Thread by @hussmanjp

THREAD: Extending the #SARSCoV2 (#COVID_19) thread I started on Feb 2nd (when U.S. had only 5 cases).

As I noted on 2/3, every new case in every new location is local "patient zero." Partial containment + mobility = spread

Click lowest "Show this thread" for latest. Please RT

https://twitter.com/hussmanjp/status/1239859310588461058

Here's the boostrap projection model I began posting weeks ago, when global fatalities were 12,000, with U.S. 300

Outside U.S., "observed" case fatality rate (CFR) is now above 6%, b/c reported cases are a fraction of total. Fatalities still predictable.

https://twitter.com/hussmanjp/status/1241353202718715905

In the U.S., the notion of 100,000 fatalities "ultimately" or "in the coming months" reflects (my view) incomplete modeling of "shadow" case dynamics, and lag structure between initial case report and fatalities. We risk 100k within weeks without a shift in therapeutic modality.

With respect to therapeutic modality, my impression is that part of the reason #SARSCoV2 (#COVID_19) is so lethal is that molecular interventions UPON ICU ENTRY, should be extended from pulmonology to rheumatology as well. Posting my updated pathway notes for research community.

Snapshot:
a) Weakly contained states, along with mobility, are propagating spread for the entire U.S.
b) Ventilators (high fatality) aren't silver bullets
c) Nor is HCQ, though it may act as DMARD
d) Asking for NIH/NIAID guidance centered on T-lymph inflamm

A friend shared this.

One way we can gauge the impact of containment is to monitor the projected dates of various catastrophic outcomes (1m U.S. cases, 100k fatalities) using a dynamic model.

Cuomo's early action stopped the future rushing toward us. We're still pushing it back, but not fast enough.

New (pre-publication) references regarding the IL6 inflammatory axis in #SARSCoV2 (#COVID_19). See my threads for molecular pathway notes.
4/3/20: medrxiv.org/content/10.110…
4/4/20: medrxiv.org/content/10.110…
I'll say it again. We need to shift focus to suppressing the cytokine storm.

Estimated an optimistic #SARSCoV2 (#COVID_19) scenario. Requires case growth to fall by half in coming week, to near zero by 4/30. This is a *continued high-containment, low mobility scenario.

When people suggest *new cases could "peak" in next 10 days, it would look like this.

Sharing a notable contraindication for #Hydroxychloroquine in metformin users (JHU). Synergy can result in fatal toxicity. Also note small but important risk of retinal damage more generally. HCQ may be useful, but it's not a magic bullet. See other posts
biorxiv.org/content/10.110…

Why interim @NIH / NIAID guidance on repurposed therapeutics urgent for #SARSCoV2 (my views lean to inflammatory T-cell axis - see thread). Among approaches to-date, corticosteroids most common (which literature broadly discourages) & HCQ risks arrhythmia.
medrxiv.org/content/10.110…

New pre-publications relating to the IL-6/TNF-a axis in #SARSCoV2 / #COVID_19 (all for ICU, not home prophylaxis):
1) medrxiv.org/content/10.110…
2) medrxiv.org/content/10.110…
3) biorxiv.org/content/10.110…
4) medrxiv.org/content/10.110…
5) medrxiv.org/content/10.110…
6) medrxiv.org/content/10.110…

Update #SARSCoV2 (#COVIDー19) April 7 estimates. The hopeful news here is U.S. case growth has slowed to ~10% daily, fatalities to ~17%, and "shadow case" estimate to ~14%. My concern is that people may not realize that this progress is wholly dependent on sustained containment.

Based on reported cases, global #SARSCoV2 (#COVIDー19) CFRs now reaching 6% or higher. While this inexorable rise implies more "shadow" cases than are actually reported, this gap doesn't reduce projected fatality *numbers* b/c the ascertainment ratio drops out (see my thread).

My impression remains that the most plausible way to blunt fatalities in #SARSCoV2 (#COVIDー19) is to focus on suppressing hyperinflammation along the IL-6/TNF-a axis. Distressing that a survey of ICUs indicates steroids being used first-line despite contrary evidence. My notes:

Update #SARSCoV2 (#COVIDー19)
4/9/20: A hopeful sign, a caveat, a warning, and an appeal.

The hopeful sign: thanks to containment efforts, daily growth rates have eased to 9% (cases), 12% (estimated "shadow" cases), and 15% (fatalities). Chart should bend toward logistic shortly

4/9/20 #SARSCoV2 (#COVIDー19) update

Next, the caveat: One way to estimate the impact of containment efforts to estimate the expected date of various outcomes using an adaptive model. It is only *continuing containment effort that prevents the future from rushing back toward us.

