Information

Is it ok to use test's sensitivity and specificity from other countries?

Is it ok to use test's sensitivity and specificity from other countries?


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

I want to calculate likelihood ratios of test scores in clinical psychological assessment setting. In my country, validation studies for many common used tests are missing or information about sensitivity and specificity of test values are missing for certain populations.

My question is: Is it valid for me (in Czech Republic) to use information about sensitivity and specificity of the test for example from Germany or UK validation studies?

Thanks


Rapid diagnostic tests for diagnosing malaria

Fever is common in malarial areas, and getting the diagnosis right (ie deciding if it is due to malaria or other causes) and treating correctly helps save lives, particularly in children. The World Health Organization (WHO) now recommends that all patients with fever suspected of being malaria are properly diagnosed before any treatment begins. This ensures that highly effective antimalarial drugs such as artemisinin-based combination treatments (ACTs) are properly used to prevent unnecessary treatments, untoward risks, and resistance developing.

Standard diagnosis of malaria in the past has depended on blood microscopy, but this requires a technician and a laboratory, and is often not feasible for basic health services in many areas. Sometimes in research studies, another technique called polymerase chain reaction (PCR) is used, but again this requires equipment and trained staff, and cannot be used routinely. Technological advances have led to rapid diagnostic tests (RDTs) for malaria. These detect parasite-specific antigens in the blood, are simple to use, and can give results as a simple positive or negative result, within 15 minutes.

This review evaluates the accuracy of RDTs compared with microscopy and PCR for detecting Plasmodium falciparum parasites in the blood. It includes 74 studies, giving a total of 111 RDT evaluations (of which 104 compared RDTs with microscopy), reporting a total of 60,396 RDT results. Results are presented by type of test, classified by the malaria antigen that they are designed to detect (either histidine-rich protein-2 (HRP-2), or plasmodium lactate dehydrogenase (pLDH)).

The results indicate that RDTs can be very accurate compared to microscopy and PCR. The performance of RDT types varied but the differences were not large. HRP-2-based tests tended to be more sensitive (ie they identified more true cases of malaria) and less specific (ie they wrongly identified more malaria that was not present) than pLDH-based tests. Choice will depend on prevalence of malaria, and we provide data in this review to assist these decisions, although policy makers will also take into account other factors relating to cost and test stability.

The sensitivity and specificity of all RDTs is such that they can replace or extend the access of diagnostic services for uncomplicated P. falciparum malaria. HRP-2 antibody types may be more sensitive but are less specific than pLDH antibody-based tests, but the differences are small. The HRP-2 antigen persists even after effective treatment and so is not useful for detecting treatment failures.

Rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria use antibodies to detect either HRP-2 antigen or pLDH antigen, and can improve access to diagnostics in developing countries.

To assess the diagnostic accuracy of RDTs for detecting P. falciparum parasitaemia in persons living in endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria by type and brand.

We undertook a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register MEDLINE EMBASE MEDION Science Citation Index Web of Knowledge African Index Medicus LILACS IndMED to January 14, 2010.

Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction) in blood samples from a random or consecutive series of patients attending ambulatory health facilities with symptoms suggestive of malaria in P. falciparum endemic areas.

For each study, a standard set of data was extracted independently by two authors, using a tailored data extraction form. Comparisons were grouped hierarchically by target antigen, and type and brand of RDT, and combined in meta-analysis where appropriate.

We identified 74 unique studies as eligible for this review and categorized them according to the antigens they detected. Types 1 to 3 include HRP-2 (from P. falciparum) either by itself or with other antigens. Types 4 and 5 included pLDH (from P. falciparum) either by itself or with other antigens. In comparisons with microscopy, we identified 71 evaluations of Type 1 tests, eight evaluations of Type 2 tests and five evaluations of Type 3 tests. In meta-analyses, average sensitivities and specificities (95% CI) were 94.8% (93.1% to 96.1%) and 95.2% (93.2% to 96.7%) for Type 1 tests, 96.0% (94.0% to 97.3%) and 95.3% (87.3% to 98.3%) for Type 2 tests, and 99.5% (71.0% to 100.0%) and 90.6% (80.5% to 95.7%) for Type 3 tests, respectively.

Overall for HRP-2, the meta-analytical average sensitivity and specificity (95% CI) were 95.0% (93.5% to 96.2%) and 95.2% (93.4% to 99.4%), respectively.

For pLDH antibody-based RDTs verified with microscopy, we identified 17 evaluations of Type 4 RDTs and three evaluations of Type 5 RDTs. In meta-analyses, average sensitivity for Type 4 tests was 91.5% (84.7% to 95.3%) and average specificity was 98.7% (96.9% to 99.5%). For Type 5 tests, average sensitivity was 98.4% (95.1% to 99.5%) and average specificity was 97.5% (93.5% to 99.1%).

Overall for pLDH, the meta-analytical average sensitivity and specificity (95% CI) were 93.2% (88.0% to 96.2%) and 98.5% (96.7% to 99.4%), respectively.

For both categories of test, there was substantial heterogeneity in study results. Quality of the microscopy reference standard could only be assessed in 40% of studies due to inadequate reporting, but results did not seem to be influenced by the reporting quality.

Overall, HRP-2 antibody-based tests (such as the Type 1 tests) tended to be more sensitive and were significantly less specific than pLDH-based tests (such as the Type 4 tests). If the point estimates for Type 1 and Type 4 tests are applied to a hypothetical cohort of 1000 patients where 30% of those presenting with symptoms have P. falciparum, Type 1 tests will miss 16 cases, and Type 4 tests will miss 26 cases. The number of people wrongly diagnosed with P. falciparum would be 34 with Type 1 tests, and nine with Type 4 tests.


Double-Edged Spike: Are SARS-CoV-2 Serologic Tests Safe Right Now?

Richard Torres, MD, MS, Henry M Rinder, MD, Double-Edged Spike: Are SARS-CoV-2 Serologic Tests Safe Right Now?, American Journal of Clinical Pathology, Volume 153, Issue 6, June 2020, Pages 709–711, https://doi.org/10.1093/ajcp/aqaa071

“Validation of new immunologic tests ain’t easy,” it’s been said validation of new tests for human antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a particularly daunting task. While we endure months of disruption to daily life prompted by the ongoing pandemic, serologic testing for antibodies to SARS-CoV-2 has now come to the limelight. SARS-CoV-2 is a highly contagious and acute severe respiratory pathogen that has produced an enormous strain on health care resources. In the United States and many other countries, specific social behavior restrictions have been enacted to moderate the impact of rapid propagation of this contagion (ie, “flatten the curve”). Scientific experts, governmental officials, and other professionals have publicly advocated for SARS-CoV-2 antibody testing to identify individuals who have developed immunity and therefore could potentially reenter the workplace safely despite ongoing high prevalence of the virus. A test for detecting “immune” individuals who will not be reinfected and who will not infect others is an appealing concept, but is it realistic?

The temporary easing of Food and Drug Administration (FDA) marketing/use regulations has enabled the rapid expansion of accurate, fast, and reliable nucleic acid tests to identify acute infection with SARS-CoV-2. Laboratory professionals, diagnostic companies, suppliers, investigators, and hospital administrators have all stepped up to manage acute supply shortages for critical testing components including instruments, test-compatible swabs, and nucleic acid extraction kits, ensuring continued availability of reliable and timely test results. As we approach the peak of severe disease prevalence in several regions (according to comprehensive models developed by epidemiologists and statisticians), we now are faced with a new laboratory crisis: SARS-CoV-2 antibody testing.

Numerous antibody tests have recently become available. Serologic tests for antibodies to SARS-CoV-2 are typically based on lateral flow immunochromatography or enzyme-linked immunosorbent assays (ELISA). Currently available tests predominantly target antibodies to 1 of 2 main surface proteins of the novel coronavirus – the nucleocapsid protein (N) and the spike protein (S). Several assays focus on the S1 subunit of the spike protein, which is somewhat specific to each coronavirus strain. 1, 2 The S1 subunits host the binding domain for the angiotensin converting enzyme 2 (ACE2) receptor, which is thought to be the mechanism by which SARS-CoV-2 gains entry into cells. 1 Because the S1 subunit is highly immunogenic and its affinity for the ACE2 receptor appears to correlate with infectivity, 1 it has been the target for SARS-CoV-2 serologic assays with reportedly high sensitivity and specificity. 2, 3

Clinical implementation urgently requires validation of these new assays. Since real-life performance data are scarce, the coronavirus disease 2019 (COVID-19) pandemic has been marked by an inspiring level of interlaboratory collaboration. At Yale-New Haven Hospital, we are particularly grateful for invaluable discussions and sharing of data with Johns Hopkins, Massachusetts General Hospital, Mount Sinai, NYU-Langone, Cornell/Columbia, ARUP, Mayo Clinic, and many others. Scientific journals have contributed via the rapid dissemination of curated studies, and preprint sites offer additional information that can be scrutinized in a shorter time frame, prior to dedicated reviewer analysis. The accumulation and exchange of valuable laboratory evidence has increased our understanding of the serologic testing landscape in a short period of time. As a result, we now know that individuals with symptomatic SARS-CoV-2 infection will generally not have detectable antibodies to SARS-CoV-2 within the first 7 days of the onset of symptoms. 3, 4 The majority of hospitalized SARS-CoV-2-infected individuals with confirmed viral RNA will have detectable IgG antibodies 14 days, and more certainly 28 days, after the onset of symptoms with assay sensitivity and specificity in the high 90 percents. 5 Total antibody concentration appears to rise to detectable levels first IgM and IgA both rise 1 to 2 days earlier than IgG 3 (unpublished observations). Preliminary data suggests older individuals produce more robust antibody responses. Assays differ in overall performance, but several methods being validated by large laboratories appear comparable. One might therefore ask: “What, exactly, is the problem?”

As valuable as this information is, it may be insufficient to support critical decisions that providers, managers, administrators, and governmental agencies will face, especially regarding immunity in individuals who have remained asymptomatic or minimally symptomatic during the pandemic.

To determine whether an individual is immune to SARS-CoV-2, we must know the pretest probability in the specific population being tested, as well as the sensitivity and specificity for protective antibodies of the assay. A significant challenge is that, to date, serologic data are largely limited to hospitalized, ill patients. There is reason to suspect that serologic findings in asymptomatic or mildly symptomatic exposures may not correlate as well as in hospitalized patients, particularly as anecdotal evidence suggests individuals with low viral loads produce lower antibody titers (unpublished data).

In addition, assessment of antibody effectiveness is problematic even in seriously ill patients. Approximately one-third of SARS-CoV-2-infected patients who developed antibodies during hospitalization have been reported to lack antibodies that neutralize virus in plaque growth assays, considered the standard laboratory test for antibody effectiveness. 6 This implies an individual with antibodies may not be immune to reinfection.

