Inside the Coronavirus Test Failure


In a conference call on January 15, a prominent scientist at the federal government’s Centers for Disease Control and Prevention assured local and national public health officials across the country that there would soon be a test for a mysterious virus spreading from China. Stephen Lindstrom told them the threat was far away and that they might not need the test that his team was developing “unless the scope is much larger than we expect,” according to an email summarizing the threat. ‘call.

“We are in good hands,” wrote a public health official who participated in the call in emails to colleagues.

Three weeks later, early February 8, one of the first CDC test kits arrived in a Federal Express package at a public health laboratory on the east side of Manhattan. At that time, the virus had reached the United States and the kits represented the government’s best hope of containing it while it was still possible.

For hours, laboratory technicians had trouble verifying that the test worked. Each time, it failed, producing unreliable results.

That night, they called their laboratory director, Jennifer Rakeman, an assistant commissioner of the New York health department, to tell her that it had failed. “Oh, s -“, ​​she replied. “What are we going to do now? “

Over the next 21 days, as Trump administration officials continued to rely on the failed CDC test, many laboratory scientists eager to contribute to the failed effort became increasingly alarmed and exasperated by federal actions, according to previously unreported emails and other documents reviewed. by the Washington Post, as well as exclusive interviews with scientists and officials involved.

In their private communications, scientists from university, hospital and public health laboratories – a layer removed from federal agency operations – expressed dismay at not acting faster and their frustration at the bureaucratic demands that delayed their attempts to develop alternatives to the CDC test.

“We have the skills and resources as a community, but we are collectively paralyzed by an inflated bureaucratic / administrative process,” Marc Couturier, medical director of the ARUP university laboratory in Utah, wrote to other microbiologists on 27 February after weeks of growing frustration.

The administration adopted a new approach behind closed doors the same day, concluding that a “much broader” effort for the tests was necessary, according to an internal note from the government explaining the plan. Two days later, the administration announced a loosening of regulations which scientists said prevented private labs from deploying their own tests.

At that time, the virus had spread across the country. In less than a month, it would disrupt everyday life, shutting down the world’s largest economy and killing thousands of Americans.

In a statement to The Post, the CDC said that an investigation into the initial problems was under way. The test is now used in all states and is “accurate and reliable,” the agency said.

Stephen Hahn, the Commissioner of the Food and Drug Administration, which regulates testing, told The Post that the agency is constantly adapting to an “unprecedented global public health crisis”.

“Right now, our efforts are focused on everything we can do to combat COVID-19, but we know there will certainly be time to learn more important lessons from the agency’s response,” said he said in a statement, referring to the disease from the new coronavirus.

In an interview Thursday, Brett P. Giroir, an admiral of public health services who, on March 12, was named the highest administrative official for the tests, admitted that the government should have acted more decisively to detect and contain the virus.

“There was an obvious need for a more aggressive posture,” said Giroir, assistant secretary to the Department of Health and Social Services.

When asked who was responsible for the delays in the early stages of the crisis, he paused.

“A problem like this is more important than any agency,” he said. “Obviously, you needed a higher level of leadership and organization. “

A hospital is built in January for coronavirus patients in Wuhan, China. (Getty Images)

The need for a test

The first reports of a strange, possibly unknown virus, started to flee China in late December. Scientists and researchers in the United States and around the world have begun to pay close attention to the apparent epicenter of the spread, a sprawling industrial city in central China called Wuhan.

Among those following closely were virologists and other specialists from the CDC, the nation’s flagship public health agency. Founded in 1946 to fight malaria in the southern states, the CDC is at the forefront of the fight against infectious diseases across the country. It employs some 22,000 epidemiologists, biologists, behavioral specialists and others. Recent successes include rapid responses to contain the Zika, MERS and Ebola viruses.

In early January, the CDC publicly treated the Wuhan virus as a distant potential threat, issuing a notice urging that “usual precautions” be taken when traveling abroad.

The agency has also started developing plans to protect the country. Led by Lindstrom, a team has begun to consider the types of tests, technically called tests, that could identify the virus.

