and Development Authority until his removal in April, said in a formal whistle-blower complaint that he had been protesting cronyism and contract abuse since 2017.
Questionable contracts have gone to companies with political connections to the administration, the complaint said, including a drug company tied to a friend of Jared Kushners, President Trumps son-in-law and senior adviser. It said Dr. Bright was retaliated against by his superiors, who pushed him out because of his efforts to prioritize science and safety over political expediency.
The 89-page complaint, filed with the Office of Special Counsel, which protects federal whistle-blowers, also said Dr. Bright encountered opposition from department superiors including Health and Human Services Secretary Alex M. Azar II when he pushed as early as January for the necessary resources to develop drugs and vaccines to counter the emerging coronavirus pandemic.
The report provides a window into the inner workings of BARDA, a tiny agency created in 2006 as a response to the Sept. 11, 2001, attacks. It partners with industry in developing medical countermeasures that can be stockpiled by the federal government to combat biological or chemical attacks and pandemic threats.
BARDA has spent billions of dollars on contracts with dozens of different suppliers, including major pharmaceutical companies and smaller biotechnology firms.
Both allies and Dr. Bright say his nearly four-year tenure as the head of BARDA was marked by clashes with his superiors especially Dr. Robert Kadlec, the assistant secretary of health for preparedness and response and tension with some industry executives. Dr. Bright conceded in the complaint that those clashes came to a head after he leaked information on the dispute over the malaria drug hydroxychloroquine to a reporter from Reuters.
A lawyer for Dr. Bright, Debra Katz, said he felt a moral obligation to get the word out that the administration was pressing to stockpile an unproven and potentially dangerous coronavirus treatment, which was supplied by drugmakers in India and Pakistan and had not been certified by the Food and Drug Administration.
The complaint says top Department of Health and Human Services officials, including Dr. Kadlec, who oversees the strategic national stockpile, overruled scientific experts while awarding contracts to firms represented by the consultant, John Clerici. Mr. Clerici, a founder of a Washington-based firm, Tiber Creek Partners, was instrumental, along with Dr. Kadlec, in writing the legislation that created BARDA.
Dr. Bright was vocal about his concerns regarding the inappropriate and possibly illegal communications between Mr. Clerici, Dr. Kadlec, Mr. Shuy and Mr. Meekins, the complaint stated, referring to Bryan Shuy and Chris Meekins, two other department officials.
A spokeswoman for the department, Caitlin Oakley, did not address the complaints about officials there.
Dr. Bright was transferred to N.I.H. to work on diagnostics testing critical to combating Covid-19 where he has been entrusted to spend upward of $1 billion to advance that effort, she said in an emailed statement. We are deeply disappointed that he has not shown up to work on behalf of the American people and lead on this critical endeavor.
Dr. Bright was initially offered a narrower role at the National Institutes of Health to work on a new Shark Tank-style program to develop coronavirus treatments, but Ms. Katz told reporters he has no role and did not receive his last paycheck. A spokeswoman, Kendra Barkoff Lamy, later said that, at his doctors direction, Dr. Bright has been on sick leave due to hypertension caused by this current situation.
In a statement, Mr. Clerici said he unequivocally denied any wrongdoing, adding: Its sad that during a pandemic, Dr. Bright and his team have chosen to distract people like Dr. Kadlec, who are critical to the response, with politically motivated allegations. The record is clear that his allegations are false and will be proven so.
The complaint, written by Ms. Katz and her law partner, Lisa Banks, identifies four specific instances in which Dr. Bright felt Mr. Clerici exerted undue influence. At one point, it said, Dr. Bright called for an investigation by the inspector general to help break up the cottage industry of marketing consultants and political influence into these contracts.
Dr. Bright also said Mr. Clerici pushed, albeit unsuccessfully, for an extension of a contract awarded to a company run by someone who was friends with Jared and has Hollywood connections. In a brief interview, Mr. Clerici said the conversation never happened.
The document paints Dr. Bright as sounding the alarm about the emerging coronavirus threat and pressing his superiors to do more to prepare including purchasing masks that would later turn out to be in short supply at a time when Mr. Azar was downplaying the crisis.
