HIV and Associated Indicators of COVID-19 Cytokine Release Syndrome: A Meta-Analysis and Meta-Regression

The aim of this review was to evaluate the risk of COVID-19 cytokine release syndrome (CRS) with HIV infection and meta-regress for indicator covariates. Electronic databases, including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID-19 Research Database, and Scopus, were systematically searched till February 30, 2022. All human studies were included, irrespective of publication date or region. Eleven studies, with a total of 2,005,274 detailing cytokine release syndrome defined by specific parameters, were included. To pool the estimate, a random-effects model with risk ratio (RR) as the effect measure was used. Moreover, publication bias and sensitivity analysis were evaluated followed by meta-regression analysis to account for any possible covariates. This systematic review, meta-analysis, and meta-regression trial was registered (CRD42021264761) on the PROSPERO register. HIV infection showed an increased risk for COVID-19 cytokine release syndrome (RR= 1.48, 95% CI (1.16, 1.88) (P=0.002)) with substantial heterogeneity (I(2) > 80%) and a 4.6% cumulative incidence. The true effects size in 95% of all the comparable populations (prediction interval) fell between 0.67 to 3.29. HIV infection further showed an increased risk for intensive care unit (ICU) admission ((P<0.0001) (I² = 0%)] and mechanical ventilation (MV) ((P=0.04) (I² = 0%)) as the key indicators of cytokine release syndrome. Meta-regression analysis demonstrated that COVID-19 cytokine release syndrome was influenced by the year a study was published (R² = 0.55) and the region from where the study was conducted (R² = 0.11). On meta-regression analysis, the combined impact of all covariates in the model explained at least some of the variance in effect size (Q = 16.21, df = 6, P= 0.0127), and the proportion of variance explained by covariates on comparing the model with and without the covariates was 73 % and highly significant (Tau² = 0.1100, Tau = 0.3317, I² = 86.5%, Q = .99, df = 10, P<0.0001) (R² = 0.73). Our updated meta-analysis indicated that HIV infection was significantly associated with an increased risk for COVID-19 cytokine release syndrome, which, in addition, might be moderated by the year a study was published and the region in which the study was conducted. Further, the risk for intensive care unit (ICU) admission and mechanical ventilation (MV) were identified as the key indicators of cytokine release syndrome. We believe the updated data anchoring cytokine release syndrome will contribute to more substantiation of the findings reported by similar earlier studies.