Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages

Wauters, Els; Mol, Pierre Van; Garg, Abhishek D.; Jansen, S.L.; Herck, Yannick Van; Vanderbeke, Lore; Bassez, Ayse; Boeckx, Bram; Malengier‐Devlies, Bert; Timmerman, Anna; Brussel, Thomas Van; Buyten, Tina Van; Schepers, Rogier; Heylen, Elisabeth; Dauwe, Dieter; Dooms, Christophe; Gunst, Jan; Hermans, Greet; Meersseman, Philippe; Testelmans, Dries; Yserbyt, Jonas; Tejpar, Sabine; Wever, Walter De; Matthys, Patrick; Bosisio, Maria; Casaer, Michaël P; Smet, Frederik De; Munter, Paul De; Humblet-Baron, Stéphanie; Liston, Adrian; Lorent, Natalie; Martinod, Kim; Proost, Paul; Raes, Jeroen; Thevissen, Karin; Vos, Robin; Weynand, Birgit; Wouters, Carine; Neyts, Johan; Wauters, Joost; Qian, Junbin; Lambrechts, Diether

doi:10.1038/s41422-020-00455-9

Cited by 243 publications

(290 citation statements)

References 90 publications

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“…Across this spectrum of disease, analysis of post-mortem lung tissue has revealed that neutrophils accumulate in bronchial lumens, alveolar spaces and pulmonary lesions (69)(70)(71)(72), with this infiltration coinciding with significantly elevated BALF concentrations of the chemokine IL-8 (70). Moreover, mirroring the changes reported in the composition of the pulmonary neutrophil pool in humans with severe COVID-19 (48,78) immature "pre-neutrophils" have been detected in the lung sections of African green monkeys with high SARS-CoV-2 viral loads (79).…”

Section: Neutrophils and Covid-19 Pathobiology -Animal Model Datamentioning

confidence: 84%

Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets

Hazeldine

Lord

2021

Front. Immunol.

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Whilst the majority of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, experience mild to moderate symptoms, approximately 20% develop severe respiratory complications that may progress to acute respiratory distress syndrome, pulmonary failure and death. To date, single cell and high-throughput systems based analyses of the peripheral and pulmonary immune responses to SARS-CoV-2 suggest that a hyperactive and dysregulated immune response underpins the development of severe disease, with a prominent role assigned to neutrophils. Characterised in part by robust generation of neutrophil extracellular traps (NETs), the presence of immature, immunosuppressive and activated neutrophil subsets in the circulation, and neutrophilic infiltrates in the lung, a granulocytic signature is emerging as a defining feature of severe COVID-19. Furthermore, an assessment of the number, maturity status and/or function of circulating neutrophils at the time of hospital admission has shown promise as a prognostic tool for the early identification of patients at risk of clinical deterioration. Here, by summarising the results of studies that have examined the peripheral and pulmonary immune response to SARS-CoV-2, we provide a comprehensive overview of the changes that occur in the composition, phenotype and function of the neutrophil pool in COVID-19 patients of differing disease severities and discuss potential mediators of SARS-CoV-2-induced neutrophil dysfunction. With few specific treatments currently approved for COVID-19, we conclude the review by discussing whether neutrophils represent a potential therapeutic target for the treatment of patients with severe COVID-19.

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Section: Neutrophils and Covid-19 Pathobiology -Animal Model Datamentioning

confidence: 84%

Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets

Hazeldine

Lord

2021

Front. Immunol.

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“…accompanying CRS in those diseases. Finally, monocytes that normally would differentiate from a pro-inflammatory state to an anti-inflammatory state with enhanced antigen presentation activity as the infection progresses remain in a chronic proinflammatory activation state, preventing the normal resolution of the host response (16,76,77). In future studies, patientderived data including the size and activation status of innate and adaptive immune cell populations would help increase the understanding of CRS mechanisms in influenzamediated diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple studies have described an increase in the proinflammatory host immune response associated with severe forms of the diseases, including cytokine storms or cytokine release syndrome (CRS) (11,14,15). Although CRS usually resolves following completion of the antiviral response, it persists in severe cases (16). It can lead to tissue damage, multiple organ failure and death in critically-ill patients if the clinical intervention is not rapid (17,18).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Causes a Different Cytokine Response Compared to Other Cytokine Storm-Causing Respiratory Viruses in Severely Ill Patients

et al. 2021

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Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with coronavirus 2019 (COVID-19) for a subgroup of patients. CRS is not unique to the SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, and H7N9). With a comprehensive literature search, we collected changing the cytokine levels from patients upon infection with the viral pathogens mentioned above. We analyzed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. Our curation indicates that the cytokine response induced by SARS-CoV-2 is different compared to other CRS-causing respiratory viruses, as SARS-CoV-2 does not always induce specific cytokines like other coronaviruses or influenza do, such as IL-2, IL-10, IL-4, or IL-5. Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.

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“…Indeed, delayed or insufficient activation of T cell responses may lead to severe lung damage or systemic inflammation, whereas early induction of functional SARS-CoV-2-specific T cells is associated with rapid viral clearance and mild disease in COVID-19 patients [366]. In agreement with analyses in the blood, functional and consistent CD8 + resident-memory (TRM) and CD4 + T-helper-17 (TH17) cells in bronchoalveolar lavages were associated with beneficial outcomes [367]. Both CD4 + and CD8 + T cell responses to SARS-CoV-2 have been determined as important parameters associated with control of SARS-CoV-2 infection, yet CD4 + T cell responses appear even more prominent than CD8 + T cell responses [191,361,362,368].…”

Section: T Cellsmentioning

confidence: 62%

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

Duerr¹,

Jimenez²,

Dittmann³

2021

Preprint

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SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped, positive-stranded RNA viruses with envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics delineating their distinct strategies for efficient spread.

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Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages

Cited by 243 publications

References 90 publications

Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets

Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets

SARS-CoV-2 Causes a Different Cytokine Response Compared to Other Cytokine Storm-Causing Respiratory Viruses in Severely Ill Patients

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

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