Humoral and cellular responses to mRNA-based COVID-19 booster vaccinations in patients with solid neoplasms under active treatment.

BACKGROUND: Patients with cancer are at high risk for severe coronavirus disease 2019 (COVID-19) infection. Knowledge regarding the efficacy of the messenger RNA (mRNA) vaccines in actively treated cancer patients is limited as they had been excluded from the pivotal studies of these vaccines. We evaluated humoral and cellular immune responses in cancer patients after double vaccination and a booster dose and identified disease- and treatment-related factors associated with a reduced immune response. We also documented the number and outcome of breakthrough infections. PATIENTS AND METHODS: Patients with metastatic solid malignancies undergoing active treatment were included if they had received two doses of the severe acute respiratory syndrome coronavirus 2 mRNA vaccines BNT162b2 or mRNA-1273 and a booster dose. Other causes of immunosuppression and previous COVID-19 infections (positive anti-nucleocapsid titers) were exclusion criteria. Anti-spike antibodies, neutralizing antibodies (nAbs) and T-cell responses were assessed about 6 months after the two-dose vaccination and 4 weeks after the booster. RESULTS: Fifty-one patients had pre-booster and 46 post-booster measurements. Anti-spike titers after two vaccine doses were highly variable and significantly lower in older patients, during treatment with chemotherapy compared to targeted and endocrine treatments and in patients with low CD4+ or CD19+ cell counts. The booster dose led to a significant increase in anti-spike antibodies and nAbs, achieving almost uniformly high titers, irrespective of baseline and treatment factors. The cellular immune response was also significantly increased by the booster, however generally more stable and not influenced by baseline factors and treatment type. Seventeen patients (33%) experienced breakthrough infections, but none required hospital care or died from COVID-19. CONCLUSIONS: An mRNA vaccine booster dose is able to increase humoral and cellular immune responses and to overcome the immunosuppressive influence of baseline and treatment factors in cancer patients. Breakthrough infections were uniformly mild in this vaccinated high-risk population.

Novel dual HIV maintenance therapy with nevirapine plus lamivudine retain viral suppression through 144 weeks-A proof-of-concept study.

OBJECTIVES: The aim of this proof-of-concept study is to test feasibility and efficacy of NVP plus Lamivudine (3TC) as novel simplified HIV maintenance dual therapy (DT) strategy. METHODS: Patients under combined antiretroviral treatment (cART) with fully suppressed HIV plasma viral load (pVL) >24 months-whereof >6 months on an NVP- containing regimen-were switched to oral NVP plus 3TC for 24 weeks. Patients could then decide whether to continue DT or return to the previous cART. HIV pVL was monitored monthly until week 144. The primary outcome was confirmed viral failure (RNA >100 copies/ml). Low-level detection of HIV-RNA in plasma was compared in each patient with pre-study viral load measurements. RESULTS: Twenty patients were included, switched to DT and all completed week 24. One patient decided thereafter to discontinue study participation for personal reasons. After a total of 144 observation weeks, none of the patients failed. The frequency of low- level HIV-RNA detection was not different from the period before randomization. CONCLUSIONS: Our findings are surprising but given the nature of a proof-of-concept study, the results do not support the use of this dual regimen. However, as this dual HIV maintenance strategy was feasible and effective, over a period of 144 weeks, we suggest NVP plus 3TC warrants further evaluation as potential maintenance option in patients tolerating nevirapine. A properly sized multicentre non-inferiority trial is ongoing to further evaluate the value of this DT maintenance strategy.

Antibiotic-resistant pathogens in different patient settings and identification of surveillance gaps in Switzerland - a systematic review.

The prevalence of antimicrobial resistance (AMR) varies significantly among different patient populations. We aimed to summarise AMR prevalence data from screening studies in different patient settings in Switzerland and to identify surveillance gaps. We performed a systematic review, searching Pubmed, MEDLINE, Embase (01/2000-05/2017) and conference proceedings for Swiss studies reporting on carbapenemase-producing Enterobacteriaceae (CPE), extended-spectrum beta-lactamases (ESBL), mobilised colistin-resistance, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) within different patient settings. We identified 2345 references and included 46 studies. For acute care patients, most screening data come from admission screenings, whereas AMR prevalence among hospitalised patients is largely unknown. Universal admission screenings showed ESBL-prevalences of 5-8% and MRSA-prevalences of 2-5%. For targeted screening, ESBL-prevalence ranged from 14-21%; MRSA-prevalence from 1-4%. For refugees, high ESBL (9-24%) and MRSA (16-24%) carriage rates were reported; returning travellers were frequently (68-80%) colonised with ESBL. Screening data for other pathogens, long-term care facility (LTCF) residents and pediatric populations were scarce. This review confirms high ESBL- and MRSA-carriage rates for risk populations in Switzerland. Emerging pathogens (CPE and VRE) and certain populations (inpatients, LTCF residents and children) are understudied. We encourage epidemiologists and public health authorities to consider these findings in the planning of future surveillance studies.