NEW YORK – A. Menarini Diagnostics has launched two point-of-care tests for COVID-19, including an antigen test that it believes detects not only whether a patient may be infected with SARS-CoV-2 but also provides information about how infected the individual may be.
The two immunofluorescence tests run on the company's AFIAS point-of-care platform, which has two available formats and can provide results in 12 minutes. The AFIAS 1 instrument can run one sample at a time, while the AFIAS 6 runs six samples simultaneously.
The two tests that Menarini is offering are the AFIAS COVID-19 AG, an antigen test using a nasopharyngeal swab that detects the presence of antigens, and the AFIAS COVID-19 Ab test, a rapid antibody test from a capillary or venous blood sample that measures IgM and IgG antibodies against SARS-CoV-2.
Menarini's AFIAS tests and platform were developed by South Korean diagnostic firm Boditech Med, and Menarini has an exclusive European distribution agreement with the company. Cost of the tests varies by countries but is "a fraction of the cost of any molecular assay," said Fabio Piazzalunga, the global head of Menarini Diagnostics.
Menarini worked with Boditech on evaluating the tests beginning in July and collaborated to improve the platform and the tests, he said, and Menarini ran multiple evaluations with regional COVID-19 centers in several countries to help fine-tune the antigen assay's sensitivity.
In particular, the antigen test, could be a differentiator. While the meaning of a high or low viral load in the context of COVID-19 is still not well understood, Menarini said that the ability of its antigen test to measure and differentiate viral loads could be clinically useful.
The test, according to the Florence, Italy-based firm, allows the highest-risk patients to be identified rapidly and treated with greater urgency. The test works by producing a "highly sensitive" fluorescent signal in an infected sample – the brighter the fluorescence, the higher the patient's viral load, Piazzalunga said, adding immunofluorescence is more sensitive than traditional lateral flow tests, the format used for many antigen tests.
According to Menarini, its antigen test has nearly 88 percent sensitivity and around 97 percent specificity and can be used for symptomatic and asymptomatic patients. Meanwhile, the antibody test has a sensitivity of nearly 96 percent and a specificity of nearly 97 percent.
Jae-Ho Lee, principle scientist at Boditech, said that while an evaluation of the test in Italy showed 88 percent sensitivity, in other countries it showed between 92 and 83 percent sensitivity. He noted that whether the sample was a fresh swab or had been preserved in transport media, and sample collection time affected the performance of the test.
Compared to three antigen tests that have received Emergency Use Authorization from the US Food and Drug Administration, Menarini's test shows similarity to Becton Dickinson's Veritor test, which has shown 84 percent sensitivity and 100 percent specificity, according to a company spokesperson.
It lags behind Quidel's Sofia SARS Antigen test, however, which has shown nearly 97 percent sensitivity and 100 percent specificity, according to documents filed with FDA, as well as Abbott's BinaxNow COVID-19 Ag Card, which has shown 97 percent sensitivity and nearly 99 percent specificity.
Both Menarini's antigen and antibody tests and the AFIAS platform have received CE marking and have been launched in Italy, and several other countries in Europe and globally. The platform has also been submitted to regional centers in Italy for evaluation, Piazzalunga said, and there has been significant interest in the tests and instruments from all countries in Europe, with interest in the antigen test especially high, particularly as the number of COVID-19 cases on the continent are surging again.
"All countries in Europe are going to adopt the antigen assays in order to increase their firepower in view of an increased number of COVID cases," Piazzalunga said.
Lee said the firm is currently undergoing clinical validation for a planned EUA application to FDA for the antigen test. It also has regulatory clearance in Brazil and is working on clinical evaluations for registration with the South Korean FDA.
One key aspect of the antigen test is that it provides a number indicating the patient's viral load, which is essential for understanding the infectiousness of the patient, Piazzalunga said. With that information available, clinicians can treat patients who have a high viral load as being "highly infectious and … should be also treated on a priority basis, because depending on the age and morbidity of other diseases, [the patient] could be in a risky situation," he said, while patients with a low viral load may be in a "a less serious situation."
The viral load measure can also be used as an indication of disease progress, with a decreasing viral load likely meaning the disease's infectiousness is waning, Piazzalunga said.
The test provides a Cut-Off Index value determining the relative amount of virus, Lee said. A value of 1 and above is positive, and less than 1 is negative. The Cut-Off Index (COI) was created using samples from 350 patients, 200 negative and 150 positive for the coronavirus. According to Lee, a value between 1 and 20 means there's a low viral load, 20 to 40 is medium, and 40 to 70 is high. He noted that it is a relative value, which can vary depending on preanalytic factors, including sampling practice, sample types, and the storage of the sample in buffer.
