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Research Article
Revised

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio predicting hospital length of stay and mortality in young COVID-19 patients: A retrospective study

[version 2; peer review: 1 approved, 1 approved with reservations]
PUBLISHED 07 Jul 2025
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OPEN PEER REVIEW
REVIEWER STATUS

This article is included in the Coronavirus (COVID-19) collection.

Abstract

Background

This study investigated the utility of platelet-to-lymphocyte ratio (PLR) and Neutrophil-to-Lymphocyte ratio (NLR) in patients with COVID-19 with respect to age, early (a week) vs. delayed recovery (> a week) and mortality.

Methods

This was a retrospective study including 1,016 COVID-19 patients. The discriminatory power and multivariate logistic regression analysis were performed.

Results

The mean age of patients was 45 (± 13.9), and 75.7% were males. Older patients had elevated NLR, PLR, D-dimer, CRP, and Interleukin-6 levels and longer hospital stay than the younger group (p < 0.001). In-hospital mortality was higher in older adults (26.9% vs. 6.6%, p =0.001). On-admission NLR (5.8 vs. 3.2; P= 0.001) and PLR (253.9±221.1 vs. 192.2±158.5; p = 0.004) were higher in the non-survivors than survivors. Both PLR and NLR displayed significant discriminatory ability for mortality. NLR had a higher AUC and specificity, while PLR exhibited slightly higher sensitivity. In individuals aged ≤55, NLR showed superior discrimination (AUC=0.717) compared to PLR (AUC=0.620). Conversely, for older adults, PLR displayed enhanced discrimination (AUC=0.710), while NLR showed AUC=0.693.

Conclusion

Higher admission NLR and PLR levels were associated with delayed recovery, whereas an enhanced NLR was associated with considerably higher mortality in older COVID-19 patients.

Keywords

COVID-19; Inflammation; Mortality; Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Hospital stay, age

Revised Amendments from Version 1

The revised manuscript confirms the association between NLR and PLR and hospitalization duration and recovery, taking into account the patient's age. The findings, interestingly, showed that higher admission NLR and PLR levels were associated with delayed recovery, whereas an enhanced NLR was associated with considerably higher mortality in older COVID-19 patients. The current study provides unique insights into biomarker behavior within a younger, predominantly male cohort, a demographic that has been underrepresented in earlier studies, which have focused mainly on elderly or critically ill populations. Stratified analysis revealed that NLR exhibited greater discriminatory ability for mortality in patients aged ≤55 years, whereas PLR performed better in those aged >55 years. These age-dependent differences in performance, which are not well documented in the previous literature, suggest a need for a tailored interpretation of these markers across age groups. Moreover, in contrast to most existing studies that focus solely on mortality or ICU admission, we also evaluated the association between NLR/PLR and hospital length of stay. The mean duration of hospital stay was 21.9 ± 17.0 days, with a median stay of 19.6 days. The study cohort comprised patients from 43 different nationalities, reflecting the ethnically diverse population of Qatar. Ethnicity-wise, most patients were of South Asian origin, followed by those of Arab ethnicity. Other represented groups included Southeast Asians, East Africans, and Central Asians.

See the authors' detailed response to the review by Lorenzo Malatino and Ivan Isaia

Key messages

  • - Simple, instant bedside laboratory tests on admission are of utmost value for patients’ stratification during a pandemic.

  • - COVID-19 patients with elevated NLR and PLR levels are associated with delayed recovery, more ICU admissions, and intubation.

  • - A greater NLR values are associated with higher mortality in older COVID-19 patients.

  • - However, none of these two parameters alone is an independent predictor of death.

  • - These findings highlight the potential utility of NLR and PLR as accessible, cost-effective tools for early risk stratification, particularly in resource-limited or surge settings.

Introduction

The severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) causing Coronavirus disease 2019 (COVID-19) has overwhelmed the healthcare infrastructure worldwide by causing recurrent waves.1 The SARS-CoV-2 infection has wide clinical variations, ranging from asymptomatic infection to moderate upper respiratory tract illness to severe viral pneumonia with respiratory failure and death.2 Of note, reliable laboratory parameters of the severity of the disease, treatment response, and outcome were not thoroughly investigated during the early phase of the pandemic due to its rapid onset and spread. Consequently, the early identification of clinical and laboratory variables linked with poor outcomes is critical for identifying low- and high-risk patients for triage and guiding appropriate management.

