Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
Case Report
Editorial
Letter to Editor
Letter to the Editor
Mini Review
Original Article
Original Articles
Point of View
Review
Review Article
Short communication
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
Case Report
Editorial
Letter to Editor
Letter to the Editor
Mini Review
Original Article
Original Articles
Point of View
Review
Review Article
Short communication
View/Download PDF

Translate this page into:

Original Article
6 (
2
); 19-26
doi:
10.7324/jhsr.2021.623

Cellular Inflammatory Indices in Hospitalized Nigerian COVID-19 Patients

Department of Chemical Pathology, University of Ibadan, Nigeria
Department of Immunology, University of Ibadan, Nigeria

*Email: drarinolaog64@yahoo.com

Licence
This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0

How to cite this article: Akinwumi JA, Edem FV, Arinola GO. Cellular Inflammatory Indices in Hospitalized Nigerian COVID-19 Patients. J Health Sci Res 2021;6(2):19-26.

Abstract

The pandemicity of coronavirus disease 2019 (COVID-19) necessitated its novel biomarkers in prognosis and monitoring in low resource settings. Changes in total white blood cell counts have been associated with the progression of diseases. This study determined the prognostic value of some cellular inflammatory cells and their indices in relation to duration of hospital admission, gender, and age of COVID-19 patients. This longitudinal and case–control study determined blood cell components (total white blood cells (TWBC), neutrophil, lymphocyte, monocyte, and platelet) and inflammatory indices (neutrophil lymphocyte ratio [NLR], lymphocyte monocyte ratio [LMR], platelet lymphocyte ratio [PLR], derived NLR [DNLR], and systemic immune inflammatory index [SII]) in 95 symptomatic hospitalized COVID-19 patients and 45 COVID-19 free controls. These parameters were related to age, sex, and days of admission of the patients. Blood samples obtained were analyzed using hematological autoanalyzer (Sysmex XN-450) and indices calculated. Data were analyzed using the Statistical Package for the Social Sciences (SPSS Inc., USA) version 20.0. The mean platelet count (P = 0.016) and PLR (P = 0.000) were significantly lower while TWBC counts (P = 0.013) were significantly increased in COVID-19 patients compared with control. The mean TWBC count (P = 0.030) and SII (P = 0.029) were significantly increased while lymphocyte count (P = 0.015) and LMR (P = 0.026) were significantly decreased in COVID-19 patients at discharge compared with COVID-19 patients at admission. The mean neutrophil count (P = 0.048), PLR (P = 0.015), and SII (P = 0.022) were significantly lower while mean lymphocyte count (P = 0.026) was significantly higher in COVID-19 patients aged <40 years compared with patients aged ≥40 years. This study concluded that inflammatory response is a phenomenon in COVID-19 patients especially in patients ≥40 years of age and that this inflammation persist till discharge, though gender has no influence on cellular inflammatory indices of COVID-19 patients.

Keywords

Hematological parameters
Inflammation
Prognosis
Severe acute respiratory syndrome coronavirus 2 infection

Introduction

Severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) disease called coronavirus disease 2019 (COVID-19) is characterized by cytokine storm, acute respiratory distress syndrome, and systemic inflammation–related pathology1. Coronaviruses (CoVs) are positive sense, single-stranded RNA, and spherical shaped virus having non-segmented club-like projecting spikes on their surface. SARS-CoV-2 binds to the cell surface Angiotensin Converting Enzyme 2 (ACE2) to infect humans2 and spike glycoprotein promotes its entry into the host target cells. Active replication and release of the virus in the lung cells lead to non-specific symptoms such as fever, myalgia, headache, and respiratory symptoms3. The binding of the virus with host cell receptors is a significant determinant for the pathogenesis of infection. Following viremia, SARS-CoV-2 primarily affects the tissues expressing high levels of ACE2 including the lungs, heart, and gastrointestinal tract4. Approximately 7–14 days from the onset of the initial symptoms, there is a surge in the clinical manifestations of the disease with a pronounced systemic increase of inflammatory mediators and cytokines5.

