Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

Kreutmair, Stefanie; Unger, Susanne; Núñez, Nicolás Gonzalo; Ingelfinger, Florian; Alberti, Chiara; Feo, Donatella De; Krishnarajah, Sinduya; Kauffmann, Manuel; Friebel, Ekaterina; Babaei, Sepideh; Gaborit, Benjamin; Lutz, Mirjam; Jurado, Nicole Puertas; Malek, Nisar P.; Goepel, Siri; Rosenberger, Peter; Häberle, Helene A.; Ayoub, Ikram; Al-Hajj, Sally; Nilsson, Jakob; Claassen, Manfred; Liblau, Roland; Martin‐Blondel, Guillaume; Bitzer, Michael; Roquilly, Antoine; Becher, Burkhard

doi:10.1016/j.immuni.2021.05.002

Cited by 84 publications

(83 citation statements)

References 81 publications

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“…BMI is strongly correlated with immune signatures that predict severe COVID-19. 10 Distinct immunological signatures discriminate severe COVID-19 from critical pneumonia that is not driven by SARS-CoV-2, 10 and the presence of obesity might shift severe manifestations of COVID-19 to younger age groups (aged <50 years), as reported by researchers at Johns Hopkins. 11 Additionally, underlying diseases might be aggravated, increasing the susceptibility of patients to serious long-term consequences.…”

Section: Introductionmentioning

confidence: 88%

COVID-19 and metabolic disease: mechanisms and clinical management

Steenblock

Schwarz

Ludwig

et al. 2021

The Lancet Diabetes & Endocrinology

189

160

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Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders. In this Review, we provide an update on the mechanisms of how metabolic and endocrine disorders might predispose patients to develop severe COVID-19. Additionally, we update the practical recommendations and management of patients with COVID-19 and post-pandemic. Furthermore, we summarise new treatment options for patients with both COVID-19 and diabetes, and highlight current challenges in clinical management.

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Section: Introductionmentioning

confidence: 88%

COVID-19 and metabolic disease: mechanisms and clinical management

Steenblock

Schwarz

Ludwig

et al. 2021

The Lancet Diabetes & Endocrinology

189

160

View full text Add to dashboard Cite

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“…3 ). Loss of the NKT cell subset has been reported as one of the prominent features of COVID-19, which became apparent already within the first week of hospital admission and could predict disease evolution [ 114 ]. On the contrary, no significant alterations were described in peripheral blood [ 115 , 116 , 48 , 49 ] for T follicular helper cells (Tfh).…”

Section: Lymphopeniamentioning

confidence: 99%

Hallmarks of immune response in COVID-19: Exploring dysregulation and exhaustion

Mazzoni

Salvati

Maggi

et al. 2021

Seminars in Immunology

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One and half year following the occurrence of COVID-19 pandemic, significant efforts from laboratories all over the world generated a huge amount of data describing the prototypical features of immunity in the course of SARS-CoV-2 infection. In this Review, we rationalize and organize the main observations, trying to define a “core” signature of immunity in COVID-19. We identified six hallmarks describing the main alterations occurring in the early infection phase and in the course of the disease, which predispose to severe illness. The six hallmarks are dysregulated type I IFN activity, hyperinflammation, lymphopenia, lymphocyte impairment, dysregulated myeloid response, and heterogeneous adaptive immunity to SARS-CoV-2. Dysregulation and exhaustion came out as the trait d’union, connecting abnormalities affecting both innate and adaptive immunity, humoral and cellular responses.

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“…Aegerter et al [41] hypothesized the very plausible notion that the initial stimulus intensity directly impacts the macrophage niche's fate: low-intensity aggression would induce protective trained immunity, whereas high-intensity aggression (potentially lethal) would induce a deleterious immune modulation from chronic inflammation to immune paralysis. Moreover, the type of pathogens, for instance viral vs. bacterial pneumonia, areassociated with different lymphocytes and monocytes response during the initiation of the reprogramming of ResAM [79]. Van der Poll et al [80] further found that long-term innate immune cell reprogramming impacted cytokine production and could be linked to post septic immune paralysis.…”

Section: The Immunologic Scar Left Over By Inflammation: Friend Of Foe?mentioning

confidence: 99%

Alveolar Macrophages: Adaptation to Their Anatomic Niche during and after Inflammation

Martin

Jacqueline

Poschmann

et al. 2021

Cells

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At the early stages of life development, alveoli are colonized by embryonic macrophages, which become resident alveolar macrophages (ResAM) and self-sustain by local division. Genetic and epigenetic signatures and, to some extent, the functions of ResAM are dictated by the lung microenvironment, which uses cytokines, ligand-receptor interactions, and stroma cells to orchestrate lung homeostasis. In resting conditions, the lung microenvironment induces in ResAM a tolerogenic programming that prevents unnecessary and potentially harmful inflammation responses to the foreign bodies, which continuously challenge the airways. Throughout life, any episode of acute inflammation, pneumonia being likely the most frequent cause, depletes the pool of ResAM, leaving space for the recruitment of inflammatory monocytes that locally develop in monocyte-derived alveolar macrophages (InfAM). During lung infection, the local microenvironment induces a temporary inflammatory signature to the recruited InfAM to handle the tissue injury and eliminate the pathogens. After a few days, the recruited InfAM, which locally self-sustain and develop as new ResAM, gain profibrotic functions required for tissue healing. After the complete resolution of the infectious episode, the functional programming of both embryonic and monocyte-derived ResAM remains altered for months and possibly for the entire life. Adult lungs thus contain a wide diversity of ResAM since every infection brings new waves of InfAM which fill the room left open by the inflammatory process. The memory of these innate cells called trained immunity constitutes an immunologic scar left by inflammation, notably pneumonia. This memory of ResAM has advantages and drawbacks. In some cases, lung-trained immunity offers better defense capacities against autoimmune disorders and the long-term risk of infection. At the opposite, it can perpetuate a harmful process and lead to a pathological state, as is the case among critically ill patients who have immune paralysis and are highly susceptible to hospital-acquired pneumonia and acute respiratory distress syndrome. The progress in understanding the kinetics of response of alveolar macrophages (AM) to lung inflammation is paving the way to new treatments of pneumonia and lung inflammatory process.

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Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

Cited by 84 publications

References 81 publications

COVID-19 and metabolic disease: mechanisms and clinical management

COVID-19 and metabolic disease: mechanisms and clinical management

Hallmarks of immune response in COVID-19: Exploring dysregulation and exhaustion

Alveolar Macrophages: Adaptation to Their Anatomic Niche during and after Inflammation

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