The effects of SARS-CoV-2 infection on modulating innate immunity and strategies of combating inflammatory response for COVID-19 therapy

Wang, Yiran; Wu, Mandi; Li, Yichen; Yuen, Ho Him; He, Ming‐Liang

doi:10.1186/s12929-022-00811-4

Cited by 11 publications

(10 citation statements)

References 173 publications

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“…Additional studies are required to interpret the functio of these amino acid changes. We highlight our findings for some of the genes (Figure 8) that have been reported to be of relevance to the immune response during SARS-CoV-2 infection [20][21][22]. The expression of some of the genes in the hypercytokinemia pathway highlights the differences between the experimental groups (Figure 8, Tables S2 and S3).…”

Section: A Dampened Proinflammatory Response In the Lung But Not The ...supporting

confidence: 51%

Upper Respiratory Infection Drives Clinical Signs and Inflammatory Responses Following Heterologous Challenge of SARS-CoV-2 Variants of Concern in K18 Mice

Nichols

Williams

Parvathareddy

et al. 2023

Viruses

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The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of several variants of concern (VOC) with increased immune evasion and transmissibility. This has motivated studies to assess protection conferred by earlier strains following infection or vaccination to each new VOC. We hypothesized that while NAbs play a major role in protection against infection and disease, a heterologous reinfection or challenge may gain a foothold in the upper respiratory tract (URT) and result in a self-limited viral infection accompanied by an inflammatory response. To test this hypothesis, we infected K18-hACE2 mice with SARS-CoV-2 USA-WA1/2020 (WA1) and, after 24 days, challenged with WA1, Alpha, or Delta. While NAb titers against each virus were similar across all cohorts prior to challenge, the mice challenged with Alpha and Delta showed weight loss and upregulation of proinflammatory cytokines in the URT and lower RT (LRT). Mice challenged with WA1 showed complete protection. We noted increased levels of viral RNA transcripts only in the URT of mice challenged with Alpha and Delta. In conclusion, our results suggested self-limiting breakthrough infections of Alpha or Delta in the URT, which correlated with clinical signs and a significant inflammatory response in mice.

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Section: A Dampened Proinflammatory Response In the Lung But Not The ...supporting

confidence: 51%

Upper Respiratory Infection Drives Clinical Signs and Inflammatory Responses Following Heterologous Challenge of SARS-CoV-2 Variants of Concern in K18 Mice

Nichols

Williams

Parvathareddy

et al. 2023

Viruses

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“…COVID-19 exhibits a highly heterogeneous clinical evolution and outcomes, ranging from a mild cold-like illness to severe disease, influenced by various factors such as viral load, co-morbidities, and host immune response ( 23 ). However, the diverse responses of the innate immune system to the infection are not yet fully understood ( 2 , 24 ). It is known that SARS-CoV-2 infection can lead to immune response suppression ( 25 ), partly due to the evasion of the innate immune system ( 26 ), resulting in significant lymphopenia ( 27 , 28 ), which we previously detected in both mild and severe COVID-19 cases ( 12 , 13 ).…”

Section: Discussionmentioning

confidence: 99%

Circulating myeloid-derived suppressor cells may be a useful biomarker in the follow-up of unvaccinated COVID-19 patients after hospitalization

Jiménez-Cortegana,

Salamanca,

Palazón-Carrión

et al. 2023

Front. Immunol.

