Why did they have more older patients and more male patients in the ivermectin + doxycycline group? To perform a good clinical trial, you would want age and gender matched active drug and placebo groups.
Edited by Hip, 11 October 2020 - 10:06 PM.
Posted 11 October 2020 - 10:06 PM
Why did they have more older patients and more male patients in the ivermectin + doxycycline group? To perform a good clinical trial, you would want age and gender matched active drug and placebo groups.
Edited by Hip, 11 October 2020 - 10:06 PM.
Posted 11 October 2020 - 11:39 PM
Why did they have more older patients and more male patients in the ivermectin + doxycycline group? To perform a good clinical trial, you would want age and gender matched active drug and placebo groups.
My first impression was that they may have been stacking the deck against ivermectin, but it worked anyway. However, looking at the study at clinicaltrials.gov, I do not see the alleged age difference, but maybe I am not reading carefully. The % males were 61.5 vs 56--close but not exact. The design is described as "randomized". So it seems like an ok study.
Posted 12 October 2020 - 07:04 PM
Yes, I want to believe they meant to say zinc instead, but who knows. I think they are spot on with B12, C, and D... but I would mention selenium and omegas as well.
Its just so bizarre you cant get govt entities to recommend a multivitamin and cut back on sugar/pasta/bread.
Still no PSAs from government agencies about the life-saving, RCT proven, effects of vitamin D3 and other essential nutrients. All we get is what I call the "run, be scared, hide" motto.
The government says "wear masks", which are proving to be the worst public policy. The vast majority of countries and states where mask mandates went into effect, have seen the virus continue to spread at ever higher rates. Numerous past RCT studies about mask-wearing demonstrated that masks were ineffective, but that "wear-masks" is all we get from government bureaucracies. Where is the support for things that work - all of the things we have kept track of in this thread. It is as if the government bureaucracies WANT people to suffer worse outcomes. What other conclusion is there? Incompetence, I suppose.
Posted 12 October 2020 - 07:07 PM
https://clinicaltria...lts/NCT04523831Found the following information, of a recent study, posted on another website: Clinical Trial of Ivermectin Plus Doxycycline for the Treatment of Covid-19 Infection: Results from Double-Blind Placebo Controlled Study
Summary:
183 patients in ivermectin+doxycycline (plus standard of care) arm: Ivermectin 6mg x 2 tablets = 12mg (given once i.e. total 12mg dose) Doxycycline 100mg x 2 tablets/day (given for 5 days)
180 patients in placebo arm (standard of care)
Ivermectin+Doxycycline arm had:
older demographic (usually do worse)
more males (usually do worse)
Number of Patients With Early Clinical Improvement (at 7 days):
60.7% patients in ivermectin+doxycycline arm
44.4% patients in placebo arm
p value < 0.03
(i.e. placebo did worse)
Mortality:
0 deaths in ivermectin+doxycycline arm
3 deaths in placebo arm
Conclusions:
Ivermectin + Doxycycline had better outcomes
Ivermectin dose was only 6mg x 2 tablets = 12mg (given once) - which is at the lower end of dosage for covid-19 (although it is typical for de-worming). Other studies have typically used 2x or 3x this dosage or higher. Also it is not clear if Ivermectin was taken with a fatty meal (which ivermectin spec sheet gives 2.5x bioavailability when taken with fatty meal).
Results are better than what we have seen for Remdesivir etc. - yet are getting scant attention (also lower interest in clinical trials by pharma since being generic drugs there is little financial incentive). Most of the work on Ivermectin is thus coming from outside the U.S./Europe (Bangladesh, Peru, Egypt).
This is not the first positive evidence of Ivermectin + Doxycyline (not to mention HCQ+Zpac+Zinc), yet not a peep from government bureaucracies or national media outlets. If I shared this positive news on social media, it would probably get censored and I might get fired from my job. What the heck is going on?!?!
Posted 12 October 2020 - 07:32 PM
I am unsure if this has been posted here yet, created by people at the economic standard, I white paper about HCQ: https://secureserver...QWhitePaper.pdf
Posted 12 October 2020 - 07:45 PM
This is not the first positive evidence of Ivermectin + Doxycyline (not to mention HCQ+Zpac+Zinc), yet not a peep from government bureaucracies or national media outlets. If I shared this positive news on social media, it would probably get censored and I might get fired from my job. What the heck is going on?!?!
