Some Meds that Might Help

A new PrEP for Covid!

Invivyd got FDA approval for Pemgarda, or pemivibart and formerly VYD222, to be used as Pre-exposure Prophylaxis (PrEP) for Covid, specifically for adults and adolescents with moderate-to-severe immune compromise. Of course it made their stock jump dramatically. They expect it to be available imminently (see more here and here).

People can't actively have an infection when taking it, but it should be a game-changer for anyone who has been stuck at home because getting a virus would be the end of them. 

In other good new, some medicine combinations have been found to be effective in treating Long Covid symptoms. Study synopsis from Kashif Pirzada, MD: 

"What we found was an astonishing reduction in acute clinical deterioration, but also a dramatic reduction in post-acute sequelae (Long Covid) symptoms, with zero patients developing brain fog/cognitive symptoms in the combo treatment arms. 

995 patients were enrolled in Thailand (in 2021 to 2022) in an open-label outpatient RCT. Eligible were those with early, mild symptoms before signs of deterioration and began treatment within 48 hours of symptoms. 96% were partially or fully vaccinated (combo of viral vector, inactivated and mRNA). Assessed were a number of outcomes: 

Four older, commonly available generic drugs were assessed
* Fluvoxamine (FLV)- an SSRI with possible antiviral, anti-inflammatory, and serotonin reducing properties
* Cyproheptadine - an older 1st generation sedating anti-histamine, potentially a blocker of serotonin effects on lungs.
* Bromhexine - a cough medicine commonly used in Europe, but also a TMPRSS2 protease blocker
* Niclosamide - an anti-helminthic (anti-worm) agent. 

The effects were dramatic. Zero patients using combination treatments suffered any clinical deterioration
 0 of 178 taking FLV + bromhexine
 0 of 147 taking FLV + cyproheptadine
 0 of 172 taking niclosamide + bromhexine 

In the control arm, 47 of 336 (14%) suffered clinical deterioration by day 9 requiring high flow O2 or mechanical ventilation. 

There were significant decreases in viral load, and marked decreases in inflammatory cytokine levels. The most astonishing finding was a dramatic reduction in PASC (Long-Covid) symptoms,with zero patients with significant cognitive symptoms in the combination treatment arms at 90 days in all three combo treatment groups. 

Dosing: These are the doses used in the trial:
Fluvoxamine: 50mg twice daily x 2 days, then 50mg in the morning, and 100mg evening for 12 more days, then 50mg twice daily for 2 days (total 14 days) This medication can be difficult to tolerate at higher doses (especially at 100mg twice daily), so easing into it may help tolerate it better, and using the higher dose at nighttime so the worst is experienced while sleeping.
Cyproheptadine: 4mg tablet three times daily for 14 days In practice this may be difficult to tolerate as this is a sedating anti-histamine (same class as Benadryl), and taking once at nighttime may mitigate the worst
Bromhexine: 8mg tablet twice daily for 10 days This is a relatively harmless and well tolerated cough medicine commonly found in Europe
Niclosamide 1000 mg twice times daily for a total of 14 days 

The trial has some limitations, one being that less effective vaccines were used by some in this population (eg AZ, Sinopharm) vs what you'd find in a western population. Another is that extinct Alpha and Delta variants made up 41% of the infected (Omicron was 59%). 

A few lessons we can draw from this:
1) Peer review takes far too long - It takes far too long for important findings like this to reach the public. Millions could have been saved in the big waves in China and India if they had tried some combo of these cheap and relatively harmless drugs. The most important paper in computer science this century has never been published in an academic journal, but its effects are felt everywhere you use AI applications. @michaelzlin recently wrote how he spent 2 years in peer review trying to publish about an anti-viral that beats Paxlovid clinically. The current system rewards gatekeeping and is costing us lives, and we might be better off moving to the model the physicists and computer scientists have been doing for decades, where the expected standard is publishing a preprint first, and peer review later.
2) We don't know enough. That these medications worked shows there are a number of mechanisms of viral injury, including the role of serotonin and blood clots, which we are are not properly appreciating in the medical world. The same mechanisms are likely behind many other severe systemic illnesses, likely including Long-Covid. There are too many unknown unknowns out there, and physicians are too timid to look into these dark corners.
3) Access needs to be improved. Antivirals like Paxlovid and Remdesivir are expensive and still hard to access for most of the world; the fact that a combo of generic and inexpensive drugs can offer similar benefits is a potential game-changer. National authorities should seriously look at these medications in the coming months and years.