Coronavirus thread

[Nephrology]

I did find 1 case of an 80 year old Covid patient with comorbidities in Iran who improved dramatically while on EPO, but he had also been prescribed Hydroxychloroquine, Oseltamivir, and Lopinavir/Ritonavir: https://onlinelibrary.wiley.com/doi/...1002/jmv.25839

The patient was given 4000 IU subcutaneous injections of rhEPO on days 1, 3, 5, & 7. Hgb went up on days 2, 4, 6, & 8, but down on days 5 & 7 suggesting pretty immediate results:
Attachment 53277

now that I'm reading it more closely, I'm noticing that they are pulling a classic "MDs doing research" move; that is, to handwave and over-extrapolate from basic science literature and assume it directly applies to human disease. e.g.

"In another animal study of lipopolysaccharide (LPS) inducedsepsis model,7EPO effect on hepatic mitochondrial damage was as-sessed and it was shown that EPO suppressed the LPS effect on theincrease of IL‐1β and reactive oxygen species levels, mitochondrialDNA copy number, and also decreased protein expressions ofcaspase‐1, and NLRP3 (NLR Family Pyrin Domain Containing 3) gene.EPO alleviated LPS‐induced cellular edema in hepatic lobules, lym-phocytic infiltration, and hepatocellular necrosis.Renoprotective effects of EPO in mice with septic acute kidneyinjury has been observed and has been linked to attenuation ofmicrovascular damage, reducing renal inflammatory response and im-provement of renal tissue oxygenation through the decrease of hypoxia‐inducible factor‐1 alpha, inducible nitric oxide synthase, and NF‐κBandalso enhancement of erythropoietin receptor (EPO‐R), PeCAM‐1, vas-cular endothelial growth factor, and VEGFR‐2 expression.8Another study conducted earlier by Heitrich et al9on a murinemodel of sepsis‐caused acute lung injury and acute kidney injurydemonstrated beneficial protective EPO effects on pulmonary andrenal outcomes through EPO‐R and VEGF/VEGFR‐2 expression.Moreover, it has been shown that EPO has cardioprotective effectsby reducing the myocardial inflammatory response in septic rats andattenuates the reduction in mitochondrial membrane potential andinhibits myocardial cell apoptosis through mitochondrial pathwayand by reducing NF‐κB p65 expression.10NF‐κB is a principle factor of multiple inflammatory pathways,and according to the above‐mentioned studies, it can be consideredan important target for treatment. Blocking the activation of NF‐κBby EPO may prevent further deterioration caused by the COVID‐19disease through cytokine modulation and its regenerative and anti-apoptotic effectsAnother mechanism for an explanation of EPO effect on the im-provement of the clinical condition of the presented case could berooted to the findings of Ito et al11on an animal study that revealed tha t24 hours after EPO administration, the number of IgDlowimmature Bcells and mature B cells, as well as CD4+ and CD8+ T cells in the bonemarrow, decreased significantly due to their egress into the peripheralblood. This backup leukocyte release into the peripheral bloodstream might be a reason for the optimized viral confrontation of the immune system. Thus in the presented case, after the first dose of rhEPO andpacked RBC transfusion, abso lute lymphocyte count increased from 333to 933/μL of blood; a rise quite larger than to be elucidated only by250 mL of packed RBCs transfusion.During inflammation, serum Hepcidin levels increase the followingstimulation by IL‐6, downregulating cellular ferroportin and this leads todecreased iron absorption and its detainment in liver and spleen mac-rophages12which could promote the survival of intracellular micro-organisms. EPO by downregulating IL‐6 and Hepcidin levels could lead toan increased release of iron from macrophages and increased absorptionof iron by the bone marrow, thus decreasing iron availability for in-tracellular organisms like Coronavirus for their required enzymatic ac-tivities. This antiviral strategy of keeping iron out of infected cells haspreviously been explored and considered to be potentially effective inhuman infections by hepatitis C virus, human immunodeficiency virus‐1,hepatitis B virus, and cytomegalovirus viral infections.13Although the above‐mentioned novel mechanisms of EPO effectin septic states could elaborate the rapid clinical improvement of thepresented COVID‐19 case, we should not underestimate the defini-tive effects of rising hemoglobin from 6.7 to 9 g/dL in the improve-ment of pulmonary oxygenation and thus relieving the existingrespiratory symptoms. However, the 2.3 g/dL rise in hemoglobin levelin only 7 days with the mentioned dose of rhEPO is both profoundand questionable considering the reported peak effects of rhEPO in2 to 6 weeks after the starting dose."

