It is time to change how we think about the sensitivity of the Kovid-19 test. The Food and Drug Administration (FDA) and the scientific community are currently focusing almost exclusively on test sensitivity, a measure of how well an individual assay can detect viral proteins or RNA molecules. Critically, this measurement ignores the context of how the test is being used. Yet when it comes to comprehensive screening of America, in dire need, the context is fundamental. The key question is not how well the molecules can be detected in a single sample, but the effective use of a given test as part of an overall testing strategy to effectively detect infection in a population. How to apply – sensitivity of the test.
A rule of routine testing works as a type of Kovid-19 filter, by identifying, isolating, and thus filtering out currently infected individuals who are asymptomatic. To measure the sensitivity of a test diet or filter we need to consider a test in context: how often it is used, to whom it is applied, when it works during an infection, And whether its results are returned in time to prevent the spread.1-3
An individual’s infection trajectory (blue line) is shown in terms of two monitoring diets (circles) with varying analytical sensitivity. Low analytical sensitivity sensitivity is frequently administered and high analytical sensitivity assay is often administered. Both tests detect the regeneration transition (orange circles), but only the high-frequency test detects it during the transmission window (shading), despite its lower analytical sensitivity, which makes it a more effective filter. The window during which the polymerase chain reaction (PCR) detects the first transition from infectivity (green) is shorter, while the corresponding successive but PCR-detectable window (purple) is longer.
Thinking about impact in the context of repeated use is a familiar concept for physicians and regulatory agencies; It is applied every time we measure the efficacy of a treatment regimen rather than a single dose. With Kovid-19 cases accelerating or plateauing around the world, we must immediately turn our attention to a narrow focus on the analytical sensitivity of a test (the lower limit of its ability to correctly detect small concentrations of molecules in a sample). Will have to move away from it. More relevant measures of susceptibility to testing for infection detection (the possibility that infected individuals learn that they become infected prematurely are filtered out of the population and prevent others from spreading). A point-of-care test, which was often significantly cheaper to use, would have a higher sensitivity for detecting infection to function without meeting the benchmark analytical threshold of detection. The diagram).
The tests we need are fundamentally different from the clinical trials currently being used, and their evaluation should vary. Clinical trials are designed for use with symptomatic people, do not need to be low-cost, and require high analytical sensitivity to return a definitive clinical diagnosis given the same opportunity for testing it occurs. Conversely, tests used in the effective surveillance regiment to reduce the spread of a respiratory virus population require results to be returned early to limit asymptomatic proliferation and are inexpensive enough to allow frequent testing and Should be easy – several times per week. The transmission of SARS-CoV-2 occurs days after exposure, when the viral load peaks.4 This time increases the importance of a higher test frequency, as the test should be used to prevent further spread at the onset of infection, and minimizes the importance of achieving very low molecular limits of detection of standard tests is.
According to several criteria, the benchmark standard clinical polymerase-chain-reaction (PCR) test fails when used in standard monitoring. After collection, PCR samples usually require transport to a centralized laboratory maintained by specialists, which increases costs, reduces frequency, and can delay results for one or more days . The cost and effort required to test with standard testing means that most people in the United States have never found one, and the slow turnaround time means that whenever current surveillance approaches identify infected people. They can still spread the infection for days before notification, which limits the effects of isolation and contact tracing.
The Centers for Disease Control and Prevention (CDC) estimated in June 2020 that several Kovid-19 cases were detected in the United States 10 times.5 In other words, despite the very high analytical sensitivity of clinical trials deployed for surveillance, today’s testing has only a 10% sensitivity minimum to detect infection and fail to form covid filters.
Furthermore, the well-characterized long tail of RNA positivity after the transmissible phase means that many, if not most, of those whose infections are detected during routine monitoring using high-analytic-sensitivity, but Low-frequency tests are no longer infectious detection (see) The diagram).2 Actually, a Recent investigation From new York Times It was found that in Massachusetts and New York, more than 50% of infections identified by PCR-based surveillance had PCR cycle threshold values in the mid to upper 30s, indicating low viral RNA counts. While such low count can cause either early or late stage infection, the longer duration of RNA positive tails suggests that most infected people are being identified after the infectious period has passed. Importantly for the economy, it also means that thousands of people are being sent for 10-day quarantine after positive RNA tests, despite the infection already transiting.
For an effective Kovid filter that will prevent this epidemic, we need tests that can enable infections that are still contagious. These tests exist today as rapid lateral-flow antigen tests, and rapid lateral-flow tests based on the CRISPR gene-editing technique are on the horizon. Such tests are cheap (The diagram).
We believe that surveillance testing regenerates that can alter transmission chains enough to reduce community prevalence should complement our current clinical clinical trials, not replace. Imaginative strategies can benefit both types of testing, using frequent, cheap, and rapid tests on a scale to reduce outbreaks,1-3 Positive results were confirmed using a second rapid test targeting a different protein or using a benchmark PCR test. The public awareness campaign should also state that no single negative test necessarily requires a clean health bill to encourage continued social distance and wearing masks.
The FDA’s late-August Emergency Use Authority (EUA) Abbott Binaxnaw’s first rapid, instrument-free antigen test to receive the European Union was a step in the right direction. The approval process emphasized the high sensitivity of the test to identify people when their infection is most likely to occur, thus relaxing the required range of detection by two orders of magnitude from the PCR benchmark. These rapid trials now need to be developed and approved for home use to enable real community-wide surveillance revision for SARS-CoV-2.
Currently, there is no FDA route for evaluation of trials and has been approved for use as a single trial or in a diet rather than their public health capacity to reduce community transmission. The regulatory lens remains focused exclusively on clinical clinical trials, but new metrics can be applied to assess trials in light of the epidemiological framework if their stated objective is to reduce community spread of the virus . In such an approval route, trade-offs between frequency, detection limits and turnaround time would be expected and would be appropriately evaluated.1-3
To defeat Kovid-19, we believe that the FDA, CDC, National Institutes of Health and others should encourage structured evaluation of tests in the context of planned testing to identify those that will provide the best Kovid filters . Repeated use of cheap, simple, rapid tests will serve that purpose, even if their analytical sensitivity is much lower than benchmark tests.1 Such a rule can help us stop Kovid in its tracks.
Herbert Needleman, MD, a physician-scientist whose lead in consumer products was removed due to research…
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