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California’s rush to detect new cases of COVID-19 has been slowed by shortages of a key chemical needed to conduct the diagnostic tests, Gov. Gavin Newsom said Thursday.
And because of this shortage, the federal government has restrictions on who gets tested, even as the cases and deaths mount.
“My great concern is we could be testing a lot more people,” said Newsom.
California now has 8,227 test kits sent by the U.S. Centers for Disease Control and Prevention, he said. The kits were welcomed, arriving after a long delay, but the good news was quickly tempered.
“The tests are not complete,” said Newsom, in a press briefing. “It is imperative that the federal government and labs across the United States get the benefit of all the ingredients that are components of the test.”
California is not alone, with other states and academic institutions reporting that they’re low on crucial supplies. This week, Harvard Medical School’s two teaching hospitals – Massachusetts General and Brigham and Women’s – appealed for donations of kits, reagents, and equipment. The University of Virginia’s hospital is also asking research labs to share.
“Many of these items are either on back-order or do not exist for us to purchase,” Harvard’s hospital leaders wrote in a letter this week to the Boston biotech community.
The surge in testing has increased demand for this chemical, called a reagent, which is a critical component used to run the test.
The labs that make the chemical are running low, and it is not contained in many of the federally-supplied tests. The shortage of reagents seems to be specific to the platform used in CDC tests.
Newsom compared it to “going to the store and purchasing a printer, but forgetting to purchase the ink. You need multiple components.”
On Friday, the Trump administration announced a series of steps Friday aimed at boosting the availability of coronavirus testing. There’s a new 24-hour emergency hotline at the U.S. Food and Drug Administration for laboratories having difficulty getting the reagent and other materials or facing other impediments. The FDA approved a new test developed by Pleasanton’s Roche Molecular Solutions that will speed up by tenfold the ability to test patients, and doesn’t rely on these chemicals. And it awarded nearly $1.3 million to two companies to develop a new approach of one-hour testing.
But the window of opportunity to detect the state’s initial infections is quickly closing.
Concerned about suspicious symptoms in their 14-year-old daughter — and seeking to be responsible — John Callon and his wife sought testing on Wednesday. But the Mountain View couple was rebuffed.
Their daughter had a headache, fever, light coughing, and major fatigue. Over the past two weeks, she had mingled with an estimated 2,000 other people at school, a major volleyball tournament and a weekend retreat, where she shared a bunk room with 11 others.
“They said, point blank, that they don’t have enough tests for everybody, and we understood they would only test her based on strict filtering criteria,” said Callon. She would only be eligible for a test, they were told by medical personnel at the Palo Alto Medical Foundation, if she had multiple symptoms, severe symptoms, recent travel to an international region of risk and contact with someone with a confirmed diagnosis.
“If there is even a small probability she has this new coronavirus,” he said, “she should be tested immediately, to know if she can be cleared — or to determine if some nearly 2000 people need to be immediately notified.”
“This inability to test except for the most obvious and egregious cases is obviously a recipe for the rapid spread of this disease,” he said.
Meanwhile, 900 Californians are in quarantine at Travis Air Force Base in Fairfield or Miramar Naval Station in San Diego after disembarking from the Grand Princess cruise ship. Many will seek testing.
In a state of nearly 40 million residents, by Thursday morning, California had conducted a total of only 1,573 tests at its 18 state test labs. By Friday, there were total of 247 positive cases and five deaths, all of them in the San Francisco Bay or Sacramento areas. No Saturday updates were available.
To test 5% of California’s population over the coming three months, the state would need, on average, 22,222 tests made available every day.
By contrast, South Korea — with a population of 50 million, only one-fifth larger than California — is testing 10,000 people a day, around the clock, at 79 designated test centers, according to reports. In Australia, where actor Tom Hanks and his wife Rita Wilson just tested positive, no test shortages have been reported.
For help, California is turning to labs at four hospitals: Stanford, UC Los Angeles, UC San Diego and the City of Hope. By next week, it hopes to also offer testing through UC Davis, UC Irvine and Kaiser. UCSF only has the capacity to do 80 tests per day and limits their use to patients who are hospitalized or in the Emergency Department.
The state is also contracting with Quest Diagnostics, a commercial lab, to conduct 1,200 tests a day and reduce the backlog of tests that had lacked all the components. Quest’s tools are automated and do not need the missing chemical. Quest is expanding its facilities and by the end of March has promised to conduct 5,000 tests a day, although not just for Californians, said Newsom.
“That would allow us to bypass the current restrictions on testing that are in place today,” said Newsom.
The missing reagent is a homopolymeric nucleic acid used to isolate the virus’ genetic material, or RNA, from the patient’s sample. It is made by the diagnostics testing giant QIAGEN.
The government test kits only contain primers and probes, according to the CDC website.
Labs are expected to provide everything else. Normally, that’s no problem; the chemicals are generally widely available and in stock for other applications of the testing technology, called RT PCR.
“We can have all of the test kits we need, but they rely on our ability to get the RNA out of a sample first, for testing,” said Dr. Michael Mina, an Assistant Professor of Epidemiology at Harvard T. H. Chan School of Public Health.
A Qiagen spokesperson told STATNews that “extraordinary” demand was limiting the company’s ability to supply some products, and said workers at its Hilden, Germany, and Barcelona, Spain, manufacturing sites were moving to work three shifts, seven days a week in order to ramp up production.
The company is also bringing on new staff and making better use of a site in Germantown, Md., to try and make the test kits, according to STAT.
The Qiagen products are not the only one on backorder, said Mina. So is an alternative reagent from Roche. Part of the problem is that these reagents are used on different pieces of laboratory equipment made by their respective manufacturers, so labs don’t have both.
And you can’t suddenly switch extraction methods without going through a whole revalidation process to prove its accuracy.
Early on, there was a faulty reagent with the CDC test which delayed the rollout of widespread screening in the U.S. But that chemical was used as a control in the test; it was not diagnostic.
When China ran short of tests, early on in their epidemic, they used CT scans to diagnose cases. But these scans are only useful in detecting disease in people who are sick and hospitalized — not for monitoring the healthy contacts of infected people or conducting wider community surveillance.
As the epidemic gains momentum, many additional reagents or other critical components may become more difficult to find, say doctors.
“We are deeply concerned that as the number of tests increases dramatically over the coming weeks, clinical labs will be unable to deploy them without these critical components,” according to a statement released by the American Society of Microbiology.
“Increased demand for testing,” it said, “has the potential to exhaust supplies needed to perform the testing itself.”
Test kits: QIAamp® Viral RNA Mini Kit, QIAamp® MinElute Virus Spin Kit or RNeasy® Mini Kit (QIAGEN), EZ1 DSP Virus Kit (QIAGEN), Roche MagNA Pure Compact RNA Isolation Kit, Roche MagNA Pure Compact Nucleic Acid Isolation Kit, Roche MagNA Pure 96 DNA and Viral NA Small Volume Kit
Instruments: Roche Magna Pure, Roche 480Z, ABI 7500DX, Qiagen EZ1 Advanced XL, QIAcube/QIAcube Connect
Source: Partners HealthCare, Brigham and Women’s Hospital, Massachusetts General Hospital Research Institute