ABSTRACT
OBJECTIVETo assess the effectiveness of SARS-CoV-2 vaccines in terms of prevention of disease and transmission. The evaluation was narrowed to two mRNA vaccines and two modified adenovirus vectored vaccines. METHODSA frequentist random effects meta-analysis was carried out after data extraction. Risk of bias of the included studies was assessed using New-Castle-Ottawa Scale. The overall risk of SARS-CoV-2 infection confirmed by real time Polymerase Chain Reaction (PCR) was estimated in partially and fully vaccinated individuals. The effect size was expressed as Relative Risk (RR) and RRR (RR reduction) of SARS-CoV-2 infection after vaccination. Potential sources of heterogeneity were investigated through between-study heterogeneity analysis and subgroup meta-analysis. RESULTSThe systematic review identified 27 studies eligible for the quantitative synthesis. Partially vaccinated individuals presented a RRR=73% (95%CI=59%-83%) for any positive SARS-CoV-2 PCR (RR=0.27) and a RRR=79% (95%CI=30%-93%) for symptomatic SARS-CoV-2 PCR (RR=0.21). Fully vaccinated individuals showed a RRR=94% (95%CI=88%-98%) for any SARS-CoV-2 positive PCR (RR=0.06) compared to unvaccinated. According to the subgroup meta-analysis, full BNT162b2 vaccination protocol achieved a RRR=84%-94% against any SARS-CoV-2 positive PCR and a RRR=68%-84% against symptomatic positive PCR. The RR for any SARS-CoV-2 positive PCR remained higher within elderly groups aged [≥]69 years (RR=0.12-0.15) compared to younger individuals (RR=0.05-0.12). The RR against B.1.351 infection approached 0.40 for any positive PCR and 0.36 for symptomatic SARS-COV-2 while the RR of any B.1.1.7 infection was 0.14. CONCLUSIONThe current licensed vaccines may be transmission blocking, especially after full vaccination protocol. Given the substantial heterogeneity, results should be interpreted with caution. Subgroups meta-analyses suggested that the risk of any SARS-CoV-2 infection may be higher for non-B.1.1.7 variants and individuals aged [≥]69 years. Further data and longer follow-up are required to investigate additional sources of heterogeneity and the effectiveness of SARS-CoV-2 vaccination within population subgroups. STRENGTHSO_LIReal-world data suggest that the current licensed vaccines may be transmission blocking, in particular after full vaccination protocol. C_LIO_LIThe risk of any SARS-CoV-2 infection either symptomatic or asymptomatic, may be higher for non-B.1.1.7 variants and individuals aged [≥]69 years. C_LI LIMITATIONSO_LIGiven the substantial heterogeneity encountered in this meta-analysis, results should be interpreted with caution C_LIO_LIFur ther evidence on the impact of SARS-CoV-2 variants are vital in order to monitor mutations associated with vaccine escape C_LI
ABSTRACT
RationaleMacrophage activation syndrome (MAS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. ObjectiveTo investigate the outcome of personalized immunotherapy in critical COVID-19. MethodsIn this open-label prospective trial, 102 patients with SOFA (sequential organ failure assessment) score [≥]2 or ARDS by SARS-CoV-2 were screened for MAS (ferritin more than 4420 ng/ml) and CID (ferritin [≤]4420 ng/ml and low expression of HLA-DR on CD14-monocytes). Patients with MAS and CID with increased aminotransferases were assigned to intravenous anakinra; those with CID and normal aminotransferases to tocilizumab. The primary outcome was at least 25% decrease of SOFA score and/or 50% increase of respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28; serum biomarkers and cytokine production by mononuclear cells were secondary endpoints. Measurements and Main ResultsThe primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (odds ratio 3.11; 95% CIs 1.29-7.73; P: 0.011). No differences were found in mortality and in SOFA score changes. By day 4, ferritin was decreased among anakinra-treated patients; interleukin (IL)-6, soluble urokinase plasminogen activator receptor (suPAR) and the expression of HLA-DR were increased among tocilizumab-treated patients. Anakinra increased capacity of mononuclear cells to produce IL-6. Survivors by day 28 who received anakinra were distributed to scales of the WHO clinical progression of lower severity. Greater incidence of secondary infections was found with tocilizumab treatment. ConclusionsBiomarkers may guide favourable anakinra responses in critically ill patients with COVID-19. Trial RegistrationClinicalTrials.gov, NCT04339712
