Coronavirus Pandemic Update 40: Ibuprofen and COVID-19 (are NSAIDs safe?), Trials of HIV medications

Welcome to another MedCram COVID-19

update

. We have a lot of news to cover today. There have been many things that have come back from a medical point of view or more than 200,000 confirmed cases worldwide. Total deaths. Almost nine thousand recovered in total. Eighty-four thousand. If we look country by country on the world meter site, we can see here only 34 new cases in total in China at the moment, most of the cases are outside China, in fact more cases in Italy in terms of active cases than everywhere else in the world Right now, cases in the United States have risen to almost 10,000, which is likely due to the increased testing now being done in the United States, even though only We have about 64 serious or critical cases in the United States out of a total of 92.

We also have here news from the CDC in its weekly morbidity and mortality report that was published yesterday March 18 says that the first preliminary description of the results among patients with kovin 19 in the United States indicates that case fatality was highest in people over 85 years of age ranging from ten to twenty-seven percent, followed by mortality of three to 11 percent among people aged 65 to 80 years , one to three percent mortality among people aged 55 to 64 and less than one percent among people twenty to fifty-four years of age and no deaths among people under 19 years of age here we see the number of new Kovan 19 cases reported daily here in the United States from February 12 to March 16 and you can see that it has increased steadily and here You can see by age group how many hospitalizations in the lavender lights and ICU admissions in the darker blue and then deaths in the darker blue and you can see that here there is a gradual increase in the different ages for those over 85 years old. there were more deaths than in intensive care, which may be due to palliative care or palliative care where there are patients who are hospitalized but never enter the intensive care unit before they pass and here is the breakdown by age group in terms of hospitalization. percentage percentage of admission to ICU and percentage of fatality this is the big news that was published today in the New England Journal of Medicine was the trial by Lope in Aver and Ratana see what are anti-HIV

medications

in adult patients hospitalized with severe covin 19 :00 this was a trial that was done in China so it was a randomized, controlled but open trial because they didn't have time to prepare the placebo pills and of course they gave them to randomized patients to see how they would improve with kovat 19:00 and the endpoint here was discharge from the hospital or an improvement on a seven-point scale that we'll talk about.

The primary endpoint was time to clinical improvement, defined as the time from randomization to an improvement of two. points on a seven-category ordinal scale or discharged alive from the hospital, whichever comes first, has been used before the seven-point scale in other influenza studies and this is scale one if not hospitalized with resumption of normal activities, if not hospitalized but unable to resume normal activities three hospitalized who did not require supplemental oxygen for those hospitalized who required supplemental oxygen five hospitalized who required high-flow nasal oxygen therapy non-invasive mechanical ventilation or both six hospitalized who required invasive mechanical ventilation ECMO or both and seven death, so if there was a two-point drop or a discharge from the hospital that would indicate an improvement, so there were 357 participants who were screened for eligibility, there were some who dropped out, leaving one hundred and ninety-one nine who underwent randomization and there were 99 who were assigned to the intervention. group that was lepen aver ritonavir and a hundred that were assigned to the standard care group and, as any good study should do, they show you what the two groups were and what their characteristics were and if you look up and down the lepen category aver ritonavir and standard care there really wasn't much difference between them statistically, which means the randomization was pretty good and if we look at this we can get an idea of ​​who these patients were.

The average age in both was 58 years. There was a majority of men here, which we've seen before, interestingly, the body temperature was not febrile, so in terms of the median 36.5 is not fever, in terms of those who had fever, we had 89% and 93% we had a number of people who had respirations greater than 24, those who had a systolic blood pressure less than 90, they noted that they were a very small percentage of people, so the blood pressure of most of these people in reality is elevated. The other thing that was interesting to note here is that the number of people with relatively low white blood cells is quite extensive, so generally this is what you will see and you can look at the other characteristics when you look at the types of interventions that were done, you can go back to see quite similar rises and falls. the categories, let's take a look at the results, so again here we have days on the x-axis and we have the cumulative rate of improvement that we see by more than two points, so if this is working well, we should see these things go up quite a bit fast and in fact what we see here is that while there is some space between the lepen aver and the Ratana vert, it is not statistically significant, so it turns out that this is a negative study, it did not show a difference between lepen aver and ritonavir and the control group, at least in these fairly severe hospitalized patients, as you can see here in terms of the viral load, which should be declining very well over time.

Again, there is no real difference between the lepen aver ritonavir intervention group and the control group and so the authors came to this conclusion in adult patients hospitalized with severe Kove at age 19, no benefit was observed with lepen treatment aver ritonavir beyond standard care, there have been a number of questions about NSAIDs and a recent issue in terms of the French minister said they also Very good summary of the key points published by an organization of pharmacists in Canada, to which we'll put a link in the description below that also discusses highlights about the possible risks and benefits of NSAIDs in kovat 19, but let's talk a little. a little bit about what our NSAIDs are and what they have to do with viruses, so NSAIDs stand for non-steroidal anti-inflammatory drugs and the reason is that for a long time what reduced inflammation was steroids, so they were a new category of drugs that were not steroids but could reduce inflammation, probably the first one that was invented was aspirin in 1899, more on that later, very important, we will talk about

ibuprofen

.

