Neutrophil:lymphocyte ratio predicts short-term outcome of COVID-19 in haemodialysis patients

Prisca Mutinelli-Szymanski, Iulia Hude, Emilie Merle, Yannis Lombardi, Pascal Seris, Medhi Abtahi, Latifa Azeroual, Cecile Bourgain, Gael Ensergueix, Ioannis Katerinis, Anne Kolko, Amir Kolta, Catherine Maheas, Saeed Mehrbanian, Pauline Morel, Rim Ossman, Hélène de Préneuf, Arthur Roux, Claudine Saltiel, Florence Vendé, Anne-Sophie Verhoeven, Béatrice Viron, Sophie Laplanche, Alban Le Monnier, Christophe Ridel, Pablo Ureña-Torres, Maxime Touzot, Prisca Mutinelli-Szymanski, Iulia Hude, Emilie Merle, Yannis Lombardi, Pascal Seris, Medhi Abtahi, Latifa Azeroual, Cecile Bourgain, Gael Ensergueix, Ioannis Katerinis, Anne Kolko, Amir Kolta, Catherine Maheas, Saeed Mehrbanian, Pauline Morel, Rim Ossman, Hélène de Préneuf, Arthur Roux, Claudine Saltiel, Florence Vendé, Anne-Sophie Verhoeven, Béatrice Viron, Sophie Laplanche, Alban Le Monnier, Christophe Ridel, Pablo Ureña-Torres, Maxime Touzot

Abstract

Background: Information regarding coronavirus disease 2019 (COVID-19) in haemodialysis (HD) patients is limited and early studies suggest a poor outcome. We aimed to identify clinical and biological markers associated with severe forms of COVID-19 in HD patients.

Methods: We conducted a prospective, observational and multicentric study. Sixty-two consecutive adult HD patients with confirmed COVID-19 from four dialysis facilities in Paris, France, from 19 March to 19 May 2020 were included.Blood tests were performed before diagnosis and at Days 7 and 14 after diagnosis. Severe forms of COVID-19 were defined as requiring oxygen therapy, admission in an intensive care unit or death. Cox regression models were used to compute adjusted hazard ratios (aHRs). Kaplan-Meier curves and log-rank tests were used for survival analysis.

Results: Twenty-eight patients (45%) displayed severe forms of COVID-19. Compared with non-severe forms, these patients had more fever (93% versus 56%, P < 0.01), cough (71% versus 38%, P = 0.02) and dyspnoea (43% versus 6%, P < 0.01) at diagnosis. At Day 7 post-diagnosis, neutrophil counts, neutrophil:lymphocyte (N:L) ratio, C-reactive protein, ferritin, fibrinogen and lactate dehydrogenase levels were significantly higher in severe COVID-19 patients. Multivariate analysis revealed an N:L ratio >3.7 was the major marker associated with severe forms, with an aHR of 4.28 (95% confidence interval 1.52-12.0; P = 0.006). After a median follow-up time of 48 days (range 27-61), six patients with severe forms died (10%).

Conclusions: HD patients are at increased risk of severe forms of COVID-19. An elevated N:L ratio at Day 7 was highly associated with the severe forms. Assessing the N:L ratio could inform clinicians for early treatment decisions.

Keywords: biomarkers; dialysis; haemodialysis; prognosis; survival analysis.

© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.

Figures

FIGURE 1:
FIGURE 1:
(A) Neutrophil count, (B) lymphocyte count and (C) N:L ratio kinetic in non-severe (blue) and severe (red) forms of COVID-19. M-1: last monthly routine measure; D0: day of COVID-19 diagnosis. Data are expressed as mean ± SD. *P 

FIGURE 2:

Circulating (A) CRP level, (B)…

FIGURE 2:

Circulating (A) CRP level, (B) ferritin level , (C) LDH level and (D)…

FIGURE 2:
Circulating (A) CRP level, (B) ferritin level, (C) LDH level and (D) fibrinogen in non-severe (blue) and severe (red) forms of COVID-19. M-1: last monthly routine measure was not available for LDH and fibrinogen; D0: day of COVID-19 diagnosis. Data are expressed as mean ± SD. *P < 0.05, **P < 0.01, ns: non-significant (Mann–Whitney test).