Finally, a positive antibody result (in a potentially immune individual) does not guarantee noninfectious status there may be continuing active viral shedding, particularly if their antibodies are nonneutralizing. The molecular heterogeneity of SARS-CoV-2 subtypes, 7 could also have an effect on the sensitivity and specificity of serologic assays. The imperfect performance of comparable, more established, serologic tests for other diseases (eg, toxoplasma IgM) may be acceptable because we have a much better understanding of the clinical scenarios. Unfortunately, the same confidence does not hold true for SARS-CoV-2 serologic testing.

Quality will play a pivotal role in ensuring we are able to obtain the data required to understand COVID-19 immunity. Some of the serologic tests currently available are simply bound to be inferior and that needs to be documented. The United Kingdom abandoned large-scale purchasing of test kits when the kits failed to satisfy minimum validation metrics. 8 Predictably, online direct-to-consumer tests are being aggressively marketed without any published information to evaluate their clinical performance. 9 While some antigenic targets have shown minimal cross-reactivity with the 4 prevalent non-SARS-CoV-2 coronaviruses, 2 without validation studies there is a real risk that some assays may simply reflect prior exposure to the common cold. Fortunately, reputable commercial entities with experienced scientists, sophisticated equipment, and good manufacturing practices have begun to release serologic assays under FDA guidance. Commercial assays typically undergo extensive prerelease standardization, including testing for interferences and matrix effects, quality control, and test results in large patient cohorts. This sets the stage for acquisition of clinical and epidemiologic data.

But concerns remain when proposals call for testing populations different from those used to validate the assay. What if a health care worker (HCW) who had a fever and no other symptoms 14 days ago wants to return to work and tests positive for SARS-CoV-2 antibodies can we assume with high confidence that this HCW is both immune and noninfectious? If we are wrong, then we have placed patients and coworkers at risk. A failed prevention is also likely to erode faith in the integrity of laboratory tests for the disease. We have heard the argument that any testing is better than none, providing a path to restoring normalcy, and the lack of which has high ongoing societal costs. As laboratory professionals, we can only respond that for anti-SARS-CoV-2 serology: (1) bad assays will always be counterproductive (2) good assays have not been proven in the proposed test population and (3) more experience is needed to help us properly interpret the serologic test results.

Regulatory and health officials appear to recognize these limitations eg, return to work guidelines from the Centers for Disease Control and Prevention currently do not include serologic testing. The role of serologic testing in identifying potential donors for convalescent plasma remains to be fully investigated (as does the therapeutic benefit of such an intervention in this setting), but other uses for serologic testing may emerge. One such clinical scenario where SARS-CoV-2 serologic assays may be particularly useful is when a positive serology is accompanied by repeatedly negative nucleic acid testing in the setting of a highly suggestive clinical presentation serology may provide the basis for specific therapies for COVID-19 infection. Still, until we understand the patterns of antibody response to SARS-CoV-2 in asymptomatic individuals, and the correlation of antibody response with susceptibility to reinfection, it seems prudent to apply caution to the criteria used to frame economic, social, and corporate policy.

Biological variability is the bane of clinical pathology in the setting of validation and clinical application of serologic testing, this variability presents a daily struggle. Reputable diagnostic companies and both commercial and academic clinical laboratories have repeatedly demonstrated that the value of dedication to testing quality ensures clinical utility. Health industry manufacturing experts, engineers, quality and regulatory managers, sales professionals, scientists, and physicians have been working diligently under significant duress during the COVID-19 pandemic, to the great benefit of society. As laboratory medicine professionals, we must now leverage these efforts by ensuring that: (1) serologic tests for SARS-CoV-2 antibodies perform as well as intended and (2) we provide information that enables health care providers, administrators, and health officials to best interpret and apply the available evidence. At this point in the evolution of serologic testing for SARS-CoV-2, we must say in unison “caveat emptor.”


PCR, antigen and antibody: Five things to know about coronavirus tests

To diagnose and contain the spread of coronavirus, testing is critical. There are two types of Covid-19 tests — those that are designed to detect whether you have the infection now, or those crafted to check whether you have been previously infected by the virus — SARS-CoV-2 — that causes the disease. Like any other product these tests have varying degrees of accuracy and reliability, and can be used to achieve different aims.

We want technologies that are fast, accurate, have high capacity, that don't require expensive, complex laboratory equipment or the expertise of highly trained people, but there's nothing which fills all of those criteria at the moment, says Professor Jon Deeks, a biostatistician and testing expert at the University of Birmingham, UK. ‘We haven't got any perfect test like that, but there are some which are sort of good in some aspects, but not in others.’

See also

Here are five things to know about coronavirus tests:

While antigen tests look for proteins on the surface of the virus to ascertain the presence of the pathogen, PCR (polymerase chain reaction) tests are engineered to seek genetic material called RNA that instructs the virus to make these proteins.

Both tests also require a swab from the back of your nose or throat as a sample and cannot determine whether you are contagious if positive but that’s where the similarities end.

In the case of PCR, the sample is sent to a lab where it is heated and cooled using special reagents to convert the virus's RNA into DNA, and then make millions of copies of the DNA, which allows for the identification of the organism. This process can take hours, requires sophisticated lab equipment and technicians, and is typically done one sample at a time, although there are machines that can process multiple samples. Although the sample needs to be sent to a lab, the time consuming process delivers as the results are almost 100% accurate in spotting infected people when there is virus on the swab.

In contrast, antigen tests — often referred to as rapid tests — work by mixing the sample with a solution that unleashes specific viral proteins. That combination is then applied to a paper strip that contains a bespoke antibody optimised to bind these proteins if they are present. Like a home pregnancy test the result is reflected as a band on the paper strip.

The process doesn’t require a lab, and can be done in up to 30 minutes, but that speed comes at the cost of sensitivity. Although these tests are reliable when an individual has a high viral load, they are far more prone to false-negative results if a person has low amounts of the virus in their body.

These two measures are used to determine the credibility of a test: ‘How well does it detect disease, and how well does it detect the absence of disease,’ explained Prof. Deeks.

Sensitivity is defined as the proportion of patients with Covid-19 who correctly get a positive result, while specificity is the proportion of patients without an infection that the test correctly identifies as negative.

In general, a highly sensitive test has a low false negative rate but runs a risk of false positives if its specificity is not up to scratch. On the other hand, a highly specific test runs a risk of false negatives if the test’s sensitivity is poor, but will generally have a low false positive rate. PCR tests are considered the gold standard because they are generally highly sensitive and highly specific.

  1. When it comes to rapid tests, the person who administers the test can be crucial

In the UK, an antigen test called the Innova lateral flow test was piloted in the city of Liverpool as part of the government’s plans to carry out mass vaccinations in the country. The aim was to allow workers back into offices and allow families to hug their loved ones again in care homes, Prof. Deeks notes.

But this ‘test to enable’ strategy backfired when scientists found that in a population of mostly people with symptoms the test’s sensitivity fell to about 58% when administered by self-trained staff, versus 73% when tested by skilled research nurses and 79% when tested by laboratory scientists. In a study that looked at people without symptoms, the sensitivity fell to roughly 49% versus PCR tests.

‘So, there's this gradient of saying, the more experienced people are at doing the test, then less cases will be missed,’ he said. There are some stages that have to be followed very carefully, he says, like reading it accurately. ‘Sometimes it's hard to tell whether that's a line or whether it's a smudge,’ said Prof. Deeks.

PCR tests are processed in the lab, so the potential for error is much lower, he adds.

Test makers are also trying to develop at-home tests but given the lessons we've already learned about how rapid test accuracy depends on who administers it, that's a problem, Prof. Deeks suggests.

‘If people can do tests more easily, then more people will be tested… but I don't think we've got the test to do it yet,’ he said. He adds that there aren’t any good studies looking at what benefit this extra testing would have, for instance, what impact repeated false-negative results could have on behaviour.

In a proposal for common rules on rapid antigen tests published on 18 December, the European Commission said that rapid antigen testing should be carried out by trained healthcare personnel or other trained operators.

‘If people can do tests more easily, then more people will be tested… but I don't think we've got the test to do it yet.'

Prof. Jon Deeks, University of Birmingham, UK

  1. Until rapid tests are made more accurate, negative results should not be used to encourage risky activities

If a test, like the Innova test, is missing up to half the cases then nobody can really be considered free of the risk of having or transmitting infection, Prof. Deeks notes.

‘You're always going have a small percentage of those people who are missed by all tests,’ said Gary Keating, chief technology officer of HiberGene, an Ireland-based company that has a Covid-19 test. The test utilises LAMP technology, which is a low-cost alternative to PCR technology.

‘I think it's always dangerous to taking a single diagnostic test in isolation, and use that as the basis to go and make a very significant medical or lifestyle decision,’ said Keating.

Used on a large scale, results could lead to false sense of security, according to Prof. Deeks.

Governments are keen to use rapid tests as they are cheaper and faster to deploy for mass vaccination campaigns, but because they have limitations in terms of accuracy then it is key to not use negative results to enable more risky activities such as meeting your elderly or vulnerable loved ones, he says.

Some countries, like the United States, advise getting a PCR test if individuals with symptoms test negative with a rapid antigen test to confirm the result.

Although rapid tests are good at catching people who have high viral loads, it isn’t yet clear what the viral threshold must be to thwart contagiousness. With Covid-19, those that are infected see a peak in viral load in the early phase of the infection, but viral RNA can stick around for weeks or even months.

  1. Antibody tests could be useful in measuring the durability of vaccine responses

Antibodies are soldiers deployed by the immune system in response to a foreign invader — in this case SARS-CoV-2. ‘Originally, there was hope that antibody tests might enable us to diagnose disease quickly and easily. But it turns out, the tests don't turn positive for two to four weeks (post infection),’ said Prof. Deeks.

And the plot thickens, because even if you test positive for antibodies — that information doesn’t tell you much, apart from the high likelihood that you had contracted Covid-19 in the past.

‘We don't really know what levels of antibodies leads to protection (from disease) and indeed, which kind of antibody is the most important — I'm not sure whether there's consensus on that either,’ he said.

It is also unclear how long Covid-19 antibodies persist in the body, or that anybody who has tested positive for antibodies won’t catch the virus again.

Where these tests could come handy is in estimating the spread of Covid-19 at a population level — for instance, what percentage of the population and what ethnic groups have contracted Covid-19, as well as in measuring the durability of vaccine responses, Prof. Deeks adds.

HiberGene’s coronavirus test was one of the initial 18 emergency projects funded by the EU. If you liked this article, please consider sharing it on social media.


