The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

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 I 2 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.

A Canadian perspective on severe acute respiratory syndrome coronavirus 2 infection and treatment: how prevalent underlying inflammatory disease contributes to pathogenesis

“…The serum levels of several cytokines are dramatically increased in severe COVID-19 disease as compared with patients that have milder disease. For example, IL-6 is thought to be one of the key cytokines involved in SARS-CoV-2 pathogenesis, as high serum levels have been associated with more severe disease (Akbari et al 2020;Kermali et al 2020). IL-6 is a proinflammatory cytokine involved in activation of the acute phase response and controlling the activity of various immune cells (Tanaka et al 2014).…”

“…Another pro-inflammatory cytokine, IL-1β, is also elevated in the plasma of SARS-CoV-2 infected patients, but is not associated with severe disease (Akbari et al 2020;Huang et al 2020a). Mature IL-1β is released from cells following processing of the pro-IL-1β by the NLRP3 inflammasome, a multi-protein complex that is activated by molecular patterns associated with infection, such as viral RNA, and cellular damage, such as ATP (Franchi et al 2012).…”

“…This indicates that direct activation of proinflammatory pathways, like the NLRP3 inflammasome, by SARS-CoV and SARS-CoV-2 could be important for viral replication and pathogenesis. IL-10 is another cytokine that is commonly found at higher levels in the plasma of SARS-CoV-2 patients, especially those with severe disease requiring hospitalization (Akbari et al 2020). IL-10 is an anti-inflammatory cytokine and is often exploited by viruses to establish persistent infections (Rojas et al 2017).…”

Endothel, vaskuläre Funktion und COVID-19

“…In einer Metaanalyse [19] konnte unter Einschluss von 7865 Patienten gezeigt werden, dass bei schwereren verglichen mit milderen COVID-19-Verläufen insbesondere CD4 + -und CD8 + -T-Zellen sowie CD3-, CD19-Zellen und natürliche Killerzellen vermindert waren. Die CD4/CD8-Ratio zeigte sich dabei nicht signifikant verändert, was auf eine Reduktion beider T-Zellen zurückzuführen ist [19]. Andere Untersuchungen zeigten auch nach Rekonvaleszenz weiterhin verminderte CD4 + -T-Zellen [21].…”

“…The global involvement of coronavirus disease 19 (COVID- 19) provokes multiple findings about the clinical course in three phases, the infection pathway and the vascular function. Severe course of SARS-CoV-2-infection is defined as massive inflammatory reaction with elevated pro-inflammatory cytokines resulting in acute respiratory stress syndrome and the involvement of secondary organ damages with even lifethreatening cardiovascular and pulmonary complications.…”