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Yaghmour N, Alramini D, Alsarayrah M, Abuassi M, Al-Rameni A, Aladaileh M, Al-Abdallat H, Rawashdeh B. COVID-19's impact on heart and lung transplantation: Citation-based analysis of research output. World J Transplant 2025; 15:99992. [DOI: 10.5500/wjt.v15.i2.99992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 12/26/2024] [Accepted: 01/11/2025] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND Since being declared as a pandemic on March 11, 2020, coronavirus disease 2019 (COVID-19) has profoundly influenced heart and lung transplant programs, impacting donor availability, patient management, and healthcare resources. This study offers a citation-based review of the research output on this subject, seeking to understand how the transplant community has responded to these challenges. Through a review of literature from the beginning of the pandemic to early 2023, we evaluate the shifts in academic emphasis and the emerging trends in heart and lung transplantation during the COVID-19 period.
AIM To assess the impact of COVID-19 on heart and lung transplantation research, highlighting key themes, contributions, and trends in the literature during the pandemic.
METHODS We conducted an extensive search of the Web of Science database on February 9, 2023. We employed the terms "transplant" and "transplantation", as well as organ-specific terms like "heart", "cardiac", and "lung", combined with COVID-19-related terms such as "COVID-19", "coronavirus", and "SARS-CoV-2". The search encompassed publications from March 11, 2020 to February 9, 2023. Data on authors, journals, countries, institutions, and publication types (articles, reviews, conference papers, letters, notes, editorials, brief surveys, book chapters, and errata) were analyzed. The data was visualized and processed with VOSviewer 1.6.18 and Excel.
RESULTS We included 847 research items. There were 392 articles (46.3%) and 88 reviews (10.3%). The studies included were referenced 7757 times, with an average of 9.17 citations per article. The majority of the publications (n = 317) were conducted by institutes from the United States with highest citations (n = 4948) on this subject, followed by Germany, Italy, and France. The majority of papers (n = 101) were published in the Journal of Heart and Lung Transplantation.
CONCLUSION To the fullest extent of our knowledge, this is the first bibliometric study of COVID-19's impact on heart and lung transplantation to offer a visual analysis of the literature in order to predict future frontiers and provide an overview of current research hotspots.
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Affiliation(s)
- Nisreen Yaghmour
- Department of Cardiology, MercyOne Iowa Heart Center, Des Moines, IO 52302, United States
| | - Dina Alramini
- Department of Cardiothoracic Surgery, University of Arizona, Tucson, AZ 85702, United States
| | - Mohammad Alsarayrah
- Department of Vascular Surgery, University of North Carolina, Chapel Hill, NC 27599, United States
| | - Mohammad Abuassi
- Department of Internal Medicine, Jordan Hospital, Amman 00962, Al jamaimah, Jordan
| | - Awn Al-Rameni
- Department of Internal Medicine, University of Jordan, Amman 11698, Al jamaimah, Jordan
| | - Mohammad Aladaileh
- Department of Thoracic Surgery, University of Florida, Gainesville, FL 32605, United States
| | - Haneen Al-Abdallat
- Department of Medicine, Jordan University Hospital, Amman 11263, Al jamaimah, Jordan
| | - Badi Rawashdeh
- Department of Transplant Surgery, Medical College of Wisconsin, Milwaukee, WI 53202, United States
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Iriyama C, Ichikawa T, Tamura T, Takahata M, Ishio T, Ibata M, Kawai R, Iwata M, Suzuki M, Adachi H, Nao N, Suzuki H, Kawai A, Kamiyama A, Suzuki T, Hirata Y, Iida S, Katano H, Ishii Y, Tsuji T, Oda Y, Tanaka S, Okazaki N, Katayama Y, Nakagawa S, Tsukamoto T, Doi Y, Fukuhara T, Murata T, Tomita A. Clinical and molecular landscape of prolonged SARS-CoV-2 infection with resistance to remdesivir in immunocompromised patients. PNAS NEXUS 2025; 4:pgaf085. [PMID: 40160532 PMCID: PMC11950820 DOI: 10.1093/pnasnexus/pgaf085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 02/15/2025] [Indexed: 04/02/2025]
Abstract
Patients with hematologic diseases have experienced coronavirus disease 2019 (COVID-19) with a prolonged, progressive course. Here, we present clinical, pathological, and virological analyses of three cases of prolonged COVID-19 among patients undergoing treatment for B-cell lymphoma. These patients had all been treated with anti-CD20 antibody and bendamustine. Despite various antiviral treatments, high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels persisted for >4 weeks, and two of them succumbed to COVID-19. The autopsy showed bronchopneumonia, interstitial pneumonia, alveolar hemorrhage, and fibrosis. Overlapping cytomegalovirus, fungal and/or bacterial infections were also confirmed. Sequencing of SARS-CoV-2 showed accumulation of mutations and changes in variant allele frequencies over time. NSP12 mutations V792I and M794I appeared independently in two cases as COVID-19 progressed. In vitro drug susceptibility analysis and an animal experiment using recombinant SARS-CoV-2 demonstrated that each mutation, V792 and M794I, was independently responsible for remdesivir resistance and attenuated pathogenicity. E340A, E340D, and F342INS mutations in the spike protein were found in one case, which may account for the sotrovimab resistance. Analysis of autopsy specimens indicated heterogeneous distribution of these mutations. In summary, we demonstrated temporal and spatial diversity in SARS-CoV-2 that evolved resistance to various antiviral agents in malignant lymphoma patients under immunodeficient conditions caused by certain types of immunochemotherapies. Strategies may be necessary to prevent the acquisition of drug resistance and improve outcomes, such as the selection of appropriate treatment strategies for lymphoma considering patients' immune status and the institution of early intensive antiviral therapy.
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Affiliation(s)
- Chisako Iriyama
- Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Japan
| | - Takaya Ichikawa
- Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo 060-8638, Japan
- Department of Hematology, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan
- Department of Hematology, Sapporo City General Hospital, Sapporo 060-8604, Japan
| | - Tomokazu Tamura
- Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo 060-8638, Japan
- Institute for Vaccine Research and Development (IVReD), Hokkaido University, Sapporo 001-0021, Japan
- One Health Research Center, Hokkaido University, Sapporo 060-0818, Japan
| | - Mutsumi Takahata
- Department of Hematology, Sapporo-Kosei General Hospital, Sapporo 060-0033, Japan
| | - Takashi Ishio
- Department of Hematology, Sapporo-Kosei General Hospital, Sapporo 060-0033, Japan
| | - Makoto Ibata
- Department of Hematology, Sapporo-Kosei General Hospital, Sapporo 060-0033, Japan
| | - Ryuji Kawai
- Department of Emergency and General Internal Medicine, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
| | - Mitsunaga Iwata
- Department of Emergency and General Internal Medicine, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
| | - Masahiro Suzuki
- Department of Microbiology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
| | - Hirokazu Adachi
- Department of Microbiology and Medical Zoology, Aichi Prefectural Institute of Public Health, Nagoya 462-8576, Japan
| | - Naganori Nao
- One Health Research Center, Hokkaido University, Sapporo 060-0818, Japan
- Division of International Research Promotion, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan
| | | | - Akito Kawai
- Department of Microbiology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
| | - Akifumi Kamiyama
- Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo 060-8638, Japan
| | - Tadaki Suzuki
- Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
| | - Yuichiro Hirata
- Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
| | - Shun Iida
- Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
| | - Harutaka Katano
- Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
| | - Yasushi Ishii
- Department of Pathology, Sapporo City General Hospital, Sapporo 060-8604, Japan
| | - Takahiro Tsuji
- Department of Pathology, Sapporo City General Hospital, Sapporo 060-8604, Japan
| | - Yoshitaka Oda
- Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan
| | - Shinya Tanaka
- Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan
- Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo 001-0021, Japan
| | - Nanase Okazaki
- Department of Pathology, Sapporo City General Hospital, Sapporo 060-8604, Japan
| | - Yuko Katayama
- Department of Pathology, Sapporo City General Hospital, Sapporo 060-8604, Japan
| | - Shimpei Nakagawa
- Department of Pathology, Sapporo City General Hospital, Sapporo 060-8604, Japan
| | - Tetsuya Tsukamoto
- Department of Diagnostic Pathology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
| | - Yohei Doi
- Department of Microbiology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
- Center for Infectious Disease Research, Fujita Health University, Toyoake 470-1192, Japan
- Department of Infectious Diseases, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
- Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
| | - Takasuke Fukuhara
- Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo 060-8638, Japan
- Institute for Vaccine Research and Development (IVReD), Hokkaido University, Sapporo 001-0021, Japan
- One Health Research Center, Hokkaido University, Sapporo 060-0818, Japan
- Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan
- AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo 100-0004, Japan
| | - Takayuki Murata
- Center for Infectious Disease Research, Fujita Health University, Toyoake 470-1192, Japan
- Department of Virology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
| | - Akihiro Tomita
- Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Japan
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Kashima K, Matsuyama H, Yoshishige Y, Nakazono S. A Case of Interstitial Pneumonia Leading to Respiratory Failure Several Months After COVID-19 Infection. Cureus 2025; 17:e77153. [PMID: 39925489 PMCID: PMC11805603 DOI: 10.7759/cureus.77153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/08/2025] [Indexed: 02/11/2025] Open
Abstract
While acute pneumonia is commonly observed in the early stages of coronavirus disease 2019 (COVID-19) infection, isolated cases of interstitial pneumonia have been reported several months later. In this case, interstitial lung disease was identified on a routine follow-up examination five months after infection. Eight months after infection, the patient developed worsening interstitial lung disease, pulmonary hypertension, and worsening symptoms, leading to respiratory failure. Careful follow-up is necessary for patients with COVID-19 who experience progressive pulmonary lesions.
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Wang C, Liu S, Li C, Wang Z, Ming R, Huang L. Monitoring the Cascade of Monocyte-Derived Macrophages to Influenza Virus Infection in Human Alveolus Chips. ACS APPLIED MATERIALS & INTERFACES 2024; 16:60045-60055. [PMID: 39450775 DOI: 10.1021/acsami.4c15125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/26/2024]
Abstract
Respiratory viruses ravage the world and seriously threaten people's health. Despite intense research efforts, the immune mechanism underlying respiratory virus-induced acute lung injury (ALI) and pulmonary fibrosis (PF) has not been fully elucidated. Here, the cascade of monocyte-derived macrophages to influenza A virus infection is monitored on an optimized human alveolus chip to reveal the role of macrophages in the development of ALI and PF. We find that viral infection causes damage to the alveolar air-liquid barrier and the release of inflammatory cytokines, which induce the M0 macrophages to gather and polarize to the M1 phenotype at the damaged site through recruitment, adhesion, migration, and activation, leading to ALI. Afterward, M1 macrophages polarize into the M2 phenotype, and then transform into myofibroblasts, followed by enhanced secretion of various anti-inflammatory cytokines and profibrotic cytokines, to promote PF. Our study provides an insight into the pathogenesis of virus-induced ALI and PF, which will assist in the development of therapeutic strategies and drugs for treating influenza and other respiratory virus infections.
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Affiliation(s)
- Chenguang Wang
- School of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China
| | - Shujun Liu
- School of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China
| | - Chuyu Li
- School of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China
| | - Zhongjie Wang
- School of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China
| | - Ruiqi Ming
- School of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China
| | - Lili Huang
- School of Medical Technology, Beijing Institute of Technology, Beijing 100081, P. R. China
- Tangshan Research Institute, Beijing Institute of Technology, Tangshan 063000, P. R. China
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Molinengo L, Estrin-Serlui T, Hanley B, Osborn M, Goldin R. Infectious diseases and the role of needle biopsy post-mortem. THE LANCET. MICROBE 2024; 5:707-716. [PMID: 38604206 DOI: 10.1016/s2666-5247(24)00044-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 02/04/2024] [Accepted: 02/07/2024] [Indexed: 04/13/2024]
Abstract
Post-mortem examinations continue to play a crucial role in understanding the epidemiology and pathogenesis of infectious diseases. However, the perceived infection risk can preclude traditional, invasive, complete diagnostic autopsy. Post-mortem examination is especially important in emerging infectious diseases with potentially unknown infection risks, but rapid acquisition of good quality tissue samples is needed as part of the scientific and public health response. Needle biopsy post-mortem is a minimally invasive, rapid, closed-body autopsy technique that was originally developed to minimise the infection risk to practitioners. Since its inception, needle biopsy post-mortem has also been used as a technique to support complete diagnostic autopsy provision in poorly resourced regions and to facilitate post-mortem examinations in communities that might have religious or cultural objections to an invasive autopsy. This Review analyses the evolution and applicability of needle biopsy post-mortem in investigating endemic and emerging infectious diseases.
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Affiliation(s)
- Lucia Molinengo
- Cellular Pathology Department, Northwest London Pathology hosted by Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, UK.
| | - Theodore Estrin-Serlui
- Cellular Pathology Department, Northwest London Pathology hosted by Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, UK
| | - Brian Hanley
- Cellular Pathology Department, Northwest London Pathology hosted by Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, UK; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK; Department of Metabolism, Digestion and Reproduction, South Kensington Campus, Imperial College, London, UK
| | - Michael Osborn
- Cellular Pathology Department, Northwest London Pathology hosted by Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, UK
| | - Robert Goldin
- Department of Metabolism, Digestion and Reproduction, South Kensington Campus, Imperial College, London, UK
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6
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Schädler J, Azeke AT, Ondruschka B, Steurer S, Lütgehetmann M, Fitzek A, Möbius D. Concordance between MITS and conventional autopsies for pathological and virological diagnoses. Int J Legal Med 2024; 138:431-442. [PMID: 37837537 PMCID: PMC10861633 DOI: 10.1007/s00414-023-03088-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 09/04/2023] [Indexed: 10/16/2023]
Abstract
In pandemics or to further study highly contagious infectious diseases, new strategies are needed for the collection of post-mortem tissue samples to identify the pathogen as well as its morphological impact. In this study, an ultrasound-guided minimally invasive tissue sampling (MITS) protocol was developed and validated for post-mortem use. The histological and microbiological qualities of post-mortem specimens were evaluated and compared between MITS and conventional autopsy (CA) in a series of COVID-19 deaths. Thirty-six ultrasound-guided MITS were performed. In five cases more, specimens for histological and virological examination were also obtained and compared during the subsequently performed CA. Summary statistics and qualitative interpretations (positive, negative) were calculated for each organ tissue sample from MITS and CA, and target genes were determined for both human cell count (beta-globin) and virus (SARS-CoV-2 specific E gene). There are no significant differences between MITS and CA with respect to the detectability of viral load in individual organs, which is why MITS can be of utmost importance and an useful alternative, especially during outbreaks of infectious diseases.
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Affiliation(s)
- Julia Schädler
- Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Akhator Terence Azeke
- Department of Anatomic Pathology, Irrua Specialist Teaching Hospital, Irrua, Nigeria
| | - Benjamin Ondruschka
- Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marc Lütgehetmann
- Institute of Medical Microbiology, Virology, and Hygiene, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany
| | - Antonia Fitzek
- Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Dustin Möbius
- Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Narasaraju T, Neeli I, Criswell SL, Krishnappa A, Meng W, Silva V, Bila G, Vovk V, Serhiy Z, Bowlin GL, Meyer N, Luning Prak ET, Radic M, Bilyy R. Neutrophil Activity and Extracellular Matrix Degradation: Drivers of Lung Tissue Destruction in Fatal COVID-19 Cases and Implications for Long COVID. Biomolecules 2024; 14:236. [PMID: 38397474 PMCID: PMC10886497 DOI: 10.3390/biom14020236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 02/04/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Pulmonary fibrosis, severe alveolitis, and the inability to restore alveolar epithelial architecture are primary causes of respiratory failure in fatal COVID-19 cases. However, the factors contributing to abnormal fibrosis in critically ill COVID-19 patients remain unclear. This study analyzed the histopathology of lung specimens from eight COVID-19 and six non-COVID-19 postmortems. We assessed the distribution and changes in extracellular matrix (ECM) proteins, including elastin and collagen, in lung alveoli through morphometric analyses. Our findings reveal the significant degradation of elastin fibers along the thin alveolar walls of the lung parenchyma, a process that precedes the onset of interstitial collagen deposition and widespread intra-alveolar fibrosis. Lungs with collapsed alveoli and organized fibrotic regions showed extensive fragmentation of elastin fibers, accompanied by alveolar epithelial cell death. Immunoblotting of lung autopsy tissue extracts confirmed elastin degradation. Importantly, we found that the loss of elastin was strongly correlated with the induction of neutrophil elastase (NE), a potent protease that degrades ECM. This study affirms the critical role of neutrophils and neutrophil enzymes in the pathogenesis of COVID-19. Consistently, we observed increased staining for peptidyl arginine deiminase, a marker for neutrophil extracellular trap release, and myeloperoxidase, an enzyme-generating reactive oxygen radical, indicating active neutrophil involvement in lung pathology. These findings place neutrophils and elastin degradation at the center of impaired alveolar function and argue that elastolysis and alveolitis trigger abnormal ECM repair and fibrosis in fatal COVID-19 cases. Importantly, this study has implications for severe COVID-19 complications, including long COVID and other chronic inflammatory and fibrotic disorders.
