IN THIS ISSUE
Evidence Commons launches
Hype about “The pandemic is over” misses an even bigger point
The search for less-invasive analytes
New and Noteworthy
Yes, tests are less sensitive when it comes to Omicron - but not necessarily for the reasons you might think.
Anecdotal reports over the last few months suggest that folks with Omicron get symptoms one to two days before they start to show up positive on antigen tests. While some have chalked up this discrepancy to the swift workings of our vaccine-primed immune systems, might there be another, more concerning reason for the delay?
A recent Emory study crossed one possibility off the list. According to its findings, viral evolution and mutation in the N (nucleocapsid) protein is not to blame, at least for 11 popular antigen tests. The study examined all 17 antibodies these tests use (some use more than one) against every possible single mutation. As importantly, it provides a detailed methodology and blueprint to aid selection of the best antibodies (and primers and probes) to use in any test - and, critically, explains how to decide which not to use. To our knowledge this is the first public data about antigen-test vulnerability to N-protein evolution under real-world selection pressure. (Commentary: We would like to see all antibodies used in all EUA antigen tests evaluated against this blueprint, please.)
But even if N protein mutation isn’t the culprit, lower test sensitivity is nevertheless real. A recent BMJ study of the three most popular antigen tests in Holland (two with FDA EUAs: Flowflex & Clinitest) reported a decline of 10-20% as Omicron became dominant. And it isn’t just an antigen issue. It appears to affect all tests, including PCR: The September 9th, 2022 CDC MMWR reported Ct counts 4.5 points higher (lower viral load) for Omicron BA.1 than Delta, even though BA.1 had slightly higher transmissibility: 76% versus 71%.
Bottom line? Recent evidence confirms loss of early sensitivity is real, but not because SARS-CoV-2 is mutating away from available antigen tests. There may simply be more Omicron virus in exhaled aerosols than in nasal samples, and/or Omicron may just be more effective at gaining entrance into the human body. Either way, it is more important than ever to isolate whenever you have COVID-like symptoms and take two tests 48 hours apart to be sure you are not contagious.
Data on COVID diagnostics now collected at Evidence Commons.
We have said it so many times over the last two years - diagnostics have been underappreciated and misunderstood. There has been constant debate about their usage, value, and impact, as well as debate about what the best technology is for each stage of an infection.
So, instead of just complaining about it, we decided to do something about it. ASU’s College of Health Solutions has created EvidenceCommons.com with a grant from The Rockefeller Foundation (Mara is the principal investigator). The only repository of its kind, Evidence Commons is a searchable database with more than 3,000 published papers on COVID tests and testing protocols. Users can search these publications by test technology, sample used, trial protocols, and other criteria. Perhaps some of the debates about COVID diagnostics will be resolved, now that there’s easy access to research on the subject. (If you want to find out more or submit a publication for inclusion in Evidence Commons, email Mara.)
Food for Thought
“Is the pandemic over?” is the wrong question
Pundits and members of the COVID press have been either wringing their hands or celebrating - depending on their point of view - ever since President Biden’s 60 Minutes statement that the pandemic is over. While we think that the statement is correct on a psychological level, if not a medical/epidemiological one (for all the reasons mentioned in this STAT News article), we also think that the question “Is the pandemic really over?” isn’t even the central issue right now. The big question is whether we as a nation prioritize public health adequately when we’re not facing a global or national emergency.
In a way, the very fact that the US has its knickers in a twist about Biden’s statement tells you what you need to know. The implication of all the headlines - especially those that assume that the pandemic is over - is that without that emergency, there is no reason anyone would want to continue to get boosted, mask around high-risk people, or really take any precautions. It is not that big of a leap for some to say that without an emergency, there’s no longer a reason to care about or fund public health.
We had dearly hoped that living through COVID-19 would help the nation - and perhaps the world - understand and respect the essential role that public health plays in all our lives. That the average person would begin to recognize how critical surveillance testing is. That mask-wearing as an easy, inexpensive tool to help prevent the spread of respiratory disease would become so commonplace that it wasn’t even worth remarking on anymore.
Apparently we’re not there yet.
But whether we’re in pandemic mode or not, the fact remains: COVID-19 isn’t going away. Right now, it’s still killing about 400 people a day in this country, which amounts to close to one 9/11 event every week. While most people in the nation are now behaving as if the pandemic is over - and that behavior itself means that the pandemic is, in one sense, actually over, like it or not - that does not mean that we should go back to ignoring and underfunding public health the way most of us did before March 2020. Instead, we need to start realizing that the time to adequately fund public health is always now. If we wait for the next emergency to happen, it will always be too late.
Starting with this issue, Sensitive and Specific will expand its coverage to include news and analysis of issues relating to medical diagnostics that are not connected with COVID-19 or other viral outbreaks.
Want a less-invasive analyte? Try sweat.
The COVID era has seen an unprecedented surge in efforts to find effective diagnostic technologies that are quicker, easier, and more foolproof. As COVID testing needs decline (fingers crossed), it is time to leverage all this creativity into better diagnostics across the board. The connection between sampling and analytic technologies is critical: higher-sensitivity analysis can offset less-direct sampling methods. Examples:
Sequencing cell-free DNA for solid tumor detection through liquid biopsies;
Continuous glucose monitoring (less accurate than a fingerstick, but the real-time dynamic trends it measures are a better overall solution to blood-sugar management);
Analysis of volatile compounds in breath for COVID testing.
Now comes another option for sampling: Sweat capture. Historically, measurement of chloride ions in sweat was the definitive test for cystic fibrosis, but the potential today is so much more, as a recent Medscape by WebMD review describes. Married to innovative analysis techniques (one recent paper describes battery-free electronic sensing), the introduction of minimally invasive sampling such as this is opening up new diagnostic possibilities.
Quick Hits
Scientists in China have developed a bioelectronic mask with ion-gated transistors that can detect respiratory viruses - including SARS-CoV-2. Reporting in the journal Matter, they say their device can provide results in as little as 10 minutes.
An Austrian team has developed a global dataset of SARS-CoV-2 “events” in animals. Published in Nature back in July, it can also be accessed via an online dashboard with what may be the coolest-looking COVID-19 map we’ve seen yet. The dataset will be updated weekly for at least one year.