COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases DOI Creative Commons
Silvana Valdebenito,

Simon Bessis,

Djillali Annane

и другие.

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Окт. 4, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. COVID-19 considered an airway/multi-systemic disease, and demise has been associated with uncontrolled immune response cytokine storm in to the virus. However, lung pathology, response, tissue damage are poorly described understood due safety concerns. Using post-mortem tissues from uninfected deadly cases as well unbiased combined analysis of histology, multi-viral host markers staining, correlative microscopy, confocal, image analysis, we identified three distinct phenotypes COVID-19-induced damage. First, hemorrhage characterized by minimal infiltration large thrombus; Second, excessive cell but no hemorrhagic events. The third phenotype correspond combination two previous ones. We observed loss alveolar wall integrity, detachment pieces, fibroblast proliferation, extensive fibrosis all phenotypes. Although studied were lethal COVID-19, strong was analyzed significant B poor T infiltrations, suggesting exhausted or compromised cellular these patients. Overall, our data show that SARS-CoV-2-induced highly heterogeneous. These individual differences need be understand long-term consequences.

Язык: Английский

MAIT cells, guardians of skin and mucosa? DOI Creative Commons
Isabelle Nel, Léo Bertrand, Amine Toubal

и другие.

Mucosal Immunology, Год журнала: 2021, Номер 14(4), С. 803 - 814

Опубликована: Март 22, 2021

Язык: Английский

Процитировано

97
The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate DOI Creative Commons
Sarah Gee, Manju Chandiramani, Jeffrey Seow

и другие.

Nature Immunology, Год журнала: 2021, Номер 22(12), С. 1490 - 1502

Опубликована: Окт. 6, 2021

Язык: Английский

Процитировано

97
Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia DOI Creative Commons
Stefanie Kreutmair, Susanne Unger, Nicolás Gonzalo Núñez

и другие.

Immunity, Год журнала: 2021, Номер 54(7), С. 1578 - 1593.e5

Опубликована: Май 9, 2021

Язык: Английский

Процитировано

85
Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19 DOI Creative Commons
Anno Saris, Tom D. Y. Reijnders, Esther J. Nossent

и другие.

Thorax, Год журнала: 2021, Номер 76(10), С. 1010 - 1019

Опубликована: Апрель 12, 2021

Knowledge of the pathophysiology COVID-19 is almost exclusively derived from studies that examined immune response in blood. We here aimed to analyse pulmonary during severe and compare this with blood responses.This was an observational study patients admitted intensive care unit (ICU). Mononuclear cells were purified bronchoalveolar lavage fluid (BALF) blood, analysed by spectral flow cytometry; inflammatory mediators measured BALF plasma.Paired samples obtained 17 patients, four whom died ICU. Macrophages T most abundant BALF, a high percentage expressing ƴδ cell receptor. In lungs, both CD4 CD8 predominantly effector memory (87·3% 83·8%, respectively), these expressed higher levels exhaustion marker programmad death-1 than peripheral Prolonged ICU stay (>14 days) associated reduced proportion activated even more so BALF. activation but not fatal cases. Increased pronounced plasma.The has unique local profile strongly differs Fully elucidating will require investigation response.

Язык: Английский

Процитировано

64
Integrating single-cell sequencing data with GWAS summary statistics reveals CD16+monocytes and memory CD8+T cells involved in severe COVID-19 DOI Creative Commons
Yunlong Ma, Fei Qiu, Chunyu Deng

и другие.