Lindstrom is a microbiologist with an impressive track record: he helped develop a critical test method to detect the H1N1 virus in 2009. During a conference call on January 7, he told public health officials that the CDC had aim to “plan the worst, let’s hope for the best”, according to an exchange of emails between scientists and others. Lindstrom, like several other officials named in this report, did not respond to requests for interviews.

On January 10, CDC scientists had a major break when the Chinese government released the genetic sequence of the pathogen. The sequence, a long chain of letters representing the structure of the RNA of SARS-CoV-2, describes a coronavirus never seen before in humans. It also gave scientists a way to create an accurate diagnostic test that could detect the virus.

The CDC has long spearheaded the country’s efforts to create diagnostic tests when a public health threat emerges. The agency typically distributes the tests to a network of state and county public health laboratories, using the results to track and contain new pathogens until large-scale commercial tests are released online.

But state and local public health labs juggle an immense range of responsibilities, including food and water safety, and government studies dating back two decades have found that public health labs often lack money and resources to keep pace with demands.

During the January 15 call, Lindstrom told more than a dozen public health officials that the CDC plans to make the test available to all state and county public health labs. He assured them “that there will be no pressure for everyone (at least from the CDC) to implement it unless the scope is much greater than what we currently foresee”, according to the Summary of email from Kelly Wroblewski, Director of Infectious Disease Control Programs at the Association. public health laboratories.

The CDC scientists weren’t the only ones who wanted to create a test. Commercial laboratories have started to mobilize and scientists from major hospitals and universities have taken action to develop their own tests.

One of them was Alex Greninger, 38, deputy director of the University of Washington’s clinical virology laboratory. For Greninger, the possibility of creating a diagnostic test for a new coronavirus was a rare opportunity.

Researchers from the University of Nebraska, Stanford University and elsewhere have also started to take their first steps towards inventing tests for the virus for use in their own laboratories. These university laboratories did not have the capacity to process the millions of tests that would be required in the event of a pandemic, a scale that is only achievable by commercial laboratories, but their limited testing capacities could have helped efforts to detect and slow the virus to its beginnings.

On January 16, the day Greninger started buying test supplies, a 35-year-old man who had recently visited Wuhan fell ill with flu-like symptoms after returning to the Seattle area, according to a report by incident of the CDC. The man went to his doctor, who dabbed his nose and sent the sample to the CDC, the report said.

Four days later, using its new test, the CDC confirmed that the man was the first person in the United States known to be infected with the new coronavirus.

In an interview with CNBC two days after that, President Trump downplayed the threat to the Americans.

“We have it completely under control,” he said.

Early December

December 31st

January 7

January 8

January 10

January 15

January 16

January 17

January 20

Early December

The first suspected case of the new coronavirus, which causes covid-19 disease, appears in Wuhan, China.

December 31st

China is informing the World Health Organization of a strange disease similar to pneumonia.

January 7

The Centers for Disease Control and Prevention are beginning to plan the tests. In an email, Stephanie Chester of the Association of Public Health Laboratories told colleagues that the CDC’s chief microbiologist said the agency’s goal was “to plan the worst, hope for the best”.

Currently, the pathogen is still unidentified, but if it is identified and is truly new, they will set up an EUA test. He said they were in a “plan for the worst, hope for the best”. Much of their response efforts depend on the availability of data and information from China. The main concern of the US PHL concerns travel in general and people returning from the Chinese New Year in the coming weeks. Will let you know if I hear more.

January 8

The CDC issues an official health advisory recommending that travelers take the usual precautions.

Read the full document

January 10

China publishes the genetic sequence of the pathogen.

January 15

The first known person in the United States to become infected with the virus arrives in Seattle from China. On the same day, CDC scientists say the agency will make its tests available to all state and county public health laboratories.

January 16

Alex Greninger, a scientist at the University of Washington who created a coronavirus test, orders the necessary chemical reagents. He is one of many scientists in the country to rush to design their own test.

January 17

Nancy Messonnier, a CDC official, says that “for a family sitting around the dinner table tonight is not something they should generally worry about.”

Since the MERS and SARS outbreaks, we have improved our capabilities in the United States and around the world. We are now in a better position to respond to this new threat quickly and collaboratively. Based on the information currently available to the CDC, we believe that the current risk of this virus to the general public is low. For a family sitting around the dinner table tonight, this is not something they usually have to worry about.

