Share this page!

Enter URL or ID to Unroll

You can paste full URL like: https://x.com/threadreaderapp/status/1644127596119195649
or just the ID like: 1644127596119195649

How to get URL link on X (Twitter) App

  1. On the Twitter thread, click on or icon on the bottom
  2. Click again on or Share Via icon
  3. Click on Copy Link to Tweet
  4. Paste it above and click "Unroll Thread"!
  5. More info at Twitter Help
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
@NickAnderegg
Jul 19, 2024 • 12 tweets • 5 min read • Read on X
Scrolly
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!

1/12 Remdesivir treatment does not reduce viral titers in patients with COVID-19 "ABSTRACT The relationship (or lack thereof) between the clinical activity of remdesivir and its ability to reduce viral titers in patients with COVID-19 has not been fully delineated. There is a misconception that remdesivir was FDA-approved for COVID-19 due to its ability to reduce viral titers. Here, we analyze all clinical studies of remedesivir in COVID-19 that quantifed SARS-CoV-2 titers. As of 28 June 2024, we show there is no significant decrease in SARS-CoV-2 viral titers in patients treted with remd...
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!

2/
"Remdesivir (RDV) was the first FDA-approved treatment for COVID-19 based on results from the NIH-sponsored ACTT-1 trial demonstrating shorter time to recovery in patients with severe COVID-19 treated with remdesivir compared to placebo (10 vs 15 days, respectively) (1). While RDV demonstrated benefit in ACTT-1, its efficacy and clinical benefit have been marginal-to-ineffective in other contexts, making its FDA approval controversial. Several subsequent randomized controlled trials (RCTs) found no benefit with RDV treatment compared to placebo or the standard of care (SOC) (2-4), incl...
"Marginal clinical benefit with RDV treatment calls into question whether there is a relationship between the mechanism of viral load inhibition with RDV treatment and corresponding clinical outcomes. RDV is a prodrug of an ATP-analogue (GS-443902) that exhibits broad-spectrum antiviral activity (5). GS-443902 exhibits low Km for SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and cell-based assays have demonstrated low nanomolar EC50 values in SARS-CoV-2 infected cells treated with remdesivir (68)(9). Cells infected with SARS-CoV-2 and treated with remdesivir in vitro also show dose-de...
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.

3/ "The preclinical pharmacodynamics of remdesivir have been extensively well-validated; it thus stands to reason that the observed decreases in viral load should translate in the clinic. If remdesivir demonstrates clinical benefit, it would stand to reason that there is a concomitant decrease in viral load associated with remdesivir treatment. However, this was not the case. Limited pharmacodynamic activity of RDV in humans was foreshadowed by the weak reductions in viral titers observed in rhesus macaque models of COVID-19 (11). Treatment with RDV lead to statistically significant decr...
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.

4/ "In humans, RDV has failed to demonstrate statistically significant reductions in viral titers compared to placebo control groups. [...] However, only two studies have documented the changes in viral titers associated with RDV treatment: (i) Wang et al. Lancet (2020), who published the first double-blind RCT of remdesivir versus placebo-treated patients hospitalized with severe COVID-19 and (ii) Killingley et al. Nature Medicine (2022), who published the results of the SARS-CoV-2 challenge study in healthy human volunteers. In the study by Wang and colleagues, viral titers were measur...
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!

5/ "While critiqued for its low sample size, this study demonstrates: (i) there is no patently obvious clinical benefit with RDV treatment, thus necessitating a larger sample size to detect group differences and (ii) the clinical dose of 200 mg loading followed by 100 mg maintenance for 10 days does not produce a pharmacodynamic benefit."
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.

6/ "In the study by Killingley et al., healthy human volunteers ages (18-29) were intranasally challenged with SARS-CoV-2 with the goal of characterizing the replica- tion kinetics of SARS-CoV-2 early in the pandemic (13). Participants were inoculated intranasally with a pipette at 10 TCID50 of SARS-CoV-2/(GBR/484861/2020). The original protocol indicated that all participants were to receive RDV treatment as a precaution to mitigate the risk of COVID-19 progression. As a result, the first 10 participants were preemptively given RDV after two consecutive quantifiable viral detections and ...
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.
7/ "Interestingly, this situation inadvertently enables one to compare the effects of RDV treatment versus no treatment in young, healthy participants with a standardized baseline viral titer challenge. Viral titers were measured by qPCR in nasal and throat swabs for the duration of the 28-day study (RDV N = 6; no RDV N = 12). No statistically significant differences in viral titers were observed in nasal or throat swabs between groups following SARS-CoV-2 challenge as measured by focus forming assay" Figure 1 "(C) Area under the curve for SARS-CoV-2 nasal viral titers measured...
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/ "The studies by Wang et al. and Killingley et al. demonstrate no correlation between RDV treatment and decrease in viral titers compared to untreated controls. This finding highlights the discordance between RDV's mechanism of action and purported clinical benefit and re-emphasizes the controversial basis of RDV's FDA approval. Our finding once again calls attention to a central predicament of RDV's design: the inability to increase the dose to augment the weak pharmacodynamic activity observed in the clinic due to extensive hepatic metabolism (14-17). Finally, in a post-pandemic world...
HOWEVER! Meta-analyses have noted SOME sort of SMALL impact on mortality, for SOME patients, e.g.:

