The biggest flaw with this study is that it does not account for prior natural infection. It has been thoroughly demonstrated that individuals who acquire immunity through natural infection have a robust and durable immune response [1][2][3]. Recent vaccination on top of this immunity is likely to further prime and improve immune responses to subsequent infection [4][5].
Not accounting for this fact is a significant confounding factor in the study, and I'm disappointed the authors made no distinction between unvaccinated and immunologically naive. This is a distinction that every sensible scientific discussion needs to acknowledge.
EDIT: please leave a comment down voters, I’m starting to think there’s some sort of targeted campaign against this type of information
> Vaccine breakthrough infections exhibited similar proliferation dynamics as infections in unvaccinated individuals (mean peak Ct: 20.5, 95% credible interval [19.0, 21.0] vs. 20.7 [19.8, 20.2], and mean proliferation time 3.2 days[2.5, 4.0] vs. 3.5 days [3.0, 4.0]); however, vaccinated individuals exhibited faster clearance (mean clearance time: 5.5 days [4.6, 6.6] vs. 7.5 days [6.8, 8.2]).
> If the Ct values in vaccinated and unvaccinated infected individuals reflect the same amounts of infectious virus, then this implies that individuals with breakthrough infections may be as infectious as unvaccinated individuals in the early stage of the infection, but remain infectious for a shorter time, reducing the total degree of onward transmission. These findings are in keeping with the hypothesis that vaccination protects against the severe manifestations of disease but offers less protection against infection in the upper airway. Precautions are therefore necessary to prevent onward transmission even from vaccinated individuals.
[2] SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN)
https://pubmed.ncbi.nlm.nih.gov/33844963/
> authors made no distinction between unvaccinated and immunologically naive. This is a distinction that every sensible scientific discussion needs to acknowledge.
Ideally, everyone would be tested for antibodies before receiving a vaccine, then we would have data to differentiate naive+vaccine from survivor+vaccine. This would be helpful for both science and public policy.
CDC needs to stop labelling people who are 13 days after their 2nd vaccine dose as "unvaccinated". A more accurate label would be "partly vaccinated".
> Ideally, everyone would be tested for antibodies before receiving a vaccine
I agree that would help make optimal decisions with regards to distributing a limited supply of vaccine doses.
However it's worth noting that even when antibodies drop below levels detectable by standard tests, individuals are likely to retain robust immune responses that provide sufficient protection from severe outcomes [1][2].
The window for SARS-CoV-2 antibody tests would be at least 8 months to a year for many individuals.
More expensive tests can detect immunity based on T cells for example, which would provide an even longer window.
And of course really expensive and invasive bone marrow aspirate tests could provide a window approaching a lifetime - but the tradeoffs involved there would likely be unfavorable for practical “proof”. Who knows what technology we’ll come up with in the future though.
It might be that you alluded to the term “natural immunity” which now comes with extra baggage.
There seems to be a recent talking point for “natural immunity”, and two of my [uk based!] friends who seem to end up on the wrong side of every issue are parroting this. They are somehow both tuned in to US YouTube talking heads, Tucker etc despite being in the UK.
The message that is being pushed as I understand it is “let the virus rip” since if(!) you come through unscathed you will end up with better immunity? Maybe I misunderstand it but they both in a “anti covid vaxx” stance so I think that’s their reasoning - it is somehow better to take your chances with the virus than get the vaccine.
> it is somehow better to take your chances with the virus than get the vaccine.
As i understand it that statement is more true when the age (and presence of comorbidities) of the subject goes down.
<10y: why on earth would we vaccinate these people?
>70y: why on earth not?
Many of us are in the middle, and that means things are not that clear cut. I believe everyone should choose for themselves, as herd-immunity is off the table and outbreaks amoung the young do not cause much strain on the health care system.
I think it’s true age is a big factor, but I’m not sure if we can rule out young people from straining the healthcare system (depending on your definition of young or course).
