Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients

Abstract

<jats:p>Objective Evidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers. Methods Based on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission, and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease. Results Cohorts with elevated levels of white blood cells (WBCs) (OR=1.75), neutrophil count (OR=2.62), D-dimer (OR=3.97), prolonged prothrombin time (PT) (OR=1.82), fibrinogen (OR=3.14), erythrocyte sedimentation rate (OR=1.60), procalcitonin (OR=4.76), IL-6 (OR=2.10), and IL-10 (OR=4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity=100%, specificity=81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74 x109/L for identifying patients at high risk of severe COVID‐19. Likewise, ICU admission was associated with higher levels of WBCs (OR=5.21), neutrophils (OR=6.25), D-dimer (OR=4.19), and prolonged PT (OR=2.18). Patients with high IL-6 (OR=13.87), CRP (OR=7.09), D-dimer (OR=6.36), and neutrophils (OR=6.25) had the highest likelihood of mortality. Conclusions Several hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.</jats:p>

Dementia and outcomes from coronavirus disease 2019 (COVID-19) pneumonia: A systematic review and meta-analysis

“…( Harrison et al, 2020 ) On the other side, a meta-analysis study has shown that a high level of leukocyte counts and the high neutrophil-lymphocyte ratio was associated with a higher risk of developing severe COVID-19 and mortality from COVID-19. ( Elshazli et al, 2020 ) Finally, people with dementia, due to the nature of their cognitive decline, would require the care and support of carers such as dementia caregivers in order to be able to follow healthcare and preventive measures such as wearing face masks and washing their hands with water and soap or hand sanitizers. ( Suzuki et al, 2020 ) However, during this COVID-19 pandemic, the availability of caregivers becomes limited which may cause dementia patients unable to follow healthcare and preventive measures therefore making them posed a higher risk of contracting an infection from COVID-19.…”

IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression

“…However, performance of prognosis for progression to severe disease was poorer with AUC = 0.75. In the recently reported meta-analysis over a large number of studies, classifier performance was found to be higher for neutrophil count (AUC = 0.831), lymphocyte (AUC = 0.867) and D-dimer (AUC = 0.876) than using IL-6 as covariate(AUC = 0.632) [ 13 ]. Another research with 102 COVID-19 patients used logistic regression to evaluate potential of multiple cytokines to diagnose severe and critical patients [ 20 ].…”

“…A recently published extensive meta-analysis summarized elevated levels of IL-2, IL-2R, IL-4, IL-6, IL-8, IL-10, TNF-α and Interferon-γ (IFN-γ) in severe group of patients, whereas no significant increase was found in the levels of IL-1β and IL-17 [ 12 ]. A two-arm meta-analysis study synthesized from individual patient data reported statistically significant odds ratio (p < 0.05) to severe disease for only two cytokines - IL-6 and IL-10 [ 13 ]. Some meta-analysis efforts reported difference in IL-6 level between severe and non-severe COVID-19 patients in terms of Standardized Mean Difference (SMD) [ 14 ], mean difference [ 15 ] or ratio of means [ 16 ] values that can potentially be used as cut-off to discriminate between severe and non-severe patients.…”

“…Clinical studies with COVID-19 patient cohorts explored the role of IL-6 alone [ 19 ] or IL-6 along with other cytokines including IL-10, IL-2, IL-4, TNF-α and IFN-γ as prognosticator for severe disease [ 20 ]. Meta-analysis studies described before 12 , 14 , 15 , 16 , 21 , 22 concluded elevated levels of cytokines in severe COVID-19 patients but did not attempt to establish their prognostic significance, except the study by Elshazli et al who performed decision tree and Receiver Operating Characteristics (ROC) curve analysis to assess prognostic potential of multiple laboratory parameters including IL-6 [ 13 ]. Another study with a cohort of 501 patients [ 23 ] attempted to establish a mortality risk model using multiple clinical parameters and IL-6 level.…”

Frailty and mortality in patients with COVID-19 – Authors' reply

“…Our findings concur with those from other studies, suggesting admission CRP can guide the management of COVID-19. 6 …”