January 20

After developing a test over the weekend, the CDC in an internal incident report confirms the first positive case of coronavirus in the United States.

A significant moment

The CDC scientists took seven days to design the test – an incredibly short time for a healthcare system built around the principles of medical quality and patient safety, not speed.

The CDC could use the test in its Atlanta laboratories, but could not send it to public health laboratories until it has obtained FDA approval. On January 28, Lindstrom and other CDC members assured public health scientists in a conference call that “the goal of the CDC is to get (FDA approval) as soon as possible and expects that the test is ready to be deployed within two weeks, perhaps sooner, ”said the summary of the call from the Association of Public Health Laboratories.

Although CDC testing is a priority, the FDA also responded to requests from other test developers. At the end of January, around twenty companies and scientific groups were discussing with the FDA their plan to develop tests, according to two government officials familiar with these surveys, which, like many others interviewed for this story, expressed themselves subject to conditions. anonymity to discuss sensitive topics. imported.

At the same time, pressure was mounting on the Trump administration to take action. The number of people dying from the infection worldwide reached 200 to 30 January, when the World Health Organization declared the virus to be a public health emergency of international concern.

The next day, the Secretary of Health and Human Services, Alex Azar, announced a health emergency in the United States. At the time, Azar was the head of the newly created White House Coronavirus task force.

Health and Social Services Secretary Alex Azar speaks at a briefing in January with members of President Trump’s coronavirus task force. (Jabin Botsford / The Washington Post)

The declaration was one of the most significant moments of the current crisis. These statements provide the FDA with the flexibility to expedite approvals for critical medical products, including commercial diagnostic testing. But they also impose strict limits on scientists in government-certified clinical laboratories in universities, research centers and hospitals.

These laboratories are generally authorized by the FDA to perform and use their own tests without government approval, including for making decisions about patient care, as long as they use them only in their own facilities and do not sell them. not.

But once Azar announced a public health emergency, the tests created in these laboratories had to receive an “emergency use authorization”, or EUA, from the FDA. The additional regulation aims to ensure the effectiveness of testing in public health crises in which inaccurate results could be detrimental.

The new regulatory hurdle has blocked efforts like the one underway by Greninger at the University of Washington. Greninger and other scientists were in some of the country’s first coronavirus hotspots, where successful tests could have helped reveal the scale of the epidemic. Suddenly their hands were tied.

Clinicians have pissed off the new hurdle, according to discussions in private online discussion groups between academics and scientists.

“The EUA process is faulty, broken and ineffective,” wrote Couturier, medical director and diagnostic specialist at ARUP Laboratories in Utah, on ClinMicroNet, a private messaging system for directors of microbiology laboratories at worldwide.

Alex Greninger, deputy director of the University of Washington’s clinical virology laboratory, said his efforts to develop a test for the coronavirus were blocked by FDA regulations. (Jovelle Tamayo for The Washington Post)

In a statement this week, the FDA said its regulations “had not obstructed or been a roadblock” in the deployment of the tests.

“All of the measures the FDA has taken during this public health emergency to combat the COVID-19 pandemic have balanced the urgent need to make diagnostic tests available with a level of surveillance that ensures the deployment of accurate tests.” said the agency.

But in his interview, Giroir proposed a different analysis.

“If someone says it was an obstacle, to me, you have to believe it,” he told the Post. “If they thought it was a barrier, it would become a barrier.”

A person familiar with the emergency declaration told The Post that career FDA staff had not raised concerns about the charges by the EAA on clinical laboratories for Azar or FDA officials. Azar oversees the FDA.

Hahn had been confirmed by the Senate as FDA commissioner on December 12 – just seven weeks before Azar’s statement. Prior to that, Hahn was a radiation oncologist and medical director at the MD Anderson Cancer Center in Houston.

Hahn’s agency approved the CDC test on February 4, making it the only nationally accepted test for the new coronavirus. Public health officials in New York, Nebraska, Colorado, Minnesota, New York State, and elsewhere began receiving them four days later.

