Prognostic Value of Immune-Inflammatory Index in PSI IV-V Patients with COVID-19

Han, Rui; Su, Honghui; Guo, Gangwen; Wang, Qiao; Ma, Jiahui; Li, Zhenxing; Huang, Shitong; Ni, Yuncheng; Hu, Rong; Huang, Dong; Zhou, Haocheng

doi:https://doi.org/10.1155/2021/9987931

BioMed Research International

On this page

Abstract Introduction Methods Results Discussion Conclusion Data Availability Conflicts of Interest Authors’ Contributions References Copyright Related Articles

Research Article | Open Access

Volume 2021 | Article ID 9987931 | https://doi.org/10.1155/2021/9987931

Prognostic Value of Immune-Inflammatory Index in PSI IV-V Patients with COVID-19

Rui Han,^1,2Honghui Su,^1,2Gangwen Guo,^1,2Qiao Wang,¹Jiahui Ma,¹Zhenxing Li,¹Shitong Huang,¹Yuncheng Ni,¹Rong Hu,¹Dong Huang,¹and Haocheng Zhou¹

Academic Editor: Mario Frías

Received01 Apr 2021

Accepted04 Aug 2021

Published19 Aug 2021

Abstract

Objective. Respiratory failure is the leading cause of mortality in COVID-19 patients, characterized by a generalized disbalance of inflammation. The aim of this study was to investigate the relationship between immune-inflammatory index and mortality in PSI IV-V patients with COVID-19. Methods. We retrospectively reviewed the medical records of COVID-19 patients from Feb. to Apr. 2020 in the Zhongfa Xincheng Branch of Tongji Hospital, Wuhan, China. Patients who presented high severity of COVID-19-related pneumonia were enrolled for further analysis according to the Pneumonia Severity Index (PSI) tool. Results. A total of 101 patients diagnosed with COVID-19 were identified at initial research. The survival analysis revealed that mortality of the PSI IV-V cohort was significantly higher than the PSI I-III group (). The overall mortality in PSI IV-V patients was 32.1% (9/28). The fatal cases of the PSI IV-V group had a higher level of procalcitonin () and neutrophil-to-lymphocyte ratio () compared with the survivors. Procalcitonin was the most sensitive predictor of mortality for the severe COVID-19 population with area under receiver operating characteristic curve of 0.78, higher than the neutrophil-to-lymphocyte ratio (0.75) and total lymphocyte (0.68) and neutrophil (0.67) counts. Conclusion. Procalcitonin and neutrophil-to-lymphocyte ratio may potentially be effective predictors for mortality in PSI IV-V patients with COVID-19. Increased procalcitonin and neutrophil-to-lymphocyte ratio were associated with greater risk of mortality.

1. Introduction

The rapid spread of the Coronavirus Disease 2019 (COVID-19) epidemic has affected almost 190 million people across the world since December 2019. Respiratory failure is the leading cause of mortality in COVID-19, accounting for more than 56% of mortalities in hospitalized patients [1]. The risk factors of mortality include obesity, smoking, comorbid condition, and advancing age [2–5]. Early recognition of a severe case is essential to improve the clinical outcome and reduce mortality [6].

Pneumonia Severity Index (PSI) is a well-established severity assessment tool, which has been widely used to evaluate the severity of pneumonia caused by a bacterial or viral pathogen [7, 8]. The PSI scoring tool is based on 20 demographic, comorbid, and clinical variables. Higher PSI scores indicate greater risk of adverse outcome, such as ICU admission, mechanical ventilation, and mortality. The overall mortality rate ranged from 9 to 27% in severe pneumonia patients (defined as PSI class IV-V) [9]. Recently, PSI has been applied in severity assessment for COVID-19 patients. PSI could provide moderate to good predictive value in the mortality rate of COVID-19 [10, 11]. However, many fatal cases are asymptomatic or present mild symptoms after viral infection [4]. Thus, the criteria of real “severe cases” classified by the PSI system needs to be reconsidered.