Infectious diseases are associated with inflammation, and existing data supports the central role of inflammation in the progression and pathogenesis of COVID-19.2 SARS-COV-2 viral replication causes cellular destruction, leading to the release of cytokines and chemokines from the activated macrophages.3 As a result, these mediators set off immunological responses, which in turn cause cytokine storms and aggravate the disease. As a result, they elicit immune responses, which create cytokine storms and exacerbate the problem. This imbalance arises because the adaptive immune response depends on the strength of the inflammatory response.4 Consequently, patients with a pre-existing chronic inflammatory status may be more vulnerable to a severe form of COVID-19 disease.

The Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are straightforwardly obtainable ratios from complete blood count (CBC) panels. Emerging evidence suggests that peripheral NLR and PLR can be used as markers of systemic inflammation in various disease processes.59 Several studies have reported the prognostic role of NLR in differentiating mild/moderate cases from severe COVID-19 cases and have proposed that NLR can be a reliable predictor of COVID-19 progression associated with high mortality in COVID-19.1016 Moreover, several studies have also suggested PLR to be a promising and reliable indicator of disease severity, exhibiting good predictive values on progression and clinical outcomes in patients with COVID-19.1722

However, a limiting factor of these ratios is the inability to account for ethnic differences.23 Also, these ratios can be profoundly influenced by age and gender,24,25 though the extent of this influence has not yet been fully explored in COVID-19. Moreover, Qatar has a distinct demographic profile, with around 88% of the expatriate workforce of Qatar’s 2.8 million citizens. While the bulk of the population (75%) is male gender, the pyramid shape of population distribution is disproportionately concentrated in the 20–50-year age group.25 COVID-19 affects males disproportionately, and older adults tend to have worse outcomes.26,27

We sought to evaluate the association of NLR and PLR and the recovery and mortality in COVID-19 patients, and to assess age-stratified differences in these outcomes.

Methods

Study population and data collection

A retrospective observational study was conducted, including patients with COVID-19 admitted to the different affiliated Hospitals of Hamad Medical Corporation (HMC) in Qatar at the beginning of the coronavirus pandemic (from March 01 to June 01, 2020). The subjects included in the study were laboratory-confirmed cases of COVID-19 disease (>18 years old) of both genders. Patients with an inconclusive diagnosis of COVID-19 by RT-PCR testing, undefined diagnosis, and missing data were excluded from the study. Data were extracted from the electronic medical record (CERNER), which included patients’ demographics such as (age, gender, nationality); recent exposure history, clinical symptoms and signs, comorbidities (Hypertension, diabetes mellitus, cancer, renal failure, chronic obstructive pulmonary disease, and others), initial vitals (Systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, blood oxygen saturation), routine laboratory findings (initial and repeated readings) including CBC, blood chemistry and C-reactive protein (CRP), chest X-ray and computed tomographic scans, treatment, mechanical ventilation, hospital and intensive critical care (ICU) length of stay, speed of recovery (within one week, and more than one week), discharge from hospital and mortality.

TaqPath COVID-19 Combo KitTM (Thermo Fisher Scientific, Waltham, Massachusetts, USA) or Cobas SARS-CoV-2 Test® (Roche Diagnostics, Rotkreuz, Switzerland) were used to identify SARS-CoV-2 infection utilizing Nasopharyngeal and throat samples. All COVID-19 testing was performed at the central laboratory of the HMC, which manages over 85% of the country’s inpatient bed capacity and is responsible for delivering public healthcare.

Study definitions

  • - Every patient who experienced COVID-19-like manifestations and at the same time tested positive for COVID-19 in respiratory samples using a real-time reverse-transcription polymerase chain reaction (RT-PCR) assay was deemed a confirmed COVID-19 case.

  • - The platelet-to-lymphocyte ratio (PLR) was defined as the ratio between absolute Platelet counts to absolute lymphocyte count, and the neutrophil-to-lymphocyte ratio (NLR) was defined as the ratio between absolute neutrophil counts to absolute lymphocyte count.

  • - Recovery referred to two negative swab tests done consecutively.

Statistical analysis

The data was collated in Microsoft Excel, and statistical analysis was performed using SPSS, version 28.0. for Windows (Armonk, NY: IBM Corp, USA). Data were expressed as proportions, means ± standard deviations, or medians as appropriate for continuous variables or as absolute counts and percentages for categorical variables. Data were compared using the student-t-test for continuous variables and the Pearson χ2 test for categorical variables. The Fisher exact test was used if the expected cell frequency was below five. For skewed continuous data, a nonparametric Mann-Whitney test was performed. The independent predictors of mortality were identified using multivariable logistic regression analysis after adjusting for age, gender, comorbidities, complications, NLR, and PLR as covariates of interest.

