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Prognostic value of Neutrophil-to-lymphocyte ratio in ......Prognostic value of...
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Posted on Authorea 1 Feb 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.161219450.09442742/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. Prognostic value of Neutrophil-to-lymphocyte ratio in COVID-19 patients: A systematic review and meta-analysis Juan R. Ulloque-Badaracco 1 , Ivan Salas-Tello 1 , Ali Al-kassab-Cordova 1 , Esteban A. Alarcon-Braga 1 , Vicente Benites-Zapata 2 , Jorge Magui˜ na 1 , and Adrian V. Hernandez 2 1 Universidad Peruana de Ciencias Aplicadas 2 Universidad San Ignacio de Loyola February 1, 2021 Abstract Background: Neutrophil-to-lymphocyte ratio (NLR) is an accessible and widely used biomarker. NLR may be used as an early marker of poor prognosis in patients with COVID-19. Methods: We conducted a systematic review and meta-analysis. Observational studies that reported the association between baseline NLR values (i.e. at hospital admission) and severity or all-cause mortality in COVID-19 patients were included. The quality of the studies was assessed using the Newcastle-Ottawa scale (NOS). Random effects models and inverse variance method were used for meta-analyses. The effects were expressed as odds ratios (OR) and their 95% confidence intervals (CI). Small study effects were assessed with the Egger’s test. Results: Twenty studies, 19 cohorts and one case-control were included. An increase of one unit of NLR was associated with a higher odds of COVID-19 severity (OR 6.6, 95% CI: 4.71 - 7.19; p<0.001) and higher odds of all-cause mortality (OR 12.7, 95% CI: 1.32, 123.36; p=0.025). No differences were found in subgroup analyses by study design. The subgroup analysis of the studies, by country of origin, showed that the strength of the association between NLR and mortality was greater in Chinese studies (OR 31.1; 95%CI 19.57 to 49.3; p<0.0001) with moderate heterogeneity (I2 =43%). In our sensitivity analysis, we found that 7 studies with low risk of bias maintained strong association between both outcomes and the NLR values (severity: OR 4.7; 95% CI 3.5 to 6.34; p < 0.001 vs mortality: OR 31.1; 95% CI 19.57 to 49.3; p <0.0001), with low (I2 = 37%) and moderate (I2 = 43%) heterogeneity for severity and mortality outcomes, respectively. No publication bias was found for studies that evaluated effects for the severity of disease. Conclusions: Higher values of NLR were associated with severity and all-cause mortality in hospitalized COVID-19 patients. Prognostic value of Neutrophil-to-lymphocyte ratio in COVID-19 patients: A systematic re- view and meta-analysis Running title: Prognostic value of NLR in COVID-19 patients Juan R. Ulloque-Badaracco 1 , W. Ivan Salas-Tello 1 , Ali Al-kassab-C´ ordova 1 , Esteban A. Alarc´ on-Braga 1 , Vicente A. Benites-Zapata 2 , Jorge L. Magui˜ na 1, Adrian V.Hernandez 3, 4 Filiation: 1 Escuela de Medicina, Universidad Peruana de Ciencias Aplicadas, Lima, Peru. 2 Vicerrectorado de Investigaci´ on, Universidad San Ignacio de Loyola (USIL), Lima, Peru 3 Unidad de Revisiones sistem´ aticas y Meta-an´ alisis, Gu´ ıas de Pr´ actica Cl´ ınica y Evaluaciones de Tecnolog´ ıa Sanitaria (URSIGET), Vicerrectorado de Investigaci´ on, Universidad San Ignacio de Loyola (USIL), Lima, Peru. 1
Transcript of Prognostic value of Neutrophil-to-lymphocyte ratio in ......Prognostic value of...
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Prognostic value of Neutrophil-to-lymphocyte ratio in COVID-19
patients: A systematic review and meta-analysis
Juan R. Ulloque-Badaracco1, Ivan Salas-Tello1, Ali Al-kassab-Cordova1, Esteban A.Alarcon-Braga1, Vicente Benites-Zapata2, Jorge Maguina1, and Adrian V. Hernandez 2
1Universidad Peruana de Ciencias Aplicadas2Universidad San Ignacio de Loyola
February 1, 2021
Abstract
Background: Neutrophil-to-lymphocyte ratio (NLR) is an accessible and widely used biomarker. NLR may be used as an
early marker of poor prognosis in patients with COVID-19. Methods: We conducted a systematic review and meta-analysis.