Genome Medicine, Год журнала: 2022, Номер 14(1)

Опубликована: Фев. 17, 2022

Understanding the host genetic architecture and viral immunity contributes to development of effective vaccines therapeutics for controlling COVID-19 pandemic. Alterations immune responses in peripheral blood mononuclear cells play a crucial role detrimental progression COVID-19. However, effects factors on severe remain largely unknown.We constructed computational framework characterize genetics that influence cell subpopulations by integrating GWAS summary statistics (N = 969,689 samples) with four independent scRNA-seq datasets containing healthy controls patients mild, moderate, symptom 606,534 cells). We collected 10 predefined gene sets including inflammatory cytokine genes calculate state score evaluating immunological features individual cells.We found 34 risk were significantly associated COVID-19, number highly expressed increased severity Three subtypes are CD16+monocytes, megakaryocytes, memory CD8+T enriched COVID-19-related association signals. Notably, three causal CCR1, CXCR6, ABO these types, respectively. CCR1+CD16+monocytes ABO+ megakaryocytes up-regulated genes, S100A12, S100A8, S100A9, IFITM1, confer higher dysregulated response among patients. CXCR6+ CD8+ T exhibit notable polyfunctionality elevation proliferation, migration, chemotaxis. Moreover, we observed an increase cell-cell interactions both CCR1+ CD16+monocytes compared normal PBMCs lung tissues. The enhanced epithelial facilitate recruitment this specific population airways, promoting cell-mediated against infection.We uncover major genetics-modulated shift between mild infection, elevated expression genetics-risk cytokines, functional subsets aggravating disease severity, which provides novel insights into parsing determinants

Язык: Английский

Процитировано

56
The Robustness of Cellular Immunity Determines the Fate of SARS-CoV-2 Infection DOI Creative Commons
Esther Moga, Elionor Lynton-Pons, Peré Domingo

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июнь 27, 2022

Two years after the appearance of SARS-CoV-2 virus, causal agent current global pandemic, it is time to analyze evolution immune protection that infection and vaccination provide. Cellular immunity plays an important role in limiting disease severity resolution infection. The early appearance, breadth magnitude specific T cell response has been correlated with thought responses may be sufficient clear minimal COVID-19 patients X-linked or autosomal recessive agammaglobulinemia. However, our knowledge phenotypic functional diversity CD8+ cytotoxic lymphocytes, CD4+ helper cells, mucosal-associated invariant (MAIT) cells follicular (Tfh), which play a critical control as well long-term protection, still evolving. It described how lymphocytes interrupt viral replication by secreting antiviral cytokines (IFN-γ TNF-α) directly killing infected negatively correlating stages progression. In addition, have reported key pieces, leading, coordinating ultimately regulating immunity. For instance, some more severe cases dysregulated signature contribute greater production pro-inflammatory responsible for pathogenic inflammation. Here we discuss cellular axis around rest system components revolve, since orchestrates leads inflammatory cascade and, consequence, innate system, promoting correct humoral through Tfh cells. This review also analyses modulating development high-affinity neutralizing antibodies germinal center B differentiation memory long-lived antibody Finally, there currently high percentage vaccinated population cases, vaccine booster doses are even being administered certain countries, summarized newer approaches long-lasting protective cross-protection against SARS-CoV-2.

Язык: Английский

Процитировано

47
Single‐cell transcriptomic atlas reveals distinct immunological responses between COVID‐19 vaccine and natural SARS‐CoV‐2 infection DOI
Yi Wang, Xiaoxia Wang, Laurence Don Wai Luu

и другие.

Journal of Medical Virology, Год журнала: 2022, Номер 94(11), С. 5304 - 5324

Опубликована: Июль 21, 2022

To control the ongoing coronavirus disease-2019 (COVID-19) pandemic, CoronaVac (Sinovac), an inactivated vaccine, has been granted emergency use authorization by many countries. However, underlying mechanisms of COVID-19 vaccine-induced immune response remain unclear, and little is known about its features compared to (Severe acute respiratory syndrome 2) SARS-CoV-2 infection. Here, we implemented single-cell RNA sequencing (scRNA-seq) profile longitudinally collected PBMCs (peripheral blood mononuclear cells) in six individuals immunized with these profiles infected patients from a Single Cell Consortium. Both vaccines infection altered proportion different cell types, caused B activation differentiation, induced expression genes associated antibody production plasma. The vaccine SARS-COV-2 also alterations peripheral activity such as interferon response, inflammatory cytokine expression, innate apoptosis migration, effector T exhaustion cytotoxicity, however, magnitude change was greater patients, especially those severe disease, than individuals. Further analyses revealed distinct phenotype immunization (HLA class II upregulation IL21R naïve versus downregulation cells disease individuals). There were differences important proinflammatory cytokines thrombosis. In conclusion, this study provides atlas systemic responses between