Government bureaucrat doctors all have their vaccine blinders on. They don't treat pandemics, they study them! Any outpatient therapeutic that reduced morbidity/mortality lower than it already is would jeopardize their Emergency Use Authorization for the new vaccines, where anticipated compliance is already sliding.
Hate myself for thinking this, but I almost hope their vaccine unicorn turns on them. It will be interesting to see if serious adverse events or lack of effectiveness (particularly in the elderly) will be censored from public view.
The suppression of outpatient therapeutics has crushed my faith in modern medical science. I wonder if that old courtroom in Nuremberg is still standing. Trials are needed for crimes against humanity.
Posted 12 October 2020 - 08:25 PM
The suppression of outpatient therapeutics has crushed my faith in modern medical science. I wonder if that old courtroom in Nuremberg is still standing. Trials are needed for crimes against humanity.
Posted 12 October 2020 - 08:40 PM
I am unsure if this has been posted here yet, created by people at the economic standard, I white paper about HCQ: https://secureserver...QWhitePaper.pdf
Fantastic paper, & I learned something new from it. I've come to understand the greatest benefit from HCQ most likely is immune modulation to prevent cytokine storm. Dr Been pointed out on one of his lectures HCQ was the only immune suppressant that has not been significantly associated with predisposing or potentiating opportunistic infections, which has been problematic with steroids and other immune modulators. I've been taking low-dose quinine, in a (perhaps) forlorn hope of damping viral replication, but worried any immune modulation might delay an initial response to infection.
Was pleasantly surprised to find this on page 17: "HCQ has multiple proposed mechanisms of action which can interact with this disease process, many of which have been confirmed in cell culture and in human studies. It can strengthen the early innate immune response to the virus in the nose and mouth through boosting of the immune response of a particular master immune cell, called a dendritic cell, to viral proteins (antigens). This allows stimulation of specific T cells called cytolytic CD8 cells against the virus in the nose and mouth, and can help to limit the viral infection to these areas."
-----------------------
Oh Wow! So not only does it not dampen early immune response, but may help with early activation? My Gin & Tonic will taste better than ever tonight!
Thanks for posting this paper, & hope it "goes viral". Truth will out in the end. A shame it sometimes takes time.
Posted 13 October 2020 - 02:03 AM
Oh Wow! So not only does it not dampen early immune response, but may help with early activation? My Gin & Tonic will taste better than ever tonight!
Thanks for posting this paper, & hope it "goes viral". Truth will out in the end. A shame it sometimes takes time.
Probably tastes better than this honeysuckle concoction, this is the best I could find. Heres another alternative for those interested. However not sure either one contains the MIR2911 anti-viral component.
Bottoms up...
Posted 13 October 2020 - 03:55 AM
Johnson & Johnson suspends trial of potential coronavirus vaccine after participant becomes ill
https://www.statnews...in-participant/
Edited by lancebr, 13 October 2020 - 03:56 AM.
Posted 13 October 2020 - 05:47 PM
Johnson & Johnson suspends trial of potential coronavirus vaccine after participant becomes ill
This seems to be fairly common in vaccine trials as a precaution, from what I have (casually) heard and read. It would be nice if a safe and effective vaccine can be developed, but I am not too hopeful, considering the failure of vaccines for other respiratory diseases, including other coronaviruses (detailed here: https://www.longecit...no-guarantees/)
Posted 14 October 2020 - 01:28 AM
The government says "wear masks", which are proving to be the worst public policy. The vast majority of countries and states where mask mandates went into effect, have seen the virus continue to spread at ever higher rates. Numerous past RCT studies about mask-wearing demonstrated that masks were ineffective, but that "wear-masks" is all we get from government bureaucracies.
I'd like to see the evidence for these claims. As far as I know, there are no "numerous past RCT studies about mask-wearing," and most of the studies I've seen claim that mask wearing helps reduce the spread of the virus in most cases.
Posted 14 October 2020 - 05:55 PM
A few pages back, Dorian Grey asked about famotidine dosage.
https://www.drugs.co...amotidine.html
OTC reflux dosage, 20 mg twice a day.
