Immune-Inflammatory Parameters in COVID-19 Cases: A Systematic Review and Meta-Analysis.
ABSTRACT: Background: The recent outbreak of coronavirus disease 2019 (COVID-19) has been rapidly spreading on a global scale and poses a great threat to human health. Acute respiratory distress syndrome, characterized by a rapid onset of generalized inflammation, is the leading cause of mortality in patients with COVID-19. We thus aimed to explore the effect of risk factors on the severity of the disease, focusing on immune-inflammatory parameters, which represent the immune status of patients. Methods: A comprehensive systematic search for relevant studies published up to April 2020 was performed by using the PubMed, Web of Science, EMBASE, and China National Knowledge Internet (CNKI) databases. After extracting all available data of immune-inflammatory indicators, we statistically analyzed the risk factors of severe and non-severe COVID-19 patients with a meta-analysis. Results: A total of 4,911 patients from 29 studies were included in the final meta-analysis. The results demonstrated that severe patients tend to present with increased white blood cell (WBC) and neutrophil counts, neutrophil-lymphocyte ratio (NLR), procalcitonin (PCT), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), and Interleukin-6 (IL-6) and a decreased number of total lymphocyte and lymphocyte subtypes, such as CD4+ T lymphocyte and CD8+ T lymphocyte, compared to the non-severe patients. In addition, the WBC count>10 × 109/L, lymphocyte count<1 × 109/L, PCT>0.5 ng/mL, and CRP>10 mg/L were risk factors for disease progression in patients with COVID-19 (WBC count>10 × 109/L: OR = 2.92, 95% CI: 1.96-4.35; lymphocyte count<1 × 109/L: OR = 4.97, 95% CI: 3.53-6.99; PCT>0.5 ng/mL: OR = 6.33, 95% CI: 3.97-10.10; CRP>10 mg/L: OR = 3.51, 95% CI: 2.38-5.16). Furthermore, we found that NLR, as a novel marker of systemic inflammatory response, can also help predict clinical severity in patients with COVID-19 (OR = 2.50, 95% CI: 2.04-3.06). Conclusions: Immune-inflammatory parameters, such as WBC, lymphocyte, PCT, CRP, and NLR, could imply the progression of COVID-19. NLR has taken both the levels of neutrophil and lymphocyte into account, indicating a more complete, accurate, and reliable inspection efficiency; surveillance of NLR may help clinicians identify high-risk COVID-19 patients at an early stage.
Project description:Background:Procalcitonin (PCT), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) have emerged as important markers of inflammation, and these markers, especially PCT and CRP, have been studied in patients with neutropenia. This study was designed to evaluate their value in differentiating infectious fever from tumor fever (TF) and to investigate their role in assessing outcomes in nonneutropenic lung cancer patients (NNLCPs). Methods:This retrospective clinical study included 588 febrile NNLCPs between January 2019 and December 2019. The levels of PCT, CRP, and conventional inflammatory markers, including white blood cells (WBC) and neutrophils (NEU), were measured. NLR was defined as the ratio of the absolute neutrophil count to the absolute lymphocyte count. Patients' clinical and bacteriological data were recorded. Results:This study included 311 NNLCPs with bacterial infections and 277 with TF. Inflammatory markers such as PCT, CRP, WBC, and NEU levels and NLR were significantly higher in patients with bacterial infections than in those with TF (p?<?0.0001). However, PCT level was the best predictor of bacterial infections, with an area under the curve (AUC) of 0.874, followed by CRP level (AUC?=?0.855) and NLR (AUC?=?0.792) (p?<?0.0001). Additionally, PCT level was significantly elevated in patients with bacterial infections with progressive disease after radiotherapy and chemotherapy (p?<?0.01). Conclusions:The present study demonstrated the superiority of PCT over CRP and NLR in the diagnosis of febrile patients with bacterial infections. Additionally, PCT can be used to assess the clinical outcomes and cancer progression in NNLCPs.
