The role of human C5a as a non-genomic target in corticosteroid therapy for management of severe COVID19

Das, Aurosikha; Rana, Soumendra

doi:10.1016/j.compbiolchem.2021.107482

Cited by 14 publications

(20 citation statements)

References 86 publications

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“…Corticosteroids act over diverse immune pathways but, overall, by inhibition of complement activation [178] and producing the apoptosis of T-lymphocytes and granulocytes [179]. In cases of RM/RPL, corticosteroids favor the establishment of early pregnancy by the suppression of dNK cells and improvement of trophoblast proliferation and invasion [180].…”

Section: Corticosteroidsmentioning

confidence: 99%

Pathogenesis, Diagnosis and Management of Obstetric Antiphospholipid Syndrome: A Comprehensive Review

Alijotas‐Reig

Esteve-Valverde

Anunciación-Llunell

et al. 2022

JCM

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Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity associated with persistent antiphospholipid antibody positivity. Cases fulfilling the Sydney criteria for obstetric morbidity with no previous thrombosis are known as obstetric antiphospholipid syndrome (OAPS). OAPS is the most identified cause of recurrent pregnancy loss and late-pregnancy morbidity related to placental injury. Cases with incomplete clinical or laboratory data are classified as obstetric morbidity APS (OMAPS) and non-criteria OAPS (NC-OAPS), respectively. Inflammatory and thrombotic mechanisms are involved in the pathophysiology of OAPS. Trophoblasts, endothelium, platelets and innate immune cells are key cellular players. Complement activation plays a crucial pathogenic role. Secondary placental thrombosis appears by clot formation in response to tissue factor activation. New risk assessment tools could improve the prediction of obstetric complication recurrences or thromboses. The standard-of-care treatment consists of low-dose aspirin and prophylactic low molecular weight heparin. In refractory cases, the addition of hydroxychloroquine, low-dose prednisone or IVIG improve pregnancy outcomes. Statins and eculizumab are currently being tested for treating selected OAPS women. Finally, we revisited recent insights and concerns about the pathophysiology, diagnosis and management of OAPS.

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Section: Corticosteroidsmentioning

confidence: 99%

Pathogenesis, Diagnosis and Management of Obstetric Antiphospholipid Syndrome: A Comprehensive Review

Alijotas‐Reig

Esteve-Valverde

Anunciación-Llunell

et al. 2022

JCM

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“…Furthermore, modulation of dendritic cell function, dysregulation of IFN-γ production, exhaustion of NK cell-mediated cytotoxicity [ 90 ] and antigenic variation [ 91 ] are some other ways to escape the innate immune defense. Likewise, hyperactivation of the complement cascade by SARS-CoV-2 triggers a vicious cycle of “hypercytokinaemia” [ 92 , 93 ] that aids in elevating levels of pro-inflammatory modulators, such as C3a and C5a [ 94–96 ] ( Figure 4 ) and increases the susceptibility to develop the severe acute respiratory distress syndrome [ 97 ]. Therefore, this modulation of the innate antiviral response induced by both host and viral factors gives a good head start to the viral replication in the URT and hyper-inflammation in the lungs, resulting in conditions that lead to COVID-19 severity.…”

