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"It’s possible to be contagious yet have a negative rapid test. Four of the 30 people in this study spread COVID19 between negative rapid tests." - How, if at all, would you change your recommendations around using rapid tests before you see elderly or at risk people? I think we'd hoped that a negative rapid test meant that at the very least you weren't (very) contagious and you could have some comfort from that before seeing at risk family/friends. This seems to contradict that and is so disheartening.

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unfortunately there will always be some level of risk. that's why a layered approach is best (wear masks around high risk people too). one trick is to use antigen tests earlier. so test 2 days before you see them. then test the morning of. this will reduce the chances of a false negative. also pay attention if there is a faint line (this would mean you're in the beginning of infection).

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Is there any evidence to show that fully vaccinated and boosted (if relevant) are taking longer to test positive on rapid antigen tests even though they end up truly being covid positive? I know of 4 instances now among two different families where individuals continuously tested negative on serial testing but ultimately were positive on days 7 - 12 after exposure. Given how virulent omicron is reported to be and the replication of it in a human system being more rapid, is this just a fluke or do vaccines play a role in trying to shut the incoming virus down but ultimately succumb to its high replication rate? For the record, all illness in these individuals was mild and short-lived.

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Some evidence for earlier symptom onset in vaccinated people, since the symptoms in this case are from the primed immune system rather than from the virus per se. That in turn can shift the window of observation early. Good question about suppressing the virus temporarily.

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Might also want to swab the NAA swab on tonsils and then nose to increase yield. As they do in UK and at UCSF.

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This is discussed in the article.

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Not really. NBA players and PCR dual swabbing but don’t know anyone with access to home PCR testing.

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It's not limited to PCR. She's discussed the difference between saliva and nostril based sample collection for several blog posts.

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Given that PCR does not measure virus, and that the preprint reviewed here found that there isn’t a correlation between actual virus and PCR -shouldn’t we stop referring to PCR CT results as ‘viral load’?-it isn’t, it’s merely a proxy that may not hold up well, and the terminology used to date is misleading. Virologists have been very careful about this distinction for 2 years now-the rest of us need to catch up. Now that some are finally looking at actual virus it may turn out PCR testing has not been used appropriately and that we may need to narrow the situations in which it is used.

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I would agree with all of this. I think we used PCR tests too liberally throughout the pandemic. they have their place, but not for what the majority of Americans want to know: am I infectious

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CT has always been a murky marker to me. And as noted, viral load isn't the same as reproductive-capable particles. That said, rt-PCR, as a molecular test, was the right test at the start of the pandemic to assure we had "the right virus" in our detection. We failed with rt-PCR in CDC's requirement that only THEY could produce the base test, when we had a large number of competent hospital, academic and commercial labs capable of spinning up quickly. Our subsequent failure to appropriately evaluate antigen tests early on, resulting in a flood of tests, some of which provided erroneous results, AND no mechanism to really track these tests and their results reliably, was a significant loss. Finally, the misinformation stream that claimed we were inflating cases by including antigen tests when in fact, a case is a person who's been confirmed infected by some means (NAAT or antigen, or both) led some to determine that antigen tests were causing a statistical problem, not providing critical information. Couple all of that to the amount of wait-time for PCR results, and, simply put, we didn't test enough to know what our viral load within the population (not, as referenced in this posting, within a potentially contagious person) really was.

I'd love to see serology used to determine the overall coverage of circulating antibodies in the population at large. Unfortunately, the political bias and self-selection for a volunteer study of this sort would skew the numbers, I suspect.

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Why would antigen tests be getting darker late in infection? My son had mild symptoms last Wednesday and tested positive on the morning with all symptoms basically resolved. He bounced off the walls all week. On Sunday I started feeling sick and tested positive Monday. I tested him and saw a faint line. Tuesday would have been his back-to-school day so I tested him again and he still had a faint positive so I kept him home. My toddler also tested faintly positive for the first time on Tuesday. Since then, I've tested my son each morning and his lines are getting darker. Today, Thursday, 8 days post-onset, the line is as dark as it was on day 0. He remains asymptomatic. My daughter and I (I am vaxxed and boosted) have had coughs and runny noses, mild fevers and chills and aches. Could we be contaminating his sample just by being around? Or could our viral load be making him 'sick' again?

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Only a PCR test and an expert can tell you for sure what's going on.

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A PCR test unfortunately wouldn't tell me anything. PCRs are not advised after infection as they can detect the virus for months but do not indicate anything about infectiousness. At this point it is moot because my sons test is now nearly negative at 11 days post-infection so I'm confident he'll be negative in a day or two.

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What I was thinking, and I am definitely no expert, is that the cycle count of the PCR test could tell you what is going on. For example, this is what I just found: "In addition, Bullard and colleagues used cycle threshold (ct) values as quantitative measure for viral RNA load and reported that infectious virus could not be isolated from diagnostic samples when ct values were above 24"

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Interesting. They may be able to do that at the lab level. None of the places I've had a PCR test provided anything to me other than detected or not-detected. I did speak to a doctor and an epidemiologist who both said that it's likely dead virus being detected and possible that reexposure (because my daughter and I were still early in infection) was contributing to lots of dead virus in his nose.

