The faulty coronavirus test kits developed by the Centers for Disease Control and Prevention in the early weeks of the pandemic were not only contaminated but also showed a fundamental design flaw, according to an internal review by the agency.
Health officials had already acknowledged the test kits were contaminated, but the internal report, the findings of which were published Wednesday in PLOS ONE, also documented a design flaw that caused false positives.
The proliferation of defective test kits, at a time when no other tests were authorized, slowed health officials’ efforts to detect and track the virus.
“It delayed the availability of more widespread tests,” says Dr. Benjamin Pinsky, the director of clinical virology for Stanford Health Care. He added: “I think it’s important that they got to the bottom of what went wrong.”
In January 2020, the CDC developed a polymerase chain reaction, or PCR, test for the virus. PCR tests, which are performed in labs, can detect the virus at very low levels and are considered the gold standard for diagnosing a coronavirus infection.
Problems arose shortly after the CDC began shipping its test kits to public health labs in early February. Within days, many labs reported that the tests yielded inconclusive results.
In mid-February, the agency acknowledged the kits were flawed, and in April officials with the U.S. Food and Drug Administration said poor manufacturing practices had led to contamination of the test kits.
The new paper presents the results of the CDC’s own internal investigation into the problems with the tests.
The CDC’s test is designed to detect three different regions, or target sequences, of the virus’s genetic material. The test kits contain a set of primers, which bind to and make copies of the target sequences, and probes, which produce a fluorescent signal when these copies are made, indicating that genetic material from the virus is present.
The primers and probes must be carefully designed so that they bind to the target sequences and not to each other. In this case, that didn’t happen. One of the probes in the kit sometimes bound to one of the primers, producing the fluorescent signal and generating a false positive.
“It’s something that should have been taken care of at the design stage,” said Susan Butler-Wu, a clinical microbiologist at the University of Southern California’s Keck School of Medicine. “That’s something you check for.”
The investigation also confirmed that the test kits were contaminated with synthetic fragments of the virus’s genetic material. These synthetic sequences, often used to ensure the tests work properly, were manufactured in the same CDC lab where the test kits underwent quality analysis. It is “probable” that the test kits there were contaminated, the agency concluded.
The contamination suggests the agency has violated standard manufacturing protocols, officials said.
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The problems may also have been a sign of a hasty agency, experts said.
“I’m not at all surprised they ran into some issues at the gate,” said Dr. Emily Volk, president of the College of American Pathologists, who also praised the agency for its transparency. “They were asked to step up production in a way that I’m not sure they had ever been asked to do before.”
The problems with the early tests have prompted the CDC to implement “a more extensive and rigorous review process” in developing a new test that can detect both the coronavirus and the flu, the authors reported. The new test was also tried in three public health labs to make sure it worked, they noted.
“Since the rollout of the first Covid-19 test, CDC has implemented corrective actions and remains committed to the highest quality laboratory science and safety,” the agency said in a statement.
The bigger lesson, said Dr. Butler-Wu, is that the responsibility for developing diagnostic tests should be more widely distributed during a public health emergency. Rather than relying on the CDC to be the sole test developer, officials could also engage clinical and commercial labs to create and deploy tests.
“It’s great that there are all these extra checks, but what are you going to do when a new pathogen shows up and we need to react quickly?” she said. “I don’t think that’s a viable model for responding to a pandemic.”