Changes in blood cell counts and functions have important roles in early diagnosis of diseases, considering the information it provides during various disease conditions6. Inflammatory response plays a critical role in the progression of COVID-19 disease and hematological parameters had been reported to be altered by the coronavirus in infected patients7. Blood cells such as neutrophils, lymphocytes, and thrombocytes are essential in the pathophysiology of inflammation, immune responses, homeostasis, and oncogenesis8-10. Systemic inflammation changes the features of circulating blood cells and this has been suggested to be biomarkers for assessment of inflammatory activity11. Total white blood cells (TWBC) count, neutrophil, lymphocyte, monocyte, basophil, eosinophil, platelet count (PLT), and their ratios have been used as inflammatory markers in health conditions10,12,13. Some inflammatory factors such as cytokines (interleukin [IL]-6 and IL-10) and C- reactive protein have been found to be raised in COVID-19 patients14. Furthermore, COVID-19 infection affects the hematopoietic system with hematological abnormalities such as anemia, leucopenia, leukocytosis, thrombocytopenia, lymphocytopenia, and neutrophilia15-17.Since the number and activities of these blood cells have been reported to change in COVID-19 patients7, this present study conjectured that hematological parameters (total- and differential- white blood cell counts), calculated inflammation parameters (neutrophil: lymphocyte ratio [NLR], lymphocyte: monocyte ratio [LMR], platelet: lymphocyte ratio [PLR], and Derived NLR [DNLR]) and systemic immune-inflammatory index (SII) might be useful prognostic predictors of COVID-19 disease.

Materials and Methods

Participants

This study involved a total of 95 hospitalized COVID-19 patients aged between 15 and 80 years (28 females and 67 males) was carried out between April 27, 2020, and June 20, 2020. They were confirmed to be infected with SARS-CoV-2 using nucleic acid reverse-transcriptase polymerase chain reaction (RT-PCR) on nasal and pharyngeal swab specimens according to the WHO guideline18. Patients with co-morbidities/blood cells disorders and those who did not consent for follow-up study were excluded among COVID-19 patients. The control subjects consisted of 45 uninfected healthy adults (25 males and 20 females) aged between 18 and 65 years.

Sample collection

3 ml venous blood sample was collected using pyrogen-free needle and syringes from each participant and dispensed into K3-EDTA (Potassium Ethylene Diamine Tetra Acetic Acid) bottle and immediately analyzed using hematological auto analyzer of specification Sysmex XN-450. Patients’ blood sample was collected on the day of admission and at the point of discharge when patients had been tested negative after 5–15 days for SARS-CoV-2 virus using nucleic acid RT-PCR.

Autoanalyzer principle

This was done using the Sysmex auto-analyzer. The Sysmex XN-450 is a multi-parameter quantitative automated hematology analyzer whose function is based on the hydrodynamically focused impedance measurement, the flow cytometry method (using a semiconductor laser) and the SLS-hemoglobin method19.

Inflammatory indices

NLR, LMR, PLR, DNLR, and SII were determined using the following equations20:

 NLR = Absolute Number of Neutrophil  Absolute Number of Lymphocyte  NLR = Absolute Number of Neutrophil   Absolute Neutrophl Count PLR = Absolute Numberof Platelet  Absolute Number of Lymphocyte  LMR = Absolute Numberof Lymphocyte  Absolute Number of monocyte  SII = Platelets Count × Neutrophil Count  Lymphocytes Count 

Statistical analysis

Data obtained were analyzed using Statistical Package for the Social Science (SPSS) (version 20). Gender, age, and days of admission were presented as frequencies and percentages in each category. Blood cell counts and inflammatory indices were presented as Mean ± SD. Mean between two groups were compared using Student’s t-test. Pearson’s correlation was used to test the relationship between variables. Difference was considered significant when P < 0.05.

Ethical consideration

The study was conducted after obtaining approval from the University of Ibadan/University College Hospital (UI/ UCH) Joint Ethics Review Committee (UI/EC/20/0233) and informed consent was obtained from each study participant.