Test kits contain compact collections of chemicals called reagents. The chemicals help isolate the viral genetic material and then amplify it so that it can be detected by probes supplied with the kit.

Scientists in local laboratories quickly recognized that something was wrong. Tests have often produced results suggesting that the virus was present in samples in which scientists knew it was not.

On February 8, when laboratory technicians from the New York Department of Health tested the virus for samples, they saw an upwardly sloping logarithmic curve on their computer screens, indicating that the virus was present. The problem was that they saw something similar when they tested on distilled water that did not contain any traces of the virus.

When they finally gave up that night, the technicians called their manager, Rakeman. Shortly before midnight, she relayed the bad news in an email to the local health authorities. “The problem will need to be investigated and could have a significant impact on the availability of testing at the CDC and across the country until the problem is resolved,” she wrote.

Officials from the New York State laboratory also passed the news on, according to documents and interviews. “There is a technical problem with one of the reagents that invalidates the test and will not allow us to perform the test,” wrote New York State Wadsworth Center laboratory director Jill Taylor to State health officials in an email the same evening. .

“I’m sorry I don’t have better news,” she wrote. “It is a disappointment. “

The fact that some laboratories encountered problems with the test quickly came back to the CDC.

“Is this something to fear? Daniel Jernigan, a leader in the CDC’s response to coronaviruses, wrote to the Association of Public Health Labs the next morning as he was about to board a plane.

It was, she was told.

Later that day, Scott Becker, the association’s chief executive, shared his concerns with another CDC official. “The states and their governors will take off,” he wrote, adding later, “if the CDC does not get ahead, it will be a disaster. “

As they struggled to operate the test kit, many public health laboratories realized that they could be successful in eliminating one of its three main chemical components. But according to FDA emergency rules, they could only use the test as it had been approved. The flaw meant that they couldn’t use it at all.

“The CDC’s silence … is deafening,” wrote Joanne Bartkus, laboratory director of the Minnesota Department of Health in Becker on February 10. “What’s going on? We receive questions from our governor’s office and other laboratories receive requests from the media asking when we will start. “

As of February 12, a total of 2,009 tests had been completed in the United States, according to data from the CDC.

“We’re screwed up about testing if this thing takes off in the United States,” warned Susan Butler-Wu, director of medical microbiology at Los Angeles County and the University of Southern California Medical Center, in an email from February 13 to a scientific colleague.

Falling behind

The United States was clearly behind in the fight against Covid-19. Other countries, such as Singapore and Taiwan, quickly accelerated testing. In South Korea, 1,000 people were being tested daily in mid-February, a figure that would have increased more than tenfold by the end of the month.

The Geneva-based World Health Organization has already delivered 250,000 diagnostic tests designed and manufactured by a German laboratory to 70 laboratories around the world.

University and hospital researchers, including Greninger, experimented early with the design of the German laboratory and found it viable, but American health officials continued on their own path.

“To our knowledge, no discussion has taken place between WHO and the CDC (or other agencies of the United States government) regarding the provision by WHO of COVID-19 tests in the United States,” said WHO spokesperson Tarik Jasarevic told The Post.

Hahn defended the US government’s approach at a press conference weeks later.

“In the United States, we have policies in place that strike the right balance during public health emergencies to ensure critical review by scientific and public health experts and the availability of timely testing,” a- he said at a press briefing in the White House. “What is important here is that we have a test that the American people can trust. “

FDA’s confidence in the failed test was based in part on assurances from the CDC that it could be corrected easily, officials familiar with the agency’s deliberations said.

In its statement to The Post, the CDC said it was working closely with the FDA and “encouraged our government partners to work with the private sector to develop diagnostic tests for commercial use and to remove restrictions for … laboratories hospitals and universities across the county. ”

On February 16, officials from the FDA and CDC met to discuss solutions, including the possibility of eliminating the problem component of the test, officials said. FDA officials said it would be a quick fix that could quickly set up public health labs. But over the next few days, the FDA learned that some public labs were reporting persistent problems with the test, officials said.

While officials struggled to understand the flaws in the tests, the major clinical laboratories spent a great deal of their time and energy on paperwork and requests for FDA data to get their tests approved.