Section: Host Virus Interaction (The Host Immune Response)mentioning

confidence: 99%

An update on host immunity correlates and prospects of re-infection in COVID-19

Negi

Maurya

Singh

et al. 2021

International Reviews of Immunology

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Reinfection with SARS-CoV-2 is not frequent yet the incidence rate of it is increasing globally owing to the slow emergence of drift variants that pose a perpetual threat to vaccination strategies and have a greater propensity for disease reoccurrence. Long-term protection against SARS-CoV-2 reinfection relies on the induction of the innate as well as the adaptive immune response endowed with immune memory. However, a multitude of factors including the selection pressure, the waning immunity against SARS-CoV-2 over the first year after infection possibly favors evolution of more infectious immune escape variants, amplifying the risk of reinfection. Additionally, the correlates of immune protection, the novel SARS-CoV-2 variants of concern (VOC), the durability of the adaptive and mucosal immunity remain major challenges for the development of therapeutic and prophylactic interventions. Interestingly, a recent body of evidence indicated that the gastrointestinal (GI) tract is another important target organ for SARS-CoV-2 besides the respiratory system, potentially increasing the likelihood of reinfection by impacting the microbiome and the immune response via the gut-lung axis. In this review, we summarized the latest development in SARS-CoV-2 reinfection, and explored the untapped potential of trained immunity. We also highlighted the immune memory kinetics of the humoral and cell-mediated immune response, genetic drift of the emerging viral variants, and discussed the current challenges in vaccine development. Understanding the dynamics and the quality of immune response by unlocking the power of the innate, humoral and cell-mediated immunity during SARS-CoV-2 reinfection would open newer avenues for drug discovery and vaccine designs.

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“…CD8+ lymphocytes destroy infected alveolar cells, while neutrophil and macrophage activation leads to the systematic inflammatory reaction syndrome (SIRs) and cytokine release syndrome [ 23 ]. Complement component C5a, acting as chemoattractant of neutrophils, potentiates the development of a deleterious hypercytokinaemia [ 24 ]. T-helper 17 polarization, occurring after neutrophil hyperactivation, seems to hold a central role in triggering a vicious cycle of inflammation and fibrosis [ 25 ].…”

Section: Covid-19 Clinical and Pathophysiological Aspectsmentioning

confidence: 99%

“…The endothelium is central to coagulation physiology, and its dysfunction explains at least partly the clinical complications (venous thromboembolic disease) and the laboratory hallmarks (elevated d-dimer, prothrombin time prolongation) of severe COVID-19 infection cases [ 12 , 32 ]. Of note, inflammation and coagulation share molecular pathways involving cytokines such as IL-8, IL-6, IL-1b [ 20 ] and complement components C3 and C5 [ 24 , 38 ]. Immune complexes containing antibodies against SARS-COV2 spike protein are also implicated in COVID-19 hypercoagulability through enhanced of FcγRIIA signaling [ 39 , 40 ].…”

Section: Covid-19 Clinical and Pathophysiological Aspectsmentioning

confidence: 99%

Immunologic Dysregulation and Hypercoagulability as a Pathophysiologic Background in COVID-19 Infection and the Immunomodulating Role of Colchicine

Vrachatis

Papathanasiou

Giotaki

et al. 2021

JCM

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In 2020, SARS-COV-2 put health systems under unprecedented resource and manpower pressure leading to significant number of deaths. Expectedly, researchers sought to shed light on the pathophysiologic background of this novel disease (COVID-19) as well as to facilitate the design of effective therapeutic modalities. Indeed, early enough the pivotal role of inflammatory and thrombotic pathways in SARS-COV-2 infection has been illustrated. The purpose of this article is to briefly present the epidemiologic and clinical features of COVID-19, analyze the pathophysiologic importance of immunologic dysregulation and hypercoagulability in developing disease complications and finally to present an up-to-date systematic review of colchicine’s immunomodulating capacity in view of hindering coronavirus complications.

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The role of human C5a as a non-genomic target in corticosteroid therapy for management of severe COVID19

Abstract: Graphical abstract Illustrations of the C5a-prednisone complexes highlighting the range of estimated binding affinity.

Cited by 14 publications

References 86 publications

Pathogenesis, Diagnosis and Management of Obstetric Antiphospholipid Syndrome: A Comprehensive Review

Pathogenesis, Diagnosis and Management of Obstetric Antiphospholipid Syndrome: A Comprehensive Review

An update on host immunity correlates and prospects of re-infection in COVID-19

Immunologic Dysregulation and Hypercoagulability as a Pathophysiologic Background in COVID-19 Infection and the Immunomodulating Role of Colchicine

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