Areas under the curve (AUC) of ROC curves were employed to determine the ratios’ performance in age discrimination regarding NLR and PLR. The best cut-off points of the ratios were the points on the curves with the highest sensitivity and specificity. The sample size for the current study was not determined a priori as we intended to include all the laboratory-confirmed COVID-19 cases during the study period. A two-sided P-value < 0.05 was considered statistically significant.

This observational study was conducted in accordance with the STROBE principles. The study was authorized by the Institutional Review Board and Medical Research Council (MRC-01-20-672 & MRC-05-213) of Hamad Medical Corporation. A waiver of consent was granted for this retrospective study as there was no direct contact was made with the participants, and the data was collected anonymously.

Results

During the study period, 1016 persons tested positive for SARS-CoV-2. The mean age of the cohort was 45±13.9 years, and an overwhelming majority of infected persons were male (75.7 %). The most common chronic medical conditions were hypertension (40.3%), followed by diabetes mellitus (39.0%), chronic kidney disease (14.0%), cancer (5.4%) and chronic obstructive pulmonary disease (4.8%). The mean duration of hospital stay was 21.9 ± 17.0 days, with a median stay of 19.6 days (range: 0.1–153 days). The study cohort consisted of patients representing 43 different nationalities, reflecting the ethnically diverse population of Qatar. Ethnicity wise, the majority of patients were of South Asian origin (55.0%), followed by those of Arab ethnicity (29.6%). Other represented groups included Southeast Asians (8.2%), East Africans (2.7%), and Central Asians (2.5%). Smaller proportions of patients were from European (0.9%), Latin American (0.8%), Central African, West African, and North American, backgrounds (each 0.1%).

Table 1 outlines the comparison of clinical characteristics, in-hospital complications, comorbidities, and outcomes of COVID-19 patients according to hospital length of stay. Patients in the long-stay group were older (45.9±13.9 vs. 40.6±13.2), had significantly lower SpO2 (97.1±3.6 vs. 98.4±2.0), and were more likely to have significant medical comorbidities compared to ‘short stay’ group. Compared with the short-stay group, patients in the long-stay group were presented with lower lymphocyte and platelet counts and higher inflammation-related indices (CRP, IL-6). Further significant elevations in NLR [3.7 (0.3-72.0) vs. 2.8 (0.6(0.6-53.0)); P=0.002] and the PLR indices was found [205.4±178.8 vs. 199.6±168.2; P=0.001]. Concerning the major in-hospital complications, patients in the long-hospital stay group were more likely to have renal failure (16.7% vs. 5.1%; P=0.001) and ARDS (3.7% vs. 0.0%; P=0.009) than patients in the short-stay group. The in-hospital mortality rate was 11.9% (121/1016). Patients in the long-stay group had higher in-hospital mortality than those in the short-stay group (12.8% vs. 7.9%; P<0.06).

Table 1. Comparisons of clinical characteristics, and outcomes of COVID-19 patients according to hospital length of stay.

VariablesLength of hospital stays P -value
Short stay (≤ 1 week) (n =178, 17.5%) Long stay (> 1 week) (n = 838, 82.5%)
Age (years) 40.6±13.245.9±13.90.001
Males 105 (59.0%)664 (79.2%)0.001
Number of admissions 2 (1-14)1 (1-57)0.001
Initial vital signs
Systolic blood pressure125.9±20.3127.1±18.60.45
Diastolic blood pressure75.6±11.576.8±11.80.21
Pulse90.3±15.190.8±15.70.73
Respiratory rate19.3±2.520.8±5.60.001
Oxygen saturation98.4±2.097.1±3.60.001
Comorbidities
Hypertension50 (28.1%)359 (42.8%)0.001
Diabetes Mellitus50 (28.1%)346 (41.3%)0.001
Cancer6 (3.4%)49 (5.8%)0.18
Chronic Kidney Disease17 (9.6%)125 (14.9%)0.06
COPD10 (5.6%)39 (4.7%)0.58
Initial laboratory findings
Creatinine (μmol/L) (n=950)75 (22-1254)85 (20-1891)0.001
CRP (mg/L) (n=891)6.8 (0.3-318.9)42.4 (0.3-444.8)0.001
D-Dimer (mg/L FEU) (n=532)0.97 (0.19-64.5)0.89 (0.19-91.6)0.86
Ferritin (μg/L) (n=623)344.8 (9.0-28677)590 (4.2-45878)0.001
IL-6 (pg/mL) (n=209)79 (15-1923)112.5 (2-4021)0.61
Lymphocytes (×109/L)1.72±0.741.44±0.750.001
Neutrophils (×109/L)5.7±3.65.8±4.10.91
Platelet (×109/L)250.7±83.6231.3±85.40.006
Troponin (ng/L) (n=421)20 (3-1278)11 (3-2979)0.50
WBC (×109/L)8.2±3.77.9±4.50.47
Platelet-to-lymphocyte ratio (PLR)172.4±101.2205.4±178.80.001
Neutrophil-to-lymphocyte ratio (NLR)2.8 (0.6-53.0)3.7 (0.3-72.0)0.002
ECMO 1 (0.6%)26 (3.1%)0.05
Intubation 11 (6.2%)233 (27.8%)0.001
ICU admission 19 (10.7%)335 (40.0%)0.001
ICU length of stay (Days) 2.2 (0.16-45.1)13.6 (0.1-83.4)0.001
Ventilatory days 1.8 (0.3-5.3)11.9 (0.1-87.8)0.001
Complications
ARDS0 (0.0%)31 (3.7%)0.009
Renal Failure9 (5.1%)140 (16.7%)0.001
Pulmonary embolism0 (0.0%)8 (1.0%)0.19
Sepsis2 (1.1%)4 (0.5%)0.30
DVT0 (0.0%)4 (0.5%)0.35
Mortality 14 (7.9%)107 (12.8%)0.06

