Considering innate immune responses in SARS-CoV-2 infection and COVID-19

Diamond, Michael S.; Lambris, John D.; Ting, Jenny P.Y.; Tsang, John S.

doi:10.1038/s41577-022-00744-x

Cited by 19 publications

(22 citation statements)

References 59 publications

(65 reference statements)

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“…The rapid spread of COVID-19 has induced an urgent demand for understanding the role of immunity in the progression of viral infection and subsequent pneumonia. As a new member of the coronavirus family, infection with COVID-19 can cause a cytokine storm, leading to a high incidence of immune disorders [ 22 ]. It is known that lymphocytes and their subsets play important roles in the maintenance of immune system function [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity

Dai

Zhong²,

Qiao

et al. 2022

Virol J

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Background Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which had rapidly spread all over the world and caused public health emergencies in the past two years. Although the diagnosis and treatment for COVID-19 have been well defined, the immune cell characteristics and the key lymphocytes subset alterations in COVID-19 patients have not been thoroughly investigated. Methods The levels of immune cells including T cells, B cells, and natural killer (NK) cells in 548 hospitalized COVID-19 patients, and 30 types of lymphocyte subsets in 125 hospitalized COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China were measured using flow cytometry. The relationship between lymphocytes subsets with the cytokine interleukin-6 (IL-6) and the characteristics of lymphocyte subsets in single-cell RNA sequencing (scRNA-seq) data obtained from peripheral blood mononuclear cells (PBMCs) were also analysed in COVID-19 patients. Results In this study, we found that patients with critical COVID-19 infection exhibited an overall decline in lymphocytes including CD4+ T cells, CD8+ T cells, total T cells, B cells, and NK cells compared to mild and severe patients. However, the number of lymphocyte subsets, such as CD21low CD38low B cells, effector T4 cells, and PD1+ depleted T8 cells, was moderately increased in critical COVID-19 patients compared to mild cases. Notably, except for effector memory T4 cells, plasma blasts and Tregs, the number of all lymphocyte subsets was markedly decreased in COVID-19 patients with IL-6 levels over 30-fold higher than those in healthy cases. Moreover, scRNA-seq data showed obvious differences in the distribution and numbers of lymphocyte subsets between COVID-19 patients and healthy persons, and subsets-specific marker genes of lymphocyte subsets including CD4, CD19, CCR7, and IL7R, were markedly decreased in COVID-19 patients compared with those in healthy cases. Conclusion A comprehensive decrease in immune cell and lymphocyte subsets in critical COVID-19 patients, and peripheral lymphocyte subset alterations showed a clear association with clinical characteristics.

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Section: Discussionmentioning

confidence: 99%

Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity

Dai

Zhong²,

Qiao

et al. 2022

Virol J

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“…This phenomenon has been primarily attributed to respiratory failure from SARS-CoV-2 pneumonia and acute respiratory distress syndrome (ARDS) subsequent to mechanical ventilation for general anesthesia during surgical procedures (4). In addition to the well-known pulmonary complications, young patients with COVID-19 are particularly susceptible to adverse effects originating from a dysfunction of the innate immune system (5)(6)(7). This includes the release of a "cytokine storm" and activation of the complement system which promotes a systemic environment of hyperinflammation and hypercoagulability (8)(9)(10)(11)(12)(13)(14)(15).…”

Section: Editorial On the Research Topic The Impact Of Covid-19 On Im...mentioning

confidence: 99%

Editorial: The impact of COVID-19 on immune system-related complications in surgical patients

Stahel

Weckbach²,

Huber‐Lang

et al. 2023

Front. Surg.

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“…Our current understanding of the complement implies a broader role of this pathway within the immune system and inflammation, 18 which includes a key function in immune surveillance against not only microbes and other foreign intruders, but also damaged host tissues (such as cellular debris and apoptotic cells possibly generating due to ageing or malignant transformation) 19 . Furthermore, the complement system is by‐directionally embedded with the inflammation, since inflammatory cells and cytokines may activate the complement cascade, and vice versa the complement anaphylatoxins may promote inflammation, creating an amplification loop which emerged once more in the recent description of COVID‐19 pathophysiology 20 . Thus it is not surprising that its pivotal role in tuning both innate and adaptive immune response evolved together with its fine regulatory role, and that impairment of such regulation is implicated in the pathophysiology of several human diseases 21 …”

Section: The Role Of the Alternative Pathway In The Pathophysiology O...mentioning

confidence: 99%

“…19 Furthermore, the complement system is by-directionally embedded with the inflammation, since inflammatory cells and cytokines may activate the complement cascade, and vice versa the complement anaphylatoxins may promote inflammation, creating an amplification loop which emerged once more in the recent description of COVID-19 pathophysiology. 20 Thus it is not surprising that its pivotal role in tuning both innate and adaptive immune response evolved together with its fine regulatory role, and that impairment of such regulation is implicated in the pathophysiology of several human diseases. 21 In the context of impaired complement regulation which may lead to human disease, we have PNH, and the GPI-linked proteins CD55 and CD59.…”

Section: The Role Of the Alternative Pathway In The Pathophys I Ology...mentioning

confidence: 99%

The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target

Risitano

Frieri

Urciuoli

et al. 2022

Immunological Reviews

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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal, not malignant, hematological disease characterized by intravascular hemolysis, thrombophilia and bone marrow failure. While this latter presentation is due to a T-cell mediated auto-immune disorder resembling acquired aplastic anemia, the first two clinical presentations are largely driven by the complement pathway. Indeed, PNH is characterized by a broad impairment of complement regulation on affected cells, which is due to the lack of the complement regulators CD55 and CD59. The deficiency of these two proteins from PNH blood cells is due to the somatic mutation in the phosphatidylinositol Nacetylglucosaminyltransferase subunit A gene causing the disease, which impairs the surface expression of all proteins linked via the glycosylphosphatidylinositol anchor.The lack of the complement regulators CD55 and CD59 on PNH erythrocytes accounts for the hallmark of PNH, which is the chronic, complement-mediated intravascular hemolysis. This hemolysis results from the impaired regulation of the alternative pathway upstream in the complement cascade, as well as of the downstream terminal pathway. PNH represented the first indication for the development of anticomplement agents, and the therapeutic interception of the complement cascade at the level of C5 led to remarkable changes in the natural history of the disease. Nevertheless, the clinical use of an inhibitor of the terminal pathway highlighted the broader derangement of complement regulation in PNH, shedding light on the pivotal role of the complement alternative pathway. Here we review the current understanding of the role of the alternative pathway in PNH, including the emergence of C3-mediated extravascular hemolysis in PNH patients on anti-C5 therapies. These observations provide the rationale for the development of novel complement inhibitors for the treatment of PNH. Recent preclinical and clinical data on proximal complement inhibitors intercepting the alternative pathway with the aim of improving the treatment of PNH are discussed, together with their clinical implications which are animating a lively debate in the scientific community. This article is part of a series of reviews covering The Alternative Pathway or Amplification Loop of Complement appearing in Volume 313 of Immunological Reviews.

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Considering innate immune responses in SARS-CoV-2 infection and COVID-19

Cited by 19 publications

References 59 publications

Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity

Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity

Editorial: The impact of COVID-19 on immune system-related complications in surgical patients

The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target

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