More extreme conditions:
-Initial dose: 20 mg orally every 6 hours
https://gut.bmj.com/...jnl-2020-321852
Results Ten consecutive patients with COVID-19 who self-administered high-dose oral famotidine were identified. The most frequently used famotidine regimen was 80 mg three times daily (n=6) for a median of 11 days (range: 5–21 days). Famotidine was well tolerated. All patients reported marked improvements of disease related symptoms after starting famotidine. The combined symptom score improved significantly within 24 hours of starting famotidine and peripheral oxygen saturation (n=2) and device recorded activity (n=1) increased.
Conclusions The results of this case series suggest that high-dose oral famotidine is well tolerated and associated with improved patient-reported outcomes in non-hospitalised patients with COVID-19.
That high a dose requires medical supervision?
LIke any antihistamine, famotidine can irritate the prostate.
Posted 14 October 2020 - 06:10 PM
Hydrogen Peroxide was briefly mentioned on page 41 and it is something my dentist had me rinse with before replacing my amalgam fillings(mercury) about 2 months ago.
Somehow I missed the boat on this back in April, Medical Dail and Mercola both did an article about nebulizing it(cpap can be used as a nebulizer, my wife uses one). Seems like it would be really effective early treatment?
"Your immune cells actually produce hydrogen peroxide. This is in part how your immune system kills cells that have been infected with a virus. By killing the infected cell, viral reproduction is stopped. So, hydrogen peroxide therapy is in essence only aiding your immune cells to perform their natural function more effectively."
Both quote Thomas Levy who put out this article in August
"For early onset and treatment of coronavirus:
Regular off-the shelf 3% HP can be utilized. Preparations of greater pharmacological purity can be obtained if desired (food grade). Food grade HP typically comes in concentrations greater than 3% and must be appropriately diluted. HP in a concentration greater than 3% should never be nebulized.
For most adults, the 3% concentration can be utilized in the nebulization chamber undiluted. This optimizes the degree and rapidity of the antiviral and anti-pathogen effect. However, don't be reluctant to dilute the 3% solution if not easily tolerated. Note that the first few partial inhalations might not be well-tolerated, but these initial inhalations effectively "coat" the mucous membranes with the HP mist, and subsequent inhalations are not only well-tolerated but relaxing. However, never continue inhaling any agent that makes breathing more difficult."
So much isolated information on various things like honeysuckle, hesperiden, quercetin, NAC, and glutathione..
Edited by Gal220, 14 October 2020 - 06:12 PM.
Posted 14 October 2020 - 09:35 PM
Thomas levy rundown on what he believes prevents/helps/cures covid HERE
"General Recommendations
While many supplement regimens can be used for COVID-19 prevention, such regimens should include at a minimum vitamin C, vitamin D, magnesium chloride, and zinc. Any of many additional quality nutrient and antioxidant supplements can be added as desired, largely dependent on expense and personal preference.
Nebulizations of powerful antipathogen agents, especially hydrogen peroxide, can readily prevent respiratory viral infections like COVID-19 from taking hold, and initiating such nebulizations even after an infection has been contracted will still make a substantial contribution to a more rapid and complete recovery."
Posted 15 October 2020 - 02:05 AM
Two negatives on the hydrogen peroxide treatment - Youtube video(IV treatment) and Truth or Fiction article that targets Mercola.
Neither one are very helpful as none of the people talking are familiar with the treatment and give more off the cuff answers. Mercola is an easy punching bag, they didnt go after the originators.
Frank Shallenberger and Thomas Levy are the ones with the protocol, there are some active users of the protocol on this webpage.
It seems certain hydrogen peroxide kills the virus, does the nebulized version? Hard to believe it doesnt. Again, amazing we dont have more information on this, just like quercetin.
Posted 15 October 2020 - 04:56 AM
Why magnesium CHLORIDE in particular?
Posted 15 October 2020 - 05:21 AM
Why magnesium CHLORIDE in particular?
I noticed this too. Never seen this form of mag in a supplement. From Gal220's link:
https://orthomolecul...dff8a46af6f.167
"Magnesium, especially as magnesium chloride, has been documented to have substantial antipathogen properties, and it has been reported to cure poliovirus infections as a monotherapy when ingested orally. [11] While it remains unclear what an aggressive regimen of this agent would do as a monotherapy for COVID-19, it can be expected to be a positive adjunctive agent in any COVID-19 prevention or treatment protocol."