Table 2 summarizes the impact of age. Of the total COVID-19 patients, 74% were aged ≤55, and 26% were >55. Hypertension (75% vs. 8.1%), diabetes mellitus (DM) (70.8% vs. 27.8%), and chronic kidney disease (30.3% vs. 8.2%) were more evident in older subjects than in the younger group. Regarding vital signs, the older patients had significantly lower diastolic blood pressure (DBP), pulse rate, and oxygen saturation than the younger patients. The initial laboratory results showed that, compared with the younger patients, older patients had significantly higher NLR, PLR, creatinine, CRP, IL-6, and D-dimer levels. Intubation was performed more in older patients (42% vs.17.7%; P=0.001). Besides, the median length of ICU [14.1 (0.1-74.3) vs. 11.7 (0.16-83.4) days] and ventilatory days [13.7 (0.4-74.7) vs. 9.3 (0.1-87.8)] were significantly longer in the older group. The older patient group experienced a higher frequency of renal failure (29.2% vs. 9.6%), ARDS (4.2% vs.2.7%), pulmonary embolism (1.5% vs. 0.5%), and a higher mortality rate than the younger group (26.9% vs. 6.6 %, P<0.001).

Table 2. Comparisons of clinical characteristics, complications, and outcomes among COVID-19 patients according to age.

VariablesAge ≤55 (n = 752, 74.0%)Age >55 (n = 264, 26.0%) P-value
Age (years) 38.6±9.663.4±5.40.001
Males 564 (75.0%)205 (77.7%)0.38
Number of admissions 2 (1-14)1 (1-57)0.001
Initial vital signs
Systolic blood pressure125.2±17.5131.6±21.60.001
Diastolic blood pressure76.8±11.975.7±11.30.18
Pulse91.3±15.888.8±14.70.02
Respiratory rate20.2±5.121.3±5.40.003
Oxygen saturation97.7±3.196.5±3.90.001
Comorbidities
Hypertension211 (28.1%)198 (75.0%)0.001
Diabetes Mellitus209 (27.8%)187 (70.8%)0.001
Cancer35 (4.7%)20 (7.6%)0.07
Chronic Kidney Disease62 (8.2%)80 (30.3%)0.001
COPD27 (3.6%)22 (8.3%)0.002
Initial laboratory findings
Creatinine (μmol/L) (n=950)80 (20-1891)97 (32-1401)0.001
CRP (mg/L) (n=891)26.0 (0.3-1891)60.3 (0.3-387.6)0.001
D-Dimer (mg/L FEU) (n=532)0.79 (0.19-91.6)1.06 (0.22-84.4)0.001
Ferritin (μg/L) (n=623)520 (4.2-28677)659.5 (18.3-45878)0.001
IL-6 (pg/mL) (n=209)94.5 (2.0-4021.0)133 (3-2351)0.04
Lymphocytes (×109/L)1.58±0.781.24±0.640.001
Neutrophils (×109/L)5.9±4.15.6±3.90.30
Platelet (×109/L)241.6±83.2215.1±88.60.001
Troponin (ng/L) (n=421)9 (3-2979)19 (3-2351)0.001
WBC (×109/L)8.3±4.57.4±4.10.006
Platelet-to-lymphocyte ratio (PLR)194.2±168.2214.8±167.70.08
Neutrophil-to-lymphocyte ratio (NLR)3.3 (0.27-72.0)4.0 (0.4-53.0)0.002
ECMO 22 (2.9%)5 (1.9%)0.37
Intubation 133 (17.7%)111 (42.0%)0.001
ICU admission 205 (27.3%)149 (56.4%)0.001
ICU length of stay (Days) 11.7 (0.16-83.4)14.1 (0.1-74.3)0.06
Ventilatory days 9.3 (0.1-87.8)13.7 (0.4-74.7)0.04
Short stay (≤ 1 week) 152(20.2%)26 (9.8%)0.001
Long-stay (> 1 week) 600(79.8%)238(90.2%)
Complications
ARDS20 (2.7%)11 (4.2%)0.22
Renal Failure72 (9.6%)77 (29.2%)0.001
Pulmonary embolism4 (0.5%)4 (1.5%)0.12
Sepsis5 (0.7%)1 (0.4%)0.60
Deep vein thrombosis4 (0.5%)0 (0.0%)0.23
Mortality 50 (6.6%)71 (26.9%)0.001

