Connor_Flexman

Connor_Flexman's Comments

Self-priming

These are great!

(Although the media one seems like it would take ages and be more about actual exploration than priming per se.)

As to your comment at the end, I want to note that the point isn't actually novelty! Yours are in fact more novel than mine were. You just want your brain to be chewing on something. If you choose things you like, they won't be very novel, but they *should* hook your brain and get you idly replaying them in the back of your head. Hopefully just basking in cool/interesting things for a bit will take care of the "artificial" objection?

Taking Initial Viral Load Seriously

The second link was meant to be to incubation times, now fixed.

I meant ~95% of the times you become sick, i.e. mostly "colds and flus".

Taking Initial Viral Load Seriously

I think the common factor between COVID and smallpox is their long incubation times, which isn't shared by something like 95% of current ambient disease (not sure about historically).

This makes sense with the proposed mechanism. There must be some short length of incubation period where your immune system wouldn't have time to get much stronger even if given double the notice, some longer period where it can definitely grow much stronger given double the notice, and some even longer period where the body has ample time to react no matter the starting load. It also fits the immune response time relatively well: the short term response of IgM antibodies takes around a week, so diseases that took around 1-3 weeks of progression would be right in the sweet spot of getting substantially more exponential response from your immune system from advance notice of a few doublings (several days of viral growth).

The one countervailing consideration is that the incubation periods for a lot of diseases are a bit longer than I had thought. I can't tell if this is an artifact of them including outliers rather than just the middle 95% or something. But it still seems like the difference between a 4-day and 10-day incubation period could explain why viral load doesn't matter much in most diseases. It also suggests that chickenpox, rubeola, rubella, whooping cough, and mumps are good places to look for outcome dependence on initial viral load.

Coronavirus: Justified Practical Advice Thread

I'm leaning on the expected value rather than robust evidence.

Definitely seems plausible to me that it's not useful for immune function outside bone health. But priors (it's the one vitamin not in diet, so everyone is deficient) and the small amount of evidence are enough to make me think it's net-positive, and even 20% likely to help by a small amount is a relatively large benefit (~ a day of life).

It seems hard enough to find small effect sizes of things via study that I'm not at all surprised meta-analyses showed no evidence for it—and when I don't really expect to see evidence, defaulting to "do what seems like it would be healthy in the ancestral environment" says sunlight is probably a better bet than supplements, but being non-deficient in vitamin D is probably a better bet than being deficient. (And again, this doesn't apply to other vitamins because they're in the diet. It does apply to e.g. sleep and exercise though.)

What should we do once infected with COVID-19?

Blood oxygen can certainly vary between people, but I think this gives a misleading picture for many people. Most of my friends have blood oxygenation of >98, and getting to 90 would imply rampant infection and warrant hospitalization if the hospitals aren't overrun yet. Certainly 90-95% is not "normal", as the OP now says (the link specifically says it's not normal).

I think people should be considering hospitalization once they've dropped 6% in SpO2 AND they've dropped below 92% SpO2. More thoughts are in my longer comment here. This covers people with unnaturally low SpO2 to begin with, while also acknowledging that many people do start from ~100% and should not wait until they have such an infection that their lungs have dropped past chronic smoker levels of impairment.

Connor_Flexman's Shortform

I’ve updated toward significantly less risk from COVID than I expected a week ago, for people aged 25-30:

Old numbers:

  • .2% mortality = 1 expected month
  • 1.5% long-term side effect = 2 expected months
  • 1% mortality from lack of ventilators = 5 expected months (10% hospitalized, 10% of those on ventilators, n_vent is .03% of pop and older people need more ventilators so we run out at ~1% of population infected, and no shutdown measures had been taken approximately 2 days before we hit 1% of population by my estimates)
  • Total = 8 expected months

New numbers (from ICL report; someone please tell me if I’m misunderstanding their context):

  • .05% mortality = .3 expected months
  • .7% long-term side effect = 1 expected month
  • .1% mortality from lack of ventilators = .5 expected months (2% hospitalized, 5% of those on ventilators)
  • Total = 2 expected months (maybe less if we never go above 2% of population infected in most places due to new shutdown measures, and ventilators are sufficiently mobile to move to crisis zones)

For older people, the numbers changed less (about a factor of 2), e.g. a healthyish parent in their 60s went from about 3 years of expected life lost to roughly 1.5 years.

In general, I feel fine with this outcome—the old numbers I was using were more an average than a median, so the most likely update was downward. I also adjusted the mortality rates downward somewhat, but I didn’t know how far, and the final update was further than I should have guessed. Lastly, a week ago the response was so abysmal that I think it was correct to have a factor of two worse expectation than I do now, just from failures to contain, treat, etc.

The one thing I wish I had done differently was weight South Korea’s numbers a little higher a little earlier, since priors were already on the side of lots of undiscovered/mild cases. I thought Wuhan’s testing was relatively good and things were partially adjusted for the missing cases, but I went like two weeks between looking at South Korea and that caused my numbers to lag somewhat. I think I could have been estimating 4-6 weeks as of a week ago, if I had flagged that better to come back to.

