Prof. Univ. Dr. Iulia Popescu
Allergy and Critical Care Division, Department Medicine, University of Pittsburgh, Pittsburgh, PA

Infliximab therapies targeting TNF- may be beneficial of CD4+ T cell dysfunction in severe COVID-19

Author: Iulia Popescu

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine; Pittsburgh, PA, 15213, USA

Rationale: Lymphopenia is common in severe COVID-19 disease, yet the immune mechanisms are poorly understood. As inflammatory cytokines are increased in severe SARS-CoV-2 infection, we hypothesized a role in contributing to reduced T-cell numbers. Objectives: We sought to characterize the functional SARS-CoV-2 T-cell responses in severe versus recovered, mild COVID-19 patients to determine whether differences were detectable. Methods: Using flow cytometry and single cell RNA sequence analyses we assessed SARS-CoV-2-specific responses in our cohort. Measurements/Main Results: Here we show it is associated with worse survival and is CD4+ T-cell predominant. We further demonstrate that Spike-1(S1) induces high levels of in vitro TNF- in CD4+ T-cells from severe COVID-19 patients but demonstrate impaired T-cell proliferation and increased susceptibility to activation-induced cell death (AICD). In 148 patients with severe COVID-19, we found lymphopenia was associated with worse survival. CD4+ lymphopenia predominated, with lower CD4+/CD8+ ratios in severe COVID-19 compared to patients with mild disease (p<0.0001). In severe disease, immunodominant CD4+ T-cell responses to Spike-1(S1) produced increased in vitro TNF-, but demonstrated impaired S1-specific proliferation and increased susceptibility to activation-induced cell-death (AICD) following antigen exposure. CD4+TNF-+ T-cell responses inversely correlated with absolute CD4+ counts from severe COVID-19 patients (n=76; R=-0.797, P<0.0001). In vitro TNF- blockade including infliximab or anti-TNFRI antibodies strikingly rescued S1-specific CD4+ T-cell proliferation and abrogated S1-specific AICD in PBMC from severe COVID-19 patients (P<0.001). Single-cell RNAseq demonstrated downregulation of Type-1 cytokines and NFB signaling in S1-stimulated CD4+ cells with infliximab treatment. We also evaluated bronchoalveolar lavage (BAL) and lung explant CD4+ T-cells recovered from severe COVID-19 patients and observed that lung T-cells produced higher TNF- compared to PBMC.
Conclusions: Together, our findings show CD4+ dysfunction in severe COVID-19 is TNF-/TNFRI-dependent through immune mechanisms that may contribute to lymphopenia. TNF- blockade may be beneficial in severe COVID-19.

Short CV

I am a Associate Professor in the Division of Pulmonary, Allergy, and Critical Care Medicine at the University of Pittsburgh in Dr. John McDyer’s laboratory. I have significant experience in transplant and viral immunology. My work has focused on T cell mechanisms of rejection, tolerance, and host immunity to viruses such as CMV, EBV and HIV, including the measurement of lung mucosal responses. I have focused on CMV-specific T cell immunity in lung transplant recipients in a leading clinical transplant program. I am CO-I on a U01 award (AI125050-Dr. McDyer) to perform a novel clinical trial to perform tandem lung and bone marrow transplantation in select individuals with primary immunodeficiencies and end-stage lung disease, and to perform mechanistic pathogen-specific and alloimmune tolerance studies in these study participants. In U01AI125050 I measure systemic and lung pathogen-specific immune responses. As immunologist my focuses are on mechanisms of CMV-specific lung mucosal/systemic immunity and viral control, demonstrating an important role for the Type-1 transcription factor T-bet and other immune parameters. I also study immune mechanisms of allograft rejection/tolerance in lung transplantation with an established divisional research group performing studies in the human studies. I also perform work on Dr. McDyer and Dr. Kirks’ collaborative U01 award (HL121814) to study immune mechanisms of HIV-associated COPD. I am the Co-I on an R01 award HL133184-01 (Dr. McDyer), “Role of F-box Proteins in Lung Transplantation.” In addition, common to these experimental systems above, Dr. McDyer’s laboratory is highly proficient in measuring lung mucosal and systemic viral-specific and allospecific multifunctional T cell immunity and phenotyping in lung transplant recipients. I have a good track record of training medical students and fellows and junior faculty in Dr. McDyer’s lab. the field of lung transplant immunology. Pertinent to this proposal I also have significant experience assessing human alloimmunity, using flow cytometry, in addition to viral immunity, and evaluate the phenotype of T cells, proliferation and effector multifunction. In addition, I am very experienced in ELISA and ELISPOT assays to measure inflammatory responses. Recently, we showed that IPF lung transplant recipients with short telomeres have impaired CMV T cell immunity. Here at Pitt, Dr. Alder, Dr. Snyder, Dr. Chen, Dr. Iasella and Dr. Popescu have a track record of working closely together. Therefore, based on my established and current role in Dr. McDyer’s laboratory and my expertise in transplant immunology in the field of lung transplantation makes me well-suited to fulfill my role as Co-I on this project R01 project, “The Role of Telomeres in Lung Transplant Recipient Immunity and Outcomes”.

