Well, case patterns continue to vary greatly across the world. For example, after reaching ridiculous heights, France and Australia are on the descent. Japan’s cases are gaining speed, and interestingly, U.K., Canada, and South Africa have stalled after their initial descent.
Just wanted to let you know that I shared this information, particularly the info on the effectiveness of boosters against the new variants, with the woman who cleans our house (and does myriad other things beyond my capacity). It convinced her to go get her booster shot today. So THANKS
(I just want to take a quick moment to say how much I appreciate your efforts to make all this data and technical information accessible and understandable to a general audience. As someone who develops technical documentation for a living, I know how much work it takes to do that well. Thank you!)
In the UK part of the reason for the stall may be increasing use of RATs finding more asymptomatic patients.
I have a strong suspicion that using cases to determine vaccine efficacy results in bias. The assumption required for the analysis is that the unvaccinated behave the same as the vaccinated, and this is unlikely to be true. Less concern about Covid and less interaction with the health system would be likely with unvaccinated subjects. Page 13 of https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1018416/Vaccine_surveillance_report_-_week_37_v2.pdf shows that there is something happening unless you want to believe that the vaccinated are at higher risk of Covid.
The vaccine and boosters don't completely prevent infection with Omicron. What they do have is a good effect on hospitalisations and ICU use. You need to think about where Gibraltar or anywhere else would be without vaccines. The answer is Romania where they've had to reintroduce a lot of restrictions because a lot of stupid people don't want to be vaccinated. Their case numbers are still climbing.
That is not what the article says. What it does say is that the effect of vaccines is less for BA.2 compared to BA.1 or in their words “vaccinated people have a higher risk of becoming infected with BA.2 compared to BA.1”.
Thanks for another great article. Do you know- are there data and discussions out there about post-covid syndrome? Experiencing it in my house and it’s incredibly disruptive; and, there seems to be very little known about it or how to address it. Would love to read a post of yours on it, if possible. Thanks, D.
First, I'm glad whoever in your household is recovered but I'm sorry to hear they're still suffering long-term effects.
There's a lot more being learned about post-COVID or long-COVID syndrome, and a lot of work is also ongoing in kids. I don't have my article archive handy while traveling, but there are at least case reports of people whose long-covid symptoms resolved fully or partially with post-disease vaccination. Postmortem examination has found viable virus in "recovered" but long-covid patients in a variety of tissue diseases. A number of inflammatory markers are elevated in these patients. I've spent literally no time clinically on post-covid or long-covid syndromes, so all I can offer is what I've seen in the literature.
The article referenced heavily is one I'd read but somehow, I didn't recall it. There's a lot more material out there. Look at COVID resources on STAT+, JAMA, JHU. I'd say Medpage and Medscape, but the comments, if you get into them are generally not helpful but can make you wonder if you're reading something worthwhile unless your training is in medicine or biosciences.
It's going to be several days before we're settled and I have the "big computer" back up and can look.
Don't know if you know about Prof Tim Spector and the Zoe app and study in the UK. There is a weekly YouTube update on data from people's input. They've touched on long covid but not much lately. Hope you and yours feel better soon and I hope you find help.
Have some questions about the graph showing evolution of covid-19's infection fatality ration in England. Am having a discussion with someone about how to think about the info in it, and need to know more. It appears that this graph was put together for this blog, is that right? If not, can you provide a link to the original source, so I can read the info there?
Here are the things I'm wondering about: Are the Covid cases & fatalities on the graph for vaccinated and unvaccinated people combined? Or just for vaccinated people? Same question regarding the flu cases and fatalities. Also, seems a bit odd that graph compares covid data from England with flu data from New Zealand. Any special reason for that?
I am not complaining about the graph! Just need clarification about the IFR's show there, so as to be more able to draw conclusions about where things stand.
