1/ #COVID19 #Tweetorial, calling #MedStudentTwitter / #medtwitter to help search the literature as we refine treatment protocols @YaleMedicine @The_BMC @Pranay_md @KaminskiMed for the benefit of all.
Background: We need to tackle antiviral and hyperinflammation pathoimmunology
Background: We need to tackle antiviral and hyperinflammation pathoimmunology
2/ Given no known efficient therapy, chloroquine was investigated given its prior described inhibition of several coronaviruses. This became a backbone of therapy (pubmed.ncbi.nlm.nih.gov/32171740/). Chloroquine is not readily available in the US at this time.
3/ Hydroxychloroquine (in vitro) was shown to reach 3x the potency of chloroquine (pubmed.ncbi.nlm.nih.gov/32150618/). More readily available in the US. Retinal toxicity of HCQ at the very short intervals we use for COVID19 is unlikely. Trials in South Korea and China are ongoing.
4/ Clinical trials in the US are focused on remdesivir (adapted use from Ebola work) as well as a vaccine (NCT04283461). In terms of anti-virals, ritonavir/lopinavir is utilized at some centers while MDs wait on remdesivir (if patient meets criteria for remdesivir use).
5/Inflammation is driven by many cytokines including IL-6. Pre-print data from 21 patients in China (Xu et al. chinaXiv:202003.00026v1) utilizing tocilizumab (IL6-R inhibitor) showed improvements in multiple parameters with 90.5% discharged ~13.5 days after treatment with toci: 
6/For those who will not respond to HCQ + an anti-viral + toci, we need to think ahead to additional options ala clinical trial. Here are the three different modes of IL-6 signaling from Garbers et al. (doi:10.1038/nrd.2018.45):
7/ This is why repurposing JAK inhibitors with particular interest on JAK1 selective inhibition (JAK2 and JAK3 are not significant parts of IL-6 signaling) is an interest @YaleIMed @YaleCancer. Agents like ruxolitinib, tofacitinib are accessible.
8/ We are also interested in therapies beyond IL6 that can additionally help with the ARDS component. NCT04275414 is looking at the VEGF inhibitor bevacizumab (note: VEGF levels often do not predict response to bev in other disorders).
9/One can see how a potential regimen like HCQ + antiviral + toci +/- selective JAK inhibition vs an agent like bev outside of the IL6 pathway then comes to be. @CGhaznavi @AnnaGoshua as a start can we harness #MedStudentTwitter to review the following questions at this time:
10/
1) Review of data on selective JAK inhibitors including ruxolitinib and tofacitinib (with a focus on JAK1) in HLH OR cytokine release syndrome
2) Review of data on ARDS and anti-VEGF therapy
To our med students: thank you for all you do, always. @YaleIM_Chiefs
1) Review of data on selective JAK inhibitors including ruxolitinib and tofacitinib (with a focus on JAK1) in HLH OR cytokine release syndrome
2) Review of data on ARDS and anti-VEGF therapy
To our med students: thank you for all you do, always. @YaleIM_Chiefs
11/
@CGhaznavi has a spreadsheet open for those able to contribute.
docs.google.com/spreadsheets/d…
Additional request (updating in real time):
3) Review of data on TNFalpha inhibitors in HLH OR cytokine release syndrome
@CGhaznavi has a spreadsheet open for those able to contribute.
docs.google.com/spreadsheets/d…
Additional request (updating in real time):
3) Review of data on TNFalpha inhibitors in HLH OR cytokine release syndrome