Positions and Employment
2020-pres. Research Associate Professor, Pulmonary, Allergy and Critical Care Division, Department Medicine, University of Pittsburgh, Pittsburgh, PA
2014-2020 Research Assistant Professor, Pulmonary, Allergy and Critical Care Division, Department Medicine, University of Pittsburgh, Pittsburgh, PA
2019-pres. Member – International Society of Heart and Lung Transplantation
2012-2014 Research Associate/Manager Flow Cytometry Core, Pulmonary, Allergy and Critical Care Division, Department Medicine, University of Pittsburgh, Pittsburgh, PA
2010-2011 Senior Scientist/Technical Application Specialist, Cellular Technology Limited, Shaker Heights, OH
2006-2010 Faculty Research Instructor, Dept of Surgery Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA
2006-pres. Member – American Society of Transplantation (AST)
2007-pres. Member – American Immunology Association (AIA)
2001-2006 Postdoctoral Research Associate, Dept of Surgery Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA
2000-2001 Research Scientist, Dept. of Cellular Immunology and Signal Transduction, Center of Immunology, Institute of Virology Bucharest, Romania
1997- 2000 Junior Research Scientist, Department Clinical Immunology, Center for Immunology, Bucharest, Romania
1998-pres. Member – European Association for Cancer Research (EACR)
1997 3 months Visiting Research PhD, Doctoral Scientist, Cancer Institute, University of Pittsburgh, Pittsburgh, PA.
1994-1997 Research Associate – Dept. of Cellular Immunology and Signal Transduction, Center of Immunology, Institute of Virology, Bucharest, Romania
1991-1994 Resident Scientist- Department Clinical Immunology, Center for Immunology, Bucharest, Romania
1986-1991 Research Assistant, Department of Interferon Research / Immune-modulators, V. Babes Institute, Bucharest, Romania
1990-pres. Member – Federation of European Biochemical Societies (FEBS)
1986-pres. Member – Romanian Society of Immunology (SNI)
Memberships
Member – American Society of Transplantation (AST) 2006-present
Member – American Immunology Association (AIA) 2007-present
Member – European Association for Cancer Research (EACR) 1998-present
Member – Federation of European Biochemical Societies (FEBS) 1990-present
Member – Romanian Society of Immunology (SNI) 1986-present
Member – International Society of Heart and Lung Transplantation 2019-present

Prof. Dr. Torello Lotti
University of Studies Guglielmo Marconi, Roma, Italia

Future of Dermatology and Applied Cosmetology
Autor: Torello Lotti, Professor & Chairman of Dermatology and Regenerative Medicine, University of Rome “Guglielmo Marconi”, Rome, Italy   

Torello Lotti

University of Rome “Guglielmo Marconi”, Rome, Italy
President World Health Academy of Dermatology

Skin ageing is an irreversible process during which ultrastructural and physiologic alterations happen. Dermatology has focused a lot of attention on the reversal of signs of ageing and photodamage, with the purposes of achieving cosmetic benefits and preventing photocancerogenesis. Recent advances in skin biology have clarified the mechanisms by which photoageing occurs and have given rise to new treatments to prevent and reverse this process. The understanding of the role of key receptors involved in the complex pathomechanism of skin ageing probably will lead to the development of the new therapeutic agents in the near future.

Our contribution in Understanding an treating Covid-19 Skin Disorders

Torello Lotti

University of Rome “Guglielmo Marconi”, Rome, Italy
President World Health Academy of Dermatology

Keywords: COVID-19, SARS-CoV-2, acro-ischemia, androgenetic alopecia, chilblain-like eruptions, maculopapular rash, purpuric rash, urticaria

Coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the epithelium of the airways. With the increasing involvement of dermatologist in management of this crisis, cutaneous symptoms gained more and more attention. In this review, we will describe cutaneous symptoms of patients of all ages in association with COVID-19. We will focus on such disorders that are caused by direct action of SARS-CoV-2 on tissues, complement, and coagulation system and on nonspecific eruption of the systemic viral infection. Drug-induced reactions are only mentioned in the differential diagnoses. Although more systematic investigations are warranted, it becomes clear that some symptoms are clinical signs of a milder COVID-19 course, while others are a red flag for a more severe course. Knowledge of the cutaneous manifestations of COVID-19 may help in early diagnosis, triage of patients, and risk stratification.