Results

Demography and length of hospital admission of the 95 COVID-19 patients are shown in Table 1. Most of the COVID-19 patients aged <40 years (72.6%) and were employees of private establishments (45.3%). Most of the patients spent ≤10 days (60%) and were males (71%) (Table 1). Blood cell components and cellular inflammatory indices of COVID-19 patients were compared with un-infected controls as shown in Table 2. The mean levels of PLT and PLR were significantly lower in COVID-19 patients (P = 0.016 and P = 0.000, respectively) compared with control. Mean TWBC count was significantly higher in COVID-19 patients compared with control (P = 0.013) (Table 2). The mean TWBC count (P = 0.030) and SII (P = 0.029) were significantly increased in COVID-19 patients at discharge compared with those at admission. There were significant decreases in lymphocyte count and LMR of COVID-19 patients at discharge compared with COVID-19 patients at admission (P = 0.015 and P = 0.026), respectively (Table 3). There were no significant differences in the mean ages, blood cell components, and cellular inflammatory indices of males COVID-19 patients compared with females COVID-19 patients (Table 4). The mean neutrophil count (P = 0.048), PLR (P = 0.015), and SII (P = 0.022) was significantly lower in COVID-19 patients aged <40 years compared with patients aged ≥40 years. However, the mean lymphocyte count (P = 0.026) was significantly higher in COVID-19 patients aged <40 years compared with those aged ≥40 years (Table 5).

Table 1. Demography and length of hospital admission of COVID-19 patients
Variable Categories Frequency Percentage
Gender Male 67 71
Female 28 29
Age (years) <40 years 69 72.6
≥ 40 years 26 27.4
Occupation Self employed 28 29.5
Private 43 45.3
Civil servant 14 14.7
Unemployed 10 10.5
DOA ≤10 days 57 60
>10 days 38 40

DOA: Days of admission

Table 2. Comparison of age, blood cell components and cellular inflammatory indices in COVID-19 patients with un-infected controls
Variables COVID-19 Positive (n=70) COVID-19 Negative (n=45) t-values P-values
Age (years) 33.80±11.80 37.11±9.06 −1.111 0.270
TWBC count (×109/L) 5.58±1.78 4.45±1.97 2.530 0.013*
Lymphocyte count (%) 48.21±12.78 45.34±11.92 1.291 0.200
Monocyte count (%) 7.68±3.86 9.24±3.76 −1.680 0.097
Neutrophil (%) 40.07 ±13.22 46.14±13.65 −1.454 0.118
Platelet count (×109/L) 229.89 ± 88.73 305.35 ± 197.50 −2.459 0.016*
NLR 0.98±0.66 0.77±0.49 1.417 0.160
DNLR 0.77±0.49 0.61±0.39 1.416 0.161
PLR 94.98±44.24 162.96±109.72 −4.137 0.000*
LMR 7.85 ± 7.36 6.30±2.58 0.983 0.328
SII (×109/L) 239 ± 200 229 ± 187 0.204 0.839

TWBC: Total white blood cell count, NLR: Neutrophil lymphocytes ratio, DNLR: Derived neutrophil lymphocyte ratio, PLR: Platelet-lymphocyte ratio, LMR: Lymphocyte monocyte ratio, SII: Systemic immune inflammatory index. *Significant at P<0.05

Table 3. Comparison of blood cell components and cellular inflammatory indices in COVID-19 patients at admission and at discharge
Variables At admission (n=25) At discharge (n=25) t – values P– values
TWBC count (×109/L) 5.25±0.67 6.34±1.25 −2.519 0.030*
Lymphocyte count (%) 53.42±12.80 47.16±8.60 2.939 0.015*
Monocyte count (%) 7.46±2.42 7.30±1.31 0.210 0.838
Neutrophil (%) 34.94±13.16 41.10±7.68 −1.932 0.082
Platelet count (×109/L) 236.55±88.73 241.64±63.89 −0.223 0.828
NLR 0.73±0.38 0.92±0.32 −2.113 0.061
DNLR 0.59±0.30 0.72±0.23 −1.685 0.123
PLR 89.31±34.31 100.78±29.95 −1.550 0.152
LMR 7.97±3.76 5.76±2.21 2.612 0.026*
SII (×109/L) 173±105 283±163 −2.557 0.029*

TWBC: Total white blood cell count, NLR: Neutrophil lymphocyte ratio, DNLR: Derived neutrophil lymphocyte ratio, PLR: Platelet lymphocyte ratio, LMR: Lymphocyte monocyte ratio, SII: Systemic immune inflammatory index. *Significant at P<0.05

