MaltSci 麦伴科研

Appearance

Curated Papers > Recent high-impact research on "organoids" (IF≥30, last 5 years)

SARS-CoV-2 pathogenesis. ​

Literature Information ​

DOI10.1038/s41579-022-00713-0
PMID35354968
JournalNature reviews. Microbiology
Impact Factor103.3
JCR QuartileQ1
Publication Year2022
Times Cited446
KeywordsSARS-CoV-2, pathophysiology, acute respiratory distress syndrome, immune response, novel therapies
Literature TypeJournal Article, Review
ISSN1740-1526
Pages270-284
Issue20(5)
AuthorsMart M Lamers, Bart L Haagmans

TL;DR ​

This review examines the pathophysiology of SARS-CoV-2, highlighting how the virus can lead to severe pneumonia and acute respiratory distress syndrome (ARDS) through mechanisms such as dysfunctional immune responses and alveolar damage. By leveraging advanced technologies, the study provides insights that may facilitate the development of novel therapeutic strategies for COVID-19.

Search for more papers on MaltSci.com ​

SARS-CoV-2 · pathophysiology · acute respiratory distress syndrome · immune response · novel therapies

Abstract ​

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating pandemic. Although most people infected with SARS-CoV-2 develop a mild to moderate disease with virus replication restricted mainly to the upper airways, some progress to having a life-threatening pneumonia. In this Review, we explore recent clinical and experimental advances regarding SARS-CoV-2 pathophysiology and discuss potential mechanisms behind SARS-CoV-2-associated acute respiratory distress syndrome (ARDS), specifically focusing on new insights obtained using novel technologies such as single-cell omics, organoid infection models and CRISPR screens. We describe how SARS-CoV-2 may infect the lower respiratory tract and cause alveolar damage as a result of dysfunctional immune responses. We discuss how this may lead to the induction of a 'leaky state' of both the epithelium and the endothelium, promoting inflammation and coagulation, while an influx of immune cells leads to overexuberant inflammatory responses and immunopathology. Finally, we highlight how these findings may aid the development of new therapeutic interventions against COVID-19.

MaltSci.com AI Research Service ​

Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining

Primary Questions Addressed ​

  1. What specific mechanisms contribute to the progression from mild SARS-CoV-2 infection to severe pneumonia?
  2. How do novel technologies like single-cell omics enhance our understanding of SARS-CoV-2 pathogenesis?
  3. In what ways can organoid infection models provide insights into the infection process of SARS-CoV-2 in the lower respiratory tract?
  4. What role does the immune response play in the development of acute respiratory distress syndrome (ARDS) in COVID-19 patients?
  5. How might the findings on SARS-CoV-2-induced inflammation and coagulation inform future therapeutic strategies for COVID-19?

Key Findings ​

Key Insights on SARS-CoV-2 Pathogenesis ​

1. Research Background and Objective ​

The emergence of SARS-CoV-2 has led to a global pandemic characterized by varying disease severity among infected individuals. While the majority experience mild to moderate symptoms, a significant subset develops severe complications, including pneumonia and acute respiratory distress syndrome (ARDS). The objective of this review is to synthesize recent advances in understanding the pathophysiology of SARS-CoV-2, particularly the mechanisms contributing to severe disease and ARDS, using state-of-the-art research technologies.

2. Main Methods and Findings ​

The review highlights recent clinical and experimental insights gained through the application of advanced methodologies such as single-cell omics, organoid infection models, and CRISPR screens. Key findings suggest that SARS-CoV-2 primarily infects the upper respiratory tract but can also extend to the lower respiratory tract, leading to significant alveolar damage. This damage is exacerbated by dysfunctional immune responses, which result in a "leaky state" of both epithelial and endothelial barriers. The review discusses how this permeable state facilitates increased inflammation and coagulation processes, with an influx of immune cells contributing to an overactive inflammatory response. This dysregulated immune response is posited as a critical factor in the progression to severe disease and ARDS.

