Followup to: and

It's been ~4 months since COVID-19 become a globally relevant topic; most of the treatment work that I've seen is focused on reducing mortality in the context of high-severity cases (usually post hospitalization) ie remdesivir, dexamethasone etc. Wanted to share my current synthesis around "what should I take if I'm experiencing covid-like symptoms?"; would greatly appreciate any feedback as well as info around other positive-effect-on-current-balance-of-evidence treatments that I've missed.

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The big ones I think:

DON'T take dextromethorphan, the substance in a lot of cough syrup. Preliminary untested-in-animals results that it increases viral reproduction in tissue culture.

DO take N-acetyl cysteine (NAC).

Recharges glutathione, one of the primary reducing-agent intermediaries in cells (not involved in energy metabolism).

Several likely good effects. Mucolytic - breaks the disulfide bonds between mucous proteins to make it more fluid. Known to decrease the symptom strength of flu and other respiratory diseases. Believed to reduce pathological clots (while not really being a classic anticoagulant) via changing the disulfide bond status in some of the clotting proteins in capillary walls. Possibly an effect decreasing the amount of NET production by neutrophils in the inappropriate inflammation that's going on here.

Smaller ones:

For the same effect on NET production I also might suggest L-carnosine, there's mouse work to the effect that it reduces immune-mediated lung damage from a wide variety of different insults. Lots of people around here are also fans of niagen, and I would take it while actively sick based entirely on the fact that the virus has enzymes that cleave off NAD-generated tags from proteins as part of its actions against the innate immune system.

Agree with the things listed above.


On a side note, I am appalled and flabbergasted that there are not multiple clinical trials ongoing for indomethacin, a prescription NSAID. There's in vitro data from SARS classic and SARS-2 that it dramatically suppresses viral replication via triggering the PKR pathway that senses dsRNA and makes ribosomes more selective against viral proteins. There's the fact that it's known to stop the cough that high doses of ACE2-inhibitors cause, suggesting something of the mechanism of this virus triggering cough and inflammation. There's in vivo data in dogs infected by canine enteric coronavirus that twenty four hours into the dose you give people for arthritis there's 1/100 the viral load. And there's anecdotal reports from large numbers of doctors in NYC and India of massive symptom relief in non-hospitalized patients, way above and beyond other NSAIDs.

Also still quite interested in the ivermectin trials when they come out.

Would also love your thoughts on this one I posted a while back if convenient - not sure if I'm thinking about this one correctly or not:

Unfortunately this is not a direction I have done a lot of looking, sorry.

Thanks for this, super helpful! Is NAC something to start taking when feeling symptomatic or something to start taking way ahead of time (like vitamin D)? Re indomethacin, it sounds like this is something that it would be worth getting a prescription of when feeling symptomatic (assuming it's not a controlled substance or something similarly difficult for a doctor to prescribe) - wanted to feedback this to you to make sure I'm understanding correctly.

Apparently I am still consistently a month or two ahead of the curve.
You can take NAC every day, it's basically an amino acid and acetate joined together in a peptide bond. Some people do take it every day. I would be hesitant taking it for very long times, since there are a few mouse studies in which mice that got a high dose constantly had higher cancer risks, but mice and cancer are a weird combo already and may not be representative. I would up the dose when actively sick. Indomethacin is a 1960s NSAID that is used less these days because there are slightly safer NSAIDs for most indications - it has several times the rate of causing ulcers compared to advil for example, but I think that's mostly for chronic use rather than short term. They recommend you take it with an antacid, so I would definitely take it with... famotidine, a drug that blocks histamine receptors involved both in stomach acid production AND possibly involved in the inappropriate inflammation that COVID is causing, and which was associated with higher recoveries in some studies. These days I think indomethacin it is mostly used for gout, some types of arthritis, migraines, and some edge cases like helping premature babies rewire their hearts for breathing instead of using a placenta. It's DEFINITELY something you would only take while actively sick, 5-10 days. It's prescription-only in the US, but not exactly 'controlled', it's not like anybody takes it for fun.
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To state the obvious, if you experience COVID-like symptoms, you should contact your doctor, get tested, and stay isolated. Beyond that, staying hydrated and monitoring your temperature and (if possible) oxygenation are probably advisable.