Your posts are wonderful, and I write this comment Not to criticize. But I often find interpretations of risk ratios when they include adjectives, so during my latter decades of teaching I advised my students to avoid phrases like "times higher". So when I read "BA.2 has a +126% growth rate over BA.1" I think if BA.2 and BA.1 had the same growth rate, I would write BA.2 had +0% growth rate over BA.1, so +126% growth rate over BA.1 must mean that BA.1 has (1 + 1.26) times the BA.1 growth rate, which I doubt is the intended meaning. Similarly, when I read "IFR is still about two times higher than the flu," I'm thinking it could mean that the SARS-CoV-2 IFR is about three times that of the flu (i.e., "two times higher" = as high plus two times more). Without the actual numbers, I find the phrasing ambiguous. But I have neither a day job nor two young children nor write a daily column, so this is just my attempt to be helpful. https://go.unc.edu/vjs, https://go.unc.edu/EPID
Should vac & boosted seniors 76-85 yrs old get tests to see their levels of antibodies & if low ( whatever that is), get a third booster shot ( & mix Pfizer/Moderna)? Natalie Shawn
I fully expect a recommendation for another booster at some point, perhaps 4 months, perhaps longer after the first one. If boosting after a J&J single-dose, I'd use one of the mRNAs for the booster. I'm waiting to hear what ACIP thinks about Novavax although I expect its EUA will be recommended. I wouldn't try to get an antibody level. quantitative antibody assay remains a bit of a black art for COVID.
Yes totally get that but...How do we set the bar for how likely "probably" needs to be to authorize it? I'm asking from a science perspective, a policy perspective...and a parent perspective. I'm curious to see if Pfizer has any data whatsoever on shot 3. (I think you're an epi? I'm a clinical trial PI but not in immunology/vaccines).
You're looking at a finding of no harm followed by the potential benefit of a third dose. I'm doing epi work now. I've dinner clinical trials in a past life both as a PI and as control statistician. Having the clinical perspective while exercising the daily statistical analysis was an interesting change.
Essentially, if there's no harm seen in vaccinations, and potential benefit especially if we add an earlier third dose (not 6 months out but perhaps 3) does this offer sufficient rationale to issue an EUA ?considera
Bigger isn't always better. And fever is generally an indication that the immune response is spinning up. What wasn't happening at the 10 mcg dose was that we weren't seeing appreciable antibody production compared to other age groups.
That’s great if omicron’s case fatality rate is lower than delta’s, yet is anyone assessing the prevalence of and impact of people taking off-label early treatment such as Fluvoxamine (which as of November 2021 is now part of Johns Hopkins covid protocol, see link below)
Also... The data in that guide are fairly dated. I've not subscribed to their guide so I'll need to do so, but most of the guidance including remdesivir and convalescent plasma has cycled out of a lot of conventional therapeutic guidance.
Fluvoxamine is cheap and well-tolerated, and evidence it improves the odds of high-risk people seems decent even if not airtight. Why discard it as an option? Especially since Paxlovid is in very short supply, and also cannot be used for quite a few high-risk people because of interactions with their meds or danger of using in people who have problems with liver and whatnot?
Fluvoxamine is being used primarily for its anti-inflammatory properties. Well-powered clinical trials are underway but its use is not in violation of any FDA orders/edicts. It's not a proven wonder-drug. risk-benefit evaluation is a daily part of clinical care, especially in a pandemic setting.
Yes, am aware of all of these points: how it's anti-inflammatory properties are probably what's helpful, not a wonder drug, importance of risk-benefit evals, use not in violation of FDA orders.
But let's think about what's happening in practice at this point. Had a recent discussion with a number of MD's about use of fluvoxamine w/ high-risk covid patients, and all of them said they were not comfortable prescribing it. It's really an OCD drug more than an antidepressant. Many internists are willing to prescribe antidepressants, but prescribing fluvoxamine feels like one step too far to them, especially prescribing it off-label for covid. And they are extra-nervous about prescribing it off-label for covid because they're worried about getting hassled like the docs who prescribe treatments that are almost certainly useless, like ivermectin. So in practice, virtually no high-risk patients have been given a course of fluvoxamine after diagnosis, even though the stuff is cheap, plentiful, well-tolerated and overall looks pretty decent cost/benefit-wise, especially when you're trying to improve the odds of some unvaccinated 79-year old in mediocre general health who just got diagnosed with covid.
The medical system is being forced to do all kinds of sub-optimal things in order to keep addressing the problem of covid -- postponing liver resections for cancer patients, housing patients in hallways, having staff return to work after covid without taking a rapid to test to make sure they're not contagious. What I'm saying is that taking steps to up the use of fluvoxamine for covid patients is suboptimal, given that the well-powered clinical trials are not yet complete, but probably worth the downsides, just like these other steps. Fluvoxamine use for covid is only going to happen if steps are taken to legitimize using it that way, so that docs feel comfortable doing so.