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Affiliation(s)
- Teluguakula Narasaraju
- Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA; or (T.N.); (I.N.); (V.S.)
- Department of Microbiology, Adichunchanagiri Institute of Medical Sciences, Center for Research and Innovation, Adichunchanagiri University, Mandya 571448, India
| | - Indira Neeli
- Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA; or (T.N.); (I.N.); (V.S.)
| | - Sheila L. Criswell
- Department of Diagnostic and Health Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA;
| | - Amita Krishnappa
- Department of Pathology, Adichunchanagiri Institute of Medical Sciences, Adichunchanagiri University, Mandya 571448, India;
| | - Wenzhao Meng
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; (W.M.); (E.T.L.P.)
| | - Vasuki Silva
- Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA; or (T.N.); (I.N.); (V.S.)
| | - Galyna Bila
- Department of Histology, Cytology, Histology & Embryology, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine; (G.B.); (R.B.)
| | - Volodymyr Vovk
- Department of Pathological Anatomy and Forensic Medicine, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine;
- Lviv Regional Pathological Anatomy Office, CU ENT (Pulmonology Lviv Regional Diagnostic Center), 79000 Lviv, Ukraine;
| | - Zolotukhin Serhiy
- Lviv Regional Pathological Anatomy Office, CU ENT (Pulmonology Lviv Regional Diagnostic Center), 79000 Lviv, Ukraine;
| | - Gary L. Bowlin
- Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, USA;
| | - Nuala Meyer
- Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;
- Pulmonary, Allergy, and Critical Care Medicine and Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Eline T. Luning Prak
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; (W.M.); (E.T.L.P.)
- Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;
| | - Marko Radic
- Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA; or (T.N.); (I.N.); (V.S.)
| | - Rostyslav Bilyy
- Department of Histology, Cytology, Histology & Embryology, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine; (G.B.); (R.B.)
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Soliman S, Soliman H, Crézé M, Brillet PY, Montani D, Savale L, Jais X, Bulifon S, Jutant EM, Rius E, Devilder M, Beurnier A, Colle R, Gasnier M, Pham T, Morin L, Noel N, Lecoq AL, Becquemont L, Figueiredo S, Harrois A, Bellin MF, Monnet X, Meyrignac O. Radiological pulmonary sequelae after COVID-19 and correlation with clinical and functional pulmonary evaluation: results of a prospective cohort. Eur Radiol 2024; 34:1037-1052. [PMID: 37572192 DOI: 10.1007/s00330-023-10044-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 05/29/2023] [Accepted: 06/20/2023] [Indexed: 08/14/2023]
Abstract
OBJECTIVES Whether COVID-19 leads to long-term pulmonary sequelae or not remains unknown. The aim of this study was to assess the prevalence of persisting radiological pulmonary fibrotic lesions in patients hospitalized for COVID-19. MATERIALS AND METHODS We conducted a prospective single-center study among patients hospitalized for COVID-19 between March and May 2020. Patients with residual symptoms or admitted into intensive care units were investigated 4 months after discharge by a chest CT (CCT) and pulmonary function tests (PFTs). The primary endpoint was the rate of persistent radiological fibrotic lesions after 4 months. Secondary endpoints included further CCT evaluation at 9 and 16 months, correlation of fibrotic lesions with clinical and PFT evaluation, and assessment of predictive factors. RESULTS Among the 1151 patients hospitalized for COVID-19, 169 patients performed a CCT at 4 months. CCTs showed pulmonary fibrotic lesions in 19% of the patients (32/169). These lesions were persistent at 9 months and 16 months in 97% (29/30) and 95% of patients (18/19) respectively. There was no significant clinical difference based on dyspnea scale in patients with pulmonary fibrosis. However, PFT evaluation showed significantly decreased diffusing lung capacity for carbon monoxide (p < 0.001) and total lung capacity (p < 0.001) in patients with radiological lesions. In multivariate analysis, the predictive factors of radiological pulmonary fibrotic lesions were pulmonary embolism (OR = 9.0), high-flow oxygen (OR = 6.37), and mechanical ventilation (OR = 3.49). CONCLUSION At 4 months, 19% of patients investigated after hospitalization for COVID-19 had radiological pulmonary fibrotic lesions; they persisted up to 16 months. CLINICAL RELEVANCE STATEMENT Whether COVID-19 leads to long-term pulmonary sequelae or not remains unknown. The aim of this study was to assess the prevalence of persisting radiological pulmonary fibrotic lesions in patients hospitalized for COVID-19. The prevalence of persisting lesions after COVID-19 remains unclear. We assessed this prevalence and predictive factors leading to fibrotic lesions in a large cohort. The respiratory clinical impact of these lesions was also assessed. KEY POINTS • Nineteen percent of patients hospitalized for COVID-19 had radiological fibrotic lesions at 4 months, remaining stable at 16 months. • COVID-19 fibrotic lesions did not match any infiltrative lung disease pattern. • COVID-19 fibrotic lesions were associated with pulmonary function test abnormalities but did not lead to clinical respiratory manifestation.
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Affiliation(s)
- Samer Soliman
- Service de Radiologie Diagnostique Et Interventionnelle, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
| | - Heithem Soliman
- Service de Gastro-Entérologie, Université Paris-Cité, AP-HP Nord, Hôpital Louis Mourier, Colombes, France
| | - Maud Crézé
- Service de Radiologie Diagnostique Et Interventionnelle, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
| | - Pierre-Yves Brillet
- Service de Radiologie Diagnostique, Université Sorbonne Paris-Nord, AP-HP, Hôpital Avicenne, Bobigny, France
| | - David Montani
- DMU 5, Thorinno, Service de Pneumologie Et Soins Intensifs Respiratoires, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Inserm UMR_S999, Le Kremlin-Bicêtre, France
| | - Laurent Savale
- DMU 5, Thorinno, Service de Pneumologie Et Soins Intensifs Respiratoires, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Inserm UMR_S999, Le Kremlin-Bicêtre, France
| | - Xavier Jais
- DMU 5, Thorinno, Service de Pneumologie Et Soins Intensifs Respiratoires, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Inserm UMR_S999, Le Kremlin-Bicêtre, France
| | - Sophie Bulifon
- DMU 5, Thorinno, Service de Pneumologie Et Soins Intensifs Respiratoires, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Inserm UMR_S999, Le Kremlin-Bicêtre, France
| | - Etienne-Marie Jutant
- DMU 5, Thorinno, Service de Pneumologie Et Soins Intensifs Respiratoires, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Inserm UMR_S999, Le Kremlin-Bicêtre, France
| | - Emily Rius
- Service de Radiologie Diagnostique Et Interventionnelle, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
| | - Matthieu Devilder
- Service de Radiologie Diagnostique Et Interventionnelle, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
| | - Antoine Beurnier
- DMU 5 Thorinno, Service de Physiologie Et d'Explorations Fonctionnelles Respiratoires, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Inserm UMR_S999, Le Kremlin-Bicêtre, France
| | - Romain Colle
- DMU 11 Psychiatrie, Santé Mentale, Addictologie Et Nutrition, Service de Psychiatrie, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Équipe MOODS, INSERM U1178, CESP (Centre de Recherche en Epidémiologie Et Santé Des Populations), Le Kremlin-Bicêtre, France
| | - Matthieu Gasnier
- DMU 11 Psychiatrie, Santé Mentale, Addictologie Et Nutrition, Service de Psychiatrie, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Équipe MOODS, INSERM U1178, CESP (Centre de Recherche en Epidémiologie Et Santé Des Populations), Le Kremlin-Bicêtre, France
| | - Tài Pham
- DMU 4 CORREVE Maladies du Cœur Et Des Vaisseaux,Service de Médecine Intensive-Réanimation, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, FHU Sepsis, Le Kremlin-Bicêtre, France
| | - Luc Morin
- Service de Réanimation Pédiatrique Et Médecine Néonatale, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Santé de L'Enfant Et de L'Adolescent, Le Kremlin-Bicêtre, France
| | - Nicolas Noel
- DMU 7 Endocrinologie-Immunités-Inflammations Cancer-Urgences, Service de Médecine Interne Et Immunologie Clinique, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
| | - Anne-Lise Lecoq
- DMU 13 Santé Publique, Information Médicale, Appui À La Recherche Clinique, Centre de Recherche Clinique Paris-Saclay, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, INSERM U1018, CESP, Le Kremlin-Bicêtre, France
| | - Laurent Becquemont
- DMU 13 Santé Publique, Information Médicale, Appui À La Recherche Clinique, Centre de Recherche Clinique Paris-Saclay, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, INSERM U1018, CESP, Le Kremlin-Bicêtre, France
| | - Samy Figueiredo
- DMU 12 Anesthésie, Réanimation, Douleur, Service de Réanimation Chirurgicale, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
| | - Anatole Harrois
- DMU 12 Anesthésie, Réanimation, Douleur, Service de Réanimation Chirurgicale, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
| | - Marie-France Bellin
- Service de Radiologie Diagnostique Et Interventionnelle, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
| | - Xavier Monnet
- DMU 4 CORREVE Maladies du Cœur Et Des Vaisseaux,Service de Médecine Intensive-Réanimation, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, FHU Sepsis, Le Kremlin-Bicêtre, France
| | - Olivier Meyrignac
- Service de Radiologie Diagnostique Et Interventionnelle, Université Paris-Saclay, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
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Lahmer T, Weirich G, Porubsky S, Rasch S, Kammerstetter FA, Schustetter C, Schüffler P, Erber J, Dibos M, Delbridge C, Kuhn PH, Jeske S, Steinhardt M, Chaker A, Heim M, Heemann U, Schmid RM, Weichert W, Stock KF, Slotta-Huspenina J. Postmortem Minimally Invasive Autopsy in Critically Ill COVID-19 Patients at the Bedside: A Proof-of-Concept Study at the ICU. Diagnostics (Basel) 2024; 14:294. [PMID: 38337812 PMCID: PMC10854968 DOI: 10.3390/diagnostics14030294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/15/2024] [Accepted: 01/22/2024] [Indexed: 02/12/2024] Open
Abstract
BACKGROUND Economic restrictions and workforce cuts have continually challenged conventional autopsies. Recently, the COVID-19 pandemic has added tissue quality and safety requirements to the investigation of this disease, thereby launching efforts to upgrade autopsy strategies. METHODS In this proof-of-concept study, we performed bedside ultrasound-guided minimally invasive autopsy (US-MIA) in the ICU of critically ill COVID-19 patients using a structured protocol to obtain non-autolyzed tissue. Biopsies were assessed for their quality (vitality) and length of biopsy (mm) and for diagnosis. The efficiency of the procedure was monitored in five cases by recording the time of each step and safety issues by swabbing personal protective equipment and devices for viral contamination. FINDINGS Ultrasound examination and tissue procurement required a mean time period of 13 min and 54 min, respectively. A total of 318 multiorgan biopsies were obtained from five patients. Quality and vitality standards were fulfilled, which not only allowed for specific histopathological diagnosis but also the reliable detection of SARS-CoV-2 virions in unexpected organs using electronic microscopy and RNA-expressing techniques. INTERPRETATION Bedside multidisciplinary US-MIA allows for the fast and efficient acquisition of autolytic-free tissue and offers unappreciated potential to overcome the limitations of research in postmortem studies.
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Affiliation(s)
- Tobias Lahmer
- Department of Internal Medicine II, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Straße 22, 81675 Munich, Germany; (S.R.); (J.E.); (M.D.); (R.M.S.)
| | - Gregor Weirich
- Institute of Pathology, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany; (G.W.); (F.A.K.); (C.S.); (P.S.); (C.D.); (P.H.K.); (W.W.); (J.S.-H.)
| | - Stefan Porubsky
- Institut für Pathologie, Universitätsklinikum Mainz, Langenbeckstraße 1, 55131 Mainz, Germany;
| | - Sebastian Rasch
- Department of Internal Medicine II, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Straße 22, 81675 Munich, Germany; (S.R.); (J.E.); (M.D.); (R.M.S.)
| | - Florian A. Kammerstetter
- Institute of Pathology, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany; (G.W.); (F.A.K.); (C.S.); (P.S.); (C.D.); (P.H.K.); (W.W.); (J.S.-H.)
| | - Christian Schustetter
- Institute of Pathology, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany; (G.W.); (F.A.K.); (C.S.); (P.S.); (C.D.); (P.H.K.); (W.W.); (J.S.-H.)
| | - Peter Schüffler
- Institute of Pathology, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany; (G.W.); (F.A.K.); (C.S.); (P.S.); (C.D.); (P.H.K.); (W.W.); (J.S.-H.)
| | - Johanna Erber
- Department of Internal Medicine II, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Straße 22, 81675 Munich, Germany; (S.R.); (J.E.); (M.D.); (R.M.S.)
| | - Miriam Dibos
- Department of Internal Medicine II, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Straße 22, 81675 Munich, Germany; (S.R.); (J.E.); (M.D.); (R.M.S.)
| | - Claire Delbridge
- Institute of Pathology, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany; (G.W.); (F.A.K.); (C.S.); (P.S.); (C.D.); (P.H.K.); (W.W.); (J.S.-H.)
| | - Peer Hendrik Kuhn
- Institute of Pathology, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany; (G.W.); (F.A.K.); (C.S.); (P.S.); (C.D.); (P.H.K.); (W.W.); (J.S.-H.)
| | - Samuel Jeske
- Institute of Virology, School of Medicine, Technical University of Munich/Helmholtz Zentrum München, Trogerstraße 30, 81675 Munich, Germany;
| | - Manuel Steinhardt
- Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Ismaninger Straße 22, 81675 Munich, Germany;
| | - Adam Chaker
- Department of Otorhinolaryngology, University Hospital Klinikum Rechts der Isar, Ismaninger Straße 22, 81675 Munich, Germany;
| | - Markus Heim
- Department of Anesthesiology and Intensive Medicine, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany;
| | - Uwe Heemann
- Department of Nephrology, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany; (U.H.); (K.F.S.)
| | - Roland M. Schmid
- Department of Internal Medicine II, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Straße 22, 81675 Munich, Germany; (S.R.); (J.E.); (M.D.); (R.M.S.)
| | - Wilko Weichert
- Institute of Pathology, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany; (G.W.); (F.A.K.); (C.S.); (P.S.); (C.D.); (P.H.K.); (W.W.); (J.S.-H.)
| | - Konrad Friedrich Stock
- Department of Nephrology, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany; (U.H.); (K.F.S.)
| | - Julia Slotta-Huspenina
- Institute of Pathology, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany; (G.W.); (F.A.K.); (C.S.); (P.S.); (C.D.); (P.H.K.); (W.W.); (J.S.-H.)
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10
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Nagaraju S, Ramalingam S, Mani S. Pulmonary Manifestations of COVID-19. TEXTBOOK OF SARS-COV-2 AND COVID-19 2024:100-136. [DOI: 10.1016/b978-0-323-87539-4.00005-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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11
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Cha MJ, Solomon JJ, Lee JE, Choi H, Chae KJ, Lee KS, Lynch DA. Chronic Lung Injury after COVID-19 Pneumonia: Clinical, Radiologic, and Histopathologic Perspectives. Radiology 2024; 310:e231643. [PMID: 38193836 PMCID: PMC10831480 DOI: 10.1148/radiol.231643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 09/06/2023] [Accepted: 09/26/2023] [Indexed: 01/10/2024]
Abstract
With the COVID-19 pandemic having lasted more than 3 years, concerns are growing about prolonged symptoms and respiratory complications in COVID-19 survivors, collectively termed post-COVID-19 condition (PCC). Up to 50% of patients have residual symptoms and physiologic impairment, particularly dyspnea and reduced diffusion capacity. Studies have also shown that 24%-54% of patients hospitalized during the 1st year of the pandemic exhibit radiologic abnormalities, such as ground-glass opacity, reticular opacity, bronchial dilatation, and air trapping, when imaged more than 1 year after infection. In patients with persistent respiratory symptoms but normal results at chest CT, dual-energy contrast-enhanced CT, xenon 129 MRI, and low-field-strength MRI were reported to show abnormal ventilation and/or perfusion, suggesting that some lung injury may not be detectable with standard CT. Histologic patterns in post-COVID-19 lung disease include fibrosis, organizing pneumonia, and vascular abnormality, indicating that different pathologic mechanisms may contribute to PCC. Therefore, a comprehensive imaging approach is necessary to evaluate and diagnose patients with persistent post-COVID-19 symptoms. This review will focus on the long-term findings of clinical and radiologic abnormalities and describe histopathologic perspectives. It also addresses advanced imaging techniques and deep learning approaches that can be applied to COVID-19 survivors. This field remains an active area of research, and further follow-up studies are warranted for a better understanding of the chronic stage of the disease and developing a multidisciplinary approach for patient management.