The Mayo Clinic has created its very first rapid response team. A third of the 15 members were dedicated only to FDA data and paperwork requests. Like the other members of the team, they worked 15 hours a day for three weeks.

“It doesn’t sound like anything we’ve done before,” said Matt Binnicker, director of clinical virology at Mayo.

He said they decided to persist because, in the worst case, public health labs alone could not test on the scale that would be needed. “The public health infrastructure is really not in place to deal with a pandemic,” he said.

At the University of Washington, Greninger and his fellow scientists were initially baffled by an FDA process they considered baroque. They have always worked under strict guidelines, aimed at protecting patients and guaranteeing quality. But the EU was a bureaucratic puzzle they had never encountered.

“The most pernicious effect of the current regulatory environment is that it reduces our preparedness for a real emergency,” Greninger wrote to colleagues on February 14.

Greninger devoted his energy to the paperwork problem, spending more than 100 hours filling out forms and collecting the information necessary for the candidacy, he told The Post. But when he finally submitted the material, an FDA official told him the agency couldn’t accept it – because he emailed it.

“We have received your email and attachments regarding the UW 2019-nCoV pre-EUA test,” an FDA official wrote on February 20. “However, we have not received the official submission through DCC. “

“What is DCC? Greninger replied.

“The Document Control Center,” came the answer.

“What is the Document Control Center? “

Greninger then learned of another requirement. Under FDA rules, he was supposed to digitally copy the electronic documents he emailed to the FDA, burn the copies to a disc, and mail the hard drive to an office in the suburban district of Columbia.

Greninger shared his exasperation in a February 20 email to a colleague: “Repeat after me, urgently. “

In a statement, an FDA official said that the information sent by Greninger on February 19 had been promptly reviewed, although it was not submitted correctly, and was insufficient to demonstrate that the test would work. The official said that after this interaction, “we immediately addressed how we received the applications.”

“The FDA is improving the way we interact with product developers to fight the pandemic, including those we don’t normally interact with,” said the official.

At the time Greninger sent his email, the FDA was in discussions with dozens of test developers, a number that was growing rapidly. But none had successfully completed an official FDA application, according to officials familiar with the agency’s actions. FDA officials interpreted the scarcity of requests as a sign of capacity or limited interest, officials said.

Some private laboratories have struggled to obtain samples of the virus needed to verify their tests and complete their requests, according to government officials and laboratory representatives. An FDA official said that at the time, the agency supported efforts to help these laboratories secure the necessary samples.

L’anxiété s’intensifie

Le 22 février, un responsable de la FDA nommé Timothy Stenzel s’est envolé pour Atlanta. Directeur d’un bureau de diagnostic à la FDA, Stenzel a été un personnage clé dans les décisions concernant les tests. Le but de sa visite n’était pas clair pour les responsables du CDC, mais il a dit qu’il voulait comprendre le développement des tests et aider à trouver un moyen de corriger le test en difficulté, selon trois personnes familières avec la visite.

Stenzel a passé une grande partie de la semaine suivante à assister aux réunions du CDC, à visiter les installations et à proposer des suggestions pour concocter des tests viables à partir de matériaux existants, ont déclaré les responsables.

Dans le même temps, des responsables du CDC, dont Jernigan de la division grippe de l’agence, ont exhorté Stenzel à convaincre la FDA d’approuver d’autres tests en cours de développement dans des laboratoires privés.

L’inquiétude quant au manque de tests généralisés, quant à elle, a atteint un sommet parmi les scientifiques et les responsables de la santé publique à l’échelle nationale. Beaucoup ont estimé que le pays ne pouvait plus attendre.

Le 24 février, l’Association des laboratoires de santé publique a officiellement demandé à Hahn d’assouplir les règles de la FDA.

« Nous en sommes maintenant à plusieurs semaines de réponse sans aucun test de diagnostic ou de surveillance disponible en dehors du CDC pour la grande majorité de nos laboratoires membres », indique la lettre de l’association. « Bien que nous comprenions que le processus de l’EUA est [public health labs], nous pensons qu’une route plus rapide est nécessaire pour le moment. “

Deux jours plus tard, la FDA a autorisé les laboratoires de santé publique à commencer à utiliser le test CDC, le composant en difficulté étant éliminé.