As for the well-powered clinical trials that are underway: That's good, interested to see results, but are you saying that until the results of them seep through multiple bureaucratic filters we should just do nothing to encourage and legitimize use of fluvoxamine? If so, why?
Clinically, off-label use requires a degree of comfort usually derived from either first-hand or trusted-entity messaging about that treatment. The trusted agent could be a report of a well-designed and powered clinical trial, or experience from a trusted colleague. Or something the doc experimented with during a research rotation. We've seen what happens when FDA says something's OK, lots of people prescribe it, and we subsequently discover that its adverse effects profile reared its head at the doses thought needed to provide clinical effect (e.g., ivermectin, hydroxychloroquine). FDA and CDC staff follow clinical trials, and reports of clinical trials often are released in preprint or print well before the agencies act on them. For instance, it was painfully obvious to me, before the declarations on ivermectin and hydroxychloroquine that they would be found ineffective and dangerous. Then again, I also was well aware of the pharmacology and side effects of the drugs, and not everyone is.
Expect that, if the clinical trials produce solid supporting data, use of a prospective agent off-label will rise to provide another useful drug on the list.
Ideally we would have well-powered clinical trials that produce results right when we need them. However, in crises we often do not have rock-solid data to go by, and have to make judgment calls, and there are often people in a position to make decent judgment calls. You felt that you were in a position to make good calls about ivermectin and hydroxychloroquine -- they were useless and in fact harmful -- and I believe you. I am asking for your judgment call about fluvoxamine.
Without some registry of off-label usage and trials, and an idea of case numbers where the intervention is used, no, there's not a good way of making that assessment.
Thanks, Gerry! I guess what I’m trying to get after is it seems there are a number of people who, upon testing positive, turn to non-FDA approved early treatments (with their doctor’s approval), especially now that omicron has disqualified some of the approved therapeutics. And as you rightly point out, there’s no great way to track this. So no good way to know the degree to which omicron is more mild versus people taking early treatment under radar.
Nearly everyone I know who has tested positive in last year has sought non-FDA approved early treatment from their doctor, so this phenomenon isn’t small.
JH link is from mid-Nov so listed treatments don’t take in to account omicron.
Omicron's only "more mild" for people who were at least fully vaccinated. It approaches a mild or even non-event for those with recent boosters. An article in Nature I saw today suggests unvaccinated persons are 23x more likely to die in the latest surge than those who have been vaccinated.
Dr Jetelina- Could you please provide information regarding Pfizer request to FDA for 6mths - 4 year olds that could be happening today? I would really like your guidance and insights here. Thank you!
Yes I’d love to hear why you think they are considering this when the study showed it didn’t work. I want it to as much as anyone (I’m a pediatrician who has given over 1000 COVID shots to 5-11 year olds), but I worry giving EUA to something with such poor evidence may erode public trust.
It seems pretty clear the 2–5 group should have a higher dose. Maybe 5–6 mcg? One possibility is that the FDA will give it the okay, but ACIP will only allow it for 6mo to 2yr. Not a great situation overall.
I was wondering if any studies have been done on the difference in rates with people who had the J&J vaccine vs the others. Especially in regards to boosters vs no booster. I know someone who had the J&J but refused to get a booster. He ended up with Covid and 3 weeks later is still sick with it. Others I know who have been positive for Covid have had much milder symptoms and have had boosters - none of them originally had the J&J
Very interesting material today. I don't like to comment at COVID-related venues like some broken record or like some morbidly obese person sitting in his basement eating cookies (that's a Trump wisecrack) obsessing about ONE hobby horse (viz. flawed communication issues during the pandemic) BUT . . . . . I need to know what you meant by "Cases" in the text below, copied from today's report. This is important because there is the continuing conflation in both medical literature about, and news coverage regarding, the concepts "case", "infection", "PCR positivity", etc. This is materially important because Case Definition is almost the number one thing to get locked in for every epidemiology inquiry, including even when reading pertinent literature, not to mention the obvious confusion that can arise, for example, from the definition of "Case" as used in the Pfizer and Moderna randomized controlled trials of mRNA vaccine, etc. As well, it is my understanding that various states use a wandering array of definitions of "COVID case" in their reporting. In some places, just "blowing a positive" on your PCR test makes that person a "Case". In other places, you must not only have a positive PCR test result but also have a CLINICAL picture that "fits" (i.e. some combo of signs, symptoms, etc.). Hell, in some states we are not even told anything about COVID case dynamics.