Basically, they gave a single sick person epo and a bunch of other drugs, they got better quickly and are attributing this to the EPO. Correlation != causation, etc.

Also - my biggest pet peeve - is the handwaving re: mechanism of EPO benefit. It is very common for many MDs with a poor grasp of the basic sciences to piece together a tenuous and poorly supported hypothesis by simply searching on PubMed for papers that give plausibility to what they think are the molecular mechanisms of a given phenomenon.

The problems with this are: 1) Not all basic science research is of equivalent quality, and it is rare those who produce this kind of commentary give their sources a close read; 2) they piece together results from different experiments by different people to support their presumed mechanism of action, even if the model systems in these experiments are not the same; 3) they assume these findings apply to humans and human disease, even though there are often extremely important differences between the animal model for a human disease and the human disease itself. For example, the PVL toxin secreted by MRSA binds to a complement component in humans that does not have an equivalent in mice, so you can give them IV MRSA and they basically shrug it off until you hit the threshold dose of bacteria and they die from massive SIRS. This is not what happens in people, of course, but you wouldn't know that unless you'd actually tried to study PVL toxin in a lab, or at least were familiar with relevant basic literature.

So, yeah, in short, wouldn't draw any conclusions based on this paper. It's a lot of baseless speculation layered over a single case report, which is kinda worthless, to be blunt.

The medical equivalent of throwing everything against the wall to see what sticks?

Yes, except instead of throwing spaghetti or jello, you're throwing bricks

[45dotACP]

I don't know the patient's sex, but they started out anemic at baseline. Normal hgb in men is ~13-18, in women 12-16 g/dL. Haven't looked at the paper but it sounds like they were treating a pre-existing anemia, which is what EPO would be indicated for. As far as I know COVID19 doesn't cause hemolysis, but it has been reported anecdotally to cause GI bleeds, which may (?) explain their low hgb. with a HGB of 5 I am surprised they went for EPO instead of a transfusion. trigger for transfusion here is hgb of 6 or 7, iirc, but that's in the setting of known or suspected hemorrhage.

It's conceivable treating the anemia would help their oxygenation, but like YVK said it wouldn't do anything to address the root cause of their hypoxemia (ie ARDS)

edit: I took a peak at the paper, the patient's medical history doesn't provide a good explanation for their anemia, but later they claim it may have been due to a combination of Fe deficiency +/- anemia of chronic dz. It also does look like they pulled the trigger on transfusion - article says he got a unit of prbcs on day 1, and epo after.

I'm also really bewildered by their use of tamiflu, which 1) doesn't really work anyway and 2) is specific to the way that infliuenza enters and exits human cells. SARS CoV2 uses an entirely different mechanism to enter and exit human cells, so I really do not understand the rationale for its use in this patient.

The main problem with EPO in my understanding is two fold. Cost and side effects. It's prohibitively expensive for one, but the side effects don't match well with the risk of these patients.

EPO increases risk for clots if the hgb is above a certain point and these COVID-19 patients have a lot of coagulopathies that aren't fully understood (e.g. elevated D-dimer levels present very frequently). So much so that patients tend to be placed on Heparin drips pretty regularly (this might also explain the spike in GI bleeds in COVID patients unless anticoagulation is being accounted for).

We had a code just the other day where a patient who had some bleeding issues had to have the heparin drip DC'ed because of significant nose bleeds, bleeding gums and GI bleeding. Unfortunately the lack of anticoagulation meant that the enormous blood clot that turned the right ventricle into a balloon animal couldn't be stopped and death was unavoidable.

I would think anything that increases risk of clotting is a bad idea. Especially for the minimal benefit it might offer when the issue is more one of ventilation and less of perfusion.

And I wouldn't trust a single ounce of data coming from Iran.

Sent from my moto g(6) using Tapatalk

[Nephrology]

The main problem with EPO in my understanding is two fold. Cost and side effects. It's prohibitively expensive for one, but the side effects don't match well with the risk of these patients.