On Jan. 23, he met with Mr. Azar and Dr. Kadlec to press for urgent access to funding, personnel and clinical specimens, including viruses, that would be necessary to develop treatments, the complaint said. But Mr. Azar and Dr. Kadlec asserted that the United States would be able to contain the virus through travel bans, the complaint said, adding that Dr. Bright was cut out of future department meetings related to Covid-19.
But the complaint says Dr. Bright found an ally in Peter Navarro, Mr. Trumps trade adviser, who shared Dr. Brights sense of urgency, recognized his expertise and was prepared to help. In early February, an official from a company that makes masks connected Dr. Bright with Mr. Navarro, and the two met at the White House on Feb. 8, a Saturday, more than a month before Mr. Trump declared a national emergency.
In that meeting, the complaint said, Dr. Bright urged Mr. Navarro to have the government stop exporting high-quality N95 masks, stock up on remdesivir, an antiviral drug approved last week by the F.D.A. to treat Covid-19, and develop a Manhattan Project for a vaccine an idea Mr. Trump recently adopted.
Mr. Navarro invited Dr. Bright back the following day to help him draft recommendations for the presidents coronavirus task force a move that angered top department officials, the complaint said.
Dr. Bright is asking the Office of Special Counsel to take steps to force the department to reinstate him as head of BARDA. In a brief statement during a conference call convened by his lawyers, he said the past few years have been beyond challenging.
Time after time, I was pressured to ignore or dismiss expert scientific recommendations and instead to award lucrative contracts based on political connections, Dr. Bright said.
Dr. Bright was named to lead BARDA a day after Mr. Trumps election in November 2016, inheriting an agency full of fights with companies over contracting approvals. He proved a polarizing figure.
Bruce Gellin, the former director of the departments National Vaccine Program Office, described Dr. Bright as a visionary thinker who pushed BARDA to take risks and innovate. But some lobbyists and pharmaceutical executives say that under Dr. Bright, the disputes over contracting worsened, a situation that led to a review by an outside consulting firm to evaluate the situation.
The consultant, Mitre Corporation, issued two reports; neither is publicly available. The first concluded that some companies were badly treated by BARDA and included criticism that it lacked technical prowess and professionalism, according to two people who were told about its contents. It was later rewritten to include more flattering information about BARDA that was left out of the first report.
But the final straw for Dr. Bright came when Mr. Trump started pushing hydroxychloroquine as a possible game changer in the treatment of the virus. Dr. Bright pushed to limit access to the drug to hospitalized patients, but grew troubled when administration officials, including Dr. Kadlec, continued to press for its widespread usage, the complaint said.
When a Reuters reporter contacted him, he shared emails with the news outlet. Its story was published on April 16, and Dr. Bright was removed less than a week later.
Michael D. Shear contributed reporting.
The text messages to the Chinese activist streamed in from ordinary Wuhan residents, making the same extraordinary request: Help me sue the Chinese government. One said his mother had died from the coronavirus after being turned away from multiple hospitals. Another said her father-in-law had died in quarantine.
But after weeks of back-and-forth planning, the seven residents who had reached out to Yang Zhanqing, the activist, suddenly changed their minds in late April, or stopped responding. At least two of them had been threatened by the police, Mr. Yang said.
The Chinese authorities are clamping down as grieving relatives, along with activists, press the ruling Communist Party for an accounting of what went wrong in Wuhan, the city where the coronavirus killed thousands before spreading to the rest of China and the world.
Lawyers have been warned not to file suit against the government. The police have interrogated bereaved family members who connected with others like them online. Volunteers who tried to thwart the states censorship apparatus by preserving reports about the outbreak have disappeared.
They are worried that if people defend their rights, the international community will know what the real situation is like in Wuhan and the true experiences of the families there, said Mr. Yang, who is living in New York, where he fled after he was briefly detained for his work in China.
The crackdown underscores the partys fear that any attempt to dwell on what happened in Wuhan, or to hold officials responsible, will undermine the states narrative that only Chinas authoritarian system saved the country from a devastating health crisis.
