1/n Our Collaborative "Single-Cell Omics Reveals Dyssynchrony of the Innate & Adaptive Immune System in Progressive #COVID19" paper is now on @medrxivpreprint. We provide @10xGenomics #scRNAseq, #Cite, #TCRseq & #BCRseq: my nonimmunologist's tweets follow medrxiv.org/content/10.110…
2/n As expected, type-1 IFN signature dominates all cell types (with a uniquely IFN-activated CD8 T cell cluster). The signature correlates strongly with initial viral load and in repeated samples with time #COVID19 #Covid19CellAtlas medrxiv.org/content/10.110…
3/n A skewed immunopralysis like anti-inflammatory signature is found in monocytes of #COVID19 progressive patients, connectome analysis suggested disrupted connectivity between LAG3 and MHC signalling medrxiv.org/content/10.110…
4/n Using #Citeseq and flow cytometry-based validation
we found increase of a unique activated T cell population marked by higher expression of HLADR, CD38, and KI67 with a pre-terminally exhausted T cell signature in progressive #COVID19 patients
medrxiv.org/content/10.110…
5/n Single-cell T cell receptor repertoire analysis reveal a skewed clonal distribution of CD8 T cells with #COVID19 specific CDR3 regions medrxiv.org/content/10.110…
6/n Single Cell B-Cell Receptor repertoire provided evidence of a primary B cell response with possible contribution from memory B cells in #COVID19 @skleinstein @NimaNouri_NN medrxiv.org/content/10.110…
7/n You don't need to be a bioinformatician - the #CovidCellAtlas website courtesy of @life_of_carlos allows exploring gene expression information by cell type, across #COVID19 disease states & time-course - look for your favorite genes & cells!! covidcellatlas.com
8/n Taken together, Our results reveal a dyssynchrony of innate and adaptive immune interactions in progressive #COVID19, which may contribute to delayed virus clearance & have implications for therapeutic interventions #CureCovid19 #ImmuneDyssynchrony
medrxiv.org/content/10.110…
9/n Proud of Drs. Unterman, Sumida, Nouri, Yan for driving this collaborative, the generous & selfless contributions by so many other team members & grateful to Drs Iwasaki, Ko, Dela Cruz, Montgomery, Shaw & Hafler for the @YaleMed #COVID19 biorepository medrxiv.org/content/10.110…

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More from @KaminskiMed

8 Jul
1/n The #IPFCellAtlas is finally out! We profiled 312,928 cells from 32 IPF, 28 controls, 18 COPD lungs using @10xGenomics #scRNAseq & identified previously unidentified populations of epithelial & endothelial cells enriched in IPF #CureIPF advances.sciencemag.org/content/6/28/e…
2/n Among epithelial cells, we identified cells DISTINCT from ANY epithelial cells previously described in human lungs. These aberrant basaloid cells are at the edge of myofibroblast foci & express fibrotic molecules & regulators #IPFCellAtlas #CureIPF advances.sciencemag.org/content/6/28/e…
3/n Among enodthelial cells we discovered a previously undescribed population of COL15A1+ CD31+ cells. They are usually restricted to the airway but in IPF are found in the lung parenchyma - what are they doing there? #IPFCellAtlas #scRNAseq #CureIPF advances.sciencemag.org/content/6/28/e…
Read 9 tweets
4 Jul
1/n Dr. Mark Siegel is a superb critical care physician, ethicist & legendary Internal Medicine Residency Program Director whose weekly notes I read eagerly. This week’s note is titled “what I’d say to new interns” #MarksWisdom #TipsForNewDocs #MedEd
facebook.com/1444114056/pos…
2/n Siegel starts saying #COVID19 took away joys of orientation: pizza, hot dogs, cold beer, gelato, unscripted conversations & new friendships. But don’t worry, show up, work hard, don't worry, you'll do great & then follows with 14 SPECIFIC TIPS: #MarksWisdom #TipsForNewDocs
3/n Tip #1: Take your own histories. Charts are rife with inaccurate, missing information. Key exposures, mounting symptoms, details patients held back- until you asked. To paraphrase Osler, patients will tell you the diagnosis, if you listen. #MarksWisdom #TipsForNewDocs #MedEd
Read 16 tweets
23 Jun
1/n This is a thread about microRNA therapeutics in pulmonary fibrosis summarizing the MiRagen call today - we've been collaborating for >6 years now through an NIH-NHLBI funded CADET II grant to develop mir-29 as a therapy - the progress is amazing! #CureIPF #Mir29
2/n And first and most important is the patient: Teresa Barnes, a patient advocate, speaks about the unmet need of highly specific and effective therapies in IPF #PeopleILookUpTo #CureIPF #CurePF #MircroRNATherapies #Mir29
3/n Rusty Montgomery @rmontonio of MiRagen: The Mir-29 mimic Remlarsen has hit fibrosis targets in a phase 1 trial of Keloid formation - a phase II trial is happening #AntiKeloid #CureScarring
Read 8 tweets
30 May
Reopening thread to our patients 1/8 (relevant also friends, neighbors, family, peers, all) - many years ago, a veteran of many wars told me that the days of ceasefire were very dangerous. This was because precautions were lifted but risk was still there (see next) #COVID19
Reopening thread to our patients 2/8 - During ceasefires soldiers & civilians are often injured because they let down their guards, while local commanders are not aware of ceasefire or simply disregard it. Do not let your guards down - #COVID19 is not gone yet #KeepSafe
Reopening thread to our patients 3/8 - The decision to open up now is operational and involves risk. There is nothing magical about June 1 - #COVID19 does not read the calendar & is not involved in local politics. The Pandemic is not over yet. Maintain your precautions
Read 8 tweets
20 Apr
1/n Our teams at @YalePCCSM are awestruck by the courage and esprit de corps exhibited by so many of our @YaleMed colleagues that have joined forces with us to help care for the increasing numbers of critically ill #COVID19 patients in our units medicine.yale.edu/intmed/news-ar…
2/n We feel that the commitment and dedication exhibited without hesitation by so many of our colleagues who do not regularly care for medically critically ill patients need to be highlighted medicine.yale.edu/intmed/news-ar…
3/n Leaving your comfort zone is no easy task in normal times. But to be able to do it in the face of stress, uncertainty and even potential personal risk is simply nothing short of heroic.#COVID19 #Solidarity #Heroes
Read 5 tweets
15 Mar
1/n Dr. Mark Siegel is a superb critical care physician, ethicist, colleague & a legendary Internal Medicine Residency Program director whose weekly note I read eagerly. I tuned this week' note: #wellness in times of #COVID19 into a #weetorial #MarksWisom facebook.com/mark.d.siegel.…
2/ First 4 are about continuing to live: Eat. Sleep. Exercise. Socialize. At times of crisis we tend to consider these luxuries - they are not. They are fuels that keep us effective as physician, during normal or abnormal situations #StaySafe but #KeepLiving #MarksWisdom
3/ #StaySafe basics: Wash your hands long & often! Clean your phones with appropriate wipes. Avoid crowding in work room. Never, ever go into to a possible #COVID19 room without PPE, even in emergencies. Carefully don and doff PPE & ask if concerned #wellness #MarksWisdom
Read 8 tweets

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