Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Specific Memory B Cells From Individuals With Diverse Disease Severities Recognize SARS-CoV-2 Variants of Concern.

The unprecedented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has called for substantial investigations into the capacity of the human immune system to protect against reinfection and keep pace with the evolution of SARS-CoV-2. We evaluated the magnitude and durability of the SARS-CoV-2-specific antibody responses against parental WA-1 SARS-CoV-2 receptor-binding domain (RBD) and a representative variant of concern (VoC) RBD using antibodies from 2 antibody compartments: long-lived plasma cell-derived plasma antibodies and antibodies encoded by SARS-CoV-2-specific memory B cells (MBCs). Thirty-five participants naturally infected with SARS-CoV-2 were evaluated; although only 25 of 35 participants had VoC RBD-reactive plasma antibodies, 34 of 35 (97%) participants had VoC RBD-reactive MBC-derived antibodies. Our finding that 97% of previously infected individuals have MBCs specific for variant RBDs provides reason for optimism regarding the capacity of vaccination, prior infection, and/or both, to elicit immunity with the capacity to limit disease severity and transmission of VoCs as they arise and circulate.

Open-Label Trial of Amikacin Liposome Inhalation Suspension in Mycobacterium abscessus Lung Disease.

BACKGROUND: Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance. RESEARCH QUESTION: Does treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease? STUDY DESIGN AND METHODS: In an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance. RESULTS: Of 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%). INTERPRETATION: In a cohort of patients primarily with macrolide-resistant M abscessus, one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03038178; URL: www. CLINICALTRIALS: gov.

SARS-CoV-2 specific memory B-cells from individuals with diverse disease severities recognize SARS-CoV-2 variants of concern.

In this investigation we examined the magnitude, breadth, and durability of SARS-CoV-2 specific antibodies in two distinct B-cell compartments: long-lived plasma cell-derived antibodies in the plasma, and peripheral memory B-cells along with their associated antibody profiles elicited after in vitro stimulation. We found that magnitude varied amongst individuals, but was the highest in hospitalized subjects. Variants of concern (VoC) -RBD-reactive antibodies were found in the plasma of 72% of samples in this investigation, and VoC-RBD-reactive memory B-cells were found in all but 1 subject at a single time-point. This finding, that VoC-RBD-reactive MBCs are present in the peripheral blood of all subjects including those that experienced asymptomatic or mild disease, provides a reason for optimism regarding the capacity of vaccination, prior infection, and/or both, to limit disease severity and transmission of variants of concern as they continue to arise and circulate.