3. Core Conclusions ​

The review concludes that the pathogenesis of SARS-CoV-2 involves complex interactions between viral infection, immune responses, and tissue damage. The findings suggest that the severe respiratory complications associated with COVID-19 are not solely due to direct viral damage but also to an exaggerated immune response that leads to significant inflammation and potential tissue injury. Understanding these mechanisms is crucial for developing targeted therapies to mitigate severe disease outcomes.

4. Research Significance and Impact ​

The insights derived from this review have significant implications for the ongoing management and treatment of COVID-19. By elucidating the mechanisms underlying severe disease and ARDS, researchers and clinicians can better identify potential therapeutic targets and interventions. The application of novel technologies in this field underscores the importance of integrating advanced methodologies in infectious disease research. Ultimately, these findings may inform the development of more effective therapeutic strategies and enhance our preparedness for future pandemics caused by similar viral pathogens.

References ​

  1. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. - Christian Drosten;Stephan Günther;Wolfgang Preiser;Sylvie van der Werf;Hans-Reinhard Brodt;Stephan Becker;Holger Rabenau;Marcus Panning;Larissa Kolesnikova;Ron A M Fouchier;Annemarie Berger;Ana-Maria Burguière;Jindrich Cinatl;Markus Eickmann;Nicolas Escriou;Klaus Grywna;Stefanie Kramme;Jean-Claude Manuguerra;Stefanie Müller;Volker Rickerts;Martin Stürmer;Simon Vieth;Hans-Dieter Klenk;Albert D M E Osterhaus;Herbert Schmitz;Hans Wilhelm Doerr - The New England journal of medicine (2003)
  2. Coronavirus as a possible cause of severe acute respiratory syndrome. - J S M Peiris;S T Lai;L L M Poon;Y Guan;L Y C Yam;W Lim;J Nicholls;W K S Yee;W W Yan;M T Cheung;V C C Cheng;K H Chan;D N C Tsang;R W H Yung;T K Ng;K Y Yuen; - Lancet (London, England) (2003)
  3. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. - Thijs Kuiken;Ron A M Fouchier;Martin Schutten;Guus F Rimmelzwaan;Geert van Amerongen;Debby van Riel;Jon D Laman;Ton de Jong;Gerard van Doornum;Wilina Lim;Ai Ee Ling;Paul K S Chan;John S Tam;Maria C Zambon;Robin Gopal;Christian Drosten;Sylvie van der Werf;Nicolas Escriou;Jean-Claude Manuguerra;Klaus Stöhr;J S Malik Peiris;Albert D M E Osterhaus - Lancet (London, England) (2003)
  4. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. - Ali M Zaki;Sander van Boheemen;Theo M Bestebroer;Albert D M E Osterhaus;Ron A M Fouchier - The New England journal of medicine (2012)
  5. A Novel Coronavirus from Patients with Pneumonia in China, 2019. - Na Zhu;Dingyu Zhang;Wenling Wang;Xingwang Li;Bo Yang;Jingdong Song;Xiang Zhao;Baoying Huang;Weifeng Shi;Roujian Lu;Peihua Niu;Faxian Zhan;Xuejun Ma;Dayan Wang;Wenbo Xu;Guizhen Wu;George F Gao;Wenjie Tan; - The New England journal of medicine (2020)
  6. Coronavirus biology and replication: implications for SARS-CoV-2. - Philip V'kovski;Annika Kratzel;Silvio Steiner;Hanspeter Stalder;Volker Thiel - Nature reviews. Microbiology (2021)
  7. Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses - are we our own worst enemy? - Lok-Yin Roy Wong;Stanley Perlman - Nature reviews. Immunology (2022)
  8. SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns. - Natalia Redondo;Sara Zaldívar-López;Juan J Garrido;Maria Montoya - Frontiers in immunology (2021)
  9. Coronavirus Spike Protein and Tropism Changes. - R J G Hulswit;C A M de Haan;B-J Bosch - Advances in virus research (2016)
  10. A pneumonia outbreak associated with a new coronavirus of probable bat origin. - Peng Zhou;Xing-Lou Yang;Xian-Guang Wang;Ben Hu;Lei Zhang;Wei Zhang;Hao-Rui Si;Yan Zhu;Bei Li;Chao-Lin Huang;Hui-Dong Chen;Jing Chen;Yun Luo;Hua Guo;Ren-Di Jiang;Mei-Qin Liu;Ying Chen;Xu-Rui Shen;Xi Wang;Xiao-Shuang Zheng;Kai Zhao;Quan-Jiao Chen;Fei Deng;Lin-Lin Liu;Bing Yan;Fa-Xian Zhan;Yan-Yi Wang;Geng-Fu Xiao;Zheng-Li Shi - Nature (2020)