Project description:AIMS:This study aimed to make a comparison between the clinical laboratory-related factors, complete blood count (CBC) indices, cytokines, and lymphocyte subsets in order to distinguish severe coronavirus disease 2019 (COVID-19) cases from the non-severe ones. MATERIALS AND METHODS:Relevant studies were searched in PubMed, Embase, Scopus, and Web of Science databases until March 31, 2020. Cochrane's Q test and the I2 statistic were used to determine heterogeneity. We used the random-effect models to pool the weighted mean differences (WMDs) and 95% confidence intervals (CIs). KEY FINDINGS:Out of a total of 8557 initial records, 44 articles (50 studies) with 7865 patients (ranging from 13 to 1582), were included. Our meta-analyses with random-effect models showed a significant decrease in lymphocytes, monocyte, CD4+ T cells, CD8+ T cells, CD3 cells, CD19 cells, and natural killer (NK) cells and an increase in the white blood cell (WBC), neutrophils, neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP)/hs-CRP, erythrocyte sedimentation rate (ESR), ferritin, procalcitonin (PCT), and serum amyloid A (SAA), interleukin-2 (IL-2), IL-2R, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-?), and interferon-gamma (INF-?) in the severe group compared to the non-severe group. However, no significant differences were found in IL-1?, IL-17, and CD4/CD8 T cell ratio between the two groups. SIGNIFICANCE:Decrease in total lymphocytes and lymphocyte subsets as well as the elevation of CRP, ESR, SAA, PCT, ferritin, and cytokines, but not IL-1? and IL-17, were closely associated with COVID-19 severity, implying reliable indicators of severe COVID-19.
Project description:<b>Background:</b> Corona virus disease (COVID-19) is an infectious respiratory disease that has spread rapidly across the world. Many studies have already evaluated the clinical features of COVID-19, but how it compares with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative community-acquired pneumonia (SN-CAP) is still unclear. Moreover, COVID-19 mortality is correlated with disease severity, but indicators for severity grading have not been specified. We aimed to analyze the clinical characteristics of COVID-19 in comparison with SN-CAP and find indicators for disease severity in COVID-19. <b>Methods:</b> Patients diagnosed with COVID-19 and SN-CAP were enrolled. Clinical, radiological, and laboratory data were analyzed. <b>Results:</b> The numbers of COVID-19 and SN-CAP patients enrolled were 304 and 138, respectively. The age of the patients was not significantly different between the groups. Compared with SN-CAP, COVID-19 patients had more symptoms of fever and dyspnea; and showed significant difference in blood count results. Computed tomography (CT) imaging of COVID-19 patients showed patchy ground-glass opacities that correlated with disease severity, whereas the CT imaging of SN-CAP patients showed patchy high-density shadows. COVID-19 patients were classified into moderate, severe, and critically severe groups. The severe and critically severe groups had elevated levels of white blood cells (WBC), neutrophils, platelets, C-reaction protein (CRP), lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), troponin-I, creatinine, and blood urea nitrogen (BUN). However, they had decreased levels of lymphocytes, lymphocyte ratio, and albumin. Compared with the younger patients, the older COVID-19 individuals had more chronic diseases and significantly elevated levels of WBC, neutrophil, and CRP levels. <b>Conclusion:</b> SN-CAP showed more inflammatory reaction than COVID-19. Old people with chronic diseases are more susceptible to COVID-19 and have a high likelihood of developing severe and critically severe infection. Levels of WBC, lymphocytes, neutrophils, CRP, NLR, PLR, troponin-I, creatinine, and BUN are important indicators for severity grading in COVID-19.
Project description:To conduct a systematic review and meta-analysis to characterize inflammatory markers in comparisons of multisystem inflammatory syndrome in children (MIS-C) versus severe/non-severe COVID-19, severe MIS-C versus non-severe MIS-C, and among age groups of MIS-C. Nine databases were searched for studies on inflammatory markers of MIS-C. After quality checks, data were pooled using a fixed or random effects model. Inflammatory markers included white blood cell count (WBC) or leukocytes, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), platelet count (PLT), C-reactive protein (CRP), procalcitonin (PCT), ferritin, D-dimer, lactate dehydrogenase (LDH), fibrinogen, and erythrocyte sedimentation rate (ESR) for comparisons by severity and age. Twenty-one studies with 1735 participants yielded 787 MIS-C patients. Compared to non-severe COVID-19 patients, MIS-C patients had lower ALC and higher ANC, CRP, and D-dimer levels. Compared to severe COVID-19 patients, MIS-C patients had lower LDH and PLT counts and higher ESR levels. Severe MIS-C patients had higher levels of WBC, ANC, CRP, D-dimer, and ferritin than non-severe MIS-C patients. For MIS-C, younger children (0-5 years) had lower CRP and ferritin levels than middle-aged/older children/adolescents. Measurement of inflammatory markers might assist clinicians in accurate evaluation and diagnosis of MIS-C and the associated disorders.
