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Frontiers in Immunology 2021Activation of the complement system has been observed in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis with meta-regression to... (Meta-Analysis)
Meta-Analysis
Activation of the complement system has been observed in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis with meta-regression to investigate possible differences in the serum concentrations of two routinely measured complement components, C3 and C4, in COVID-19 patients with different severity and survival status. We searched PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting serum complement C3 and C4, measures of COVID-19 severity, and survival. Eligibility criteria were a) reporting continuous data on serum C3 and C4 concentrations in COVID-19 patients, -b) investigating COVID-19 patients with different disease severity and/or survival status, c) adult patients, d) English language, e) ≥10 patients, and f) full-text available. Using a random-effects model, standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated to evaluate differences in serum C3 and C4 concentrations between COVID-19 patients with low vs. high severity or survivor vs. non-survivor status. Risk of bias was assessed using the Newcastle-Ottawa scale whereas publication bias was assessed with the Begg's and Egger's tests. Certainty of evidence was assessed using GRADE. Nineteen studies in 3,764 COVID-19 patients were included in the meta-analysis. Both C3 and C4 concentrations were significantly lower in patients with high disease severity or non-survivor status than patients with low severity or survivor status (C3 SMD=-0.40, 95% CI -0.60 to -0.21, p<0.001; C4 SMD=-0.29, 95% CI -0.49 to -0.09, p=0.005; moderate certainty of evidence). Extreme between-study heterogeneity was observed (C3, I = 82.1%; C4, I = 84.4%). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. There was no publication bias. In meta-regression, the SMD of C3 was significantly associated with white blood cell count, C-reactive protein (CRP), and pro-thrombin time, whereas the SMD of C4 was significantly associated with CRP, pro-thrombin time, D-dimer, and albumin. In conclusion, lower concentrations of C3 and C4, indicating complement activation, were significantly associated with higher COVID-19 severity and mortality. C3 and C4 might be useful to predict adverse clinical consequences in these patients. PROSPERO, Registration number: CRD42021239634.
Topics: Biomarkers; COVID-19; Complement Activation; Complement C3; Complement C4; Humans; SARS-CoV-2; Severity of Illness Index
PubMed: 34163491
DOI: 10.3389/fimmu.2021.696085 -
Schizophrenia Research Aug 2020There is renewed focus on the complement system in the pathogenesis of schizophrenia. In addition to providing aetiological insights, consistently dysregulated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is renewed focus on the complement system in the pathogenesis of schizophrenia. In addition to providing aetiological insights, consistently dysregulated complement proteins in serum or plasma may have clinical utility as biomarkers.
METHODS
We performed a systematic literature review searching PubMed, Embase and PsycINFO for studies measuring complement system activity or complement protein concentrations in serum or plasma from patients with schizophrenia compared to controls. Random-effects meta-analyses were performed to calculate pooled effect estimates (Hedges' g standardised mean difference [SMD]) for complement proteins whose concentrations were measured in three or more studies. The review was pre-registered on the PROSPERO database (CRD42018109012).
RESULTS
Database searching identified 1146 records. Fifty-eight full-text articles were assessed for eligibility and 24 studies included. Seven studies measured complement system activity. Activity of the classical pathway did not differ between cases and controls in four of six studies, and conflicting results were noted in two studies of alternative pathway activity. Twenty studies quantified complement protein concentrations of which complement components 3 (C3) and 4 (C4) were measured in more than three studies. Meta-analyses showed no evidence of significant differences between cases and controls for 11 studies of C3 (SMD 0.04, 95% confidence interval [CI] -0.29-0.36) and 10 studies of C4 (SMD 0.10, 95% CI -0.21-0.41).
CONCLUSIONS
Serological studies provide mixed evidence regarding dysregulation of the complement system in schizophrenia. Larger studies of a longitudinal nature, focusing on early phenotypes, could provide further insights regarding the potential role of the complement system in psychotic disorders.
Topics: Biomarkers; Complement System Proteins; Humans; Psychotic Disorders; Schizophrenia
PubMed: 32456884
DOI: 10.1016/j.schres.2020.05.036