Thread by @TxID_Edu

1/18
Going along with @cardionerds Part 1 of 4 (Episode 24), here’s some info regarding #COVID19 treatment

cardionerds.com/episodes/covid…

2/
In your opinion, which medication will be most effective for #SARSCoV2/#COVID19?

3/
There are no FDA approved meds for SARSCoV2/COVID19

Try to get your patients onto a clinical trial so we can learn!

Thus far, treatments have been geared towards viral replications and pro-inflammatory cytokines

4/
Recently, SOLIDARITY trial started enrolling patients into 4 arms:
🐶Remdesivir
🐱Chloroquine/Hydroxychloroquine
🐭Lopinavir/ritonavir
🐹Lopinavir/ritonavir + interferon beta

More info below, along with a nice graphic

sciencemag.org/news/2020/03/w…

5/
Remdesivir
- inhibits RNA-dependent RNA polymerase activity
- Inhibit MERS in human epithelial cells
- only IV

Several trials ongoing

Side effects:
- LFTs
- co-formulation with SBECD, ?renal injury- similar to IV vori

ncbi.nlm.nih.gov/pubmed/32020029

academic.oup.com/ofid/advance-a…

6/
Lopinavir/ritonavir
- protease inhibitor
- with SARS1- lower rate of death and intubation
- coronavirus protease is different that HIV protease
- Kaletra is highly protein-bound, unclear what is getting into alveoli and nasopharynx, requires higher doses in in-vitro trials

7/
@NEJM
lopinavir–ritonavir did not significantly accelerate clinical improvement, reduce mortality, or diminish throat viral RNA detectability in pts with serious COVID19
- ?underpowered
- ?use earlier in disease course

S/E:
GI
Drug drug interactions

nejm.org/doi/full/10.10…

8/
Chloroquine/Hydroxychloroquine (HCQ)

Antiparasitic drugs

HCQ used in RA & SLE

HCQ is only med to improve survival in SLE (keep this in mind)

May interfere with ACE2-R

It's a weak base, may impair acidification of endosomes (interferes with virus trafficking within cells)

9/
Chloroquine/HCQ
- In-vitro data to support MERS & SARS1
- in-vitro against SARS-CoV2

- Notable studies include failure in:
🧙animal models for Ebola
🧙‍♂️human studies for influenza & HIV

S/E
- ⬆️QTc
- careful in myocarditis/cardiomyopathy
- retinopathy, myelosuppression

10/
HCQ+Azithro

Non-randomized, non-controlled study
- 26 pts (6 lost to f/u->3 ICU, 1 died)
- 20 got HCQ, 6 got HCQ+Azithro
-> improved viral clearance

- no S/E report
- no Azithro mono arm
- no long term f/u
- ?clinical meaning

mediterranee-infection.com/wp-content/upl…

11/
Other HCQ studies:

Efficacy of HCQ in pts w/ COVID19: results of RCT
- mild disease; improved time to recovery
- all received O2, antivirals, antibacterials, IVIG, +/- steroids
medrxiv.org/content/10.110…

Pilot RCT HCQ in COVID19
- no diff in outcome
zjujournals.com/med/EN/10.3785…

12/
Tocilizumab
- IL-6 blocker

- damage in 1st phase of disease is mostly from virus,
- damage in 2nd phase is inflammatory

- early immune response is critical to suppressing viral activity
- may have abnormal inflammation if early immunity fails

els-jbs-prod-cdn.literatumonline.com/pb/assets/raw/…

13/
Here's another graphic of the mechanisms of each drug, including Tocilizumab in this figure

aac.asm.org/content/early/…

14/
21 pts with severe COVID19 received Tocilizumab
- improved fever, oxygenation, symptoms, and CT findings

These are prelim findings

🌊Difficult to know at what immune stage & viral control status patients are presenting at

Should be used in RCTs

ser.es/wp-content/upl…

15/
Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury

In fact, it may be harmful!

thelancet.com/journals/lance…

16/
Convalescent Sera
- Ab from #COVID19 pts and give as prophy and/or tx

If for tx, more effective if given shortly after sympt onset

Risk
Known
- inadvertent infxn
- TRALI

Theoretical
- Ab-dependent enhancement of infxn
- attenuate humoral response

jci.org/articles/view/…

17/
Convalescent sera

- 5 critically ill patients
- received IgG
- fever improved, SOFA decreased, P/F ratio improved, viral load decreased

Obviously small sample size, but hopeful!

jamanetwork.com/journals/jama/…

18/
Summary
🔧Get patient in RCT!
🔨Tx geared toward viral replication & pro-inflammatory cytokines
🛠️Damage in 1st phase is from virus, damage in 2nd phase is inflammatory
⛏️Hard to know at what immune stage & viral control status pts are presenting at
🪓Steroids may be harmful

End/
@tony_breu @gradydoctor @CarlosdelRio7 @JenniferSpicer4 @ChidaNatasha @thecurbsiders @COREIMpodcast @CPSolvers @cardionerds @DxRxEdu @mugecevik @rabihmgeha @HannahNamMD @PaulSaxMD @ErinMcCreary