Thread by @hussmanjp

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

Click the lowest "Show this thread" for the latest posts.

Feb 2, Mar 17, and Apr 5 threads collected below to keep them together.

If useful, please RT

https://twitter.com/hussmanjp/status/1246798221160169472

Update 4/27 #SARSCoV2 (#COVID19): Reposting this chart from 4/18 when the U.S. began to depart from the optimistic scenario. That's when it became clear that we were jumping to a different trajectory. Updated chart next.

https://twitter.com/hussmanjp/status/1251506292071501824

Here's the current "optimistic scenario" for the U.S.

Two adjustments define the new trajectory:

1) A longer glide path to zero growth, due to looser containment
2) A larger gap between reported and "shadow" cases due to limited testing capacity.

See prior threads for detail.

This paper on pulmonary care in acute respiratory distress syndrome (ARDS) is quite good (though steroids may have selective use in late-stage COVID19 hyperinflammation).

Some of what's being discovered in #SARSCoV2 overlaps what's been reported in ARDS.
rc.rcjournal.com/content/63/1/9…

https://mobile.twitter.com/hussmanjp/status/1255862510936379393

Andrew Cuomo crushing it on the “reopening” question. One of the most well-informed answers I’ve heard.

Other quotes:

“It is not going down. There is no ‘it.’ We are bringing it down.”

“How can you not wear masks? It’s a sign of respect for other people.”

@NYGovCuomo

5/4/20 Update: #SARSCoV2 (#COVIDー19)

Why are U.S. fatality projections rising?

As I noted a week ago, two features define this

1) A longer glide path to zero growth, due to looser containment
2) A larger gap between reported and "shadow" cases due to limited testing capacity

Why use a mask in public, especially indoors?
1) Lungs are most vulnerable. #SARSCoV2 primarily enters lung cells (ACE2-expressing alveolar), with weak interferon response
2) See also here: medrxiv.org/content/10.110… Airborne virus level has a half-life of >1hr, and ~3h to fall ~85%

I'm actually ok with this strategy in areas where new case totals have persistently declined. But understand what "strict" means. I was once at the intersection of a tiny German street with zero traffic, and NOBODY would cross until the green man went on.
wsj.com/articles/how-g…

Of all the tragic misconceptions surrounding #SARSCoV2 (#Covid_19), the most distressing is the notion that projections about the epidemic curve are somehow independent of our own behavior.

For details, see my full thread, which I started Feb 2, when the U.S. had just 5 cases.

Wrote a paper on #SARSCoV2 (#COVID19)

Cellular and molecular pathways of COVID-19 and potential points of therapeutic intervention

Emphatically, the discussion of therapeutics is not prescriptive. Hoping it will help to support research & critical care.
osf.io/p69g8/

NYC data: 20% of tested residents have #COVID19 antibodies. Even assuming sample is random with no selection bias, 20% of 8.40m residents is 1.68m. 20,934 NYC fatalities would imply a "true" fatality rate of 1.25%.

U.S. pop is 330m. Containment matters.
usnews.com/news/national-…

Just out. "Our findings demonstrate SARS-CoV-2 induces a strong pro-inflammatory cytokine response yet blocks the production of type I and III IFNs."

Yep. Those type-III (lambda) interferons are the first line of defense for respiratory epithelia.
biorxiv.org/content/10.110…

The use of masks is reported to be substantially more effective in reducing #SARSCoV2 (#COVID19) infection than flu or even prior SARS. My impression - b/c SARSCoV2 selectively disables the defense mechanisms of respiratory epithelia, and masks compensate.
medrxiv.org/content/10.110…

Preprint of my paper on #SARSCoV2 (#COVID19) here:

Cellular and molecular pathways of COVID-19
osf.io/p69g8/

Kate Savage (who also did my molecular pathway diagrams for papers in Molecular Autism and Nature) turned my pencil scribbles into this graphic.

Two things #COVID_19 has in common with #Kawasaki
1) Tissue infiltration of proinflammatory CD14+CD16+ monocytes (30239141)
2) Elevated neutrophil-to-lymphocyte ratio, with minimal decline in KD cases refractory to IVIG (28097746).

See my latest paper
osf.io/p69g8/

Table 1 is an eye-opener.
Survivors vs. Nonsurvivors:
Obesity: 26.9% vs 60.9%
Female: 47.1 vs 39.8
Male: 52.9 vs 60.2
White: 67.4 vs 62.8
Black: 8.5 vs 17.2
Hispanic 5.8 vs 9.6
Coronary Disease 11.5 vs 22.1
Diabetes 12.8 vs 21.5
CQ/HCQ (all) 13.7 vs 29.6
thelancet.com/journals/lance…

I hold my face in my two hands.
No, I am not crying.
I hold my face in my two hands
to keep the loneliness warm –
two hands protecting,
two hands nourishing,
two hands preventing
my soul from leaving me
in anger.