Язык: Английский

Процитировано

42
Immune responses in mildly versus critically ill COVID-19 patients DOI Creative Commons
Hamid Nasrollahi, Atefe Ghamar Talepoor, Zahra Saleh

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Янв. 30, 2023

The current coronavirus pandemic (COVID-19), caused by SARS-CoV-2, has had devastating effects on the global health and economic system. cellular molecular mediators of both innate adaptive immune systems are critical in controlling SARS-CoV-2 infections. However, dysregulated inflammatory responses imbalanced immunity may contribute to tissue destruction pathogenesis disease. Important mechanisms severe forms COVID-19 include overproduction cytokines, impairment type I IFN response, overactivation neutrophils macrophages, decreased frequencies DC cells, NK cells ILCs, complement activation, lymphopenia, Th1 Treg hypoactivation, Th2 Th17 hyperactivation, as well clonal diversity B lymphocyte function. Given relationship between disease severity an system, scientists have been led manipulate system a therapeutic approach. For example, anti-cytokine, cell, IVIG therapies received attention treatment COVID-19. In this review, role development progression is discussed, focusing aspects mild vs. Moreover, some immune- based approaches being investigated. Understanding key processes involved developing agents optimizing related strategies.

Язык: Английский

Процитировано

42
Host Recovery from Respiratory Viral Infection DOI Creative Commons
Xiaoqin Wei, Harish Narasimhan, Bibo Zhu

и другие.

Annual Review of Immunology, Год журнала: 2023, Номер 41(1), С. 277 - 300

Опубликована: Янв. 30, 2023

Emerging and re-emerging respiratory viral infections pose a tremendous threat to human society, as exemplified by the ongoing COVID-19 pandemic. Upon invasion of tract, host initiates coordinated innate adaptive immune responses defend against virus promote repair damaged tissue. However, dysregulated immunity can also cause acute morbidity, hamper lung regeneration, and/or lead chronic tissue sequelae. Here, we review our current knowledge mechanisms regulating antiviral protection, pathogenesis, inflammation resolution, regeneration following infections, mainly using influenza SARS-CoV-2 examples. We hope that this sheds light on future research directions elucidate cellular molecular cross talk recovery pave way development pro-repair therapeutics augment injury.

Язык: Английский

Процитировано

40
A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome DOI Creative Commons
Terese Hammond,

Marco A. Purbhoo,

Sapana Kadel

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 6, 2024

Abstract Invariant natural killer T (iNKT) cells, a unique cell population, lend themselves for use as adoptive therapy due to diverse roles in orchestrating immune responses. Originally developed cancer, agenT-797 is donor-unrestricted allogeneic ex vivo expanded iNKT therapy. We conducted an open-label study virally induced acute respiratory distress syndrome (ARDS) caused by the severe syndrome-2 virus (trial registration NCT04582201). Here we show that rescues exhausted cells and rapidly activates both innate adaptive immunity. In 21 ventilated patients including 5 individuals receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO), there are no dose-limiting toxicities. observe anti-inflammatory systemic cytokine response infused persistent during follow-up, inducing only transient donor-specific antibodies. Clinical signals of associated survival prevention secondary infections evident. Cellular using off-the-shelf safe, can be scaled with response. The safety therapeutic potential across diseases warrants randomized-controlled trials.

Язык: Английский

Процитировано

15