Covid drug drives viral mutations – and now some want to halt its use
nature.com
nature.com
Never have had that type of experience with any drug.
Infuriating that, in the midst of the opioid crisis, the government wouldn't even consider permitting safe and effective treatment.
This paper [2] is a review of deaths associated with ibogaine known to the authors. They contacted different clinics around the world known to use ibogaine. They found 19 deaths over an 18 year period. 14 of these deaths had post-mortem data and 12 of the 14 had clear comorbidities that likely substantially contributed (e.g. also using heroin and meth, or having severe heart problems already).
You can find a number of papers[3], here is one for example, where no side effects are reported for ibogaine - "In two Phase 1 studies using very low doses, single 20 mg doses of ibogaine were well tolerated (N = 21), with no effect on vital signs and no adverse effects". And, here is the conclusion of that paper, just for fun - "A single ibogaine treatment reduced opioid withdrawal symptoms and achieved opioid cessation or sustained reduced use in dependent individuals as measured over 12 months".
Even if those were valid side effects, you'd still have to put them in context - being an opiod addict is likely much riskier than taking a one time dose of ibogaine in a clinical setting with a doctor's supervision. Net - ibogaine treatment is negative side effect.
1 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837967/
2 - https://pubmed.ncbi.nlm.nih.gov/22268458/
3 - https://www.tandfonline.com/doi/full/10.1080/00952990.2017.1...
If you’re a high risk patient like an addict, when you end up in the ER for whatever, they’re just going to cut off whatever medication you’re on, keep you from dying, and kick you out as soon as they aren’t liable.
Still a big improvement, but it makes me wonder whether a longer course of Paxlovid might have cleared the symptoms more completely. I have read that there have been suggestions that the five day course still leaves a significant amount of virus in the body and that lengthening it has been considered, but the FDA has not done anything about it.
The immune system often reacts to viral fragments leftover from replication or destruction. Some viruses are (hypothesized to be?) adapted to this, e.g. delaying sneezing and coughing (or at least the deliberate exacerbation of it) until viral load and viral shedding can be higher. Viral fragments can linger much longer than the primary infection, and in the case of COVID-19 are hypothesized to be responsible for or at least part of the process of some long-COVID symptoms.
Yes, agreed. But I have also read that studies of patients who took the 5-day course of Paxlovid showed that there were still significant numbers of "unassembled" viruses--i.e., the only reason they had not become full COVID viruses that could infect other cells was that Paxlovid was blocking the last stage of virus assembly--remaining at the end of the 5-day course, and once the Paxlovid stops, those unassembled viruses can now assemble themselves and cause further infection. This has been hypothesized to account not only for lingering symptoms but for recurrence of more severe symptoms in a significant number of patients.
That's wild, and apparently has only seen relatively recent confirmation as an evolved phenomenon according to this 2019 Quanta Magazine article: https://www.quantamagazine.org/viruses-can-scatter-their-gen...
What I was describing is a consequence of the way Paxlovid works: it doesn't "kill" the virus or get your immune system to kill it, it just stops the last step of virus assembly inside cells by inhibiting the enzyme, protease, that catalyzes that step. So while you are taking Paxlovid the virus can still go through all the stages of getting inside cells (the normal way, not the different way described in the Quanta article--each virus particle just infects one cell and does all of its replication there), replicating its RNA there, and expressing all of the proteins that form a complete virus particle along with the RNA; it just can't do the very last step, assembling all of those pieces into more complete virus particles, while the protease inhibitor from Paxlovid is present. But once you stop Paxlovid, the protease inhibitor goes away and all of those virus pieces can now assemble (each set of pieces inside a single cell) to become full virus particles that can infect more cells.
You may have recovered quickly regardless.
I never took paxlovid and my covid symptoms lasted 2 days and i recovered quickly.
N = 1 experiences arent convincing data.
https://www.empr.com/home/news/drugs-in-the-pipeline/mixed-r...
So, it's not a strong enough or consistent enough difference between treatment and placebo to be certain that it isn't just chance. (this could happen if for example if out of our 1000 data points, 2 people on placebo were hospitalised but only 1 on the treatment was hospitalised. That'd be "a 50% reduction in risk", but not be statistically significant since it could easily have just been random chance when we're talking about such a small difference).
