Viral and Bacterial Co-Infections in the Lungs: Dangerous Liaisons DOI Creative Commons
Justine Oliva, Olivier Terrier

Viruses, Journal Year: 2021, Volume and Issue: 13(9), P. 1725 - 1725

Published: Aug. 30, 2021

Respiratory tract infections constitute a significant public health problem, with therapeutic arsenal that remains relatively limited and is threatened by the emergence of antiviral and/or antibiotic resistance. Viral-bacterial co-infections are very often associated severity these respiratory have been explored mainly in context bacterial superinfections following primary influenza infection. This review summarizes our current knowledge mechanisms underlying between viruses (influenza viruses, RSV, SARS-CoV-2) bacteria, at both physiological immunological levels. also explores importance microbiome pathological evolution presents different vitro vivo experimental models available. A better understanding complex functional interactions viruses/bacteria host cells will allow development new, specific, more effective diagnostic approaches.

Language: Английский

S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters DOI Creative Commons
Michihito Sasaki, Koshiro Tabata, Mai Kishimoto

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 15(679)

Published: Nov. 3, 2022

In parallel with vaccination, oral antiviral agents are highly anticipated to act as countermeasures for the treatment of coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2). Oral medication demands not only high activity but also target specificity, favorable bioavailability, and metabolic stability. Although a large number compounds have been identified potential inhibitors SARS-CoV-2 infection in vitro, few proven be effective vivo. Here, we show that administration S-217622 (ensitrelvir), an inhibitor main protease (Mpro; known 3C-like protease), decreases viral load ameliorates severity SARS-CoV-2-infected hamsters. inhibited proliferation at low nanomolar submicromolar concentrations cells. demonstrated pharmacokinetic properties accelerated recovery from hamster recipients. Moreover, exerted against variants concern, including pathogenic Delta variant recently emerged Omicron BA.5 BA.2.75 variants. Overall, our study provides evidence S-217622, agent is under evaluation phase 3 clinical trial (clinical registration no. jRCT2031210350), has remarkable potency efficacy prospective therapeutic option COVID-19.

Language: Английский

Citations

80
TLR2 and TLR7 mediate distinct immunopathological and antiviral plasmacytoid dendritic cell responses to SARS‐CoV‐2 infection DOI Creative Commons
Renée M. van der Sluis, Lamin B. Cham, Albert Gris‐Oliver

et al.

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(10)

Published: Feb. 18, 2022

Understanding the molecular pathways driving acute antiviral and inflammatory response to SARS-CoV-2 infection is critical for developing treatments severe COVID-19. Here, we find decreasing number of circulating plasmacytoid dendritic cells (pDCs) in COVID-19 patients early after symptom onset, correlating with disease severity. pDC depletion transient coincides decreased expression type I IFNα systemic cytokines CXCL10 IL-6. Using an vitro stem cell-based human model, further demonstrate that pDCs, while not supporting replication, directly sense virus produce multiple (interferons: IFNλ1) (IL-6, IL-8, CXCL10) protect epithelial from de novo infection. Via targeted deletion virus-recognition innate immune pathways, identify TLR7-MyD88 signaling as crucial production interferons (IFNs), whereas Toll-like receptor (TLR)2 responsible IL-6 response. We show engages neuropilin-1 on pDCs selectively mitigate interferon response, but suggesting potential therapeutic target stimulation TLR7-mediated protection.

Language: Английский

Citations

78
Innate immunity, cytokine storm, and inflammatory cell death in COVID-19 DOI Creative Commons
Rajendra Karki, Thirumala‐Devi Kanneganti

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Nov. 22, 2022

Abstract The innate immune system serves as the first line of defense against invading pathogens; however, dysregulated responses can induce aberrant inflammation that is detrimental to host. Therefore, careful regulation critical during infections. coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) and has resulted in global morbidity mortality well socio-economic stresses. Innate sensing SARS-CoV-2 multiple host cell pattern recognition receptors leads production various pro-inflammatory cytokines induction inflammatory death. These processes contribute cytokine storm, tissue damage, distress syndrome. Here, we discuss activation contribution this signaling development severity COVID-19. In addition, provide a conceptual framework for immunity driving storm organ damage patients with A better understanding molecular mechanisms regulated needed targeted modalities improve patient outcomes mitigating disease.

Language: Английский

Citations

78
Recent developments in the immunopathology of COVID‐19 DOI Creative Commons
Huanping Zhang,

Yuanli Sun,

Yanfen Wang

et al.

Allergy, Journal Year: 2022, Volume and Issue: 78(2), P. 369 - 388

Published: Nov. 24, 2022

Abstract There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID‐19) patients during pandemic thanks to extensive vaccination programs. Here, we highlight recent studies on COVID‐19, from immunological protective risk factors for severity mortality COVID‐19. The efficacy COVID‐19 vaccines potential allergic reactions after administration are also discussed. occurrence new variants concerns such as Omicron BA.2, BA.4, BA.5 global have changed scenario Multisystem inflammatory syndrome children (MIS‐C) may cause severe heterogeneous but with a lower rate. Perturbations immunity T cells, B mast well autoantibodies metabolic reprogramming contribute long‐term symptoms is conflicting evidence about whether atopic diseases, asthma rhinitis, associated susceptibility better outcomes At beginning pandemic, European Academy Allergy Clinical Immunology (EAACI) developed guidelines that provided timely information management diseases preventive measures reduce transmission clinics. distribution emerging acute respiratory coronavirus 2 (SARS‐CoV‐2) reduced pathogenic dramatically decreased morbidity, severity, Nevertheless, breakthrough infection remains challenge control. Hypersensitivity (HSR) low compared other vaccines, these were addressed EAACI statements indications reactions, including anaphylaxis vaccines. We gained depth knowledge experience over years since start yet full eradication SARS‐CoV‐2 not horizon. Novel strategies warranted prevent high‐risk groups, development MIS‐C long

