Immune characteristics distinguish patients with severe disease associated with SARS-CoV-2

Li, Xiaolei; Liu, Yang; Li, Junming; Sun, Longhua; Yang, Jibin; Xu, Fei; Wan, Lei; Xu, Xinping; Le, Aiping; Zhang, Wei

doi:10.1007/s12026-020-09156-2

Cited by 18 publications

(13 citation statements)

References 14 publications

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“…Recent SARS-CoV-2 studies have revealed pyroptotic events in infected monocytes using NLRP3 inflammasome activation, contributing to release of pro-inflammatory cytokines through lytic monocyte death (29,80). Significantly elevated levels of monocyte-associated chemokines CCL2 and CCL8 have been observed, as well as CXCL2 and CXCL8, which function as chemotactic factors for neutrophils ( 7), consistent with clinical data showing elevated neutrophil levels in severe SARS-CoV-2 patients (58).…”

Section: Cytokine Stormsupporting

confidence: 62%

Pathogenesis of Coronaviruses Through Human Monocytes and Tissue Macrophages

Huang

2021

Viral Immunology

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Coronaviruses (CoVs) contribute significantly to the burden of respiratory diseases, frequently as upper respiratory tract infections. Recent emergence of novel coronaviruses in the last few decades has highlighted the potential transmission, disease, and mortality related to these viruses. In this literature review, we shall explore the disease-causing mechanism of the virus through human monocytes and macrophages. Common strains will be discussed; however, this review will center around coronaviruses responsible for epidemics, namely severe acute respiratory syndrome coronavirus (SARS-CoV)-1 and -2 and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Macrophages are key players in the immune system and have been found to play a role in the pathogenesis of lethal coronaviruses. In physiology, they are white blood cells that engulf and digest cellular debris, foreign substances, and microbes. They play a critical role in innate immunity and help initiate adaptive immunity. Human coronaviruses utilize various mechanisms to undermine the innate immune response through its interaction with macrophages and monocytes. It is capable of entering immune cells through DPP4 (dipeptidyl-peptidase 4) receptors and antibody-dependent enhancement, delaying initial interferon response which supports robust viral replication. Pathogenesis includes triggering the production of overwhelming pro-inflammatory cytokines that attract other immune cells to the site of infection, which propagate prolonged pro-inflammatory response. The virus has also been found to suppress the release of anti-inflammatory mediators such as IL-10, leading to an aberrant inflammatory response. Elevated serum cytokines are also believed to contribute to pathological features seen in severe disease such as coagulopathy, acute lung injury, and multiorgan failure.

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Section: Cytokine Stormsupporting

confidence: 62%

Pathogenesis of Coronaviruses Through Human Monocytes and Tissue Macrophages

Huang

2021

Viral Immunology

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“…The studies' risk of bias, as measured on the Newcastle-Ottawa Scale, as suggested by Bazerbachi 2018 [10], ranged from 2/5 [19,45] to 5/5 [15,20,23,24,29,37,43,[46][47][48][49], with higher scores indicating lower risk of bias (Table 2). All evaluated studies succeeded in excluding PLOS ONE cases that were not pertinent to the research question.…”

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis

et al. 2021

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Objective To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. Methods A search with standardized descriptors and synonyms was performed on November 28th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters—including serum interleukin-6 levels—from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. Data synthesis The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. Conclusions This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.

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“…The TMPRSS2 facilitates hCoVs, including SARS-CoV-2 infections via two independent mechanisms: (i) proteolytic cleavage of hACE2R which promotes viral uptake, and (ii) CoV Spike proteins cleavage which triggers glycoprotein activation for host cell entry. [72] It has also been suggested that the gut is a potential site of SARS-CoV-2 replication. Besides, TMPRSS2 and TMPRSS4 were seen to facilitate SARS-CoV-2 spike fusogenic activity, thereby promoting virtual entrance into the host.…”

Section: Discussionmentioning

confidence: 99%

Amentoflavone, New Hope against SARS-CoV-2: An Outlook through its Scientific Records and an in silico Study

Hossain¹,

Islam²,

Ray³

et al. 2021

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Background:The plant-derived bioflavonoid amentoflavone has many important biological activities, among them remarkable antiviral effects, even against severe acute respiratory syndrome Coronavirus (SARS-CoV). It inhibits severe acute respiratory syndrome coronavirus (SARS-CoV) with an IC 50 value of 8.3 µM. TMPRSS-2 activity is now thought to be the only factor necessary for cell entry and viral pathogenesis). In comparison, 3CL PRO is needed for COVID-19 replication and maturation during its life cycle. Aim: This study aims to perform an in silico study on amentoflavone activity against structural and non-structural severe acute respiratory syndrome coronavirus (SARS-CoV)-2 3-chymotrypsin-like protease (3CL PRO ) and human transmembrane protease serine 2 (TMPRSS-2) proteins. Materials and Methods: Molecular docking studies were carried out using compounds against 3CL PRO and TMPRSS-2 proteins through the Swiss model, Uniport, PROCHECK, Swiss PDB viewer, PyMol, PyRx, and Desmond (Schrödinger package) computerized software. Results: Amentoflavone showed strong interactions -9.5 and -7.4 kcal/mol with 3CL PRO and TMPRSS2 proteins, respectively. In any case, it had higher binding affinities than currently approved antiviral drugs, which are underutilized in coronavirus disease . Conclusion: Amentoflavone may be one of the potential leads (drug candidate) to fight human coronavirus, including SARS-CoV-2. Further in vivo studies are needed to support the findings of this study.

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Immune characteristics distinguish patients with severe disease associated with SARS-CoV-2

Cited by 18 publications

References 14 publications

Pathogenesis of Coronaviruses Through Human Monocytes and Tissue Macrophages

Pathogenesis of Coronaviruses Through Human Monocytes and Tissue Macrophages

Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis

Amentoflavone, New Hope against SARS-CoV-2: An Outlook through its Scientific Records and an in silico Study

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