Probably needs an even larger sample population to really nail down whether it's real or not. Seems suggestive that all the various reported tests showed (inconclusive) benefits when you'd expect an actually-ineffective treatment to show results varying randomly in both "effective" and "not-effective" directions, though that could certainly be positive reporting bias, especially since it's being run and reported by a company with a financial stake in the results.
But since we know the strains have changed over time it seems the most reasonable explanation as to why efficacy has dropped off.
Then the secondary analysis of another 1163 patients failed to show a difference AND the delta between the two arms was smaller than the first analysis.
Its trending towards no difference between arms.
And symptom relief has a huge subjective aspect to it since it based on a patient questionnaire.
If it shows no difference in hospitalization or death but some small effect on symptoms it has little value as a treatment. It going to end up like Tamiflu.
And i just checked clinicaltrials.gov, Pfizer terminated the trial.
This study just isn't powered well enough to say for sure whether Paxlovid provides a hospitalization/death benefit or not for the standard risk group. It also doesn't really provide any good information about whether newer variants cause Paxlovid to work better or worse.
Well, quite.
Of the four confirmed Covid cases we've had in our immediate family in the last 12 months, three of us took nothing stronger than standard painkillers and didn't even need to speak to a doctor; my OH spoke to our doctor and was given an inhaler to help with the cough.
The worst side effect was the blood pressure. My eyes almost popped out of their sockets!
And then I've heard from too many patients their doctor doesn't think they need it because they're not that sick, so it's not worth managing the drug interactions. Unfortunately, paxlovid needs to be started within five days of symptom onset, but most patients aren't going to be hospitalized within those first five days.
Given the lack of monoclonal antibodies, the potential mutagenic effect of molupiravir, and the less-than-steller impact of remdesivir... if I or someone I loved got covid, I'd be jumping on paxlovid since there aren't many other options right now.
According to the CDC, risk factors that make you at "high risk" include being over 50, having a mood disorder (including anxiety and depression), being obese or overweight, being physically inactive, being a current or former smoker, or having asthma: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/...
Most Americans would check one of those boxes, even the healthy and young among us. And some of those (e.g., "physically inactive") are pretty ill-defined that you could argue even more fit in that category. Just saying you're anxious about covid outcomes should qualify you for paxlovid because anxiety is a risk factor.
Many of the infectious disease doctors I work with think that paxlovid should be offered to virtually everybody because it seems to decrease your viral load (this could decrease the chance of onward transmission), there may be a decrease in risk of long covid, it may shorten your symptom duration, and there aren't many other treatment options if you get sicker. So, short of being on one of the medications that's absolutely contraindicated, their opinion is generally if you want paxlovid you should get it.
So if your doctor is saying you don't need it or don't qualify, and you want to take it, I would find a different doctor or use a telemedicine provider.
Managing drug interactions for paxlovid isn't much more complicated than inputting meds into a web form and looking at the color of the box that pops up after. I think most providers can handle that if they know these tools exist and get past the reflex of "paxlovid has drug interactions, you don't want to take it."
Managing drug interactions is part of ordering medications, and if it's really taking that much time (i.e., the EHR isn't just doing all the work for you), then it'd result in a higher E&M code when it's billed out. Medication management, in some cases, can also be billed and reimbursed by the pharmacist.
So, totally agree that the US medical system is optimized for billing. I don't think those of us in the US should be ok with that, and I don't think it's an excuse in this case to not prescribe paxlovid to patients who want it and would qualify for it.
By whom?
Medical professionals are overwhelmed, so you can't hospitalize these patients to monitor their compliance. And this is, in the large, not a demographic you can trust for maximal patient compliance.
One's ability to "trust" a patient isn't a factor here, and is, frankly, pretty condescending. The patient and provider have aligned interests, it's just a matter of ensuring the provider is making sure the patient understands what's going on. The provider should be doing that in all of their encounters, so that's nothing specific to paxlovid.
I suspect you haven't worked with elderly patients.
I help a relative manage his care. I keep having to hide the DayQuil so he doesn't take it alongside his arthritis medication and overdose on acetamenophin. He "knows" he's not supposed to, but it doesn't click when the pills are in his hand and his nose is running (because he took it for decades prior to the arthritis prescription and deeply-ingrained habits are not easily replaced). He definitely tells the doctor he understands, and the doctor believes him, but it's not like the doctor is in any way responsible for verifying that information.
