From labs to homes: where COVID-19 testing is headed in 2021

A year into the pandemic, the U.S. appears to have reached a new phase in its battle against the coronavirus with vaccinations taking precedence over testing.

With the rollout of COVID-19 vaccines across the country, the number of Americans getting tested has dropped significantly since January, according to data from the Johns Hopkins Coronavirus Resource Center.

While labs and other testing sites in January completed an average of almost 1.9 million tests per day, the average daily testing dropped to 1.5 million in February and 1.3 million in early March.

“Right now, one of the factors that we’re faced with is reduction in testing in part because the testing that’s being done in some of the public health jurisdictions is being supplanted by vaccinations,” said Mary Hayden, chief of the Division of Infectious Diseases at Rush University Medical Center.

Hayden contends that public health authorities don’t have the bandwidth to simultaneously conduct widespread testing and administer vaccines, so they are focusing on the latter.

The decrease in test volumes has negatively impacted at least one diagnostics maker, with others no doubt to follow as they tally and report first-quarter results.

Quidel last week lowered 2021 revenue guidance from $2.9 billion to roughly $2.5 billion, as the company has had to adjust for the “drop off” in U.S. COVID-19 testing demand in the first quarter.

CEO Doug Bryant delivered the bad news at the virtual Barclays Global Healthcare Conference, reporting that test demand has plunged between 30% and 40% in February and March compared to the fourth quarter.

“We didn’t see the continued level of demand for the symptomatic testing that we had in the fourth quarter,” Bryant said during last week’s Barclays event. “Fewer people are getting tested as a consequence of having symptoms.”

However, public health experts warn that widespread COVID-19 testing is still critical to tracking and preventing the spread of the virus, including symptomatic and asymptomatic patients, as well as the detection of new variants and their impact on vaccines and immunity.

“If we don’t test, we don’t know how much infection is there. And while the infection rates are much lower, they’re still high. In many places, they’re higher than they were over the summer,” said Hayden. “We’re still seeing a good amount of infection and we’re not at a place yet where we can relax our overall strategies and reduce testing.”

Whether COVID-19 testing will return to earlier levels, particularly as vaccines are more widely distributed, remains an open question. Undaunted, Abbott Laboratories and Quidel are both ramping up their manufacturing capabilities for cranking out tests.

Abbott in late January reported a 110% jump in diagnostics sales in the fourth quarter compared to the prior year, driven by demand for its rapid antigen and PCR-based coronavirus tests. At the time, CEO Robert Ford told investors that he sees “sustainability” in 2021 for testing despite the rollout of COVID-19 vaccines. However, that was nearly two months ago before a significant drop in U.S. testing.

Nonetheless, Quidel’s Bryant said he expects “significant demand” for COVID-19 tests beginning in the second quarter as the company continues work on an at-home, over-the-counter antigen test that analysts see as the first step in the emergence of a consumer-focused diagnostics business.

Emergence of at-home tests 
FDA started 2021 laying out its COVID-19 testing priorities with a focus on home-based testing. Tim Stenzel, director of the FDA’s Office of In Vitro Diagnostics and Radiological Health, told test developers in January that the agency was particularly focused on at-home tests and home collection kits, as well as point-of-care diagnostics and tests that can be performed in “super-high volume” in central labs.

The agency in rapid succession has provided emergency use authorizations for home-based testing. The number of at-home diagnostics has grown during the recent phase of the pandemic, but most kits test for antigens and require a prescription.

However, FDA on Tuesday issued a new supplemental template for test developers seeking EUAs of certain tests for screening with serial testing, which involves testing the same individual multiple times within a few days. Jeff Shuren, director of FDA’s Center for Devices and Radiological Health, and Stenzel issued a joint statement noting that at-home tests could be authorized for over-the-counter use without the need for validating their use in asymptomatic individuals prior to authorization.

“The FDA believes that evidence of a test’s strong performance in symptomatic patients combined with serial testing can mitigate the risk of false results when testing asymptomatic individuals,” Shuren and Stenzel said.

As of Tuesday, EUAs have been granted to one molecular prescription at-home test, two antigen prescription at-home tests, one over-the-counter home antigen test and one OTC molecular test, as well as 38 molecular authorizations that can be used with home-collected samples.

FDA in November granted Lucira Health an EUA for the first coronavirus diagnostic test for complete self-testing at home. Lucira’s single-use molecular test kit is authorized for prescription home use.

Australia’s Ellume in December became the first over-the-counter self-test for COVID-19 to receive an EUA . The Department of Defense, in coordination with HHS, last month awarded $231.8 million to Ellume to expand U.S. production of its rapid antigen at-home test.

