Plain language summary
Literature shows that lymphopenia [reduced level of the blood cell lymphocyte] and cytokine release syndrome are among the characteristics caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - the new infectious Coronavirus Disease 2019 (COVID-19). The main aims of this study were (a) to analyse the different characteristics of cytokine levels, lymphocyte subsets, complete blood count (CBC) indices, and a number of infection-related factors between mild/moderate and severe/critical patients, and (b) to screen out suitable indicators for the prediction of the disease severity in order to provide some insight into the subsequent clinical interventions. This study is a systemic review and meta-analysis of 50 studies (44 articles) with a total of 7865 patients including 2286 in the severe group and 5579 in the non-severe group. Results demonstrated a significant lymphopenia in severe/critical infected cases compared to mild/moderate COVID-19 ones across 46 studies. The severity of COVID-19 has also a significant, positive association with a number of infection related factors (such as C-reactive protein) and ferritin levels. Moreover, with respect to CBC indices, the findings revealed significantly higher levels in white blood cells and neutrophil, while lower lymphocyte and monocyte levels in severe than in non-severe confirmed COVID-19 patients. Authors conclude that it is essential that clinicians have access to reliable quick pathogen tests and feasible differential diagnoses based on the clinical descriptions in their first contact with suspected patients.
Abstract
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-α), and interferon-gamma (INF-γ) in the severe group compared to the non-severe group. However, no significant differences were found in IL-1β, 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-1β and IL-17, were closely associated with COVID-19 severity, implying reliable indicators of severe COVID-19.
Methodological quality
Jadad score
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