FIGURE 3:

Survival free of oxygen therapy,…

FIGURE 3:

Survival free of oxygen therapy, ICU admission or death among HD patients diagnosed…

FIGURE 3:
Survival free of oxygen therapy, ICU admission or death among HD patients diagnosed with SARS-CoV-2 infection. Kaplan–Meier method was used to draw survival curves and the log-rank test was used for comparison of survival curves.
FIGURE 2:
FIGURE 2:
Circulating (A) CRP level, (B) ferritin level, (C) LDH level and (D) fibrinogen in non-severe (blue) and severe (red) forms of COVID-19. M-1: last monthly routine measure was not available for LDH and fibrinogen; D0: day of COVID-19 diagnosis. Data are expressed as mean ± SD. *P < 0.05, **P < 0.01, ns: non-significant (Mann–Whitney test).
FIGURE 3:
FIGURE 3:
Survival free of oxygen therapy, ICU admission or death among HD patients diagnosed with SARS-CoV-2 infection. Kaplan–Meier method was used to draw survival curves and the log-rank test was used for comparison of survival curves.

References

    1. Ruan Q, Yang K, Wang W. et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020; 46: 1294–1297
    1. Shi S, Qin M, Shen B. et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020; 5: 802–810.
    1. Guan WJ, Ni ZY, Hu Y. et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382: 1708–1720.
    1. Kelly CJ. T cell function in chronic renal failure and dialysis. Blood Purif 1994; 12: 36–41
    1. Kato S, Chmielewski M, Honda H. et al. Aspects of immune dysfunction in end-stage renal disease. Clin J Am Soc Nephrol 2008; 3: 1526–1533
    1. Goicoechea M, Sa LA, Mun A. et al. COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain. Kidney Int 2020; 98: 27–34
    1. Alberici F, Delbarba E, Manenti C. et al. A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection. Kidney Int 2020; 98: 20–26.
    1. Wang R, Liao C, He H. et al. COVID-19 in hemodialysis patients: a report of 5 cases. Am J Kidney Dis 2020; 76: 141–143.
    1. Xu X, Han M, Li T. et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA 2020; 117: 10970–10975
    1. Ma Y, Diao B, Lv X. et al. 2019 novel coronavirus disease in hemodialysis (HD) patients: report from one HD center in Wuhan, China. medRxiv 2020; 10.1101/2020.02.24.20027201
    1. Bataille S, Pedinielli N, Bergounioux J-P.. Could ferritin help the screening for COVID-19 in hemodialysis patients? Kidney Int 2020; 98: 235–236
    1. Basile C, Combe C, Pizzarelli F.. Recommendations for the prevention, mitigation and containment of the emerging SARS-CoV-2 (COVID-19) pandemic in haemodialysis centres. Nephrol Dial Transplant 2020; 35: 737–741. doi: 10.1093/ndt/gfaa069
    1. Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497–506
    1. Chen G, Wu D, Guo W. et al. Clinical and immunologic features in severe and moderate coronavirus disease 2019. J Clin Invest 2020; 130: 2620–2629.
    1. Mehta P, McAuley DF, Brown M. et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395: 1033–1034
    1. Connors JM, Levy JH.. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135: 2033–2040
    1. Pedersen SF, Ho YC.. SARS-CoV-2: a storm is raging. J Clin Invest 2020; 130: 2202–2205
    1. Qin C, Zhou L, Hu Z. et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis 2020; 71: 762–768.
    1. Aouba A, Baldolli A, Geffray L. et al. Targeting the inflammatory cascade with anakinra in moderate to severe COVID-19 pneumonia: case series. Ann Rheum Dis 2020; doi: 10.1136/annrheumdis-2020-217706
    1. Danser AHJ, Epstein M, Batlle D.. Renin–angiotensin system blockers and the COVID-19 pandemic: at present there is no evidence to abandon renin-angiotensin system blockers. Hypertension 2020; 75: 1382–1385
    1. Mancia G, Rea F, Ludergnani M. et al. Renin–angiotensin–aldosterone system blockers and the risk of COVID-19. N Engl J Med 2020; 382: 2431–2440
    1. Reynolds HR, Adhikari S, Pulgarin C. et al. Renin–angiotensin–aldosterone system inhibitors and risk of COVID-19. N Engl J Med 2020; 382: 2441–2448.

Source: PubMed

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