Thread by @NickAnderegg

An interesting re-analysis was published today: "Remdesivir treatment does not reduce viral titers in patients with COVID-19"

Basically, remdesivir has no impact on *viral load* in acute COVID!

Here's a summary of the findings—and controversy—for a general audience!

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Initially, remdesivir received emergency FDA approval because in one NIH-sponsored trial, the remdesivir group recovered quicker than the control group. That's ALL.

It was trialed because it does seem to be a great drug in cell cultures in the lab!

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It SEEMED like it would be a great drug, because it does exactly what we want *in cell cultures*. Unfortunately, even in animal models, it seemingly had issues.

In particular, viral load was lower in fluid from the lungs, but not in nose, throat, or rectal swabs.

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In humans, no study has shown a statistically significant decrease in viral load as a result of remdesivir treatment!

Only two studies looked at changes in viral load under remdesivir treatment and both found NO significant differences compared to controls.

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Apparently, one of the studies is criticized for having a small sample size... but that makes it much more likely that they'll have a false POSITIVE result, especially when it seemed to be so effective in preclinical research!

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In a challenge trial in 2022 (dear researchers: NO SC2 CHALLENGE TRIALS, WTF?), they provided remdesivir as a prophylactic against severe COVID, but the data suggested it might not be needed.

Thus, they discontinued administration for the rest of the participants.

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This change in protocol created a quasi-experiment, which is the focus here!

So, even in a study where participants were exposed to a standardized quantity of virus, no differences in viral load were found between the treated-with-remdesivir group and the no-remdesivir group.
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Boiling it down:

- It shows a certain level of viral inhibition in the lab
- Some studies have found it may have an impact on OUTCOMES
- But it DOESN'T have an impact on the viral load

The issue seems to be that the dose in the body can't get high enough!

8/

HOWEVER! Meta-analyses have noted SOME sort of SMALL impact on mortality, for SOME patients, e.g.:

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Maybe especially immunocompromised:
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So what's up?
9/pubmed.ncbi.nlm.nih.gov/35598856/
pubmed.ncbi.nlm.nih.gov/36828006/
pubmed.ncbi.nlm.nih.gov/35512728/
pubmed.ncbi.nlm.nih.gov/38105461/

IMO, I think the most likely answer is that some sort of latent viral reactivation is playing a role here (e.g.: ).

Remdesivir does seem to be a good antiviral in vitro, so if it has an impact on some other virus, it could skew the clinical outcomes!

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That means a lot more research is needed on the specific factors that lead to severe acute outcomes (and LC!), allowing specific diagnostics, allowing specific treatments.

No clinical trial can be successful if unidentified underlying issues aren't being addressed!

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For the record, this is very different from my first draft of this thread.

After I realized it was written by *current* grad/med students, I rewrote it as an actual critique, instead of my usual incisive schtick

Paper:

12/12journals.asm.org/doi/10.1128/aa…