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Affiliation(s)
- Min Jae Cha
- From the Department of Radiology, Chung-Ang University Hospital,
Seoul, Korea (M.J.C., H.C.); Departments of Medicine (J.J.S.) and Radiology
(K.J.C., D.A.L.), National Jewish Health, 1400 Jackson St, Denver, CO 80206;
Department of Radiology, Chonnam National University Hospital, Gwangju, Republic
of Korea (J.E.L.); Department of Radiology, Research Institute of Clinical
Medicine of Jeonbuk National University, Biomedical Research Institute of
Jeonbuk National University Hospital, Jeonju, Republic of Korea (K.J.C); and
Department of Radiology, Sungkyunkwan University School of Medicine and Samsung
ChangWon Hospital, Gyeongsangnam, Republic of Korea (K.S.L.)
| | - Joshua J. Solomon
- From the Department of Radiology, Chung-Ang University Hospital,
Seoul, Korea (M.J.C., H.C.); Departments of Medicine (J.J.S.) and Radiology
(K.J.C., D.A.L.), National Jewish Health, 1400 Jackson St, Denver, CO 80206;
Department of Radiology, Chonnam National University Hospital, Gwangju, Republic
of Korea (J.E.L.); Department of Radiology, Research Institute of Clinical
Medicine of Jeonbuk National University, Biomedical Research Institute of
Jeonbuk National University Hospital, Jeonju, Republic of Korea (K.J.C); and
Department of Radiology, Sungkyunkwan University School of Medicine and Samsung
ChangWon Hospital, Gyeongsangnam, Republic of Korea (K.S.L.)
| | - Jong Eun Lee
- From the Department of Radiology, Chung-Ang University Hospital,
Seoul, Korea (M.J.C., H.C.); Departments of Medicine (J.J.S.) and Radiology
(K.J.C., D.A.L.), National Jewish Health, 1400 Jackson St, Denver, CO 80206;
Department of Radiology, Chonnam National University Hospital, Gwangju, Republic
of Korea (J.E.L.); Department of Radiology, Research Institute of Clinical
Medicine of Jeonbuk National University, Biomedical Research Institute of
Jeonbuk National University Hospital, Jeonju, Republic of Korea (K.J.C); and
Department of Radiology, Sungkyunkwan University School of Medicine and Samsung
ChangWon Hospital, Gyeongsangnam, Republic of Korea (K.S.L.)
| | - Hyewon Choi
- From the Department of Radiology, Chung-Ang University Hospital,
Seoul, Korea (M.J.C., H.C.); Departments of Medicine (J.J.S.) and Radiology
(K.J.C., D.A.L.), National Jewish Health, 1400 Jackson St, Denver, CO 80206;
Department of Radiology, Chonnam National University Hospital, Gwangju, Republic
of Korea (J.E.L.); Department of Radiology, Research Institute of Clinical
Medicine of Jeonbuk National University, Biomedical Research Institute of
Jeonbuk National University Hospital, Jeonju, Republic of Korea (K.J.C); and
Department of Radiology, Sungkyunkwan University School of Medicine and Samsung
ChangWon Hospital, Gyeongsangnam, Republic of Korea (K.S.L.)
| | - Kum Ju Chae
- From the Department of Radiology, Chung-Ang University Hospital,
Seoul, Korea (M.J.C., H.C.); Departments of Medicine (J.J.S.) and Radiology
(K.J.C., D.A.L.), National Jewish Health, 1400 Jackson St, Denver, CO 80206;
Department of Radiology, Chonnam National University Hospital, Gwangju, Republic
of Korea (J.E.L.); Department of Radiology, Research Institute of Clinical
Medicine of Jeonbuk National University, Biomedical Research Institute of
Jeonbuk National University Hospital, Jeonju, Republic of Korea (K.J.C); and
Department of Radiology, Sungkyunkwan University School of Medicine and Samsung
ChangWon Hospital, Gyeongsangnam, Republic of Korea (K.S.L.)
| | - Kyung Soo Lee
- From the Department of Radiology, Chung-Ang University Hospital,
Seoul, Korea (M.J.C., H.C.); Departments of Medicine (J.J.S.) and Radiology
(K.J.C., D.A.L.), National Jewish Health, 1400 Jackson St, Denver, CO 80206;
Department of Radiology, Chonnam National University Hospital, Gwangju, Republic
of Korea (J.E.L.); Department of Radiology, Research Institute of Clinical
Medicine of Jeonbuk National University, Biomedical Research Institute of
Jeonbuk National University Hospital, Jeonju, Republic of Korea (K.J.C); and
Department of Radiology, Sungkyunkwan University School of Medicine and Samsung
ChangWon Hospital, Gyeongsangnam, Republic of Korea (K.S.L.)
| | - David A. Lynch
- From the Department of Radiology, Chung-Ang University Hospital,
Seoul, Korea (M.J.C., H.C.); Departments of Medicine (J.J.S.) and Radiology
(K.J.C., D.A.L.), National Jewish Health, 1400 Jackson St, Denver, CO 80206;
Department of Radiology, Chonnam National University Hospital, Gwangju, Republic
of Korea (J.E.L.); Department of Radiology, Research Institute of Clinical
Medicine of Jeonbuk National University, Biomedical Research Institute of
Jeonbuk National University Hospital, Jeonju, Republic of Korea (K.J.C); and
Department of Radiology, Sungkyunkwan University School of Medicine and Samsung
ChangWon Hospital, Gyeongsangnam, Republic of Korea (K.S.L.)
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de Souza Xavier Costa N, Ribeiro Júnior G, do Nascimento ECT, de Brito JM, Antonangelo L, Faria CS, Monteiro JS, Setubal JC, Pinho JRR, Pereira RV, Seelaender M, de Castro GS, Lima JDCC, de Almeida Monteiro RA, Duarte-Neto AN, Saldiva PHN, Ferraz da Silva LF, Dolhnikoff M, Mauad T. COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS. Respir Res 2023; 24:281. [PMID: 37964271 PMCID: PMC10648646 DOI: 10.1186/s12931-023-02555-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 10/05/2023] [Indexed: 11/16/2023] Open
Abstract
BACKGROUND Lung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS. METHODS We have quantified different ECM elements and TGF-β expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile. RESULTS We observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-β, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-β was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course. CONCLUSIONS Fatal COVID-19 is associated with an early TGF-β expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.
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Affiliation(s)
| | - Gabriel Ribeiro Júnior
- Departamento de Patologia (LIM 05), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | | | - Jôse Mara de Brito
- Departamento de Patologia (LIM 05), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Leila Antonangelo
- Laboratório de Investigação Médica (LIM03), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo, Brazil
- Divisão de Patologia Clínica, Departamento de Patologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Caroline Silvério Faria
- Laboratório de Investigação Médica (LIM03), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo, Brazil
| | | | - João Carlos Setubal
- Departamento de Bioquímica, Instituto de Química Universidade de São Paulo, São Paulo, Brazil
| | - João Renato Rebello Pinho
- Laboratório de Investigação Médica (LIM03), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo, Brazil
| | - Roberta Verciano Pereira
- Laboratório de Investigação Médica (LIM03), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo, Brazil
| | - Marilia Seelaender
- Cancer Metabolism Research Group, University of São Paulo, São Paulo, Brazil
- Department of Surgery and LIM 26, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil
| | - Gabriela Salim de Castro
- Cancer Metabolism Research Group, University of São Paulo, São Paulo, Brazil
- Department of Surgery and LIM 26, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil
| | - Joanna D C C Lima
- Cancer Metabolism Research Group, University of São Paulo, São Paulo, Brazil
- Department of Surgery and LIM 26, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil
| | | | - Amaro Nunes Duarte-Neto
- Departamento de Patologia (LIM 05), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | | | - Luiz Fernando Ferraz da Silva
- Departamento de Patologia (LIM 05), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Serviço de Verificação de Óbitos da Capital, Universidade de São Paulo, São Paulo, Brazil
| | - Marisa Dolhnikoff
- Departamento de Patologia (LIM 05), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Thais Mauad
- Departamento de Patologia (LIM 05), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
- Departamento de Patologia, Laboratório de Patologia Ambiental (LIM- 05), Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455, sala 1155, Cerqueira Cesar, São Paulo, Brazil.
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13
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Noack P, Grosse C, Bodingbauer J, Almeder M, Lohfink-Schumm S, Salzer HJF, Meier J, Lamprecht B, Schmitt CA, Langer R. Minimally invasive autopsies for the investigation of pulmonary pathology of COVID-19-experiences of a longitudinal series of 92 patients. Virchows Arch 2023; 483:611-619. [PMID: 37653260 PMCID: PMC10673967 DOI: 10.1007/s00428-023-03622-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 07/20/2023] [Accepted: 08/07/2023] [Indexed: 09/02/2023]
Abstract
Minimally invasive autopsies (MIAs) allow the collection of tissue samples for diagnostic and research purposes in special situations, e.g., when there is a high risk of infection which is the case in the context of COVID-19 or restrictions due to legal or personal reasons. We performed MIA to analyze lung tissue from 92 COVID-19 patients (mean age 78 years; range 48-98; 35 women, 57 men), representing 44% of all patients who died from the disease between October 2020 and April 2021. An intercostal approach was used with removal of a 5-cm rib section followed by manual collection of four lung tissue samples (5-8 cm in size). Diffuse alveolar damage (DAD) was found in 89 (97%) patients at various stages. Exudative DAD (eDAD) predominated in 18 (20%) patients, proliferative DAD (pDAD) in 43 (47%) patients, and mixed DAD (mDAD) in 31 (34%) patients. There were no significant differences in the predominant DAD pattern between tissue samples from the same patient. Additional purulent components were present in 46 (50%) cases. Fungi were detected in 11 (12%) patients. The pDAD pattern was associated with longer hospital stay including intensive care unit (p=0.026 and p<0.001) and younger age (p=0.019). Positive bronchoalveolar lavage and blood cultures were observed more frequently in pDAD patterns (p<0.001; p=0.018). In contrast, there was no significant association between intravital positive microbiological results and superimposed bronchopneumonia or fungal infection at autopsy. Having demonstrated the characteristic lung changes in a large longitudinal autopsy series, we conclude that the presented MIA approach can be considered a reliable and safe method for performing post mortem lung diagnostics in COVID-19 and other high-risk situations. The lack of correlation between histological changes indicative of bacterial or fungal superinfection and microbiology could have clinical implications for disease and treatment surveillance.
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Affiliation(s)
- Petar Noack
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria
- Medical Faculty, Johannes Kepler University, Linz, Austria
| | - Claudia Grosse
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria
| | - Jacob Bodingbauer
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria
- Medical Faculty, Johannes Kepler University, Linz, Austria
| | - Marion Almeder
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria
- Medical Faculty, Johannes Kepler University, Linz, Austria
| | - Sylvia Lohfink-Schumm
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria
- Medical Faculty, Johannes Kepler University, Linz, Austria
| | - Helmut J F Salzer
- Medical Faculty, Johannes Kepler University, Linz, Austria
- Division of Infectious Diseases and Tropical Medicine, Department of Pulmonary Medicine, Kepler University Hospital, Linz, Austria
- Ignaz-Semmelweis-Institute, Interuniversity Institute for Infection Research, Vienna, Austria
| | - Jens Meier
- Medical Faculty, Johannes Kepler University, Linz, Austria
- Department of Anesthesiology and Intensive Care Medicine, Kepler University Hospital, Linz, Austria
| | - Bernd Lamprecht
- Medical Faculty, Johannes Kepler University, Linz, Austria
- Department of Pulmonary Medicine, Kepler University Hospital, Linz, Austria
| | - Clemens A Schmitt
- Medical Faculty, Johannes Kepler University, Linz, Austria
- Department of Hematology and Medical Oncology, Kepler University Hospital, Linz, Austria
| | - Rupert Langer
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria.
- Medical Faculty, Johannes Kepler University, Linz, Austria.
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14
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Kim S, Seok H, Kim BK, Hwang J, Park DW, Shin JS, Kim JH. COVID-19 versus Other Disease Etiologies as the Cause of ARDS in Patients Necessitating Venovenous Extracorporeal Membrane Oxygenation-A Comparison of Patients' Data during the Three Years of the COVID-19 Pandemic. J Clin Med 2023; 12:6752. [PMID: 37959217 PMCID: PMC10647761 DOI: 10.3390/jcm12216752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 10/22/2023] [Accepted: 10/24/2023] [Indexed: 11/15/2023] Open
Abstract
Considering the characteristics of coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS), we compared the clinical course and outcomes of patients with ARDS who received venovenous extracorporeal membrane oxygenation (VV ECMO) based on the etiology of ARDS. This retrospective single-center study included adult patients with severe ARDS necessitating VV ECMO during the COVID-19 pandemic. Among 45 patients who received VV ECMO, 21 presented with COVID-19. COVID-19 patients exhibited lower sequential organ failure assessment scores (9 [8-12.75] versus 8 [4-11.5], p = 0.033) but longer duration of VV ECMO support (10.5 days [3.25-29.25] versus 28 days [10.5-70.5] p = 0.018), which was accompanied by an weaning off rate from VV ECMO in 12/24 (50%) versus 12/21 (57.1%) and 28-day mortality in 9/24 [37.5%] versus 2/21 [9.5%] in non-COVID-19 and COVID-19 patients (p = 0.767, p = 0.040), respectively. Finally, in the adjusted Cox regression model for hospital mortality, the hazard ratio of COVID-19 was not significant (hazard ratio 0.350, 95% confidence interval 0.110-1.115, p = 0.076). Although the VV ECMO period was longer, COVID-19 did not significantly impact ECMO weaning off and mortality rates. Nonetheless, judicious patient selections based on risk factors should be followed.
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Affiliation(s)
- Sua Kim
- Department of Critical Care Medicine, Korea University College of Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea;
| | - Hyeri Seok
- Division of Infectious Disease, Department of Internal Medicine, Korea University College of Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea; (H.S.); (D.W.P.)
| | - Beong Ki Kim
- Division of Pulmonology, Department of Internal Medicine, Korea University College of Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea;
| | - Jinwook Hwang
- Department of Thoracic and Cardiovascular Surgery, Korea University College of Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea; (J.H.); (J.S.S.)
| | - Dae Won Park
- Division of Infectious Disease, Department of Internal Medicine, Korea University College of Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea; (H.S.); (D.W.P.)
| | - Jae Seung Shin
- Department of Thoracic and Cardiovascular Surgery, Korea University College of Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea; (J.H.); (J.S.S.)
| | - Je Hyeong Kim
- Department of Critical Care Medicine, Korea University College of Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea;
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15
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Erickson R, Huang C, Allen C, Ireland J, Roth G, Zou Z, Lu J, Lafont BAP, Garza NL, Brumbaugh B, Zhao M, Suzuki M, Olano L, Brzostowski J, Fischer ER, Twigg HL, Johnson RF, Sun PD. SARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition. Nat Commun 2023; 14:6380. [PMID: 37821447 PMCID: PMC10567911 DOI: 10.1038/s41467-023-42140-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 09/27/2023] [Indexed: 10/13/2023] Open
Abstract
Severe COVID-associated lung injury is a major confounding factor of hospitalizations and death with no effective treatments. Here, we describe a non-classical fibrin clotting mechanism mediated by SARS-CoV-2 infected primary lung but not other susceptible epithelial cells. This infection-induced fibrin formation is observed in all variants of SARS-CoV-2 infections, and requires thrombin but is independent of tissue factor and other classical plasma coagulation factors. While prothrombin and fibrinogen levels are elevated in acute COVID BALF samples, fibrin clotting occurs only with the presence of viral infected but not uninfected lung epithelial cells. We suggest a viral-induced coagulation mechanism, in which prothrombin is activated by infection-induced transmembrane serine proteases, such as ST14 and TMPRSS11D, on NHBE cells. Our finding reveals the inefficiency of current plasma targeted anticoagulation therapy and suggests the need to develop a viral-induced ARDS animal model for treating respiratory airways with thrombin inhibitors.
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Affiliation(s)
- Rachel Erickson
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Chang Huang
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Cameron Allen
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Joanna Ireland
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Gwynne Roth
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Zhongcheng Zou
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Jinghua Lu
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Bernard A P Lafont
- SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Nicole L Garza
- SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Beniah Brumbaugh
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT, 59840, USA
| | - Ming Zhao
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Motoshi Suzuki
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Lisa Olano
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Joseph Brzostowski
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Elizabeth R Fischer
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT, 59840, USA
| | - Homer L Twigg
- Division of Pulmonary, Critical Care, Sleep, and Occupational Medicine, Indiana University Medical Center, 1120 West Michigan Street, CL 260A, Indianapolis, IN, 46202, USA
| | - Reed F Johnson
- SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Peter D Sun
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA.