4/9/20 #SARSCoV2 (#COVIDー19) update

Next, the warning: Even with a desperately needed flattening of the curve from exponential to logistic, even a peaking of daily new cases this week would imply that most U.S. fatalities are *ahead. For that reason...

https://twitter.com/hussmanjp/status/1247167822507192320

4/9/20 #SARSCoV2 (#COVIDー19)

The appeal: we came to this crisis w/ a rich volume of research on prior CoV serotypes. Connecting dots of available research, ICUs need @NIH interim guidance, beyond pulmonology, addressing IL6/TNFa/Th17 inflammatory axis (w/prelim ORs from RCTs).

4/9/20 Updated estimate of the plausibly optimistic scenario. Growth rates assume that new daily cases peak on Monday 4/13.

When we talk about "flattening the curve," this is what it might look like. Please don't assume the word "peak" means containment efforts can be relaxed.

Ending the day with some hopeful news. While it's difficult to see from actuals, sustained containment efforts have been slowing the growth rate of #SARSCoV2 (#COVIDー19) cases and fatalities, from 25-30% daily in March, to 8-14% today. Projected curve finally starting to bend.

I posted my 4/3/20 #SARSCoV2 (#COVID19) research correspondence to the Foundation website.

Notes on SARS-CoV-2 (COVID-19) inflammatory pathway, and rationale for interim clinical guidance on repurposed therapeutics (possibly on the IL-6/TNF/Th17 axis).

hussmanfoundation.org/articles/SARSC…

Even w/sustained containment efforts, *most U.S. fatalities are likely ahead, unless the therapeutic response in ICUs more directly considers the inflammatory pathway (IL6/TNF-a/Th17/IL17).

My 4/3 memo to research colleagues and NIH/NIAID here. Please RT
hussmanfoundation.org/articles/SARSC…

Reported global #SARSCoV2 (#Covid19) cases just passed 2 million. Given that a case is reported, the fatality rate of those reported cases is now 6-7.5%. The inexorable rise in the CFR reflects an increasing ratio of unreported (possibly subclinical) cases to reported ones.

Assuming sustained containment efforts, the "optimistic" projection (my adaptive model) suggests that U.S. daily new cases may have peaked. This does NOT mean these efforts can now be abandoned. Most U.S. fatalities are still ahead, and we still lack capacity to test/track/trace.

Damn. This isn't good. U.S. fatalities just jumped off book. We shouldn't see 31,000 yet.

My hope (if it's possible to hope for such things) is this reflects a lump-sum adjustment for non-ICU fatalities, not a shift in trajectory.

Either way, we have more cases than we thought

Yes, I think *provided sustained containment efforts (patience...) the number of new daily cases has peaked. My concern, and the reason for patience (for now) is that even in the optimistic scenario, #COVID19 HAS A LONG FAT TAIL. It's not like a storm that's just passed overhead.

Simple, but important. Worth embedding these in the #SARSCoV2 (#COVID_19) thread.

https://twitter.com/AndrewPGregory/status/1241055854687735808

cnn.com/2020/04/14/hea…

cnn.com/2020/04/14/hea…

Update 4/18/20 #SARSCoV2 (#COVID_19)

So much for the optimistic scenario.

We're way off book. I had hoped this was just a one-time adjustment.

Understand this: PEAK daily new cases in a containment scenario is also PEAK infectivity if containment is abandoned at that moment.

… thus continuing a crisis response that is nearly indistinguishable from manslaughter.

This is like throwing gasoline on an inferno the very moment firefighters begin to get the blaze under control.

See thread since Feb 2, when we had only 5 cases.

https://twitter.com/realDonaldTrump/status/1251169217531056130

When the history of #SARSCoV2 (#COVID_19) is written, the Santa Clara study will be used as a case study in ascertainment bias, representativeness, and extrapolation.

You don't think a Facebook ad offering serologic testing won't enrich 1.5% of your sample with actual cases?

A Scottish study similar to Santa Clara sampled donated blood. 4/6 positive cases were drawn from the Edinburgh Health Board area.

They wisely concluded "we cannot use the rise in numbers seropositive to infer the contemporary seropositive or the growth rate of the epidemic."

A useful article on designing informed seroprevalence sampling to estimate population infections. With a sample of 3330, the 1.5% prevalence in the Santa Clara study can't exclude zero from its confidence interval. Sample representativeness is an issue.
medrxiv.org/content/10.110…