Table 4. Comparison of age, blood cell components and cellular inflammatory indices in males with females COVID-19 patients
Variables Males (n=49) Females (n=21) t – values P– values
Age(years) 34.03±10.66 33.25±14.59 0.219 0.827
TWBC count (×109/L) 5.23±1.73 6.20±1.80 −1.854 0.069
Lymphocyte count (%) 50.30±12.22 45.95±15.18 1.112 0.271
Monocyte count (%) 8.38±4.65 6.66±1.79 1.428 0.159
Neutrophil (%) 36.68±12.03 44.14±14.92 −1.936 0.058
Platelet count(×109/L) 226.16±100.23 221.19±63.95 0.183 0.856
NLR 0.86±0.62 1.15±0.66 −1.589 0.118
DNLR 0.66±0.46 0.91±0.48 −1.778 0.081
PLR 95.00±50.84 88.50±35.71 0.464 0.645
LMR 8.17±9.25 7.48±3.52 0.289 0.774
SII (×109/L) 206±197 268±193 −1.073 0.288

TWBC: Total white blood cell count, NLR: Neutrophil lymphocyte ratio, DNLR: Derived neutrophil lymphocyte ratio, PLR: Platelet lymphocyte ratio, LMR: Lymphocyte monocyte ratio, SII: Systemic immune inflammatory index. *Significant at P<0.05

Table 5. Comparison of age, blood cell components and cellular inflammatory indices of COVID-19 patients with age<40 with those ≥ 40 years
Variables Age <40years (n= 51) Age ≥40 years (n= 19) t – values P– values
Age (years) 27.88±6.57 49.60±7.02 −10.721 0.000
TWBC count (×109/L) 5.47±1.88 5.66±1.58 −0.344 0.732
Lymphocyte count (%) 51.47±13.33 42.63±10.71 2.297 0.026*
Monocyte count (%) 7.60±4.27 8.56±3.57 −0.766 0.447
Neutrophil count (%) 36.68±13.40 44.61±11.41 −2.024 0.048*
Platelet count (×109/L) 214.82±74.40 250.33±122.28 −1.301 0.199
NLR 0.85±0.58 1.20±0.72 −1.856 0.069
DNLR 0.67±0.44 0.90±0.54 −1.659 0.103
PLR 83.65±31.57 117.57±68.09 −2.511 0.015*
LMR 8.85±6.13 5.70±2.43 1.313 0.195
SII (×109/L) 187±157 322±254 −2.364 0.022*

TWBC: Total white blood cell count, NLR: Neutrophil lymphocyte ratio, DNLR: Derived neutrophil lymphocyte ratio, PLR: Platelet lymphocyte ratio, LMR: Lymphocyte monocytes ratio, SII: Systemic immune inflammatory index. *Significant at P<0.05

Blood cell components and inflammatory indices were not significantly different in COVID-19 patients with ≤10 days of admission compared with those who spent >10 days on admission (Table 6). Pearson’s correlation showed significant negative correlation between days of admission with LMR (r = −0.290, P = 0.035) or positive correlation between days of admission with monocyte (r = 0.039, P = 0.003) (Table 7).

Table 6. Comparison of age, blood cell components and cellular inflammatory indices of COVID-19 patients based on their days of admission
Variables DOA ≤10 days (n=42) DOA >10 days (n=28) t – values P– values
Age (years) 34.22±11.24 33.22±12.78 0.308 0.759
TWBC count (×109/L) 5.58±2.01 5.44±1.48 0.264 0.793
Lymphocyte count (%) 51.78±13.41 45.28±12.14 1.833 0.073
Monocyte count (%) 7.19±2.53 8.78±5.46 −1.430 0.159
Neutrophil count (%) 37.17±13.12 41.21±13.40 −1.109 0.272
Platelet count (×109/L) 233.81±85.88 212.39±96.77 0.858 0.395
NLR 0.85±0.58 1.07±0.70 −1.206 0.233
DNLR 0.68±0.43 0.81±0.53 −1.021 0.312
PLR 90.59±41.27 96.42±53.80 −0.451 0.654
LMR 9.37±6.19 6.13±2.36 1.491 0.142
SII (×109/L) 208±181 246±216 −0.709 0.481

TWBC: Total white blood cell count, TC: Total cholesterol, NLR: Neutrophil lymphocyte ratio, DNLR: Derived neutrophil lymphocyte ratio, PLR: Platelet-lymphocyte ratio, LMR: Lymphocyte monocyte ratio, SII: Systemic immune inflammatory index, DOA: Days of admission. *Significant at P<0.05