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16
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Kramer D, Hilton R, Roman J. Pulmonary fibrosis and COVID-19. Am J Med Sci 2023; 366:245-253. [PMID: 37481205 DOI: 10.1016/j.amjms.2023.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 07/10/2023] [Accepted: 07/17/2023] [Indexed: 07/24/2023]
Abstract
The COVID-19 pandemic has caused the death of millions and many more have been infected worldwide. The causative virus, SARS-CoV-2, affects the lung where it elicits an aggressive inflammatory response leading to respiratory failure in severe cases. This infection has been linked to pulmonary fibrosis, a process characterized by fibroproliferation and the exaggerated deposition of collagen and other extracellular matrices. These events damage the lung architecture, especially its gas-exchanging units, leading to hypoxemic respiratory failure. The mechanisms by which the virus affects the lung remain incompletely understood, but it is postulated that after entering the airways, the virus binds to Angiotensin Converting Enzyme (ACE) receptors on the surface of epithelial cells, not only stimulating oxidative stress and inflammation, but also promoting the expression of soluble pro-fibrotic factors responsible for the accumulation of fibroblasts, their activation into myofibroblasts, and their unregulated expression of extracellular matrices. These events may trigger the rapid progression or exacerbation of underlying interstitial lung disorders or promote fibrosis in a previously healthy lung. Although the natural progression of such conditions cannot always be predicted, fibrosis may progress even after the virus has been eliminated or, in cases where it does not progress, may become irreversible, leading to long-standing symptoms like shortness of breath and exercise intolerance resulting from loss of lung function. Although COVID-19 related pulmonary fibrosis is not common, preventive measures like vaccination are encouraged, as they are expected to reduce infection or its severity, thereby decreasing the possibility of life-changing respiratory conditions such as pulmonary fibrosis.
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Affiliation(s)
- Daniel Kramer
- Division of Pulmonary, Allergy and Critical Care, Department of Medicine; Jane & Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Robert Hilton
- Division of Pulmonary, Allergy and Critical Care, Department of Medicine; Jane & Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Jesse Roman
- Division of Pulmonary, Allergy and Critical Care, Department of Medicine; Jane & Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
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17
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Das S, Roy A, Das R. New autopsy technique in COVID-19 positive dead bodies: opening the thoracic cavity with an outlook to reduce aerosol spread. J Clin Pathol 2023; 76:664-670. [PMID: 35701143 PMCID: PMC9240445 DOI: 10.1136/jclinpath-2022-208173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 05/20/2022] [Indexed: 11/19/2022]
Abstract
AIMS After the advent of the COVID-19 pandemic, most countries have modified some of their health-related regulations. However, this has not been in the case of the postmortem of deceased because it has a legal aspect. Thus, the healthcare providers knowingly or unknowingly faced the threat of COVID-19 exposure from those dead bodies. To introduce an autopsy technique that reduces the droplet spreads, especially in those mortuaries where the biosafety mechanism is not highly equipped. METHODS The validity of the new incision was achieved through the calculation of the Scale Content Validity Index (SCVI) taking inputs from 17 forensic specialists. The subjects for the new technique were selected from the patients who were RTPCR positive for COVID-19 or clinically or radiologically showing features of COVID-19. RESULTS The dissection procedure was finalised by achieving the SCVI at 0.92. The chest cavity was approached through the abdominal cavity by opening the diaphragm and dissecting out the contents of the chest using a long blade knife. CONCLUSIONS The advantage of this approach is that the autopsy surgeon and pathologists do not have to open the chest cavity by dissecting the Sternum, and hence the chance of droplet infection becomes almost nil. This technique is complete, simple, less time-consuming and conducive for sample collection, and even reduces the possibility of body fluid seepage following a postmortem examination.
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Affiliation(s)
- Somnath Das
- Forensic Medicine and Toxicology, RG Kar Medical College, Kolkata, West Bengal, India
| | - Anshuman Roy
- Anatomy, Raiganj Government Medical College, Raiganj, West Bengal, India
| | - Rina Das
- Forensic Medicine and Toxicology, NRS Medical College, Kolkata, West Bengal, India
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18
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Vicens-Zygmunt V, Pérez-Rubio G, Chavez-Galan L, Buendia-Roldan I, Falfán-Valencia R. Editorial: Translational research in severe COVID-19 and long-term symptoms post-COVID-19. Front Med (Lausanne) 2023; 10:1261211. [PMID: 37828951 PMCID: PMC10565468 DOI: 10.3389/fmed.2023.1261211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 09/13/2023] [Indexed: 10/14/2023] Open
Affiliation(s)
- Vanesa Vicens-Zygmunt
- Interstitial Lung Disease Unit, Department of Respiratory, University Hospital of Bellvitge, CIBERES, University of Barcelona (UB)-IDIBELL, Barcelona, Spain
| | - Gloria Pérez-Rubio
- HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico
| | - Leslie Chavez-Galan
- Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico
| | - Ivette Buendia-Roldan
- Translational Research Laboratory on Aging and Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico
| | - Ramcés Falfán-Valencia
- HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico
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19
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Fukihara J, Kondoh Y. COVID-19 and interstitial lung diseases: A multifaceted look at the relationship between the two diseases. Respir Investig 2023; 61:601-617. [PMID: 37429073 PMCID: PMC10281233 DOI: 10.1016/j.resinv.2023.05.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 04/09/2023] [Accepted: 05/22/2023] [Indexed: 07/12/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although it has been a fatal disease for many patients, the development of treatment strategies and vaccines have progressed over the past 3 years, and our society has become able to accept COVID-19 as a manageable common disease. However, as COVID-19 sometimes causes pneumonia, post-COVID pulmonary fibrosis (PCPF), and worsening of preexisting interstitial lung diseases (ILDs), it is still a concern for pulmonary physicians. In this review, we have selected several topics regarding the relationships between ILDs and COVID-19. The pathogenesis of COVID-19-induced ILD is currently assumed based mainly on the evidence of other ILDs and has not been well elucidated specifically in the context of COVID-19. We have summarized what has been clarified to date and constructed a coherent story about the establishment and progress of the disease. We have also reviewed clinical information regarding ILDs newly induced or worsened by COVID-19 or anti-SARS-CoV-2 vaccines. Inflammatory and profibrotic responses induced by COVID-19 or vaccines have been thought to be a risk for de novo induction or worsening of ILDs, and this has been supported by the evidence obtained through clinical experience over the past 3 years. Although COVID-19 has become a mild disease in most cases, it is still worth looking back on the above-reviewed information to broaden our perspectives regarding the relationship between viral infection and ILD. As a representative etiology for severe viral pneumonia, further studies in this area are expected.
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Affiliation(s)
- Jun Fukihara
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi, 489-8642, Japan
| | - Yasuhiro Kondoh
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi, 489-8642, Japan.
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20
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Ashwin H, Milross L, Wilson J, Majo J, Hang Lee JT, Calder G, Hunter B, James S, Lagos D, Signoret N, Filby A, Bayraktar OA, Fisher AJ, Kaye PM. Identification of a protein expression signature distinguishing early from organising diffuse alveolar damage in COVID-19 patients. J Clin Pathol 2023; 76:561-565. [PMID: 36894313 PMCID: PMC10423525 DOI: 10.1136/jcp-2023-208771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 02/09/2023] [Indexed: 03/11/2023]
Abstract
Diffuse alveolar damage (DAD) is the histological expression of acute respiratory distress syndrome and characterises lung pathology due to infection with SARS-CoV-2, and other respiratory pathogens of clinical significance. DAD reflects a time-dependent immunopathological process, progressing from an early/exudative stage through to an organising/fibrotic stage, yet within an individual these different stages of DAD may coexist. Understanding the progression of DAD is central to the development of new therapeutics to limit progressive lung damage. Here, we applied highly multiplexed spatial protein profiling to autopsy lung tissues derived from 27 patients who died from COVID-19 and identified a protein signature (ARG1, CD127, GZMB, IDO1, Ki67, phospho-PRAS40 (T246) and VISTA) that distinguishes early DAD from late DAD with good predictive accuracy. These proteins warrant further investigation as potential regulators of DAD progression.
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Affiliation(s)
- Helen Ashwin
- York Biomedical Research Institute, Hull York Medical School, University of York, York, UK
| | - Luke Milross
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Julie Wilson
- Department of Mathematics, University of York, York, UK
| | - Joaquim Majo
- Department of Cellular Pathology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | | | - Grant Calder
- Biosciences Technology Facility, University of York, York, UK
| | - Bethany Hunter
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Sally James
- Biosciences Technology Facility, University of York, York, UK
| | - Dimitris Lagos
- York Biomedical Research Institute, Hull York Medical School, University of York, York, UK
| | - Nathalie Signoret
- York Biomedical Research Institute, Hull York Medical School, University of York, York, UK
| | - Andrew Filby
- Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | | | - Andrew J Fisher
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
- Institute of Transplantation, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Paul M Kaye
- York Biomedical Research Institute, Hull York Medical School, University of York, York, UK
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21
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Ruiz-Cáceres I, Hermida Romero T, Guerra Merino I, Portu Zapirain J, Pérez-Mies B, Sánchez-Conde M, Riaño MA, Rubio R, Fortés Alen J, Vidal González Á, Salas Antón C, Múñez E, Sánchez Sánchez R, Corona-Mata D, Aldecoa Ansorregui I, Miró JM, Beloqui Pérez de Obanos R, Ibero C, Gómez-Román J, Fariñas MC, Tabuyo Bello T, de Alava E, Cisneros JM, Matías-Guiu X, Rivero A, on behalf of the NECROCOVID Study Group. Post-mortem findings in Spanish patients with COVID-19; a special focus on superinfections. Front Med (Lausanne) 2023; 10:1151843. [PMID: 37484846 PMCID: PMC10359908 DOI: 10.3389/fmed.2023.1151843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 06/15/2023] [Indexed: 07/25/2023] Open
Abstract
Introduction Whole-body autopsies may be crucial to understand coronavirus disease 2019 (COVID-19) pathophysiology. We aimed to analyze pathological findings in a large series of full-body autopsies, with a special focus on superinfections. Methods This was a prospective multicenter study that included 70 COVID-19 autopsies performed between April 2020 and February 2021. Epidemiological, clinical and pathological information was collected using a standardized case report form. Results Median (IQR) age was 70 (range 63.75-74.25) years and 76% of cases were males. Most patients (90%,) had at least one comorbidity prior to COVID-19 diagnosis, with vascular risk factors being the most frequent. Infectious complications were developed by 65.71% of the patients during their follow-up. Mechanical ventilation was required in most patients (75.71%) and was mainly invasive. In multivariate analyses, length of hospital stay and invasive mechanical ventilation were significantly associated with infections (p = 0.036 and p = 0.013, respectively). Necropsy findings revealed diffuse alveolar damage in the lungs, left ventricular hypertrophy in the heart, liver steatosis and pre-infection arteriosclerosis in the heart and kidneys. Conclusion Our study confirms the main necropsy histopathological findings attributed to COVID-19 in a large patient series, while underlining the importance of both comorbid conditions and superinfections in the pathology.
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Affiliation(s)
- Inmaculada Ruiz-Cáceres
- Department of Infectious Diseases, Reina Sofía University Hospital, The Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba University (UCO), Córdoba, Spain
- CIBERINFEC, ISCIII – CIBER de Enfermedades Infecciosas Instituto de Salud Carlos III, Madrid, Spain
| | - Teresa Hermida Romero
- Department of Pathological Anatomy, A Coruña University Hospital Complex, A Coruña, Spain
| | - Isabel Guerra Merino
- Department of Pathological Anatomy, University Hospital of Álava, Vitoria-Gasteiz, Spain
| | - Joseba Portu Zapirain
- Bioaraba, Microbiology, Infectious Diseases, Antimicrobials and Gene Therapy Research Group, Vitoria-Gasteiz, Spain
- Osakidetza Basque Health Service, Álava University Hospital, Vitoria-Gasteiz, Spain
| | - Belén Pérez-Mies
- Department of Pathological Anatomy, Ramón y Cajal University Hospital, Madrid, Spain
| | - Matilde Sánchez-Conde
- Department of Infectious Diseases, Ramón y Cajal University Hospital-IRYCIS, CIBERINFEC, Madrid, Spain
| | - Marina Alonso Riaño
- Department of Pathological Anatomy, 12 de Octubre University Hospital, Madrid, Spain
| | - Rafael Rubio
- Section of Internal Medicine, 12 de Octubre University Hospital, Department of Medicine, School of Medicine, Complutense University of Madrid, Madrid, Spain
| | - Jose Fortés Alen
- Department of Pathological Anatomy, Fundación Jiménez Díaz University Hospital, Madrid, Spain
| | - Ánxela Vidal González
- Department of Intensive Care Medicine, Fundación Jiménez Díaz University Hospital, Madrid, Spain
| | - Clara Salas Antón
- Department of Pathological Anatomy, Puerta de Hierro University Hospital, Majadahonda, Spain
| | - Elena Múñez
- Infectious Diseases Unit, Puerta de Hierro University Hospital, Majadahonda, Spain
| | | | - Diana Corona-Mata
- Department of Infectious Diseases, Reina Sofía University Hospital, The Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba University (UCO), Córdoba, Spain
| | | | - José M. Miró
- Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
- CIBERINFEC, Instituto Carlos III, Madrid, Spain
| | | | - Carlos Ibero
- Infectious Diseases, COVID Coordination at University Hospital of Navarra, Pamplona, Spain
| | - Javier Gómez-Román
- Department of Pathological Anatomy, Marqués de Valdecilla University Hospital, Santander, Spain
| | - M. Carmen Fariñas
- Department of Infectious Diseases, Marqués de Valdecilla University Hospital, IDIVAL, CIBERINFEC, University of Cantabria, Santander, Cantabria, Spain
| | - Teresa Tabuyo Bello
- Department of Intensive Care, A Coruña University Hospital Complex, A Coruña, Spain
| | - Enrique de Alava
- Department of Pathological Anatomy, Virgen del Rocío University Hospital, Seville, Spain
| | - José Miguel Cisneros
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain
| | - Xavier Matías-Guiu
- Department of Pathological Anatomy, Bellvitge University Hospital, Barcelona, Spain
| | - Antonio Rivero
- Department of Infectious Diseases, Reina Sofía University Hospital, The Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba University (UCO), Córdoba, Spain
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22
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Cîrjaliu RE, Deacu M, Gherghișan I, Marghescu AȘ, Enciu M, Băltățescu GI, Nicolau AA, Tofolean DE, Arghir OC, Fildan AP. Clinicopathological Outlines of Post-COVID-19 Pulmonary Fibrosis Compared with Idiopathic Pulmonary Fibrosis. Biomedicines 2023; 11:1739. [PMID: 37371834 DOI: 10.3390/biomedicines11061739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 06/06/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
This review brings together the current knowledge regarding the risk factors and the clinical, radiologic, and histological features of both post-COVID-19 pulmonary fibrosis (PCPF) and idiopathic pulmonary fibrosis (IPF), describing the similarities and the disparities between these two diseases, using numerous databases to identify relevant articles published in English through October 2022. This review would help clinicians, pathologists, and researchers make an accurate diagnosis, which can help identify the group of patients selected for anti-fibrotic therapies and future therapeutic perspectives.
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Affiliation(s)
- Roxana-Elena Cîrjaliu
- Department of Pneumology, Faculty of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
- Clinical Emergency "St. Andrew" Hospital of Constanta, 900591 Constanta, Romania
| | - Mariana Deacu
- Clinical Emergency "St. Andrew" Hospital of Constanta, 900591 Constanta, Romania
- Department of Anatomopathology, Faculty of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
| | - Ioana Gherghișan
- Department of Pneumology, Faculty of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
- Pneumology Hospital of Constanta, 900002 Constanta, Romania
| | - Angela-Ștefania Marghescu
- Department of Anatomopathology, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Pneumology Institute "Marius Nasta", 50158 Bucharest, Romania
| | - Manuela Enciu
- Clinical Emergency "St. Andrew" Hospital of Constanta, 900591 Constanta, Romania
- Department of Anatomopathology, Faculty of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
| | - Gabriela Izabela Băltățescu
- Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology-CEDMOG, "Ovidius" University of Constanta, 900591 Constanta, Romania
| | - Antonela Anca Nicolau
- Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology-CEDMOG, "Ovidius" University of Constanta, 900591 Constanta, Romania
| | - Doina-Ecaterina Tofolean
- Department of Pneumology, Faculty of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
- Clinical Emergency "St. Andrew" Hospital of Constanta, 900591 Constanta, Romania
| | - Oana Cristina Arghir
- Department of Pneumology, Faculty of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
- Pneumology Hospital of Constanta, 900002 Constanta, Romania
| | - Ariadna-Petronela Fildan
- Department of Pneumology, Faculty of Medicine, "Ovidius" University of Constanta, 900470 Constanta, Romania
- Pneumology Hospital of Constanta, 900002 Constanta, Romania
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23
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Lassan S, Tesar T, Tisonova J, Lassanova M. Pharmacological approaches to pulmonary fibrosis following COVID-19. Front Pharmacol 2023; 14:1143158. [PMID: 37397477 PMCID: PMC10308083 DOI: 10.3389/fphar.2023.1143158] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 06/05/2023] [Indexed: 07/04/2023] Open
Abstract
Background: In the past few years, COVID-19 became the leading cause of morbidity and mortality worldwide. Although the World Health Organization has declared an end to COVID-19 as a public health emergency, it can be expected, that the emerging new cases at the top of previous ones will result in an increasing number of patients with post-COVID-19 sequelae. Despite the fact that the majority of patients recover, severe acute lung tissue injury can in susceptible individuals progress to interstitial pulmonary involvement. Our goal is to provide an overview of various aspects associated with the Post-COVID-19 pulmonary fibrosis with a focus on its potential pharmacological treatment options. Areas covered: We discuss epidemiology, underlying pathobiological mechanisms, and possible risk and predictive factors that were found to be associated with the development of fibrotic lung tissue remodelling. Several pharmacotherapeutic approaches are currently being applied and include anti-fibrotic drugs, prolonged use or pulses of systemic corticosteroids and non-steroidal anti-inflammatory and immunosuppressive drugs. In addition, several repurposed or novel compounds are being investigated. Fortunately, clinical trials focused on pharmacological treatment regimens for post-COVID-19 pulmonary fibrosis have been either designed, completed or are already in progress. However, the results are contrasting so far. High quality randomised clinical trials are urgently needed with respect to the heterogeneity of disease behaviour, patient characteristics and treatable traits. Conclusion: The Post-COVID-19 pulmonary fibrosis contributes to the burden of chronic respiratory consequences among survivors. Currently available pharmacotherapeutic approaches mostly comprise repurposed drugs with a proven efficacy and safety profile, namely, corticosteroids, immunosuppressants and antifibrotics. The role of nintedanib and pirfenidone is promising in this area. However, we still need to verify conditions under which the potential to prevent, slow or stop progression of lung damage will be fulfilled.