Ibuprofen is probably one of the most used and mentioned in the world. It is used to reduce inflammation reduce fever It is used for osteoarthritis Various indications for NSAIDs Well, NSAIDs, among other things, have a special impact on an enzyme that we are going to talk about, which is cox-2. cox-2 stands for cyclooxygenase 2 as opposed to cyclooxygenase 1, which it can also inhibit, but that's not really relevant to our discussion, what does Cox do? It takes a substance called arachidonic acid which will abbreviate AAA and convert it into prostaglandins, specifically pge2. Now the helmsman also produces thromboxane and that is used. in platelets, but that has nothing to do with what we are talking about.

What we want to look at here is the cox-2 enzyme that converts arachidonic acid to prostaglandin e2. ¿Why is it so important? Because prostaglandin e2 is involved with pain, so it would, it's also related to fever, which you would see in a viral infection, but it's also involved in the production of antibodies or, more specifically, cox-2 is involved. in the production of antibodies and what NSAIDs do is they stop it, they prevent it, now the antibodies are The important antibodies are produced by the B cells and the B cells cause these antibodies to go out into the serum and attack things that should not be there, like viruses, so you could see why NSAIDs can cause a problem, yes, while eliminating pain and fever.

It can also affect antibody production, but NSAIDs, specifically

ibuprofen

and to a lesser extent other SEDs, also have another function because they also inhibit some other things, apparently they can inhibit viral replication and have been shown to affect Czar's Cove v-not. too, but the original which was from 2002 has also been shown to attack the canine version of the corona virus and has also been shown to be toxic and inhibitory to both influenza A and B, so the question is which one is it doing? more and You can see why there may be benefits on both sides and risks on both sides.

What do we do? This pharmaceutical organization that published this statement from Canada that was prepared a couple of days ago says that more research is required here, including randomized control

trials

. To determine the impact of NSAIDs on

coronavirus

infection and subsequent disease, they continue to talk about confounding variables. NSAIDs could be treating comorbid conditions that put them at higher risk for more severe Kovat 19 disease, so the bottom line is that a randomized controlled study is needed. essay, so I think the answer right now is that we don't know based on this data, so I did something really strange: I went back in time to an epidemic of a viral disease that was a

pandemic

and at that time they actually had a final set and it was given quite liberally so the question is what happened at that time and what were the observations and it was actually quite interesting and here is an article that was published in 2009 salicylates and influenza

pandemic

mortality from 1918 to 1919 pharmacology pathology and historical evidence and we will put a link to this as well in the description below and what he talks about is that aspirin had just come out in 1899 and it was a new medication that was being used at the time and it was a great way to get rid of the fever and some people thought that if the symptoms of the flu could be treated, the patient would get better and one of the big symptoms of the flu, of course, was the fever.

The article analyzes what the current toxic doses are based on. From what we know at the time, people were given large doses of aspirin until they saw toxicity and then they were withdrawn, they talk about four lines of evidence supporting the role of salicylate poisoning in 1918 influenza mortality, pharmacokinetics, mechanism of action, pathology. and official recommendations for toxic aspirin regimens immediately before the peak of deaths in October 1918 and for those who do not know that one grain is equal to 65 milligrams, so when we talk about grains you will see that it is now known that the aspirin regimens recommended in 1918 regularly produce toxicities and you can read about that here, we know that salicylates cause immediate lung toxicity and can predispose to bacterial infections by increasing lung fluid and protein levels and altering mucociliary clearance and the pathology of the premature deaths we saw in 1918 was consistent with aspirin toxicity and virus-induced pathology and remember that aspirin, which is a salicylate, is also an NSAID, so this puts an interesting twist on the discussion about whether we should use NSAIDs in Kovat 19 and then , interestingly, there is talk of aspirin ads in August. of 1918 and a series of official recommendations for aspirin in September and early October preceded the October 1918 publication and it is interesting that young adults returning from World War I were most likely to take aspirin, while the least Mortality in younger children may have been the result of less use of aspirin and, interestingly, the most important pediatric text of the time in 1918 and remember that they don't have antibiotics, they don't have antivirals, they don't have ventilators, essentially, what would happen in a significant increase does not recommend aspirin or salicylate, but actually recommends hydrotherapy. for fever these were the great thinkers working with what they had at that time and we can see at that time that there was a dichotomy that was established in the treatment of the Spanish flu back in 1918 1919 those who really believed in pharmacodynamics and pharmacokinetics of aspirin and those I would treat with hydrotherapy, this is dr.

Quote from William to Pearson in 1999 No one is as blind as those who cannot see that the average mortality of influenza patients treated by homeopathic doctors was actually only about one-thirtieth and that is one-thirtieth, not one-thirteenth, but one thirtieth of the average mortality reported by all doctors and then Dr. C J Louise L of Des Moines in 1919 and since German aspirin has killed more people than German bullets, the question comes down to what are we getting in terms ofrisks and benefits of these NSAIDs and ibuprofen or even aspirin. Are we confusing mortality? of 1918 with the aspirin dose some would say yes, is this simply a larger magnitude of the effect that we might be seeing with NSAIDs with kovat 19?

I think it's worth trying. I don't think we have enough answers for that right now. However, I would say that in my research on the 1918 Spanish flu epidemic and pandemic I think there are some parallels that we could learn from because, if we do in fact have a surge in this country like we are having in Italy, the question What worked in 1918? Can we learn something from there? Because it is very possible that we will be in a similar situation if we do not have ventilators like they did not have, if we do not have pharmacological interventions.

Since they didn't have them back then, we don't have antivirals, like they didn't have them back then, and we don't have antibiotics, in other words, are there any lessons we can learn from them that we can apply in our own homes? instance to improve survival. I think it is worth reflecting on and worthy of investigation. Thank you for joining us.you