Summary

WHO recommends a minimum of 80% sensitivity and 97% specificity for antigen-detection rapid diagnostic tests (Ag-RDTs), which can be used for patients with symptoms consistent with COVID-19. However, after the acute phase when viral load decreases, use of Ag-RDTs might lead to high rates of false negatives, suggesting that the tests should be replaced by a combination of molecular and serological tests. When the likelihood of having COVID-19 is low, such as for asymptomatic individuals in low prevalence settings, for travel, return to schools, workplaces, and mass gatherings, Ag-RDTs with high negative predictive values can be used with confidence to rule out infection. For those who test positive in low prevalence settings, the high false positive rate means that mitigation strategies, such as molecular testing to confirm positive results, are needed. Ag-RDTs, when used appropriately, are promising tools for scaling up testing and ensuring that patient management and public health measures can be implemented without delay.


The Fast Lane for COVID Testing Has Opened Up in the U.S.

For a recent flight that required a negative COVID-19 test result, I went through a process so silly and laborious that it got me wondering. First, I booked an appointment at an approved testing center, about a 25-minute drive from my home. Upon arriving, I paid $175 to take a polymerase chain reaction (PCR) test. I then drove home, downloaded an app and waited 24 hours&mdashall to receive results that, in many other countries, can be obtained in a fraction of the time without ever leaving the house.

So why, more than a year into a pandemic, does the U.S. lag behind other developed nations in the deployment of rapid antigen testing? Recently, for the first time, we received a hint that our nation&rsquos top health officials have been wondering the same thing.

On March 31 the Food and Drug Administration effectively made a game-changing announcement: two rapid at-home antigen tests, Abbott&rsquos BinaxNOW and Quidel&rsquos QuickVue, will soon be sold over the counter (OTC) on drugstore shelves, without the need for a prescription.

That may sound like a little. It&rsquos a lot. It is of such critical potential impact, in fact, that Harvard University epidemiologist Michael Mina&mdashwho has for months been a vocal advocate of rapid antigen testing for screening purposes for months&mdashproclaimed in an April 1 media call that March 31 &ldquowas a massively important day &hellip on the testing front.&rdquo

There&rsquos no prescription needed. You can self-administer the test at home&mdashor, depending upon the need, at schools, workplaces and community centers, for example&mdashso that you and the people around you can know almost immediately whether it&rsquos safe to congregate. Because the virus that causes COVID-19, SARS-CoV-2, and its variants can spread asymptomatically, experts believe these tests could help detect them early, while people may be vectors of infection, and thus break the chain of transmission.

&ldquoHad we had these tests in a widely scalable at-home, simple to use fashion last summer, we could have prevented hundreds of thousands of deaths. We could have prevented surges of cases,&rdquo Mina said in the April 1 press conference. This pandemic &ldquois still a massive tragedy every single day. And if we can use these types of tests to mitigate spread moving forward &hellip that alone might be enough to ensure that outbreaks don't grow.&rdquo

This is clearly a shared view that is acted upon in other countries. Switzerland&rsquos Federal Council recently announced it is &ldquomassively expanding&rdquo its rapid testing system with "free tests for all." As of March 8, everyone in Germany can receive rapid antigen testing once a week for free at a screening center or pharmacy, according to Sandra Ciesek, director of the Institute of Medical Virology at University Hospital Frankfurt in Germany. The Federal Council aims to increase this to five free self-tests per person a month as better tests become available. "To ensure that everyone can be tested immediately, all tests in pharmacies and test centres will be free of charge, even for people without symptoms,&rdquo the council wrote in a news release.

And in January, England committed to scaling up its rapid testing program. By March, free testing for all businesses was offered, and as of April 9th, twice-a-week free testing is available to everyone in the country. Regular workplace testing is a vital part of our route back to normal life,&rdquo said U.K. health secretary Matt Hancock in a March statement. &ldquoThese rapid tests will [allow] positive cases of COVID-19 to be caught quickly, which is crucial in helping businesses protect their workplaces and employees as we cautiously lift restrictions.&rdquo

In the U.S., by comparison, things moved at an agonizingly sludgy pace. An FDA official told me the agency cannot compel manufacturers to submit applications for specific tests. Rather the developers decide for themselves whether to apply for a test that will be prescription or over-the-counter. Prior to the FDA&rsquos statement March 31, of the 16 rapid antigen tests that had been approved, only one was greenlit for home over-the-counter use (without a prescription) by Ellume, and it is not yet available to the public for purchase. That is about to change dramatically.

The newly approved tests are authorized by the FDA for serial use, meaning an individual could be tested now and then again within 24 to 36 hours. Serial testing is important because it can improve the sensitivity of the test. If you&rsquore in the early phase of infection, when viral levels are low, a test&rsquos result may be a false negative&mdashthat is, it might show negative when, in fact, you&rsquore positive for COVID. A test repeated the next day would more likely be positive, due to rapid increases in viral levels during the acute stage.

Mina and others hope that Americans will soon use these tests in the morning. Brush your teeth, take a quick 30-second test (it&rsquos similar to a pregnancy test), come back in 10 to 15 minutes to check the results and, if clear, head to school or work. If you&rsquore positive, do a more accurate nucleic acid amplification test (such as a PCR test) to be sure and then self-isolate.

Mina has pushed hard for the approval of these less expensive, simpler antigen tests for several reasons. One is simply scale. Manufacturers can ramp up production to tens of millions of tests per day, according to Mina&mdashan amount that would be necessary if much of the population is using these assays. With Abbott&rsquos BinaxNOW manufacturing facilities able to produce tens of millions of test per month and Quidel&rsquos goal of 50 million of its QuickVue tests per month by the end of 2021, according to company spokespersons, Mina is hoping more companies will enter the space so availability in the near term does not become a big issue.

In a March 31 press release, Abbott said its test should be available nationally in &ldquolarge quantities" at major food, drug and mass merchandiser retailers&mdashand it has said they will be sold to retailers at a cost that will be in the &ldquosingle digits.&rdquo A Quidel spokesperson wrote in an email exchange that the company will soon announce pricing on its two-test unit carton.

The need remains high for a continued buildup of fast, accessible testing, particularly for screening. &rdquoWe are in a risky period with variant growth, incomplete vaccination, return to school, increased population mobility and reduced mask wearing,&rdquo says Bruce Tromberg, director of the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health in an interview. &ldquoThe need to do screening, using accessible tests at home, on a large scale and on a regular cadence, is even more important.&rdquo

PCR tests have been recognized as the gold standard to diagnose acute infection with SARS-CoV-2 because of their high sensitivity&mdashbut they often require a central lab for processing and many cannot be done quickly, and delays in reporting the results increase the chance that someone is spreading the virus while waiting to hear back on their test. While not every PCR test costs the $175 that I paid (the Centers for Disease Control and Prevention (CDC) website estimates an average price of $75 to $100), its higher cost means that lower-income Americans will be less likely to be able afford it. Easier access to testing for these communities, which have shouldered much of the burden of COVID-19 and are facing health inequities, is welcome.

How accurate are these tests? The scientific community has debated the performance of rapid antigen tests. Officials at the CDC, along with most experts, believe antigen tests are less sensitive than PCR tests. In the April press conference, however, Mina contended that while PCR is the standard for diagnostic tests, it is &ldquohorribly not specific&rdquo for knowing who needs to isolate. He said it detected far too many remnants of viral RNA a week to two weeks, or more, after someone has become infectious. &ldquoThis is not a public health test,&rdquo he said. &ldquoYou can&rsquot take a test that&rsquos meant to be specific to the infectious period and make a gold standard against it that is totally not specific to the infectious period.&rdquo

In contrast, Mina believes rapid antigen tests have &ldquoexcellent contagiousness sensitivity&rdquo (more than 98 percent sensitive) and that they're good at detecting people who have COVID during the period when they are most infectious and capable of transmitting virus to others. At this point, viral titers are high, and &ldquothe rapid tests will be positive,&rdquo Mina says. &ldquoWhen viral levels fall, the tests turn negative.&rdquo The Infectious Disease Society of America&rsquos Website states, &ldquoRapid tests may ultimately contribute to better SARS-CoV-2 containment via more efficient detection and subsequent isolation,&rdquo but it makes &ldquono recommendations for or against using rapid tests.&rdquo

Where more experts do agree, and the CDC and FDA concur, is that rapid antigen tests, when performed serially, may increase the chances of detecting individuals who might be missed early with a single test. In a recent press release, Quidel indicated the test &ldquoshows excellent performance, with positive results agreeing with PCR 83.5 % of the time, and negative results agreeing 99.2% of the time.&rdquo A spokesperson at Abbott says BinaxNOW&rsquos overall performance demonstrates 84.6 percent sensitivity and 98.5 percent specificity in people at seven days or less post-symptom onset at all Ct (cycle threshold) counts.

(If you&rsquore curious as to whether these tests will detect the new variants, many experts believe they will. Mina explained at the press conference that they are unlikely to lose their effectiveness because the virus is mutating at a different part than the proteins these rapid tests are targeting.)

Approval of these tests comes on the heels of the FDA&rsquos recent announcement of a streamlined pathway to emergency use authorization (EUA) for at-home screening tests, which allows companies to take already authorized prescription-based tests and apply to sell an over-the-counter claim without completing large trials. This appears to be working now with several over-the-counter tests approved.

In an interview, an FDA spokesperson said that based on more positive data related to serial testing that demonstrates good performance, a developer could potentially get an EUA approval for less sensitive tests, and be able to submit data post authorization. They indicated too that they do not hold any of the point-of-care tests or at-home tests to near the same high threshold as lab-based PCR test. In a press release, Jeff Shuren, M.D., J.D., director of the FDA&rsquos Center for Devices and Radiological Health said, &ldquoAs we've said all along, if it&rsquos a good test, we&rsquoll authorize it.&rdquo

Both the Biden administration and the CDC have indicated support for rapid testing. In February, President Joe Biden&rsquos team announced that it would contribute $230 million to increase production of the Ellume antigen tests&mdashthe only OTC product on the market at the time authorized for both symptomatic and asymptomatic use. The company is expected to supply the U.S. with approximately 100,000 tests per month through July (and a total of 8.5 million guaranteed to the U.S. government), which is a start. Andy Slavitt, senior adviser for COVID-19 response at the White House, told reporters, &ldquoThat&rsquos good, but it&rsquos obviously not where we will need to be.&rdquo

The CDC recently issued extensive new guidance related to the use of screening tests for COVID-19. In collaboration with the NIH, the agency announced a new public health initiative on March 31. The &ldquoSay Yes! COVID Test&rdquo initiative will enable 160,000 residents across two communities to perform free, rapid antigen tests three times a week for a month. &ldquoThe new initiative is exciting,&rdquo Tromberg says. &ldquoIt&rsquos a real-world demonstration of how rapid-accessible tests can be used to stop the chain of transmission and reduce prevalence.&rdquo

This is our future, and it&rsquos one way to help open our country. &ldquoReliable and widely available testing is a critical part of our efforts to stop the spread of COVID-19,&rdquo said CDC director Rochelle Walensky in a recent statement. Abbott CEO Robert Ford took it a step further in the company&rsquos March 31 press release, saying, "Together with vaccines, the BinaxNOW Self Test will help Americans get back to doing what they want and need to do&mdashlike going to work and school or seeing friends and family&mdashwith greater confidence."