I've tried a lot of different mag supps, but the only one that doesn't give me exploding BM's is Doctors Best high absorption magnesium 100% chelated (magnesium lysinate glycinate chelate).
Would like to learn more about this mag chloride.
Posted 15 October 2020 - 01:38 PM
Would like to learn more about this mag chloride.
I think it is mainly due to the polio cure that he feels it is the best form. Other articles like the one below really stresses the importance of Mag. He seems to really hate calcium..
Levy has some interesting thoughts in general in this interview
"It became apparent to me and I’ve not found an exception to this yet, which is every cell that is “diseased” has increased calcium levels inside the cell… It’s the highest levels of calcium that also result in cancer."
"I consider Vitamin C, magnesium, Vitamin D, and Vitamin K2 to be the premier, top four supplements for promoting and maintaining good health. Mainly because they’re the primary antagonists to calcium accumulation and excess calcium inside the cell"
On Vitamin C and hydrocortisone
"In this one particular study we also looked at the effects of hydrocortisone, in particularly with the liposome C and we were looking at Vitamin C concentration inside lipocytes, the intracellular levels. And we found that the presence of the hydrocortisone massively increased the amount of Vitamin C that goes inside the cell. And this is very interesting because when you think about the fact that probably, I would think, among all prescription medicines, although it’s a natural agent as well, hydrocortisone is considered your number one antiinflammatory agent. And it’s my opinion, not fact, but opinion that the primary reason hydrocortisone is your primary antiinflammatory agent is because it exerts such a profound effect on putting Vitamin C inside the cells"
I wonder how many hospitals doing IV C for coronavirus are also using hydrocortisone, probably close to 0. Hopefully my cynsim is getting the better of me here.
Edited by Gal220, 15 October 2020 - 01:39 PM.
Posted 15 October 2020 - 09:27 PM
How anti-ageing drugs could boost COVID vaccines in older people
https://www.nature.c...586-020-02856-7
Discussion of metformin, rapamycin, and fisetin
Posted 16 October 2020 - 08:27 AM
Preventative measures look to me even more important ...
Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results
....
CONCLUSIONS These Remdesivir, Hydroxychloroquine, Lopinavir and Interferon regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay. The mortality findings contain most of the randomized evidence on Remdesivir and Interferon, and are consistent with meta-analyses of mortality in all major trials.
https://www.medrxiv....0.15.20209817v1
Posted 16 October 2020 - 04:42 PM
A subreddit reporting IVERMECTIN studies has been running for a few weeks. There are a few dozen posts.
https://www.reddit.c.../r/ivermectin/
Posted 16 October 2020 - 04:49 PM
TELMISARTAN
In the early days of this thread there was a debate about whether to discontinue ARBs or ACE inhibitors (taken to control blood pressure). I almost switched from telmisartan, but the eventually the debate here tilted me towards continuation.
Abstract
Background. Covid-19 is associated with respiratory-related morbidity and mortality. Angiotensin receptor blockers (ARB) have been postulated as tentative pharmacological agents to treat Covid-19-induced inflammation. Methods. This is a randomized, two-arm, open, multicenter trial. Participants were 18 years or older and had been hospitalized with confirmed Covid-19 with 4 or fewer days since symptom onset. Exclusion criteria included intensive care unit admission prior to randomization and ARB or angiotensin converting enzyme inhibitors use. Treatment arm received telmisartan 80 mg bid during 14 days plus standard care; control arm received standard care. Primary outcome were differences in C-reactive protein levels at days 5 and 8. Secondary outcomes included time to discharge evaluated at 15 days and death at 30 days post randomization. Results. This interim analysis included 40 patients in telmisartan and 38 in control groups. CRP levels in the control and telmisartan groups were 51.1+/-44.8 mg/L vs 24.2+/-31.4 mg/L at day 5 (mean +/- SD; n=28 and n=32, p<0.05), and 41.6+/-47.6 mg/L vs 9.0+/-10.0 mg/L at day 8 (mean +/- SD; n=16 and n=13; p<0.05), respectively. Telmisartan treated patients had statistically significant lower time to discharge (log-rank test p=0.0124, median time: 15 days in control group vs 9 days in telmisartan group). Mortality at day 30 was 11.76% in control group vs 5.26% in telmisartan group (p=0.41). Conclusions. In this study, ARB telmisartan, a well-known inexpensive safe antihypertensive drug, administered in high doses, was superior to standard care demonstrating anti-inflammatory effects and improved morbidity in hospitalized patients infected with SARS -CoV-2 (NCT04355936).