------------------------------
You wrote today [asterisks are mine]: "In the United States, *cases* and test positivity rates continue to decline. Because both metrics are mirroring each other (rather than showing opposite trends), I’m confident this is the “true” trend and not a testing capacity or testing behavior phenomenon. The raw number of *cases*, though, continues to be greatly underreported".
'Cases' in this case corresponds to incidence. And cases, normalized to 100k population are almost certainly underreported. Although a common ratio of 1:3 or 1:4 for underreporting is bandied about, in some areas of the Country, I suspect it's even worse. The reasons have nothing to do with PCR sensitivity, inclusion of "official" antigen testing results, etc., but more to some states' or localities' rules that patients should have been symptomatic for at least 5 days before being referred for PCR testing. Similarly, the lack of acceptance of home test results means that if you test positive at home, you should call your doctor or public health clinic and attempt to schedule a PCR test for confirmation. Indeed, I'm aware of cases where a patient presents to their PCP with the clinical picture of COVID-19 but they are not manifesting symptoms that would gain them admission to the hospital, a diagnosis goes into the chart, never to be seen again, and no testing is ordered.
There's a history of underreporting engendered in the early days of the pandemic where you couldn't even get tested if you didn't present with all the symptoms present including a mandatory fever > 100.4F, followed by a positive PCR test. And recall we then did serial PCR testing to determine when you were "recovered" not fully understanding that viral fragments could engender a positive result. We were slow to field a working PCR test, slow to authorize home test kits and manufacturers were slow to the manufacture process fearing they'd never be used.
And, you're correct. Various states have varying definitions of what they'll accept as a "real" diagnosis although almost all require a positive PCR test. Some, lately, will accept an antigen result if it was performed in a CLIA-Waived facility such as a physician's office, pharmacy, or non-profit mass-testing environment usually associated with a non-profit. I'll let you sort out all the possible issues with that set of criteria.
In general, if you "blow a positive" on either PCR or even the home rapid antigen tests, you're really positive. You don't have to wait for symptoms, or a repeat test. I can think of at least one state where that's now the case generally speaking, although they cannot record a home test result officially. The staff epi's are noting even the home cases when they're notified of them.
Well your exegesis above could not have made a stronger "case" for my belief that there is GIANT confusion afoot regarding the meaning of words ever since the pandemic arrived. Perhaps one quip that EVERY epidemiologist in the land should have chiseled over her/his office door comes from the late Jacques Barzun: "Trouble begins when there is disagreement about the meaning of words".
Question about household attack rates vs primary attack rates. Is there a way of "factoring out" household spread when evaluating the benefits of living alone? I've read different estimates at various times during the pandemic, for various places. How much risk am I mitigating simply by being a single person household?
Also - based on covidestim.org the "stalling" in the decline seems to be emerging in NYC as well.
Just wanted to let you know that I shared this information, particularly the info on the effectiveness of boosters against the new variants, with the woman who cleans our house (and does myriad other things beyond my capacity). It convinced her to go get her booster shot today. So THANKS
(I just want to take a quick moment to say how much I appreciate your efforts to make all this data and technical information accessible and understandable to a general audience. As someone who develops technical documentation for a living, I know how much work it takes to do that well. Thank you!)
In the UK part of the reason for the stall may be increasing use of RATs finding more asymptomatic patients.
I have a strong suspicion that using cases to determine vaccine efficacy results in bias. The assumption required for the analysis is that the unvaccinated behave the same as the vaccinated, and this is unlikely to be true. Less concern about Covid and less interaction with the health system would be likely with unvaccinated subjects. Page 13 of https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1018416/Vaccine_surveillance_report_-_week_37_v2.pdf shows that there is something happening unless you want to believe that the vaccinated are at higher risk of Covid.
The data is becoming clear that the triple vaccinated are at higher risk.
Curious about this. Can you provide some good links?
Google "Gibraltar covid" Note that the 3x vax rate is near 90%, then look at today's cases.