Observational studies that reported the association between baseline NLR values (i.e. at hospital admission) and severity or
all-cause mortality in COVID-19 patients were included. The quality of the studies was assessed using the Newcastle-Ottawa
scale (NOS). Random effects models and inverse variance method were used for meta-analyses. The effects were expressed as
odds ratios (OR) and their 95% confidence intervals (CI). Small study effects were assessed with the Egger’s test. Results:
Twenty studies, 19 cohorts and one case-control were included. An increase of one unit of NLR was associated with a higher
odds of COVID-19 severity (OR 6.6, 95% CI: 4.71 - 7.19; p<0.001) and higher odds of all-cause mortality (OR 12.7, 95% CI:
1.32, 123.36; p=0.025). No differences were found in subgroup analyses by study design. The subgroup analysis of the studies,
by country of origin, showed that the strength of the association between NLR and mortality was greater in Chinese studies
(OR 31.1; 95%CI 19.57 to 49.3; p<0.0001) with moderate heterogeneity (I2 =43%). In our sensitivity analysis, we found that 7
studies with low risk of bias maintained strong association between both outcomes and the NLR values (severity: OR 4.7; 95%
CI 3.5 to 6.34; p < 0.001 vs mortality: OR 31.1; 95% CI 19.57 to 49.3; p <0.0001), with low (I2 = 37%) and moderate (I2 =
43%) heterogeneity for severity and mortality outcomes, respectively. No publication bias was found for studies that evaluated
effects for the severity of disease. Conclusions: Higher values of NLR were associated with severity and all-cause mortality in
hospitalized COVID-19 patients.
Prognostic value of Neutrophil-to-lymphocyte ratio in COVID-19 patients: A systematic re-view and meta-analysis
Running title: Prognostic value of NLR in COVID-19 patients
Juan R. Ulloque-Badaracco1, W. Ivan Salas-Tello1, Ali Al-kassab-Cordova1, Esteban A. Alarcon-Braga1,Vicente A. Benites-Zapata2, Jorge L. Maguina1,Adrian V.Hernandez3, 4
Filiation:
1 Escuela de Medicina, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.
2 Vicerrectorado de Investigacion, Universidad San Ignacio de Loyola (USIL), Lima, Peru
3 Unidad de Revisiones sistematicas y Meta-analisis, Guıas de Practica Clınica y Evaluaciones de TecnologıaSanitaria (URSIGET), Vicerrectorado de Investigacion, Universidad San Ignacio de Loyola (USIL), Lima,Peru.
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4 Health Outcomes, Policy, and Evidence Synthesis (HOPES) Group, University of Connecticut School ofPharmacy
Corresponding author:
Jorge L. Maguina
Escuela de Medicina, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
Av. Alameda San Marcos, Distrito de Chorrillos 15067. Lima, Peru.
Telephone: +511 630 3333
E-mail: [email protected]
Acknowledgments: None. No funding to declare.
Conflicts of interest : No conflicts of interest for all authors.
Authors Contributions
Study design and concept: IST, JRUB, JLM, AVH, VB-Z. Acquisition of data: AAC, EA-B, JRUB, IST,AVH, VB-Z, JLM. Drafting of the manuscript: JRUB, IST, AAC, EA-B. Critical revision of the manuscript:AVH, VB-ZM, JLM, Statistical analysis: VB-ZM, JRUB, IST, AVH. Study supervision: AVH, JLM, VB-Z.
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lymphocyte-ratio-in-covid-19-patients-a-systematic-review-and-meta-analysis
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FIGURE 1 : PRISMA 2009 Flow Diagram
Records identified through PubMed, Embase, OvidMedline, Scopus, WHO COVID-19 Global Research
Database, Scielo, LILACS, Cochrane Library,medRxiv, ScienceDirect, SpringerLink and CNKI
databases.
(N = 221)
Screening
Included
Eligibility
Identification
Records after duplicates removed(n =77)
Records screened(n = 77 )
Records excluded(n = 38 )
Full-text articles assessedfor eligibility
(n =39)
Full-text articles excluded,with reasons
(n = 19)
- wrong study design
- wrong analysis
-wrong exposure
- patients were notexclusively older than 18years
-Data Duplication
-Group Imbalance
Studies included inqualitative synthesis
(n =20)
Studies included inquantitative synthesis
(meta-analysis)(n = 20)
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Figure 2: Association between NLR and severity
Figure 2A. Forest Plot for studies that evaluated the association of NLR and
severity
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Figure 2B. Subgroup analysis according to study design of the studies that
evaluated the association between NLR and severity
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Figure 2C. Sensitivity analysis according to the risk of bias of the studies that
evaluated the association between NLR and severity
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Figure 3: Association between NLR and mortality
Figure 3A. Forest Plot for studies that evaluated the association between NLR and mortality
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Figure 3 B: Subgroup analysis according to origin country of the studies that
evaluated the association between NLR and mortality
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Figure 3C: Sensitivity analysis according to the risk of bias of the studies that
evaluated the association between NLR and mortality
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