It&rsquos the kind of development Mina has been lobbying for during the better part of a year. Now, he said in the April 1 press conference, the FDA, CDC, NIH and White House &ldquoare all sort of simultaneously recognizing this is a very powerful tool over the last two, two and a half weeks&hellip. I think that we should consider this sort of a pivotal change in the &hellip testing landscape in the U.S.&rdquo

In Germany, meanwhile, the famed Berliner Ensemble theater has reopened to sold-out audiences. To attend the show, visitors must wear masks, social distance and present not only their tickets but a negative COVID result from a rapid test taken just 12 hours prior to showtime. It&rsquos working quite well. Very soon, Americans, too, may be able to make their own curtain call.


Beroni Group’s SARS-CoV-2 Antigen Test Kit (Colloidal Gold Method) Has Received Export Permit

NEW YORK and SYDNEY, Australia, April 27, 2021 (GLOBE NEWSWIRE) -- Beroni Group (OTCQX: BNIGF NSX: BTG) (“Beroni” or the “Company”), an Australia-based diversified biopharmaceutical enterprise today announced that it has received the notification that its SARS-CoV-2 Antigen Test Kit (Colloidal Gold Method) is granted authorization for export.

As announced in December 2020, Beroni Group’s SARS-CoV-2 Antigen Test Kit (Colloidal Gold Method) has received the CE certification for distribution to the EU markets. This test kit requires no blood, and only a nasopharyngeal swab is needed to collect samples. It can also deliver the test results within 10 minutes. Based on clinical tests, the sensitivity, specificity and total coincidence rate of anterior nasal sampling are 95.90%, 99.19% and 97.55% respectively, while the sensitivity, specificity and total coincidence rate of nasopharyngeal and oropharyngeal sampling are 98.36%, 99.19% and 98.78% respectively. Our test results showed that the test kit could provide users with a safe, reliable and rapid way of detecting the COVID-19 virus.

“COVID-19 is a global health crisis faced by each of us. Getting the export authorization is an important achievement in our effort to overcome the coronavirus. This new test kit can let testers know whether they have the antigen before the vaccination. We know there have been cases where the person, who was still in isolation, returned several negative PCR tests, however serology testing conducted brought back a positive result,” commented Jacky Zhang, Chairman and CEO of Beroni Group. “At present, our other COVID-19 test kit - Beroni SARS-CoV-2 IgG/IgM Antibody Detection Kit - has been exported to Britain, Japan and other countries. With CE certification and export authorization, we are ready to integrate our multi-centered resources to distribute the antigen test kit to the needed markets.”

About Beroni Group Limited

Beroni Group is an international biopharmaceutical enterprise dedicated to the innovation and commercialization of drugs and therapies to combat various global diseases such as cancer and infectious diseases. Its diversified portfolio is comprised of a US FDA approved virus diagnostic kit, an e-commerce platform for the sale of pharmaceutical products and a development pipeline targeting oncology and cell therapies. Beroni has operations in Australia, United States, China and Japan. To learn more about Beroni, please visit www.beronigroup.com.

Forward-Looking Statements Disclaimer

This press release contains forward-looking statements or forward-looking information, within the meaning of applicable United States and Australian securities laws with respect to the Company. By their nature, forward-looking statements are subject to a variety of factors that could cause actual results to differ materially from the results suggested by the forward-looking statements. Accordingly, readers should not place undue reliance on the forward-looking statements. Generally forward-looking statements can be identified by the use of terminology such as “anticipate”, “will”, “expect”, “may”, “continue”, “could”, “estimate”, “forecast”, “plan”, “intend”, “believe”, “potential” and similar expressions.

Forward-looking information contained in this press release is based on Company management’s opinions, estimates and assumptions in light of its experience and perception of historical trends, current conditions and expected future developments, as well as other factors that management currently believes are appropriate and reasonable in the circumstances. Forward-looking statements involve significant risks, uncertainties and assumptions, and there can be no assurance that such statements, or its underlying risks, uncertainties and assumptions will prove to be accurate. Factors that could cause actual results or events to differ materially include, without limitation, risks related to laws, rules and regulation applicable to the Company as well as the industry in which it operates (including in respect of taxes and other levies), economic or market conditions on both a national and global level, currency fluctuations, risks inherent to other entities at a similar stage of development and industry in which the Company currently is, competition from the Company’s competitors, unsatisfactory development or marketing of the Company and/or its products or services, regulatory action or litigation (including product liability claims), and failure to enter into agreements or arrangements with other parties on fair or reasonable terms. Forward-looking information is made only as of the date on which it is provided and, except as may be required by applicable laws, the Company disclaims any intent or obligation to update such forward-looking information whether as a result of new information, future events or otherwise.

For more information, please contact our IR consultants at:


Disclaimer

This list is updated twice weekly, and only includes tests that have received a US Food and Drug Administration EUA. It only includes tests for which data and documentation is available and for which their stated intended use aligns with their regulatory status. This site is not intended to be used as a reference for funding or grant proposals. Noninclusion in this list should not be interpreted as judgment on validity or legitimacy of tests.

Note on sensitivity and specificity data

The manufacturer-reported sensitivity and specificity data is listed, where available. A highly sensitive test should capture all true positive results. A highly specific test should rule out all true negative results. These measures are not independently validated by the Johns Hopkins Center for Health Security. If a sensitivity or specificity is not listed, it was not listed/available at the time of posting. When available, the number of samples used for sensitivity/specificity definitions are listed in the product description in the extended versions of the tables.

The terms “sensitivity” and “specificity” may not appear in the manufacturers’ information sheets, but rather these values are often reported as “positive percent agreement” and “negative percent agreement.” The US FDA recommends that manufacturers use these terms to indicate that a non-reference standard was used when evaluating the test.

More information on serology tests:

This page was last updated on June 11, 2021.


Covid-19: Safety of lateral flow tests questioned after they are found to miss half of cases

The lateral flow devices used in the community testing pilot in Liverpool only picked up half the covid-19 cases detected by polymerase chain reaction (PCR) tests and missed three out of 10 cases with higher viral loads, according to the government’s own policy paper.1

Given the low sensitivity of the Innova lateral flow devices when used in the field, experts are questioning how they can be used to allow care home residents to have contact with relatives over Christmas safely or for students to know for certain that they are not infected before returning home.

The information can only be found by looking in annex B of the document, Community testing: a guide for local delivery, which was published on 30 November. This is the first publicly available information about the field evaluation of the Innova tests in Liverpool which has been criticised for its lack of transparency, accuracy of the tests used, and costs and potential harms.23

Jon Deeks, professor of biostatistics at the University of Birmingham and leader of the Cochrane Collaboration’s covid-19 test evaluation activities, told The BMJ, “The results are hidden as a single sentence in the annex of a document. This is not the way important scientific findings should be made public, particularly when the test is going to be used off label with hundreds of thousands of people.”

The Department of Health and Social Care said that over a million lateral flow tests have already been sent to 385 care homes and more would be sent over December to roll out visiting by Christmas.

A spokesperson said, “Extensive testing has shown that lateral flow devices are suitable for use in care homes where they can identify people who are the most likely to spread the virus further and prevent transmission of the disease from staff and visitors. Testing is only part of the approach and it’s essential visitors wear personal protective equipment and follow all infection control methods to keep their loved ones, other residents, and staff safe.”

Susan Hopkins, senior medical adviser to Public Health England and NHS Test and Trace, told The BMJ, “These tests are an additional tool in helping us detect cases that we wouldn’t otherwise know about, in doing so helping us to break chains of transmission and save lives. No test will detect every single case, but these tests are proving to be accurate and reliable and we are confident that they can be used to rapidly identify many people who are silently carrying the virus.”

She added, “In care homes, these tests can help make planned visits safer by identifying visitors that are unknowingly carrying high levels of virus, and so prevent them from passing it on to their loved one.”

However, public health and social care directors in some areas, including Greater Manchester and Sheffield, have written to care homes warning them not to use the rapid tests until they have had more information from the government on the accuracy of the tests and training in how to use them.4

The government has invited all tier 3 areas to offer community testing of asymptomatic people after what it described as “the positive impact” of the Liverpool pilot scheme. The guidance says that the Innova lateral flow tests offer 99.6% specificity and “the measured test sensitivity, in ideal hands is 76.8%” but “is likely to be lower under operational conditions.”

The document then adds, “In the field evaluation in Liverpool, compared with PCR tests, these tests picked up five out of 10 of the cases PCR detected and more than seven out of 10 cases with higher viral loads, who are likely to be the most infectious.”

Deeks said, “These results are devastating—they are missing a third of those with high viral loads. How can these tests be used for safe entry into care homes, for healthcare workers to safely return to work, or for the safe return of students? They are not fit for purpose.”

Allyson Pollock, director of the Newcastle University Centre for Excellence in Regulatory Science and a member of Independent SAGE, said, “This is scandalous. Where are the data underpinning the statement in the document? Mass testing should be paused until we see the evidence and Liverpool evaluation.”

She added, “The Liverpool public who went for testing seem to have been grossly deceived and misinformed about the usefulness of the test and purpose of testing. They were not told that one of the purposes was research on the lateral flow test in healthy people.” She said that the pilot should have first gone for advice to the UK national screening committee and have had ethics approval.

The Scottish National Party MP Neale Hanvey has submitted two written parliamentary questions calling for publication of the full data about the community testing pilot in Liverpool. He told The BMJ, “My main concern is false reassurance. There is a clear risk that those with a false negative result will feel overly confident about mixing with vulnerable people over Christmas.”

An earlier assessment of the Innova test by Public Health England’s Porton Down laboratory and the University of Oxford found an overall sensitivity of 76.8%, but said that sensitivity dropped to 58% when carried out by self-trained members of the public.5 However, when health secretary Matt Hancock was asked at a health select committee about the test missing almost half of cases, he said he “didn’t recognise” the 58% figure.


Precision

If you look close enough, you can find that the precision is actually calculated as True Positive/Total Classified Positive. That’s right! Precision measures the accuracy under the circumstance that when the testing result is positive. In other words, how accurate it is if you are tested positive.

Precision reflects what proportion of positive classification is actually correct.

If you are tested positive by this testing tool, there’s a 50% chance that you actually didn’t contract the virus. That is pretty high! You probably don’t want to use a swab with this accuracy.

Precision is useful when the cost of FP is high. For example, if we have low precision in our COVID-19 testing, it means there are a lot of healthy people diagnosed as positive. These people will be falsely sent to the hospital and treated for a disease they don’t have. This is not only a total waste of our health-care resources but also exposing healthy people to a dangerous environment, and therefore potentially create more patients. This vicious cycle could crash the health-care system in a very short period of time. This, to some extent, explains why most of the countries don’t send people who are tested positive to hospitals.