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Affiliation(s)
- Stefan Lassan
- Department of Pneumology, Phthisiology and Functional Diagnostics, Slovak Medical University and Bratislava University Hospital, Bratislava, Slovakia
| | - Tomas Tesar
- Department of Organisation and Management of Pharmacy, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia
| | - Jana Tisonova
- Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Monika Lassanova
- Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University, Bratislava, Slovakia
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Abstract
As the world emerges from the COVID-19 pandemic, clinicians and researchers across the world are trying to understand the sequelae in patients recovered from COVID-19 infection. In this article, the authors review post-acute sequelae of SARS-COV-2, interstitial lung disease, and other lung sequelae in patients recovering from COVID-19 infection.
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Yan MZ, Yang M, Lai CL. Post-COVID-19 Syndrome Comprehensive Assessment: From Clinical Diagnosis to Imaging and Biochemical-Guided Diagnosis and Management. Viruses 2023; 15:v15020533. [PMID: 36851746 PMCID: PMC9964207 DOI: 10.3390/v15020533] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 02/04/2023] [Accepted: 02/05/2023] [Indexed: 02/17/2023] Open
Abstract
The COVID-19 outbreak was first reported in 2019, causing massive morbidity and mortality. The majority of the COVID-19 patients survived and developed Post-COVID-19 Syndrome (PC19S) of varying severity. Currently, the diagnosis of PC19S is achieved through history and symptomatology that cannot be explained by an alternative diagnosis. However, the heavy reliance on subjective reporting is prone to reporting errors. Besides, there is no unified diagnostic assessment tool to classify the clinical severity of patients. This leads to significant difficulties when managing patients in terms of public resource utilization, clinical progression monitorization and rehabilitation plan formulation. This narrative review aims to review current evidence of diagnosis based on triple assessment: clinical symptomatology, biochemical analysis and imaging evidence. Further assessment tools can be developed based on triple assessment to monitor patient's clinical progression, prognosis and intervals of monitoring. It also highlights the high-risk features of patients for closer and earlier monitoring. Rehabilitation programs and related clinical trials are evaluated; however, most of them focus on cardiorespiratory fitness and psychiatric presentations such as anxiety and depression. Further research is required to establish an objective and comprehensive assessment tool to facilitate clinical management and rehabilitation plans.
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Affiliation(s)
- Michael Zhipeng Yan
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China
- Correspondence: (M.Z.Y.); (C.-L.L.)
| | - Ming Yang
- Department of Ophthalmology, The University of Hong Kong, Hong Kong SAR, China
| | - Ching-Lung Lai
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China
- Correspondence: (M.Z.Y.); (C.-L.L.)
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26
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Dillard JA, Martinez SA, Dearing JJ, Montgomery SA, Baxter AK. Animal Models for the Study of SARS-CoV-2-Induced Respiratory Disease and Pathology. Comp Med 2023; 73:72-90. [PMID: 36229170 PMCID: PMC9948904 DOI: 10.30802/aalas-cm-22-000089] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Emergence of the betacoronavirus SARS-CoV-2 has resulted in a historic pandemic, with millions of deaths worldwide. An unprecedented effort has been made by the medical, scientific, and public health communities to rapidly develop and implement vaccines and therapeutics to prevent and reduce hospitalizations and deaths. Although SARS-CoV-2 infection can lead to disease in many organ systems, the respiratory system is its main target, with pneumonia and acute respiratory distress syndrome as the hallmark features of severe disease. The large number of patients who have contracted COVID-19 infections since 2019 has permitted a detailed characterization of the clinical and pathologic features of the disease in humans. However, continued progress in the development of effective preventatives and therapies requires a deeper understanding of the pathogenesis of infection. Studies using animal models are necessary to complement in vitro findings and human clinical data. Multiple animal species have been evaluated as potential models for studying the respiratory disease caused by SARSCoV-2 infection. Knowing the similarities and differences between animal and human responses to infection is critical for effective translation of animal data into human medicine. This review provides a detailed summary of the respiratory disease and associated pathology induced by SARS-CoV-2 infection in humans and compares them with the disease that develops in 3 commonly used models: NHP, hamsters, and mice. The effective use of animals to study SARS-CoV-2-induced respiratory disease will enhance our understanding of SARS-CoV-2 pathogenesis, allow the development of novel preventatives and therapeutics, and aid in the preparation for the next emerging virus with pandemic potential.
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Key Words
- ace2, angiotensin-converting enzyme 2
- agm, african green monkey
- ali, acute lung injury
- ards, acute respiratory distress syndrome
- balf, bronchoalveolar lavage fluid
- cards, covid-19-associated acute respiratory distress syndrome
- dad, diffuse alveolar damage
- dpi, days postinfection
- ggo, ground glass opacities
- s, spike glycoprotein
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Affiliation(s)
- Jacob A Dillard
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Sabian A Martinez
- Division of Comparative Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Justin J Dearing
- Biological and Biomedical Sciences Program, Office of Graduate Education, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Stephanie A Montgomery
- Division of Comparative Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Andvictoria K Baxter
- Division of Comparative Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;,
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27
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Sadretdinova LD, Gantseva KK, Galina II, Tyurin AV. The duration of gastrointestinal symptom persistence at various periods of coronavirus infection. ALMANAC OF CLINICAL MEDICINE 2023; 50:392-399. [DOI: 10.18786/2072-0505-2022-50-025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Aim: To analyze prevalence and type of symptomatic gastrointestinal involvement during symptomatic COVID-19 (up to 412 weeks after the disease) and post-COVID-19 syndrome (more than 12 weeks from the disease onset).
Materials and methods: We retrospectively analyzed the data from 785 in-patients with the diagnosis of COVID-19, who were treated in the infectious disease hospital from May to December 2020. At the first phase of the study we analyzed how frequently they were referred for out-patient care by a gastroenterology specialist after they were discharged from the hospital (all 785 patient medical files). At the 2nd study phase we performed phone calls to 247 patients, that were discharged from the infectious disease hospital, during which a specially designed questionnaire was filled with items on their comorbidities, general and specific complaints, as well as the standardized Gastrointestinal Symptom Rating Scale (GSRS).
Results: Within 2 years after their discharge from the infectious disease hospital, 88 patients asked for specialized gastroenterological care on an out-patient basis. The most common diagnoses were pancreatic diseases (33%), gastric disorders (31%), intestinal disorders (25%), liver and biliary disorders (11%). At referral, the most common complaints were dyspeptic: nausea, bitter taste in the mouth, heartburn, bloating (25%), abdominal pains of various location (17%) and stool abnormalities, such as diarrhea and constipation (11%).
Among patients who participated in the phone survey (N = 247), symptomatic COVID-19 was observed in 90 (11.46%) cases, with predominant complaints being loss of taste, loss of smell, and fever. Post-COVID-19 syndrome was identified in 157 (20%) cases, with their main complaints being weakness, shortness of breath and joint pain. Stool abnormalities and abdominal pain occurred during symptomatic COVID-19 and in the post-COVID-19 period with the same frequency (9% and 10%, respectively). According to the GSRS results, the post-COVID-19 dyspeptic syndrome was characterized by prevailing complaints of heartburn (24%), upper abdominal pain and discomfort (20%), and bloating (15%).
Conclusion: In the patients with a history of COVID-19, along with respiratory syndromes, gastrointestinal symptoms are seen, with their types being variable at various period of the coronavirus infection. In the early COVID-19, these are stool abnormalities and abdominal pain, and during the post-COVID-19 syndrome, nausea, bitter taste in the mouth, heartburn and bloating are more common.
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Yaqoob H, Greenberg D, Huang L, Henson T, Pitaktong A, Peneyra D, Spencer PJ, Malekan R, Goldberg JB, Kai M, Ohira S, Wang Z, Murad MH, Chandy D, Epelbaum O. Extracorporeal membrane oxygenation in COVID-19 compared to other etiologies of acute respiratory failure: A single-center experience. Heart Lung 2023; 57:243-249. [PMID: 36274533 PMCID: PMC9582301 DOI: 10.1016/j.hrtlng.2022.10.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 09/03/2022] [Accepted: 10/06/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND The COVID-19 pandemic has led to a boom in the use of V-V ECMO for ARDS secondary to COVID. Comparisons of outcomes of ECMO for COVID to ECMO for influenza have emerged. Very few comparisons of ECMO for COVID to ECMO for ARDS of all etiologies are available. OBJECTIVES To compare clinically important outcome measures in recipients of ECMO for COVID to those observed in recipients of ECMO for ARDS of other etiologies. METHODS V-V ECMO recipients between March 2020 and March 2022 consisted exclusively of COVID patients and formed the COVID ECMO group. All patients who underwent V-V ECMO for ARDS between January 2014 and March 2020 were eligible for analysis as the non-COVID ECMO comparator group. The primary outcome was survival to hospital discharge. Secondary outcomes included ECMO decannulation, ECMO duration >30 days, and serious complications. RESULTS Thirty-six patients comprised the COVID ECMO group and were compared to 18 non-COVID ECMO patients. Survival to hospital discharge was not significantly different between the two groups (33% in COVID vs. 50% in non-COVID; p = 0.255) nor was there a significant difference in the rate of non-palliative ECMO decannulation. The proportion of patients connected to ECMO for >30 days was significantly higher in the COVID ECMO group: 69% vs. 17%; p = 0.001. There was no significant difference in serious complications. CONCLUSION This study could not identify a statistically significant difference in hospital survival and rate of successful ECMO decannulation between COVID ECMO and non-COVID ECMO patients. Prolonged ECMO may be more common in COVID. Complications were not significantly different.
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Affiliation(s)
- Hamid Yaqoob
- Division of Pulmonary, Critical Care, and Sleep Medicine, Westchester Medical Center, 100 Woods Road Macy Pavilion, Valhalla, NY 10595, USA.
| | - Daniel Greenberg
- Department of Medicine, Westchester Medical Center, Valhalla, NY, USA
| | - Lawrence Huang
- Department of Medicine, Westchester Medical Center, Valhalla, NY, USA
| | - Theresa Henson
- Division of Pulmonary, Critical Care, and Sleep Medicine, Westchester Medical Center, 100 Woods Road Macy Pavilion, Valhalla, NY 10595, USA
| | - Areen Pitaktong
- Department of Medicine, Westchester Medical Center, Valhalla, NY, USA
| | - Daniel Peneyra
- Department of Medicine, Westchester Medical Center, Valhalla, NY, USA
| | - Philip J Spencer
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN, USA
| | - Ramin Malekan
- Division of Cardiothoracic Surgery, Westchester Medical Center, Valhalla, NY, USA
| | - Joshua B Goldberg
- Division of Cardiothoracic Surgery, Westchester Medical Center, Valhalla, NY, USA
| | - Masashi Kai
- Division of Cardiothoracic Surgery, Westchester Medical Center, Valhalla, NY, USA
| | - Suguru Ohira
- Division of Cardiothoracic Surgery, Westchester Medical Center, Valhalla, NY, USA
| | - Zhen Wang
- Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA
| | - M Hassan Murad
- Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA
| | - Dipak Chandy
- Division of Pulmonary, Critical Care, and Sleep Medicine, Westchester Medical Center, 100 Woods Road Macy Pavilion, Valhalla, NY 10595, USA
| | - Oleg Epelbaum
- Division of Pulmonary, Critical Care, and Sleep Medicine, Westchester Medical Center, 100 Woods Road Macy Pavilion, Valhalla, NY 10595, USA
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29
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The Global Prevalence of Pulmonary Fibrosis Among Post–COVID-19 Follow-up Patients. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2023. [DOI: 10.1097/ipc.0000000000001190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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30
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Maddani SS, Rao R, Deepa HC, Noronha AK, Chaudhuri S, Vishwas P. Pathological Lung Patterns of COVID-19 and its Clinical Correlation to Disease Severity. Indian J Crit Care Med 2022; 26:1285-1292. [PMID: 36755635 PMCID: PMC9886025 DOI: 10.5005/jp-journals-10071-24364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 11/02/2022] [Indexed: 12/02/2022] Open
Abstract
Introduction Coronavirus disease-2019 (COVID-19) infection can result in pulmonary complications ranging from mild illness to severe life-threatening disease. There are limited studies correlating the association between the clinical course of COVID-19 and histopathological findings. This study aimed to examine the postmortem histopathological changes in lung tissue of COVID-19-positive patients and to correlate those changes with disease severity. Materials and methods This prospective observational study was conducted in adult COVID-19-positive patients. Postmortem core needle biopsy (CNB) of the lung was done using ultrasonography guidance within 1 hour of death. Histopathological analyses were performed by two expert pulmonary pathologists. The demographic and clinical data of the patients were recorded to correlate them with histopathological findings. Results In total, 48 patients were assessed for inclusion, and 21 patient relatives consented for the study. The median duration of illness was 21 (range 9-38) days, the predominant histopathological finding was diffuse alveolar damage (DAD) in most patients (19/21), followed by pneumonia (13/21). Exudative, intermediate, and advanced DAD patterns were seen in 9.5%, 52.4%, and 28.6% of cases, respectively. Advanced DAD was associated with a longer duration of disease. The pneumonia findings were associated with positive respiratory and blood cultures. The microvascular thrombus was seen only in one patient. Conclusion The predominant pathological findings in our patients were DAD and pneumonia. The DAD type correlated with the duration of illness, and we attributed pneumonia findings to secondary infection. The incidence of microvascular thrombi was low, and it might reflect the effect of treatment with anticoagulation. How to cite this article Maddani SS, Rao R, Deepa HC, Noronha AK, Chaudhuri S, Vishwas P. Pathological Lung Patterns of COVID-19 and its Clinical Correlation to Disease Severity. Indian J Crit Care Med 2022;26(12):1285-1292.
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Affiliation(s)
- Sagar Shanmukhappa Maddani
- Department of Critical Care Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Raghavendra Rao
- Department of Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - HC Deepa
- Department of Pathology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India,HC Deepa, Department of Pathology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India, Phone: +91 9632355325, e-mail:
| | - Adrian Keith Noronha
- Department of Critical Care Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Souvik Chaudhuri
- Department of Critical Care Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - P Vishwas
- Department of Critical Care Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
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31
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Pérez-Mies B, Caniego-Casas T, Bardi T, Carretero-Barrio I, Benito A, García-Cosío M, González-García I, Pizarro D, Rosas M, Cristóbal E, Ruano Y, Garrido MC, Rigual-Bobillo J, de Pablo R, Galán JC, Pestaña D, Palacios J. Progression to lung fibrosis in severe COVID-19 patients: A morphological and transcriptomic study in postmortem samples. Front Med (Lausanne) 2022; 9:976759. [PMID: 36405615 PMCID: PMC9669577 DOI: 10.3389/fmed.2022.976759] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 10/17/2022] [Indexed: 09/02/2023] Open
Abstract
The development of lung fibrosis is a major concern in patients recovered from severe COVID-19 pneumonia. This study aimed to document the evolution of diffuse alveolar damage (DAD) to the fibrosing pattern and define the transcriptional programs involved. Morphological, immunohistochemical and transcriptional analysis were performed in lung samples obtained from autopsy of 33 severe COVID-19 patients (median illness duration: 36 days). Normal lung and idiopathic pulmonary fibrosis (IPF) were used for comparison. Twenty-seven patients with DAD and disease evolution of more than 2 weeks had fibrosis. Pathways and genes related with collagen biosynthesis and extracellular matrix (ECM) biosynthesis and degradation, myofibroblastic differentiation and epithelial to mesenchymal transition (EMT) were overexpressed in COVID-19. This pattern had similarities with that observed in IPF. By immunohistochemistry, pathological fibroblasts (pFBs), with CTHRC1 and SPARC expression, increased in areas of proliferative DAD and decreased in areas of mature fibrosis. Immunohistochemical analysis demonstrated constitutive expression of cadherin-11 in normal epithelial cells and a similar pattern of cadherin and catenin expression in epithelial cells from both normal and COVID-19 samples. Transcriptomic analysis revealed downregulation of the Hippo pathway, concordant with the observation of YAP overexpression in hyperplastic alveolar epithelial cells. Progression to fibrosis in severe COVID-19 is associated with overexpression of fibrogenic pathways and increased in CTHRC1- and SPARC-positive pFBs. Whereas the Hippo pathway seemed to be implicated in the response to epithelial cell damage, EMT was not a major process implicated in COVID-19 mediated lung fibrosis.