Coronavirus: Justified Practical Advice Thread

Hospitalization and oxygen therapy thresholds

Tl;dr: Not knowing much about this, my current policy is to go to a hospital if PaO2 drops below ~92% and my hospital isn’t completely overrun, unless my PaO2 is naturally low or some other extenuating circumstance. If I was forced to use an oxygen concentrator outside of a hospital, I would target a ~~94-96% PaO2 range, trying very hard to make sure I didn’t hit 99%

If you do have COVID and shortness of breath, when do you go to a hospital?

Hopefully you already have a pulse oximeter as Julia Wise recommends. But sources say anywhere between 90 and 95% PaO2 is the threshold for hospitalization (WHO says <= 93% is classified as severe, ctrl+f “O2”), while other sources say you should threshold on trouble breathing and shortness of breath, not the actual PaO2 number.

It seems to me that using “trouble breathing” as the indicator would track the lung blockages and thus immune response relatively well, while O2 as an indicator would track the danger metric directly (if in fact the primary source of death is insufficient oxygen; if anyone knows this, would be useful).

The benefit of looking at trouble breathing is that it’s an advance indicator. Usually people progress from oxygen therapy to ventilators relatively quickly. If you have naturally low PaO2, your O2 might drop under threshold (say, 93%) in the early stages with mild trouble breathing, but you wouldn’t have much of a dangerous immune response until later. In this case, you’d have wanted to use difficulty breathing as your indicator instead of PaO2.

That being said, having low oxygen seems pretty bad for you, both by common sense and science. For example, 92% or lower is associated with increased morbidity in pneumonia patients; <90% is increased with 36% increased morbidity. Since it’s hard to measure even moderate effects due to the treatment-correlated-with-severity issue, my guess is that there’s some general bodily harm from reduced oxygen even at levels like 95%, though I don’t know how much. So at some PaO2 threshold, I think you want to be supplementing oxygen even if your breathing doesn’t feel that difficult.

Unfortunately, it seems like you can’t supplement oxygen at 95%, because over-oxygenating causes neuronal damage. Standard targets appear to be 94-98% or 92-96%. This study says it seems bad to set your target range during oxygen therapy to greater than 92-96%, because one inevitably exceeds the upper target occasionally. This review/musing muses that it’s a difficult problem, evidence for hyperoxaemia being pretty bad is “comparatively strong”, but not strong enough to warrant especially conservative oxygen titration. Because of these numbers, I think 92-93% is a reasonable threshold to self-hospitalize, since anything above this means they probably shouldn’t be oxygenating you anyways.

If hospitals are overloaded and you have to do oxygen therapy yourself (really try not to do this), I think the targets above are still reasonable, subject to your ability to titrate well with the machine. If you have lots of trouble, of course be conservative. However, you may be able to do better than hospitals: the first study above says that “even in a research setting in the intensive care unit, in which patients receiving mechanical ventilation are closely monitored, most patients who were randomized to an SpO2 target of 90–92% and were receiving supplementary oxygen did not have their inspired oxygen reduced if the SpO2 was 99% or 100%.” So—seems like you could easily do better monitoring than this if you were oxygenating at home. This is why I would probably shoot for 94-96% myself.

Coronavirus: Justified Practical Advice Thread

This is a good point, but for what it's worth I don't fully endorse coppering your phone (mine isn't coppered). Several people have anecdotally reported it being uncomfortable or irritating on their hands, or receiving tiny cuts from the copper, etc.

Absorption through skin is incredibly low, but I do take the risk of open (if tiny) hand wounds seriously, and also generally try to reduce my total copper contact in case anything weird does happen, since this is not tested by time.

Coronavirus: Justified Practical Advice Thread

Sorry, forgot to modify this for a virus-specific claim, but yes.

On solid copper, H1N1 decreased by 4 logs in 6 hours in this review; vaccinia and monkeypox viruses were reduced by 6 logs in 3 minutes in this study; murine norovirus was destroyed in 30 minutes in this study, though it doesn't work very well at 4C; and another review says that copper oxide filters neutralize all of "bacteriophages [58-62], Infectious Bronchitis Virus [63], Poliovirus [61,64], Junin Virus [59], Herpes Simplex Virus [58,59], Human Immunodeficiency Virus Type 1 (HIV-1) [11,65-67], West Nile Virus [11], Coxsackie Virus Types B2 & B4, Echovirus 4 and Simian Rotavirus SA11 [68]. More recently, the inactivation of Influenza A [55,65], Rhinovirus 2, Yellow Fever, Measles, Respiratory Syncytial Virus, Parainfluenza 3, Punta Toro, Pichinde, Adenovirus Type 1, Cytomegalovirus, and Vaccinia [65]".

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