In Scotland this week we had 14 people under 10 admitted to hospital and 78 who were 70+. A big difference but not as big as you’d think. The distribution is also not concentrated around older age groups at the moment, it’s got significant numbers in all age groups:
Hospital admission is not a good metric to go by, because they may be discharged/not occupy it for long. If you check death by age you see no one young died, suggesting the disease is more easy on them ajd they won't need to be 2 weeks in ICU.
You could try the 'scared straight' approach and direct them to this thread on the /r/nursing subreddit about what other ICU nurses are seeing right now regarding unvaccinated Covid patients in the ICUs:
"They’re dropping like flies in our ICU. 20- and 30-year-olds on vent and 99% of them unvaccinated."
"There are really only 2 options we are seeing for patients here.
-you die
-you become permanently disabled. And they are sent to Rehab or Long Term Care"
"Dialysis here. All my new patients in the past six months have had their kidneys damaged due to covid. All of them."
Lesser. They do say that vaccinated individuals clear the infection more quickly, and indeed cellular immunity takes some time to kick in. From that a good guess is that long covid risk is lower.
Also, remember that selection bias still exists. There are going to be individuals with replication but lower viral loads that never get tested because they have no symptoms, and there will likely be a higher proportion of those in the vaccinated group.
I suspect that long COVID risk is lower in vaccinated individuals (and hope so as an expat who traveled halfway around the world to get vaccinated) but the risk should be quantified.
There are a growing number of reports of people with breakthrough infections who are experiencing symptoms that aren't "mild", and some reports of people with "long COVID" like symptoms. It's not reason enough to panic, but it's concerning, especially in light of the fact that until very recently, health experts and the media kept telling us that breakthrough infections were "rare" even as it was becoming evident they weren't.
Yeah it's probably not so rare. The errors in this case never fall on the side of false positive, and it's impossible they caught every breakthrough case. It follows that there are more breakthrough cases than what's reported. The point of contention is by what margin the CDC is off.
If you really want to embiggen the problem, ask yourself how many people got covid but never got tested. The rate of mild infection is probably a lot higher than reported because only people with anxiety and/or serious covid bothered to get tested or hospitalized. Everyone else called in sick or didn't know/care.
I think so. All evidence points to systemic infection being rarer in vaccinated people.
Probably once the initial rush of antibodies dissipates, the virus can get a foothold in the sinuses easy enough. But most the time the immune system will squash it without much trouble.
My feeling so far seems if you think of infection as a continuum then vaccines probably reduce detectable by PCR infection by 2/3rds. Symptomatic illness by 8 to 1. And serious illness by 30 to 1.
But the risk from community spread can be high enough to overwhelm those odds. Where I live case rates are 25 higher than they were 8 weeks ago.
- It is impossible to contact the owners of the website
- The website has gotten direct critique of spreading misinformation in two papers
- They draw their own conclusions from the paper.
But let's ignore all these red flags and focus on this. They claim that each of the following individual medicines works,
Fluvoxamine, Proxalutamide, Iota-carrageenan, Molnupiravir,
Quercetin, Povidone-Iodine, Curcumin, Casirivimab, Sotrovimab, Bamlanivimab,
Nitazoxanide, Budesonide, Zinc, Bromhexine, Colchicine, Vitamin D, Aspirin,
Favipiravir, Hydroxychloroquine, Remdesivir, and Vitamin C. I find it unlikely that ALL
those claims are true which in turn makes me question their scientific approach.
> The website has gotten direct critique of spreading misinformation in two papers - They draw their own conclusions from the paper.
Good to know, is that critique public?
> They claim that each of the following individual medicines works
The site text says:
> Analysis of the efficacy of early treatments for COVID-19. Treatments do not replace vaccines and other measures. All practical, effective, and safe means should be used. Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Denying the efficacy of any method increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage ... We focus on the most effective/promising early treatments. There are many treatments that are helpful for late stage patients, however we do not have the resources to cover everything and currently focus on early treatment.
That text doesn't say that each of the listed therapeutics "works", it says they are presenting an analysis/summary of the efficacy of each treatment, with data from referenced studies. If there's a critique of a referenced study, or an error in the summary which is derived from references, that would be good to identify publicly.
