Identification of SARS-CoV-2–specific immune alterations in acutely ill patients

Rébillard, Rose Marie; Charabati, Marc; Grasmuck, Camille; Filali-Mouhim, Abdelali; Tastet, Olivier; Brassard, Nathalie; Daigneault, Audrey; Bourbonnière, Lyne; Anand, Sai Priya; Balthazard, Renaud; Beaudoin-Bussières, Guillaume; Gasser, Romain; Benlarbi, Mehdi; Moratalla, Ana Carmena; Solorio, Yves Carpentier; Boutin, Marianne; Farzam‐kia, Negar; Descôteaux-Dinelle, Jade; Fournier, Antoine; Gowing, Elizabeth; Laumaea, Annemarie; Jamann, Hélène; Lahav, Boaz; Goyette, Guillaume; Lemaître, Florent; Mamane, Victoria Hannah; Prévost, Jérémie; Richard, Jonathan; Thai, Karine; Cailhier, Jean François; Chomont, Nicolas; Finzi, Andrés; Chassé, Michaël; Durand, Madéleine; Arbour, Nathalie; Kaufmann, Daniel E.; Prat, Alexandre; Larochelle, Catherine

doi:10.1172/jci145853

Cited by 32 publications

(41 citation statements)

References 89 publications

(92 reference statements)

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“…Indeed, the ability of our model to recapitulate severe disease by, in part, regulating monocyte differentiation raises the possibility that patients with low monocyte levels [7] may benefit from treatments that better regulate monocyte differentiation. This is in line with recent studies identifying distinct transcriptional factors as regulators of differentiated monocyte fates in inflammatory conditions [74,75], and clinical observations that monocyte dysregulation is present in severe COVID-19 [76,77]. It also raises the possibility that modulation by exogenous cytokines, including macrophage colony-stimulating factor in combination with IL-4 and tumour necrosis factor-alpha (TNF-α), may be able to direct monocyte differentiation in favour of monocyte-derived dendritic cells and reduce this response [74].…”

Section: Plos Pathogenssupporting

confidence: 90%

COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes

et al. 2021

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To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results suggest that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these in silico patients, the maximum concentration of IL-6 was also a major predictor of CD8+ T cell depletion. Our analyses predicted that individuals with severe COVID-19 also have accelerated monocyte-to-macrophage differentiation mediated by increased IL-6 and reduced type I IFN signalling. Together, these findings suggest biomarkers driving the development of severe COVID-19 and support early interventions aimed at reducing inflammation.

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Section: Plos Pathogenssupporting

confidence: 90%

COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes

et al. 2021

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“…According to several studies, the proportions of neutrophils were increased in severe patients compared to mild [ 38 , 39 , 40 , 41 ]. In particular, severe hospitalized patients had higher levels of CD16 low , CD16 Int compared to mild and moderate ones, while increased levels of CD16 Int associated with elevated levels of D-dimer are reported in a severe patient until he passed away [ 39 , 42 ] and mature and activated ICAM-1 neutrophils [ 43 ]. The latter likely boost the proinflammatory cascade in COVID-19, as they contribute to inflammation spreading through reverse transendothelial migration, neutrophil aggregation, and effector functions [ 44 , 45 ].…”

Section: Association Of Alterations Of Cell Populations and Covid-19 ...mentioning

confidence: 99%

“…The latter likely boost the proinflammatory cascade in COVID-19, as they contribute to inflammation spreading through reverse transendothelial migration, neutrophil aggregation, and effector functions [ 44 , 45 ]. Neutrophilia has been suggested as a predictive marker of disease severity [ 46 ]; however, according to Rebillard and colleagues, elevated neutrophil counts are predictive of disease severity in general and not COVID-19 specifically [ 43 ]. In general, the studies referring to granulocytes, including neutrophils, eosinophils, and basophils, present contradictory results.…”

Section: Association Of Alterations Of Cell Populations and Covid-19 ...mentioning

confidence: 99%

Molecular and Clinical Prognostic Biomarkers of COVID-19 Severity and Persistence

et al. 2022

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The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), poses several challenges to clinicians, due to its unpredictable clinical course. The identification of laboratory biomarkers, specific cellular, and molecular mediators of immune response could contribute to the prognosis and management of COVID-19 patients. Of utmost importance is also the detection of differentially expressed genes, which can serve as transcriptomic signatures, providing information valuable to stratify patients into groups, based on the severity of the disease. The role of biomarkers such as IL-6, procalcitonin, neutrophil–lymphocyte ratio, white blood cell counts, etc. has already been highlighted in recently published studies; however, there is a notable amount of new evidence that has not been summarized yet, especially regarding transcriptomic signatures. Hence, in this review, we assess the latest cellular and molecular data and determine the significance of abnormalities in potential biomarkers for COVID-19 severity and persistence. Furthermore, we applied Gene Ontology (GO) enrichment analysis using the genes reported as differentially expressed in the literature in order to investigate which biological pathways are significantly enriched. The analysis revealed a number of processes, such as inflammatory response, and monocyte and neutrophil chemotaxis, which occur as part of the complex immune response to SARS-CoV-2.

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“…Lymphocytes from COVID-19 patients have been found to have increased expressions of inhibitory molecules, such as PD-1 or CTLA-4, producing an ineffective immune response (13,14). Upregulation of PD-1 on CD4 + T cells in SARS-CoV-2 patients has also been associated with poor outcomes at 30 days (15).…”

Section: Introductionmentioning

confidence: 99%

Low Levels of Granulocytic Myeloid-Derived Suppressor Cells May Be a Good Marker of Survival in the Follow-Up of Patients With Severe COVID-19

et al. 2022

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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a disease (coronavirus disease 2019, COVID-19) that may develop into a systemic disease with immunosuppression and death in its severe form. Myeloid-derived suppressive cells (MDSCs) are inhibitory cells that contribute to immunosuppression in patients with cancer and infection. Increased levels of MDSCs have been found in COVID-19 patients, although their role in the pathogenesis of severe COVID-19 has not been clarified. For this reason, we raised the question whether MDSCs could be useful in the follow-up of patients with severe COVID-19 in the intensive care unit (ICU). Thus, we monitored the immunological cells, including MDSCs, in 80 patients admitted into the ICU. After 1, 2, and 3 weeks, we examined for a possible association with mortality (40 patients). Although the basal levels of circulating MDSCs did not discriminate between the two groups of patients, the last measurement before the endpoint (death or ICU discharge) showed that patients discharged alive from the ICU had lower levels of granulocytic MDSCs (G-MDSCs), higher levels of activated lymphocytes, and lower levels of exhausted lymphocytes compared with patients who had a bad evolution (death). In conclusion, a steady increase of G-MDSCs during the follow-up of patients with severe COVID-19 was found in those who eventually died.

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Identification of SARS-CoV-2–specific immune alterations in acutely ill patients

Cited by 32 publications

References 89 publications

COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes

COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes

Molecular and Clinical Prognostic Biomarkers of COVID-19 Severity and Persistence

Low Levels of Granulocytic Myeloid-Derived Suppressor Cells May Be a Good Marker of Survival in the Follow-Up of Patients With Severe COVID-19

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