-
-
-

Maybe especially immunocompromised:
-

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!

10/
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!

11/
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…

• • •

Missing some Tweet in this thread? You can try to force a refresh
　

Keep Current with Nick #RespiratorsFilterPathogens😷 Anderegg

Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

PDF

Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @NickAnderegg

Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Sep 7
Let’s talk about systemic risk from negligent public health: Catastrophe doesn’t require population-wide illness.

The worst case isn’t sickness. Worst case is infrastructure collapse due to overstressed resources.

You know power plants need stable power to operate?

1/many “8. Performance of Nuclear Power Plants Affected by the Blackout On August 14, 2003, nine U.S. nuclear power plants experienced rapid shutdowns (reactor trips) as a consequence of the power outage. Seven nuclear power plants in Canada operating at high power levels at the time of the event also experienced rapid shutdowns. […]. Many non-nuclear generating plants in both countries also tripped during the event. Numerous other nuclear plants observed disturbances on the electrical grid but continued to generate electrical power without interruption. […] - The severity of the grid transient...
If there is a widespread disruption in the service area of, e.g., a nuclear power plant, it shuts down for safety. Massive blackouts like in 2003 or in Spain this year are caused by safety systems!

If too much trips out at once, it has a ripple effect across the grid
2/ Source: https://www.insurancejournal.com/news/international/2025/04/29/821703.htm Why Restarting a Power Grid After Massive Collapse Is So Hard April 29, 2025 by Rachel Morison and William Mathis It’s a worst case scenario that grid operators plan for but hope never to encounter. After one of the worst blackouts in Europe in more than a decade, electricity grid operators in Spain and Portugal are trying to get networks back up and running from the ground up. The initial estimate from grid operator Red Electrica was that restoring all power supply in Spain may take between six and 10 hour...
Frequency Factor So far, the only information about what caused the crisis was a comment from grid operator Red Electrica that the blackout was a result of “oscillation,” which suggests a disruption in the grid’s frequency or voltage — both crucial factors for maintaining stability. The frequency, which normally stays pretty steady around 50 hertz, is the heartbeat of the grid. Frequency monitoring specialist Gridradar said it identified a rapid movement in frequency just after noon in Spain — right before the blackout hit. Such oscillations can cause chain reactions that ultimately lead ...
In 2003, it took 2 days to fully restore most power. The infrastructure is 20 years older than it was back then and higher demand creates risk of cascading failure.

As of 2003, recommendations from blackouts in 1965, 1977, 1982, 1996, and 1998 had not been implemented.
3/ “Recommendations to Prevent or Minimize the Scope of Future Blackouts As reported in previous chapters, the blackout on August 14, 2003, was preventable. It had several direct causes and contributing factors, including: • Failure to maintain adequate reactive power support • Failure to ensure operation within secure limits • Inadequate vegetation management • Inadequate operator training • Failure to identify emergency conditions and communicate that status to neighboring systems • Inadequate regional-scale visibility over the bulk power system.”
“Further, as discussed in Chapter 7, after each major blackout in North America since 1965, an expert team of investigators has probed the causes of the blackout, written detailed technical reports, and issued lists of recommendations to prevent or minimize the scope of future blackouts. Yet several of the causes of the August 14 blackout are strikingly similar to those of the earlier blackouts. Clearly, efforts to implement earlier recommendations have not been adequate. Accordingly, the recommendations presented below emphasize comprehensiveness, monitoring, training, and enforcement of r...
“1. Market mechanisms should be used where possible, but in circumstances where conflicts between reliability and commercial objectives cannot be reconciled, they must be resolved in favor of high reliability. 2. Regulators and consumers should recognize that reliability is not free, and that maintaining it requires ongoing investments and operational expenditures by many parties. Regulated companies will not make such outlays without assurances from regulators that the costs will be recoverable through approved electric rates, and unregulated companies will not make such outlays unless th...
“3. Recommendations have no value unless they are implemented. Accordingly, the Task Force emphasizes strongly that North American governments and industry should commit themselves to working together to put into effect the suite of improvements mapped out below. Success in this area will require particular attention to the mechanisms proposed for performance monitoring, accountability of senior manage-ment, and enforcement of compliance with standards. 4. The bulk power systems are among the most critical elements of our economic and social infrastructure. Although the August 14 blackout ...
Read 20 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Sep 4
If Florida drops vaccine mandates, society is probably officially over. I really, really, really don’t think most people get that herd immunity is the only thing keeping measles from ripping through the population, and a measles infection wipes out all pre-existing immunity