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Affiliation(s)
- Belén Pérez-Mies
- Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
- Faculty of Medicine, Alcalá University, Alcalá de Henares, Spain
| | - Tamara Caniego-Casas
- Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
| | - Tommaso Bardi
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Department of Anesthesiology and Surgical Critical Care, Hospital Ramón y Cajal, Madrid, Spain
| | - Irene Carretero-Barrio
- Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Faculty of Medicine, Alcalá University, Alcalá de Henares, Spain
| | - Amparo Benito
- Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Faculty of Medicine, Alcalá University, Alcalá de Henares, Spain
| | - Mónica García-Cosío
- Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Faculty of Medicine, Alcalá University, Alcalá de Henares, Spain
| | - Irene González-García
- Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
| | - David Pizarro
- Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
| | - Marta Rosas
- Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
| | - Eva Cristóbal
- Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
| | - Yolanda Ruano
- Department of Pathology, Medical School, Universidad Complutense, Instituto i + 12, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - María Concepción Garrido
- Department of Pathology, Medical School, Universidad Complutense, Instituto i + 12, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Juan Rigual-Bobillo
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Department of Respiratory, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Raúl de Pablo
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Faculty of Medicine, Alcalá University, Alcalá de Henares, Spain
- Medical Intensive Care Unit, Hospital Ramón y Cajal, Madrid, Spain
| | - Juan Carlos Galán
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Clinical Microbiology Unit, Hospital Ramón y Cajal, Madrid, Spain
- Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - David Pestaña
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Faculty of Medicine, Alcalá University, Alcalá de Henares, Spain
- Department of Anesthesiology and Surgical Critical Care, Hospital Ramón y Cajal, Madrid, Spain
| | - José Palacios
- Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Instituto Ramon y Cajal de Investigación Sanitaria, Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
- Faculty of Medicine, Alcalá University, Alcalá de Henares, Spain
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Iqbal N, Khanum I, Kazi MAI, Riaz SU, Khawaja UA, Awan S, Irfan M, Zubairi ABS, Khan JA. Post COVID-19 sequelae of the respiratory system. A single center experience reporting the compromise of the airway, alveolar and vascular components. Monaldi Arch Chest Dis 2022. [DOI: 10.4081/monaldi.2022.2412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 10/03/2022] [Indexed: 11/06/2022] Open
Abstract
The long-term sequelae of COVID-19 have now become more common and appreciable. The SARS-CoV-2 virus can cause a variety of infectious and non-infectious pulmonary complications. The purpose of this study is to raise awareness about post-COVID-19 pulmonary sequelae, both infectious and non-infectious, in this geographical area. A retrospective study was conducted from July 1st 2020 to December 20th 2020. A total of 1200 patients were evaluated, with 83 suffering from post-COVID-19 pulmonary complications. The patients' mean age was 62 years (IQR 55-69), with 63 (75.9%) being male. The most common co-morbid illnesses were hypertension (49, 59%) and diabetes (45, 54.2%). The majority of them (37, 44.6%) had severe COVID-19, followed by critical COVID-19 (33, 39.8%). There was no statistically significant difference in recurrence of respiratory symptoms or duration of current illness between non-severe, severe, and critical COVID-19 patients. Non-infectious complications were observed in the majority of patients (n=76, 91.5%), including organizing pneumonia/ground glass opacities in 71 (88%) patients, fibrosis in 44 (55%), pulmonary embolism in 10 (12.5%), pneumomediastinum in 6 (7.4%) and pneumothorax in 7 (8.6%). Infective complications (25, 30.1%) included aspergillus infection in 10 (12.0%) and bacterial infection in 5 (8.47%), with more gram-negative infections and one patient developing Mycobacterium tuberculosis. Post COVID-19 mortality was 11 (13.3%). The long-term pulmonary sequelae of COVID-19 are not rare. Cryptogenic organizing pneumonia, ground glass opacities, and fibrosis were common post-COVID-19 sequelae in our patients. This necessitates frequent close monitoring of these patients in order to initiate early appropriate management and prevent further morbidity and eventual mortality.
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Milross L, Majo J, Pulle J, Hoggard S, Cooper N, Hunter B, Duncan CJ, Filby A, Fisher AJ. The trajectory of COVID-19 cardiopulmonary disease: insights from an autopsy study of community-based, pre-hospital deaths. ERJ Open Res 2022; 8:00303-2022. [PMID: 36575708 PMCID: PMC9571221 DOI: 10.1183/23120541.00303-2022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 10/04/2022] [Indexed: 12/30/2022] Open
Abstract
Background Post mortem examination of lung and heart tissue has been vital to developing an understanding of COVID-19 pathophysiology; however studies to date have almost uniformly used tissue obtained from hospital-based deaths where individuals have been exposed to major medical and pharmacological interventions. Methods In this study we investigated patterns of lung and heart injury from 46 community-based, pre-hospital COVID-19-attributable deaths who underwent autopsy. Results The cohort comprised 22 females and 24 males, median age 64 years (range 19-91) at time of death with illness duration range 0-23 days. Comorbidities associated with poor outcomes in COVID-19 included obesity (body mass index >30 kg·m-2) in 19 out of 46 cases (41.3%). Diffuse alveolar damage in its early exudative phase was the most common pattern of lung injury; however significant heterogeneity was identified with bronchopneumonia, pulmonary oedema consistent with acute cardiac failure, pulmonary thromboembolism and microthrombosis also identified and often in overlapping patterns. Review of clinical records and next of kin accounts suggested a combination of unexpectedly low symptom burden, rapidly progressive disease and psychosocial factors may have contributed to a failure of hospital presentation prior to death. Conclusions Identifying such advanced acute lung injury in community-based deaths is extremely unusual and raises the question why some with severe COVID-19 pneumonitis were not hospitalised. Multiple factors including low symptom burden, rapidly progressive disease trajectories and psychosocial factors provide possible explanations.
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Affiliation(s)
- Luke Milross
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Joaquim Majo
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Julian Pulle
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Sam Hoggard
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Nigel Cooper
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Bethany Hunter
- Innovation Methodology and Application Research Theme, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Christopher J.A. Duncan
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
- Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Andrew Filby
- Innovation Methodology and Application Research Theme, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Andrew J. Fisher
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
- Institute of Transplantation, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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Dinnon KH, Leist SR, Okuda K, Dang H, Fritch EJ, Gully KL, De la Cruz G, Evangelista MD, Asakura T, Gilmore RC, Hawkins P, Nakano S, West A, Schäfer A, Gralinski LE, Everman JL, Sajuthi SP, Zweigart MR, Dong S, McBride J, Cooley MR, Hines JB, Love MK, Groshong SD, VanSchoiack A, Phelan SJ, Liang Y, Hether T, Leon M, Zumwalt RE, Barton LM, Duval EJ, Mukhopadhyay S, Stroberg E, Borczuk A, Thorne LB, Sakthivel MK, Lee YZ, Hagood JS, Mock JR, Seibold MA, O’Neal WK, Montgomery SA, Boucher RC, Baric RS. SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice. Sci Transl Med 2022; 14:eabo5070. [PMID: 35857635 PMCID: PMC9273046 DOI: 10.1126/scitranslmed.abo5070] [Citation(s) in RCA: 79] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 06/17/2022] [Indexed: 01/27/2023]
Abstract
A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted SARS-CoV-2 strain MA10 produces an acute respiratory distress syndrome in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases. At 15 to 120 days after virus clearance, pulmonary histologic findings included subpleural lesions composed of collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal up-regulation of profibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early antifibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.
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Affiliation(s)
- Kenneth H. Dinnon
- Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Sarah R. Leist
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Kenichi Okuda
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Hong Dang
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Ethan J. Fritch
- Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Kendra L. Gully
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Gabriela De la Cruz
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Mia D. Evangelista
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Takanori Asakura
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Rodney C. Gilmore
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Padraig Hawkins
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Satoko Nakano
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Ande West
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Alexandra Schäfer
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Lisa E. Gralinski
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Jamie L. Everman
- Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado 80206, USA
| | - Satria P. Sajuthi
- Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado 80206, USA
| | - Mark R. Zweigart
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Stephanie Dong
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Jennifer McBride
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Michelle R. Cooley
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Jesse B. Hines
- Golden Point Scientific Laboratories, Hoover, Alabama 35216, USA
| | - Miriya K. Love
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Steve D. Groshong
- Division of Pathology, Department of Medicine, National Jewish Health, Denver, Colorado 80206, USA
| | | | | | - Yan Liang
- NanoString Technologies, Seattle, Washington 98109, USA
| | - Tyler Hether
- NanoString Technologies, Seattle, Washington 98109, USA
| | - Michael Leon
- NanoString Technologies, Seattle, Washington 98109, USA
| | - Ross E. Zumwalt
- Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
| | - Lisa M. Barton
- Office of the Chief Medical Examiner, Oklahoma City, Oklahoma 73105, USA
| | - Eric J. Duval
- Office of the Chief Medical Examiner, Oklahoma City, Oklahoma 73105, USA
| | | | - Edana Stroberg
- Office of the Chief Medical Examiner, Oklahoma City, Oklahoma 73105, USA
| | - Alain Borczuk
- Weill Cornell Medicine, New York, New York 10065, USA
| | - Leigh B. Thorne
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Muthu K. Sakthivel
- Department of Radiology, University of North Carolina at Chapel Hill, North Carolina 27599, USA
| | - Yueh Z. Lee
- Department of Radiology, University of North Carolina at Chapel Hill, North Carolina 27599, USA
- Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - James S. Hagood
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
- Department of Pediatrics, Pulmonology Division and Program for Rare and Interstitial Lung Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Jason R. Mock
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
- Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Max A. Seibold
- Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado 80206, USA
- Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA
- Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado 80045, USA
| | - Wanda K. O’Neal
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Stephanie A. Montgomery
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Richard C. Boucher
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
| | - Ralph S. Baric
- Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
- Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
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Zhong H, Zhou Y, Mei SY, Tang R, Feng JH, He ZY, Xu QY, Xing SP. Scars of COVID-19: A bibliometric analysis of post-COVID-19 fibrosis. Front Public Health 2022; 10:967829. [PMID: 36203683 PMCID: PMC9530282 DOI: 10.3389/fpubh.2022.967829] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 08/19/2022] [Indexed: 01/25/2023] Open
Abstract
Background The coronavirus disease 2019 (COVID-19) becomes a worldwide public health threat. Increasing evidence proves that COVID-19-induced acute injuries could be reversed by a couple of therapies. After that, post-COVID-19 fibrosis (PCF), a sequela of "Long COVID," earns rapidly emerging concerns. PCF is associated with deteriorative lung function and worse quality of life. But the process of PCF remains speculative. Therefore, we aim to conduct a bibliometric analysis to explore the overall structure, hotspots, and trend topics of PCF. Materials and methods A comprehensive search was performed in the Web of Science core database to collect literature on PCF. Search syntax included COVID-19 relevant terms: "COVID 19," "COVID-19 Virus Disease," "COVID-19 Virus Infection," "Coronavirus Disease-19," "2019 Novel Coronavirus Disease," "2019 Novel Coronavirus Infection," "SARS Coronavirus 2 Infection," "COVID-19 Pandemic," "Coronavirus," "2019-nCoV," and "SARS-CoV-2"; and fibrosis relevant terms: "Fibrosis," "Fibroses," and "Cirrhosis." Articles in English were included. Totally 1,088 publications were enrolled. Searching results were subsequentially exported and collected for the bibliometric analysis. National, organizational, and individual level data were analyzed and visualized through biblioshiny package in the R, VOSviewer software, the CiteSpace software, and the Graphical Clustering Toolkit (gCLUTO) software, respectively. Results The intrinsic structure and development in the field of PCF were investigated in the present bibliometric analysis. The topmost keywords were "COVID-19" (occurrences, 636) surrounded by "SARS-CoV-2" (occurrences, 242), "coronavirus" (occurrences, 123), "fibrosis" (occurrences, 120), and "pneumonia" (occurrences, 94). The epidemiology, physiopathology, diagnosis, and therapy of PCF were extensively studied. After this, based on dynamic analysis of keywords, hot topics sharply changed from "Wuhan," "inflammation," and "cytokine storm" to "quality of life" and "infection" through burst detection; from "acute respiratory syndrome," "cystic-fibrosis" and "fibrosis" to "infection," "COVID-19," "quality-of-life" through thematic evolution; from "enzyme" to "post COVID." Similarly, co-cited references analysis showed that topics of references with most citations shift from "pulmonary pathology" (cluster 0) to "COVID-19 vaccination" (cluster 6). Additionally, the overview of contributors, impact, and collaboration was revealed. Summarily, the USA stood out as the most prolific, influential, and collaborative country. The Udice French Research University, Imperial College London, Harvard University, and the University of Washington represented the largest volume of publications, citations, H-index, and co-authorships, respectively. Dana Albon was the most productive and cited author with the strongest co-authorship link strength. Journal of Cystic Fibrosis topped the list of prolific and influential journals. Conclusion Outcomes gained from this study assisted professionals in better realizing PCF and would guide future practices. Epidemiology, pathogenesis, and therapeutics were study hotspots in the early phase of PCF research. As the spread of the COVID-19 pandemic and progress in this field, recent attention shifted to the quality of life of patients and post-COVID comorbidities. Nevertheless, COVID-19 relevant infection and vaccination were speculated to be research trends with current and future interest. International cooperation as well as in-depth laboratory experiments were encouraged to promote further explorations in the field of PCF.
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Tarraso J, Safont B, Carbonell-Asins JA, Fernandez-Fabrellas E, Sancho-Chust JN, Naval E, Amat B, Herrera S, Ros JA, Soler-Cataluña JJ, Rodriguez-Portal JA, Andreu AL, Marín M, Rodriguez-Hermosa JL, Gonzalez-Villaescusa C, Soriano JB, Signes-Costa J. Lung function and radiological findings 1 year after COVID-19: a prospective follow-up. Respir Res 2022; 23:242. [PMID: 36096801 PMCID: PMC9466319 DOI: 10.1186/s12931-022-02166-8] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 08/29/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND The coronavirus disease (COVID-19) pandemic has already affected more than 400 million people, with increasing numbers of survivors. These data indicate that a myriad of people may be affected by pulmonary sequelae of the infection. The aim of this study was to evaluate pulmonary sequelae in patients with bilateral COVID-19 pneumonia according to severity 1 year after hospital discharge. METHODS COVID-FIBROTIC is a multicenter prospective observational cohort study for admitted patients with bilateral COVID-19 pneumonia. Pulmonary functional outcomes and chest computed tomography sequelae were analyzed 12 months after hospital discharge and we classified patients into three groups according to severity. A post hoc analysis model was designed to establish how functional test changed between groups and over time. A multivariable logistic regression model was created to study prognostic factors for lung diffusion impairment and radiological fibrotic-like changes at 12 months. RESULTS Among 488 hospitalized patients with COVID-19 pneumonia, 284 patients had completed the entire evaluation at 12 months. Median age was 60.5 ± 11.9 and 55.3% were men. We found between-group differences in male sex, length of hospital stay, radiological involvement and inflammatory laboratory parameters. The functional evaluation of pulmonary sequelae showed that severe patients had statistically worse levels of lung diffusion at 2 months but no between group differences were found in subsequent controls. At 12-month follow up, however, we found impaired lung diffusion in 39.8% unrelated to severity. Radiological fibrotic-like changes at 12 months were reported in 22.7% of patients (102/448), only associated with radiological involvement at admission (OR: 1.55, 95% CI 1.06-2.38; p = 0.02) and LDH (OR: 0.99, 95% CI 0.98-0.99; p = 0.046). CONCLUSION Our data suggest that a significant percentage of individuals would develop pulmonary sequelae after COVID 19 pneumonia, regardless of severity of the acute process. Trial registration clinicaltrials.gov NCT04409275 (June 1, 2020).