Language: Английский

Citations

76
SARS-CoV-2 variants evolve convergent strategies to remodel the host response DOI Creative Commons
Mehdi Bouhaddou, Ann‐Kathrin Reuschl, Benjamin J. Polacco

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(21), P. 4597 - 4614.e26

Published: Sept. 21, 2023

Language: Английский

Citations

72
Type I interferons and SARS-CoV-2: from cells to organisms DOI Creative Commons
Paul Bastard, Qian Zhang, Shen‐Ying Zhang

et al.

Current Opinion in Immunology, Journal Year: 2022, Volume and Issue: 74, P. 172 - 182

Published: Jan. 25, 2022

Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type IFNs SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of IFNs, proteins can inhibit various steps IFN production response. Exogenous viral growth vitro. In animal species vivo, deficiencies underlie higher loads more severe disease than control animals. The early administration exogenous improves infection control. humans, inborn errors of, auto-antibodies against life-threatening COVID-19 pneumonia. Overall, are essential for host defense individual whole organisms.

Language: Английский

Citations

71
The roles of critical pro‐inflammatory cytokines in the drive of cytokine storm during SARS‐CoV‐2 infection DOI Creative Commons
Muhammad Suhaib Qudus, Mingfu Tian,

Summan Sirajuddin

et al.

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(4)

Published: April 1, 2023

Abstract In patients with severe COVID‐19, acute respiratory distress syndrome (ARDS), multiple organ dysfunction (MODS), and even mortality can result from cytokine storm, which is a hyperinflammatory medical condition caused by the excessive uncontrolled release of pro‐inflammatory cytokines. High levels numerous crucial cytokines, such as interleukin‐1 (IL‐1), IL‐2, IL‐6, tumor necrosis factor‐α, interferon (IFN)‐γ, IFN‐induced protein 10 kDa, granulocyte‐macrophage colony‐stimulating factor, monocyte chemoattractant protein‐1, IL‐10 so on, have been found in COVID‐19. They participate cascade amplification pathways responses through complex inflammatory networks. Here, we review involvements these critical cytokines SARS‐CoV‐2 infection discuss their potential roles triggering or regulating help to understand pathogenesis So far, there rarely effective therapeutic strategy for storm besides using glucocorticoids, proved fatal side effects. Clarifying key involved network will develop an ideal intervention, neutralizing antibody certain inhibitor some signal pathways.

Language: Английский

Citations

50
Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants DOI Creative Commons
Ann‐Kathrin Reuschl, Lucy Thorne, Matthew Whelan

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(2), P. 451 - 463

Published: Jan. 16, 2024

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human adaptation resulted in distinct lineages with enhanced transmissibility called variants of concern (VOCs). Omicron is the first VOC to evolve globally dominant subvariants. Here we compared their replication cell lines and primary airway cultures measured host responses infection. We discovered that subvariants BA.4 BA.5 have improved suppression innate immunity when earlier BA.1 BA.2. Similarly, more recent (BA.2.75 XBB lineages) also triggered reduced immune activation. This correlated increased expression viral antagonists Orf6 nucleocapsid, reminiscent VOCs Alpha Delta. Increased levels suppressed infection by decreasing IRF3 STAT1 signalling transcription factor phosphorylation nuclear translocation. Our data suggest convergent evolution antagonist a common pathway link subvariant dominance evasion.

Language: Английский

Citations

48
Covid-19 a triggering factor of autoimmune and multi-inflammatory diseases DOI Creative Commons

Emina Karahmet Sher,

Adnan Ćosović,

Amina Džidić-Krivić

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 319, P. 121531 - 121531

Published: Feb. 27, 2023

SARS-CoV-2 virus has attracted a lot of attention globally due to the autoimmune and inflammatory processes that were observed during development Covid-19 disease. Excessive activation immune response triggering autoantibodies synthesis as well an excessive cytokines onset cytokine storm vital role in disease outcome occurring complications. This scenario is reminiscent infiltration lymphocytes monocytes specific organs increased production chemoattractants noted other diseases. The main goal this study investigate complex occur find similarities with diseases such multiple sclerosis (MS), acute respiratory distress syndrome (ARDS), rheumatoid arthritis (RA) Kawasaki advance existing diagnostic therapeutic protocols. therapy Interferon-gamma (IFN-γ) use S1P receptor modulators showed promising results. However, there are many unknowns about these mechanisms possible novel therapies. Therefore, inflammation autoimmunity triggered by should be further investigated improve procedures protocols for Covid-19.

Language: Английский

Citations

46
MDA5-autoimmunity and interstitial pneumonitis contemporaneous with the COVID-19 pandemic (MIP-C) DOI
Paula David, Saptarshi Sinha,

Khizer Iqbal

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 104, P. 105136 - 105136

Published: May 8, 2024

Citations

17