To inspire patriotic fervor, state propaganda has portrayed the dead not as victims, but as martyrs. Censors have deleted Chinese news reports that exposed officials early efforts to hide the severity of the outbreak.
The party has long been wary of public grief and the dangers it could pose to its rule.
In 2008, after an earthquake in Sichuan Province killed at least 69,000 people, Chinese officials offered hush money to parents whose children died. Following a deadly train crash in the city of Wenzhou in 2011, officials prevented relatives from visiting the site. Each June, the authorities in Beijing silence family members of protesters who were killed in the 1989 crackdown on the Tiananmen Square pro-democracy movement.
Now, some say the government is imposing the same kind of collective amnesia around the outbreak.
Three volunteers involved in Terminus2049, an online project that archived censored news articles about the outbreak, went missing in Beijing last month and are presumed to have been detained.
I had previously told him: You guys probably face some risk doing this project. But I didnt know how much, said Chen Kun, whose brother, Chen Mei, is one of the volunteers who disappeared.
I had said that maybe he would be summoned by the police for a talk, and they would ask him to take down the site, he said. I didnt think it would be this serious.
Mr. Chen said he had no information about his brothers disappearance. But he had spoken to the relatives of one of the other missing volunteers, Cai Wei, who said that Mr. Cai and his girlfriend had been detained and accused of picking quarrels and provoking trouble, a vague charge that the government often uses against dissidents.
Reached by telephone on Tuesday, an employee at a police station in the Beijing district where Chen Mei lives said he was unclear about the case. The groups site on GitHub, a platform popular with coders, is now blocked in China.
Volunteers for similar online projects have also been questioned by the authorities in recent days. In blog posts and private messages, members of such communities have warned each other to scrub their computers. The organizers of another GitHub project, 2019ncovmemory, which also republished censored material about the outbreak, have set their archive to private.
To the authorities, it seems no public criticism can be left unchecked. The police in Hubei, the province that includes Wuhan and was hardest hit by the outbreak, arrested a woman last month for organizing a protest against high vegetable prices. An official at a Wuhan hospital was removed from his post after he criticized the use of traditional Chinese medicine to treat coronavirus patients, which the authorities had promoted.
The crackdown has been most galling to people mourning family members. They say they are being harassed and subjected to close monitoring as they try to reckon with their losses.
The coronavirus killed nearly 4,000 people in Wuhan, according to Chinas official figures. Some residents believe the true toll is much higher. The government fired two high-ranking local officials, but that is not enough for many grieving relatives, who say they want fair compensation for their losses and harsher punishment for officials.
Zhang Hai is certain that his father, who died in February, was infected with the coronavirus at a Wuhan hospital. He says he still supports the party but thinks local officials should be held responsible for initially hiding the fact that the virus could spread among humans. Had he known the risk, he said, he would not have sent his father to the hospital for treatment.
Mr. Zhang said several Chinese reporters who had interviewed him about his demands later told him that their editors had pulled the articles before publication. He posted calls online to set up a monument in honor of the victims of the epidemic in Wuhan, but censors quickly scrubbed the messages. Officials have pressed him to bury his fathers ashes, but he has so far refused; he says they have insisted on assigning him minders, who he believes would be there to ensure that he caused no trouble.
They spend so much time trying to control us, Mr. Zhang said. Why cant they use this energy to address our concerns instead?
In March, the police visited a Wuhan resident who had started a chat group of more than 100 people who lost relatives to the virus, according to two members of the group, one of whom shared a video of the encounter. The group was ordered to disband.
Mr. Yang, the activist in New York, said at least two of the seven Wuhan residents who had contacted him about taking legal measures against the government dropped the idea after being threatened by the police.
Even if the other plaintiffs were willing to move forward, they might have trouble finding lawyers. After Mr. Yang and a group of human rights lawyers in China issued an open call in March for people who wanted to sue the government, several lawyers around the country received verbal warnings from judicial officials, Mr. Yang said.
The officials told them not to write open letters or create disturbances by filing claims for compensation, according to Chen Jiangang, a member of the group. Mr. Chen, who fled to the United States last year, said he had heard from several lawyers who were warned.
