Recent developments in the immunopathology of COVID‐19

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

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Age-specific nasal epithelial responses to SARS-CoV-2 infection

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(5), P. 1293 - 1311

Published: April 15, 2024

Abstract Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in people over 85 years age remains high. Here we investigate differences cellular landscape and function paediatric (<12 years), adult (30–50 years) older (>70 ex vivo cultured nasal epithelial cells response infection SARS-CoV-2. We show that cell tropism SARS-CoV-2, expression ACE2 TMPRSS2 subtypes, differ between groups. While ciliated are viral replication centres across all groups, a distinct goblet inflammatory subtype emerges cultures shows high interferon-stimulated genes incomplete replication. In contrast, proportional increase basaloid-like cells, which facilitate spread associated altered repair pathways. confirm age-specific induction these types by integrating data from COVID-19 studies validate our vitro model recapitulates early responses infection.

Language: Английский

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Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating

mBio, Journal Year: 2024, Volume and Issue: 15(4)

Published: March 13, 2024

ABSTRACT The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features each VOC linked variations replication rate. Patient-derived primary nasal cultures grown at air-liquid interface used model upper respiratory infection compared cell lines derived from lung epithelia. All VOCs replicated higher titers than ancestral virus, suggesting a for efficiency. In cultures, Omicron highest early time points, followed by Delta, paralleling comparative studies population sampling. viruses entered primarily via transmembrane serine protease 2 (TMPRSS2)-dependent pathway, more likely use an endosomal route entry. activated overcame dsRNA-induced cellular responses, including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation, protein kinase R activation. Among VOCs, induced expression most IFN IFN-stimulated genes. Infections resulted damage, compromise barrier integrity loss cilia ciliary beating function, especially during Delta infection. Overall, optimized tract least favorable lower line, cytopathic both cells. Our findings highlight differences among level imply distinct mechanisms pathogenesis infected individuals. IMPORTANCE Comparative analysis infections virus concern, Alpha, Beta, Omicron, indicated that selected efficiency replication. patient-derived infection, reached finding confirmed parallel sampling studies. While all dsRNA-mediated host strongest interferon-stimulated gene response. damaging cells syncytia formation, integrity, function.

Language: Английский

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Choosing a cellular model to study SARS-CoV-2

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 21, 2022

As new pathogens emerge, challenges must be faced. This is no different in infectious disease research, where identifying the best tools available laboratories to conduct an investigation can, at least initially, particularly complicated. However, context of emerging virus, such as SARS-CoV-2, which was recently detected China and has become a global threat healthcare systems, developing models infection pathogenesis urgently required. Cell-based approaches are crucial understanding coronavirus biology, growth kinetics, tropism. Usually, laboratory cell lines first line experimental study viral pathogenicity perform assays aimed screening antiviral compounds efficient blocking replication viruses, saving time resources, reducing use animals. determining ideal type can challenging, especially when several researchers have adapt their studies specific requirements. review strives guide scientists who venturing into studying SARS-CoV-2 help them choose right cellular models. It revisits basic concepts virology presents currently

Language: Английский

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Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(15)

Published: April 6, 2023

The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize epithelial cells grown at air-liquid interface, which recapitulate heterogeneous cellular population as well mucociliary clearance functions of in vivo epithelium, compare lethal [Severe acute respiratory syndrome (SARS)-CoV-2 Middle East syndrome-CoV (MERS-CoV)] seasonal (HCoV-NL63 HCoV-229E) HCoVs. All four HCoVs replicate productively cultures, though replication differentially modulated temperature. Infections conducted 33 °C vs. 37 (reflective temperatures upper lower airway, respectively) revealed that both -229E) significantly attenuated °C. In contrast, SARS-CoV-2 MERS-CoV temperatures, enhanced late infection. These also diverge terms cytotoxicity induced following infection, cause disruption, while does not. Treatment cultures with type 2 cytokine IL-13 mimic asthmatic airways impacts HCoV receptor availability replication. DPP4 expression increases treatment, whereas ACE2, used HCoV-NL63, down-regulated. treatment enhances HCoV-229E but reduces reflecting impact on availability. This study highlights diversity among during likely influence downstream outcomes such disease severity transmissibility.

