肺の細胞分析と臨床指針

新型コロナウィルスの後遺症の頻度で一番高いのが
息切れ、せきなどの呼吸器系の疾患です。
おおよそ3%程度で、重症になると頻度が顕著にあがります(2)。
新型コロナウィルスの治療を考える場合には
通常は入院した人に対してであり、
かつ重症の人の比重が高いですから、
ICUに入った後、後遺症として肺に疾患を抱える確率は
上述した3%よりも顕著に高い数字だと考えられます。
ー
新型コロナウィルスはインフルエンザや肺炎など
他の呼吸器系疾患に比べて、
炎症性サイトカインであるIL-1β、IL-6の分泌量が
マクロファージ、単球、上皮細胞から
顕著に多くなっています(Ref.(1) Fig.3k.iより)。
ー
また肺(肺胞)の組織の修復に関わる
AT1、AT2の細胞は新型コロナウィルス感染で少なくなっています(1,3)。
マクロファージも含めて、
肺胞の組織の修復に関わりますが、
上述したIL-1β、IL-6が多くなると
肺が線維化しやすくなります。
(Ref.(1)Extended Data Fig.12kより)
ー
従って、IL-1β、IL-6の分泌を抑えることで
肺の線維化を阻止する事ができ、
肺胞の組織の損傷を緩和できる可能性があります。
これは非常に重要な情報です。
従って、
レムデシビルや今後開発される抗ウィルス薬を投与しながら
これらのサイトカインを抑える薬を投与することで
肺のダメージを減らせる可能性があります。
すでに
レムデシビルとバリシチニブは
人工呼吸器が必要な重症患者において効果がある事が示されています(4)。
このバリシチニブは
Janus kinase (JAK) 1 and 2に作用して
interleukin-2, interleukin-6,  interleukin-10,  interferon-γ, 
granulocyte–macrophage colony-stimulating factor
に作用すると言われています(4)。
従って、IL-6を含みます。
このRef.(4)Figure.2を見ると
短期間では差が表れにくくなっています。
これを1日でも、1時間でも早めるためには
肺胞に送ることが目的ですから
吸引式の薬剤はどうか？という提案があります。
あるいは身体の循環から
肺胞に速く、効率的に届くルートを考えるという事です。
そうなるとタブレットではなく注射ということになります。
あるいはタブレットでも粉末の方が代謝が早ければ
それを検討する事もできます。
これは下のAnakinraに対してもいえます。
薬剤を作用させたいのは肺胞です。
ー
IL-1βに関しては
Anakinraがアンタゴニストとして働き、
大規模な調査の価値を示しています。
Ref.(5)のTable1を見ると
Anakinra投与後に大きく変わっているのが
フェリチンの量です。
慢性貧血の場合にこの数字が上がりますが、
投与後に血流の状態が変わっている可能性があります。
高ビリルビン血症も解決されています。
ビルビリンの循環が悪くなると高くなるので
肝臓、腸、腎臓などを通した
循環器、血流に関係すると考えられます。
ただし血栓を示すタンパク質のDダイマーが
投与後、顕著に上がっています。
投与を中断したらDダイマーが下がっているので
ひょっとするとこの薬は
副作用として血栓があるかもしれません。
このIL-1βの抑制はRef.(1)からは
肺胞の組織の修復にあたるAT1の生成に貢献するはずなので
投薬した時にそれが達成されているか？
これが臨床においても重要です。
ー
抗ウィルス薬、IL-6、IL-1βを抑制するような
3つの薬の併用とヘパリンなどの循環器の維持など
が臨床としての選択肢に入ってくると考えられます。
その時にできれば
肺胞のAT1とAT2の細胞の量が健常者に近づいているか？
その評価ができれば好ましいです。

(Reference)
(1)
Johannes C. Melms, Jana Biermann, Huachao Huang, Yiping Wang, Ajay Nair, Somnath Tagore, Igor Katsyv, André F. Rendeiro, Amit Dipak Amin, Denis Schapiro, Chris J. Frangieh, Adrienne M. Luoma, Aveline Filliol, Yinshan Fang, Hiranmayi Ravichandran, Mariano G. Clausi, George A. Alba, Meri Rogava, Sean W. Chen, Patricia Ho, Daniel T. Montoro, Adam E. Kornberg, Arnold S. Han, Mathieu F. Bakhoum, Niroshana Anandasabapathy, Mayte Suárez-Fariñas, Samuel F. Bakhoum, Yaron Bram, Alain Borczuk, Xinzheng V. Guo, Jay H. Lefkowitch, Charles Marboe, Stephen M. Lagana, Armando Del Portillo, Emmanuel Zorn, Glen S. Markowitz, Robert F. Schwabe, Robert E. Schwartz, Olivier Elemento, Anjali Saqi, Hanina Hibshoosh, Jianwen Que & Benjamin Izar 
A molecular single-cell lung atlas of lethal COVID-19
Nature (2021)
ー
Author information
---
Author notes
These authors contributed equally: Johannes C. Melms, Jana Biermann, Huachao Huang, Yiping Wang, Ajay Nair, Somnath Tagore, Igor Katsyv, André F. Rendeiro, Amit Dipak Amin
These authors jointly supervised this work: Robert E. Schwartz, Olivier Elemento, Anjali Saqi, Hanina Hibshoosh, Jianwen Que, Benjamin Izar
---
Affiliations
Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA
Johannes C. Melms, Jana Biermann, Yiping Wang, Amit Dipak Amin, Meri Rogava, Sean W. Chen, Patricia Ho & Benjamin Izar
Columbia Center for Translational Immunology, New York, NY, USA
Johannes C. Melms, Jana Biermann, Yiping Wang, Amit Dipak Amin, Meri Rogava, Sean W. Chen, Patricia Ho, Adam E. Kornberg, Arnold S. Han, Emmanuel Zorn & Benjamin Izar
Columbia Center for Human Development and Division of Digestive and Liver Diseases, New York, NY, USA
Huachao Huang, Yinshan Fang & Jianwen Que
Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
Huachao Huang, Ajay Nair, Aveline Filliol, Yinshan Fang, Robert F. Schwabe & Jianwen Que
Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA
Somnath Tagore
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
Igor Katsyv, Jay H. Lefkowitch, Charles Marboe, Stephen M. Lagana, Armando Del Portillo, Glen S. Markowitz, Anjali Saqi & Hanina Hibshoosh
Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
André F. Rendeiro & Olivier Elemento
Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
André F. Rendeiro, Hiranmayi Ravichandran, Niroshana Anandasabapathy & Olivier Elemento
Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA
Denis Schapiro
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Denis Schapiro & Chris J. Frangieh
Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, Cambridge, MA, USA
Chris J. Frangieh
Department of Cancer Immunology and Virology, Dana-Farber Cancer Center, Boston, MA, USA
Adrienne M. Luoma
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA
Hiranmayi Ravichandran
WorldQuant Initiative for Quantitative Prediction, New York, USA
Hiranmayi Ravichandran & Olivier Elemento
Human Immune Monitoring Core, Columbia University Irving Medical Center, New York, NY, USA
Mariano G. Clausi & Xinzheng V. Guo
Department of Medicine, Division of Pulmonary and Critical Care, Massachusetts General Hospital, Boston, MA, USA
George A. Alba
Cell Circuits, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Daniel T. Montoro
Systems Biology, Harvard Medical School, Boston, MA, USA
Daniel T. Montoro
Department of Ophthalmology, University of California San Diego, La Jolla, CA, USA
Mathieu F. Bakhoum
Department of Dermatology and Meyer Cancer Center, Weill Cornell Medical College, New York, NY, USA
Niroshana Anandasabapathy
Department of Genetics and Genomic Science and Department of Population Health Science and Policy, Icahn School of medicine at Mount Sinai, New York, NY, USA
Mayte Suárez-Fariñas
Human Oncology and Pathogenesis Program and Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Samuel F. Bakhoum
Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
Yaron Bram & Robert E. Schwartz
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
Alain Borczuk
Department of Medicine, Weill Cornell Medicine, New York, NY, USA
Alain Borczuk
Institute of Human Nutrition, Columbia University, New York, NY, USA
Robert F. Schwabe
Herbert Irving Comprehensive Cancer Center, New York, NY, USA
Jianwen Que & Benjamin Izar
Program for Mathematical Genomics, Columbia University, New York, NY, USA
Benjamin Izar
ーーー
(2)
Ziyad Al-Aly, Yan Xie & Benjamin Bowe 
High-dimensional characterization of post-acute sequalae of COVID-19
Nature (2021)
ー
Author information
Affiliations
Clinical Epidemiology Center, Research and Development Service, VA Saint Louis Health Care System, Saint Louis, MO, USA
Ziyad Al-Aly, Yan Xie & Benjamin Bowe
Veterans Research and Education Foundation of Saint Louis, Saint Louis, MO, USA
Ziyad Al-Aly, Yan Xie & Benjamin Bowe
Nephrology Section, Medicine Service, VA Saint Louis Health Care System, Saint Louis, MO, USA
Ziyad Al-Aly
Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA
Ziyad Al-Aly
Institute for Public Health, Washington University in Saint Louis, Saint Louis, MO, USA
Ziyad Al-Aly
Department of Epidemiology and Biostatistics, College for Public Health and Social Justice, Saint Louis University, Saint Louis, MO, USA
Yan Xie & Benjamin Bowe
ーーー
(3)