If anyone dares to make a request and the government fails to meet it, they immediately are seen as a threat to national security, Mr. Chen said. It doesnt matter whether youre a lawyer or a victim, its like youre imprisoned.
Some aggrieved residents have pressed ahead despite the government clampdown. Last month, Tan Jun, a civil servant in Yichang, a city in Hubei Province, became the first person to publicly attempt to sue the authorities over their response to the outbreak.
Mr. Tan, who works in the citys parks department, accused the provincial government of concealing and covering up the true nature of the virus, leading people to ignore the viruss danger, relax their vigilance and neglect their self-protection, according to a copy of the complaint shared online. He pointed to officials decision to host a banquet for 40,000 families in Wuhan in early January, even as the virus was spreading.
He urged the government to issue an apology on the front page of the Hubei Daily, a local newspaper.
In a brief phone call, Mr. Tan confirmed that he had submitted a complaint to the Intermediate Peoples Court in Wuhan, but he declined to be interviewed because he is a civil servant.
With Chinas judiciary tightly controlled by the central government, it was unclear whether Mr. Tan would get his day in court. Articles about Mr. Tan have been censored on Chinese social media. Calls to the court in Wuhan on Thursday rang unanswered.
Liu Yi contributed research.
Demand for rides has dropped sharply during the pandemic, exacerbating Uber's financial woes. David Paul Morris/Bloomberg via Getty Images hide caption
Demand for rides has dropped sharply during the pandemic, exacerbating Uber's financial woes.
Uber is cutting 3,700 jobs about 14% of its corporate workforce as demand for ride-hailing has dried up during the coronavirus pandemic.
The layoffs affect people who do customer support and recruiting, CEO Dara Khosrowshahi told employees in an email seen by NPR. He said work for those departments had dried up as trip volumes dropped "significantly" and the company instituted a hiring freeze.
"Days like this are brutal," he wrote.
Uber is also closing around 180 help centers for drivers, and Khosrowshahi is forgoing the rest of his $1 million salary through the end of this year.
In his email, Khosrowshahi hinted at more cuts to come.
"This is one part of a broader exercise to make the difficult adjustments to our cost structure (team size and office footprint) so that it matches the reality of our business (our bookings, revenue and margins)," he wrote. "We are looking at many scenarios and at each and every cost, both variable and fixed, across the company."
Uber already was losing money before the pandemic. The crisis has only exacerbated that situation as millions of people stay home. In March, Khosrowshahi said demand was down at least 60% in Seattle, and he was expecting a similar trend in other big cities such as New York, Los Angeles and San Francisco.
Other U.S. tech companies have also been hit hard by the pandemic. Both Uber's rival Lyft and travel booking site Airbnb laid off thousands of employees in recent days.
As the coronavirus pandemic cuts through the country, it is leaving behind large numbers of deaths that surpass those of recent history. A New York Times analysis of state data from the Centers for Disease Control and Prevention shows just how many lives are being lost in the pandemic in each place as the virus kills some people directly, and other lives are lost to an overwhelmed health care system and fears about using it.
Our analysis examines deaths from all causes, beginning in mid-March when the virus took hold in the country, and examines every state with reliable data. The death count so far is not uniform around the nation. Some places have seen staggering death tolls, while others have seen smaller aberrations from historic patterns. In some states, the number of deaths so far looks roughly in line with those in a typical year, suggesting that the virus and its effects throughout medicine and society have not yet had a major impact on survival.
New York City, long the epicenter of the U.S. outbreak, has experienced the most extreme increase in deaths, which surged to six times the usual number. Altogether, since mid-March deaths there are 23,000 higher than normal.
Note: The weekly allocation of deaths in New York City since March 15, 2020, is an approximation based on how mortality data has lagged in previous weeks this year.
All of these numbers are likely to be a substantial undercount of the ultimate death toll, since death counting takes time and many states are weeks or months behind in reporting.