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There's been a lot of debate in the past about whether to supply such data to "civilians" as we might hurt ourselves with it it. It's the same level of argument as with masks when they all worried that because we might self-contaminate, maybe we shouldn't be allowed to play with them at all. In other words, because some of us might screw up, then nobody gets to have nice things.

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I would love some guidance. I’m on day 12 since first symptom; 11 days since positive PCR; 10 days since positive rapid test; 6 days since I last had symptoms!!! I’m still testing positive on rapid antigen test. Is this a personal anomaly or is there something about Omicron? I am still in isolation and will continue until I test negative, but I wonder how infectious I am and if I am, how common is it that people are following guidance to leave isolation after x number of days (be it 5 or 10 or 5 past last symptoms)…..And as a side note, my husband is still negative.

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Thanks for sharing! When did you eventually test negative? My son is on day 8 and not only positive but it's suddenly been getting darker again and now as dark as it was on day one after having looked like it was on the way out at 5 days! He had symptoms for less than 24 hours and has been completely asymptomatic and bouncing off the walls since.

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I finally tested negative on day 14 since first symptom. I assume your son has to test negative to go back to school? My colleague at the Health Department reminded me that CDC is not recommending testing out of isolation.

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The CDC, it seems, will recommend anything out of convenience. Of course we don't want contagious people to rejoin the general population. The only way to prevent that is to test negative with rapid or with a PCR above a given cycle count indicating strong likelihood of the end of being infectious.

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Wow, day 14. At least then I would have faith in a negative rapid. My friend tested strong positive on a rapid, then a few hours later it was negative. Got a PCR as a tie breaker, it was positive. Same day as PCR, did another rapid and it was negative. His work really tried to tell him to leave for the second rapid negative, just 2 days after a rapid positive. Thank goodness he was caring enough to get a PCR. It's very disturbing to see people just go by symptoms or one rapid negative. Initial symptoms would have been written off as allergies certainly if it was pollen season instead of winter.

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14 days was the initial recommended period to isolate before all of the corner-cutting emerged in order to accommodate economic objectives.

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You can scroll down to my Jan 19 post but it said this: "I tested positive on home antigen test through Day 12, despite the fact that my very mild symptoms were over by Day 5. I also did not infect a single person among the seven I was seeing daily indoors in the week before my first positive test, including my daughter (young adult, triple-vaxed) who I slept in the same bed with for that time. Very mysterious. I'm curious if you have thoughts on this."

Similar trajectory. I am mystified, so this doesn't help you except to not feel alone. Mine was almost definitely omicron, fit the symptoms to a T. I was notified by my county DOH on Day 10 that I could stop isolating. I was a little uncertain but I did go grocery shopping and actually went to a museum -- all very masked of course and not getting near anyone -- because I couldn't believe I would be contagious. But I did not see anyone indoors unmasked until I finally tested negative on Day 15 (tested positive Day 12 then was too demoralized to test again until Day 15 when I really wanted to see a friend). I also got a response from someone saying that chance of household transmission 1 in 3.

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Thanks. Helpful. Would love to understand the science.

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Me too! I'm not sure anyone does at this point.

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I found this line: “ It may be due to weakened virus that continues to replicate, Benjamin tenOever, PhD, a microbiologist at NYU Grossman School of Medicine, told MedPage Today. It may also happen as a result of broken virus genomes.” in this article: I'm Over COVID Symptoms, but Still Testing Positive. Am I Infectious?

by Jennifer Henderson, medpagetoday.com

January 20, 2022 12:00 PM

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Thank you! No real answers but good to know it's under discussion.

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btw, the covidtests.gov page just contains the link to the special usps order form. if that helps anyone.

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Does this data say anything about the relative likelihood of false positives among different brands of antigen tests? I have taken Quidel Quickvue tests twice, and both times got a positive result which was followed by a negative PCR test, and the second time, also followed by two negative Binax tests. The two Quidel tests that gave me false positives were from different boxes purchased months apart, one before Omicron and one last weekend. I've taken PCR and Binax tests at least a dozen times and never had a positive result, so it's hard not to conclude that the Quidel tests are untrustworthy. Because these false positives ruined my whole weekend, I started looking into the data for different brands, and these two studies do suggest that the PPV is much worse for Quidel than for Binax:

Binax: https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e3.htm

Quidel: https://www.cdc.gov/mmwr/volumes/69/wr/mm695152a3.htm

And I know that this isn't scientific at all, but there are way more online reviews complaining of false positives for the Quidel tests than for the Binax tests.

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Good questions, especially when I have purchased whatever brand I could get my hands on.

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This update on testing (with antigen and PCR) is another very good addition to our understanding of how best to use these tests. If I may be so bold, I would make one suggestion, Dr Jetelina. The use of the term “viral load” in the context of PCR testing could be misunderstood. You come close to a clarification in the discussion of the fifth study reviewed. However, my preference would be to use the term “viral RNA load” in place of “viral load” in the context of PCR testing. As you know, neither antigen tests nor PCR tests detect infectious virion or measure infectious viral titers. Antigen and PCR tests measure PIECES of virus which are NOT infectious. Yes, there may be a relationship, but viral load (interpreted by many people as meaning infectious virus) is NOT the same thing as what PCR tests measure which is viral RNA load.