Posted 16 October 2020 - 05:27 PM
DIY HOME TREATMENT
Why home treatment of COVID-19 with several drugs is crucial
We are more than nine months into the consequences of the COVID-19 pandemic in the United States and as the months wear on, it is becoming apparent that there is no single drug that can be considered a “silver bullet” for SARS-CoV2. In almost all other viral infections — including HIV, hepatitis C and zoster, or shingles — multiple drugs are needed to treat the infection and its complications. COVID-19 in many ways is more complex than these other infections, since the virus does direct organ damage, triggers an immune cytokine storm, and stimulates excessive internal blood clotting.
Worldwide, doctors have learned that a rational approach to treating COVID-19 is using in combination appropriate non-labelled, off-target antivirals (zinc, favipiravir, hydroxychloroquine, azithromycin, doxycycline, ivermectin), steroids (oral dexamethasone, prednisone, inhaled budesonide) and antithrombotics (low-molecular weight heparin, oral anticoagulants). My colleagues and I, a consortium of U.S. and Italian physicians, offered American physicians and patients important guidance and support in the Aug. 7, 2020, issue of the American Journal of Medicine — a treatment algorithm, according to age and underlying medical problems, based upon the pathophysiological principles of what has been learned from 58,000 scientific publications on SARS-CoV2 infection cited in the National Library of Medicine.If a healthy individual under age 50 contracts COVID-19, no medical treatment is advised. However, for someone 50 years and older or anyone with one or more underlying medical conditions, treatment should be started at the onset of symptoms before the results of testing are known. This is important, since the treatment of any infection is always most effective when started as early as possible in the course of illness. Because each medication by itself has a modest effect, two or more drugs must be used early to slow down viral replication....Currently, the average American with COVID-19 shelters in illness and fear without home treatment for about two weeks. Some may then need hospitalization. Once in the hospital, the treatments discussed above are variously deployed — but far too late in the course of illness. Intravenous remdesivir and convalescent plasma are used in a minority of hospitalized patients and are probably far less effective than they could be because the patients have been ill for so long. Thus, there is strong rationale for early treatment of COVID-19 at home with available drugs used in a sequenced combination, with the intent of shortening the course of illness and reducing the risks of hospitalization and death.It is certainly not too late for the U.S. to catch up to other countries regarding home treatment. We rank among the 10 worst countries for COVID-19 mortality per million population, despite having first-class hospitals. The common theme of these countries is the lack of government agency and medical community support for home treatment for COVID-19.The report of AstraZeneca halting its large vaccine trial because of a safety event has given the academic medical community concern over the timing and certainty of our rescue by COVID-19 vaccination. The return to school and the tepid reopening of restaurants and businesses means a likely third wave of COVID-19 cases, building upon a large base. In my view, this strengthens the call for physicians to develop the confidence — and patients, the expectations — for prompt home treatment of available medications for COVID-19 based upon currently available medical science.There are no signs that single drugs in randomized trials are going to be proven efficacious alone, and large randomized trials of combination drugs at home are years away. The medical community must act now to provide combination therapy to COVID-19 patients to reduce Americans’ suffering, and unnecessary hospitalizations and deaths.
Because of data snobbery, my academic health system will only use FDA-approved treatments or novel substances in official trials. That's why I've been on this thread, to study, learn, and prepare a defensive armamentarium of prevention and treatment of early stages of disease.
There's lots of good information in that ivermectin subreddit I mentioned; including treatment regimens from low-income countries. Here is an informative chart for the entire course of the disease, the Aguirre protocol from Peru
Posted 16 October 2020 - 07:47 PM
Preventative measures look to me even more important ...
Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results
....
CONCLUSIONS These Remdesivir, Hydroxychloroquine, Lopinavir and Interferon regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay. The mortality findings contain most of the randomized evidence on Remdesivir and Interferon, and are consistent with meta-analyses of mortality in all major trials.
