only one dose for all those available vaccines except the Ad26

only one dose for all those available vaccines except the Ad26.COV2.S Janssen vaccine), review or recommendation articles lacking original data, studies reporting only safety data, case reports, case series reporting fewer than ten patients and case series of breakthrough infections. Search and data extraction strategies We searched the databases Medline through PubMed and Embase from inception until 31 August 2021. tool developed by the National Institutes of Health on interventional and observational studies. Immunogenicity was assessed through nonresponse rate defined as no anti-SARS-CoV-2 spike protein antibodies, efficacy and effectiveness by the relative reduction in risk of SARS-CoV-2 contamination or COVID-19. We collected factors associated with the risk of nonresponse. We presented collected data by immunosuppression type. Results We screened 5917 results, included 162 studies. There were 157 on TRX 818 immunogenicity in 25?209 participants, including 7835 cancer or haematological malignancy patients (31.1%), 6302 patients on dialysis (25.0%), 5974 sound organ transplant recipients (23.7%) and 4680 immune-mediated disease patients (18.6%). Proportion of nonresponders seemed higher among solid organ TRX 818 transplant recipients (range 18C100%) and patients with haematological malignancy TRX 818 (range 14C61%), and lower in patients with cancer (range 2C36%) and patients on dialysis (range 2C30%). Risk factors for non-response included older age, use of corticosteroids, immunosuppressive or anti-CD20 agent. Ten studies evaluated immunogenicity of an additional dose. Five studies evaluated vaccine efficacy or effectiveness: three on SARS-CoV-2 contamination (range 71C81%), one on COVID-19-related hospitalization (62.9%), one had a too small sample size. Conclusions This systematic review highlights the risk of low immunogenicity of COVID-19 vaccines in immunocompromised populations, especially solid organ transplant recipients and patients with haematological malignancy. Despite lack of vaccine effectiveness data, enhanced vaccine H3F1K regimens may be necessary. Keywords: Cancer, COVID-19, Dialysis, Effectiveness, Efficacy, Immunogenicity, SARS-CoV-2 immunocompromised, Solid organ transplant, Vaccine Introduction A set of COVID-19 vaccines has been rapidly developed with high vaccine efficacy in phase 3 studies. However, these large-scale pre-marketing studies provide little information TRX 818 on vaccine efficacy in immunocompromised populations, while current evidence shows an increased risk of severe COVID-19 in patients with cancer [1], solid organ transplant [2,3], end-stage renal disease [4,5] and rheumatic immune-mediated diseases on immunosuppressive treatment [6]. Available data with other vaccines indicate a lower vaccine immunogenicity and efficacy in immunocompromised patients, such as patients undergoing haemodialysis, solid organ transplant recipients [7,8], patients with cancer or haematological malignancy [9,10] and those with autoimmune inflammatory diseases [11], hence raising the concern of potentially decreased immunogenicity and effectiveness of COVID-19 vaccines. Several studies have been published in the past few months around the immunogenicity of COVID-19 vaccines in different populations of immunocompromised subjects, leading some countries such as France, and more recently the United States, to recommend an additional dose of vaccine [12,13]. We aimed to summarize available evidence on vaccine immunogenicity and factors associated with non-response to vaccine, efficacy and effectiveness in these populations through a systematic review of literature. Materials and methods Objectives and outcomes of interest We conducted a systematic review of literature until 31 August 2021. The main objective was to assess evidence on COVID-19 vaccine immunogenicity, efficacy and effectiveness in immunocompromised populations. The secondary objectives were to determine factors associated with lack of post-vaccine immunity or low post-vaccine antibody titres, elements of cellular response following vaccination and benefits of additional doses. Outcomes of interest were vaccine efficacy assessed by the relative reduction in risk of COVID-19 in randomized placebo-controlled trials, vaccine effectiveness, assessed by the relative reduction in risk of SARS-CoV-2 contamination in observational TRX 818 studies on RT-PCR-confirmed SARS-CoV-2 infections or in relative reduction in risk of SARS-CoV-2-related hospitalizations or death, and immunogenicity assessed by the rate of nonresponders defined as no anti-SARS-CoV-2 spike protein antibodies (IgG, total antibodies if IgG unavailable) as per cut-off defined in each study. If only neutralization assay data were available, we defined non-response as absence of neutralizing antibodies as per cut-off defined in the study. Factors associated with lack of post-vaccine immunity or lower post-vaccine antibody titres, compared with the rest of the population of interest or to a control group (if any), were defined according to associations found in each study. Inclusion and exclusion criteria We included reports of COVID-19 vaccine immunogenicity, efficacy and effectiveness in any of the following populations: cancer, haematological malignancy, solid organ transplantation, allogenic stem cell transplantation, autoimmune systemic disease, autoimmune organ specific disease, inflammatory bowel.