But comparing recent totals of deaths from all causes can provide a more complete picture of the pandemics impact than tracking only deaths of people with confirmed diagnoses. Indeed, in nearly every state with an unusual number of deaths in recent weeks, that number is higher than the states reported number of deaths from Covid-19. Epidemiologists refer to fatalities in that gap between the observed and normal numbers of deaths as excess deaths.
Measuring excess deaths is crude because it does not capture all the details of how people died. But many epidemiologists believe it is the best way to measure the impact of the virus in real time. It shows how the virus is altering normal patterns of mortality where it strikes and undermines arguments that it is merely killing vulnerable people who would have died anyway.
Our charts show weekly deaths above or below normal in each state through the most recent week, with data the C.D.C. estimates to be at least 90 percent complete. Those determinations are based on states speed at reporting deaths in the past, and they mean that these state charts show death trends for slightly different time periods.
We supplemented the C.D.C. data with any coronavirus deaths that have been reported by The Times that have not yet been added to the C.D.C. database. Those totals were compared with a simple model of expected deaths based on the number of deaths in the past five years, adjusted to account for trends over time, like population changes. Public health researchers use such methods to measure the impact of catastrophic events when official measures of mortality are flawed.
Measuring excess deaths does not tell us precisely how each person died. It is likely that most of the excess deaths in this period are because of the coronavirus itself, given the dangerousness of the virus and the well-documented problems with testing. But it is also possible that deaths from other causes have risen too, as hospitals have become stressed and people have been scared to seek care for ailments that are typically survivable. Some causes of death may be declining, as people stay inside more, drive less and limit their contact with others.
Even in a normal year, it takes up to eight weeks for full death counts to be reported by the C.D.C. But this is not a normal year, and it is possible that because of the unusual number of recent deaths and the stresses they are placing on medical examiners and public health officials, the totals will take even longer than usual to become complete. We will keep updating the numbers regularly as new data becomes available.
In a larger group of states, the increases in deaths were more modest during the early phase of the pandemic, but deaths are still higher than normal.
There are still some states that appear to have been largely spared from an unusual number of deaths during this period. In those places, the patterns of death look roughly similar to those in recent years. A few states in this category have seen their fortunes worsen in recent weeks, and they may begin showing excess deaths as more weeks of complete data are reported.
In some of these states, deaths are actually below the normal trend. That may be because of data reporting lags. But it could be because of the pandemic, too: Stay-at-home orders may be lowering death rates from car accidents in some places, or flu in others.
In nearly every state with more deaths than normal, the total number of them exceeded the official number of measured Covid-19 deaths. Given the limitations on coronavirus testing in the United States, this gap is not a big surprise. Similar gaps have been found in other countries with high numbers of Covid-19 deaths.
Our analysis aims to show mortality statistics for as much of the country as possible, but there are some places that are so far behind in submitting death certificates to the C.D.C. that comparing their reported totals to historical trends would not show much. In Connecticut, for example, zero deaths have been reported to the federal government at all since February 1.
Several other states and Puerto Rico have less extreme data lags, but are far enough behind that the C.D.C. does not recommend relying on their recent death reporting. In Pennsylvania and Ohio, death reporting seems to be lagging far behind the normal rate all year, according to the C.D.C., even though their reporting is usually more timely, so we have omitted data from them as well. The complete list of missing places is: Alaska, Connecticut, Louisiana, North Carolina, Ohio, Pennsylvania, Puerto Rico, Rhode Island, South Dakota, Virginia and West Virginia.
It is the sixth week of lockdown, and for many people things are getting progressively more intense. Most families are physically distancing at home. People are only leaving the house for their weekly shop and spending a lot of that time waiting in the queue or to exercise once a day.
In my family things are a bit different. Our driveway is usually empty during the day as my parents, who are doctors, go in to work. It is difficult to imagine how only some weeks ago my main worries were around my GCSEs. Now every day, I hear about deaths from coronavirus. I cannot help but feel a surge of fear for my parents as I watch these updates with my brother. Im painfully aware of the many healthcare workers who have lost their lives.