Toni M. Delorey, Carly G. K. Ziegler, Graham Heimberg, Rachelly Normand, Yiming Yang, Åsa Segerstolpe, Domenic Abbondanza, Stephen J. Fleming, Ayshwarya Subramanian, Daniel T. Montoro, Karthik A. Jagadeesh, Kushal K. Dey, Pritha Sen, Michal Slyper, Yered H. Pita-Juárez, Devan Phillips, Jana Biermann, Zohar Bloom-Ackermann, Nick Barkas, Andrea Ganna, James Gomez, Johannes C. Melms, Igor Katsyv, Erica Normandin, Pourya Naderi, Yury V. Popov, Siddharth S. Raju, Sebastian Niezen, Linus T.-Y. Tsai, Katherine J. Siddle, Malika Sud, Victoria M. Tran, Shamsudheen K. Vellarikkal, Yiping Wang, Liat Amir-Zilberstein, Deepak S. Atri, Joseph Beechem, Olga R. Brook, Jonathan Chen, Prajan Divakar, Phylicia Dorceus, Jesse M. Engreitz, Adam Essene, Donna M. Fitzgerald, Robin Fropf, Steven Gazal, Joshua Gould, John Grzyb, Tyler Harvey, Jonathan Hecht, Tyler Hether, Judit Jané-Valbuena, Michael Leney-Greene, Hui Ma, Cristin McCabe, Daniel E. McLoughlin, Eric M. Miller, Christoph Muus, Mari Niemi, Robert Padera, Liuliu Pan, Deepti Pant, Carmel Pe’er, Jenna Pfiffner-Borges, Christopher J. Pinto, Jacob Plaisted, Jason Reeves, Marty Ross, Melissa Rudy, Erroll H. Rueckert, Michelle Siciliano, Alexander Sturm, Ellen Todres, Avinash Waghray, Sarah Warren, Shuting Zhang, Daniel R. Zollinger, Lisa Cosimi, Rajat M. Gupta, Nir Hacohen, Hanina Hibshoosh, Winston Hide, Alkes L. Price, Jayaraj Rajagopal, Purushothama Rao Tata, Stefan Riedel, Gyongyi Szabo, Timothy L. Tickle, Patrick T. Ellinor, Deborah Hung, Pardis C. Sabeti, Richard Novak, Robert Rogers, Donald E. Ingber, Z. Gordon Jiang, Dejan Juric, Mehrtash Babadi, Samouil L. Farhi, Benjamin Izar, James R. Stone, Ioannis S. Vlachos, Isaac H. Solomon, Orr Ashenberg, Caroline B. M. Porter, Bo Li, Alex K. Shalek, Alexandra-Chloé Villani, Orit Rozenblatt-Rosen & Aviv Regev -
COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets
Nature (2021)
---
Author information
Affiliations
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
Toni M. Delorey, Graham Heimberg, Yiming Yang, Åsa Segerstolpe, Domenic Abbondanza, Ayshwarya Subramanian, Karthik A. Jagadeesh, Michal Slyper, Devan Phillips, Malika Sud, Liat Amir-Zilberstein, Phylicia Dorceus, Tyler Harvey, Judit Jané-Valbuena, Hui Ma, Cristin McCabe, Carmel Pe’er, Ellen Todres, Timothy L. Tickle, Samouil L. Farhi, Orr Ashenberg, Caroline B. M. Porter, Bo Li, Orit Rozenblatt-Rosen & Aviv Regev
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
Carly G. K. Ziegler, Rachelly Normand, Domenic Abbondanza, Daniel T. Montoro, Pritha Sen, Yered H. Pita-Juárez, Erica Normandin, Siddharth S. Raju, Linus T.-Y. Tsai, Katherine J. Siddle, Shamsudheen K. Vellarikkal, Deepak S. Atri, Jonathan Chen, Jesse M. Engreitz, Michael Leney-Greene, Christoph Muus, Jenna Pfiffner-Borges, Melissa Rudy, Rajat M. Gupta, Nir Hacohen, Gyongyi Szabo, Pardis C. Sabeti, Samouil L. Farhi, Ioannis S. Vlachos, Alex K. Shalek & Alexandra-Chloé Villani
Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA, 02115, USA
Carly G. K. Ziegler & Alex K. Shalek
Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
Carly G. K. Ziegler & Alex K. Shalek
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
Carly G. K. Ziegler, Alex K. Shalek & Aviv Regev
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA
Carly G. K. Ziegler & Alex K. Shalek
Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, 02138, USA
Carly G. K. Ziegler & Alex K. Shalek
Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
Rachelly Normand, Yiming Yang, Pritha Sen, Hui Ma, Bo Li & Alexandra-Chloé Villani
Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
Rachelly Normand, Nir Hacohen & Alexandra-Chloé Villani