Language: Английский

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Glycosylated extracellular mucin domains protect against SARS-CoV-2 infection at the respiratory surface

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(8), P. e1011571 - e1011571

Published: Aug. 10, 2023

Mucins play an essential role in protecting the respiratory tract against microbial infections while also acting as binding sites for bacterial and viral adhesins. The heavily O-glycosylated gel-forming mucins MUC5AC MUC5B eliminate pathogens by mucociliary clearance. Transmembrane MUC1, MUC4, MUC16 can restrict invasion at apical surface of epithelium. In this study, we determined impact host mucin glycans on epithelial entry SARS-CoV-2. Human lung Calu-3 cells express SARS-CoV-2 receptor ACE2 high levels glycosylated but not MUC4 MUC16, their cell surface. O-glycan-specific mucinase StcE specifically removed part MUC1 extracellular domain leaving underlying SEA cytoplasmic tail intact. treatment significantly enhanced infection with pseudovirus authentic virus, removal terminal sialic acid fucose from did entry. cells, transmembrane are located to close proximity results purified spike protein. Both expressed human organoid-derived air-liquid interface (ALI) differentiated airway cultures led increased replication. these cultures, was highly non-ciliated enriched goblet cells. conclusion, domains different might have similar protective functions types restricting

Language: Английский

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Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection

Matrix Biology, Journal Year: 2023, Volume and Issue: 116, P. 49 - 66

Published: Feb. 1, 2023

Language: Английский

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SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 114076 - 114076

Published: April 1, 2024

The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants concern (VOCs) that replace ancestral strains. Here, we dissect complex selective pressures evaluating variant fitness and adaptation in human tissues. We evaluate viral properties host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. observe differential replication airway epithelia, differences cellular tropism, virus-induced cytotoxicity. accumulates most mutations after infection, supporting zoonosis airway. perform head-to-head competitions highest for Gamma Delta. Under these conditions, RNA recombination favors encoding B.1.617.1 lineage 3' end. Based on growth kinetics, Alpha, Gamma, Delta exhibit increased compared D614G. In contrast, global success likely derives from transmission antigenic variation. Our data provide molecular evidence support epidemiological observations VOC

Language: Английский

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Neutrophils play a major role in the destruction of the olfactory epithelium during SARS-CoV-2 infection in hamsters

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(12)

Published: Dec. 1, 2022

Language: Английский

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Safety and Efficacy of Dupilumab for the Treatment of Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019: A Phase 2a Trial

Open Forum Infectious Diseases, Journal Year: 2022, Volume and Issue: 9(8)

Published: July 27, 2022

Abstract Background Based on studies implicating the type 2 cytokine interleukin 13 (IL-13) as a potential contributor to critical coronavirus disease 2019 (COVID-19), this trial was designed an early phase study assess dupilumab, monoclonal antibody that blocks IL-13 and 4 signaling, for treatment of inpatients with COVID-19. Methods We conducted 2a randomized, double-blind, placebo-controlled (NCT04920916) safety efficacy dupilumab plus standard care vs placebo in mitigating respiratory failure death those hospitalized Results Forty eligible subjects were enrolled from June November 2021. There no statistically significant difference adverse events nor primary endpoint ventilator-free survival at day 28 between arms. However, secondary mortality 60, there deaths group compared 5 (60-day survival: 89.5% 76.2%; adjusted hazard ratio [HR], 0.05 [95% confidence interval {CI}, .004–.72]; P = .03). Among who not intensive unit (ICU) randomization, 3 arm admitted ICU 6 (17.7% 37.5%; HR, 0.44 CI, .09–2.09]; .30). Last, we found evidence signaling blockade through analysis immune biomarkers over time. Conclusions Although outcome reached, observed higher by 60. Clinical Trials Registration NCT04920916.

Language: Английский

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