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- Parthasarathi, A, et al.
(författare)
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The Role of Neutrophil-to-Lymphocyte Ratio in Risk Stratification and Prognostication of COVID-19: A Systematic Review and Meta-Analysis
- 2022
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Ingår i: Vaccines. - : MDPI AG. - 2076-393X. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have proposed that the neutrophil–lymphocyte ratio (NLR) is one of the various biomarkers that can be useful in assessing COVID-19 disease-related outcomes. Our systematic review analyzes the relationship between on-admission NLR values and COVID-19 severity and mortality. Six different severity criteria were used. A search of the literature in various databases was conducted from 1 January 2020 to 1 May 2021. We calculated the pooled standardized mean difference (SMD) for the collected NLR values. A meta-regression analysis was performed, looking at the length of hospitalization and other probable confounders, such as age, gender, and comorbidities. A total of sixty-four studies were considered, which included a total of 15,683 patients. The meta-analysis showed an SMD of 3.12 (95% CI: 2.64–3.59) in NLR values between severe and non-severe patients. A difference of 3.93 (95% CI: 2.35–5.50) was found between survivors and non-survivors of the disease. Upon summary receiver operating characteristics analysis, NLR showed 80.2% (95% CI: 74.0–85.2%) sensitivity and 75.8% (95% CI: 71.3–79.9%) specificity for the prediction of severity and 78.8% (95% CI: 73.5–83.2%) sensitivity and 73.0% (95% CI: 68.4–77.1%) specificity for mortality, and was not influenced by age, gender, or co-morbid conditions. Conclusion: On admission, NLR predicts both severity and mortality in COVID-19 patients, and an NLR > 6.5 is associated with significantly greater the odds of mortality.
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- Rahman, M, et al.
(författare)
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Differential Effect of SARS-CoV-2 Spike Glycoprotein 1 on Human Bronchial and Alveolar Lung Mucosa Models: Implications for Pathogenicity
- 2021
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The SARS-CoV-2 spike protein mediates attachment of the virus to the host cell receptor and fusion between the virus and the cell membrane. The S1 subunit of the spike glycoprotein (S1 protein) contains the angiotensin converting enzyme 2 (ACE2) receptor binding domain. The SARS-CoV-2 variants of concern contain mutations in the S1 subunit. The spike protein is the primary target of neutralizing antibodies generated following infection, and constitutes the viral component of mRNA-based COVID-19 vaccines. Methods: Therefore, in this work we assessed the effect of exposure (24 h) to 10 nM SARS-CoV-2 recombinant S1 protein on physiologically relevant human bronchial (bro) and alveolar (alv) lung mucosa models cultured at air–liquid interface (ALI) (n = 6 per exposure condition). Corresponding sham exposed samples served as a control. The bro-ALI model was developed using primary bronchial epithelial cells and the alv-ALI model using representative type II pneumocytes (NCI-H441). Results: Exposure to S1 protein induced the surface expression of ACE2, toll like receptor (TLR) 2, and TLR4 in both bro-ALI and alv-ALI models. Transcript expression analysis identified 117 (bro-ALI) and 97 (alv-ALI) differentially regulated genes (p ≤ 0.01). Pathway analysis revealed enrichment of canonical pathways such as interferon (IFN) signaling, influenza, coronavirus, and anti-viral response in the bro-ALI. Secreted levels of interleukin (IL) 4 and IL12 were significantly (p < 0.05) increased, whereas IL6 decreased in the bro-ALI. In the case of alv-ALI, enriched terms involving p53, APRIL (a proliferation-inducing ligand) tight junction, integrin kinase, and IL1 signaling were identified. These terms are associated with lung fibrosis. Further, significantly (p < 0.05) increased levels of secreted pro-inflammatory cytokines IFNγ, IL1ꞵ, IL2, IL4, IL6, IL8, IL10, IL13, and tumor necrosis factor alpha were detected in alv-ALI, whereas IL12 was decreased. Altered levels of these cytokines are also associated with lung fibrotic response. Conclusions: In conclusion, we observed a typical anti-viral response in the bronchial model and a pro-fibrotic response in the alveolar model. The bro-ALI and alv-ALI models may serve as an easy and robust platform for assessing the pathogenicity of SARS-CoV-2 variants of concern at different lung regions.
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