One key feature of a fatal COVID-19 case is the generalized disbalance of inflammation. The latest systematical review has suggested the prognostic value of immune-inflammatory parameters in the progression of COVID-19 [12]. Specifically, severe COVID-19 patients are likely to present elevated levels of white blood cell (WBC), neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), D-dimer, procalcitonin (PCT), C-reaction protein (CRP), and erythrocyte sedimentation rate (ESR) [11, 13–18]. On the other hand, the total lymphocyte count is decreased in severe cases [19, 20]. However, few studies have focused on the potential role of immune-inflammatory index in severe pneumonia patients with COVID-19. In this study, we analyzed the relationship between immune-inflammatory parameter and mortality in PSI IV-V patients with COVID-19.

2. Patients and Methods

2.1. Study Design

We conducted a retrospective review of all adult patients admitted to one temporary ward in the Zhongfa Xincheng Branch of Tongji Hospital, temporarily built for the management of COVID-19 patients between Feb. and Apr. 2020. The study was conducted in accordance with the Declaration of Helsinki and approved by the Third Xiangya Hospital. Due to the retrospective nature of the study, consent could be waived. The study was performed by one of the medical assistance teams from the Third Xiangya Hospital, Hunan, Changsha. This medical term was responsible for 54 beds in the ward. Severe and critically ill patients were transferred to one ICU with 30 beds if needed.

2.2. Patient Selection

All the enrolled patients had clear epidemic history, who were from the Wuhan district in the last 14 days before admission. In addition to contact history, COVID-19 patients either presented abnormal pulmonary CT imaging decribed as previously [21] or showed a positive PCR test for COVID-19.

2.3. Data Collection

One standard data collection form was used to collect the information of enrolled patients. with respect to the demographic, clinical, laboratory, and radiographic data. The first data available following admission was recorded and applied for further analysis. Missing data was assumed to be at normal range based on the regular principle of practice. Peripheral blood was obtained for the test of white blood cell (WBC), neutrophil, and lymphocyte counts; neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and procalcitonin.

2.4. Calculation of Pneumonia Severity Index

The Pneumonia Severity Index (PSI), also known as the PORT score was initially developed by Fine et al. to evaluate the severity of disease [9]. The calculation of PSI scores is based on 20 demographic, comorbid, and clinical variables. Patients were stratified into five risk categories according to the PSI scores. Patients with PSI class IV-V were considered as severe pneumonia, who should be admitted for further treatment.

2.5. Statistical Analysis

The Student -test, Mann–Whitney test, Chi-squared test, and the Fisher exact test were applied when appropriate. The Kaplan–Meier methods and log rank tests were used to determine survival curves for PSI I-III and IV-V patients. The receiver operator characteristic (ROC) curve was plotted using the variables of each immune-inflammatory index and the area under the curve (AUC) was calculated. Statistical significance was set at . Data were analyzed using Prism v8 (GraphPad, San Diego, CA, USA). Logistic analysis was performed by MATLAB vR2018b (MathWorks, Natick, MA, USA).

3. Results

3.1. Correlation between the PSI Scores and COVID-19 Severity

101 patients diagnosed with COVID-19 were confirmed at initial search. The COVID-19 patients were classified into two groups according to the PSI scores. That is, 72.3% of the patients (73 of 101) presented mild symptoms (PSI I-III) at admission. 28 (27.7%) patients were classified into PSI IV-V (Figure 1). Next, we compared the survival curves for each group (Figure 2). The findings showed that those with higher PSI scores had a greater mortality and shorter survival duration than the mild symptom cohort (). Specifically, most PSI IV-V patients died within 10 days after admission. The majority of fatal cases occurred within 30 days.

3.2. Demographics of the PSI IV-V Patients

The PSI IV-V cohort was divided into two subgroups based on the clinical outcome (Table 1). Nineteen (67.9%) patients survived, and nine (32.1%) passed away. The average age was and years for the survivor and mortality groups, respectively. Hypertension was the most common comorbidity in all enrolled patients (). The incidence of hypoxemia () was significantly associated with fatal outcome (). As for the immune-inflammatory parameter, the median concentration of procalcitonin was 0.12, 0.31 for the survivor and nonsurvivor groups. The risk of adverse outcome also increased with higher neutrophil-to-lymphocyte ratio, as shown in Table 1. However, the difference in total white blood cell, neutrophil, and lymphocyte counts and C-reaction protein was not significant in this study.