Table 3 compares clinical characteristics, laboratory results, and complications among COVID-19 patients stratified according to survival status. The deceased patients were significantly older than those who survived (56.4±11.4 vs. 43.5±13.25 years, respectively, P<0.001) with more comorbidities as well. Creatinine, CRP, D-dimer, ferritin, IL-6, neutrophil, troponin, PLR, and NLR were significantly higher, whereas lymphocyte and platelet counts were significantly lower in the deceased patients.

Table 3. Comparisons of clinical characteristics, complications, and outcomes among COVID-19 patients according to mortality.

VariablesSurvivors (n=895)Non-survivors (n=121) P -value
Age (years) 43.5±13.556.4±11.40.001
Males 664 (74.2%)105 (86.8%)0.002
Comorbidities
Hypertension336 (37.5%)73 (60.3%)0.001
Diabetes Mellitus318 (35.5%)78 (64.5%)0.001
Cancer43 (4.8%)12 (9.9%)0.02
Chronic Kidney Disease115 (12.8%)27 (22.3%)0.005
COPD43 (4.8%)6 (5.0%)0.94
Initial laboratory findings
Creatinine (μmol/L) (n=950)82 (20-1891)101 (32-1131)0.001
CRP (mg/L) (n=891)28.0 (0.3-444.8)94.2 (0.4-387.6)0.001
D-Dimer (mg/L FEU) (n=532)0.82 (0.19-91.6)1.24 (0.3-84.4)0.001
Ferritin (μg/L) (n=623)527 (4.2-45878)868.5 (66.5-39695)0.001
IL-6 (pg/mL) (n=209)87 (2-4021)185.5 (4-2599)0.006
Lymphocytes (×109/L)1.55±0.771.03±0.520.001
Neutrophils (×109/L)5.7±3.87.0±5.30.008
Platelet (×109/L)238.6±83.9206.2±91.10.001
Troponin (ng/L) (n=421)9 (3-2351)27 (3-2979)0.001
WBC (×109/L)117 (36.1%)65 (67.0%)0.001
Platelet-to-lymphocyte ratio (PLR)192.2±158.5253.9±221.10.004
Neutrophil-to-lymphocyte ratio (NLR)3.2 (0.27-72.0)5.8 (0.9-53.0)0.001
ICU length of stay (days) 10.9 (0.1-72)16.6 (0.16-83.4)0.001
Hospital length of stay (days) 19.6 (0.13-153)20.7(0.61-89.4)0.002
Ventilatory days 8.0 (0.1-78.5)16.4 (0.3-87.8)0.001
Complications
ARDS16 (1.8%)15 (12.4%)0.001
Renal failure90 (10.1%)59 (48.8%)0.001
Pulmonary embolism5 (0.6%)3 (2.5%)0.02
Sepsis4 (0.4%)2 (1.7%)0.10
Deep vein thrombosis4 (0.4%)0 (0.0%)0.46

Figure 1(a) and (b) show the result of the ROC analysis plotting the sensitivity and specificity of the PLR and NLR and their discriminatory ability to predict overall mortality and their performance by age categories in COVID-19 patients, respectively.

0b9a5418-c0f5-4379-b8b4-dc1faabe2521_figure1a.gif0b9a5418-c0f5-4379-b8b4-dc1faabe2521_figure1b.gif

Figure 1. Receiver operating characteristic (ROC) curves analyses for predicting discriminatory power analysis of initial Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio for the prediction of mortality in COVID-19 patients (a) overall mortality (b) mortality by age groups.

