Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients. This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8–12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti–SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined. NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both P < .001) in the solid organ transplant group, 41.5% and 19.2% (both P < .0001) in the autoimmune rheumatic diseases group, 43.3% (P < .001) and 21.4% (P<.01 or P = .001) in the cancer with solid tumors group, 45.5% and 28.7% (both P < .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; P < .0001), rheumatic diseases (61%; P < .001), and HIV groups (70.9%; P = .003), compared with the control group (92.3%). On the other hand, the number of interferon γ spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups. Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients. NCT04888793.

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10⁻⁵) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate −0.006 kg/m², 95% CI −0.009 to −0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population‐based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non‐genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision‐recall curve (AUC‐PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC‐PRC for the Baseline Model (0.44%, 95%CI 0.42‐0.46) increased by 0.22 (95%CI 0.15‐0.29) when non‐genetic factors were included, and by 0.25 (95%CI 0.20‐0.30) when incorporating non‐genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104‐131) decreased to 92 (95%CI 60‐128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59‐110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non‐genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.

PURPOSE: Gallbladder cancer (GBC) is a biliary tract malignancy characterized by its high lethality. Although the incidence of GBC is low in most countries, specific areas such as Chile display a high incidence. Our collaborative study sought to compare clinical and molecular features of GBC cohorts from Chile and the United States with a focus on ERBB2 alterations. METHODS: Patients were accrued at Memorial Sloan Kettering Cancer Center (MSK) or the Pontificia Universidad Católica de Chile (PUC). Clinical information was retrieved from medical records. Genomic analysis was performed by the next-generation sequencing platform MSK-Integrated Mutation Profiling of Actionable Cancer Targets. RESULTS: A total of 260 patients with GBC were included, 237 from MSK and 23 from PUC. There were no significant differences in the clinical characteristics between the patients identified at MSK and at PUC except in terms of lithiasis prevalence which was significantly higher in the PUC cohort (85% v 44%; P = .0003). The prevalence of ERBB2 alterations was comparable between the two cohorts (15% v 9%; P = .42). Overall, ERBB2 alterations were present in 14% of patients (8% with ERBB2 amplification, 4% ERBB2 mutation, 1.5% concurrent amplification and mutation, and 0.4% ERBB2 fusion). Notably, patients with GBC that harbored ERBB2 alterations had better overall survival (OS) versus their ERBB2 -wild type counterparts (22.3 months v 11.8 months; P = .024). CONCLUSION: The prevalence of lithiasis seems to be higher in Chilean versus US patients with GBC. A similar prevalence of ERBB2 alterations of overall 14% and better OS suggests that a proportion of them could benefit from human epidermal growth factor receptor type 2–targeted therapies. The smaller cohort of Chile, where the disease prevalence is higher, is a reminder and invitation for the need of more robust next-generation sequencing analyses globally.

Cancer patients on chemotherapy have a lower immune response to SARS-CoV-2 vaccines. Therefore, through a prospective cohort study of patients with solid tumors receiving chemotherapy, we aimed to determine the immunogenicity of an mRNA vaccine booster (BNT162b2) among patients previously immunized with an inactivated (CoronaVac) or homologous (BNT162b2) SARS-CoV-2 vaccine. The primary outcome was the proportion of patients with anti-SARS-CoV-2 neutralizing antibody (NAb) seropositivity at 8–12 weeks post-booster. The secondary end points included IgG antibody (TAb) seropositivity and specific T-cell responses. A total of 109 patients were included. Eighty-four (77%) had heterologous vaccine schedules (two doses of CoronaVac followed by the BNT162b2 booster) and twenty-five had (23%) homologous vaccine schedules (three doses of BNT162b2). IgG antibody positivity for the homologous and heterologous regimen were 100% and 96% (p = 0.338), whereas NAb positivity reached 100% and 92% (p = 0.13), respectively. Absolute NAb positivity and Tab levels were associated with the homologous schedule (with a beta coefficient of 0.26 with p = 0.027 and a geometric mean ratio 1.41 with p = 0.044, respectively). Both the homologous and heterologous vaccine regimens elicited a strong humoral and cellular response after the BNT162b2 booster. The homologous regimen was associated with higher NAb positivity and Tab levels after adjusting for relevant covariates.

Background The use of convalescent plasma (CP) to treat COVID-19 has shown promising results; however, its effectiveness remains uncertain. The purpose of this study was to determine the safety and mortality of CP among patients hospitalized with COVID-19. Study Design and Methods This multicenter, open-label, uncontrolled clinical trial is currently being conducted at nine hospitals in Chile. Patients hospitalized due to COVID-19 who were still within 14 days since symptom onset were classified into four groups: Patients with cancer and severe COVID-19. Patients with cancer and non-severe COVID-19. Patients with severe COVID-19 and patients with non-severe COVID-19 only. The intervention involved two 200-cc. CP transfusions with anti-SARS-CoV-2 IgG titers ≥ 1:320 collected from COVID-19-recovered donors. Results 192 patients hospitalized for COVID-19 received CP transfusions. At the first transfusion, 90.6% fulfilled the criteria for severity, and 41.1% required mechanical ventilation. 11.5% of the patients had cancer. Overall 7-day and 30-day mortality since the first CP transfusion was 5.7% and 16.1% respectively. There were no differences at either time point in mortality between the four groups. Patients on mechanical ventilation when receiving CP had higher mortality rates than those who were not (22.8% vs. 11.5%; p = 0.037). Overall 30-day mortality was higher in patients over 65 than in younger patients (p = 0.019). Severe adverse events were reported in four patients (2.1%) with an overall transfusion-related lung injury rate of 1.56%. No CP-related deaths occurred. Discussion CP is safe when used in patients with COVID-19 even when also presenting severity criteria or risk factors. Our mortality rate is comparable to reports from larger studies. Controlled clinical trials are required to determine efficacy. Registration NCT04384588