3.3. Performance of Immune-Inflammatory Index in Prediction for Mortality

The predictive performance of each immune-inflammatory parameter at different cut-off values for COVID-19 mortality is given in Table 2. PCT and neutrophil counts gave similar predictive sensitivity for COVID-19 mortality at all cut-offs. In addition, PCT provided the highest NPV in fatality prediction (100%, 86.7%, and 77.3%).

The ROC curves for prediction of COVID-19 mortality for each immune-inflammatory parameter are shown in Table 2 and Figure 3. The area under ROC curve of PCT was 0.78 (95% CI: 0.60 to 0.96), which was higher than the NLR (AUC: 0.75; 95% CI: 0.56 to 0.95), neutrophil (AUC: 0.67; 95% CI: 0.44 to 0.89), and lymphocyte counts (AUC: 0.68; 95% CI: 0.56 to 0.95).

4. Discussion

Respiratory failure is the most common and fatal complication in severe pneumonia patients with COVID-19. One key feature of the severe cases is the generalized disorder of the immune system, which subsequently contributes to the disease progression. Thus, it is essential to determine the relationship between dysfunctional immune responses and COVID-19 mortality, especially for those with severe pneumonia.

To elucidate the risk factor for COVID-19 mortality, we retrospectively reviewed the medical records of 101 patients. By introducing the well-established severity assessment tool (Pneumonia Severity Index (PSI)), patients were classified into two subgroups. Patients who presented with mild-moderate pneumonia were scored with PSI class I to III, and severe cases were scored with PSI class IV to V. Consistent with a previous study [9], the risk of COVID-19 mortality increased significantly with higher PSI scores. The general mortality ratio of COVID-19 patients was 2.7% (2 out of 73) for the nonsevere group and 32.1% (9 out of 28) for the severe cohort. Our finding suggests that COVID-19 patients presented greater risk of adverse clinical outcome compared with other typical community-acquired pneumonia [22, 23]. Likewise, recent studies [10, 11] have demonstrated moderate to good predictive performance of the PSI tool, in prediction for clinical outcome among the COVID-19 population. However, the validation of additional index such as erythrocyte sedimentation rate added into the PSI tool remains controversial [11].

The potential diversity of immune responses to SARS-CoV-2 is associated with the disease severity [24]. The characterized feature of immune dysfunction includes increased white blood cell and neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), C-reaction protein, erythrocyte sedimentation rate (ESR), and reduction of total lymphocyte counts [12]. However, previous data mainly focus on the general infected population with mild to severe symptoms. The prognostic value of these immune-inflammatory parameter in severe COVID-19 patients remains uncertain. In this study, we found that the difference of WBC and neutrophil counts and CRP is not significant in severe cases with COVID-19. Only PCT and NLR are sensitive predictors for mortality. Given that only severe pneumonia cases were included, the optimal cut-off threshold of NLR (8.3) for mortality was much higher than the value () reported previously [14]. Thus, the higher levels of PCT and NLR may be effective predictors of COVID-19 death, especially for the severe pneumonia cases. In addition to COVID-19, accruing evidence has demonstrated that NLR can be a useful biomarker of cerebral infarct [25], cerebral hemorrhage [26, 27], major cardiac events [28], cancers [29], sepsis, and other infectious pathologies [30]. The easy and well-established test may help physicians improve the clinical decision in time.

Our study has several limitations. First, the number of participants was relatively small. We think it necessary to examine the validation of immune-inflammatory parameters in a larger cohort, especially for the severe cases. Second, some important immune-inflammatory parameters, such as interleukin 6 and tumor necrosis factor- (TNF-) α, were not evaluated due to the retrospective study design. Finally, we only observed the clinical outcome during hospitalization; the long-term outcome may be useful for the decision of public health strategy in the future.

5. Conclusion

Taken together, our findings suggest that procalcitonin and neutrophil-to-lymphocyte ratio may potentially be an effective predictor for mortality in PSI IV-V patients with COVID-19. Increased levels of procalcitonin and neutrophil-to-lymphocyte ratio were associated with greater risk of mortality.