Harvard Medical School, Boston, MA, 02115, USA
Rachelly Normand, Yered H. Pita-Juárez, Erica Normandin, Pourya Naderi, Yury V. Popov, Sebastian Niezen, Linus T.-Y. Tsai, Jonathan Hecht, Winston Hide, Stefan Riedel, Gyongyi Szabo, Z. Gordon Jiang, Ioannis S. Vlachos & Alex K. Shalek
Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
Rachelly Normand
Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
Stephen J. Fleming, Nick Barkas, Joshua Gould, Timothy L. Tickle & Mehrtash Babadi
Precision Cardiology Laboratory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
Stephen J. Fleming & Mehrtash Babadi
Department of Epidemiology, Harvard School of Public Health, Boston, USA
Kushal K. Dey & Alkes L. Price
Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
Pritha Sen
Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA
Pritha Sen, Christopher J. Pinto, Dejan Juric, Bo Li & Alexandra-Chloé Villani
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA
Yered H. Pita-Juárez, Pourya Naderi, Jonathan Hecht, Winston Hide, Stefan Riedel & Ioannis S. Vlachos
Harvard Medical School Initiative for RNA Medicine, Boston, MA, 02115, USA
Yered H. Pita-Juárez, Pourya Naderi, Winston Hide & Ioannis S. Vlachos
Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA
Yered H. Pita-Juárez, Winston Hide & Ioannis S. Vlachos
Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA
Jana Biermann, Johannes C. Melms, Yiping Wang & Benjamin Izar
Columbia Center for Translational Immunology, New York, NY, USA
Jana Biermann, Johannes C. Melms, Yiping Wang & Benjamin Izar
Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
Zohar Bloom-Ackermann, James Gomez, Victoria M. Tran, Alexander Sturm, Shuting Zhang & Deborah Hung
Institute for Molecular Medicine Finland, Helsinki, Finland
Andrea Ganna & Mari Niemi
Analytical & Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02115, USA
Andrea Ganna
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
Igor Katsyv & Hanina Hibshoosh
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA
Yury V. Popov, Sebastian Niezen, Linus T.-Y. Tsai, Adam Essene, Deepti Pant, Gyongyi Szabo, Robert Rogers & Z. Gordon Jiang
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA
Yury V. Popov, Sebastian Niezen & Z. Gordon Jiang
Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA
Siddharth S. Raju
FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, 02138, USA
Siddharth S. Raju
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA
Linus T.-Y. Tsai, Adam Essene & Deepti Pant
Boston Nutrition and Obesity Research Center Functional Genomics and Bioinformatics Core Boston, Boston, MA, 02115, USA
Linus T.-Y. Tsai, Adam Essene & Deepti Pant
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA
Katherine J. Siddle & Pardis C. Sabeti
Divisions of Cardiovascular Medicine and Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA
Shamsudheen K. Vellarikkal, Deepak S. Atri & Rajat M. Gupta
NanoString Technologies Inc., Seattle, WA, 98109, USA
Joseph Beechem, Prajan Divakar, Robin Fropf, Tyler Hether, Eric M. Miller, Liuliu Pan, Jason Reeves, Marty Ross, Erroll H. Rueckert, Sarah Warren & Daniel R. Zollinger
Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA
Olga R. Brook
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02115, USA
Jonathan Chen & James R. Stone
Department of Genetics and BASE Initiative, Stanford University School of Medicine, Stanford, USA
Jesse M. Engreitz
Massachusetts General Hospital Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