Disclaimer

This list is updated twice weekly, and only includes tests that have received a US Food and Drug Administration EUA. It only includes tests for which data and documentation is available and for which their stated intended use aligns with their regulatory status. This site is not intended to be used as a reference for funding or grant proposals. Noninclusion in this list should not be interpreted as judgment on validity or legitimacy of tests.

Note on sensitivity and specificity data

The manufacturer-reported sensitivity and specificity data is listed, where available. A highly sensitive test should capture all true positive results. A highly specific test should rule out all true negative results. These measures are not independently validated by the Johns Hopkins Center for Health Security. If a sensitivity or specificity is not listed, it was not listed/available at the time of posting. When available, the number of samples used for sensitivity/specificity definitions are listed in the product description in the extended versions of the tables.

The terms “sensitivity” and “specificity” may not appear in the manufacturers’ information sheets, but rather these values are often reported as “positive percent agreement” and “negative percent agreement.” The US FDA recommends that manufacturers use these terms to indicate that a non-reference standard was used when evaluating the test.

More information on serology tests:

This page was last updated on June 11, 2021.


Rapid diagnostic tests for diagnosing malaria

Fever is common in malarial areas, and getting the diagnosis right (ie deciding if it is due to malaria or other causes) and treating correctly helps save lives, particularly in children. The World Health Organization (WHO) now recommends that all patients with fever suspected of being malaria are properly diagnosed before any treatment begins. This ensures that highly effective antimalarial drugs such as artemisinin-based combination treatments (ACTs) are properly used to prevent unnecessary treatments, untoward risks, and resistance developing.

Standard diagnosis of malaria in the past has depended on blood microscopy, but this requires a technician and a laboratory, and is often not feasible for basic health services in many areas. Sometimes in research studies, another technique called polymerase chain reaction (PCR) is used, but again this requires equipment and trained staff, and cannot be used routinely. Technological advances have led to rapid diagnostic tests (RDTs) for malaria. These detect parasite-specific antigens in the blood, are simple to use, and can give results as a simple positive or negative result, within 15 minutes.

This review evaluates the accuracy of RDTs compared with microscopy and PCR for detecting Plasmodium falciparum parasites in the blood. It includes 74 studies, giving a total of 111 RDT evaluations (of which 104 compared RDTs with microscopy), reporting a total of 60,396 RDT results. Results are presented by type of test, classified by the malaria antigen that they are designed to detect (either histidine-rich protein-2 (HRP-2), or plasmodium lactate dehydrogenase (pLDH)).

The results indicate that RDTs can be very accurate compared to microscopy and PCR. The performance of RDT types varied but the differences were not large. HRP-2-based tests tended to be more sensitive (ie they identified more true cases of malaria) and less specific (ie they wrongly identified more malaria that was not present) than pLDH-based tests. Choice will depend on prevalence of malaria, and we provide data in this review to assist these decisions, although policy makers will also take into account other factors relating to cost and test stability.

The sensitivity and specificity of all RDTs is such that they can replace or extend the access of diagnostic services for uncomplicated P. falciparum malaria. HRP-2 antibody types may be more sensitive but are less specific than pLDH antibody-based tests, but the differences are small. The HRP-2 antigen persists even after effective treatment and so is not useful for detecting treatment failures.

Rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria use antibodies to detect either HRP-2 antigen or pLDH antigen, and can improve access to diagnostics in developing countries.

To assess the diagnostic accuracy of RDTs for detecting P. falciparum parasitaemia in persons living in endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria by type and brand.

We undertook a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register MEDLINE EMBASE MEDION Science Citation Index Web of Knowledge African Index Medicus LILACS IndMED to January 14, 2010.

Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction) in blood samples from a random or consecutive series of patients attending ambulatory health facilities with symptoms suggestive of malaria in P. falciparum endemic areas.

For each study, a standard set of data was extracted independently by two authors, using a tailored data extraction form. Comparisons were grouped hierarchically by target antigen, and type and brand of RDT, and combined in meta-analysis where appropriate.

We identified 74 unique studies as eligible for this review and categorized them according to the antigens they detected. Types 1 to 3 include HRP-2 (from P. falciparum) either by itself or with other antigens. Types 4 and 5 included pLDH (from P. falciparum) either by itself or with other antigens. In comparisons with microscopy, we identified 71 evaluations of Type 1 tests, eight evaluations of Type 2 tests and five evaluations of Type 3 tests. In meta-analyses, average sensitivities and specificities (95% CI) were 94.8% (93.1% to 96.1%) and 95.2% (93.2% to 96.7%) for Type 1 tests, 96.0% (94.0% to 97.3%) and 95.3% (87.3% to 98.3%) for Type 2 tests, and 99.5% (71.0% to 100.0%) and 90.6% (80.5% to 95.7%) for Type 3 tests, respectively.

Overall for HRP-2, the meta-analytical average sensitivity and specificity (95% CI) were 95.0% (93.5% to 96.2%) and 95.2% (93.4% to 99.4%), respectively.

For pLDH antibody-based RDTs verified with microscopy, we identified 17 evaluations of Type 4 RDTs and three evaluations of Type 5 RDTs. In meta-analyses, average sensitivity for Type 4 tests was 91.5% (84.7% to 95.3%) and average specificity was 98.7% (96.9% to 99.5%). For Type 5 tests, average sensitivity was 98.4% (95.1% to 99.5%) and average specificity was 97.5% (93.5% to 99.1%).

Overall for pLDH, the meta-analytical average sensitivity and specificity (95% CI) were 93.2% (88.0% to 96.2%) and 98.5% (96.7% to 99.4%), respectively.

For both categories of test, there was substantial heterogeneity in study results. Quality of the microscopy reference standard could only be assessed in 40% of studies due to inadequate reporting, but results did not seem to be influenced by the reporting quality.

Overall, HRP-2 antibody-based tests (such as the Type 1 tests) tended to be more sensitive and were significantly less specific than pLDH-based tests (such as the Type 4 tests). If the point estimates for Type 1 and Type 4 tests are applied to a hypothetical cohort of 1000 patients where 30% of those presenting with symptoms have P. falciparum, Type 1 tests will miss 16 cases, and Type 4 tests will miss 26 cases. The number of people wrongly diagnosed with P. falciparum would be 34 with Type 1 tests, and nine with Type 4 tests.


Double-Edged Spike: Are SARS-CoV-2 Serologic Tests Safe Right Now?

Richard Torres, MD, MS, Henry M Rinder, MD, Double-Edged Spike: Are SARS-CoV-2 Serologic Tests Safe Right Now?, American Journal of Clinical Pathology, Volume 153, Issue 6, June 2020, Pages 709–711, https://doi.org/10.1093/ajcp/aqaa071

“Validation of new immunologic tests ain’t easy,” it’s been said validation of new tests for human antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a particularly daunting task. While we endure months of disruption to daily life prompted by the ongoing pandemic, serologic testing for antibodies to SARS-CoV-2 has now come to the limelight. SARS-CoV-2 is a highly contagious and acute severe respiratory pathogen that has produced an enormous strain on health care resources. In the United States and many other countries, specific social behavior restrictions have been enacted to moderate the impact of rapid propagation of this contagion (ie, “flatten the curve”). Scientific experts, governmental officials, and other professionals have publicly advocated for SARS-CoV-2 antibody testing to identify individuals who have developed immunity and therefore could potentially reenter the workplace safely despite ongoing high prevalence of the virus. A test for detecting “immune” individuals who will not be reinfected and who will not infect others is an appealing concept, but is it realistic?

The temporary easing of Food and Drug Administration (FDA) marketing/use regulations has enabled the rapid expansion of accurate, fast, and reliable nucleic acid tests to identify acute infection with SARS-CoV-2. Laboratory professionals, diagnostic companies, suppliers, investigators, and hospital administrators have all stepped up to manage acute supply shortages for critical testing components including instruments, test-compatible swabs, and nucleic acid extraction kits, ensuring continued availability of reliable and timely test results. As we approach the peak of severe disease prevalence in several regions (according to comprehensive models developed by epidemiologists and statisticians), we now are faced with a new laboratory crisis: SARS-CoV-2 antibody testing.

Numerous antibody tests have recently become available. Serologic tests for antibodies to SARS-CoV-2 are typically based on lateral flow immunochromatography or enzyme-linked immunosorbent assays (ELISA). Currently available tests predominantly target antibodies to 1 of 2 main surface proteins of the novel coronavirus – the nucleocapsid protein (N) and the spike protein (S). Several assays focus on the S1 subunit of the spike protein, which is somewhat specific to each coronavirus strain. 1, 2 The S1 subunits host the binding domain for the angiotensin converting enzyme 2 (ACE2) receptor, which is thought to be the mechanism by which SARS-CoV-2 gains entry into cells. 1 Because the S1 subunit is highly immunogenic and its affinity for the ACE2 receptor appears to correlate with infectivity, 1 it has been the target for SARS-CoV-2 serologic assays with reportedly high sensitivity and specificity. 2, 3

Clinical implementation urgently requires validation of these new assays. Since real-life performance data are scarce, the coronavirus disease 2019 (COVID-19) pandemic has been marked by an inspiring level of interlaboratory collaboration. At Yale-New Haven Hospital, we are particularly grateful for invaluable discussions and sharing of data with Johns Hopkins, Massachusetts General Hospital, Mount Sinai, NYU-Langone, Cornell/Columbia, ARUP, Mayo Clinic, and many others. Scientific journals have contributed via the rapid dissemination of curated studies, and preprint sites offer additional information that can be scrutinized in a shorter time frame, prior to dedicated reviewer analysis. The accumulation and exchange of valuable laboratory evidence has increased our understanding of the serologic testing landscape in a short period of time. As a result, we now know that individuals with symptomatic SARS-CoV-2 infection will generally not have detectable antibodies to SARS-CoV-2 within the first 7 days of the onset of symptoms. 3, 4 The majority of hospitalized SARS-CoV-2-infected individuals with confirmed viral RNA will have detectable IgG antibodies 14 days, and more certainly 28 days, after the onset of symptoms with assay sensitivity and specificity in the high 90 percents. 5 Total antibody concentration appears to rise to detectable levels first IgM and IgA both rise 1 to 2 days earlier than IgG 3 (unpublished observations). Preliminary data suggests older individuals produce more robust antibody responses. Assays differ in overall performance, but several methods being validated by large laboratories appear comparable. One might therefore ask: “What, exactly, is the problem?”

As valuable as this information is, it may be insufficient to support critical decisions that providers, managers, administrators, and governmental agencies will face, especially regarding immunity in individuals who have remained asymptomatic or minimally symptomatic during the pandemic.