Drug interactions are way past the maximum complexity capacity of the median patient at high risk for death by COVID.
> but it's not like the doctor is in any way responsible for verifying that information.
Yeah, that's the exact point. Everybody does things that the doctor says they shouldn't, but that doesn't mean we withhold care as a result.
People stop antibiotics before the scripts are done. People smoke and drink too much, some even drink and drive. People don't take their blood pressure or cholesterol or even HIV meds as prescribed. Some people take half a pill because the pill they were prescribed is "too big" -- people are weird and do all kinds of things.
Paxlovid is no different. The provider can be checking drug interactions, making adjustments as needed and counseling the patient. That's their job. They can't babysit the patient all of the time. If it's clear the patient doesn't understand and can't care for themselves, then there are larger conversations to be had.
My point is that deciding not to prescribe a medication to a qualifying patient because it generally has too many drug interactions and patients can't be trusted with their health is not ok. Patients don't need to understand that ritonavir is a protease inhibitor that was incidentally found to inhibit cytochrome P450-3A4, which subsequently boosts the levels of many other medications. They just need to know to stop taking their cholesterol pill for the next week. That's all. Some, like your elderly relative, may not be able to follow that direction. But there are millions of high risk people who are able to do that, and shouldn't be denied care based on the assumption they're incompetent.
If you're going to construct a new strawman argument, don't make up quotes that I never wrote. I also have a lot of thoughts about how controlled substance laws create problems and harm patients. But I'll stick to the main point of this thread: paxlovid drug interactions are easily checked and managed for the majority of patients, and should not be a reason for providers to reflexively deny prescription requests for it.
[0] https://www.npr.org/sections/health-shots/2016/09/28/4956945... [1] https://thehill.com/blogs/congress-blog/politics/452654-for-...
https://www.scientificamerican.com/article/what-is-paxlovid-...
As you note, there absolutely is the risk of incorporation of the viral nucleoside analogues into host genomic dna and ultimately cancer.
of the two rodent genotoxicity / mutagenesis assays, only ONE passed. The other was equivocal. The FDA concluded that based on the short 5 day course, the risk was acceptable. This decision was, IMO, colored by COVID hysteria that still permeates many aspects of medicine and government.
The types of risks (genotoxic, but also viral mutagenesis) of Molnupiravir would never be acceptable or approved in any other context.
Similar statistical model as control rods in a nuclear reactor - they don't stop neutrons, they significantly reduce the numbe of free neutrons flying about and avoid an exponential increase and runaway chain reaction.
> Seat belts reduce serious crash-related injuries and deaths by about half
Do you have some evidence that the vaccines are in that ballpark against infection/transmission in 2023?
And even if it was 99% effective, it certainly doesn’t justify leaving drugs in the market where one mutation potentially has humanity ending consequences.
The Covid vaccine was great for helping the elderley and vulnerable from day one. For the rest of us, it was a busted flush.
Similar thing happened in Manitoba where 80% of an elderly long term care facility got infected despite everyone being fully vaxxed.
Comparing a seat belt to a permanent medical procedure inside the body is asinine. Seat belts don’t go inside the body, can be taken off, don’t need a new belt on top of old one every few months, get recalled if defective, manufacturer can be sued, belts don’t cause blood clot or heart inflammation.
There is not a vaccine in the world that provides 100% protection to every individual. ALL vaccines work by reducing R0 to <1 so outbreaks shrink rather than growing.
I can’t believe we’re still doing the nutty antivax thing in 2023.
They are not in the same category at all
Vaccines are typically very effective. So effective they can eliminate a virus among vaccinated populations.
Covid-19 vaccines are sorta effective. They didn’t eliminate virus transmission among vaccinated populations. But they reduced the severity of cases.
Pretending the vaccines weren’t underwhelming in terms of efficacy doesn’t do us any favors, because people know from their own experience that most vaccinated people have had Covid.
As I stated above the COVID vaccines didn't eliminate transmission they reduced transmission rates.
I've just replied to another comment and provided two (of many) statistically significant studies (for professional epidemiologists) that confirm that (specifically for two vaccines in the UK). There are other studies across the globe that affirm the same conclusion.
The important truths about "people know from their own experience that most vaccinated people have had Covid." are that many vaccinated people had COVID .. a milder form with greatly reduced rates of hospitalisation, reduced rates of critical care, and reduced rates of death.