Data Availability

The authors declare that all the data supporting the findings of this study are available from the corresponding author upon reasonable request.

Conflicts of Interest

The authors declare that this research was conducted in the absence of commercial or financial relationships that could be construed as a potential conflict of interest.

Authors’ Contributions

H. Zhou and R. Han designed the study. R. Han, H. Su, and G. Guo collected the data. Q. Wang, J. Ma, S. Huang, Y. Ni, and R. Hu conducted data analyses. H. Zhou and Q. Wang wrote the manuscript. Rui Han and Honghui Su contributed equally to this paper.

References

Q. Ruan, K. Yang, W. Wang, L. Jiang, and J. Song, “Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China,” Intensive Care Med., vol. 46, no. 5, pp. 846–848, 2020.
View at: Publisher Site | Google Scholar
T. Guo, Y. Fan, M. Chen et al., “Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19),” JAMA Cardiology, vol. 5, no. 7, pp. 1–8, 2020.
View at: Google Scholar
D. Wang, B. Hu, C. Hu et al., “Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China,” Journal of the American Medical Association, vol. 323, no. 11, pp. 1061–1069, 2020.
View at: Publisher Site | Google Scholar
Z. Wu and J. M. McGoogan, “Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention,” Journal of the American Medical Association, vol. 323, no. 13, pp. 1239–1242, 2020.
View at: Publisher Site | Google Scholar
F. Zhou, T. Yu, R. Du et al., “Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study,” Lancet, vol. 395, no. 10229, pp. 1054–1062, 2020.
View at: Publisher Site | Google Scholar
X. Li and X. Ma, “Acute respiratory failure in COVID-19: is it “typical” ARDS?” Critical care., vol. 24, no. 1, p. 198, 2020.
View at: Publisher Site | Google Scholar
For Beijing Network for Adult Community-Acquired Pneumonia (BNACAP), J. X. Qu, L. Gu et al., “Viral etiology of community-acquired pneumonia among adolescents and adults with mild or moderate severity and its relation to age and severity,” BMC Infectious Diseases, vol. 15, no. 1, 2015.
View at: Publisher Site | Google Scholar
C. Cilloniz, S. Ewig, E. Polverino et al., “Microbial aetiology of community-acquired pneumonia and its relation to severity,” Thorax, vol. 66, no. 4, pp. 340–346, 2011.
View at: Publisher Site | Google Scholar
M. J. Fine, T. E. Auble, D. M. Yealy et al., “A prediction rule to identify low-risk patients with community-acquired pneumonia,” The New England Journal of Medicine, vol. 336, no. 4, pp. 243–250, 1997.
View at: Publisher Site | Google Scholar
G. Fan, C. Tu, F. Zhou et al., “Comparison of severity scores for COVID-19 patients with pneumonia: a retrospective study,” The European Respiratory Journal, vol. 56, no. 3, p. 2002113, 2020.
View at: Publisher Site | Google Scholar
C. Satici, M. A. Demirkol, E. Sargin Altunok et al., “Performance of pneumonia severity index and CURB-65 in predicting 30-day mortality in patients with COVID-19,” International Journal of Infectious Diseases, vol. 98, pp. 84–89, 2020.
View at: Publisher Site | Google Scholar
X. Feng, S. Li, Q. Sun et al., “Immune-inflammatory parameters in COVID-19 cases: a systematic review and meta-analysis,” Frontiers in Medicine, vol. 7, p. 301, 2020.
View at: Publisher Site | Google Scholar
K. Zhao, R. Li, X. Wu et al., “Clinical features in 52 patients with COVID-19 who have increased leukocyte count: a retrospective analysis,” European Journal of Clinical Microbiology & Infectious Diseases, vol. 10, pp. 1–9, 2020.
View at: Google Scholar
J. Liu, Y. Liu, P. Xiang et al., “Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage,” Journal of Translational Medicine, vol. 18, no. 1, p. 206, 2020.
View at: Publisher Site | Google Scholar
