⭐ Merited by vapourminer (2)
We see this kind of thing not infrequently in medicine, and even more so in critical care. Drugs or treatments which show promising results in vitro, show promising results in rodent models, maybe even show promising results in healthy volunteers, but when we apply them to critically ill patients, they either don't work or even make things worse.
Take colloids for example. They were going to be the next big thing and replace crystalloids for treating septic shock. They provided a bigger increase in blood pressure than crystalloids, and this increase lasted longer. They stayed in the intravascular space longer, they caused less peripheral and pulmonary edema and fewer third space losses. They allowed us to wean vasopressors more quickly. They made all our numbers and parameters better. And then the studies came out which showed that actually they were pro-inflammatory, they were bad for the kidneys, and they worsened mortality. So we are back with crystalloids except in very specific cases.
Take ventilation for example. When we first ventilated patients, we used large tidal volumes and high respiratory rates to help clear CO2. We did this to get their PaCO2 down to a physiological level, which helped to correct the acidosis associated with sepsis and bring their pH back to a normal level, which definitely improved things in the short term, stabilized the patient, reduced the requirement for inotropes and vasopressors, etc. And then the studies likes ARDSnet came out which showed we were causing volutrauma and barotrauma and allowing what we call "permissive hypercapnia" with lower tidal volumes improved mortality.
So then we get a treatment like antioxidants, which logically should work, and which give good looking data in rodents or healthy volunteers, but when applied to a critically ill population, simply don't work.
Take colloids for example. They were going to be the next big thing and replace crystalloids for treating septic shock. They provided a bigger increase in blood pressure than crystalloids, and this increase lasted longer. They stayed in the intravascular space longer, they caused less peripheral and pulmonary edema and fewer third space losses. They allowed us to wean vasopressors more quickly. They made all our numbers and parameters better. And then the studies came out which showed that actually they were pro-inflammatory, they were bad for the kidneys, and they worsened mortality. So we are back with crystalloids except in very specific cases.
Take ventilation for example. When we first ventilated patients, we used large tidal volumes and high respiratory rates to help clear CO2. We did this to get their PaCO2 down to a physiological level, which helped to correct the acidosis associated with sepsis and bring their pH back to a normal level, which definitely improved things in the short term, stabilized the patient, reduced the requirement for inotropes and vasopressors, etc. And then the studies likes ARDSnet came out which showed we were causing volutrauma and barotrauma and allowing what we call "permissive hypercapnia" with lower tidal volumes improved mortality.
So then we get a treatment like antioxidants, which logically should work, and which give good looking data in rodents or healthy volunteers, but when applied to a critically ill population, simply don't work.
Well, you're absolutely right. Something that seems promising in vitro is not always useful in vivo. A drug that works great on a cell culture may never even reach the cells in question when applied to a living body, which is basically a giant maze.
However, that's not what I meant. Look at those links I posted again. Many trials have failed to post any results at all, even over a year after their completion. Not positive, not negative. Nothing. No data. That's so frustrating to see.
Emphasis mine. These people would have had a near 100% mortality rate without intubation. I've intubated a lot of people with COVID, and in every single one they were critically hypoxic and, at most, a couple of hours from dying without intervention. It's also worth noting that the article with a mortality rate of 88% was published in April 2020, during the first wave, when we had no specific treatments for this disease. Less than a year later and the mortality rate is now down at 45% precisely because we have evidence showing us which "adjunct therapy", as you put it, is effective. As time goes on, and with other treatments being studied and widespread vaccination, that number will reduce further.
Isn't there anything that can be done in terms of surveillance and early treatment before they become critically hypoxic?
The public don't care. What can they do with knowledge that COVID causes severe DIC or pericarditis? They want to know when they can go on vacation again or go to a concert.
That's the wrong way of thinking about things. If there's no outreach at all, then people will become hostile and angry, simply because their bread and circuses are gone and they have no valid explanation for why this is the case, other than "there's a spooky pneumonia around".
I have seen so many instances where people go over the topic of COVID-19 death certificates, hear that a PE, stroke, or myocardial infarction killed someone who was sick with COVID-19, and then angrily grumble something about how hospitals are inflating COVID-19 numbers by designating deaths from infarcts as COVID deaths. I've spoken with a nurse with a biology degree who I see on my commute periodically, and he told me about a COVID-19 patient he saw who needed both her legs to be amputated from the knees down because of clots. People don't even comprehend the notion of an airborne virus that causes aggressive coagulopathy that can progress to disseminated intravascular coagulation. It does not compute.
I know they're trying to prevent a panic, but at this stage, more information is better. It has to be. What's going to fill the void if no one comes forward with answers? Long rants filled with angry and paranoid speculation? Mass unrest?
