Coronavirus/COVID-19 ARDS Protocol

As you know, most people who contract coronavirus/COVID-19 experience a flu-like illness. A percentage of suffered will develop pneumonia and a percentage of those will develop ARDS/ALI. ARDS has about a 50% mortality which would be expected to increase in a pandemic situation where resources become scarce.

The sample’s overall case-fatality rate was 2.3%, higher than World Health Organization official 0.7% rate. No deaths occurred in those aged 9 years and younger, but cases in those aged 70 to 79 years had an 8% fatality rate and those aged 80 years and older had a fatality rate of 14.8%.

ARDS is not well understood, but the leading understanding is acute lung injury is caused by a combination of pro- inflammatory cytokine cascade, high FIO2 exposure, and barotrauma.

Leading experimental measures which may amiliorate ARDS and maximize survival:

1. Limit high FIO2 exposure, increase PEEP

2. Low tidal volumes and increased frequency.

3.Program vent with regular (10/hr) sigh breaths (2xVT) to aid recruitment. 

3. Early tracheostomy.

4. Sedation with Precedex (dexmedetomidine).

5.Taurine infusion or NAC (antioxidant)

6. Treatment with ARB (angiotensin 2 blocker).  Coronavirus binds to and enters cells via AT2 receptor and early studies with SARS/MERS/CoVID-19 show benefit with ARBs.  

7. Kaletra effective for SARS/MERS/CoVID-19

8. Actemra, IL-6 

https://www.nature.com/articles/d41587-020-00003-1

ARBs in SARS/MERS/COVID-19

https://www.bmj.com/content/368/bmj.m406/rr-2

Vitamin C: 500mg as good as 2000mg

https://www.ncbi.nlm.nih.gov/m/pubmed/8317379/

Vitamin C Infusion didn't help ARDS/ALI

https://jamanetwork.com/journals/jama/article-abstract/2752063

Coronavirus Source

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797993/

"Experiments with the full length and chimeric SHC014 recombinant viruses were initiated and performed prior to the gain of function research funding pause and have since been reviewed and approved for continued study by NIH."

Level 3 lab at the University of North Carolina at Chapel Hill together with the Level 4 lab in Wuhan are responsible for creating a chimera/hybrid virus that showed increased human infectivity. This reasearch was funded by NIH and China. This virus was accidentally or not accidently released from Wuhan level 4 labs.  The level 4 designation is based on the Chinese lab's work with bioweapons but not based on precautions taken. The following paper demonstates examples of lax precautions and accidental contaminations at Wuhan lab.

https://www.scribd.com/document/447056518/Originsof2019-NCoV-XiaoB-Res

This coronavirus seems to target a race-specific Angiotensin 2 receptor polymorphism (+1166 C allele). 

https://www.nature.com/articles/hr2010156

https://www.nature.com/news/engineered-bat-virus-stirs-debate-over-risky-research-1.18787

Therapeutics

https://www.ncbi.nlm.nih.gov/m/pubmed/29557770/

https://www.medscape.com/answers/300455-107917/which-medications-are-used-for-the-treatment-of-coronavirus-pneumonia

https://www.biorxiv.org/content/10.1101/2020.01.24.915157v1.full.pdf

Co2019 is most similar to Bat-SARS-Co2015

https://www.nature.com/articles/nature12711

Interesting that coronavirus binds to the angiotensin 2 receptor.  AT2 is one of the most studied receptors in science. When I was in grad school, the lab next door did AT2 work (Dr. Terry S. Elton). The receptor has been fully sequenced, cloned, and is known to have several ethnic dna sequence polymorphisms. 

Also interesting that there is currently a global recall of ARBs or angiotensin receptor binding medications which have been shown to convey significant protection from the coronovirus. (Losartan, Telmisartan)

https://www.bmj.com/content/368/bmj.m406/rr-2

Vitamin C: 500mg as good as 2000mg

https://www.ncbi.nlm.nih.gov/m/pubmed/8317379/

Vitamin C Infusion didn't help ARDS/ALI

https://jamanetwork.com/journals/jama/article-abstract/2752063