Natural heteroclitic-like peptides are generated by SARS-CoV-2 mutations.

Humoral immunity is sensitive to evasion by SARS-CoV-2 mutants, but CD8 T cells seem to be more resistant to mutational inactivation. By a systematic analysis of 30 spike variant peptides containing the most relevant VOC and VOI mutations that have accumulated overtime, we show that in vaccinated and convalescent subjects, mutated epitopes can have not only a neutral or inhibitory effect on CD8 T cell recognition but can also enhance or generate de novo CD8 T cell responses. The emergence of these mutated T cell function enhancing epitopes likely reflects an epiphenomenon of SARS-CoV-2 evolution driven by antibody evasion and increased virus transmissibility. In a subset of individuals with weak and narrowly focused CD8 T cell responses selection of these heteroclitic-like epitopes may bear clinical relevance by improving antiviral protection. The functional enhancing effect of these peptides is also worth of consideration for the future development of new generation, more potent COVID-19 vaccines.

Immune tolerance induction by nonmyeloablative haploidentical HSCT combining T-cell depletion and posttransplant cyclophosphamide.

The establishment of safe approaches to attain durable donor-type chimerism and immune tolerance toward donor antigens represents a major challenge in transplantation biology. Haploidentical hematopoietic stem cell transplantation (HSCT) is currently used for cancer therapy either as a T-cell-depleted megadose HSCT following myeloablative conditioning or with T-cell-replete HSCT following nonmyeloablative conditioning (NMAC) and high-dose posttransplant cyclophosphamide (PTCY). The latter approach suffers from a significant rate of chronic graft-versus-host disease (GVHD), despite prolonged immunosuppression. The use of T-depleted grafts, although free of GVHD risk, is not effective after NMAC because of graft rejection. We now demonstrate in mice conditioned with NMAC that combining the power of high-dose PTCY with T-cell-depleted megadose HSCT can overcome this barrier. This approach was evaluated in 2 patients with multiple myeloma and 1 patient with Hodgkin lymphoma. The first myeloma patient now followed for 25 months, exhibited full donor-type chimerism in the myeloid and B-cell lineages and mixed chimerism in the T-cell compartment. The second myeloma patient failed to attain chimerism. Notably, the low toxicity of this protocol enabled a subsequent successful fully myeloablative haploidentical HSCT in this patient. The third patients was conditioned with slightly higher total body irradiation and engrafted promptly. All patients remain in remission without GVHD. Both engrafted patients were able to control cytomegalovirus reactivation. Enzyme-linked immunospot analysis revealed immune tolerance toward donor cells. Our results demonstrate a novel and safer nonmyeloablative haplo-HSCT offering a platform for immune tolerance induction as a prelude to cell therapy and organ transplantation.

Two rare cases of Acremonium acute endophthalmitis after cataract surgery in a tertiary care hospital.

This report describes two cases of Acremonium sp. endophthalmitis, occurring in two patients who underwent cataract surgery on the same day in the same operating room of our hospital ophthalmology clinic. Diagnosis of fungal endophthalmitis was established by the repeated isolation of the same fungal agent from vitreous washing, acqueous fluid and intraocular lens samples and by its identification on the basis of morphological and molecular features. The cases reported in this study emphasize the need for clinical microbiology laboratories to be prepared to face the diagnosis of uncommon infectious diseases such as exogenous fungal endophthalmitis by Acremonium, and to enhance the awareness of surgeons and clinicians of this occurrence.

Candida sake as the causative agent of spondylodiscitis in a hemodialysis patient.

BACKGROUND CONTEXT: Fungal spondylodiscitis is often because of Candida albicans or other common Candida species, whereas unusual strains such as Candida sake are often thought to be nonpathogenic. PURPOSE: To report the first case of spondylodiscitis caused by C sake and its outcome after antimycotic therapy; as the disease occurred in a patient undergoing hemodialysis (HD), we also discuss the potential conditions related to the uremic state and to HD itself, which may predispose to spondylodiscitis. STUDY DESIGN/SETTING: Case report. METHODS: Report of the patient's clinical findings and review of the literature concerning spondylodiscitis in HD patients and infections caused by C sake. RESULTS: The patient was a 48-year-old woman with end-stage renal disease (ESRD) undergoing HD who presented with back pain; spine computed tomographic (CT) scans showed lumbar spondylodiscitis with large bilateral abscesses in the psoas muscles, with an imaging appearance resembling that of Pott's disease. Surprisingly, C sake was isolated from the cultures of the liquid obtained by CT-guided aspiration of both abscesses, and fluconazole therapy was strikingly effective in inducing abscess regression and healing of spondylodiscitis. CONCLUSIONS: In patients with chronic disorders such as ESRD, spondylodiscitis can also be caused by rare fungal strains that are usually thought to be nonpathogenic; a correct diagnostic workup is essential, as such forms can promptly respond to common antimycotic agents.

Two-center collaborative evaluation of the performance of the BD Phoenix automated microbiology system for identification and antimicrobial susceptibility testing of Enterococcus spp. and Staphylococcus spp.

The performance of the BD Phoenix Automated Microbiology System (BD Diagnostic Systems, Sparks, Md.) was assessed for identification (ID) and antimicrobial susceptibility testing (AST) for the majority of clinically encountered bacterial isolates in a European collaborative two-center trial. A total of 469 bacterial isolates of the genera Staphylococcus (275 isolates), Enterococcus (179 isolates), and Streptococcus (15 isolates, for ID only) were investigated; of these, 367 were single patient isolates, and 102 were challenge strains tested at one center. Sixty-four antimicrobial drugs were tested, including the following drug classes: aminoglycosides, beta-lactam antibiotics, beta-lactam-beta-lactamase inhibitors, carbapenems, cephems, folate antagonists, quinolones, glycopeptides, macrolides-lincosamides-streptogramin B (MLS), and others. Phoenix ID results were compared to those of the laboratories' routine ID systems (API 32 Staph, API 32 Strep, and VITEK 2 [bioMérieux, Marcy l'Etoile, France]); Phoenix AST results were compared to those of frozen standard broth microdilution (SBM) panels according to NCCLS guidelines (NCCLS document M 100-S 9, approved standard M 7-A 4). Discrepant results were repeated in duplicate. Concordant IDs of 97.1, 98.9, and 100% were observed for staphylococci, enterococci, and streptococci, respectively. For AST results the overall essential agreement was 93.3%; the category agreement was 97.3%; and the very major error rate, major error rate, and minor error rate were 1.2, 1.9, and 1.3%, respectively. In conclusion, the Phoenix ID results showed high agreement with results of the systems to which they were being compared; the AST performance was highly equivalent to that of the SBM reference method.