The area under the curve (AUC) for NLR was 0.710, indicating a good discriminatory performance, and for PLR, 0.614 suggesting a fair discriminatory capacity, respectively. The optimal cut-off for NLR and PLR were 5.03 (Sensitivity 66.9% and specificity 46.5%) and 150.16 (Sensitivity 61.2% and specificity 68.4%). In individuals aged ≤55 years, the PLR demonstrated moderate discrimination with an AUC of 0.620, while the NLR exhibited a higher AUC of 0.717, signifying superior discrimination compared to the PLR. Conversely, for individuals aged >55 years, PLR showed an increased higher AUC of 0.710 in comparison to those ≤55 years, implying enhanced discrimination in this age group, while NLR exhibited moderate discrimination with an AUC of 0.693 ( Figure 1(b)).

Table 4 shows the association of PLR and NLR in predicting mortality and delayed recovery in COVID-19 patients. The crude odd ratio for NLR was 1.078 (95% CI 1.049-1.109; P=0.001), and PLR was 1.001 (95% CI, 1.001-1.002; P=0.002) for mortality. The crude odd ratio for NLR was 1.034 (95% CI 0.996-1.072; P=0.078), and PLR was 1.002 (95% CI, 1.000-1.004; P=0.021) for delayed recovery.

Table 4. Association of PLR and NLR with mortality and delayed recovery.

VariablesCrude Odd ratio95% CI P value
Lower Upper
Mortality
Platelet-to-lymphocyte ratio1.0011.0011.0020.002
Neutrophil-to-lymphocyte ratio1.0781.0491.1090.001
Delayed recovery (HLOS >7 days)
Platelet-to-lymphocyte ratio1.0021.0001.0040.021
Neutrophil-to-lymphocyte ratio1.0340.9961.0720.078

Table 5 depicts the results of multivariate regression analysis to determine independent predictors of mortality. After adjusting for the relevant covariates, being older than 55 years (OR 1.068; 95% CI 1.045 to 1.091; P=0.001), hypertension (OR 0.437; 95% CI 0.255 to 0.751; P=0.003), diabetes mellitus, (OR 1.730; 95% CI 1.050 to 2.851; P=0.032), CRP (OR 1.004; 95% CI 1.002 to 1.007; P=0.001), and renal failure (OR 6.620; 95% CI 3.989 to 10.989; P=0.001) were found to be independent predictors of mortality. However, NLR (OR 1.039; 95% CI 0.998 to 1.082; P=0.051) and PLR (OR 1.000; 95% CI 0.998 to 1.001; P=0.581) were not independently associated with in-hospital mortality.

Table 5. Multivariate regression analysis for predictors of mortality.

VariablesOdd Ratio95% CI P value
LowerUpper
Age1.0681.0451.0910.001
Males1.1250.5952.1290.717
Hypertension0.4370.2550.7510.003
Diabetes Mellitus1.7301.0502.8510.032
C- reactive protein (CRP)1.0041.0021.0070.001
Platelet to lymphocyte ratio (PLR)1.0000.9981.0010.581
Neutrophil to lymphocyte ratio (NLR)1.0390.9981.0820.051
Renal Failure6.6203.98910.9890.001

Discussion

Ever since the first cases of the COVID-19 pandemic were reported, healthcare institutions have worked to develop diagnostic tools and prognostic indications. The current study investigates associations between NLR, PLR, age, duration of hospital length of stay, and mortality in COVID-19 patients in Qatar. The current study provides unique insights into biomarker behavior within a younger, predominantly male cohort (mean age 45±13.9 years), a demographic underrepresented in earlier studies that focused largely on elderly or critically ill populations. Stratified analysis revealed that NLR exhibited greater discriminatory ability for mortality in patients aged ≤55 years (AUC=0.717), whereas PLR performed better in those aged >55 years (AUC=0.710). These age-dependent differences in performance, not well documented in previous literature, suggest a need for tailored interpretation of these markers across age groups. Moreover, In contrast to most existing studies that focus solely on mortality or ICU admission, we also evaluated the association between NLR/PLR and hospital length of stay.

The study demonstrated that patients with higher admission NLR and PLR levels were associated with delayed recovery, more intubation, and ICU admissions. In contrast, an enhanced NLR was associated with considerably higher mortality in older COVID-19 patients than PLR.

Despite a high per capita SARS-CoV-2 infection rate in the early phase of the COVID-19 pandemic, the case fatality rate in Qatar was among the lowest in the world.28 In our analysis of 1016 COVID-19 patients, the overall in-hospital mortality was 11.9%. The mortality rate was lower than those reported in previous studies from other countries.29,30 Notably, lower mortality was also observed in the elderly population (aged >55).

