Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19

Liu, Yuwei; Du, Xin; Chen, Jing; Ye, Jin; Li, Peng; Wang, Haoxiang; Luo, Mingqi; Chen, Ling; Zhao, Yan

doi:10.1016/j.jinf.2020.04.002

Cited by 888 publications

(988 citation statements)

References 16 publications

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“…The simultaneous processing of S protein by elastase and TMPRSS2 proteases help the A2a subtype coronaviruses to more easily infect the large majority of Europeans and North Americans who possess the delC allele [ Figure 5]. Elevated levels of neutrophils are reported in SARS-CoV-2 infected patients with increased disease severity (48)(49)(50)(51). Our findings are indicative of the possibility of using elastase inhibitors as therapy to prevent infection by the A2a subtype of SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 71%

“…The introduction of the new cleavage site for the elastase protease in A2a possibly provides this subtype an advantage over the other subtypes for entry into the host cell. Elastase is mainly expressed by host neutrophils that is elevated in COVID-19 patients (48)(49)(50)(51). Host TMPRSS2 is a key protein that enables cleavage of was not certified by peer review) is the author/funder.…”

Section: The Clade Specific D614g Mutation Provides Advantage To A2amentioning

confidence: 99%

“…The antiviral MX1 gene activates a cascade of pro-inflammatory effectors (59,60) which leads to neutrophil infiltration (61)(62)(63). Neutrophil to leukocyte ratio is found to be higher among COVID-19 patients (48,49). Neutrophils are known to secrete the serine protease elastase which has an additional cut site at position 614 for the A2a viral subtype.…”

Section: The Clade Specific D614g Mutation Provides Advantage To A2amentioning

confidence: 99%

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Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression ofTMPRSS2andMX1Genes

Bhattacharyya

Das

Ghosh

et al. 2020

Preprint

114

112

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COVID-19 pandemic is a major human tragedy. Worldwide, SARS-CoV-2 has already infected over 3 million and has killed about 230,000 people. SARS-CoV-2 originated in China and, within three months, has evolved to an additional 10 subtypes. One particular subtype with a non-silent (Aspartate to Glycine) mutation at 614 th position of the Spike protein (D614G) rapidly outcompeted other preexisting subtypes, including the ancestral. We assessed that D614G mutation generates an additional serine protease (Elastase) cleavage site near the S1-S2 junction of the Spike protein. We also identified that a single nucleotide deletion (delC) at a known variant site (rs35074065) in a cis-eQTL of TMPRSS2, is extremely rare in East Asians but is common in Europeans and North Americans. The delC allele facilitates entry of the 614G subtype into host cells, thus accelerating the spread of 614G subtype in Europe and North America where the delC allele is common. The delC allele at the cis-eQTL locus rs35074065 of TMPRSS2 leads to overexpression of both TMPRSS2 and a nearby gene MX1. The cis-eQTL site, rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G mutated Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare.

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Section: Discussionmentioning

confidence: 71%

Section: The Clade Specific D614g Mutation Provides Advantage To A2amentioning

confidence: 99%

Section: The Clade Specific D614g Mutation Provides Advantage To A2amentioning

confidence: 99%

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Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression ofTMPRSS2andMX1Genes

Bhattacharyya

Das

Ghosh

et al. 2020

Preprint

114

112

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“…Accordingly, chest CT showed diffuse GGO with consolidation. Patients with severe virus infection are more likely to be co-infected with bacteria due to low immune functions [24]. Cytokine storm in severe and critically ill patients with COVID-19 might be associated with the activity of these infection-related biomarkers regulated by inflammatory cytokine.…”

Section: Discussionmentioning

confidence: 99%

Novel coronavirus disease 2019 (COVID-19): relationship between chest CT scores and laboratory parameters

