Abstract:The immune system is tightly regulated by the activity of stimulatory and inhibitory immune receptors. This immune homeostasis is usually disturbed during chronic viral infection. Using publicly available transcriptomic datasets, we conducted in silico analyses to evaluate the expression pattern of 38 selected immune inhibitory receptors (IRs) associated with different myeloid and lymphoid immune cells during coronavirus disease 2019 (COVID-19) infection. Our analyses revealed a pattern of overall upregulation… Show more
“…In similar meta-analyses, an overall upregulation of immunoinhibitory receptors mRNA during SARS-CoV-2 infection, expressed on both lymphoid and myeloid cells were upregulated in nasopharyngeal swabs and autopsies (e.g. BTLA, LAG3, FCGR2B, PDCD1, CEACAM1, CTLA4, CD72, and SIGLEC7), also directly correlated with viral levels (62). Integration of plasma proteomics with nine published scRNAseq datasets also revealed that disease severity in lung tissue is driven by myeloid cell phenotypes and cell-cell interactions with lung epithelial cells and T cells.…”
Section: Mdscs As Potential Biomarker In Covid-19mentioning
Clinical presentations of COVID-19 are highly variable, yet the precise mechanisms that govern the pathophysiology of different disease courses remain poorly defined. Across the spectrum of disease severity, COVID-19 impairs both innate and adaptive host immune responses by activating innate immune cell recruitment, while resulting in low lymphocyte counts. Recently, several reports have shown that patients with severe COVID-19 exhibit a dysregulated myeloid cell compartment, with increased myeloid-derived suppressor cells (MDSCs) correlating with disease severity. MDSCs, in turn, promote virus survival by suppressing T-cell responses and driving a highly pro-inflammatory state through the secretion of various mediators of immune activation. Here, we summarize the evidence on MDSCs and myeloid cell dysregulation in COVID-19 infection and discuss the potential of MDSCs as biomarkers and therapeutic targets in COVID-19 pneumonia and associated disease.
“…In similar meta-analyses, an overall upregulation of immunoinhibitory receptors mRNA during SARS-CoV-2 infection, expressed on both lymphoid and myeloid cells were upregulated in nasopharyngeal swabs and autopsies (e.g. BTLA, LAG3, FCGR2B, PDCD1, CEACAM1, CTLA4, CD72, and SIGLEC7), also directly correlated with viral levels (62). Integration of plasma proteomics with nine published scRNAseq datasets also revealed that disease severity in lung tissue is driven by myeloid cell phenotypes and cell-cell interactions with lung epithelial cells and T cells.…”
Section: Mdscs As Potential Biomarker In Covid-19mentioning
Clinical presentations of COVID-19 are highly variable, yet the precise mechanisms that govern the pathophysiology of different disease courses remain poorly defined. Across the spectrum of disease severity, COVID-19 impairs both innate and adaptive host immune responses by activating innate immune cell recruitment, while resulting in low lymphocyte counts. Recently, several reports have shown that patients with severe COVID-19 exhibit a dysregulated myeloid cell compartment, with increased myeloid-derived suppressor cells (MDSCs) correlating with disease severity. MDSCs, in turn, promote virus survival by suppressing T-cell responses and driving a highly pro-inflammatory state through the secretion of various mediators of immune activation. Here, we summarize the evidence on MDSCs and myeloid cell dysregulation in COVID-19 infection and discuss the potential of MDSCs as biomarkers and therapeutic targets in COVID-19 pneumonia and associated disease.
“…Lymphopenia can be a result of T-cell exhaustion, as overexpression of checkpoint molecules PD-1 and T cell immunoglobulin and mucin domain 3 (Tim-3) was associated with lymphopenia, and also the severity of COVID-19 [ 22 ]. Sharif-Askari et al provided a detailed analysis of several immune inhibitory receptors’ transcription in COVID-19 nasopharyngeal swabs (NPS), lung autopsies, cells from bronchoalveolar fluid (BALF), and peripheral blood mononuclear cells (PBMCs) [ 23 ]. They observed the upregulation of 31 out of 38 investigated receptors in NPS samples, while only the transcription of 9 (mostly lymphoid) receptors were upregulated in autopsies.…”
Section: Immunological Manifestations Of Covid-19mentioning
confidence: 99%
“…However, a study comparing COVID-19-pneumonia with non-COVID-19-pneumonia cases suggests that the high level of inflammatory cytokines is mostly due to neutrophils and monocytes activation rather than T cells, which (in contrast to T cells) their count is not significantly reduced in COVID-19-pneumonia cases compared to non-COVID-19-pneumonia cases [ 53 ]. Moreover, markers of T cell activation (CD25 and CD69) on the CD8 + T cells isolated from bronchoalveolar fluid in COVID-19 samples are reported to not be upregulated [ 23 ]. Figure 1.…”
Section: Ici As a Treatment For Covid-19: Pros And Consmentioning
Introduction
Immune checkpoint inhibition (ICI) is a novel cancer immunotherapy, which is administered in patients with metastatic, refractory, or relapsed solid cancer types. Since the initiation of the Coronavirus Disease 2019 (COVID-19) pandemic, many studies have reported a higher severity and mortality rate of COVID-19 among patients with cancer in general.
Areas covered
The immunomodulatory effects of ICI can modify the patients’ immune system function in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There is controversy over whether the severity of COVID-19 in cancer patients who previously received ICI compared to other patients with cancer has increased. There is evidence that the upregulation of immune checkpoint molecules in T cells, lymphopenia, and inflammatory cytokine secretion are associated with the severity of COVID-19 symptoms.
Expert opinion
ICI can interrupt the T cell exhaustion and depletion by interrupting the inhibitory signaling of checkpoint molecules in T cells, and augments the immune system response in COVID-19 patients with lymphopenia. However, ICI may also increase the risk of cytokine release syndrome. ICI can be considered not only as a cancer immunotherapy but also as immunotherapy in COVID-19. More studies are needed to assess the safety of ICI in COVID-19 patients with or without cancer.
“…and Narjes Saheb Sharif-Askari et al. found that BTLA was upregulated compared to that in controls ( 28 , 29 ). Marissa Herrmann et al.…”
Section: Btla and Infectionmentioning
confidence: 97%
“…There were some researches showing the relation between BTLA and COVID-19. Both Christoph Schultheiß et al and Narjes Saheb Sharif-Askari et al found that BTLA was upregulated compared to that in controls (28,29). Marissa Herrmann et al found that the level of BTLA on CD8 + T cell decreased in COVID-19, but not as strong as in healthy controls, and the expression of BTLA on transitional memory and effector memory CD8 + T cells in COVID-19 was higher compared to healthy controls (30).…”
B and T lymphocyte attenuator (BTLA), an immunomodulatory molecule widely expressed on the surface of immune cells, can influence various signaling pathways and negatively regulate the activation and proliferation of immune cells by binding to its ligand herpes virus entry mediator (HVEM). BTLA plays an important role in immunoregulation and is involved in the pathogenesis of various respiratory diseases, including airway inflammation, asthma, infection, pneumonia, acute respiratory distress syndrome and lung cancer. In recent years, some studies have found that BTLA also has played a positive regulatory effect on immunity system in the occurrence and development of respiratory diseases. Since severe pulmonary infection is a risk factor for sepsis, this review also summarized the new findings on the role of BTLA in sepsis.
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