To determine whether an individual is immune to SARS-CoV-2, we must know the pretest probability in the specific population being tested, as well as the sensitivity and specificity for protective antibodies of the assay. A significant challenge is that, to date, serologic data are largely limited to hospitalized, ill patients. There is reason to suspect that serologic findings in asymptomatic or mildly symptomatic exposures may not correlate as well as in hospitalized patients, particularly as anecdotal evidence suggests individuals with low viral loads produce lower antibody titers (unpublished data).

In addition, assessment of antibody effectiveness is problematic even in seriously ill patients. Approximately one-third of SARS-CoV-2-infected patients who developed antibodies during hospitalization have been reported to lack antibodies that neutralize virus in plaque growth assays, considered the standard laboratory test for antibody effectiveness. 6 This implies an individual with antibodies may not be immune to reinfection.

Finally, a positive antibody result (in a potentially immune individual) does not guarantee noninfectious status there may be continuing active viral shedding, particularly if their antibodies are nonneutralizing. The molecular heterogeneity of SARS-CoV-2 subtypes, 7 could also have an effect on the sensitivity and specificity of serologic assays. The imperfect performance of comparable, more established, serologic tests for other diseases (eg, toxoplasma IgM) may be acceptable because we have a much better understanding of the clinical scenarios. Unfortunately, the same confidence does not hold true for SARS-CoV-2 serologic testing.

Quality will play a pivotal role in ensuring we are able to obtain the data required to understand COVID-19 immunity. Some of the serologic tests currently available are simply bound to be inferior and that needs to be documented. The United Kingdom abandoned large-scale purchasing of test kits when the kits failed to satisfy minimum validation metrics. 8 Predictably, online direct-to-consumer tests are being aggressively marketed without any published information to evaluate their clinical performance. 9 While some antigenic targets have shown minimal cross-reactivity with the 4 prevalent non-SARS-CoV-2 coronaviruses, 2 without validation studies there is a real risk that some assays may simply reflect prior exposure to the common cold. Fortunately, reputable commercial entities with experienced scientists, sophisticated equipment, and good manufacturing practices have begun to release serologic assays under FDA guidance. Commercial assays typically undergo extensive prerelease standardization, including testing for interferences and matrix effects, quality control, and test results in large patient cohorts. This sets the stage for acquisition of clinical and epidemiologic data.

But concerns remain when proposals call for testing populations different from those used to validate the assay. What if a health care worker (HCW) who had a fever and no other symptoms 14 days ago wants to return to work and tests positive for SARS-CoV-2 antibodies can we assume with high confidence that this HCW is both immune and noninfectious? If we are wrong, then we have placed patients and coworkers at risk. A failed prevention is also likely to erode faith in the integrity of laboratory tests for the disease. We have heard the argument that any testing is better than none, providing a path to restoring normalcy, and the lack of which has high ongoing societal costs. As laboratory professionals, we can only respond that for anti-SARS-CoV-2 serology: (1) bad assays will always be counterproductive (2) good assays have not been proven in the proposed test population and (3) more experience is needed to help us properly interpret the serologic test results.

Regulatory and health officials appear to recognize these limitations eg, return to work guidelines from the Centers for Disease Control and Prevention currently do not include serologic testing. The role of serologic testing in identifying potential donors for convalescent plasma remains to be fully investigated (as does the therapeutic benefit of such an intervention in this setting), but other uses for serologic testing may emerge. One such clinical scenario where SARS-CoV-2 serologic assays may be particularly useful is when a positive serology is accompanied by repeatedly negative nucleic acid testing in the setting of a highly suggestive clinical presentation serology may provide the basis for specific therapies for COVID-19 infection. Still, until we understand the patterns of antibody response to SARS-CoV-2 in asymptomatic individuals, and the correlation of antibody response with susceptibility to reinfection, it seems prudent to apply caution to the criteria used to frame economic, social, and corporate policy.

Biological variability is the bane of clinical pathology in the setting of validation and clinical application of serologic testing, this variability presents a daily struggle. Reputable diagnostic companies and both commercial and academic clinical laboratories have repeatedly demonstrated that the value of dedication to testing quality ensures clinical utility. Health industry manufacturing experts, engineers, quality and regulatory managers, sales professionals, scientists, and physicians have been working diligently under significant duress during the COVID-19 pandemic, to the great benefit of society. As laboratory medicine professionals, we must now leverage these efforts by ensuring that: (1) serologic tests for SARS-CoV-2 antibodies perform as well as intended and (2) we provide information that enables health care providers, administrators, and health officials to best interpret and apply the available evidence. At this point in the evolution of serologic testing for SARS-CoV-2, we must say in unison “caveat emptor.”


PCR, antigen and antibody: Five things to know about coronavirus tests

To diagnose and contain the spread of coronavirus, testing is critical. There are two types of Covid-19 tests — those that are designed to detect whether you have the infection now, or those crafted to check whether you have been previously infected by the virus — SARS-CoV-2 — that causes the disease. Like any other product these tests have varying degrees of accuracy and reliability, and can be used to achieve different aims.

We want technologies that are fast, accurate, have high capacity, that don't require expensive, complex laboratory equipment or the expertise of highly trained people, but there's nothing which fills all of those criteria at the moment, says Professor Jon Deeks, a biostatistician and testing expert at the University of Birmingham, UK. ‘We haven't got any perfect test like that, but there are some which are sort of good in some aspects, but not in others.’

See also

Here are five things to know about coronavirus tests:

While antigen tests look for proteins on the surface of the virus to ascertain the presence of the pathogen, PCR (polymerase chain reaction) tests are engineered to seek genetic material called RNA that instructs the virus to make these proteins.

Both tests also require a swab from the back of your nose or throat as a sample and cannot determine whether you are contagious if positive but that’s where the similarities end.

In the case of PCR, the sample is sent to a lab where it is heated and cooled using special reagents to convert the virus's RNA into DNA, and then make millions of copies of the DNA, which allows for the identification of the organism. This process can take hours, requires sophisticated lab equipment and technicians, and is typically done one sample at a time, although there are machines that can process multiple samples. Although the sample needs to be sent to a lab, the time consuming process delivers as the results are almost 100% accurate in spotting infected people when there is virus on the swab.

In contrast, antigen tests — often referred to as rapid tests — work by mixing the sample with a solution that unleashes specific viral proteins. That combination is then applied to a paper strip that contains a bespoke antibody optimised to bind these proteins if they are present. Like a home pregnancy test the result is reflected as a band on the paper strip.

The process doesn’t require a lab, and can be done in up to 30 minutes, but that speed comes at the cost of sensitivity. Although these tests are reliable when an individual has a high viral load, they are far more prone to false-negative results if a person has low amounts of the virus in their body.

These two measures are used to determine the credibility of a test: ‘How well does it detect disease, and how well does it detect the absence of disease,’ explained Prof. Deeks.

Sensitivity is defined as the proportion of patients with Covid-19 who correctly get a positive result, while specificity is the proportion of patients without an infection that the test correctly identifies as negative.

In general, a highly sensitive test has a low false negative rate but runs a risk of false positives if its specificity is not up to scratch. On the other hand, a highly specific test runs a risk of false negatives if the test’s sensitivity is poor, but will generally have a low false positive rate. PCR tests are considered the gold standard because they are generally highly sensitive and highly specific.

  1. When it comes to rapid tests, the person who administers the test can be crucial

In the UK, an antigen test called the Innova lateral flow test was piloted in the city of Liverpool as part of the government’s plans to carry out mass vaccinations in the country. The aim was to allow workers back into offices and allow families to hug their loved ones again in care homes, Prof. Deeks notes.

But this ‘test to enable’ strategy backfired when scientists found that in a population of mostly people with symptoms the test’s sensitivity fell to about 58% when administered by self-trained staff, versus 73% when tested by skilled research nurses and 79% when tested by laboratory scientists. In a study that looked at people without symptoms, the sensitivity fell to roughly 49% versus PCR tests.

‘So, there's this gradient of saying, the more experienced people are at doing the test, then less cases will be missed,’ he said. There are some stages that have to be followed very carefully, he says, like reading it accurately. ‘Sometimes it's hard to tell whether that's a line or whether it's a smudge,’ said Prof. Deeks.

PCR tests are processed in the lab, so the potential for error is much lower, he adds.

Test makers are also trying to develop at-home tests but given the lessons we've already learned about how rapid test accuracy depends on who administers it, that's a problem, Prof. Deeks suggests.

‘If people can do tests more easily, then more people will be tested… but I don't think we've got the test to do it yet,’ he said. He adds that there aren’t any good studies looking at what benefit this extra testing would have, for instance, what impact repeated false-negative results could have on behaviour.

In a proposal for common rules on rapid antigen tests published on 18 December, the European Commission said that rapid antigen testing should be carried out by trained healthcare personnel or other trained operators.

‘If people can do tests more easily, then more people will be tested… but I don't think we've got the test to do it yet.'

Prof. Jon Deeks, University of Birmingham, UK

  1. Until rapid tests are made more accurate, negative results should not be used to encourage risky activities

If a test, like the Innova test, is missing up to half the cases then nobody can really be considered free of the risk of having or transmitting infection, Prof. Deeks notes.

‘You're always going have a small percentage of those people who are missed by all tests,’ said Gary Keating, chief technology officer of HiberGene, an Ireland-based company that has a Covid-19 test. The test utilises LAMP technology, which is a low-cost alternative to PCR technology.

‘I think it's always dangerous to taking a single diagnostic test in isolation, and use that as the basis to go and make a very significant medical or lifestyle decision,’ said Keating.

Used on a large scale, results could lead to false sense of security, according to Prof. Deeks.

Governments are keen to use rapid tests as they are cheaper and faster to deploy for mass vaccination campaigns, but because they have limitations in terms of accuracy then it is key to not use negative results to enable more risky activities such as meeting your elderly or vulnerable loved ones, he says.

Some countries, like the United States, advise getting a PCR test if individuals with symptoms test negative with a rapid antigen test to confirm the result.

Although rapid tests are good at catching people who have high viral loads, it isn’t yet clear what the viral threshold must be to thwart contagiousness. With Covid-19, those that are infected see a peak in viral load in the early phase of the infection, but viral RNA can stick around for weeks or even months.

  1. Antibody tests could be useful in measuring the durability of vaccine responses

Antibodies are soldiers deployed by the immune system in response to a foreign invader — in this case SARS-CoV-2. ‘Originally, there was hope that antibody tests might enable us to diagnose disease quickly and easily. But it turns out, the tests don't turn positive for two to four weeks (post infection),’ said Prof. Deeks.

And the plot thickens, because even if you test positive for antibodies — that information doesn’t tell you much, apart from the high likelihood that you had contracted Covid-19 in the past.