Table 7. Pearson’s correlation coefficients between age, days of admission with blood cell components, and cellular inflammatory indices of COVID-19 patients
Cellular Inflammatory Indices r P– values
Age
TWBCs 0.068 0.625
LYMPH −0.252 0.066
MONO 0.085 0.540
NEUT 0.245 0.075
PLAT 0.116 0.404
NLR 0.195 0.158
DNLR 0.196 0.155
PLR 0.221 0.108
LMR −0.037 0.794
SII 0.220 0.101
DOA
TWBCs −0.041 0.796
LYMPH −0.210 0.128
MONO 0.396 0.003*
NEUT 0.093 0.505
PLAT 0.076 0.584
NLR 0.120 0.386
DNLR 0.095 0.496
PLR 0.191 0.166
LMR −0.290 0.035*
SII 0.135 0.313

DOA: Days of admission, TWBC: Total white blood cells counts, LYPH: Lymphocyte count, NEUT: Neutrophil count, MONO: Monocyte count, PLT: Platelet count, NLR: Neutrophils-lymphocytes ratio, DNLR: Derived neutrophils-lymphocytes ratio, PLR: Platelet-lymphocytes ratio, LMR: Lymphocytes-monocytes ratio, SII: Systemic immune inflammatory index. *Significant at P<0.05

Discussion

The emergence of a new zoonotic pathogen (SARS-CoV-2), which causes a variety of clinical symptoms collectively termed COVID-19 is of major public health concerns as it is a global pandemic21. However, most infected people are asymptomatic or develop only mild symptoms22. This observation might have been related to non-fatal nature of SARS-CoV-2 strain as previously suggested in hospitalized COVID-19 patients in Ibadan, Nigeria23. In the present study, most (70%) of COVID-19 patients were males and this is consistent with the previous reports23,24. The reduced susceptibility of females to some viral infections could be attributed to the protection from X chromosome and sex hormones, which play an important role in innate and adaptive immunity25.

Our study showed a significant increase in TWBC counts in COVID-19 patients compared with control although this is in contrasts to the reported leucopenia by Guan et al.26. Increased mean TWBCs count was reported to be caused by inflammation27,28 and inflammation is a confirmed phenomenon in COVID-19 patients29, thus increased TWBCs counts is expected in COVID-19 patients. Significant decreases in platelet and PLR were observed in COVID-19 patients compared with controls. This might be due to the stimulation of anti-platelet auto antibodies by SARS-CoV-230, which triggers immune-mediated platelet destruction. Thus, immune complexes formed on the surfaces of platelets predispose platelets to destruction by the reticuloendothelial system. This may suggest that COVID-19 is an immune complex disease which requires further investigations30.

Mean TWBC count and SII in COVID-19 patients at discharge were significantly increased compared with COVID-19 patients at admission. This might be linked with persistence inflammatory responses in COVID-19 patients at discharge. Significant decreases in lymphocytes and LMR were also noted at discharge compared with values at admission. This suggests continuous destruction of lymphocytes in COVID-19 patients at discharge leading to reduced LMR. A significant decrease in lymphocyte was observed in COVID-19 patients older than or equal to 40 years compared with those younger than 40 years of age. Lymphopenia in this age group might have been caused by the invasion and destruction of lymphocytes by SARSCoV-2 in patient’s ≥40 years old as a result of cytokine storm. Cytokine storm characterized by markedly increased levels of interleukins (mostly IL-6, IL-2, IL-7, granulocyte colony stimulating factor, and interferon-γ inducible protein 10) and tumor necrosis factor-alpha promotes lymphocyte apoptosis31,32. Increases in the levels of certain cytokines with ages have been previously reported33. Moreover, cytokine storm and platelet activation had been directly linked34,35, thus, supporting increased PLR in COVID-19 patients ≥40 years.