The vaccine and boosters don't completely prevent infection with Omicron. What they do have is a good effect on hospitalisations and ICU use. You need to think about where Gibraltar or anywhere else would be without vaccines. The answer is Romania where they've had to reintroduce a lot of restrictions because a lot of stupid people don't want to be vaccinated. Their case numbers are still climbing.
https://www.coronaheadsup.com/science/variants/omicron/ba2/denmark-ba-2-infection-risk-higher-in-vaccinated-and-booster-vaccinated-households/
That is not what the article says. What it does say is that the effect of vaccines is less for BA.2 compared to BA.1 or in their words “vaccinated people have a higher risk of becoming infected with BA.2 compared to BA.1”.
And what do you make of that?
BA.2 is more infectious, and the estimate is about 50% more. The effect will mean that the wave will last a couple of weeks longer.
Thanks for another great article. Do you know- are there data and discussions out there about post-covid syndrome? Experiencing it in my house and it’s incredibly disruptive; and, there seems to be very little known about it or how to address it. Would love to read a post of yours on it, if possible. Thanks, D.
First, I'm glad whoever in your household is recovered but I'm sorry to hear they're still suffering long-term effects.
There's a lot more being learned about post-COVID or long-COVID syndrome, and a lot of work is also ongoing in kids. I don't have my article archive handy while traveling, but there are at least case reports of people whose long-covid symptoms resolved fully or partially with post-disease vaccination. Postmortem examination has found viable virus in "recovered" but long-covid patients in a variety of tissue diseases. A number of inflammatory markers are elevated in these patients. I've spent literally no time clinically on post-covid or long-covid syndromes, so all I can offer is what I've seen in the literature.
NIH is doling out grants right now.
Would love to read what you might be able to dig up. Thanks so much for the offer.
Here's a start: https://health.ucdavis.edu/news/headlines/antibodies-mimicking-the-virus-may-explain-long-haul-covid-19-rare-vaccine-side-effects/2021/11
The article referenced heavily is one I'd read but somehow, I didn't recall it. There's a lot more material out there. Look at COVID resources on STAT+, JAMA, JHU. I'd say Medpage and Medscape, but the comments, if you get into them are generally not helpful but can make you wonder if you're reading something worthwhile unless your training is in medicine or biosciences.
It's going to be several days before we're settled and I have the "big computer" back up and can look.
Don't know if you know about Prof Tim Spector and the Zoe app and study in the UK. There is a weekly YouTube update on data from people's input. They've touched on long covid but not much lately. Hope you and yours feel better soon and I hope you find help.
Have some questions about the graph showing evolution of covid-19's infection fatality ration in England. Am having a discussion with someone about how to think about the info in it, and need to know more. It appears that this graph was put together for this blog, is that right? If not, can you provide a link to the original source, so I can read the info there?
Here are the things I'm wondering about: Are the Covid cases & fatalities on the graph for vaccinated and unvaccinated people combined? Or just for vaccinated people? Same question regarding the flu cases and fatalities. Also, seems a bit odd that graph compares covid data from England with flu data from New Zealand. Any special reason for that?
I am not complaining about the graph! Just need clarification about the IFR's show there, so as to be more able to draw conclusions about where things stand.
Your posts are wonderful, and I write this comment Not to criticize. But I often find interpretations of risk ratios when they include adjectives, so during my latter decades of teaching I advised my students to avoid phrases like "times higher". So when I read "BA.2 has a +126% growth rate over BA.1" I think if BA.2 and BA.1 had the same growth rate, I would write BA.2 had +0% growth rate over BA.1, so +126% growth rate over BA.1 must mean that BA.1 has (1 + 1.26) times the BA.1 growth rate, which I doubt is the intended meaning. Similarly, when I read "IFR is still about two times higher than the flu," I'm thinking it could mean that the SARS-CoV-2 IFR is about three times that of the flu (i.e., "two times higher" = as high plus two times more). Without the actual numbers, I find the phrasing ambiguous. But I have neither a day job nor two young children nor write a daily column, so this is just my attempt to be helpful. https://go.unc.edu/vjs, https://go.unc.edu/EPID
Should vac & boosted seniors 76-85 yrs old get tests to see their levels of antibodies & if low ( whatever that is), get a third booster shot ( & mix Pfizer/Moderna)? Natalie Shawn
I fully expect a recommendation for another booster at some point, perhaps 4 months, perhaps longer after the first one. If boosting after a J&J single-dose, I'd use one of the mRNAs for the booster. I'm waiting to hear what ACIP thinks about Novavax although I expect its EUA will be recommended. I wouldn't try to get an antibody level. quantitative antibody assay remains a bit of a black art for COVID.