Project description:<h4>Background</h4>We sought to determine if there was a difference in the longitudinal inflammatory response measured by white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), and ferritin levels between the first and the second COVID-19 wave of ICU patients.<h4>Methods</h4>In a single-center retrospective observational study, ICU patients were enrolled during the first and second waves of the COVID-19 pandemic. Data were collected on patient demographics, comorbidities, laboratory results, management strategies, and complications during the ICU stay. The inflammatory response was evaluated using WBC count, CRP, PCT, and Ferritin levels on the day of admission until Day 28, respectively. Organ dysfunction was measured by the SOFA score.<h4>Results</h4>65 patients were admitted during the first and 113 patients during the second wave. WBC and ferritin levels were higher in the second wave. CRP and PCT showed markedly different longitudinal kinetics up until day 28 of ICU stay between the first and second wave, with significantly lower levels in the second wave. Steroid and immunomodulatory therapy use was significantly greater in the second wave. Mortality was similar in both waves.<h4>Conclusions</h4>We found that there was a significantly reduced inflammatory response in the second wave, which is likely to be attributable to the more widespread use of immunomodulatory therapies.
Project description:<h4>Objective</h4>Preliminary findings suggest a relationship between lower serum 25-hydroxyvitamin D [25(OH)D] levels and incidence and severity of COVID-19. The aim of this study was to evaluate the relationship between vitamin D status at admission and different markers of inflammation, coagulation, and sepsis in hospitalized patients with COVID-19.<h4>Method</h4>We conducted a retrospective study on 137 consecutive patients with SARS-CoV-2 infection and available data on serum 25(OH)D levels, who were admitted to our Institution between March 1 and April 30, 2020. Patients were divided into two groups: survivors (n?=?78; 57%) and non-survivors (n?=?59; 43%).<h4>Results</h4>At admission, all patients showed hypovitaminosis D. Median total serum 25(OH)D levels at admission were significantly higher in survivors than non-survivors (12?ng/mL vs 8?ng/mL; <i>p</i>?<?0.01). Non-survivors exhibited significantly higher median levels of white blood cell (WBC) count, neutrophil-to-lymphocyte count ratio (NLR), high-sensitivity C-reactive protein (hsCRP), ferritin, interleukin 6 (IL-6), D-dimer, fibrinogen, and procalcitonin (PCT) compared to survivors at three different time points during hospitalization. In a multivariate analysis performed by a logistic regression model, serum 25(OH)D levels were significantly inversely associated with risk of COVID-19-related in-hospital mortality (odds ratio, 0.91; 95% confidence interval, 0.85-0.98; <i>p</i>?=?0.01). According to receiver operating characteristic curve analysis, hsCRP, NLR, ferritin, and D-dimer were the best predictive biomarkers for poor prognosis of COVID-19, whereas IL-6, PCT, fibrinogen, 25(OH)D, WBC count, and tumor necrosis factor alpha (TNF-?) may serve as supportive biomarkers for worse clinical course of the disease.<h4>Conclusions</h4>We found a markedly high prevalence (100%) of hypovitaminosis D in patients admitted to hospital with COVID-19, suggesting a possible role of low vitamin D status in increasing the risk of SARS-CoV-2 infection and subsequent hospitalization. The inverse association between serum 25(OH)D levels and risk of in-hospital mortality observed in our cohort suggests that a lower vitamin D status upon admission may represent a modifiable and independent risk factor for poor prognosis in COVID-19.
Project description:Coronavirus disease 2019 (COVID-19) is an important and urgent threat to global health. Inflammation factors are important for COVID-19 mortality, and we aim to explore whether the baseline levels of procalcitonin (PCT), C-reaction protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) are associated with an increased risk of mortality in patients with COVID-19. A retrospective study was conducted and a total of 76 patients with confirmed COVID-19 were included between January 17, 2020 to March 2, 2020, of these cases, 17 patients were dead. After adjusting covariates, PCT (??0.10 ng/mL) and CRP (??52.14 mg/L) exhibited independent increasing risks of mortality were used hazard ratio (HR) of 52.68 (95% confidence interval [CI]: 1.77-1571.66) and 5.47 (95% CI: 1.04-28.72), respectively. However, NRL (??3.59) was not found to be an independent risk factor for death in our study. Furthermore, the elevated PCT levels were still associated with increasing risk of mortality in the old age group (age???60 y), and in the critically severe and severe patients after adjustment for complications. Thu Baseline levels of PCT and CRP have been addressed as independent predictors of mortality in patients with COVID-19.