This type of summary of public data and research papers should be on github or other public source repo (the site says the content is CC0 licensed), where issues/PRs could be used to correct errors. Maybe the site can be forked, errors removed and additional studies added. Early treatment is an important and neglected topic, which can supplement vaccines in breakthrough cases.
This HN comment [0] links to a Twitter comment by an epidemiologist criticizing a related site for cherry-picking data, among other concerns.
It seems like there are several sites that all have similar layout/content and very distinctive plot styling. I think they are related, but I’m on a phone and haven’t made time for dig queries and such. Seems dodgy though.
Anyway, there’s been a feeding frenzy of questionable research since the pandemic started (well especially so anyway) so it’s more important than ever to practice informed skepticism.
In theory, those opposed to early treatments could publish a competing analysis of studies on early treatments. Maybe that has already been done?
On some contested topics, there's almost a need for rules of evidence, so there's an agreed upon list of papers/data for discussion. Then different stakeholders/teams can debate on their (likely biased) interpretations of a pool of evidence that is clearly bounded at any point in time, but expanding as new data/studies become available.
Here is Derek Lowe on the matter back in June, with an update after the big Egyptian study was retracted: [0]. Not specifically on this website you linked, but on the body of evidence for ivermectin as a COVID therapeutic.
I was curious so I ran Whois queries on three sites: c19early.com which you linked, and ivmmeta.com and c19ivermectin.com. They all seem to be hosted through google sites, and use the same DNS privacy service. I don’t know if google sites by default uses this service or something, but just looking at the similarity of the sites I am wary.
Any idea why India is reporting success in the real world that isn't predicted by available studies? E.g. could someone design a study in Uttar Pradesh, with their huge population, to dig deeper into conflicts between the studies available for Lowe's analysis, and the claimed success in UP? There are states in India not using Ivermectin, which could be compared with the effects of UP's official state policy of making Ivermectin widely available to their population.
When experiments don't match our predictions, there is often either an error in the experiment, or an opportunity to improve the models behind the prediction. In this case, one of the experiments (UP with 200 million people) apparently has an unexpectedly good, positive, cheap outcome with minimal supply chain dependencies or safety risks.
If the observations are incorrect, that should be easy to establish.
If we are unable to explain this observed, positive, practical outcome via existing theory, that would be scientifically exciting!
India is lying and systematically undercounting their cases, hospitalizations and deaths by as much as 10 times. India does not have a robust public health system or effective record keeping. They can't even record every birth let alone keep track of deaths in a pandemic.
India isn't reporting success in the real world, what evidence do you have except some shady video? Covid went down in a similar fashion in other states in India too at the same time.
This week, the FDA added their voice to social media memes making fun of Ivermectin.
This week, there was a short video briefing for Malaysian doctors about the Indian success story in the state of Uttar Pradesh (UP), population ~200M. In India, each state can set their own health policy. Even though the central government was against Ivermectin, UP continued to use it. On June 29, the UP government released an official kit for children, containing: Paracetamol, multivitamins and Ivermectin. The briefing claims that Doxycycline, Ivermectin and Zinc were instrumental in treatment, prevention and reducing transmission of Covid.
This video was removed from YT within 24 hrs, interpret that as you will, but this is a field report from a medical professional describing a successful, real-world health outcome in a region with more humans than many countries, https://www.bitchute.com/video/ysnsHWrcqimp/
Thanks for commenting. Since it's such a short video, would you mind quoting one sentence from the video which is incorrect, e.g. did the doctor from India describe a particular event which did not take place?
In the USA, the New York Supreme Court ruled that an elderly patient was allowed to take Ivermectin, against the wishes of the hospital where she was being treated. After winning her court case, Ivermectin was administered and she made a rapid recovery, https://www.mountainhomemag.com/2021/05/01/356270/the-drug-t....