Scurt CV

Prof. Lotti is Full Professor and Chairman of Dermatology and Venereology at University of Rome Guglielmo Marconi, Rome, Italy. He is President of the World Health Academy, Dermatology since 2013. Director, Centro Studi per la Ricerca Multidisciplinare Rigenerativa (CSRMR), of the University of Rome “G.Marconi”, Rome, Italy, since 2015.
He is Honorary Professor of Dermatology – China Medical University Shenyang (2011), Lecturer at the New York Academy of Sciences “Howard Fox Memorial Lecture” (14 March 2012 – New York, NY – USA), and Chair, Executive Scientific Committee Vitiligo Research Foundation, New York, NY USA. He has been Full Professor of the Dermatology and Venereology Division at University of Florence School of Medicine, Florence, Italy, from 2006 to 2010. He is Visiting Professor in six International Universities worldwide, and Key Note Lecturer in several international dermatology Societies.
His activities in serving Dermatology have been numerous: President of the Italian Society of Dermatology and Venereology (SIDeMaST , 2009-2011) and President of the International Society of Dermatology ( ISD, 2009-2011), President of the European Society for Cosmetic and Aesthetic Dermatology (2003-2004), Editor in Chief of the Journal of the European Academy of Dermatology and Venereology (1992-2002), Editor “Therapeutic Hotline”- Dermatologic Therapy (2007-) and served as Editor in Chief of the Giornale Italiano di Dermatologia in the period of presidency of the Societa’ Italiana di Dermatologia (2009-2011).
He is Ordinary Member of the main Scientific Societies worldwide (EADV, SIDEV, ESDR, ISD, AAD, SID) and Honorary Member of several Scientific Societies of the Dermatology field.
Moreover, he is a Scientific reviewer of ten sectorial journals, among which are the British Journal of Dermatology, Journal of Investigative Dermatology, Journal of the American Academy of Dermatology , Dermatologic Therapy.
Professor Lotti is presently Editor in Chief of Dermatologic Therapy by Wiley-Blackwell (Oxford U.K, Chicago IL).
Professor Lotti is Full Professor of Dermatology of the 1st Medical Univeristy of Moscow, since January 2020 and Full Professor and Chairman of Dermatology at Univeristy of Rome G. Marconi, Rome, Italy.
He has been invited as Keynote Speaker in 2.136 international and national Congresses and has served as Congress President or Chair of a Scientific session in 827 Congresses.
Prof. Lotti has authored 3.507 scientific publications (629 peer-reviewed articles, 388 book chapters, 3.650 abstracts and has edited or co-edited 59 books in the field of Dermatology and related fileds.

Prof. Dr. Davinder Parshad
Institute of Medical Education & Research, Chandigarh, India

Recent Advances in the Management of Vitiligo
Author: Davinder Parsad, MD, PhD
Professor, Department of Dermatology, PGIMER, Chandigarh, India

The development of effective treatment for vitiligo depends on understanding the mechanisms of depigmentation and repigmentation. In our continued journey to find ideal treatment of vitiligo, we have definitely reached a new era with effective medical treatment and non-cultured epidermal suspension in the management of vitiligo.
Vitiligo an auto-immune disease and there is need to emphasise on the early treatment of vitiligo. There are two treatment goals, one is stabilization and second is repigmentation. As vitiligo is associated with sever psycho-social stress, third goal can be to consider psychological aspects also in the management.
At present combination therapy is key to the successful management of vitiligo. In the present era of post phototherapy, we have a wide spectrum of many effective treatments for vitiligo; however, we do not have ideal treatment yet. In this presentation, I will be presenting an overview of roadmaps and roadblocks to the successful treatment of vitiligo based on the experience of last 20 years with emphasis on role of JAK/Stat inhibitors.

Scurt CV

Main area of research is vitiligo– pathogenesis and treatment and innovative surgical methods.
Total of 295 publications and about 140 publications on vitiligo only in International journals with very high citation index.
President –Asian Society for Pigment Cell Research (2011-2014).
Coordinator of Asian region for World Vitiligo consensus group.
Member: European Task force on vitiligo.
Member Scientific Advisory Board: Vitiligo Research Foundation (USA).
Council member of International Federation of Pigment Cell Societies.
Chaired/co-chaired, presented invited/guest lectures, papers on vitiligo at more than 200 International conferences/meetings.
Received Ambady oration of Indian Association of Dermatologists, Venereologists & Leprologists (2006).
Associate Editor: Archives of Dermatology Research and Dermatologic Therapy.
Member Editorial Board: International Journal of Dermatology.