Zhang

Chen

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose To quantify the severity of 2019 novel coronavirus disease (COVID-19) on chest CT and to determine its relationship with laboratory parameters. Methods Patients with real-time fluorescence polymerase chain reaction (RT-PCR)-confirmed COVID-19 between January 01 and February 18, 2020, were included in this study. Laboratory parameters were retrospectively collected from medical records. Severity of lung changes on chest CT of early, progressive, peak, and absorption stages was scored according to the percentage of lung involvement (5 lobes, scores 1-5 for each lobe, range 0-20). Relationship between CT scores and laboratory parameters was evaluated by the Spearman rank correlation. The Bonferroni correction adjusted significance level was at 0.05/4 = 0.0125. Results A total of 84 patients (mean age, 47.8 ± 12.0 years [standard deviation]; age range, 24-80 years) were evaluated. The patients underwent a total of 339 chest CT scans with a median interval of 4 days (interquartile range, 3-5 days). Median chest CT scores peaked at 4 days after the beginning of treatment and then declined. CT score of the early stage was correlated with neutrophil count (r = 0.531, P = 0.011). CT score of the progressive stage was correlated with neutrophil count (r = 0.502, P < 0.001), white blood cell count (r = 0.414, P = 0.001), C-reactive protein (r = 0.511, P < 0.001), procalcitonin (r = 0.423, P = 0.004), and lactose dehydrogenase (r = 0.369, P = 0.010). However, CT scores of the peak and absorption stages were not correlated with any parameter (P > 0.0125). No sex difference occurred regarding CT score (P > 0.05). Conclusion Severity of lung abnormalities quantified on chest CT might correlate with laboratory parameters in the early and progressive stages. However, larger cohort studies are necessary.

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“…A recent study has implicated that NLR was an independent risk factor of the in-hospital mortality for COVID-19 patients. [26] Of note, the value of all variables were the baseline data of laboratory examinations. It is possible that therapeutic manipulations may rapidly in uence the value of NLR.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-to-Lymphocyte Ratio on Admission Predicts In-hospital Mortality in Patients with COVID-19

Zhou

Fang

et al. 2020

Preprint

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Background: A novel coronavirus caused an outbreak of acute infectious pneumonia are spreading over the globe. However, studies predicting prognosis are limited. We predicted outcomes of patients with coronavirus disease 2019 (COVID-19) using the neutrophil-to-lymphocyte ratio (NLR) on admission.Methods: We retrospectively analyzed the characteristics of COVID-19 patients diagnosed from February 6 to March 1. The outcomes, including the occurrence of in-hospital mortality, acute kidney injury (AKI), and endotracheal intubation (ETI), were recorded. The relationships of neutrophils, lymphocytes, C-reactive protein, lactate dehydrogenase, and NLR with outcomes were assessed using multivariate regression model. P-values for trends across quartiles of NLR was examined.Results: A total of 182 patients were included. 37 (20.3%) patients died during the hospitalization, 41 (22.5%) developed AKI, and 36 (19.8%) received ETI. The NLR had a superior predictive performance than others. Using an NLR cutoff of 11.4, the area under the curves (AUC) were 0.766 for in-hospital mortality, 0.755 for AKI, and 0.733 for ETI. In multivariate analysis, NLR >11.4 was further identified as an independent prognostic factor. Following stratification with quartiles of NLR, a positive trend between the increasing quartiles of NLR and the three outcomes were observed (p-values for trends across quartiles were 0.043, <0.001, and 0.041, respectively). The multivariate adjusted odds ratio (OR) in the highest quartile vs. the lowest quartile were 5.738 for mortality, 25.307 for AKI, and 5.136 for ETI.Conclusions: Increasing NLR obtained on admission is a powerful predictor for inpatient mortality, AKI, and ETI in COVID-19 patients.

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Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19

Abstract: Objective: To explore the clinical characteristics and prognosis of COVID-19 patients with cerebral stroke. Methods: In this retrospective study, 2474 patients with COVID-19 were admitted and treated in Tongji Hospital, Tongji Medical College,

Cited by 888 publications

References 16 publications

Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression ofTMPRSS2andMX1Genes

Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression ofTMPRSS2andMX1Genes

Novel coronavirus disease 2019 (COVID-19): relationship between chest CT scores and laboratory parameters

Neutrophil-to-Lymphocyte Ratio on Admission Predicts In-hospital Mortality in Patients with COVID-19

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