Several studies and meta-analyses have concluded that the predictive value of NLR and PLR could be used to stratify COVID-19 patients, and especially high NLR at admission has been associated with poor outcomes.11,12,3032 While previous publications included older adults, they did not perform a subgroup analysis to assess the estimated mortality risk for this age group. Ciccullo et al. demonstrated that younger age, and NLR below 3 were associated with clinical improvement, while NLR over 4 predicted ICU transfer.31

Based upon the ROC analysis, the cut-off values for predicting mortality were 5.03 for NLR, and 150.16 for PLR. This result is in concordance with previous studies, in which the proposed optimum cut-off values for NLR ranged from 3 to 6,11,32,33 and cut-off PLR values were between 140-160.32,34 Liu et al. showed that older patients (>50 years old) with NLR ≥3.13 are more likely to develop a critical illness.35 Yang et al. found that elevated NLR and advanced age were associated with severe COVID-19 illness and independently predicted the worse clinical outcomes.36

The NLR has emerged as a potent inflammatory marker with diagnostic and prognostic utility in various clinical conditions.1113,15,16,21,22,35,3739 NLR represents the equilibrium of innate and adaptive immune responses.18 A high NLR implies an aberrant immune response, characterized by increased neutrophils and decreased lymphocytes. Neutrophil production can also be augmented by virus-induced inflammatory factors such as IL-6, Interleukin-8 (IL-8), and tumor necrosis factor α (TNF- α).4,37,40 Furthermore, it appears to be a more reliable technique than PLR, absolute neutrophils, and lymphocyte counts, as it is less influenced by confounders.

The current study’s asynchronous pattern between NLR and PLR highlights that both ratios were elevated during the onset of the COVID-19 disease, but NLR continued to increase afterward, especially in older individuals. This suggests that NLR offers additional information regarding the ongoing inflammatory state in COVID-19 patients, especially those with poor prognoses. Our results suggest that NLR can be a more valuable predictor of poor prognosis across the different sub-categories of patients studied in the current study.

However, neither NLR nor PLR was shown to be independent predictor of mortality on multivariate analysis, contrasting with previous reports.1,14,24,31,38,41,42 This discrepancy could be explained by one of two factors. First, the pathogenesis of SARS-CoV-2 infection is complicated. Secondly, this could be attributed to the small sample size reported in the previous studies.

The severity of infections, hematological derangements (NLR, PLR), and mortality increased sharply with age. This trend was particularly evident for critical infection, in-hospital complications, and mortality, which remained low in patients under 50 but increased rapidly in those over 50. It has been well established that patients of advanced age are more susceptible to COVID-19 mortality.4346

Regarding the clinical outcome of patients based on recovery time, we found that delayed recovery (HLOS> seven days) was associated with advanced age, prolonged ICU stay, requiring mechanical ventilation, and higher mortality. A significantly higher proportion of the older population with prolonged HLOS had comorbidities, suggesting that advanced age and associated comorbidities require necessitate longer hospitalization and confer a greater risk of mortality.47 Moreover, a higher mean PLR in our cohort was significantly associated with delayed recovery. While NLR showed a modest and suggestive increase in the odds of delayed recovery, the association was non-significant. Studies have shown that HLOS is age-dependent.48 We could not find studies evaluating the impact of NLR and PLR as prognostic markers of early versus delayed recovery.

Limitations

Some limitations may have affected the study and warrant consideration. This retrospective analysis did not document the patient’s follow-up. Additionally, while input data were most complete at the national level, but the generalizability of the results may be constrained by variations within Qatar’s highly diversified population. In addition, the selection bias, and power of the study cannot be ignored; a larger sample would better size to reflect the prognostic significance of NLR/PLR in the prognosis of patients with COVID-19. Furthermore, the cycle threshold (Ct) value has been proposed as a potential prognostic indicator in patients with COVID-19. Although Ct data were unavailable in this study, combining NLR/PLR with Ct findings in future research could refine the prognostic evaluation of COVID-19 patients. Another notable limitation of our study was the lack of data on respiratory function parameters, specifically arterial oxygenation indices such as the PaO2/FiO2 ratio. Since hypoxemia is a key determinant of disease progression and mortality, the absence of such data may have limited our ability to fully adjust for respiratory status in the multivariable models or correlate inflammatory markers with the degree of pulmonary dysfunction. In addition, the lack of consistent documentation on types of ventilatory support modalities (non-invasive versus invasive ventilation) limited our ability to correlate inflammatory markers with the degree of pulmonary dysfunction and disease severity. Lastly, a prospective study should ideally test the predictive value of NLR and PLR longitudinally. Despite these limitations, our study tailored to the complexity of the early pandemic period, reproduces the key biochemical trends, and offers valuable insights into the prognostic utility of NLR and PLR in COVID-19 patients.