FDA earlier this month granted an EUA to Quidel’s QuickVue At-Home COVID-19 Test, which makes lateral flow technology used for decades by healthcare professionals available to the public, albeit initially only on a prescription basis.

Several other companies, including Abbott, also sell fully at-home COVID-19 tests that do not require sending samples to a lab. Abbott’s antigen-based BinaxNOW COVID-19 Ag Card Home Test, which requires a prescription, became the first at-home, virtually guided coronavirus diagnostic to get the agency’s nod.

FDA earlier this month authorized the first over-the-counter, at-home molecular test for COVID-19. Cue Health is unique in receiving an EUA for OTC use of a molecular nucleic acid amplification test.

However, Romney Humphries, medical director of the clinical microbiology laboratory at Vanderbilt University Medical Center, warns that one of the concerns regarding the use of “at-home testing by antigen or other means” is that it potentially reduces public health visibility into the results as the tests become more widely available and are used by consumers.

Humphries and other critics also see cost as a potential challenge for at-home coronavirus tests beginning to enter the market, costing about $25 per test and higher. “The populations that are impacted the most severely by COVID-19 are those that would be least able to afford that,” she added.

Abbott’s $25 cost for its test and service is the lowest currently available for at-home testing. Ellume’s tests are expected to cost approximately $30 each, while Lucira anticipates its testing kit to have a price tag of about $50 per test.

To address the problem, a study published last week in the Annals of Internal Medicine led by the Yale School of Public Health found that mailing a package of rapid home COVID-19 antigen tests to every household in America and asking people to use them once a week could greatly reduce total infections and mortality at a “justifiable” cost to taxpayers.

The study found that over a 60-day period, weekly availability of testing would avert 2.8 million infections and 15,700 deaths in the U.S. at an incremental cost of roughly $68 per person, which includes $38 for testing, $32 in additional workday productivity losses and savings of $2 in inpatient hospitalization. This works out to a cost-effectiveness ratio of $1.43 million per death averted, according to the study’s authors.

However, free at-home tests are not currently part of the Biden administration’s plan released last month to expand COVID-19 testing or the just passed American Rescue Plan Act of 2021 that includes nearly $48 billion earmarked for testing and contact tracing.

And such home self-testing has inherent challenges.

Hayden and Humphries, along with other experts from the Infectious Disease Society of America, co-authored a March 2 editorial in which they warned that home self-testing is dependent on the ability of consumers to properly follow instructions, ensure that test kits are not expired and understand the limitations of both negative and positive results. In particular, IDSA’s editorial noted that very low community prevalence rates will result in increased rates of false-positive results.

Nonetheless, Yale public health professor David Paltiel makes the case that despite the potential for home testing’s lack of adherence and potential false-negative, false-positive results “don’t let the perfect be the enemy of the good.” Paltiel contends that home-based antigen tests “could save millions of infections and thousands of lives at a reasonable cost.”

Impact of variants on tests
Molecular diagnostics and antigen tests, which detect the presence of COVID-19 infection, as well as serology tests for the detection of antibodies and potential immunity, remain critical to the public health effort to contain the spread of the coronavirus — especially as it mutates.

FDA in January alerted clinical laboratory staff and healthcare providers about the impact of the U.K. coronavirus variant and other emerging forms of the virus on the results of certain PCR tests. Diagnostics made by Applied DNA Sciences, Mesa Biotech and Thermo Fisher Scientific may be affected by the variants but FDA at the time said “the impact does not appear to be significant.”

The agency late last month also published guidance on evaluating the impact of mutations on COVID-19 tests, as new strains threaten to alter the diagnostics’ accuracy, including the potential for false negatives. Abbott, Becton Dickinson and other diagnostics makers have said that they are focused on new virus variants and testing product effectiveness and accuracy.

At the same time, Thermo Fisher, Roche and PerkinElmer in recent weeks have all expanded their respective SARS-CoV-2 assays to help laboratories identify mutations associated with the rapidly emerging variants.

Lab giant Quest Diagnostics also recently introduced a semi-quantitative serology test to measure antibody levels in previously infected and vaccinated individuals. In the U.K., a diagnostics industry coalition is pushing for antibody testing to play a bigger role in immunization campaigns, both pre- and post-vaccination, after studying the immune responses of vaccine recipients.

However, the Centers for Disease Control and Prevention has yet to recommend antibody testing to assess the effects of or need for COVID-19 vaccines.

FDA’s Stenzel has cautioned about COVID-19 vaccines and using antibody tests authorized by the agency to determine immunity in vaccinated individuals. FDA has not authorized any serology tests for use with vaccines for any purpose, either to determine whether a vaccine is needed or determine if it has taken effect and provides any sort of immunity, according to Stenzel.

“That would be something that I think would be a bit dangerous right now,” Stenzel said. Medtech Dive