Project description:BACKGROUND:Early diagnosis and treatment has proven to be of utmost importance in the outcome of sepsis patients. We compared the accuracy of the neutrophil-lymphocyte count ratio (NLCR) to conventional inflammatory markers in patients admitted to the Intensive Care Unit (ICU). METHODS:We performed a retrospective cohort study consisting of 276 ICU patients with sepsis and 388 ICU patients without sepsis. We compared the NLCR as well as C-reactive protein (CRP) level, procalcitonin (PCT) level, white blood cell (WBC) count, neutrophil count and lymphocyte count on ICU admission between sepsis and non-sepsis ICU patients. To evaluate the sensitivity and specificity, we constructed receiver operating characteristics (ROC) curves. RESULTS:Significant differences in NLCR values were observed between sepsis and non-sepsis patients (15.3 [10.8-38.2] (median [interquartile range] vs. 9.3 [6.2-14.5]; P<0.001), as well as for CRP level, PCT level and lymphocyte count. The area under the ROC curve (AUROC) of the NLCR was 0.66 (95%CI = 0.62-0.71). AUROC was significantly higher for CRP and PCT level with AUROC's of 0.89 (95%CI 0.87-0.92) and 0.88 (95%CI 0.86-0.91) respectively. CONCLUSIONS:The NLCR is less suitable than conventional inflammatory markers CRP and PCT to detect the presence of sepsis in ICU patients. TRIAL REGISTRATION:ClinicalTrials.gov NCT01274819.
Project description:<h4>Introduction</h4>As the Coronavirus disease 2019 (COVID-19) pandemic is still ongoing with patients overwhelming healthcare facilities, we aimed to investigate the ability of white blood cell count (WBC) and their subsets, high fluorescence lymphocyte cells (HFLC), immature granulocyte count (IG), and C-reactive protein (CRP) to aid diagnosis of COVID-19 during the triage process and as indicators of disease progression to serious and critical condition.<h4>Methods</h4>We collected clinical and laboratory data of patients, suspected COVID-19 cases, admitted at the emergency department of University General Hospital of Ioannina (Ioannina, Greece). We selected 197 negative and 368 positive cases, confirmed by polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2. COVID-19 cases were classified into mild, serious, and critical disease. Receiver operating characteristic curve and binary logistic regression analysis were utilized for assessing the diagnosing ability of biomarkers.<h4>Results</h4>WBC, neutrophil count (NEUT), and HFLC can discriminate efficiently negative cases from mild and serious COVID-19, whereas eosinopenia and basopenia are early indicators of the disease. The combined WBC-HFLC marker is the best diagnostic marker for both mild (sensitivity: 90.6% and specificity: 64.1%) and serious (sensitivity: 90.3% and specificity: 73.4%) disease. CRP and Lymphocyte count are early indicators of progression to serious disease whereas WBC, NEUT, IG, and neutrophil-to-lymphocyte ratio are the best indicators of critical disease.<h4>Conclusion</h4>Lymphopenia is not useful in screening patients with COVID-19. HFLC is a good diagnostic marker for mild and serious disease either as a single marker or combined with WBC whereas IG is a good indicator of progression to critical disease.
Project description:<h4>Objective</h4>Young febrile infants represent a vulnerable population at risk for serious bacterial infections (SBI). We aimed to evaluate the diagnostic accuracy of components of the complete blood count in comparison with C-reactive protein (CRP) to predict SBI among febrile infants.<h4>Design and setting</h4>Prospective cohort study conducted in a tertiary emergency department between December 2018 and November 2019.<h4>Patients</h4>We included febrile infants ≤3 months old with complete blood count results. We analysed their white blood cell count (WBC), absolute neutrophil ratio (ANC), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, mean platelet volume to platelet count ratio, and compared these to the performance of CRP.<h4>Main outcome measures</h4>SBIs were defined as urinary tract infection, bacteraemia, bacterial meningitis, sepsis, pneumonia, skin and soft tissue infection, bacterial enteritis, septic arthritis or osteomyelitis.<h4>Results</h4>Of the 187 infants analysed, 54 (28.9%) were diagnosed with SBI. Median values of WBC, ANC, NLR and CRP were significantly higher in infants with SBI: WBC (13.8 vs 11.4×10<sup>9</sup>/L, p=0.004), ANC (6.7 vs 4.1×10<sup>9</sup>/L, p<0.001), NLR (1.3 vs 0.9, p=0.001) and CRP (21.0 vs 2.3 mg/L, p<0.001), compared with those without. CRP had the best discriminatory values for SBI, with area under the curve (AUC) of 0.815 (95% CI 0.747 to 0.883), compared with WBC, ANC and NLR. A predictive model consisting of WBC, ANC and NLR in combination with clinical parameters, had an AUC of 0.814 (95% CI 0.746 to 0.883). There was increased discriminative performance when this predictive model was combined with CRP, (AUC of 0.844, 95% CI 0.782 to 0.906).<h4>Conclusion</h4>In young febrile infants, CRP was the best discriminatory biomarker for SBI. WBC, ANC and NLR when used in combination have potential diagnostic utility in this population.