Sooo what on earth is going on with these rumors about Pfizer pursuing approval for <5s? Are they just going in with "eh it's safe, so why not?"
The vaccine appears safe but not as efficacious as we'd really like. Current thought is a 3rd dose with a little more spacing will probably fix that.
Yes totally get that but...How do we set the bar for how likely "probably" needs to be to authorize it? I'm asking from a science perspective, a policy perspective...and a parent perspective. I'm curious to see if Pfizer has any data whatsoever on shot 3. (I think you're an epi? I'm a clinical trial PI but not in immunology/vaccines).
You're looking at a finding of no harm followed by the potential benefit of a third dose. I'm doing epi work now. I've dinner clinical trials in a past life both as a PI and as control statistician. Having the clinical perspective while exercising the daily statistical analysis was an interesting change.
Essentially, if there's no harm seen in vaccinations, and potential benefit especially if we add an earlier third dose (not 6 months out but perhaps 3) does this offer sufficient rationale to issue an EUA ?considera
Could they bump up the dose for 2–5s from 3mcg to 5mcg? I gather the only problem at 10mcg was an excess of fevers.
Bigger isn't always better. And fever is generally an indication that the immune response is spinning up. What wasn't happening at the 10 mcg dose was that we weren't seeing appreciable antibody production compared to other age groups.
I thought they did the phase 2 trial at 3mcg, rejecting 10mcg in phase 1 because there were too many fever issues. Did I misread?
Thank you for this invaluable snapshot of the state of this pandemic.
Thanks for the write up!
I think there is a typo in this sentence: "How much cases increases, though..."
That’s great if omicron’s case fatality rate is lower than delta’s, yet is anyone assessing the prevalence of and impact of people taking off-label early treatment such as Fluvoxamine (which as of November 2021 is now part of Johns Hopkins covid protocol, see link below)
https://www.hopkinsguides.com/hopkins/ub?cmd=repview&type=479-1225&name=30_538747_PDF
There is no information available omicron’s confirmed case fatality rate in the US. If there is, I can't find it.
Also... The data in that guide are fairly dated. I've not subscribed to their guide so I'll need to do so, but most of the guidance including remdesivir and convalescent plasma has cycled out of a lot of conventional therapeutic guidance.
Fluvoxamine is cheap and well-tolerated, and evidence it improves the odds of high-risk people seems decent even if not airtight. Why discard it as an option? Especially since Paxlovid is in very short supply, and also cannot be used for quite a few high-risk people because of interactions with their meds or danger of using in people who have problems with liver and whatnot?
Fluvoxamine is being used primarily for its anti-inflammatory properties. Well-powered clinical trials are underway but its use is not in violation of any FDA orders/edicts. It's not a proven wonder-drug. risk-benefit evaluation is a daily part of clinical care, especially in a pandemic setting.
Yes, am aware of all of these points: how it's anti-inflammatory properties are probably what's helpful, not a wonder drug, importance of risk-benefit evals, use not in violation of FDA orders.
But let's think about what's happening in practice at this point. Had a recent discussion with a number of MD's about use of fluvoxamine w/ high-risk covid patients, and all of them said they were not comfortable prescribing it. It's really an OCD drug more than an antidepressant. Many internists are willing to prescribe antidepressants, but prescribing fluvoxamine feels like one step too far to them, especially prescribing it off-label for covid. And they are extra-nervous about prescribing it off-label for covid because they're worried about getting hassled like the docs who prescribe treatments that are almost certainly useless, like ivermectin. So in practice, virtually no high-risk patients have been given a course of fluvoxamine after diagnosis, even though the stuff is cheap, plentiful, well-tolerated and overall looks pretty decent cost/benefit-wise, especially when you're trying to improve the odds of some unvaccinated 79-year old in mediocre general health who just got diagnosed with covid.