How does the flu vaccine work, except by providing some chance of protection to those taking it?
Just like covid vaccines, flu vaccines also protect unvaccinated people by making it less likely for them to be exposed to the virus in the first place.
The critical thing that antivax people miss is that they are both individuals and members of a population. Reducing the odds of infection for individuals has an exponential effect on reducing the odds for a population.
I meant this statement. No-one has ever suggested that the flu vaccines will stop the overall flu outbreak from growing.
Reducing the odds of infection also strongly depends on the extent to which that vaccine provides sterilising immunity.
Expressing safety concerns and having a rational discussion about a new genetic therapy is not a "nutty antivax thing", and it is disingenuous and argument in bad faith to suggest that it is.
The FDA defines "Gene therapy products. Human gene therapy/gene transfer is the administration of nucleic acids, viruses, or genetically engineered microorganisms that mediate their effect by transcription and/or translation of the transferred genetic material, and/or by integrating into the host genome."
mRNA (Pfizer and Moderna's vaccines) and adenovirus vector (Janssen vaccine) are the transfer of nucleic acids and viruses that mediate their effect by translation, and transcription then translation, respectively, of the transferred genetic material.
The FDA defines them as such: "Gene therapy products. Human gene therapy/gene transfer is the administration of nucleic acids, viruses, or genetically engineered microorganisms that mediate their effect by transcription and/or translation of the transferred genetic material, and/or by integrating into the host genome."
You may have misunderstood that I was drawing a distinction and suggesting that they are not "vaccines," which some people do. Similarly, but from the opposite point of view, you may also be suggesting that genetic therapies and vaccines are non-overlapping categories. I reject the false dichotomy.
For example (and there are many):
Data from studies in the United Kingdom showed that both the Pfizer and AstraZeneca COVID-19 vaccines were effective in preventing onward transmission of the virus to close contacts in case of breakthrough infections.
In one study among the general population in the United Kingdom, the effectiveness against transmission from breakthrough infections to household contacts from 21 days after the first dose was 47% (95% CI: 37–57) for the AstraZeneca COVID-19 vaccine and 49% (95% CI: 41–56) for the Pfizer COVID-19 vaccine. [1]
Another study from the United Kingdom reported that, among healthcare workers, who predominantly received the Pfizer COVID-19 vaccine, vaccination was associated with a 30% (95% CI: 22–37) reduction in transmission of SARS-CoV-2 to household contacts. [2]
[2] Shah ASV, Gribben C, Bishop J, et al. Effect of vaccination on transmission of COVID-19: an observational study in healthcare workers and their households (preprint). medRxiv 2021.
The first study you mentioned is:
https://khub.net/documents/135939561/390853656/Impact+of+vac...
This is a study of less than 2 months between "4 January 2021 to 28 February 2021". This is long long before delta and omicron and newer variants came. I specifically mentioned the changes which Delta brought.
Second study you cited is:
https://www.medrxiv.org/content/10.1101/2021.03.11.21253275v...
This is once again an outdated study from "8th December 2020 to 3rd March 2021" which is long before Delta, Omicron, and newer variants.
People repeatedly keep citing outdated studies from before Delta, Omicron and don't acknowledge the changes which those variants plus waning immunity brought. Also any study which doesn't measure asymptomatic infections is worthless.
Here's a better example. In a 94% vaccinated study, 56% reported being unaware of their infection:
https://jamanetwork.com/journals/jamanetworkopen/fullarticle...
What happens when infected people go around not knowing they are infected? They infect others and have a false sense of safety.
Seroprevalence data also shows 90% of population has already been infected. If the vax was preventing transmission, that wouldn't be happening.
" Since the vaccines didn’t stop transmission, can’t the same be said of them? "
with the broadly true statement that no vaccine that I'm aware of stops transmission .. they ideally reduce transmission* (being effectively not a vaccine if they fail to slow spread through a population (or mitigate effects of a virus that does spread)).
The studies I cite are just two (of many) first off the rank that demonstrate that the two of the more widely used vaccines did indeed slow transmission at the time they were used.