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SARS-CoV-2 infection is the cause of the disease named COVID-19, a major public health challenge worldwide. Differences in the severity, complications and outcomes of the COVID-19 are intriguing and, patients with similar baseline clinical conditions may have very different evolution. Myeloid-derived suppressor cells (MDSCs) have been previously found to be recruited by the SARS-CoV-2 infection and may be a marker of clinical evolution in these patients. We have studied 90 consecutive patients admitted in the hospital before the vaccination program started in the general population, to measure MDSCs and lymphocyte subpopulations at admission and one week after to assess the possible association with unfavorable outcomes (dead or Intensive Care Unit admission). We analyzed MDSCs and lymphocyte subpopulations by flow cytometry. In the 72 patients discharged from the hospital, there were significant decreases in the monocytic and total MDSC populations measured in peripheral blood after one week but, most importantly, the number of MDSCs (total and both monocytic and granulocytic subsets) were much higher in the 18 patients with unfavorable outcome. In conclusion, the number of circulating MDSCs may be a good marker of evolution in the follow-up of unvaccinated patients admitted in the hospital with the diagnosis of COVID-19.

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“…SARS-CoV-2 infection stimulates innate immunity that produces pro-inflammatory cytokines (PICyts) ( Diamond & Kanneganti, 2022 ). The acute phase of inflammation tries to fight the virus during the infection, but hyper-activation of innate immunity generated cytokine storm leading to chronic inflammation results in multiple organ failure and autoimmune disorders ( Vinciguerra et al, 2020 ; Wang et al, 2022 ). The activation of CS is found in the pathophysiology of acute respiratory distress syndrome (ARDS) with increased levels of plasma complement-positive regulators, particularly higher expression levels of complement anaphylatoxins C5a and C3a that are the main mediators of PICyts ( Vinciguerra et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Modelling and analysis of the complement system signalling pathways: roles of C3, C5a and pro-inflammatory cytokines in SARS-CoV-2 infection

Murad,

Zafar Paracha,

Saeed

et al. 2023

PeerJ

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The complement system is an essential part of innate immunity. It is activated by invading pathogens causing inflammation, opsonization, and lysis via complement anaphylatoxins, complement opsonin’s and membrane attack complex (MAC), respectively. However, in SARS-CoV-2 infection overactivation of complement system is causing cytokine storm leading to multiple organs damage. In this study, the René Thomas kinetic logic approach was used for the development of biological regulatory network (BRN) to model SARS-CoV-2 mediated complement system signalling pathways. Betweenness centrality analysis in cytoscape was adopted for the selection of the most biologically plausible states in state graph. Among the model results, in strongly connected components (SCCs) pro-inflammatory cytokines (PICyts) oscillatory behaviour between recurrent generation and downregulation was found as the main feature of SARS-CoV-2 infection. Diversion of trajectories from the SCCs leading toward hyper-inflammatory response was found in agreement with in vivo studies that overactive innate immunity response caused PICyts storm during SARS-CoV-2 infection. The complex of negative regulators FI, CR1 and DAF in the inhibition of complement peptide (C5a) and PICyts was found desirable to increase immune responses. In modelling role of MAC and PICyts in lowering of SARS-CoV-2 titre was found coherent with experimental studies. Intervention in upregulation of C5a and PICyts by C3 was found helpful in back-and-forth variation of signalling pattern linked with the levels of PICyts. Moreover, intervention in upregulation of PICyts by C5a was found productive in downregulation of all activating factors in the normal SCCs. However, the computational model predictions require experimental studies to be validated by exploring the activation role of C3 and C5a which could change levels of PICyts at various phases of SARS-CoV-2 infection.

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The effects of SARS-CoV-2 infection on modulating innate immunity and strategies of combating inflammatory response for COVID-19 therapy

Cited by 11 publications

References 173 publications

Upper Respiratory Infection Drives Clinical Signs and Inflammatory Responses Following Heterologous Challenge of SARS-CoV-2 Variants of Concern in K18 Mice

Upper Respiratory Infection Drives Clinical Signs and Inflammatory Responses Following Heterologous Challenge of SARS-CoV-2 Variants of Concern in K18 Mice

Circulating myeloid-derived suppressor cells may be a useful biomarker in the follow-up of unvaccinated COVID-19 patients after hospitalization

Modelling and analysis of the complement system signalling pathways: roles of C3, C5a and pro-inflammatory cytokines in SARS-CoV-2 infection

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