Thank you very much,

Dave Apgar, PharmD, CAPT(retired) US Public Health Service

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Another remarkable and informative post, thank you Dr Jetelina.

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"This study tells us that we need to be super careful when using rapid tests in the first few days of exposure or infection. To get the most from your rapid test, wait at least 48 hours after symptoms and 5 days after exposure before taking an antigen test. If you’re negative, test again 24 hours thereafter."

I don't think this is how most people are using rapid tests. From what I hear, people are testing as soon as they have any symptom. They are then acting on those results; negative, they feel free to carry on. And many people are testing as soon as they hear they have been exposed, and, again, with a negative result--the person feels free to act accordingly.

The recommendations to wait 48 hours or 5 days to test are just not part of their thinking, probably because recommendations appear to keep changing; federal and state and local officials provide conflicting recommendations; and employers put their own spin on those recommendations. AND people are tired and confused. I don't see most people being willing to follow the guidelines, if they even understand them or bother to try to figure them out.

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And we have 850,000 new cases per day.

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We definitely need more communication on this as we learn more. I heard from another doctor to wait as long as possible after symptoms to use antigen test - e.g. don't test at night if you aren't going anywhere for hours. Wait until the next day.

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So helpful, and so clearly written and explained. Thank you thank you...

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What about the other important use for rapid tests: Not just how to manage isolation after a known exposure or symptoms, but as a safety tool for gatherings with people who don't expect they've been exposed at all?

You want to get together with a few people, indoors, for several hours. Perhaps you want to eat together, so you want a way to manage the risk of getting together without masks. None of you have a known exposure or symptoms. So, you each take an antigen test. If anyone tests positive, they don't attend, and you get together with people who all just tested negative within the past hour or two.

What do we know about how reliable that is? How do these studies inform how we can judge the risks of doing that?

I realize that overall prevalence of infection is an important factor, if you can estimate it. So another way of asking this question is: Given some estimate P% of the prevalence in the set of people you're drawing from, and given a number of people N, if each person tests negative (with throat + nasal swab method) and those N people get together very shortly after they all test, what are the odds that at least one of them is infectious over the next few hours?

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I've had an epiphany regarding lateral-flow antigen testing over the last several months. For the organization I support, for our summer activities, we required a verifiable negative test (lab- or facility-based and documented) performed within 72 hours of arrival for entry and participation. A bit of research, and a requirement to rely on our participants' integrity allowed us to go to home-testing, with a picture of their negative result. Yes, we still had outbreaks, but we had a reasonable idea idea of our starting baseline. We're now considering a "home" test upon arrival observed by a designee with a repeat test 72 hours later. Also, we are employing these tests at our overnight events when someone presents with symptoms, as a rapid screen to see if we need, right now, to quarantine the cohort of participants they were with.

For another group I'm working with, where the social dynamics are a bit more fluid and not quite as well understood by Americans, I've been working with the local school district's plan, although I'm not sure I agree with it. I've been testing the school age kids who are identified as a classroom, or a close, contact at day 5 post-exposure and then 48-60 hours later with lateral-flow antigen kits (mostly, not exclusively, Abbott BinaxNow). Subjectively I'm pretty confident this approach has been an adequate screening approach. While the school doesn't recommend testing if asymptomatic, and doesn't require testing to return to school after a 5 day quarantine, I still employ it and we do NOT return a kid to school with a positive antigen test even after 5 days.

AS for cheek swabs being less effective than saliva or nasal swabs, recall that not all oral mucosa are created equal, and that omicron has been suggested to prefer a bronchial site rather than an upper-airway, or alveolar site (need to find that citation, sorry). With that in mind, I'd be surprised outperformed nasopharyngeal or posterior oropharyngeal samples.

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"the number of viral particles does not equal the number of infectious particles" -- can someone define the difference between these two 'particles'? Fragments vs. intact virus?

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Some virions can be defective - that is, packaged up in a cell and released without all of the necessary parts to function. Other virions may have been infectious when first created, but have degraded and lost function. And yet others may have been destroyed, perhaps by the immune system, but bits of their RNA came loose and are still floating around. PCR will detect any of these - as long as there's some intact RNA from this virus that matches any of the three targets the PCR is testing for. But PCR can't tell how much of that RNA came from viable intact virions.

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PCR can "see" some fragments and classify them as sufficient for a positive test. Similarly, not all virons produced in a reproductive cycle inside an infected cell are capable of reproduction. The ratio varies, but the concept has to be considered with working with these datasets.

If I recall correctly, though, the raw number of virons produced in a cycle is significantly higher for omicron than for delta, and delta was much higher than alpha and other variants before it. I am naively clinging to the belief that, knowing not all are capable of reproduction, the sheer volume increases the potential for infection. @Katelyn? Thoughts?

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Live versus dead virus. In the case of an immunized person, the virus may also be coated with antibodies, so while it's intact, it's no longer very infectious.

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Excellent reviews. Thanks for all of your hard work.

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