The medical system is being forced to do all kinds of sub-optimal things in order to keep addressing the problem of covid -- postponing liver resections for cancer patients, housing patients in hallways, having staff return to work after covid without taking a rapid to test to make sure they're not contagious. What I'm saying is that taking steps to up the use of fluvoxamine for covid patients is suboptimal, given that the well-powered clinical trials are not yet complete, but probably worth the downsides, just like these other steps. Fluvoxamine use for covid is only going to happen if steps are taken to legitimize using it that way, so that docs feel comfortable doing so.
As for the well-powered clinical trials that are underway: That's good, interested to see results, but are you saying that until the results of them seep through multiple bureaucratic filters we should just do nothing to encourage and legitimize use of fluvoxamine? If so, why?
Clinically, off-label use requires a degree of comfort usually derived from either first-hand or trusted-entity messaging about that treatment. The trusted agent could be a report of a well-designed and powered clinical trial, or experience from a trusted colleague. Or something the doc experimented with during a research rotation. We've seen what happens when FDA says something's OK, lots of people prescribe it, and we subsequently discover that its adverse effects profile reared its head at the doses thought needed to provide clinical effect (e.g., ivermectin, hydroxychloroquine). FDA and CDC staff follow clinical trials, and reports of clinical trials often are released in preprint or print well before the agencies act on them. For instance, it was painfully obvious to me, before the declarations on ivermectin and hydroxychloroquine that they would be found ineffective and dangerous. Then again, I also was well aware of the pharmacology and side effects of the drugs, and not everyone is.
Expect that, if the clinical trials produce solid supporting data, use of a prospective agent off-label will rise to provide another useful drug on the list.
Ideally we would have well-powered clinical trials that produce results right when we need them. However, in crises we often do not have rock-solid data to go by, and have to make judgment calls, and there are often people in a position to make decent judgment calls. You felt that you were in a position to make good calls about ivermectin and hydroxychloroquine -- they were useless and in fact harmful -- and I believe you. I am asking for your judgment call about fluvoxamine.
The NIH is still pushing Remdesivir.
Hospitals spent over $1b on it last year.
https://www.modernhealthcare.com/supply-chain/hospitals-spent-more-1b-remdesivir-last-year
Now pushing it for use outside of the hospital: https://www.kgw.com/article/news/health/coronavirus/remdesivir-outpatient-use/283-badaa078-5adc-4c39-ac59-094f625ee161
Without some registry of off-label usage and trials, and an idea of case numbers where the intervention is used, no, there's not a good way of making that assessment.
Thanks, Gerry! I guess what I’m trying to get after is it seems there are a number of people who, upon testing positive, turn to non-FDA approved early treatments (with their doctor’s approval), especially now that omicron has disqualified some of the approved therapeutics. And as you rightly point out, there’s no great way to track this. So no good way to know the degree to which omicron is more mild versus people taking early treatment under radar.
Nearly everyone I know who has tested positive in last year has sought non-FDA approved early treatment from their doctor, so this phenomenon isn’t small.
JH link is from mid-Nov so listed treatments don’t take in to account omicron.
Omicron's only "more mild" for people who were at least fully vaccinated. It approaches a mild or even non-event for those with recent boosters. An article in Nature I saw today suggests unvaccinated persons are 23x more likely to die in the latest surge than those who have been vaccinated.
It seems that we are hitting a plateau in the northeast US, just like they did in South Africa and the UK. Any thoughts as to why?
Dr Jetelina- Could you please provide information regarding Pfizer request to FDA for 6mths - 4 year olds that could be happening today? I would really like your guidance and insights here. Thank you!
Yes I’d love to hear why you think they are considering this when the study showed it didn’t work. I want it to as much as anyone (I’m a pediatrician who has given over 1000 COVID shots to 5-11 year olds), but I worry giving EUA to something with such poor evidence may erode public trust.
It seems pretty clear the 2–5 group should have a higher dose. Maybe 5–6 mcg? One possibility is that the FDA will give it the okay, but ACIP will only allow it for 6mo to 2yr. Not a great situation overall.
If recommended and authorized by FDA... do it. I anticipate a boost or full-up 3rd dose at 2-4 months for most of this age group.
