Available data show that COVID-19 vaccines may be less effective in immunocompromised populations, who are at increased risk of severe COVID-19.
We conducted a systematic review of literature to ...assess immunogenicity, efficacy and effectiveness of COVID-19 vaccines in immunocompromised populations.
We searched Medline and Embase databases.
We included studies of COVID-19 vaccines after complete vaccination in immunocompromised patients until 31 August 2021. Studies with <10 patients, safety data only and case series of breakthrough infections were excluded.
Risk of bias was assessed via the tool developed by the National Institutes of Health on interventional and observational studies. Immunogenicity was assessed through non-response rate defined as no anti-SARS-CoV-2 spike protein antibodies, efficacy and effectiveness by the relative reduction in risk of SARS-CoV-2 infection or COVID-19. We collected factors associated with the risk of non-response. We presented collected data by immunosuppression type.
We screened 5917 results, included 162 studies. There were 157 on immunogenicity in 25 209 participants, including 7835 cancer or haematological malignancy patients (31.1%), 6302 patients on dialysis (25.0%), 5974 solid organ transplant recipients (23.7%) and 4680 immune-mediated disease patients (18.6%). Proportion of non-responders seemed higher among solid organ transplant recipients (range 18–100%) and patients with haematological malignancy (range 14–61%), and lower in patients with cancer (range 2–36%) and patients on dialysis (range 2–30%). 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 infection (range 71–81%), one on COVID-19-related hospitalization (62.9%), one had a too small sample size.
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 regimens may be necessary.
Gastric carcinomas are heterogeneous, and the current therapy remains essentially based on surgery with conventional chemotherapy and radiotherapy. This study aimed to characterize biomarkers ...allowing the detection of cancer stem cells (CSC) in human gastric carcinoma of different histologic types.
The primary tumors from 37 patients with intestinal- or diffuse-type noncardia gastric carcinoma were studied, and patient-derived tumor xenograft (PDX) models in immunodeficient mice were developed. The expressions of 10 putative cell surface markers of CSCs, as well as aldehyde dehydrogenase (ALDH) activity, were studied, and the tumorigenic properties of cells were evaluated by
tumorsphere assays and
xenografts by limiting dilution assays.
We found that a subpopulation of gastric carcinoma cells expressing EPCAM, CD133, CD166, CD44, and a high ALDH activity presented the properties to generate new heterogeneous tumorspheres
and tumors
CD44 and CD166 were coexpressed, representing 6.1% to 37.5% of the cells; ALDH activity was detected in 1.6% to 15.4% of the cells; and the ALDH
cells represented a core within the CD44
/CD166
subpopulation that contained the highest frequency of tumorigenic CSCs
The ALDH
cells possessed drug efflux properties and were more resistant to standard chemotherapy than the ALDH
cells, a process that was partially reversed by verapamil treatment.
CD44 and ALDH are the most specific biomarkers to detect and isolate tumorigenic and chemoresistant gastric CSCs in noncardia gastric carcinomas independently of the histologic classification of the tumor.
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Patients with diabetes and obesity are populations at high-risk for severe COVID-19 outcomes and have shown blunted immune responses when administered different vaccines. Here we used the ‘ANRS0001S ...COV-POPART’ French nationwide multicenter prospective cohort to investigate early humoral response to COVID-19 vaccination in the sub-cohort (‘COVPOP OBEDIAB’) of patients with obesity and diabetes.
Patients with diabetes (n = 390, type 1 or 2) or obesity (n = 357) who had received two vaccine doses and had no history of previous COVID-19 infection and negative anti-nucleocapsid (NCP) antibodies were included and compared against healthy subjects (n = 573). Humoral response was assessed at baseline, at one month post-first dose (M0) and one-month post-second dose (M1), through percentage of responders (positive anti-spike SARS-CoV-2 IgG antibodies (Sabs), geometric means of Sabs; BAU/mL), proportion of individuals with anti-RBD antibodies, and proportion of individuals with anti-SARS-CoV-2-specific neutralizing antibodies (Nabs). Potential clinical and biological factors associated with weak response (defined as Sabs < 264 BAU/mL) and presence of non-reactive anti-RBD antibodies at M1 were evaluated. Univariate and multivariate regressions were performed to estimate crude and adjusted coefficients with 95 % confidence intervals. Poor glycemic control was defined as HbA1c ≥ 7.5 % at inclusion.
Patients with diabetes, particularly type 2 diabetes, and patients with obesity were less likely to have positive Sabs and anti-RBD antibodies after the first and second dose compared to controls (p < 0.001). At M1, we found Sabs seroconversion in 94.1 % of patients with diabetes versus 99.7 % in controls, anti-RBD seroconversion in 93.8 % of patients with diabetes versus 99.1 % in controls, and Nabs seroconversion in 95.7 % of patients with diabetes versus 99.6 % in controls (all p < 0.0001). Sabs and anti-RBD seroconversion at M0 and M1 were also significantly lower in obese patients than controls, at respectively 82.1 % versus 89.9 % (p = 0.001; M0 Sabs), 94.4 % versus 99.7 % (p 0.001; M1 Sabs), 79.0 % vs 86.2 % (p = 0.004 M0 anti-RBD), and 96.99 % vs 99.1 % (p = 0.012 M1 anti-RBD). The factors associated with low vaccine response (BAU < 264/mL) in patients with diabetes were chronic kidney disease (adjusted OR = 6.88 1.77;26.77, p = 0.005) and poor glycemic control (adjusted OR = 3.92 1.26;12.14, p = 0.018). In addition, BMI ≥ 40 kg/m2 was found to be associated with a higher vaccine response (adjusted OR = 0.10 0.01;0.91, p = 0.040) than patients with BMI < 40 kg/m2.