~ Thich Nhat Hanh

We knew the likely transmission hubs
We had only a few seed cases
We had tests from WHO enough for that
We just had respond quickly and seriously

Instead, we've lost 100k Americans running a 5th grade science experiment to learn what science already knew

https://twitter.com/hussmanjp/status/1225080391872262144

This is super-crude, and is *not an estimate of real-time reproductive rate Rt. Still, given that growth of total reported cases poorly captures those that remain infective, this may be more sensitive to short-term dynamics. The big plunges followed containment moves in NY and US

Interesting. ApoE4 is a key genetic variant in Alzheimers (found by my colleague Margaret Pericak-Vance, now at the Hussman Institute for Human Genomics @HIHGatUM). Evidently affects COVID-19 susceptibility too, my guess via altered viral endocytosis.
academic.oup.com/biomedgerontol…

"... the main facilitator wasn’t common touch points, such as doors and elevator buttons, but rather common airspace."

Exactly.

This article by @DKThomp is an important, must-read.

Brilliant acronym to limit spread of #SARSCoV2 (#COVID19):

#SAFE

theatlantic.com/ideas/archive/…

Love this acronym from Derek Thompson: #SAFE

If you want biology, aerosolized respiratory droplets carrying #SARSCoV2 preferentially infect airway cells (ciliated, alveolar) & disable their front-line defense (see my thread)

If you want a simple rule, remember #SAFE

@DKThomp

Added a section to my #SARSCoV2 (#COVID19) paper to address some recent clinical findings, including #Kawasaki-like symptoms in pediatric cases. See:

8. Adhesion and tissue retention of inflammatory leukocytes: osf.io/p69g8

Yesterday, the U.S. had the highest number of new #SARSCoV2 cases since this pandemic started, and over 1000 U.S. fatalities. Worth emphasizing again - the primary transmission mode is shared airspace, particularly indoors. Please take mask use seriously.
medrxiv.org/content/10.110…

Good paper on balancing public health and economic impacts of containment. One result is robust to weighting, and underscores why we got >100K fatalities AND a deep recession:

Optimal response starts as soon as possible, and is as strong as possible.

medrxiv.org/content/10.110…

Good paper on #COVID19 transcriptome network:
biorxiv.org/content/10.110…

Aligns nicely with my pathway paper emphasizing IL-6/TNF axis, Th1/Th17 activation, with migration (e.g. CXCL8), adhesion (e.g. ICAM-1), and tissue damage via inflammatory leukocytes: osf.io/p69g8/

Worth repeating. The reason for BOTH enormous U.S. #COVID19 fatalities AND deep economic disruption was the weak and dismissive early response to the pandemic.

Remembering this may be important a few months from now (the smartest public health researchers I know suggest Oct).

Yep. The weak, dismissive early response amplified fatalities and necessitated far harder lockdowns later.

“Between 70% and 99% of the Americans who died from this pandemic might have been saved by measures demonstrated by others to have been feasible.”
statnews.com/2020/06/19/fas…

Early GWAS results #COVID19. Notably, 3p21.31 locus is loaded w/regulators of priming, migration & tissue retention of cytotoxic CD8+ and Th lymphocytes (CXCR9, XCR1, CCR9). ABO also predictive in CD8+ lymphoma.

(Why this matters: osf.io/p69g8/)

https://twitter.com/EricTopol/status/1273364492504588288

Yep. Top hub genes in #SARSCoV2: IL6, CXCL8, IL1B, STAT1, MMP9, TLR2, CXCL1, ICAM1, CSF2, IFIH1, NFKBIA, DDX58, MX1, MMP1, PI3, SAA1, BST2, LCN2, EDN1, STAT5A, C3, SOD2, LIF, and HBEGF. CSF2 (GM-CSF) isn't similarly altered in other viral infections. biorxiv.org/content/10.110…

Across 22 countries, there's an 80% correlation between non-wearing of masks and number of deaths-per-million. That correlation is higher than for the percentage of elderly and the percentage with high body-mass index. Critical when/where growth is high.
medrxiv.org/content/10.110…

For those who are (or may be) vitamin D deficient, I actually believe this. We know vitamin D deficiency is often observed in severe COVID-19, and calcitriol binding is important in TLR-mediated inflammation. Not a cure but makes sense to avoid deficiency.
biorxiv.org/content/10.110…

Cell damage in #COVID19 (see also 8 in my paper).

"Faced with aggression of alveolar epithelial cells by SARSCoV2, capillary-alveolar endothelial cells receive a rain of cytokines (IL-1, IL-6, TNF-a) promoting activation and inducing ICAM-1 via (NFκB)."
medrxiv.org/content/10.110…