I was wondering if any studies have been done on the difference in rates with people who had the J&J vaccine vs the others. Especially in regards to boosters vs no booster. I know someone who had the J&J but refused to get a booster. He ended up with Covid and 3 weeks later is still sick with it. Others I know who have been positive for Covid have had much milder symptoms and have had boosters - none of them originally had the J&J
Very interesting material today. I don't like to comment at COVID-related venues like some broken record or like some morbidly obese person sitting in his basement eating cookies (that's a Trump wisecrack) obsessing about ONE hobby horse (viz. flawed communication issues during the pandemic) BUT . . . . . I need to know what you meant by "Cases" in the text below, copied from today's report. This is important because there is the continuing conflation in both medical literature about, and news coverage regarding, the concepts "case", "infection", "PCR positivity", etc. This is materially important because Case Definition is almost the number one thing to get locked in for every epidemiology inquiry, including even when reading pertinent literature, not to mention the obvious confusion that can arise, for example, from the definition of "Case" as used in the Pfizer and Moderna randomized controlled trials of mRNA vaccine, etc. As well, it is my understanding that various states use a wandering array of definitions of "COVID case" in their reporting. In some places, just "blowing a positive" on your PCR test makes that person a "Case". In other places, you must not only have a positive PCR test result but also have a CLINICAL picture that "fits" (i.e. some combo of signs, symptoms, etc.). Hell, in some states we are not even told anything about COVID case dynamics.
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You wrote today [asterisks are mine]: "In the United States, *cases* and test positivity rates continue to decline. Because both metrics are mirroring each other (rather than showing opposite trends), I’m confident this is the “true” trend and not a testing capacity or testing behavior phenomenon. The raw number of *cases*, though, continues to be greatly underreported".
'Cases' in this case corresponds to incidence. And cases, normalized to 100k population are almost certainly underreported. Although a common ratio of 1:3 or 1:4 for underreporting is bandied about, in some areas of the Country, I suspect it's even worse. The reasons have nothing to do with PCR sensitivity, inclusion of "official" antigen testing results, etc., but more to some states' or localities' rules that patients should have been symptomatic for at least 5 days before being referred for PCR testing. Similarly, the lack of acceptance of home test results means that if you test positive at home, you should call your doctor or public health clinic and attempt to schedule a PCR test for confirmation. Indeed, I'm aware of cases where a patient presents to their PCP with the clinical picture of COVID-19 but they are not manifesting symptoms that would gain them admission to the hospital, a diagnosis goes into the chart, never to be seen again, and no testing is ordered.
There's a history of underreporting engendered in the early days of the pandemic where you couldn't even get tested if you didn't present with all the symptoms present including a mandatory fever > 100.4F, followed by a positive PCR test. And recall we then did serial PCR testing to determine when you were "recovered" not fully understanding that viral fragments could engender a positive result. We were slow to field a working PCR test, slow to authorize home test kits and manufacturers were slow to the manufacture process fearing they'd never be used.
And, you're correct. Various states have varying definitions of what they'll accept as a "real" diagnosis although almost all require a positive PCR test. Some, lately, will accept an antigen result if it was performed in a CLIA-Waived facility such as a physician's office, pharmacy, or non-profit mass-testing environment usually associated with a non-profit. I'll let you sort out all the possible issues with that set of criteria.
In general, if you "blow a positive" on either PCR or even the home rapid antigen tests, you're really positive. You don't have to wait for symptoms, or a repeat test. I can think of at least one state where that's now the case generally speaking, although they cannot record a home test result officially. The staff epi's are noting even the home cases when they're notified of them.
Well your exegesis above could not have made a stronger "case" for my belief that there is GIANT confusion afoot regarding the meaning of words ever since the pandemic arrived. Perhaps one quip that EVERY epidemiologist in the land should have chiseled over her/his office door comes from the late Jacques Barzun: "Trouble begins when there is disagreement about the meaning of words".
A battle I’ve been fighting for the last 2 years…
Come to Minnesota and get your blood pressure elevated every day by the vaunted MN Department of Health here. I could tell you stories . . . . .
That’s ok, I’ve experience in Oklahoma and several other state health debacles and I’ll be visiting the Twin Cities and western Wisconsin soon enough.
Question about household attack rates vs primary attack rates. Is there a way of "factoring out" household spread when evaluating the benefits of living alone? I've read different estimates at various times during the pandemic, for various places. How much risk am I mitigating simply by being a single person household?
Also - based on covidestim.org the "stalling" in the decline seems to be emerging in NYC as well.