Prognostic value of Neutrophil-to-lymphocyte ratio in COVID-19 compared with Influenza and respiratory syncytial virus infection

Prozan, Lior; Shusterman, Eden; Ablin, Jacob N.; Mitelpunkt, Alexis; Weiss-Meilik, Ahuva; Adler, Amos; Choshen, Guy; Kehat, Orli

doi:10.21203/rs.3.rs-130833/v1

Cited by 9 publications

(10 citation statements)

References 46 publications

(61 reference statements)

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“…However, an elevated level of IL‐10 was associated with a decrease in lymphocyte count and increased neutrophil‐to‐lymphocyte ratio (NLR). Previous studies also quoted decreased lymphocyte count and increased NLR as a poor prognostic marker in COVID‐19 [42, 43]. Again, the TPE procedure may help eliminate the elevated IL‐10 levels, reverse the NLR and improve the cellular profile.…”

Section: Discussionmentioning

confidence: 92%

Efficacy of therapeutic plasma exchange in severe COVID‐19 disease: A meta‐analysis

et al. 2022

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Background and Objectives Therapeutic plasma exchange (TPE) has been used in severe COVID‐19 disease to eliminate the cytokine storm. This meta‐analysis aims to assess the effectiveness of TPE in reducing mortality in severe COVID‐19 disease compared to standard treatment. Materials and Methods A comprehensive literature search was performed in PubMed, the Cochrane database and the International Clinical Trial Registry Platform (ICTRP). The random‐effect model was used to calculate the risk ratio and standardized mean difference (SMD) as pooled effect size for the difference in mortality and length of the intensive care unit (ICU) stay. The risk of bias and publication bias were assessed in R version 4.1.0. The certainty of the evidence was calculated using the GradePro tool. Results The database identified 382 participants from six studies, including one randomized control trial. Egger's test did not detect any publication bias (p = 0.178). The random model analysis for mortality evaluated a risk ratio of 0.38 (95% CI: 0.28–0.52) with a significant reduction in the TPE group. The certainty of the evidence was moderate, with a risk ratio of 0.34 (95% CI: 0.24–0.49). Length of ICU stays between TPE versus standard care showed an SMD of 0.08 (95% CI: −0.38, 0.55) and was not significant. Conclusion The length of ICU stay in the TPE group was not different from standard care. However, this meta‐analysis revealed a significant benefit of TPE in reducing mortality in severe COVID‐19 disease compared to standard treatment.

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Section: Discussionmentioning

confidence: 92%

Efficacy of therapeutic plasma exchange in severe COVID‐19 disease: A meta‐analysis

et al. 2022

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“…Predose C-reactive protein (CRP), absolute lymphocyte count (ALC), and neutrophil-to-lymphocyte ratio (NLR) were similar between the groups ( P = 0.17, 0.27, and 0.2, respectively, based on a Wilcoxon rank sum test) (Table 1). An ALC of <1 × 10 9 /liter ( 27 ), CRP of ≥40 mg/liter ( 28 ), or NLR of >6.82 ( 29 ) has been shown to be independently associated with severe disease and increased mortality. Seventeen of 24 patients had lymphopenia, and 5 patients had severe lymphopenia (<0.5 × 10 9 /liter).…”

Section: Resultsmentioning

confidence: 99%

Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a phase2a clinical trial

et al. 2022

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Hyperinflammation triggered by SARS-CoV-2 is a major cause of disease severity, with activated macrophages implicated in this response. OP-101, a hydroxyl-polyamidoamine dendrimer– N -acetylcysteine conjugate that specifically targets activated macrophages, improves outcomes in preclinical models of systemic inflammation and neuroinflammation. In this multicenter, randomized, double-blind, placebo-controlled, adaptive phase 2a trial, we evaluated safety and preliminary efficacy of OP-101 in patients with severe COVID-19. Twenty-four patients classified as having severe COVID-19 with a baseline World Health Organization seven-point ordinal scale of ≥5 were randomized to receive a single intravenous dose of placebo ( n = 7 patients) or OP-101 at 2 ( n = 6), 4 ( n = 6), or 8 mg/kg ( n = 5 patients). All study participants received standard of care, including corticosteroids. OP-101 at 4 mg/kg was better than placebo at decreasing inflammatory markers; OP-101 at 4 and 8 mg/kg was better than placebo at reducing neurological injury markers, (neurofilament light chain and glial fibrillary acidic protein). Risk for the composite outcome of mechanical ventilation or death at 30 and 60 days after treatment was 71% (95% CI: 29%, 96%) for placebo and 18% (95% CI: 4%, 43%; P = 0.021) for the pooled OP-101 treatment arms. At 60 days, 3 of 7 patients given placebo and 14 of 17 OP-101–treated patients were surviving. No drug-related adverse events were reported. These data show that OP-101 was well tolerated and may have potential to treat systemic inflammation and neuronal injury, reducing morbidity and mortality in hospitalized patients with severe COVID-19.

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“…High NLR is known to differentiate active TB from bacterial pneumonia, sarcoidosis, associates with poor clinical outcomes 44 , predicts the risk of progressing to active disease in HIV-Mtb coinfection 45 and mortality with development of acute respiratory distress (ARDS) in miliary TB 46 . Interestingly, high NLR is also reported in patients with severe COVID-19 47 and poor prognosis from various cancers 48 . Our work highlights the role of G-CSF-IFN-I axis to regulate the balance between neutrophils and lymphocytes during chronic Mtb infection that can be targeted for rational designing of interventions for TB and possibly other respiratory infections.…”

Section: Discussionmentioning

confidence: 97%

Neutrophils reprograms the bone marrow to impair T-cell immunity during tuberculosis

Saqib

McDonough²,

Das

et al. 2022

Preprint

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Mycobacterium tuberculosis (Mtb) infection induces persistent influx of neutrophils that associates with poor bacterial control and clinical outcome from tuberculosis (TB). Although implicated in TB pathology, the mechanism by which these cells contribute to pathogenesis is poorly understood. Using Cell-DIVE multiplexed immunofluorescence imaging and spatial analysis of inflammatory TB lesions, we demonstrated that persistent neutrophil infiltration affects the spatiotemporal organization of T-lymphocytes and impairs their function. Instead of directly suppressing T-cells, neutrophils produce granulocyte colony stimulating factor (CSF3/G-CSF) that collaborates with type I interferon (IFN-I) to promote a granulocyte-skewed hematopoiesis impacting T-lymphocyte production. Importantly, neutrophil-intrinsic IFN-I receptor 1 (IFNAR1) is both necessary and sufficient to promote pathologic granulopoiesis. Finally, inhibition of IFNAR1-signaling alone mitigates immunopathogenesis by restoring hematopoietic equilibrium. Collectively, our work uncovers a potential immunevasion strategy by which virulent Mtb strains induce IFN-I to generate pathogen-permissive neutrophils that produce G-CSF and sustain pathogenic hematopoiesis to impair T-cell immunity during TB.

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Prognostic value of Neutrophil-to-lymphocyte ratio in COVID-19 compared with Influenza and respiratory syncytial virus infection

Cited by 9 publications

References 46 publications

Efficacy of therapeutic plasma exchange in severe COVID‐19 disease: A meta‐analysis

Efficacy of therapeutic plasma exchange in severe COVID‐19 disease: A meta‐analysis

Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a phase2a clinical trial

Neutrophils reprograms the bone marrow to impair T-cell immunity during tuberculosis

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