Let's assume that her case is an outlier, can we agree that it is a remarkably positive, happy, outlier? Are such cases worthy of scientific study, to understand the therapeutic mechanisms involved, if only to inform the design of new therapeutics? Merck, holder of the Ivermectin patent that expired in 1996, is now developing a new, patented drug for early treatment of Covid.
The plural anecdote is not data. At the end of the day it comes down to statistics and reproducibility. A lot of things can happen for a lot a reasons. It’s why things like homeopathy still exist.
The site posted at the top of this thread has 800 scientific studies of various therapeutics, https://c19early.com/faq.html
> Whether it be treatments or interventions, the plethora of seemingly similar quality research supporting contradictory positions, and the use of digital echo chambers, facilitates widespread confirmation bias - evidence supporting any initial position can be easily found. Self-serving bias and cognitive dissonance further make it challenging to alter positions, especially for those taking very public and strong positions with serious implications.
We felt that attempts to organize and make the research and data easier to navigate, highlighting areas of applicability, and analyzing limitations, could potentially be beneficial.
> What is the search strategy for papers? All significant original contributions related to the use of the treatments we cover, including searches of the typical sources augmented by contributions from the community. Covering all research is important because it is easy to choose a search strategy that results in a subset of papers reporting a desired conclusion. This is especially so if one takes the conclusions reported in papers at face value without examining the actual data, methods, or regions of applicability
- It is impossible to contact the owners of the website
- The website has gotten direct critique of spreading misinformation in two papers
- They draw their own conclusions from the paper.
- A lot of the papers in its
meta-analysis doesn’t have control
groups or randomized trials. Some
studies only compare ivermectin+X vs
ivermectin+Y
- The total sample size of all
studies are only 2000 people.
But let's ignore all these red flags and focus on this. They claim that each of the following individual medicines works, Fluvoxamine, Proxalutamide, Iota-carrageenan, Molnupiravir, Quercetin, Povidone-Iodine, Curcumin, Casirivimab, Sotrovimab, Bamlanivimab, Nitazoxanide, Budesonide, Zinc, Bromhexine, Colchicine, Vitamin D, Aspirin, Favipiravir, Hydroxychloroquine, Remdesivir, and Vitamin C. I find it unlikely that ALL those claims are true which in turn makes me question their scientific approach.
Not accounting for this fact is a significant confounding factor in the study, and I'm disappointed the authors made no distinction between unvaccinated and immunologically naive. This is a distinction that every sensible scientific discussion needs to acknowledge.
EDIT: please leave a comment down voters, I’m starting to think there’s some sort of targeted campaign against this type of information
> Vaccine breakthrough infections exhibited similar proliferation dynamics as infections in unvaccinated individuals (mean peak Ct: 20.5, 95% credible interval [19.0, 21.0] vs. 20.7 [19.8, 20.2], and mean proliferation time 3.2 days[2.5, 4.0] vs. 3.5 days [3.0, 4.0]); however, vaccinated individuals exhibited faster clearance (mean clearance time: 5.5 days [4.6, 6.6] vs. 7.5 days [6.8, 8.2]).
> If the Ct values in vaccinated and unvaccinated infected individuals reflect the same amounts of infectious virus, then this implies that individuals with breakthrough infections may be as infectious as unvaccinated individuals in the early stage of the infection, but remain infectious for a shorter time, reducing the total degree of onward transmission. These findings are in keeping with the hypothesis that vaccination protects against the severe manifestations of disease but offers less protection against infection in the upper airway. Precautions are therefore necessary to prevent onward transmission even from vaccinated individuals.
[1] Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells https://www.cell.com/cell-reports-medicine/fulltext/S2666-37...
[2] SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN) https://pubmed.ncbi.nlm.nih.gov/33844963/
[3] Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection https://jamanetwork.com/journals/jamainternalmedicine/fullar...
[4] Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection https://www.nature.com/articles/s41586-021-03696-9
[5] Initial report of decreased SARS-CoV-2 viral load after inoculation with the BNT162b2 vaccine https://www.nature.com/articles/s41591-021-01316-7