1/3
Measles specifically infects the cells that are responsible for “remembering” which pathogens your body has encountered before. So they ALL get wiped out, and all you’re left with is cells that remember your measles infection and nothing else.

2/3
Every infection, vaccination, and other pathogenic exposure you’ve ever had? Your body no longer knows how to detect them after a measles infection. The only immunity you’ll be left with is immunity to measles. That’s it. Open season for every other pathogen encountered.

3/3
Read 8 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jun 30
Can I say something? I have a BA in psych, a BPhil in linguistics, and went to grad school for cognitive psych. My research, including an undergrad fellowship, was on the cognitive relationship between written and spoken language…

Audiobooks are NO DIFFERENT than reading print.
In the last hour, there have been a dozen replies from people nitpicking the first tweet

The topic of discussion is "do audiobooks 'count' as reading?," and the answer is "Audiobooks are NO DIFFERENT than reading print."

Maybe read the thread before arguing with it? lmfao
And for all those people with indignant responses who want to nitpick every detail, the fact that so many people hold THIS exact view—that audiobooks are somehow “cheating”—is the ENTIRE point. It leads to people who would benefit from audiobooks depriving themselves the medium
Read 4 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Feb 1
Many people are asking for recommendations about what storage media to buy, so here's a buying guide from an experienced data hoarder (me)

The MOST IMPORTANT thing to know is that SOLID-STATE MEDIA IS NOT DURABLE. Flash drives, SSDs, SD cards, etc. are NOT long-term storage.

1/
That's not to say that it's impossible to use solid-state media for long-term storage. It's just that anything with durability guarantees gets prohibitively expensive quickly. Spinning hard drives—as well as DVDs and Blu-ray discs!—are your friend.

2/
- The way data is stored in solid-state media makes it much more susceptible to bit rot than other media.
- In a spinning hard drive, the moving parts are the most common point of failure.
- When you burn a DVD, that shit is fairly permanent.

3/
Read 42 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 9
I wish people would understand that insurance underwriters have armies of actuaries calculating risks, and if an insurance company drops you, it's because things have changed in such a way that insuring you will take more out of the financial pool than you're putting in

1/
It sucks, but it's a direct result of the fact that humans are widely inhabiting locations that are rapidly becoming impossible to inhabit safely. If you can't find insurance for your home, it means there's a high likelihood you'll need to move soon anyway.

2/
You get insurance so that you can replace all of your stuff in the event of a disaster. When the insurance company effectively says "the risk of disaster is so high that insuring you would almost certainly cause us to lose a lot of money," it ALSO means your life is in danger

3/
Read 7 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 5
So here’s the thing about some of the subtle neuro damage related to SARS-CoV-2 infection that I think a lot of people miss: some of the known deficits are correlated with things like impulsiveness and poor emotional control, so we might expect to see deficits there are well

1/
Consider how impatient people seem to be on the road in the last couple years relative to the 2010s, and I think we have a perfect example of where this is LIKELY already manifesting.

2/
This impact is particularly insidious for the person experiencing it, because poor impulse control, by definition, doesn’t really come on gradually. My biggest concern is how interactions under these circumstances will play out if this impact continues to become more common

3/
Read 15 tweets

Did Thread Reader help you today?

Support us! We are indie developers!

This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Don't want to be a Premium member but still want to support us?

Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal

Or Donate anonymously using crypto!

Ethereum

0xfe58350B80634f60Fa6Dc149a72b4DFbc17D341E copy

Bitcoin

3ATGMxNzCUFzxpMCHL5sWSt4DVtS8UqXpi copy

Thank you for your support!

Follow Us!

Send Email!

:(