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Affiliation(s)
- Julia Tarraso
- Pulmonary Department, Hospital Clinico, INCLIVA, Valencia, Spain
| | - Belen Safont
- Pulmonary Department, Hospital Clinico, INCLIVA, Valencia, Spain
| | | | | | | | - Elsa Naval
- Pulmonary Department, Hospital La Ribera, Alzira, Valencia, Spain
| | - Beatriz Amat
- Pulmonary Department, Hospital Vinalopo de Elche, Alicante, Spain
| | - Susana Herrera
- Pulmonary Department, Hospital Dr Peset, Valencia, Spain
| | - José A Ros
- Pulmonary Department, Hospital Virgen de la Arrixaca, Murcia, Spain
| | | | | | - Ada L Andreu
- Pulmonary Department, Hospital los Arcos, Murcia, Spain
| | | | | | | | - Joan B Soriano
- Pulmonary Department, Hospital La Princesa, Universidad Autónoma, Madrid, Spain
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Kanne JP, Little BP, Schulte JJ, Haramati A, Haramati LB. Long-term Lung Abnormalities Associated with COVID-19 Pneumonia. Radiology 2022; 306:e221806. [PMID: 36040336 PMCID: PMC9462591 DOI: 10.1148/radiol.221806] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
In the 3rd year of the SARS-CoV-2 pandemic, much has been learned about the long-term effects of COVID-19 pneumonia on the lungs. Approximately one-third of patients with moderate-to-severe pneumonia, especially those requiring intensive care therapy or mechanical ventilation, have residual abnormalities at chest CT 1 year after presentation. Abnormalities range from parenchymal bands to bronchial dilation to frank fibrosis. Less is known about the long-term pulmonary vascular sequelae, but there appears to be a persistent, increased risk of venothromboembolic events in a small cohort of patients. Finally, the associated histologic abnormalities resulting from SARS-CoV-2 infection are similar to those seen in patients with other causes of acute lung injury.
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Mogollón Hurtado SA, Sosa Báez ÁM, Blanco Pinzón EJ, Gómez Duque M, Mendoza Ramírez OE, Polo Nieto JF, Parra Medina R. Hallazgos histopatológicos pulmonares en COVID-19. Experiencia de autopsias mínimamente invasivas. REPERTORIO DE MEDICINA Y CIRUGÍA 2022. [DOI: 10.31260/repertmedcir.01217372.1348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Introducción: la COVID-19 es causada por el virus SARS-CoV-2. La presentación clínica varía desde pacientes asintomáticos hasta manifestaciones severas. Durante la pandemia se han realizado autopsias que han permitido reconocer los cambios en diferentes órganos, siendo el pulmón el más afectado. El objetivo del presente estudio es informar nuestra experiencia en cuanto a los hallazgos histopatológicos pulmonares, mediante el sistema de autopsia mínimamente invasiva. Metodología: se tomaron muestras a 8 pacientes fallecidos por COVID-19 en la unidad de cuidado intensivo (UCI) confirmado por PCR en el Hospital de San José, Bogotá, Colombia, en la primera hora después de la muerte. Los tejidos fueron analizados por dos patólogos en forma independiente. Resultados: se observó en todos daño alveolar difuso (DAD) en fases exudativa, proliferativa o ambas, además de bronconeumonía y neumonitis intersticial. Discusión: el pulmón es el principal órgano afectado por el SARS-CoV-2 y el hallazgo histopatológico más frecuente es el DAD en fases exudativa y mixta. También se han descrito alteraciones en diferentes sistemas. Conclusiones: el hallazgo histopatológico pulmonar más frecuente es el DAD en diferentes estadios. Se considera que la autopsia mínimamente invasiva es de gran utilidad en escenarios donde la convencional se encuentra limitada, pues no presenta grandes restricciones y permite obtener tejidos viables.
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Diaz A, Bujnowski D, McMullen P, Lysandrou M, Ananthanarayanan V, Husain AN, Freeman R, Vigneswaran WT, Ferguson MK, Donington JS, Madariaga MLL, Abdelsattar ZM. Pulmonary Parenchymal Changes in COVID-19 Survivors. Ann Thorac Surg 2022; 114:301-310. [PMID: 34343471 PMCID: PMC8325553 DOI: 10.1016/j.athoracsur.2021.06.076] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 06/03/2021] [Accepted: 06/23/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND As the COVID-19 pandemic moves into the survivorship phase, questions regarding long-term lung damage remain unanswered. Previous histopathologic studies are limited to autopsy reports. We studied lung specimens from COVID-19 survivors who underwent elective lung resections to determine whether postacute histopathologic changes are present. METHODS This multicenter observational study included 11 adult COVID-19 survivors who had recovered but subsequently underwent unrelated elective lung resection for indeterminate lung nodules or lung cancer. We compared these against an age- and procedure-matched control group who never contracted COVID-19 (n = 5) and an end-stage COVID-19 group (n = 3). A blinded pulmonary pathologist examined the lung parenchyma focusing on 4 compartments: airways, alveoli, interstitium, and vasculature. RESULTS Elective lung resection was performed in 11 COVID-19 survivors with asymptomatic (n = 4), moderate (n = 4), and severe (n = 3) COVID-19 infections at a median 68.5 days (range 24-142 days) after the COVID-19 diagnosis. The most common operation was lobectomy (75%). Histopathologic examination identified no differences between the lung parenchyma of COVID-19 survivors and controls across all compartments examined. Conversely, patients in the end-stage COVID-19 group showed fibrotic diffuse alveolar damage with intra-alveolar macrophages, organizing pneumonia, and focal interstitial emphysema. CONCLUSIONS In this study to examine the lung parenchyma of COVID-19 survivors, we did not find distinct postacute histopathologic changes to suggest permanent pulmonary damage. These results are reassuring for COVID-19 survivors who recover and become asymptomatic.
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Affiliation(s)
- Ashley Diaz
- Pritzker School of Medicine, University of Chicago, Chicago, Illinois
| | - Daniel Bujnowski
- Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois
| | - Phillip McMullen
- Department of Pathology, University of Chicago Medicine, Chicago, Illinois
| | - Maria Lysandrou
- Pritzker School of Medicine, University of Chicago, Chicago, Illinois
| | | | - Aliya N. Husain
- Department of Pathology, University of Chicago Medicine, Chicago, Illinois
| | - Richard Freeman
- Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, Illinois
| | - Wickii T. Vigneswaran
- Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, Illinois
| | - Mark K. Ferguson
- Section of Thoracic Surgery, Department of Surgery, University of Chicago Medicine, Chicago, Illinois
| | - Jessica S. Donington
- Section of Thoracic Surgery, Department of Surgery, University of Chicago Medicine, Chicago, Illinois
| | - Maria Lucia L. Madariaga
- Section of Thoracic Surgery, Department of Surgery, University of Chicago Medicine, Chicago, Illinois
| | - Zaid M. Abdelsattar
- Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, Illinois,Address correspondence to Dr Abdelsattar, Department of Cardiovascular & Thoracic Surgery, Loyola University Medical Center, 2160 S 1st Ave, Maywood, IL 60153
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Usami O. Two Cases of COVID-19-Related Deaths Unaccounted for: A Call for Action. Cureus 2022; 14:e26238. [PMID: 35911326 PMCID: PMC9312909 DOI: 10.7759/cureus.26238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/23/2022] [Indexed: 11/20/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) high-risk survivors experience long-term COVID-19 symptoms. Hence, these individuals require early and ubiquitous respiratory rehabilitation to avoid malnutrition. We report the case of a 93-year-old woman who recovered from moderate II severity (pneumonia requiring oxygen). The patient, after prolonged hospitalization, demonstrated low severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity and showed no COVID-19 respiratory symptoms for more than 72 hours. Subsequently, the patient became debilitated and lost her appetite without dysphagia, dysgeusia, and smell disorder, developed nosocomial pneumonia as a sequela of acute COVID-19 and died. We also report the second case of an 84-year-old man diagnosed with moderate II COVID-19 severity. After recovery, the patient was frail due to the previous onset of COVID-19 and worsened during his stay at home, losing appetite without dysphagia, dysgeusia, and smell disorder, and dying of senility as the official cause. Recovered COVID-19 appears to be a health risk by malnutrition without anorexia and depression, among other conditions. A proven rehabilitation program for each phase of the disease is required for better lung function and nutritional status.
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Lee JE, Jeong WG, Nam BD, Yoon SH, Jeong YJ, Kim YH, Kim SJ, Yoo JY. Impact of Mediastinal Lymphadenopathy on the Severity of COVID-19 Pneumonia: A Nationwide Multicenter Cohort Study. J Korean Med Sci 2022; 37:e78. [PMID: 35668683 PMCID: PMC9171349 DOI: 10.3346/jkms.2022.37.e78] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 01/06/2022] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND We analyzed the differences between clinical characteristics and computed tomography (CT) findings in patients with coronavirus disease 2019 (COVID-19) to establish potential relationships with mediastinal lymphadenopathy and clinical outcomes. METHODS We compared the clinical characteristics and CT findings of COVID-19 patients from a nationwide multicenter cohort who were grouped based on the presence or absence of mediastinal lymphadenopathy. Differences between clinical characteristics and CT findings in these groups were analyzed. Univariate and multivariate analyses were performed to determine the impact of mediastinal lymphadenopathy on clinical outcomes. RESULTS Of the 344 patients included in this study, 53 (15.4%) presented with mediastinal lymphadenopathy. The rate of diffuse alveolar damage pattern pneumonia and the visual CT scores were significantly higher in patients with mediastinal lymphadenopathy than in those without (P < 0.05). A positive correlation between the number of enlarged mediastinal lymph nodes and visual CT scores was noted in patients with mediastinal lymphadenopathy (Spearman's ρ = 0.334, P < 0.001). Multivariate analysis showed that mediastinal lymphadenopathy was independently associated with a higher risk of intensive care unit (ICU) admission (odds ratio, 95% confidence interval; 3.25, 1.06-9.95) but was not significantly associated with an increased risk of in-hospital death in patients with COVID-19. CONCLUSION COVID-19 patients with mediastinal lymphadenopathy had a larger extent of pneumonia than those without. Multivariate analysis adjusted for clinical characteristics and CT findings revealed that the presence of mediastinal lymphadenopathy was significantly associated with ICU admission.
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Affiliation(s)
- Jong Eun Lee
- Department of Radiology, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea
| | - Won Gi Jeong
- Department of Radiology, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun, Korea
| | - Bo Da Nam
- Department of Radiology, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Soon Ho Yoon
- Department of Radiology, Seoul National University Hospital, Seoul National College of Medicine, Seoul, Korea
| | - Yeon Joo Jeong
- Department of Radiology and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Yun-Hyeon Kim
- Department of Radiology, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea
| | - Sung Jin Kim
- Department of Radiology, Chungbuk National University College of Medicine, Chungbuk National University Hospital, Cheongju, Korea
| | - Jin Young Yoo
- Department of Radiology, Chungbuk National University College of Medicine, Chungbuk National University Hospital, Cheongju, Korea.
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Klein FR, Renedo MF, Vigliano CA. Evidence of Continued CD4+ and CD8+ T Cell Activity After SARS-COV-2 Clearance in a Late COVID-19 Pneumonia Heart Transplant Patient. Cureus 2022; 14:e24852. [PMID: 35702460 PMCID: PMC9176684 DOI: 10.7759/cureus.24852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/09/2022] [Indexed: 12/15/2022] Open
Abstract
We have studied an unvaccinated heart transplant 64-year-old patient admitted for low-grade fever, dry cough, general malaise, and bilateral interstitial infiltrates, after two months of a diagnosis of coronavirus disease 2019 (COVID-19) bilateral pneumonia. A bronchoalveolar lavage and transbronchial biopsy were performed. Bacterial, mycotic and viral infections were ruled out including repeated reverse transcription polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diffuse thickening of alveolar septa with fibrosis and infiltration of lymphocytes and macrophages into the alveolar septa with aggregates of CD4+ and CD8+ T cells with positive immunolabelling for granzyme B were observed, indicating a continuing cytotoxic process that might have induced proliferation and fibrosis. An intense ongoing immunopathological cellular reaction, potentially triggered by SARS-CoV-2 overcoming the anti-inflammatory and immunomodulatory effects of the immunosuppressive drugs is suggested by these findings, opening to debate the usual approach of minimizing immunosuppression after COVID-19 in transplant patients when presence of SARS-CoV-2 has been ruled out.
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Long COVID-19 Syndrome: Multiorgan Damage and Recommendations for Follow-Up and Rehabilitation. ACTA MEDICA BULGARICA 2022. [DOI: 10.2478/amb-2022-0010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
The majority of the SARS-CoV-2 infected patients fully recover within a few weeks. However, a significant proportion of them, independently of their age, still have multi-organ damage, similar to that during the acute phase of infection, or symptoms for a longer term afte r recovery. “Postacute-COVID-19 (Long COVID-19 Syndrome)” is a term used for COVID-19 patients who are still symptomatic 4 and 12 weeks after the onset of acute symptoms and “Post-COVID-19-syndrome” ‒ for those with symptoms for longer than 12 weeks after the onset of acute symptoms. The severity of the initial infection does not correlate with the probability for and with the severity of long-term symptoms. This review comments on the multiorgan effects of Long COVID-19 Syndrome: respiratory, cardiovascular, hematological, renal, gastrointestinal, neurological, and metabolic ones. Recommendations for follow-up and rehabilitation for the recovery of Long COVID-19 Syndrome patients are discussed in detail.
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Jutant EM, Meyrignac O, Beurnier A, Jaïs X, Pham T, Morin L, Boucly A, Bulifon S, Figueiredo S, Harrois A, Jevnikar M, Noël N, Pichon J, Roche A, Seferian A, Soliman S, Duranteau J, Becquemont L, Monnet X, Sitbon O, Bellin MF, Humbert M, Savale L, Montani D. Respiratory symptoms and radiological findings in post-acute COVID-19 syndrome. ERJ Open Res 2022; 8:00479-2021. [PMID: 35445129 PMCID: PMC8685862 DOI: 10.1183/23120541.00479-2021] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 10/27/2021] [Indexed: 01/08/2023] Open
Abstract
Rationale The characteristics of patients with respiratory complaints and/or lung radiologic abnormalities after hospitalisation for coronavirus disease 2019 (COVID-19) are unknown. The objectives were to determine their characteristics and the relationships between dyspnoea, radiologic abnormalities and functional impairment. Methods In the COMEBAC (Consultation Multi-Expertise de Bicêtre Après COVID-19) cohort study, 478 hospital survivors were evaluated by telephone 4 months after hospital discharge, and 177 who had been hospitalised in an intensive care unit (ICU) or presented relevant symptoms underwent an ambulatory evaluation. New-onset dyspnoea and cough were evaluated, and the results of pulmonary function tests and high-resolution computed tomography of the chest were collected. Results Among the 478 patients, 78 (16.3%) reported new-onset dyspnoea, and 23 (4.8%) new-onset cough. The patients with new-onset dyspnoea were younger (56.1±12.3 versus 61.9±16.6 years), had more severe COVID-19 (ICU admission 56.4% versus 24.5%) and more frequent pulmonary embolism (18.0% versus 6.8%) (all p≤0.001) than patients without dyspnoea. Among the patients reassessed at the ambulatory care visit, the prevalence of fibrotic lung lesions was 19.3%, with extent <25% in 97% of the patients. The patients with fibrotic lesions were older (61±11 versus 56±14 years, p=0.03), more frequently managed in an ICU (87.9 versus 47.4%, p<0.001), had lower total lung capacity (74.1±13.7 versus 84.9±14.8% pred, p<0.001) and diffusing capacity of the lung for carbon monoxide (D LCO) (73.3±17.9 versus 89.7±22.8% pred, p<0.001). The combination of new-onset dyspnoea, fibrotic lesions and D LCO <70% pred was observed in eight out of 478 patients. Conclusions New-onset dyspnoea and mild fibrotic lesions were frequent at 4 months, but the association of new-onset dyspnoea, fibrotic lesions and low D LCO was rare.