> Here's a better example. In a 94% vaccinated study, 56% reported being unaware of their infection:
I read that with interest the entire way through,
* it fails to support a claim that "vaccines did not reduce transmission of Delta or Omicron variants"
* it supports a claim that "vaccines reduced the effect of having a COVID variant (to the degree that most did not even realise they'd been infected)"
The specific statistical reason that your "better example" doesn't address the transmission rate (through vaccinated Vs unvaccinated populations) is that it exclusively looks at people infected and the bulk of those are vaccinated.
There's no larger view there of infection rates in a bigger population, and no differential look at infection rates in unavaccinated Vs vaccinated.
What the study confirms (re: transmission) is something I conceded in my first coment: vaccines do not stop transmission
(again, they ideally reduce transmission rates (not addressed in your 'better' study)).
If you're interested in a longwinded careful, multi factor analysis and model type paper (of which there are many) one such example is
https://www.frontiersin.org/articles/10.3389/fpubh.2022.8230...
which is detailed but lacks any clearcut gotcha messages .. it bears close reading and laments in places the lack of early vaccine uptake in the population (Australia) during the Delta and Omnicron waves (ie. supports vaccines reducing transmission rates, doesn't dwell on it as not enough people are vaccinated at that time and so looks at other mitigations).
> "While it is hoped this will be the case, the scientific community does not yet know if the Pfizer-BioNTech COVID-19 Vaccine will reduce such transmission."
[1] https://www.fda.gov/emergency-preparedness-and-response/coro...
> It's obvious looking at the data that vaccines reduce transmission.
Are you questioning my faith?
The Science Pope doesn't like to hear such heresy. Better watch out or else he'll sic the Science Inquisition on yo' aess!
I don't.
I know 2 people that caught covid after being vaccinated. I've never caught it. Most people I know never caught it. And it would be even worse without vaccines. Y'all are doing something wrong over there.
Anecdotal evidence can be dismissed with anecdotal evidence.
I tested myself randomly one time, no symptoms, and tested positive.
Asymptomatic infection is quite common with covid.
Individual experiences dont give any indication of population level outcomes - there is too much variability.
Some people see their cancers spontaneously go into remission but you wouldnt make a claim that cancers usually go into remission by themselves.
Your personal attack is again HN rules. And I'm not sure where you're coming from - I've been vaccinated.
This "vaccines can do no wrong" bandwagon is as damaging to science as the "vaccines are all bad" group.
They were very slow to confirm side effects (remember when people suffering with heart issues were ridiculed and ignored?).
Very slow to let everyone know that it wouldn't actually stop transmission (remember when we were told to get it to protect grandma? Or how about the messaging that 'breakthrough cases are very rare').
Very slow to reveal that effectiveness waned quite quicky.
These issues were quite obvious from the beginning. It's taken two years and only now can these be openly discussed without becoming a social pariah.
What the FDA said, simplified, is there is no evidence either way whether a breakthrough COVID case in a vaccinated person poses a greater risk of infection to other vaccinated people, BUT past vaccinations have shown that those other vaccinated people are still protected and therefore that should be the assumption here until refuted.
Original:
Q: If a person has received the Pfizer-BioNTech COVID-19 Vaccine, will the vaccine protect against transmission of SARS-CoV-2 from individuals who are infected despite vaccination?
A: Most vaccines that protect from viral illnesses also reduce transmission of the virus that causes the disease by those who are vaccinated. While it is hoped this will be the case, the scientific community does not yet know if the Pfizer-BioNTech COVID-19 Vaccine will reduce such transmission.
"These findings suggest that, although vaccinated and/or previously infected individuals remain highly infectious upon SARS-CoV-2 infection in this prison setting, their infectiousness is reduced compared to individuals without any history of vaccination or infection. This study underscores benefit of vaccination to reduce, but not eliminate, transmission."
Naumova EA, Dierkes T, Sprang J, Arnold WH. The oral mucosal surface and blood vessels. Head Face Med. 2013 Mar 12;9:8. doi: 10.1186/1746-160X-9-8. PMID: 23497446; PMCID: PMC3639856.
It also has antibodies (humoral immune response).
Immunoglobulin A (IgA) is the most abundant antibody isotype in the mucosal immune system.
Li Y, Jin L, Chen T. The Effects of Secretory IgA in the Mucosal Immune System. Biomed Res Int. 2020 Jan 3;2020:2032057. doi: 10.1155/2020/2032057. PMID: 31998782; PMCID: PMC6970489.
And the vaccine triggers the development of those antibodies.