Donna M. Fitzgerald, Daniel E. McLoughlin, Christopher J. Pinto, Jayaraj Rajagopal & Dejan Juric
Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Steven Gazal
Department of Pathology, Brigham and Women’s Hospital, Boston, MA, 02115, USA
John Grzyb, Robert Padera, Jacob Plaisted, Michelle Siciliano & Isaac H. Solomon
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA
Christoph Muus & Donald E. Ingber
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA
Robert Padera
Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA
Robert Padera
Harvard Stem Cell Institute, Cambridge, MA, USA
Avinash Waghray & Alex K. Shalek
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
Avinash Waghray
Infectious Diseases Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
Lisa Cosimi
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
Nir Hacohen
Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA
Purushothama Rao Tata
Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA
Patrick T. Ellinor
Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA
Deborah Hung
Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, 02114, USA
Deborah Hung
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
Pardis C. Sabeti
Howard Hughes Medical Institute, Chevy Chase, MD, USA
Pardis C. Sabeti & Aviv Regev
Massachusetts Consortium on Pathogen Readiness, Boston, MA, USA
Pardis C. Sabeti
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, USA
Richard Novak & Donald E. Ingber
Massachusetts General Hospital, Boston, MA, 02114, USA
Robert Rogers
Vascular Biology Program and Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
Donald E. Ingber
Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA
Benjamin Izar
Program for Mathematical Genomics, Columbia University Irving Medical Center, New York, NY, USA
Benjamin Izar
Program in Computational & Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
Alex K. Shalek
Program in Immunology, Harvard Medical School, Boston, MA, 02115, USA
Alex K. Shalek
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
Alex K. Shalek
ーーー
(4)
Andre C. Kalil, M.D., M.P.H., Thomas F. Patterson, M.D., Aneesh K. Mehta, M.D., Kay M. Tomashek, M.D., M.P.H., Cameron R. Wolfe, M.B., B.S., M.P.H., Varduhi Ghazaryan, M.D., Vincent C. Marconi, M.D., Guillermo M. Ruiz-Palacios, M.D., Lanny Hsieh, M.D., Susan Kline, M.D., Victor Tapson, M.D., Nicole M. Iovine, M.D., Ph.D., Mamta K. Jain, M.D., M.P.H., Daniel A. Sweeney, M.D., Hana M. El Sahly, M.D., Angela R. Branche, M.D., Justino Regalado Pineda, M.D., David C. Lye, M.B., B.S., Uriel Sandkovsky, M.D., Anne F. Luetkemeyer, M.D., Stuart H. Cohen, M.D., Robert W. Finberg, M.D., Patrick E.H. Jackson, M.D., Babafemi Taiwo, M.B., B.S., Catharine I. Paules, M.D., Henry Arguinchona, M.D., Nathaniel Erdmann, M.D., Ph.D., Neera Ahuja, M.D., Maria Frank, M.D., Myoung-don Oh, M.D., Eu-Suk Kim, M.D., Seow Y. Tan, M.B., B.S., Richard A. Mularski, M.D., M.S.H.S., Henrik Nielsen, M.D., Philip O. Ponce, M.D., Barbara S. Taylor, M.D., LuAnn Larson, R.N., B.S.N., Nadine G. Rouphael, M.D., Youssef Saklawi, M.D., Valeria D. Cantos, M.D., Emily R. Ko, M.D., Ph.D., John J. Engemann, M.D., Alpesh N. Amin, M.D., Miki Watanabe, M.D., Joanne Billings, M.D., M.P.H., Marie-Carmelle Elie, M.D., Richard T. Davey, M.D., Timothy H. Burgess, M.D., M.P.H., Jennifer Ferreira, Sc.M., Michelle Green, M.P.H., Mat Makowski, Ph.D., Anabela Cardoso, M.D., Stephanie de Bono, M.D., Ph.D., Tyler Bonnett, M.S., Michael Proschan, Ph.D., Gregory A. Deye, M.D., Walla Dempsey, Ph.D., Seema U. Nayak, M.D., Lori E. Dodd, Ph.D., and John H. Beigel, M.D. for the ACTT-2 Study Group Members
Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19
The New England Journal of Medicine 2021; 384:795-807
DOI: 10.1056/NEJMoa2031994
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Author Affiliations
From the University of Nebraska Medical Center, Omaha (A.C.K., L.L.); University of Texas Health San Antonio, University Health, and the South Texas Veterans Health Care System, San Antonio (T.F.P., P.O.P., B.S.T.), UT Southwestern Medical Center, Parkland Health and Hospital System (M.K.J.) and Baylor Scott and White Health (U.S.), Dallas, and Baylor College of Medicine, Houston (H.M.E.S.) — all in Texas; Emory University (A.K.M., N.G.R., Y.S., V.C.M., V.D.C.) and Grady Memorial Hospital (V.D.C.), Atlanta, and Atlanta Veterans Affairs Medical Center, Decatur (V.C.M.) — both in Georgia; the National Institute of Allergy and Infectious Diseases, National Institutes of Health (K.M.T., V.G., R.T.D., M.P., G.A.D., W.D., S.U.N., L.E.D., J.H.B.), and the Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences (T.H.B.), Bethesda, and Emmes (J.F., M.G., M.M.) and Clinical Monitoring Research Program Directorate, Frederick National Laboratory (T.B.), Rockville — both in Maryland; Duke University, Durham, NC (C.R.W., E.R.K., J.J.E.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, (G.M.R.-P.) and Instituto Nacional de Enfermedades Respiratorias (J.R.P.), Mexico City; University of California Irvine, Irvine (L.H., A.N.A., M.W.), Cedars–Sinai Medical Center, Los Angeles (V.T.), University of California, San Diego, La Jolla (D.A.S.), University of California, San Francisco, San Francisco (A.F.L.), University of California, Davis, Davis (S.H.C.), and Stanford University, Stanford (N.A.) — all in California; University of Minnesota Medical School, Minneapolis (S.K., J.B.); University of Florida, Gainesville (N.M.I., M.-C.E.); University of Rochester, Rochester, NY (A.R.B.); National Center for Infectious Diseases, Tan Tock Seng Hospital, Lee Kong Chian School of Medicine, and Yong Loo Lin School of Medicine (D.C.L.), and Changi General Hospital (S.Y.T.), Singapore; University of Massachusetts Medical School, Worcester (R.W.F.); University of Virginia, Charlottesville (P.E.H.J.); Northwestern University, Chicago (B.T.); Penn State Health Milton S. Hershey Medical Center, Hershey, PA (C.I.P.); Providence Sacred Heart Medical Center, Spokane, WA (H.A.); University of Alabama at Birmingham, Birmingham (N.E.); Denver Health and Hospital Authority, Denver (M.F.); Seoul National University Hospital, Seoul (M.O.), and Seoul National University Bundang Hospital, Seongnam (E.-S.K.) — both in South Korea; Kaiser Permanente Northwest, Portland, OR (R.A.M.); Aalborg University Hospital, Aalborg, Denmark (H.N.); and Eli Lilly, Indianapolis (A.C., S.B.).
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Giovanni Filocamo, Davide, Mangioni, Paola, Tagliabue, Stefano, Aliberti, Giorgio, Costantino, Francesca, Minoia, Alessandra, Bandera
Use of anakinra in severe COVID-19:A case report
International Journal of Infectious Diseases Volume 96, July 2020, Pages 607-609
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Author Affiliations
Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano, Italy
University of Milan, Italy
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(6)
UK Anakinra label". 
UK Electronic Medicines Compendium. 5 October 2017. Retrieved 23 March 2018.