Jen Herman 🌪️ Profile picture
Associate Professor of Biochemistry & Biophysics. Transparency & rigor in scientific process 😍. Accelerates on turns. https://t.co/lGSIocYz5N
7 May
"...it is crucial that we establish the pathways involved in the different stages of the inflammatory response to SARS-CoV-2 and determine the contribution of these pathways to ultimate disease outcome."
1/ Possible pathways based on knowns
Stage I - Viral entry into upper airway

IFN-λ response restricts viral replication to upper airway
1) Virus cleared early
2) Virus kept in check until seroconversion (~7-10 days)
Asymptomatic or mild outcome.
ncbi.nlm.nih.gov/pubmed/31821443
2/
Stage 2 - Virus enters lower airway

Could occur 2 ways:
1) Directly, through inhalation
2) If patient has IL-17A mediated inflammation in airway (thread) at time of infection, then IFN-λ⬇️- virus can replicate to higher titer
jimmunol.org/content/201/8/…
Read 9 tweets
2 May
1/ thread on ARDS, innate lymphoid cells, & IL-17A

IL-17A stimulates production of other pro-inflammatory cytokines, including IL-6, IL-8, G-CSF, MCP-1, & TNF-a & promotes macrophage & neutrophil recruitment. Image
2/
ILC2s are plastic & can switch b/w pro or anti-inflammatory forms. Inflammatory ILC2s are the major source of IL-17A in mouse ARDS model. In this paper, designated as pILC3s (c-kit+).

atsjournals.org/doi/full/10.11…
3/ ILCs can be tissue resident (go to tissue during fetal development and stay) & are found in different places around the body like the gut, respiratory tract, skin, kidney, brain, & heart.
Read 9 tweets
5 Apr
1 approach to understanding #covid19 infection is to examine co-morbidities & ask what's common?

Most prevalent Cov19 co-morbs:

1)↗️age
2)Hypertension
3)Diabetes
4)Cardiovascular disease
5)Kidney disease
6)Chronic respiratory disease (esp COPD)
8)Cancers
9)BMI>40
10)♂️>♀️ ImageImageImageImage
2/
These are diverse diseases & increasing age technically not a disease at all. However, there is at least 1 factor in common among all of the co-morbidities identified thus far:

INFLAMMATION
3/
A survey of the co-morbidities revealed another commonality; a close association w/ dysregulation of the pro-inflammatory, neutrophil-recruiting cytokine, IL-17A.

IL-17A is made by multiple immune cell types, including lung-resident innate lymphoid cells (ILC3s).
Read 35 tweets