COVID-19 vaccine humoral response was lower in patients with obesity and diabetes one month after second dose compared to controls, especially in diabetic patients with CKD or inadequate glycemic control. These findings point to the need for post-vaccination serological checks in these high-risk populations.
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Summary Background The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We ...investigated the effect of TDR on outcome in the first year of cART within a large European collaboration. Methods HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy. Findings Of 10 056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8–4·7) for patients in the no TDR group, 4·7% (2·9–7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9–19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33–4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19–2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9–4·7, p=0·093). Interpretation These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients. Funding European Community's Seventh Framework Programme FP7/2007-2013 and Gilead.
Abstract
We evaluated people living with Human Immunodeficiency Virus’ (PLWH) quality of life (QoL) and assessed whether their demographic, disease-related, socioeconomic, or behavioral ...characteristics were associated with poorer QoL. ANRS CO3 AQUIVIH-NA cohort participants (Nouvelle Aquitaine, France) were recruited to a cross-sectional study (2018–2020) and their QoL assessed (WHOQOL-BREF). We calculated median (Q1, Q3) QoL domain scores and assessed factors associated with poorer median QoL using bivariable and multivariable quartile regression. Of the 965 PLWH included, 98.4% were on antiretroviral therapy, 94.7% were virally-suppressed, 63.5% reported good/very good QoL. Median scores (0–100) were highest for physical (69;Q1, Q3: 56, 81) and environmental (69; 56, 75) QoL and lowest for social (56; 44, 69) and psychological (56; 44, 69) QoL. PLWH with ≥ 3 comorbidities, HIV-related stigma, or income of < 1500€/month had poorer median adjusted physical, psychological, social, and environmental QoL scores compared to reference groups. While more than half of PLWH reported good/very good QoL, we have not achieved good QoL in 90% of PLWH. Multi-morbidity, HIV-related stigma, and social determinants were consistently and independently associated with poorer QoL. Addressing structural factors in addition to those indirectly related to HIV is required to attain good QoL in all PLWH.
Biological assays for the quantification of markers may suffer from a lack of sensitivity and thus from an analytical detection limit. This is the case of human immunodeficiency virus (HIV) viral ...load. Below this threshold the exact value is unknown and values are consequently left-censored. Statistical methods have been proposed to deal with left-censoring but few are adapted in the context of high-dimensional data.
We propose to reverse the Buckley-James least squares algorithm to handle left-censored data enhanced with a Lasso regularization to accommodate high-dimensional predictors. We present a Lasso-regularized Buckley-James least squares method with both non-parametric imputation using Kaplan-Meier and parametric imputation based on the Gaussian distribution, which is typically assumed for HIV viral load data after logarithmic transformation. Cross-validation for parameter-tuning is based on an appropriate loss function that takes into account the different contributions of censored and uncensored observations. We specify how these techniques can be easily implemented using available R packages. The Lasso-regularized Buckley-James least square method was compared to simple imputation strategies to predict the response to antiretroviral therapy measured by HIV viral load according to the HIV genotypic mutations. We used a dataset composed of several clinical trials and cohorts from the Forum for Collaborative HIV Research (HIV Med. 2008;7:27-40). The proposed methods were also assessed on simulated data mimicking the observed data.
Approaches accounting for left-censoring outperformed simple imputation methods in a high-dimensional setting. The Gaussian Buckley-James method with cross-validation based on the appropriate loss function showed the lowest prediction error on simulated data and, using real data, the most valid results according to the current literature on HIV mutations.
The proposed approach deals with high-dimensional predictors and left-censored outcomes and has shown its interest for predicting HIV viral load according to HIV mutations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Direct-acting antivirals (DAA) lead to high sustained virological response (SVR) rates and decrease the risk of disease progression. We compared SVR rates and all-cause, liver- and non-liver-related ...deaths, liver-related events, and non-liver-related cancers in HIV/HCV-coinfected and HCV-monoinfected participants from 2 French cohort studies after initiation of DAA treatment.
Up to 4 HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to each HIV/HCV-coinfected patient from the ANRS CO13 HEPAVIH cohort; both are nationwide, prospective, multicentre, and observational. Participants were initiated on DAAs between March 2014 and December 2017. Cox proportional hazards models adjusted by age, sex, duration since HCV diagnosis, HCV transmission routes, HCV genotypes, cirrhosis, tobacco, alcohol consumption, and SVR (time dependent) were used.