Yeah, it also fundamentally doesn't address the root cause of hypoxia/hypoxemia in ARDS. Epo is great if you have CKD associated anemia or similar, but if you have ARDS the rate limiting step will be gas exchange in the lungs. Even with a hgb of 5, if you have normal lung function, you won't get hypoxic end-organ damage unless you're hemorrhaging or are otherwise intravascularly deplete and develop an ischemic organ injury. In severe anemia, you'll compensate by increasing cardiac output (tachycardia) and minute ventilation (tachypnea), but you'll still see an SpO2 of 99% on RA, and IIRC the only "anemias" that are acutely life threatening are hemolytic and hemorrhagic.

edit: For anyone who isn't familiar with what hemoglobin is and how it relates to oxygen, here is a good primer:

https://www.youtube.com/watch?v=QP8ImP6NCk8

[ccmdfd]

Can't believe this thread fell to page 2.

[willie]

My doc asked me if I wanted the prostrate screening the last time I had an exam. I said of course I do, does anyone ever say they don't. His answer was yes, I have to ask.

I guess some people just don't want to know if they have cancer. My wife isn't totally convinced cancer screenings are a good thing and she was a health care professional with a masters degree.

Your wife most likely knows that the blood test for the prostate cancer antigen no longer has the respect that it once did. She knows that the invasive biopsy procedure has many risks and further is aware that some prostate cancers grow very slowly. The scientist who devised the psa test no longer recommends it. I pointed out to my doctor that if I had a bad psa reading, I would not undergo the biopsy procedure.

Once I made clear to my doctor that he works in corporate medicine and is a low rung on a big ladder. I further stated that there were certain procedures that I will never do again and that the only reason I showed up twice a year was to have medicine refilled. We understand each other. I understand that he likes to play with his phone, and he understands that I dislike corporate medicine and wish not to live forever. I put him at ease when I declare that I will never ask him for pain medicine. That's his fear. I manipulate him by saying that he is a bright young man. His hobby is knitting. He giggles a lot. Too much.

[Tom Duffy]

Can't believe this thread fell to page 2.

Yeah, and the noise level has increased. Lots of these posts belong in the finance/politics thread. After 3 months the "novel" coronavirus in no longer "novel".

[Nephrology]

Yeah, and the noise level has increased. Lots of these posts belong in the finance/politics thread. After 3 months the "novel" coronavirus in no longer "novel".

Well, lots of really interesting stuff going on in the research world, just not necessarily much that is very accessible or exciting to most.

This article was a good read, particularly b/c it refuted the notion that people with HTN treated with ACEis/ARBs would be more susceptible to the virus due to its mechanism of cell entry. Largest retrospective study to look at this specific question AFAIK.

edit: Also, a good piece on MD burnout, in context of current pandemic

[YVK]

I further stated that there were certain procedures that I will never do again and that the only reason I showed up twice a year was to have medicine refilled.

You could ask for 90 pills / 3 refills prescriptions and reduce your inconvenience to a once a year occurrence. Personally I write almost all of my prescriptions that way.

[Nightvisionary]

CDC revises COVID-19 death rate down.



https://www.cdc.gov/nchs/nvss/vsrr/covid19/index.htm

[shootist26]

CDC revises COVID-19 death rate down.



https://www.cdc.gov/nchs/nvss/vsrr/covid19/index.htm

I knew you were going to post that stupid shit. Consider reading the actual table instead of parroting a conspiracy theory. As it states well and clear below the table:

NOTE: Number of deaths reported in this table are the total number of deaths received and coded as of the date of analysis and do not represent all deaths that occurred in that period. The United States population, based on 2018 postcensal estimates from the U.S. Census Bureau, is 327,167,434.

*Data during this period are incomplete because of the lag in time between when the death occurred and when the death certificate is completed, submitted to NCHS and processed for reporting purposes. This delay can range from 1 week to 8 weeks or more, depending on the jurisdiction, age, and cause of death.

CDC does not update that site until the death certificate is completed and processed themselves. Therefore, there is always a >2 week lag in their stats.

Second, if you actually read the table, you notice that the death count decreases on week ending 4/18 and 4/25. How is this possible? It's because of the time lag in processing and certifying death certificates.