We evaluated the serum anti-spike (anti-S) IgG, anti-nucleocapsid (anti-N) IgG and anti-S IgA response following vaccination against SARS-CoV-2 in a cohort of first-responders. Among the 378 completely vaccinated participants, 98% were positive for anti-S IgG and 96% were positive for anti-S IgA.
Montague, B.T., Wipperman, M.F., Chio, E. et al. Elevated serum IgA following vaccination against SARS-CoV-2 in a cohort of high-risk first responders. Sci Rep 12, 14932 (2022). https://doi.org/10.1038/s41598-022-19095-7
Essentially the current vaccines wouldn't give any mucosal protection worth mentioning in itself, but since there are (hopefully) relevant lymphocytes in circulation, the host has more in the way of specific countermeasures ready to infiltrate from the bloodstream and shut down the worst of the shedding, sooner than if the specific immunity had to be developed first.
So we'd have more or less unfettered susceptibility for getting infected (superficially) and pretty much just as high levels of infectious excretions, but for maybe half as long a time at the highest levels.
Would you happen to know if that picture still holds?
So yes, covid vaccines do that.
Yes, the CDC changed its definition of vaccine to be 'more transparent' https://www.king5.com/article/news/verify/coronavirus-verify...
> [T]he CDC changed its definition of vaccine from "a product that stimulates a person's immune system to produce immunity to a specific disease, protecting the person from that disease" to "a preparation that is used to stimulate the body's immune response against diseases."
The mechanism of a flu or covid shot is exactly the same as any other vaccine; the only difference is the degree of efficacy due to human mucosal immunity not having evolved to fully block infection from respiratory viruses.
https://journals.plos.org/plospathogens/article?id=10.1371/j...
> Sarah Otto, an evolutionary biologist at the University of British Columbia in Vancouver, Canada, says the paper is another blow to the continued use of molnupiravir. She notes that a large-scale UK study found that the drug had no effect on hospitalizations or deaths
The dr goes, "well, we have this drug that was proven to be slightly effective in double blind placebo controlled trials. It has no adverse side-effects. But a large scale study showed it might not actually be effective. Would you like to try that?"
The patient, who is probably on medicare or hit their deductible, is going to say yes give me that shit.
People have been saying this same thing about the over-prescription of antibiotics for ages but nothing has changed.
>There are 636 drugs known to interact with Paxlovid (nirmatrelvir/ritonavir), along with 5 disease interactions, and 2 alcohol/food interactions. Of the total drug interactions, 236 are major, 360 are moderate, and 40 are minor.
Of these interactions, several are with: statins, blood thinners, hormonal birth controls, and other heart medications. The exact high-risk population who is taking these drugs, have potential interactions with paxlovid. That wipes out a significant portion of the general population from eligibility.
Drug interaction databases aren’t complete nonsense, but you should take them with a huge grain of salt.
The vast majority of those interactions won’t prevent a physician from prescribing Paxlovid, and for most of the rest there are either alternatives or patients can lower dosages or stop taking them for the duration of treatment.
When you are asking a patient to stop taking a drug that they have habitually taken for potentially decades, and they have shown hesitancy or inability to comply in the past, maybe prescribing a drug with a potentially serious interaction isnt the best course of action.
We were talking about a hypothetical situation where someone is scared because they high risk.
The Doctor can A--tell that person to change their medication (they don't have to stop statins, not all statins can't be taken with Paxlovid) for 2 weeks and take Paxlovid.
Or B they can take Molnupiravir, which worst case doesn't do much, and best case is much less effective than Paxlovid. Also Molnupiravir has mutagenic effects (which granted probably aren't as much of a concern for someone 65+).
Molnupiravir was approved based on early data that showed it was much more effective than it has proven to be, and at a time when Paxlovid production hadn't ramped up yet. It very likely wouldn't be approved if it were being evaluated today.
Based on it's potential to produce more variants, and it's not widely studied mutagenic effects, keeping it around because some doctors might hesitate to prescribe Paxlovid to a subset of old people seems less than ideal.
Might I say the unsayable with not too scared to lose weight?