A total of 592 HIV/HCV-coinfected and 2,049 HCV-monoinfected participants were included; median age was 53.3 years (inter-quartile range: 49.6–56.9) and 52.9 years (49.6; 56.7), 1,498 (73.1%) and 436 (73.6%) were men, and 159 (28.8%) and 793 (41.2%) had cirrhosis, respectively. SVR was observed in 92.9% and 94.6%, respectively. HIV coinfection was associated with higher risk of all-cause death (hazard ratio HR 1.93; 95% CI 1.01–3.69), non-liver-related death (HR 2.84; 95% CI 1.27–6.36), and non-liver-related cancer (HR 3.26; 95% CI 1.50–7.08), but not with liver-related-death (HR 1.04; 95% CI 0.34–3.15) or liver-related events (HR 0.66; 95% CI 0.31–1.44).
After DAA treatment, HIV-coinfected individuals had similar SVR rates and risk of liver-related deaths and events compared with HCV-monoinfected individuals, but had a higher risk of all-cause and non-liver-related deaths and non-liver-related cancers.
We compared the risk of several clinical events in participants infected by human immunodeficiency virus and hepatitis C virus with those infected with hepatitis C virus alone, matched on age and sex, after treatment with contemporary direct-acting antivirals. We found a higher risk of all-cause deaths, non-liver-related deaths, and non-liver-related cancers in participants coinfected with the human immunodeficiency virus and hepatitis C virus, and no differences for the risk of liver-related deaths or events.
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•Similar rates of SVR exist between HIV/HCV co-infected and HCV mono-infected participants.•There is a higher risk of all-cause deaths, non-liver-related deaths, and cancers in HIV/HCV co-infected participants.•There is a similar risk of liver-related deaths and liver-related events in both populations.
Engagement in multiple substance use risk behaviours such as tobacco smoking, alcohol and drug use during adolescence can result in adverse health and social outcomes. The impact of interventions ...that address multiple substance use risk behaviours, and the differential impact of universal versus targeted approaches, is unclear given findings from systematic reviews have been mixed. Our objective was to assess effects of interventions targeting multiple substance use behaviours in adolescents.
Eight databases were searched to October 2019. Individual and cluster randomised controlled trials were included if they addressed two or more substance use behaviours in individuals aged 8-25 years. Data were pooled in random-effects meta-analyses, reported by intervention and setting. Quality of evidence was assessed using GRADE. Heterogeneity was assessed using between-study variance, τ2 and Ι
, and the p-value of between-study heterogeneity statistic Q. Sensitivity analyses were undertaken using the highest and lowest intra-cluster correlation coefficient (ICC).
Of 66 included studies, most were universal (n=52) and school-based (n=41). We found moderate quality evidence that universal school-based interventions are likely to have little or no short-term benefit (up to 12 months) in relation to alcohol use (OR 0.94, 95% CI: 0.84, 1.04), tobacco use (OR 0.98, 95% CI: 0.83, 1.15), cannabis use (OR 1.06, 95% CI: 0.86, 1.31) and other illicit drug use (OR 1.09, 95% CI: 0.85, 1.39). For targeted school-level interventions, there was low quality evidence of no or a small short-term benefit: alcohol use (OR 0.90, 95% CI: 0.74-1.09), tobacco use (OR 0.86, 95% CI: 0.66, 1.11), cannabis use (OR 0.84, 95% CI: 0.66-1.07) and other illicit drug use (OR 0.79, 95% CI 0.62-1.02). There were too few family-level (n=4), individual-level (n=2) and combination level (n=5) studies to draw confident conclusions. Sensitivity analyses of ICC did not change results.
There is low to moderate quality evidence that universal and targeted school-level interventions have no or a small beneficial effect for preventing substance use multiple risk behaviours in adolescents. Higher quality trials and study reporting would allow better evidence syntheses, which is needed given small benefit of universal interventions can have high public health benefit.
Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD011374. DOI: 10.1002/14651858.CD011374.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to compare the humoral responses to mRNA COVID-19 vaccination in people living with HIV (PWH) and HIV-negative individuals.
We included PWH with an undetectable viral load under ART ...and HIV-negative participants from the French nationwide ANRS COV-POPART cohort who had received two doses of vaccine as a primary vaccination. We compared humoral response between controls and PWH, stratified by CD4 cell count (<200/mm3 and ≥200/mm3 CD4 cell counts) at 1, 6, and 12 months after primary vaccination.
A total of 1776 participants were included in this analysis, 684 PWH (99% were on ART, median CD4 counts 673 cells/mm3) and 1092 controls. At 1 month, after adjustment on age, sex, and BMI, PWH had lower seroneutralization titers than controls, and PWH with <200 CD4 cell/mm3 had lower anti-Spike SARS-CoV-2 IgG antibodies. Same results were found at 6 months. However, in participants who received a booster dose between 6 and 12 months postprimary vaccination, we did not observe differences between PWH and controls at 12 months.
PWH had high responses to primary mRNA COVID-19 vaccination. In those who received a booster dose after 6 months, the humoral response at 12 months increased to similar levels to controls, even in those with low CD4 counts at baseline.
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