A significant increase in neutrophil was also observed in COVID-19 patients aged ≥40 years and this corroborate neutrophilia found in COVID-19 disease24,36. Henry et al.37 attributed neutrophilia to a compensatory mechanism due to reduced lymphocytes, monocytes, and eosinophils in COVID-19 patients. It was previously reported that neutrophilia is an expression of the cytokine storm and hyper inflammatory state which has an important pathogenetic role in SARS CoV-2 infection35,38. The SII has been proposed as a prognostic indicator in the follow-up of sepsis39. In this study, SII was found to be significantly higher in COVID-19 patients aged ≥40 years compared to those <40 years. This signifies higher systemic inflammatory reaction in older age groups of COVID-19 patients. Putting together, reduced mean lymphocyte count, increased PLR, high SII and mean neutrophil count in COVID-19 patient’s ≥40 years of age indicated raised inflammation, therefore supporting susceptibility of this age group to severe form of COVID-19 and other inflammatory conditions.

Significant negative correlation between days of admission with LMR showed that inflammation decreases with treatment or hospital stay. In addition, days of admission was positively correlated with monocyte counts. Monocytes and macrophages play key role in tissue repair, phagocytosis and protective immunity40. Thus, the positive correlation of days in admission with monocytes suggests the involvement of monocytes and macrophages in the resolution of COVID-19.

Conclusion

This study concluded that inflammatory response is a phenomenon in COVID-19 patients especially in patients ≥40 years of age and that this inflammation persist till discharge, though gender or duration of admission based on 10 days stratification (>10 days or ≤ 10 days) has no influence on cellular inflammatory indices of COVID-19 patients.

Conflicts of Interest

No conflict of interest is declared.