‘We don't really know what levels of antibodies leads to protection (from disease) and indeed, which kind of antibody is the most important — I'm not sure whether there's consensus on that either,’ he said.

It is also unclear how long Covid-19 antibodies persist in the body, or that anybody who has tested positive for antibodies won’t catch the virus again.

Where these tests could come handy is in estimating the spread of Covid-19 at a population level — for instance, what percentage of the population and what ethnic groups have contracted Covid-19, as well as in measuring the durability of vaccine responses, Prof. Deeks adds.

HiberGene’s coronavirus test was one of the initial 18 emergency projects funded by the EU. If you liked this article, please consider sharing it on social media.


Summary

WHO recommends a minimum of 80% sensitivity and 97% specificity for antigen-detection rapid diagnostic tests (Ag-RDTs), which can be used for patients with symptoms consistent with COVID-19. However, after the acute phase when viral load decreases, use of Ag-RDTs might lead to high rates of false negatives, suggesting that the tests should be replaced by a combination of molecular and serological tests. When the likelihood of having COVID-19 is low, such as for asymptomatic individuals in low prevalence settings, for travel, return to schools, workplaces, and mass gatherings, Ag-RDTs with high negative predictive values can be used with confidence to rule out infection. For those who test positive in low prevalence settings, the high false positive rate means that mitigation strategies, such as molecular testing to confirm positive results, are needed. Ag-RDTs, when used appropriately, are promising tools for scaling up testing and ensuring that patient management and public health measures can be implemented without delay.


Precision

If you look close enough, you can find that the precision is actually calculated as True Positive/Total Classified Positive. That’s right! Precision measures the accuracy under the circumstance that when the testing result is positive. In other words, how accurate it is if you are tested positive.

Precision reflects what proportion of positive classification is actually correct.

If you are tested positive by this testing tool, there’s a 50% chance that you actually didn’t contract the virus. That is pretty high! You probably don’t want to use a swab with this accuracy.

Precision is useful when the cost of FP is high. For example, if we have low precision in our COVID-19 testing, it means there are a lot of healthy people diagnosed as positive. These people will be falsely sent to the hospital and treated for a disease they don’t have. This is not only a total waste of our health-care resources but also exposing healthy people to a dangerous environment, and therefore potentially create more patients. This vicious cycle could crash the health-care system in a very short period of time. This, to some extent, explains why most of the countries don’t send people who are tested positive to hospitals.


The Fast Lane for COVID Testing Has Opened Up in the U.S.

For a recent flight that required a negative COVID-19 test result, I went through a process so silly and laborious that it got me wondering. First, I booked an appointment at an approved testing center, about a 25-minute drive from my home. Upon arriving, I paid $175 to take a polymerase chain reaction (PCR) test. I then drove home, downloaded an app and waited 24 hours&mdashall to receive results that, in many other countries, can be obtained in a fraction of the time without ever leaving the house.

So why, more than a year into a pandemic, does the U.S. lag behind other developed nations in the deployment of rapid antigen testing? Recently, for the first time, we received a hint that our nation&rsquos top health officials have been wondering the same thing.

On March 31 the Food and Drug Administration effectively made a game-changing announcement: two rapid at-home antigen tests, Abbott&rsquos BinaxNOW and Quidel&rsquos QuickVue, will soon be sold over the counter (OTC) on drugstore shelves, without the need for a prescription.

That may sound like a little. It&rsquos a lot. It is of such critical potential impact, in fact, that Harvard University epidemiologist Michael Mina&mdashwho has for months been a vocal advocate of rapid antigen testing for screening purposes for months&mdashproclaimed in an April 1 media call that March 31 &ldquowas a massively important day &hellip on the testing front.&rdquo

There&rsquos no prescription needed. You can self-administer the test at home&mdashor, depending upon the need, at schools, workplaces and community centers, for example&mdashso that you and the people around you can know almost immediately whether it&rsquos safe to congregate. Because the virus that causes COVID-19, SARS-CoV-2, and its variants can spread asymptomatically, experts believe these tests could help detect them early, while people may be vectors of infection, and thus break the chain of transmission.

&ldquoHad we had these tests in a widely scalable at-home, simple to use fashion last summer, we could have prevented hundreds of thousands of deaths. We could have prevented surges of cases,&rdquo Mina said in the April 1 press conference. This pandemic &ldquois still a massive tragedy every single day. And if we can use these types of tests to mitigate spread moving forward &hellip that alone might be enough to ensure that outbreaks don't grow.&rdquo

This is clearly a shared view that is acted upon in other countries. Switzerland&rsquos Federal Council recently announced it is &ldquomassively expanding&rdquo its rapid testing system with "free tests for all." As of March 8, everyone in Germany can receive rapid antigen testing once a week for free at a screening center or pharmacy, according to Sandra Ciesek, director of the Institute of Medical Virology at University Hospital Frankfurt in Germany. The Federal Council aims to increase this to five free self-tests per person a month as better tests become available. "To ensure that everyone can be tested immediately, all tests in pharmacies and test centres will be free of charge, even for people without symptoms,&rdquo the council wrote in a news release.

And in January, England committed to scaling up its rapid testing program. By March, free testing for all businesses was offered, and as of April 9th, twice-a-week free testing is available to everyone in the country. Regular workplace testing is a vital part of our route back to normal life,&rdquo said U.K. health secretary Matt Hancock in a March statement. &ldquoThese rapid tests will [allow] positive cases of COVID-19 to be caught quickly, which is crucial in helping businesses protect their workplaces and employees as we cautiously lift restrictions.&rdquo

In the U.S., by comparison, things moved at an agonizingly sludgy pace. An FDA official told me the agency cannot compel manufacturers to submit applications for specific tests. Rather the developers decide for themselves whether to apply for a test that will be prescription or over-the-counter. Prior to the FDA&rsquos statement March 31, of the 16 rapid antigen tests that had been approved, only one was greenlit for home over-the-counter use (without a prescription) by Ellume, and it is not yet available to the public for purchase. That is about to change dramatically.

The newly approved tests are authorized by the FDA for serial use, meaning an individual could be tested now and then again within 24 to 36 hours. Serial testing is important because it can improve the sensitivity of the test. If you&rsquore in the early phase of infection, when viral levels are low, a test&rsquos result may be a false negative&mdashthat is, it might show negative when, in fact, you&rsquore positive for COVID. A test repeated the next day would more likely be positive, due to rapid increases in viral levels during the acute stage.

Mina and others hope that Americans will soon use these tests in the morning. Brush your teeth, take a quick 30-second test (it&rsquos similar to a pregnancy test), come back in 10 to 15 minutes to check the results and, if clear, head to school or work. If you&rsquore positive, do a more accurate nucleic acid amplification test (such as a PCR test) to be sure and then self-isolate.

Mina has pushed hard for the approval of these less expensive, simpler antigen tests for several reasons. One is simply scale. Manufacturers can ramp up production to tens of millions of tests per day, according to Mina&mdashan amount that would be necessary if much of the population is using these assays. With Abbott&rsquos BinaxNOW manufacturing facilities able to produce tens of millions of test per month and Quidel&rsquos goal of 50 million of its QuickVue tests per month by the end of 2021, according to company spokespersons, Mina is hoping more companies will enter the space so availability in the near term does not become a big issue.

In a March 31 press release, Abbott said its test should be available nationally in &ldquolarge quantities" at major food, drug and mass merchandiser retailers&mdashand it has said they will be sold to retailers at a cost that will be in the &ldquosingle digits.&rdquo A Quidel spokesperson wrote in an email exchange that the company will soon announce pricing on its two-test unit carton.

The need remains high for a continued buildup of fast, accessible testing, particularly for screening. &rdquoWe are in a risky period with variant growth, incomplete vaccination, return to school, increased population mobility and reduced mask wearing,&rdquo says Bruce Tromberg, director of the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health in an interview. &ldquoThe need to do screening, using accessible tests at home, on a large scale and on a regular cadence, is even more important.&rdquo

PCR tests have been recognized as the gold standard to diagnose acute infection with SARS-CoV-2 because of their high sensitivity&mdashbut they often require a central lab for processing and many cannot be done quickly, and delays in reporting the results increase the chance that someone is spreading the virus while waiting to hear back on their test. While not every PCR test costs the $175 that I paid (the Centers for Disease Control and Prevention (CDC) website estimates an average price of $75 to $100), its higher cost means that lower-income Americans will be less likely to be able afford it. Easier access to testing for these communities, which have shouldered much of the burden of COVID-19 and are facing health inequities, is welcome.

How accurate are these tests? The scientific community has debated the performance of rapid antigen tests. Officials at the CDC, along with most experts, believe antigen tests are less sensitive than PCR tests. In the April press conference, however, Mina contended that while PCR is the standard for diagnostic tests, it is &ldquohorribly not specific&rdquo for knowing who needs to isolate. He said it detected far too many remnants of viral RNA a week to two weeks, or more, after someone has become infectious. &ldquoThis is not a public health test,&rdquo he said. &ldquoYou can&rsquot take a test that&rsquos meant to be specific to the infectious period and make a gold standard against it that is totally not specific to the infectious period.&rdquo

In contrast, Mina believes rapid antigen tests have &ldquoexcellent contagiousness sensitivity&rdquo (more than 98 percent sensitive) and that they're good at detecting people who have COVID during the period when they are most infectious and capable of transmitting virus to others. At this point, viral titers are high, and &ldquothe rapid tests will be positive,&rdquo Mina says. &ldquoWhen viral levels fall, the tests turn negative.&rdquo The Infectious Disease Society of America&rsquos Website states, &ldquoRapid tests may ultimately contribute to better SARS-CoV-2 containment via more efficient detection and subsequent isolation,&rdquo but it makes &ldquono recommendations for or against using rapid tests.&rdquo

Where more experts do agree, and the CDC and FDA concur, is that rapid antigen tests, when performed serially, may increase the chances of detecting individuals who might be missed early with a single test. In a recent press release, Quidel indicated the test &ldquoshows excellent performance, with positive results agreeing with PCR 83.5 % of the time, and negative results agreeing 99.2% of the time.&rdquo A spokesperson at Abbott says BinaxNOW&rsquos overall performance demonstrates 84.6 percent sensitivity and 98.5 percent specificity in people at seven days or less post-symptom onset at all Ct (cycle threshold) counts.

(If you&rsquore curious as to whether these tests will detect the new variants, many experts believe they will. Mina explained at the press conference that they are unlikely to lose their effectiveness because the virus is mutating at a different part than the proteins these rapid tests are targeting.)

Approval of these tests comes on the heels of the FDA&rsquos recent announcement of a streamlined pathway to emergency use authorization (EUA) for at-home screening tests, which allows companies to take already authorized prescription-based tests and apply to sell an over-the-counter claim without completing large trials. This appears to be working now with several over-the-counter tests approved.