Although neither marker emerged as an independent predictor of mortality in multivariable analysis, their early association with adverse outcomes supports their role as practical tools for initial risk stratification. The absence of independent predictive value likely reflects the multifactorial nature of COVID-19 progression, influenced by host factors such as age, comorbidities, and immune response. Taken together, our findings contribute timely evidence from the initial phase of the pandemic and underscore the nuanced role of inflammation-based hematological markers in predicting not only mortality but also recovery patterns and healthcare needs, particularly in younger or ethnically diverse populations.

Conclusion

In this retrospective study conducted during the early peak of the COVID-19 pandemic, we demonstrate that admission levels of NLR and PLR are associated with disease severity and clinical outcomes in a predominantly young and ethnically diverse population. While neither marker independently predicted mortality in multivariable analysis, patients with higher NLR and PLR levels were associated with delayed recovery, ICU admissions, and intubation, whereas an enhanced NLR was associated with considerably higher mortality in older COVID-19 patients. However, none of these two parameters was found to be an independent predictor for death. These findings highlight the potential utility of NLR and PLR as accessible, cost-effective tools for early risk stratification, particularly in resource-limited or surge settings.

Ethics and consent

This study was approved by the Research Ethics Committee of the Medical Research Center, Hamad Medical Corporation (HMC), Doha, Qatar (MRC-01-20-672 & MRC-05-213) on 29 Sep 2020. A waiver of consent was granted for this retrospective study, as there was no direct contact was made with the participants, and the data were collected anonymously.

Authors’ contributions

All authors have substantially contributed to the acquisition, analysis, and interpretation of data for the work, drafting the work or revising it critically for important intellectual content, and final approval of the version to be published.

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El-Menyar A, Khan NA, Asim M et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio predicting hospital length of stay and mortality in young COVID-19 patients: A retrospective study [version 2; peer review: 1 approved, 1 approved with reservations]. F1000Research 2025, 13:446 (https://doi.org/10.12688/f1000research.146814.2)
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Roberto Paganelli, International Medical University in Rome, UniCamillus, Rome, Italy 
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The article is acceptable ... Continue reading
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Paganelli R. Reviewer Report For: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio predicting hospital length of stay and mortality in young COVID-19 patients: A retrospective study [version 2; peer review: 1 approved, 1 approved with reservations]. F1000Research 2025, 13:446 (https://doi.org/10.5256/f1000research.184107.r397254)
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Reviewer Report 04 Jun 2025
Roberto Paganelli, International Medical University in Rome, UniCamillus, Rome, Italy 
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This is a retrospective study of COVID-19 patients' outcome at a group of Hospitals in Qatar in 2020, at the beginning of the pandemic. The authors seeked to evaluate the association of NLR and PLR at admission with mortality and ... Continue reading
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Paganelli R. Reviewer Report For: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio predicting hospital length of stay and mortality in young COVID-19 patients: A retrospective study [version 2; peer review: 1 approved, 1 approved with reservations]. F1000Research 2025, 13:446 (https://doi.org/10.5256/f1000research.160935.r385519)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Reviewer Report 06 Jun 2024
Lorenzo Malatino, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy 
Ivan Isaia, Department of Clinical and Experimental Medicine, University of Catania, Catania, Catania, Italy 
Approved with Reservations
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This paper by El Menyar et al. presents a retrospective multicenter survey conducted in a large cohort of young patients with Covid-19 disease. The key messages are: 1) elevated NLR and PLR levels are associated with longer hospitalization, increased ICU ... Continue reading
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Malatino L and Isaia I. Reviewer Report For: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio predicting hospital length of stay and mortality in young COVID-19 patients: A retrospective study [version 2; peer review: 1 approved, 1 approved with reservations]. F1000Research 2025, 13:446 (https://doi.org/10.5256/f1000research.160935.r282772)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 07 Jul 2025
    Ayman El-Menyar, Clinical Research, Trauma & Vascular Surgery Section, Hamad Medical Corporation, Doha, Qatar
    07 Jul 2025
    Author Response
    I would like to thank the reviewer for their thoughtful comments and for engaging with our research. We appreciate the opportunity to address your queries and provide further clarification on ... Continue reading
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  • Author Response 07 Jul 2025
    Ayman El-Menyar, Clinical Research, Trauma & Vascular Surgery Section, Hamad Medical Corporation, Doha, Qatar
    07 Jul 2025
    Author Response
    I would like to thank the reviewer for their thoughtful comments and for engaging with our research. We appreciate the opportunity to address your queries and provide further clarification on ... Continue reading

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Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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