To determine the COI value, "The cutoff is set by positive signal and negative noise," Lee said via email. While setting the cutoff low can increase the test's sensitivity, setting it too low could lead to an increase in the number of false positive results. "Thus, we set the cutoff by comparing two groups. One is COVID-19 positive groups (by PCR) and the other is normal or non-COVID-19 group. The distribution is compared and the cut off is set to maximize the sensitivity but does not give false-positive, i.e., the signal level can clearly distinguish two groups."
While researchers and clinicians are still trying to fully understand the significance of viral loads for COVID-19, one recent report published in the journal Cancer Cell found that higher viral loads are associated with a greater risk of death among patients hospitalized with COVID-19. "Giving this information to providers of patients with cancer who have COVID-19 could help them decide on which patients should receive more intensive monitoring when they are in the hospital and which should receive new antiviral medicines if these treatments are in short supply," senior study author Michael Satlin, an assistant professor of medicine at Weill Cornell Medicine, said in a statement about the report. The authors noted that viral load may not predict mortality rate in non-hospitalized people with COVID-19.
Satlin added via email, "In a study of over 3,000 hospitalized patients with COVID-19, we found that patients with higher viral loads on admission were at increased risk of dying during their hospitalization. Based on these results, we believe that diagnostic tests that provide quantitative viral load information would help clinicians in caring for hospitalized patients with COVID-19."
However, Nathan Ledeboer, an associate professor in pathology and laboratory medicine at the Medical College of Wisconsin, said he's not sure about the clinical value of testing for viral load.
"You could try and tie a viral load to the minimum level of virus needed for transmission or for return to work, but there would need to be a great deal of data needed to support such a change," he said via email. "There is likely a significant variation in collection technique from person to person, which could have a massive effect on the viral load detected out of the nasopharynx.
"It is a very interesting concept, may be a bit ahead of the clinical literature right now," he added.
Antigen tests also are still seen as inferior to PCR-based tests, which remain the gold standard for SARS-CoV-2 detection because of their higher sensitivity. Nonetheless, Menarini sees a need for its technology, especially if testing capacity continues to be an issue.
Piazzalunga said Menarini is currently able to produce around 500,000 tests per month and 500 instruments per month. It intends to place the first few hundred instruments in the next few weeks while the first customers in Italian hospitals have received the instruments, he noted.
The main areas of distribution for the test are airports, schools, employers, hospitals, and other areas where a quick result is needed, Piazzalunga said. In hospitals, the platforms are intended for emergency rooms and entry areas to stop patients from spreading the disease throughout the facility, especially as cases increase throughout the flu season and more people head to hospitals for treatment, he said.
"Everybody knows that you cannot run swab tests for all the populations, so you need to have additional tools in order to get the infection as soon as possible," he added. "[This is] the quickest way, at the same time allowing activities to be running safely."
Antigen tests can help laboratories avoid running molecular tests when they're not needed, Piazzalunga said, saving the capacity for confirmatory testing. The antigen tests are "a first barrier for our healthcare systems," he said. "It’s like you build up a wall around your city to defend it with the AFIAS 6 and AFIAS 1, because it's creating a sort of defensive line against the virus."
The antigen and antibody tests aren't the only ones coming down Menarini's pipeline, Piazzalunga emphasized. Currently, the company offers a full range of molecular SARS-CoV-2 tests for the centralized laboratory, most of them licensed from other companies. The firm is the exclusive distributor for Credo Diagnostics Biomedical's SARS-CoV-2 test, as well as that company's tests for diagnosing respiratory syncytial virus and Group Strep A. The test has been placed in all major laboratories across Europe, with nearly 1,000 units sold, Piazzalunga said. Menarini worked with Credo to develop the 20-minute rapid PCR assay at the beginning of the pandemic, and a new iteration of that test differentiating between influenza and SARS-CoV-2 is in the works to launch in a few weeks.
However, Menarini is also working on manufacturing and launching its own high-throughput, high-automation, real-time PCR test, which Piazzalunga said will be launched within the month. The test will be validated on Menarini's own platform, but it "can be used on many common automated systems," as well, he said. That test is expected to receive CE marking by the end of the month, he said. Menarini's test is targeting molecular labs, mostly in teaching hospitals, for use with automated instruments commonly present in central labs, while Credo's test is a point-of-care assay.
Outside of COVID-19, the AFIAS platform already has several other test offerings on its menu, including diabetes, sepsis, and cardiac tests, that can be run in satellite laboratories or emergency rooms, Piazzalunga said. There are 12 additional tests in the works, and he noted that Menarini is working to get some of them authorized in the next month.
But with predictions of a second wave of COVID-19 imminent, rapid antigen and serology tests will continue to be a key component of the coronavirus testing landscape for Menarini.
"When you have people living their normal life and going to work or going to a hospital to get a visit for a normal routine, you need to check if those patients have an asymptomatic infection," Piazzalunga said.