In an interview, an FDA spokesperson said that based on more positive data related to serial testing that demonstrates good performance, a developer could potentially get an EUA approval for less sensitive tests, and be able to submit data post authorization. They indicated too that they do not hold any of the point-of-care tests or at-home tests to near the same high threshold as lab-based PCR test. In a press release, Jeff Shuren, M.D., J.D., director of the FDA&rsquos Center for Devices and Radiological Health said, &ldquoAs we've said all along, if it&rsquos a good test, we&rsquoll authorize it.&rdquo

Both the Biden administration and the CDC have indicated support for rapid testing. In February, President Joe Biden&rsquos team announced that it would contribute $230 million to increase production of the Ellume antigen tests&mdashthe only OTC product on the market at the time authorized for both symptomatic and asymptomatic use. The company is expected to supply the U.S. with approximately 100,000 tests per month through July (and a total of 8.5 million guaranteed to the U.S. government), which is a start. Andy Slavitt, senior adviser for COVID-19 response at the White House, told reporters, &ldquoThat&rsquos good, but it&rsquos obviously not where we will need to be.&rdquo

The CDC recently issued extensive new guidance related to the use of screening tests for COVID-19. In collaboration with the NIH, the agency announced a new public health initiative on March 31. The &ldquoSay Yes! COVID Test&rdquo initiative will enable 160,000 residents across two communities to perform free, rapid antigen tests three times a week for a month. &ldquoThe new initiative is exciting,&rdquo Tromberg says. &ldquoIt&rsquos a real-world demonstration of how rapid-accessible tests can be used to stop the chain of transmission and reduce prevalence.&rdquo

This is our future, and it&rsquos one way to help open our country. &ldquoReliable and widely available testing is a critical part of our efforts to stop the spread of COVID-19,&rdquo said CDC director Rochelle Walensky in a recent statement. Abbott CEO Robert Ford took it a step further in the company&rsquos March 31 press release, saying, "Together with vaccines, the BinaxNOW Self Test will help Americans get back to doing what they want and need to do&mdashlike going to work and school or seeing friends and family&mdashwith greater confidence."

It&rsquos the kind of development Mina has been lobbying for during the better part of a year. Now, he said in the April 1 press conference, the FDA, CDC, NIH and White House &ldquoare all sort of simultaneously recognizing this is a very powerful tool over the last two, two and a half weeks&hellip. I think that we should consider this sort of a pivotal change in the &hellip testing landscape in the U.S.&rdquo

In Germany, meanwhile, the famed Berliner Ensemble theater has reopened to sold-out audiences. To attend the show, visitors must wear masks, social distance and present not only their tickets but a negative COVID result from a rapid test taken just 12 hours prior to showtime. It&rsquos working quite well. Very soon, Americans, too, may be able to make their own curtain call.


Beroni Group’s SARS-CoV-2 Antigen Test Kit (Colloidal Gold Method) Has Received Export Permit

NEW YORK and SYDNEY, Australia, April 27, 2021 (GLOBE NEWSWIRE) -- Beroni Group (OTCQX: BNIGF NSX: BTG) (“Beroni” or the “Company”), an Australia-based diversified biopharmaceutical enterprise today announced that it has received the notification that its SARS-CoV-2 Antigen Test Kit (Colloidal Gold Method) is granted authorization for export.

As announced in December 2020, Beroni Group’s SARS-CoV-2 Antigen Test Kit (Colloidal Gold Method) has received the CE certification for distribution to the EU markets. This test kit requires no blood, and only a nasopharyngeal swab is needed to collect samples. It can also deliver the test results within 10 minutes. Based on clinical tests, the sensitivity, specificity and total coincidence rate of anterior nasal sampling are 95.90%, 99.19% and 97.55% respectively, while the sensitivity, specificity and total coincidence rate of nasopharyngeal and oropharyngeal sampling are 98.36%, 99.19% and 98.78% respectively. Our test results showed that the test kit could provide users with a safe, reliable and rapid way of detecting the COVID-19 virus.

“COVID-19 is a global health crisis faced by each of us. Getting the export authorization is an important achievement in our effort to overcome the coronavirus. This new test kit can let testers know whether they have the antigen before the vaccination. We know there have been cases where the person, who was still in isolation, returned several negative PCR tests, however serology testing conducted brought back a positive result,” commented Jacky Zhang, Chairman and CEO of Beroni Group. “At present, our other COVID-19 test kit - Beroni SARS-CoV-2 IgG/IgM Antibody Detection Kit - has been exported to Britain, Japan and other countries. With CE certification and export authorization, we are ready to integrate our multi-centered resources to distribute the antigen test kit to the needed markets.”

About Beroni Group Limited

Beroni Group is an international biopharmaceutical enterprise dedicated to the innovation and commercialization of drugs and therapies to combat various global diseases such as cancer and infectious diseases. Its diversified portfolio is comprised of a US FDA approved virus diagnostic kit, an e-commerce platform for the sale of pharmaceutical products and a development pipeline targeting oncology and cell therapies. Beroni has operations in Australia, United States, China and Japan. To learn more about Beroni, please visit www.beronigroup.com.

Forward-Looking Statements Disclaimer

This press release contains forward-looking statements or forward-looking information, within the meaning of applicable United States and Australian securities laws with respect to the Company. By their nature, forward-looking statements are subject to a variety of factors that could cause actual results to differ materially from the results suggested by the forward-looking statements. Accordingly, readers should not place undue reliance on the forward-looking statements. Generally forward-looking statements can be identified by the use of terminology such as “anticipate”, “will”, “expect”, “may”, “continue”, “could”, “estimate”, “forecast”, “plan”, “intend”, “believe”, “potential” and similar expressions.

Forward-looking information contained in this press release is based on Company management’s opinions, estimates and assumptions in light of its experience and perception of historical trends, current conditions and expected future developments, as well as other factors that management currently believes are appropriate and reasonable in the circumstances. Forward-looking statements involve significant risks, uncertainties and assumptions, and there can be no assurance that such statements, or its underlying risks, uncertainties and assumptions will prove to be accurate. Factors that could cause actual results or events to differ materially include, without limitation, risks related to laws, rules and regulation applicable to the Company as well as the industry in which it operates (including in respect of taxes and other levies), economic or market conditions on both a national and global level, currency fluctuations, risks inherent to other entities at a similar stage of development and industry in which the Company currently is, competition from the Company’s competitors, unsatisfactory development or marketing of the Company and/or its products or services, regulatory action or litigation (including product liability claims), and failure to enter into agreements or arrangements with other parties on fair or reasonable terms. Forward-looking information is made only as of the date on which it is provided and, except as may be required by applicable laws, the Company disclaims any intent or obligation to update such forward-looking information whether as a result of new information, future events or otherwise.

For more information, please contact our IR consultants at:


Covid-19: Safety of lateral flow tests questioned after they are found to miss half of cases

The lateral flow devices used in the community testing pilot in Liverpool only picked up half the covid-19 cases detected by polymerase chain reaction (PCR) tests and missed three out of 10 cases with higher viral loads, according to the government’s own policy paper.1

Given the low sensitivity of the Innova lateral flow devices when used in the field, experts are questioning how they can be used to allow care home residents to have contact with relatives over Christmas safely or for students to know for certain that they are not infected before returning home.

The information can only be found by looking in annex B of the document, Community testing: a guide for local delivery, which was published on 30 November. This is the first publicly available information about the field evaluation of the Innova tests in Liverpool which has been criticised for its lack of transparency, accuracy of the tests used, and costs and potential harms.23

Jon Deeks, professor of biostatistics at the University of Birmingham and leader of the Cochrane Collaboration’s covid-19 test evaluation activities, told The BMJ, “The results are hidden as a single sentence in the annex of a document. This is not the way important scientific findings should be made public, particularly when the test is going to be used off label with hundreds of thousands of people.”

The Department of Health and Social Care said that over a million lateral flow tests have already been sent to 385 care homes and more would be sent over December to roll out visiting by Christmas.

A spokesperson said, “Extensive testing has shown that lateral flow devices are suitable for use in care homes where they can identify people who are the most likely to spread the virus further and prevent transmission of the disease from staff and visitors. Testing is only part of the approach and it’s essential visitors wear personal protective equipment and follow all infection control methods to keep their loved ones, other residents, and staff safe.”

Susan Hopkins, senior medical adviser to Public Health England and NHS Test and Trace, told The BMJ, “These tests are an additional tool in helping us detect cases that we wouldn’t otherwise know about, in doing so helping us to break chains of transmission and save lives. No test will detect every single case, but these tests are proving to be accurate and reliable and we are confident that they can be used to rapidly identify many people who are silently carrying the virus.”

She added, “In care homes, these tests can help make planned visits safer by identifying visitors that are unknowingly carrying high levels of virus, and so prevent them from passing it on to their loved one.”

However, public health and social care directors in some areas, including Greater Manchester and Sheffield, have written to care homes warning them not to use the rapid tests until they have had more information from the government on the accuracy of the tests and training in how to use them.4

The government has invited all tier 3 areas to offer community testing of asymptomatic people after what it described as “the positive impact” of the Liverpool pilot scheme. The guidance says that the Innova lateral flow tests offer 99.6% specificity and “the measured test sensitivity, in ideal hands is 76.8%” but “is likely to be lower under operational conditions.”

The document then adds, “In the field evaluation in Liverpool, compared with PCR tests, these tests picked up five out of 10 of the cases PCR detected and more than seven out of 10 cases with higher viral loads, who are likely to be the most infectious.”

Deeks said, “These results are devastating—they are missing a third of those with high viral loads. How can these tests be used for safe entry into care homes, for healthcare workers to safely return to work, or for the safe return of students? They are not fit for purpose.”

Allyson Pollock, director of the Newcastle University Centre for Excellence in Regulatory Science and a member of Independent SAGE, said, “This is scandalous. Where are the data underpinning the statement in the document? Mass testing should be paused until we see the evidence and Liverpool evaluation.”

She added, “The Liverpool public who went for testing seem to have been grossly deceived and misinformed about the usefulness of the test and purpose of testing. They were not told that one of the purposes was research on the lateral flow test in healthy people.” She said that the pilot should have first gone for advice to the UK national screening committee and have had ethics approval.

The Scottish National Party MP Neale Hanvey has submitted two written parliamentary questions calling for publication of the full data about the community testing pilot in Liverpool. He told The BMJ, “My main concern is false reassurance. There is a clear risk that those with a false negative result will feel overly confident about mixing with vulnerable people over Christmas.”

An earlier assessment of the Innova test by Public Health England’s Porton Down laboratory and the University of Oxford found an overall sensitivity of 76.8%, but said that sensitivity dropped to 58% when carried out by self-trained members of the public.5 However, when health secretary Matt Hancock was asked at a health select committee about the test missing almost half of cases, he said he “didn’t recognise” the 58% figure.