Literatures Citing This Work ​

  1. Clinical and Imaging Features of COVID-19-Associated Pulmonary Aspergillosis. - Tim Fischer;Yassir El Baz;Nicole Graf;Simon Wildermuth;Sebastian Leschka;Gian-Reto Kleger;Urs Pietsch;Manuel Frischknecht;Giulia Scanferla;Carol Strahm;Stephan Wälti;Tobias Johannes Dietrich;Werner C Albrich - Diagnostics (Basel, Switzerland) (2022)
  2. Neurotrophin Signaling Impairment by Viral Infections in the Central Nervous System. - Karen Bohmwald;Catalina A Andrade;Valentina P Mora;José T Muñoz;Robinson Ramírez;María F Rojas;Alexis M Kalergis - International journal of molecular sciences (2022)
  3. Significantly Reduced Retinol Binding Protein 4 (RBP4) Levels in Critically Ill COVID-19 Patients. - Richard Vollenberg;Phil-Robin Tepasse;Manfred Fobker;Anna Hüsing-Kabar - Nutrients (2022)
  4. What Can an Organ-on-a-Chip Teach Us About Human Lung Pathophysiology? - Haiqing Bai;Donald E Ingber - Physiology (Bethesda, Md.) (2022)
  5. COVID-19 coagulopathy - what should we treat? - Pratima Chowdary - Experimental physiology (2022)
  6. The Omicron variant BA.1.1 presents a lower pathogenicity than B.1 D614G and Delta variants in a feline model of SARS-CoV-2 infection. - Mathias Martins;Gabriela M do Nascimento;Mohammed Nooruzzaman;Fangfeng Yuan;Chi Chen;Leonardo C Caserta;Andrew D Miller;Gary R Whittaker;Ying Fang;Diego G Diel - bioRxiv : the preprint server for biology (2022)
  7. Prevalence and risk factors for postinfectious cough in discharged patients with coronavirus disease 2019 (COVID-19). - Yuehan Chen;Xu Zhang;Xiansheng Zeng;Tingting Xu;Wei Xiao;Xuejiao Yang;Wenzhi Zhan;Chen Zhan;Kefang Lai - Journal of thoracic disease (2022)
  8. Blood Hyperviscosity: A Novel Link Between Hyperinflammation and Hypercoagulability in COVID-19. - Aldo Bonaventura;Nicola Potere - Journal of the American College of Cardiology (2022)
  9. Advances in understanding interferon-mediated immune responses to enteric viruses in intestinal organoids. - Lila S Nolan;Megan T Baldridge - Frontiers in immunology (2022)
  10. Two Years into the COVID-19 Pandemic: Lessons Learned. - Severino Jefferson Ribeiro da Silva;Jessica Catarine Frutuoso do Nascimento;Renata Pessôa Germano Mendes;Klarissa Miranda Guarines;Caroline Targino Alves da Silva;Poliana Gomes da Silva;Jurandy Júnior Ferraz de Magalhães;Justin R J Vigar;Abelardo Silva-Júnior;Alain Kohl;Keith Pardee;Lindomar Pena - ACS infectious diseases (2022)

... (436 more literatures)

© 2025 MaltSci - We reshape scientific research with AI technology