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Affiliation(s)
- Etienne-Marie Jutant
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
| | - Olivier Meyrignac
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- AP-HP, Service de radiologie diagnostique et
interventionnelle, BioMaps, Hôpital de Bicêtre, DMU 14 Smart Imaging,
Le Kremlin-Bicêtre, France
| | - Antoine Beurnier
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Physiology – Pulmonary Function
Testing, DMU 5 Thorinno, Hôpital Bicêtre, Le Kremlin-Bicêtre,
France
| | - Xavier Jaïs
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
| | - Tai Pham
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- AP-HP, Service de Médecine
Intensive-Réanimation, Hôpital de Bicêtre, DMU 4 CORREVE
Maladies du Cœur et des Vaisseaux, FHU Sepsis, Le Kremlin-Bicêtre,
France
| | - Luc Morin
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- AP-HP, Service de Réanimation Pédiatrique et
Médecine Néonatale, Hôpital de Bicêtre, DMU3
Santé de l'Enfant et de l'Adolescent, Le
Kremlin-Bicêtre, France
| | - Athénaïs Boucly
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
| | - Sophie Bulifon
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
| | - Samy Figueiredo
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- AP-HP, Service
d'anesthésie-réanimation et médecine
péri-opératoire, Hôpital de Bicêtre, DMU 12
Anesthésie, réanimation, douleur, Le Kremlin-Bicêtre,
France
| | - Anatole Harrois
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- AP-HP, Service
d'anesthésie-réanimation et médecine
péri-opératoire, Hôpital de Bicêtre, DMU 12
Anesthésie, réanimation, douleur, Le Kremlin-Bicêtre,
France
| | - Mitja Jevnikar
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
| | - Nicolas Noël
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- AP-HP, Service de médecine interne et immunologie
clinique, Hôpital de Bicêtre, DMU 7
Endocrinologie-immunités-inflammations-cancer-urgences, Le
Kremlin-Bicêtre, France
| | - Jérémie Pichon
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
| | - Anne Roche
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
| | - Andrei Seferian
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
| | - Samer Soliman
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- AP-HP, Service de radiologie diagnostique et
interventionnelle, BioMaps, Hôpital de Bicêtre, DMU 14 Smart Imaging,
Le Kremlin-Bicêtre, France
| | - Jacques Duranteau
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- AP-HP, Service
d'anesthésie-réanimation et médecine
péri-opératoire, Hôpital de Bicêtre, DMU 12
Anesthésie, réanimation, douleur, Le Kremlin-Bicêtre,
France
| | - Laurent Becquemont
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- AP-HP, Centre de recherche Clinique Paris-Saclay, DMU 13
Santé publique, Information médicale, Appui à la recherche
clinique, INSERM U1018, CESP (Centre de Recherche en Epidémiologie et
Santé des Populations), Paris, France
| | - Xavier Monnet
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- AP-HP, Service de Médecine
Intensive-Réanimation, Hôpital de Bicêtre, DMU 4 CORREVE
Maladies du Cœur et des Vaisseaux, FHU Sepsis, Le Kremlin-Bicêtre,
France
| | - Olivier Sitbon
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
| | - Marie-France Bellin
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- AP-HP, Service de radiologie diagnostique et
interventionnelle, BioMaps, Hôpital de Bicêtre, DMU 14 Smart Imaging,
Le Kremlin-Bicêtre, France
| | - Marc Humbert
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
| | - Laurent Savale
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
- These authors contributed equally
| | - David Montani
- Faculty of Medicine, Université Paris-Saclay, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le
Plessis Robinson, France
- AP-HP, Dept of Respiratory and Intensive Care Medicine,
Pulmonary Hypertension National Referral Centre, Hôpital Bicêtre, DMU
5 Thorinno, Le Kremlin-Bicêtre, France
- These authors contributed equally
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Wang JY, Zhang W, Roehrl VB, Roehrl MW, Roehrl MH. An Autoantigen Atlas From Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19. Front Immunol 2022; 13:831849. [PMID: 35401574 PMCID: PMC8987778 DOI: 10.3389/fimmu.2022.831849] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 02/21/2022] [Indexed: 12/27/2022] Open
Abstract
COVID-19 is accompanied by a myriad of both transient and long-lasting autoimmune responses. Dermatan sulfate (DS), a glycosaminoglycan crucial for wound healing, has unique affinity for autoantigens (autoAgs) from apoptotic cells. DS-autoAg complexes are capable of stimulating autoreactive B cells and autoantibody production. We used DS-affinity proteomics to define the autoantigen-ome of lung fibroblasts and bioinformatics analyses to study the relationship between autoantigenic proteins and COVID-induced alterations. Using DS-affinity, we identified an autoantigen-ome of 408 proteins from human HFL1 cells, at least 231 of which are known autoAgs. Comparing with available COVID data, 352 proteins of the autoantigen-ome have thus far been found to be altered at protein or RNA levels in SARS-CoV-2 infection, 210 of which are known autoAgs. The COVID-altered proteins are significantly associated with RNA metabolism, translation, vesicles and vesicle transport, cell death, supramolecular fibrils, cytoskeleton, extracellular matrix, and interleukin signaling. They offer clues to neurological problems, fibrosis, smooth muscle dysfunction, and thrombosis. In particular, 150 altered proteins are related to the nervous system, including axon, myelin sheath, neuron projection, neuronal cell body, and olfactory bulb. An association with the melanosome is also identified. The findings from our study illustrate a connection between COVID infection and autoimmunity. The vast number of COVID-altered proteins with high intrinsic propensity to become autoAgs offers an explanation for the diverse autoimmune complications in COVID patients. The variety of autoAgs related to mRNA metabolism, translation, and vesicles suggests a need for long-term monitoring of autoimmunity in COVID. The COVID autoantigen atlas we are establishing provides a detailed molecular map for further investigation of autoimmune sequelae of the pandemic, such as "long COVID" syndrome. Summary Sentence An autoantigen-ome by dermatan sulfate affinity from human lung HFL1 cells may explain neurological and autoimmune manifestations of COVID-19.
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Affiliation(s)
| | - Wei Zhang
- Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | | | | | - Michael H. Roehrl
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States
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Guedes Baldi1 B, Todorovic Fabro2 A, Craveiro Franco3 A, C Machado3 MH, Aparecido Prudente3 R, Thomé Franco3 E, Ribeiro Marrone4 S, Alves do Vale3 S, Jacon Cezare3 T, Padovani de Toledo Moraes2 M, Vieira Machado Ferreira5 E, Pereira Albuquerque1 AL, Valente Yamada Sawamura6 M, Erico Tanni3 S. Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series. J Bras Pneumol 2022; 48:e20210438. [PMID: 35508067 PMCID: PMC9064656 DOI: 10.36416/1806-3756/e20210438] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 02/19/2022] [Indexed: 11/23/2022] Open
Abstract
This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br])
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Affiliation(s)
- Bruno Guedes Baldi1
- 1. Divisão de Pneumologia, Instituto do Coração – InCor – Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil
| | - Alexandre Todorovic Fabro2
- 2. Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo – USP – Ribeirão Preto (SP) Brasil
| | - Andreia Craveiro Franco3
- 3. Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil
| | - Marília Helena C Machado3
- 3. Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil
| | - Robson Aparecido Prudente3
- 3. Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil
| | - Estefânia Thomé Franco3
- 3. Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil
| | - Sergio Ribeiro Marrone4
- 4. Disciplina de Radiologia, Departamento de Dermatologia e Radioterapia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil
| | - Simone Alves do Vale3
- 3. Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil
| | - Talita Jacon Cezare3
- 3. Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil
| | - Marcelo Padovani de Toledo Moraes2
- 2. Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo – USP – Ribeirão Preto (SP) Brasil
| | | | - André Luis Pereira Albuquerque1
- 1. Divisão de Pneumologia, Instituto do Coração – InCor – Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil
| | | | - Suzana Erico Tanni3
- 3. Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil
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Ghoshal UC, Ghoshal U, Rahman MM, Mathur A, Rai S, Akhter M, Mostafa T, Islam MS, Haque SA, Pandey A, Kibria MG, Ahmed F. Post-infection functional gastrointestinal disorders following coronavirus disease-19: A case-control study. J Gastroenterol Hepatol 2022; 37:489-498. [PMID: 34672022 PMCID: PMC8657345 DOI: 10.1111/jgh.15717] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 10/03/2021] [Accepted: 10/13/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM Because acute infectious gastroenteritis may cause post-infection irritable bowel syndrome and functional dyspepsia and the severe acute respiratory syndrome coronavirus-2 affects gastrointestinal (GI) tract, coronavirus disease-19 (COVID-19) may cause post-infection-functional GI disorders (FGIDs). We prospectively studied the frequency and spectrum of post-infection-FGIDs among COVID-19 and historical healthy controls and the risk factors for its development. METHODS Two hundred eighty patients with COVID-19 and 264 historical healthy controls were followed up at 1 and 3 months using translated validated Rome Questionnaires for the development of chronic bowel dysfunction (CBD), dyspeptic symptoms, and their overlap and at 6-month for IBS, uninvestigated dyspepsia (UD) and their overlap. Psychological comorbidity was studied using Rome III Psychosocial Alarm Questionnaire. RESULTS At 1 and 3 months, 16 (5.7%), 16 (5.7%), 11 (3.9%), and 24 (8.6%), 6 (2.1%), 9 (3.2%) of COVID-19 patients developed CBD, dyspeptic symptoms, and their overlap, respectively; among healthy controls, none developed dyspeptic symptoms and one developed CBD at 3 months (P < 0.05). At 6 months, 15 (5.3%), 6 (2.1%), and 5 (1.8%) of the 280 COVID-19 patients developed IBS, UD, and IBS-UD overlap, respectively, and one healthy control developed IBS at 6 months (P < 0.05 for all except IBS-UD overlap). The risk factors for post-COVID-19 FGIDs at 6 months included symptoms (particularly GI), anosmia, ageusia, and presence of CBD, dyspeptic symptoms, or their overlap at 1 and 3 months and the psychological comorbidity. CONCLUSIONS This is the first study showing COVID-19 led to post-COVID-19 FGIDs. Post-COVID-19 FGIDs may pose a significant economic, social, and healthcare burden to the world.
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Affiliation(s)
- Uday C Ghoshal
- Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Ujjala Ghoshal
- Department of MicrobiologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - M Masudur Rahman
- Department of GastroenterologySheikh Russel National Gastroliver Institute and HospitalDhakaBangladesh
| | - Akash Mathur
- Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Sushmita Rai
- Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Mahfuza Akhter
- Department of GastroenterologyMugda Medical CollegeDhakaBangladesh
| | - Tanvir Mostafa
- Department of MedicineDhaka Medical College and HospitalDhakaBangladesh
| | - Mohammad Shohidul Islam
- Department of GastroenterologySheikh Russel National Gastroliver Institute and HospitalDhakaBangladesh
| | - Sheikh Ahmedul Haque
- Department of GastroenterologySheikh Russel National Gastroliver Institute and HospitalDhakaBangladesh
| | - Ankita Pandey
- Department of MicrobiologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Md Golam Kibria
- Department of GastroenterologySheikh Russel National Gastroliver Institute and HospitalDhakaBangladesh
| | - Faruque Ahmed
- Department of GastroenterologySheikh Russel National Gastroliver Institute and HospitalDhakaBangladesh
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48
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Targeting chronic COVID-19 lung injury; Tofacitinib can be used against tissue-resident memory T cells. Biomed Pharmacother 2022; 147:112614. [PMID: 34995938 PMCID: PMC8723825 DOI: 10.1016/j.biopha.2022.112614] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 12/24/2021] [Accepted: 01/02/2022] [Indexed: 02/06/2023] Open
Abstract
Post-Covid pulmonary fibrosis is evident following severe COVID-19. There is an urgent need to identify the cellular and pathophysiological characteristics of chronic lung squeals of Covid-19 for the development of future preventive and/or therapeutic interventions. Tissue-resident memory T (TRM) cells can mediate local immune protection against infections and cancer. Less beneficially, lung TRM cells cause chronic airway inflammation and fibrosis by stimulating pathologic inflammation. The effects of Janus kinase (JAK), an inducer pathway of cytokine storm, inhibition on acute Covid-19 cases have been previously evaluated. Here, we propose that Tofacitinib by targeting the CD8+ TRM cells could be a potential candidate for the treatment of chronic lung diseases induced by acute SARS-CoV-2 infection.
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49
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Dinnon KH, Leist SR, Okuda K, Dang H, Fritch EJ, Gully KL, De la Cruz G, Evangelista MD, Asakura T, Gilmore RC, Hawkins P, Nakano S, West A, Schäfer A, Gralinski LE, Everman JL, Sajuthi SP, Zweigart MR, Dong S, McBride J, Cooley MR, Hines JB, Love MK, Groshong SD, VanSchoiack A, Phelan SJ, Liang Y, Hether T, Leon M, Zumwalt RE, Barton LM, Duval EJ, Mukhopadhyay S, Stroberg E, Borczuk A, Thorne LB, Sakthivel MK, Lee YZ, Hagood JS, Mock JR, Seibold MA, O’Neal WK, Montgomery SA, Boucher RC, Baric RS. A model of persistent post SARS-CoV-2 induced lung disease for target identification and testing of therapeutic strategies. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2022:2022.02.15.480515. [PMID: 35194605 PMCID: PMC8863140 DOI: 10.1101/2022.02.15.480515] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
COVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute disease through clinical recovery. At 15-120 days post-virus clearance, histologic evaluation identified subpleural lesions containing collagen, proliferative fibroblasts, and chronic inflammation with tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal upregulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.
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Affiliation(s)
- Kenneth H. Dinnon
- Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Sarah R. Leist
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Kenichi Okuda
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Hong Dang
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Ethan J. Fritch
- Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Kendra L. Gully
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Gabriela De la Cruz
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Mia D. Evangelista
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Takanori Asakura
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Rodney C. Gilmore
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Padraig Hawkins
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Satoko Nakano
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Ande West
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Alexandra Schäfer
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Lisa E. Gralinski
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Jamie L. Everman
- Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado, USA
| | - Satria P. Sajuthi
- Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado, USA
| | - Mark R. Zweigart
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Stephanie Dong
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Jennifer McBride
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Michelle R. Cooley
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Jesse B. Hines
- Golden Point Scientific Laboratories, Hoover, Alabama, USA
| | - Miriya K. Love
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Steve D. Groshong
- Division of Pathology, Department of Medicine, National Jewish Health, Denver, Colorado, USA
| | | | | | - Yan Liang
- NanoString Technologies, Seattle, Washington, USA
| | - Tyler Hether
- NanoString Technologies, Seattle, Washington, USA
| | - Michael Leon
- NanoString Technologies, Seattle, Washington, USA
| | - Ross E. Zumwalt
- Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Lisa M. Barton
- Office of the Chief Medical Examiner, Oklahoma City, Oklahoma, USA
| | - Eric J. Duval
- Office of the Chief Medical Examiner, Oklahoma City, Oklahoma, USA
| | | | - Edana Stroberg
- Office of the Chief Medical Examiner, Oklahoma City, Oklahoma, USA
| | | | - Leigh B. Thorne
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Muthu K. Sakthivel
- Department of Radiology, University of North Carolina at Chapel Hill, North Carolina, USA
| | - Yueh Z. Lee
- Department of Radiology, University of North Carolina at Chapel Hill, North Carolina, USA
- Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - James S. Hagood
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Department of Pediatrics, Pulmonology Division and Program for Rare and Interstitial Lung Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Jason R. Mock
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Max A. Seibold
- Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado, USA
- Department of Pediatrics, National Jewish Health, Denver, Colorado, USA
- Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado-Denver, Denver, Colorado, USA
| | - Wanda K. O’Neal
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Stephanie A. Montgomery
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Richard C. Boucher
- Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Ralph S. Baric
- Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
- Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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50
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Menezes RG, Rizwan T, Saad Ali S, Hassan W, Khetpal A, Aqil M, Madadin M, Jamal Siddiqi T, Shariq Usman M. Postmortem findings in COVID-19 fatalities: A systematic review of current evidence. Leg Med (Tokyo) 2022; 54:102001. [PMID: 34952452 PMCID: PMC8648585 DOI: 10.1016/j.legalmed.2021.102001] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 08/18/2021] [Accepted: 12/01/2021] [Indexed: 12/12/2022]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). Almost 17 months after the first COVID-19 case was reported, the exact pathogenesis of the virus is still open to interpretation. Postmortem studies have been relatively scarce due to the high infectivity rate of the virus. We systematically reviewed the literature available for studies that reported gross, histological, microscopic, and immunohistochemical findings in COVID-19 fatalities with the aim of reporting any recurrent findings among different demographics. PubMed and Scopus were searched up till the second of May 2021 and 46 studies with a total of 793 patients were shortlisted after the application of inclusion and exclusion criteria. The selected studies reported gross, histological, microscopic, and immunohistochemical autopsy findings in the lungs, heart, liver, gallbladder, bowels, kidney, spleen, bone marrow, lymph nodes, CNS, pancreas, endocrine/exocrine glands, and a few other miscellaneous locations. The SARS-CoV-2 virus was detected in multiple organs and so was the presence of widespread microthrombi. This finding suggests that the pathogenesis of this highly infectious virus might be linked to some form of coagulopathy. Further studies should focus on analyzing postmortem findings in a larger number of patients from different demographics in order to obtain more generalizable results.
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Affiliation(s)
- Ritesh G Menezes
- Department of Pathology, College of Medicine, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
| | - Tehlil Rizwan
- Department of Medicine, AMITA Health Saint Joseph Hospital, Chicago, IL, USA
| | - Syed Saad Ali
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Wardah Hassan
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Akash Khetpal
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Mohammad Aqil
- Deanship of Library Affairs, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mohammed Madadin
- Department of Pathology, College of Medicine, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Tariq Jamal Siddiqi
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
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