R. Hu, C. Han, S. Pei, M. Yin, and X. Chen, “Procalcitonin levels in COVID-19 patients,” International Journal of Antimicrobial Agents, vol. 56, no. 2, p. 106051, 2020.
View at: Publisher Site | Google Scholar
L. Wang, “C-reactive protein levels in the early stage of COVID-19,” Médecine et Maladies Infectieuses, vol. 50, no. 4, pp. 332–334, 2020.
View at: Publisher Site | Google Scholar
Y. Yao, J. Cao, Q. Wang et al., “D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study,” Journal of Intensive Care, vol. 8, no. 1, 2020.
View at: Publisher Site | Google Scholar
I. Lapić, D. Rogić, and M. Plebani, “Erythrocyte sedimentation rate is associated with severe coronavirus disease 2019 (COVID-19): a pooled analysis,” Clinical Chemistry and Laboratory Medicine, vol. 58, no. 7, pp. 1146–1148, 2020.
View at: Publisher Site | Google Scholar
I. Huang and R. Pranata, “Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis,” Journal of Intensive Care, vol. 8, no. 1, 2020.
View at: Publisher Site | Google Scholar
L. Tan, Q. Wang, D. Zhang et al., “Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study,” Sig Transduct Target Ther., vol. 5, no. 1, p. 33, 2020.
View at: Publisher Site | Google Scholar
H. Shi, X. Han, N. Jiang et al., “Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study,” The Lancet Infectious Diseases, vol. 20, no. 4, pp. 425–434, 2020.
View at: Publisher Site | Google Scholar
J. D. Chalmers, A. Singanayagam, A. R. Akram et al., “Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia. Systematic review and meta-analysis,” Thorax, vol. 65, no. 10, pp. 878–883, 2010.
View at: Publisher Site | Google Scholar
M. A. Kim, J. S. Park, C. W. Lee, and W. I. Choi, “Pneumonia severity index in viral community acquired pneumonia in adults,” PLoS One, vol. 14, no. 3, article e0210102, 2019.
View at: Publisher Site | Google Scholar
D. Mathew, J. R. Giles, A. E. Baxter et al., “Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications,” Science, vol. 369, no. 6508, p. eabc8511, 2020.
View at: Publisher Site | Google Scholar
M. Świtońska, N. Piekuś-Słomka, A. Słomka, P. Sokal, E. Żekanowska, and S. Lattanzi, “Neutrophil-to-lymphocyte ratio and symptomatic hemorrhagic transformation in ischemic stroke patients undergoing revascularization,” Brain Sciences, vol. 10, no. 11, p. 771, 2020.
View at: Publisher Site | Google Scholar
S. Lattanzi, C. Cagnetti, C. Rinaldi, S. Angelocola, L. Provinciali, and M. Silvestrini, “Neutrophil-to-lymphocyte ratio improves outcome prediction of acute intracerebral hemorrhage,” Journal of the Neurological Sciences, vol. 387, pp. 98–102, 2018.
View at: Publisher Site | Google Scholar
S. Lattanzi, C. Cagnetti, L. Provinciali, and M. Silvestrini, “Neutrophil-to-lymphocyte ratio and neurological deterioration following acute cerebral hemorrhage,” Oncotarget, vol. 8, no. 34, pp. 57489–57494, 2017.
View at: Publisher Site | Google Scholar
C. H. Dong, Z. M. Wang, and S. Y. Chen, “Neutrophil to lymphocyte ratio predict mortality and major adverse cardiac events in acute coronary syndrome: a systematic review and meta-analysis,” Clinical Biochemistry, vol. 52, pp. 131–136, 2018.
View at: Publisher Site | Google Scholar
A. J. Templeton, M. G. McNamara, B. Šeruga et al., “Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis,” JNCI: Journal of the National Cancer Institute, vol. 106, no. 6, 2014.
View at: Publisher Site | Google Scholar
C. P. de Jager, P. T. van Wijk, R. B. Mathoera, J. de Jongh-Leuvenink, T. van der Poll, and P. C. Wever, “Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit,” Critical Care, vol. 14, no. 5, p. R192, 2010.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2021 Rui Han et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

402

Downloads

929

Citations