Hmmm. Another study that looked at already hospitalized (and many ventilated) patients. Seems like another study that was designed to fail. If you consult with the doctors who claim to have success, they say treatment needs to occur early in the disease, not when the patients are already on their death bed. And of course, this is another study looking at the drug use in isolation, notably without zinc and/or antibiotics.
Posted 16 October 2020 - 07:49 PM
I'd like to see the evidence for these claims. As far as I know, there are no "numerous past RCT studies about mask-wearing," and most of the studies I've seen claim that mask wearing helps reduce the spread of the virus in most cases.
I apologize for taking this thread off-topic. There is a separate mask discussion here: https://www.longecit...woefully-wrong/
Posted 17 October 2020 - 03:34 AM
Pneumonia vaccines (the pneumococcal and Hib vaccines) and perhaps the MMR vaccine may reduce deaths from COVID-19 but other vaccines such as the tuberculosis (BCG) vaccine that was mentioned earlier in this thread are not effective.
https://medicalxpres...a-vaccines.html
Posted 18 October 2020 - 01:46 AM
The Zagazig University results reveal that out of 203 subjects in the ivermectin arm 15 contacts (7.4%) developed COVID-19 as compared to 59 (58.4%) in the non-intervention arm.
Pre-exposure Prophylaxis (PrEP) consists of people at high risk of contracting COVID-19 taking medications periodically to prevent the virus from establishing in the mucosa and spreading through the body. When taken weekly or every 2 weeks, we are observing that it has a high effectiveness in preventing contracting COVID-19. PrEP becomes less effective when it is taken every 30 to 45 days. In people who have been using PrEP, we are seeing that Ivermectin reduces the risk of contracting the virus by approximately 99% when taken weekly, and by 94% if taken every 2 weeks (every 14 days). In people who are not exposed to places with High Viral Load, it could be justified to give doses every 14 days, since in them PrEP would reduce the risk of contracting the virus by 97% if taken every 14 days, and it is reduced by approximately one 89% when taken monthly.
… of the participants in the control group (e.g. not taking the study drug combination) 58% of the participants were infected with COVID-19 during the duration of the trial. The study team reported no contagions were recorded in the carrageenan and ivermectin arm, showcasing the compounds’ virucidal effects can potentially protect against COVID-19.
• If you have contacted covid+ people:Day 1 & Day 7• All health care workers:Day 1 and Day 7, then dosing every Day 1 in subsequent monthsTreatment:• One dose each of 3 consecutive daysAll doses at 200mcg/kg, to be taken 2 hours after dinner.
Edited by bladedmind, 18 October 2020 - 01:57 AM.
Posted 18 October 2020 - 03:56 AM
US NIH Covid-19 Management Protocols
https://www.covid19t...elines.nih.gov/
No!
Maybe
Don’t bother
Compare US NIH to management protocols elsewhere in the world.
Dr. Aguirre, Peru
Picture1.png 881.89KB 0 downloads
MATH+ https://www.evms.edu...19_Protocol.pdf
Picture2.png 207.29KB 0 downloads
Followed by 50 specific recommendations over 5 stages of the disease.
Prestigious advocates of early out patient treatment
https://www.ncbi.nlm...les/PMC7410805/
Picture3.png 514.67KB 0 downloads
Edited by bladedmind, 18 October 2020 - 04:04 AM.
Posted 18 October 2020 - 04:51 AM
Recently I posted on doxycycline as prophylactic: a course in the prior year is “associated with a 75% reduced likelihood for mechanical ventilation during hospital stay.” https://www.medrxiv....7.22.20154542v1.
So in that study about doxycycline being used as a prophylaxis for ARDS....it states the following:
"Of the three tetracycline antibiotics studied, there was no significant effect in timing of administration
compared to diagnosis of ARDS, except for doxycycline"
and
"The use of minocycline, doxycycline, or tetracycline for up to a year prior to diagnosis was compared to
use of the antibiotic during ARDS diagnosis, which demonstrated a treatment difference only in patients
that had taken doxycycline."
So how is doxy different from the other antibiotics concerning timing?
https://www.medrxiv....4542v1.full.pdf
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