Perhaps doctors should be ignoring the pride of their patients and telling them, after 3 years, to take their health seriously instead of waiting for the grim reaper to knock on their door? Doctors are also able to prescribe weight loss drugs, surgeries, and generally tell people what they really need to hear so we might ask why the problem persists. Maybe it's because they don't listen to advice they don't want to hear. From [1]:
> The researchers found that disagreement between GPs and patients increased with patients' excess weight and was particularly pronounced for advice given by GPs on weight and lifestyle issues. Overweight patients were more likely to disagree with their GP regarding advice given on weight loss (odds ratio, 10.7), advice given on doing more physical activity (odds ratio, 1.9), and nutritional advice (odds ratio, 2.9) compared with patients with a "normal" body mass index.
I'm not suggesting doctors be rude, and, as that study points out, if doctors are taking such steps and obese patients ignore them and it harms the relationship then should we not be considering other things to push them?
Some people propose sugar taxes and the like but I think that still pushes responsibility away from the main cause of the problem, which is the person. Obese people should pay higher taxes and/or insurance fees that are then mitigated by efforts such as slimming classes, gym attendance etc.
Or, we can continue to allow a section of society to risk their own health and mortality while putting enormous strain and cost on the health service and thus risking everyone's health and mortality. Arguing about a drug that most of them wouldn't need if they weren't obese seems a bit like rearranging deck chairs on the Titanic to me, even if they do need rearranging.
[1] https://www.drugs.com/news/patient-doctor-disagreements-more...
Molnupiravir should never have been approved for sars-cov-2 caused covid-19 for out patient use. It was never given except in the context of supervised hospital care for other viral diseases. There's an argument that it could've been approved for this limiting situation but out-patient use was and is absurd.
Clinical data supporting this EUA are based on data from 1,433 randomized subjects in the Phase 3 MOVe-OUT trial (NCT04575597). MOVe-OUT is a randomized, placebo-controlled, double-blind clinical trial studying LAGEVRIO for the treatment of non-hospitalized patients with mild-to-moderate COVID-19 who are at risk for progressing to severe COVID-19 and/or hospitalization. Eligible subjects were 18 years of age and older and had one or more pre-defined risk factors for disease progression: over 60 years of age, diabetes, obesity (BMI ≥30), chronic kidney disease, serious heart conditions, chronic obstructive pulmonary disease, or active cancer.
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?set...
>On December 22, 2021, the FDA issued an EUA for emergency use of PAXLOVID for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg)...
And from your linked document,
>LAGEVRIO™ (molnupiravir) capsules, for oral use Original EUA Authorized Date: 12/23/2021
Paxlovid was approved 1 day before molnupiravir. Everything I said was true.
Molnupiravir was never given except in the context of supervised hospital care for other viral diseases. And your link does not disprove that. My knowledge about Molnupiravir is not direct, but only from the research I, and others on IRC did, back in 2021. It is much harder to research this now with all the sars-cov-2 studies improperly using the drug muddying the results. But I assure you, your search will be 99% in-patient usage for other viral diseases. This usage is weird. And it was available only after paxolovid was approved.
But it was never used as an out patient drug in prior studies or FDA approvals for other viral infections. I'm starting to think you aren't debating in good faith...
Paxlovid, which was approved first and is more effective.
https://www.covid19treatmentguidelines.nih.gov/therapies/mis...
Every research so far indicated some benefit in covid (if patients managed to adhere to treatment protocol). And yet no research was solid enough to merit any type of recommendation.
Oh yes! Where I am (UK), the public messaging during the later stages of Covid had everyone convinced that we needed to both vaccinate and keep up all sorts of existing restrictions, to stop Covid spreading and mutating. Everyone who doesn't take all the precautions and catches Covid is a potential source of the next variant that might kill grandma!!
As far as I understand, viruses tend to be only resistant in one direction: either antibiotics or phages, but they can't be resistant to both.
In the 2010s there were a lot of public talks at the DKFZ (German cancer research center) where research teams were looking for getting more attention and funds for that area, but I have no clue what happened to that.
Sars-cov-2 was kind of the prime example of a virus that you can't beat with antibiotics, so I was assuming that every pharma company would now direct their research at bacteriophage research...but there's not much information about it as far as I can tell.
Anyone have some interesting papers on that?
However, antibiotics do not work on viruses.
I believe you mean bacterial infections, which seem to either evolve protections against antibiotics or protections against bacteriophages, but not both.
There are viruses which affect other viruses with arguably more than a side effect ( https://en.wikipedia.org/wiki/Virophage ), but for natural reasons it seems a bit off from fully analogous to bacteriophages.