References

  1. . Coronavirus Disease 2019 (COVID-19) Situation Report-12. Available from: https://www.who.int›docs›situation-reports [Last accessed on 2020 Feb 20
    [Google Scholar]
  2. , , , , , , et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270-3.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , . COVID-19 pandemic-a focused review for clinicians. Clin Microbiol Infect. 2020;26:842-7.
    [CrossRef] [PubMed] [Google Scholar]
  4. , , , , , . Single-cell RNAseq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020;14:185-92.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , . Clinical observation and management of COVID-19 patients. Emerg Microbes Infect. 2020;1:687-90.
    [CrossRef] [PubMed] [Google Scholar]
  6. , . Cecil Textbook of Medicine (17th ed). Philadelphia, PA: W.B. Saunders; .
    [Google Scholar]
  7. , , , , . Study of hematological parameters in patients with coronavirus disease 2019 in Basra. Iraq J Hematol. 2020;9:160.
    [CrossRef] [Google Scholar]
  8. , , , , , , et al. Baseline peripheral blood neutrophil-to-lymphocyte ratio could predict survival in patients with adult polymyositis and dermatomyositis: A retrospective observational study. PLoS One. 2018;13:e0190411.
    [CrossRef] [PubMed] [Google Scholar]
  9. , , , , . The platelet-to-lymphocyte ratio as an inflammatory marker in rheumatic diseases. Ann Lab Med. 2019;39:345.
    [CrossRef] [PubMed] [Google Scholar]
  10. , , , , , , et al. Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio can predict clinical outcomes in patients with metastatic non-small-cell lung cancer treated with nivolumab. J Clin Lab Anal. 2019;33:e22964.
    [CrossRef] [Google Scholar]
  11. , , , , , . Prognostic significance of neutrophil-to-lymphocyte ratio in patients with sepsis: A prospective observational study. Med Inflamm. 2016;2016:8191254.
    [CrossRef] [PubMed] [Google Scholar]
  12. , , , , , , et al. Predictive role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for diagnosis of acute appendicitis during pregnancy. Kaohsiung J Med Sci. 2015;31:591-6.
    [CrossRef] [PubMed] [Google Scholar]
  13. , , , , , . Evaluation of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and red blood cell distribution width-platelet ratio as early predictor of acute pancreatitis in pregnancy. J Matern Fetal Neonatal Med. 2016;29:1476-80.
    [CrossRef] [PubMed] [Google Scholar]
  14. , . Interleukin-6 as a potential biomarker of COVID-19 progression. Med Mal Infect. 2020;50:382-3.
    [CrossRef] [PubMed] [Google Scholar]
  15. . Hematologic parameters in patients with COVID-19 infection: A reply. Am J Hematol. 2020;95:E131-4.
    [CrossRef] [Google Scholar]
  16. , , , , , , et al. Hematological findings and complications of COVID-19. Am J Hematol. 2020;95:834-47.
    [CrossRef] [PubMed] [Google Scholar]
  17. , , , , , , et al. Changes of hematological and immunological parameters in COVID-19 patients. Int J Hematol. 2020;112:553-9.
    [CrossRef] [PubMed] [Google Scholar]
  18. . Diagnosis and Clinical Management of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: An Operational Recommendation of Peking Union Medical College Hospital (V2.0) China: Working Group of 2019 Novel Coronavirus, Peking Union Medical College Hospital; . p. :582-5.
    [CrossRef] [PubMed] [Google Scholar]
  19. . XN-L Series General Information (North American Edition) Kobe, Japan: Sysmex Corporation; .
    [Google Scholar]
  20. , , , , , , et al. The prognostic value of preoperative NLR, d-NLR, PLR and LMR for predicting clinical outcome in surgical colorectal cancer patients. Med Oncol. 2014;31:305.
    [CrossRef] [PubMed] [Google Scholar]
  21. , , , . Public health might be endangered by possible prolonged discharge of SARS-CoV-2 in stool. J Infect Dis. 2020;80:e18-9.
    [CrossRef] [PubMed] [Google Scholar]
  22. , , , , , . Presymptomatic transmission of SARS-CoV-2-Singapore, January 23-march 16, 2020. Morbidity Mortal Wkly Rep. 2020;69:411-5.
    [CrossRef] [PubMed] [Google Scholar]
  23. , , , , , , et al. Demographic attributes of COVID-19 patients in an infectious disease center of Nigeria. Afr J Clin Exper Microbiol. 2021;22:21-7.
    [CrossRef] [Google Scholar]
  24. , , , , , , et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet. 2020;395:507-13.
    [CrossRef] [PubMed] [Google Scholar]
  25. , , . Sexual dimorphism in innate immunity. Clin Rev Allergy Immunol. 2019;56:308-21.
    [CrossRef] [PubMed] [Google Scholar]
  26. , , , , , , et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708-20.
    [CrossRef] [PubMed] [Google Scholar]
  27. , , , , , , et al. Laboratory parameters in detection of COVID-19 patients with positive RT-PCR; a diagnostic accuracy study. Arch Acad Emerg Med. 2020;8:e43.
    [Google Scholar]
  28. . Neutrophil-to-lymphocyte ratio and lymphocyte-to-C reactive protein in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. J Med Virol. 2020;92:1733-4.
    [CrossRef] [PubMed] [Google Scholar]
  29. , , . Respiratory burst functions in COVID-19 Nigerian patients. J Basic Appl Res Biomed. 2021;7:210.
    [CrossRef] [Google Scholar]
  30. , , . Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol. 2020;99:1205-8.
    [CrossRef] [PubMed] [Google Scholar]
  31. , , . Increased TNF-alpha-induced apoptosis in lymphocytes from aged humans: Changes in TNF-alpha receptor expression and activation of caspases. J Immunol. 1999;162:2154-61.
    [CrossRef] [PubMed] [Google Scholar]
  32. , , , , , . IL-19 induces production of IL-6 and TNF-alpha and results in cell apoptosis through TNF-alpha. J Immunol. 2002;169:4288-97.
    [CrossRef] [PubMed] [Google Scholar]
  33. , , , , , . Age and age-related diseases: Role of inflammation triggers and cytokines. Front Immunol. 2018;9:586.
    [CrossRef] [PubMed] [Google Scholar]
  34. , , , , , , et al. Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19. J Med Virol. 2020;92:1533-41.
    [CrossRef] [PubMed] [Google Scholar]
  35. , , . Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020;71:762-8.
    [CrossRef] [Google Scholar]
  36. , , . Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clin Infect Dis. 2020;2020:ciaa270.
    [Google Scholar]
  37. , , , , . Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): A meta-analysis. Clin Chem Lab Med. 2020;58:1021-8.
    [CrossRef] [PubMed] [Google Scholar]
  38. , , , , , . COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033-4.
    [CrossRef] [PubMed] [Google Scholar]
  39. , , , , , , et al. Systemic immune inflammatory index in sepsis. Med Intern Méx. 2017;33:303-9.
    [Google Scholar]
  40. , , , . Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design. Exp Biol Med. 2016;241:1084-97.
    [CrossRef] [PubMed] [Google Scholar]
Show Sections