The health and social care secretary, Matt Hancock, has announced that the families of NHS and care workers who died from the coronavirus will get 60,000. Im sure they would much rather have their loved ones with them. It is unthinkable to put a price on someones life. Maybe if this money had been spent on personal protective equipment (PPE) there would have been fewer deaths.
My parents are carrying on with their work with as much semblance of normality as possible. They change before they leave work and again straight after coming home. They avoid all contact with us until theyve had a shower and disinfected things thoroughly.
At the start they discussed my dad moving into a hotel; there was more risk of infection as he works in a hospital. In spite of their best efforts to wash their hands repeatedly and set up a hygiene station in the hallway, they both caught coronavirus one after the other.
I wasnt surprised. PPE guidelines and supplies have been inadequate. Many hospitals have been running out of gowns and the guidelines surrounding what level of PPE should be used have been changing constantly. My mums surgery has had to supplement its own PPE. They have bought gowns, visors and safety goggles as well as masks.
My dad caught the virus in the first week of lockdown. It was a Thursday and as everyone clapped for NHS workers outside, he just about climbed the stairs to his bed. He said it felt like he was trying to climb Everest. He remained isolated from the rest of us, suffering from fever, rigors and severe muscle pains. I often heard him scream in pain. My mum did her best to help, giving him regular paracetamol and nourishing soups that he would barely eat. She would don a mask and leave food outside his door.
My parents werent able to get tested despite the governments claim that NHS staff would be tested for Covid-19. We stayed isolated for 14 days, assuming that my dad had the virus. My mum worked from home, struggling with technology, delivering food to my dad and answering up to 50 phone calls a day.
After multiple attempts to be tested my dad finally accessed a drive-through on day 11 of his illness, when he had recovered. The swab was negative, presumably because he was tested too late.
My mum was sick next. In the first week she lost her sense of smell and had a mild fever. But in the second week her health deteriorated. She became very breathless and could not stop coughing. On day 10 of her illness she was admitted to a coronavirus ward. I have never been more scared in my life. She thankfully got better and came home but Im still worried about whether they might be able to catch the virus again.
This experience has taught me the importance of time and how we can never predict what the future may hold. This week I would have been sitting my first GCSE exam, which now seems trivial compared with what people are going through.
Before this pandemic I took for granted time spent with family and loved ones. But now I have learned to cherish all these priceless moments. While my parents were ill I questioned whether life would ever go back to normal, or even if I would be able to speak to them again.
After everything, I am incredibly grateful for the Thursday clap for the amazing dedication of key workers including those in healthcare, delivery drivers, supermarket staff, school and nursery teachers, and care workers.
There has been so much death, heartache and disappointment in recent weeks for people around the world, many of whom are feeling very isolated. We are all thinking about how this virus has affected us in many ways, but there have also been things to celebrate too such as how communities have come together to offer love, sympathy and camaraderie. I hope this can bring some light to those in darkness right now.
If you would like to contribute to our Blood, sweat and tears series about experiences in healthcare during the coronavirus outbreak, get in touch by emailing sarah.johnson@theguardian.com
You can listen to the latest episode of Today in Pa at this link, or on your favorite app including Alexa, Apple, Google, Spotify and Stitcher. Episodes are available every weekday on PennLive. Subscribe/follow and rate the podcast via your favorite app.
A new civilian coronavirus corps could help the states reopening efforts. Meanwhile, healthcare workers are granted civil immunity for their work treating those for COVID-19. The murder of a coronavirus researcher in Pittsburgh had nothing to do with his work, according to police. Pennsylvania has its 4th straight day of less than 1,000 new cases and Gritty is bringing some much needed joy to Delaware County.
Those are the stories we cover in the latest episode of Today in Pa, a daily weekday podcast from PennLive.com and hosted by Julia Hatmaker. Today in Pa is dedicated to sharing the most important and interesting stories in the state.
Todays episode refers to the following articles:
If you enjoy Today in Pa, consider leaving us a review on Apple Podcasts or on Amazon. Reviews help others find the show and, besides, we like to know what you think of the program.
Thanks for visiting PennLive. Quality local journalism has never been more important. We need your support. Not a subscriber yet? Please consider supporting our work.