Coronaviruses are at the high end of size and complexity among RNA-viruses, but it's still hard for me to see that virophages would be relevant to combat SARS-CoV-2.
Your point about bacterial resistance to antibiotics vs phages is almost correct; increasing resistance against one attack broadly tends to decrease efficacy defending against the other, though as I am not familiar with the mechanisms for this, my uninformed hypothesis would be that the gene expression required comes at a high price - you can't defend against antibiotics and phage and outcompete your Petri-dishmates.
I suspect that for the future, medicine will be antibiotics in combination with phage cocktails of several phage strains that sabotage in different ways (targeting capsular polysaccharides vs surface proteins vs flagella, for example), to prevent a repeat of antibiotic resistance.
“Bloom thinks the researchers make a good case that molnupiravir treatment is yielding some highly mutated viruses with the capacity to spread. But it’s not clear whether this could contribute to new coronavirus variants, or whether it is simply creating weakling viruses that are unlikely to spread very far.”
If it’s the former then I imagine the case is pretty strong to discontinue usage and switch to Paxlovid.
Molnupiravir is already the last line treatment, it's been that way from the start. It should never be used in cases where the patient can take Paxlovid. Well it's above Convalescent Plasma, but that's because that's barely beneficial and I don't know if anyone is even using it now.
In order of preference:
1. Paxlovid 2. Remdesivir 3. Various IV Monoclonals 4. Molnupiravir 5. Plasma
https://twiv.s3.amazonaws.com/COVID+treatment+summary+020223...
I believe Remdesivir is also one of only treatments that has any effectiveness past the first week of infection as well.
You could argue it prevented transmissions, but given the vast majority of people everywhere have been infected, it's hard to argue the covid vaccines prevent infection, no? They only delay it.
The more vaccinated/up to date boosted the population then the less chance for overall spread and transmission, leading to less mutations.
Continued nonstop spread of the virus because the population refuses to take vaccines, refuses to take boosters, refuses to keep up effective NPIs like masking, etc... that can all lead to more mutations.
Let's not spread misinformation; this kind of rhetoric is precisely why I'm forever skeptical of this whole ordeal.
Any factor that causes a population bottleneck effect will inevitably cause "mutations" as you call it, more appropriately described as evolution or to cause survivors and their descendants to subsequently replace the prior population.
Factors that cause a population bottleneck effect include vaccination, among many other things; the most infamous example in medical contexts is perhaps antibiotics.
"Mutations", more appropriately evolution, is fundamental to life on Earth as we know it and is inevitable. New covid variants that are resistant to prior vaccines and immune responses are an evolutionary response to the population bottleneck effects imposed by vaccines and our immune systems.
Actual mutations will happen with or without vaccines; errors and accidents in the transcribing of DNA are inevitable. Most such transcribing errors are benign and inconsequential, but some lead to significant differences (eg: cancers, resistance to certain chemicals, etc.).
So no, vaccines DO NOT CAUSE mutations. Mutations are a natural consequence of replication. Vaccines CAN cause FEWER mutations, as they reduce how much the virus can replicate inside you before your immune system clears it, reducing how many chances at mutation the population of covid viruses have.
Actual mutations, as in DNA transcribing errors, will occur regardless of vaccines. It's an inevitable part of DNA replication. Such mutations can lead to evolution when faced with certain environmental factors such as a population bottleneck effect.
Vaccines, by way or increasing immune system response, can cause a population bottleneck effect and encourage evolution. We're seeing it with covid variants resistant to prior vaccines and immune responses.
Noticed the typo too late to edit it. :V
And actually, are the effects not basically the same? They both increase the likelihood of a new variant outcompeting existing variants, but in different ways - this drug increases the rate of mutations to new variants, whereas vaccination reduces the rate of mutations to existing variants. The effect in both cases is to favor new variants.
It's like how China banning Google and degrading service of US internet companies created an opportunity for domestic Chinese companies like Baidu to offer a lower-quality yet viable substitute to the firewalled service of its American counterpart, allowing them to grow their market-share to fund development toward feature parity with the original American apps.
Poverty, education, corruption, actual warzones, famines and natural disasters, even month long riots in developed countries - all these are happening now and happened every year since 2019. It's completely impossible for the world to stop the virus as a world.