Le 27 février, Anthony S. Fauci, le plus grand expert du gouvernement en matière de maladies infectieuses, a accru la pression pour étendre les tests. Il s’est entretenu en personne avec Brian Harrison, chef de cabinet d’Azar, et a souligné la nécessité urgente d’accélérer l’approbation de nouveaux tests, selon deux personnes familières avec l’appel. À midi ce jour-là, Harrison a convoqué une téléconférence de responsables de la FDA, du CDC et d’autres agences.

Dans un langage fort, Harrison a dit au groupe de proposer un nouveau plan d’approbation des tests avant de quitter la réunion. Les participants se sont précipités pour échanger des idées. À la FDA et au CDC, Stenzel, Jernigan et d’autres ont travaillé sur une note de service dans la soirée qui décrivait une nouvelle stratégie.

La note de service, «Un plan pour augmenter les tests Covid-19 aux États-Unis», reconnaissait franchement que l’approche originale n’avait pas fonctionné. La propagation du virus «a eu un impact significatif sur les systèmes de santé et a provoqué des perturbations sociales», a-t-il déclaré.

«Le CDC a travaillé avec la FDA pour s’assurer que les tests sont disponibles dans les laboratoires de santé publique pour soutenir les enquêtes de santé publique et les efforts de contrôle; cependant, une approche interinstitutions beaucoup plus large est nécessaire pour répondre au besoin accru de diagnostics des fabricants commerciaux et des laboratoires capables de développer leurs propres tests.

Il a recommandé de donner aux laboratoires cliniques, tels que l’Université de Washington, une latitude pour créer et commencer à utiliser leurs propres tests tout en recherchant l’approbation de la FDA. La note a été transmise aux hauts responsables du gouvernement, y compris Azar, qui a soutenu l’assouplissement de la réglementation.

Le lendemain, Greninger et des dizaines d’autres cliniciens ont fait appel au Congrès dans une lettre à eux. Ils se sont plaints que les règles de la FDA «beaucoup plus strictes» avaient presque gelé la lutte du pays contre le virus.

« Notamment, aucun fabricant de tests ou laboratoire clinique n’a réussi à naviguer dans le processus EUA pour le SRAS-CoV-2 à ce jour », indique la lettre du 28 février. « Par conséquent, le test CDC reste le seul test disponible avec le statut EUA, et il n’a pas été mis à la disposition des laboratoires hospitaliers. “

Redressement de la FDA

On Feb. 29, the FDA finally reversed course, opening the way for clinical labs outside the government to begin testing for coronavirus. Under a revised policy Hahn announced at a White House briefing, the labs would have to notify the FDA when testing began, but they would not have to submit paperwork for 15 days.

“The FDA recognized the urgent need for even faster testing availability,” the agency said in a statement this week. “Although laboratories could use the EUA pathway, many were hesitant or didn’t know the pathway was available to them.”

Giroir told The Post that the FDA was right to reverse itself but could have done so sooner.

“In retrospect, it might have been useful earlier, right?” he said. “I mean, it was the right decision to make.”

On March 2, Greninger and his colleagues at the University of Washington went live, testing 30 patients in a single day. Two days later, they tested 202 people. That number soon soared to over 2,800 per day, roughly the equivalent of a quarter of tests done by all state and federal public health labs on the same day.

About two weeks after the FDA loosened its grip on testing, two major manufacturing giants, Roche and Thermo Fisher Scientific, won approval. By then the number of confirmed cases in the United States had grown to more than 2,000.

On March 12, Fauci, who runs the National Institute of Allergy and Infectious Diseases, told lawmakers the problem was not simply the failure of the CDC test. The coronavirus testing debacle had exposed deep structural problems in the nation’s public health system, he said.

“Yeah, it is a failing, let’s admit it,” il a dit. “The idea of anybody getting it easily the way people in other countries are doing it, we’re not set up for that. Do I think we should be? Yes, but we’re not.”

Emily Rauhala, Yasmeen Abutaleb and Josh Dawsey contributed to this report.


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