The T cell immune response against SARS-CoV-2

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(2), P. 186 - 193

Published: Feb. 1, 2022

Language: Английский

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Pathological sequelae of long-haul COVID

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(2), P. 194 - 202

Published: Feb. 1, 2022

Language: Английский

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The interferon landscape along the respiratory tract impacts the severity of COVID-19

Cell, Journal Year: 2021, Volume and Issue: 184(19), P. 4953 - 4968.e16

Published: Aug. 19, 2021

Severe coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role interferons (IFNs) type I (IFN-I) or III (IFN-III) families remains debated. We scrutinized production IFNs along respiratory tract COVID-19 patients and found that high levels IFN-III, to a lesser extent IFN-I, characterize upper airways with viral burden reduced risk severity. Production specific not members denotes mild pathology efficiently drives transcription genes protect against severe acute syndrome 2 (SARS-CoV-2). In contrast, compared subjects other infectious noninfectious lung pathologies, are overrepresented in lower exhibit gene pathways associated increased apoptosis decreased proliferation. Our data demonstrate dynamic SARS-CoV-2-infected show play opposing roles at distinct anatomical sites.

Language: Английский

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Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

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

Published: Jan. 14, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious virus which responsible for the disease 2019 (COVID-19) pandemic. It increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms many months after infection, condition referred to as "long COVID", post-acute sequelae of COVID-19 (PASC), syndrome, or post condition. However, despite plethora research on relatively little known about molecular underpinnings these long-term effects.We have undertaken an integrated analysis immune responses in blood at transcriptional, cellular, and serological level 12, 16, 24 weeks post-infection (wpi) 69 patients recovering mild, moderate, severe, critical comparison healthy uninfected controls. Twenty-one were long COVID clinic > 50% reported ongoing more than 6 post-infection.Anti-Spike anti-RBD IgG largely stable up wpi correlated with severity. Deep immunophenotyping revealed significant differences multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) adaptive populations (T helper, T follicular regulatory cells) convalescent individuals compared controls, most strongly evident 12 16 wpi. RNA sequencing perturbations gene expression convalescents until least post-infection. We also uncovered transcriptome not.Variation rate recovery infection cellular transcriptional may explain persistence associated some individuals.

Language: Английский

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The germinal centre B cell response to SARS-CoV-2

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(1), P. 7 - 18

Published: Dec. 6, 2021

The germinal centre (GC) response is critical for the generation of affinity-matured plasma cells and memory B capable mediating long-term protective immunity. Understanding whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination elicits a GC has profound implications capacity responding to contribute protection against infection. However, direct assessment in humans remains major challenge. Here we summarize emerging evidence importance establishment durable broad immunity SARS-CoV-2 discuss new approaches modulate better protect newly variants. We also findings showing that cell persists draining lymph nodes at least 6 months some individuals following with mRNA-based vaccines. In this Review, Brian Laidlaw Ali Ellebedy outline our current understanding its establishing virus. They consider responses seen how may be modulated induce variants SARS-CoV-2.

Language: Английский

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Immunological memory to SARS‐CoV ‐2 infection and COVID ‐19 vaccines

Immunological Reviews, Journal Year: 2022, Volume and Issue: 310(1), P. 27 - 46

Published: June 22, 2022

Immunological memory is the basis of protective immunity provided by vaccines and previous infections. can develop from multiple branches adaptive immune system, including CD4 T cells, CD8 B long-lasting antibody responses. Extraordinary progress has been made in understanding to SARS-CoV-2 infection COVID-19 vaccines, addressing development; quantitative qualitative features different cellular anatomical compartments; durability each component antibodies. Given sophistication measurements; size human studies; use longitudinal samples cross-sectional head-to-head comparisons between or for 1 year already supersedes that any other acute infectious disease. This knowledge may help inform public policies regarding as well scientific development future against diseases.

Language: Английский

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Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Cell, Journal Year: 2021, Volume and Issue: 185(3), P. 493 - 512.e25

Published: Dec. 28, 2021

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, it remains unclear whether T cells contribute disease pathology. Here, we combined single-cell transcriptomics proteomics with mechanistic studies assess pathogenic cell functions inducing signals. We identified highly activated CD16

Language: Английский

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Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome

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

Published: June 30, 2022

The duration and severity of COVID-19 are related to age, comorbidities, cytokine synthesis. This study evaluated the impact these factors on patients with clinical presentations in a Brazilian cohort. A total 317 diagnosed were included; cases distributed according status as severe (n=91), moderate (n=56) mild (n=170). Of patients, 92 had acute at sample collection, 90 already recovered from without sequelae, 135 sequelae (long COVID syndrome). In group, form higher IL-6 levels (p=0.0260). post-COVID-19 there was no significant difference between groups different conditions. younger TNF-α, comorbidities IL-4 IL-2 (p<0.05). contrast, over age 60 IL-6. subjects long IL-17 (p<0.05), IL-10, IL- 4 Our results suggest that advanced elevated serum associated good markers differentiate cases. Furthermore, high low IL-10 appear constitute profile COVID-19, potential targets for treatment prevention strategies.

Language: Английский

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COVID-19 therapeutics: Challenges and directions for the future

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(15)

Published: April 6, 2022

The emergence of SARS-CoV-2 triggering the COVID-19 pandemic ranks as arguably greatest medical emergency last century. has highlighted health disparities both within and between countries will leave a lasting impact on global society. Nonetheless, substantial investment in life sciences over recent decades facilitated rapid scientific response with innovations viral characterization, testing, sequencing. Perhaps most remarkably, this permitted development highly effective vaccines, which are being distributed globally at unprecedented speed. In contrast, drug treatments for established disease have delivered limited benefits so far. Innovative approaches design execution large-scale clinical trials repurposing existing drugs saved many lives; however, more remain risk. review we describe challenges unmet needs, discuss therapeutics, address future opportunities. Consideration is given to factors that hindered order support planning next challenge allow cost-effective new therapeutics equitable delivery.

Language: Английский

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Human immune diversity: from evolution to modernity

Nature Immunology, Journal Year: 2021, Volume and Issue: 22(12), P. 1479 - 1489

Published: Nov. 18, 2021

Language: Английский

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