My condolences, sincerely. It's personal for a lot of us.
It is good to hear that the protocols for the ventilators have been adjusted and that mortality is dropping. Perhaps I came off as a little hyperbolic about them. I will have to correct that.
See? It's hard even for me, someone digging relentlessly into all this, to get up-to-date information on how patients are responding to adjustments in the protocols. Imagine the kind of dread and desperation for good-quality answers that the public must feel. Imagine how someone whose loved one is dying in the hospital feels. They don't know anything at all.
Back in February of 2020, I realized there was a shortage of PPE and equipment for healthcare workers that was about to make the following weeks and months into a living hell. I tried emailing HHS and the CDC about my concerns over supply shortages, but they never got back to me. Then, there were indeed shortages.
What we have is a crisis of trust. Public officials have done everything in their power to make millions of people very distrustful of them. The constant vacillation is appalling. First, masks are derided as useless, and travel bans are called racist. Then, they're mandatory; put these diapers on your face and cancel your travel plans. First, COVID is mostly transmitted by touch surfaces, then they say droplets, then they say aerosols. Two weeks to slow the spread and then it'll all be over, but it's actually two years and it's still going. The whole point of the stimulus checks was essentially to keep Wall Street afloat in the midst of an ongoing economic downturn due to the pandemic log-jamming just-in-time logistics, but we're told that this is to help people back up on their feet. Meanwhile, trillions of dollars were transferred from working-class people to the very rich.
Everything that they have done seems almost calculated to induce existential dread. People are demanding answers, but are receiving pepper spray and a truncheon to the face instead. Democracies have transformed, almost overnight, into brutal authoritarian hells. Everyone in the Anglosphere is watching Australia with open-mouthed horror and wondering if we're next.
How many people have lost their jobs over this? How many have slit their wrists in the bathtub or ODed on the sofa because they couldn't take it anymore?
Maybe if people hadn't been lied to and had their trust abused so flagrantly, we wouldn't be in this mess. People don't like to be turned into outcasts and pariahs in our own damn countries.
Mostly low quality evidence. Cohort studies or self selecting studies, low number of patients, confounding factors, etc. One of those studies you linked even found that physical activity was a risk factor for COVID. If you take high quality meta-analyses which only include high quality RTCs, such as the one I linked previously or this one - https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015017.pub2 - we generally find very sporadic and inconclusive evidence. I'm not saying there definitely isn't something there, but there is no good quality evidence to support it at present.
Very disappointing. I would have hoped that there would be something even better than dexamethasone for treating COVID-19 hyperinflammation by now.
A lot of people don't realize that antivirals can range from mildly toxic, like Ivermectin, to highly toxic and injurious to the liver and/or kidneys, like Kaletra and Remdesivir. Antivirals generally work by inhibiting the cellular machinery that viruses hijack to make their proteins. However, our own bodies need that machinery to express our own genes, too.
These patients' own bodies are killing them. It's not even really the virus itself; it's a SARS-like over-exuberant immune response, like carpet bombing an entire city with B-52s to kill a few guerrillas. Everything is a balancing act when one proposes to suppress the immune system. Too much suppression, and the patient ends up with co-infections, as was seen in India when the heavy use of steroids led to mucormycosis. Disabling the armaments of phagocytes, suppressing DAMPs, and preventing the activity of inflammatory transcription factors like NF-kB, AP-1 and STAT is not always beneficial.
Some inflammation is good, just not the crazy inflammation seen in COVID-19.
Almost all anti-vaxxers deliberately just turn a blind eye to published data and trials. I'm curious as to how you can understand how trials like these are the only way to reach firm conclusions and build an evidence base, but then simultaneously choose to ignore the evidence that the vaccine is reducing symptoms, reducing critical care admissions, and saving lives.
I am aware of the reports of lessened morbidity and mortality. What I'm worried about is ADE and the possibility that mortality from vaccine-related complications might eclipse any benefit over time, thus rendering the short-term benefits worthless. Yes, you're right in that quality, well-designed trials that produce good data are important, absolutely. However, all we have so far is a limited slice of time. We can make predictions, but we don't quite know what this picture will look like a year from now.
I keep hearing reports that adverse effects from the vaccines are being suppressed and kept hush-hush. Reports to the VAERS system are not being filled out, and even then, with the limited data available, the adverse events from COVID-19 vaccines seem to greatly outstrip vaccines for other diseases in previous years. The anecdotal reports are appalling. One news station asked people what their experiences were with COVID-19, and if they'd lost family from the virus. They instead got replies from hundreds of people claiming their family members were injured by the vaccines.
Lots and lots of people are very scared.