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IMPORTANCE Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines. OBJECTIVE To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses. DESIGN, SETTING, AND PARTICIPANTS Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S. INTERVENTIONS Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 10 10 viral particles or 1 × 10 11 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group). MAIN OUTCOMES AND MEASURES Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses. RESULTS Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced. CONCLUSION AND RELEVANCE In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine.

Background The epidemiology of invasive mold infections (IMI) in transplant recipients differs, based on geography, hosts, preventative strategies, and methods of diagnosis. Methods We conducted a retrospective observational study to evaluate the epidemiology of proven and probable IMI, using prior definitions, among all adult hematopoietic stem cell (HSCT) and solid organ transplant (SOT) recipients in the era of “classic” culture-based diagnostics (2000–2009). Epidemiology was evaluated before and after an initiative was begun to increase bronchoscopy in HSCT recipients after 2005. Results In total, 106 patients with one IMI were identified. Invasive aspergillosis (IA) was the most common IMI (69; 65.1%), followed by mucormycosis (9; 8.5%). The overall rate of IMI (and IA) was 3.5% (2.5%) in allogeneic HSCT recipients. The overall incidence for IMI among lung, kidney, liver, and heart transplant recipients were 49, 2, 11, and 10 per 1000 person-years, respectively. The observed rate of IMI among HLA-matched unrelated and haploidentical HSCT recipients increased from 0.6% annually to 3.0% after bronchoscopy initiation (P<0.05). The 12-week mortality among allogeneic HSCT, liver, kidney, heart, and lung recipients with IMI was 52.4%, 47.1%, 27.8%, 16.7%, and 9.5%, respectively. Among allogeneic HSCT (odds ratio [OR]: 0.07, P=0.007) and SOT (OR: 0.22, P=0.05) recipients with IA, normal platelet count was associated with improved survival. Male gender (OR: 14.4, P=0.007) and elevated bilirubin (OR: 5.7, P=0.04) were significant predictors of mortality for allogeneic HSCT and SOT recipients with IA, respectively. Conclusions During the era of culture-based diagnostics, observed rates of IMI were low among all transplants except lung transplant recipients, with relatively higher mortality rates. Diagnostic aggressiveness and host variables impact the reported incidence and outcome of IMI and likely account for institutional variability in multicenter studies. Definitions to standardize diagnoses among SOT recipients are needed.

Clostridium difficile infection (CDI) is increasingly prevalent, dangerous and challenging to prevent and manage. Despite intense national and international attention the incidence of primary and of recurrent CDI (PCDI and RCDI, respectively) have risen rapidly throughout the past decade. Of major concern is the increase in cases of RCDI resulting in substantial morbidity, morality and economic burden. RCDI management remains challenging as there is no uniformly effective therapy, no firm consensus on optimal treatment, and reliable data regarding RCDI-specific treatment options is scant. Novel therapeutic strategies are critically needed to rapidly, accurately, and effectively identify and treat patients with, or at-risk for, RCDI. In this review we consider the factors implicated in the epidemiology, pathogenesis and clinical presentation of RCDI, evaluate current management options for RCDI and explore novel and emerging therapies.

We sought to describe the epidemiology of Clostridium difficile infection (CDI) among adult recipients of autologous hematopoietic stem cell transplantation (auto HSCT) within the first year after HSCT in centers with variable epidemiology of hyper-toxigenic strains. A multicenter, retrospective nested case-control study was conducted among 873 auto HSCT recipients at Johns Hopkins Hospital (JHH, Baltimore, MD) and Hôpital Maisonneuve-Rosemont (HMR, Montreal, Canada) between 1/2003-12/2008. Despite center differences in the prevalence of NAP-1 strains over the time period (21-43% JHH; 80-84% HMR), the 1-year incidence of CDI was similar (6.2% JHH; 5.7% HMR). The median time to infection was 11 days (interquartile range [IQR] 1 to 27). In case control analysis, the following were predictors for CDI: grade 2 or higher mucositis (odds ratio [OR]: 3.00, P=0.02) and receipt of a 4th generation cephalosporin (OR: 2.76, P=0.04). Mucositis was the strongest predictor of risk for CDI in multivariate analysis (adjusted OR [AOR]: 2.77; P=0.03). CDI is a common and early complication of auto HSCT. Treatment-related gastrointestinal mucosal damage, in addition to the potentially modifiable risk of antimicrobial exposure, influence risk for CDI early post-auto HSCT.

Purpose of review To review the most recent data regarding the epidemiology, risks factors, and outcomes among hematopoietic stem cell transplant recipients with Clostridium difficile infection (CDI). Recent findings With the emergence of an epidemic strain of C. difficile known as NAP1 in the early 2000s, rates of this infection have escalated globally. Hematopoietic stem cell transplant recipients appear to be one of the most vulnerable populations for the development of CDI. Traditional risk factors for CDI including antimicrobial exposure and older age are likely only a piece of the overall risk profile, with recent study results also emphasizing other factors such as transplant type, conditioning regimen, and graft-versus-host disease (GVHD). The relationship between CDI and subsequent development of GVHD, particularly of the gastrointestinal tract, is of specific interest. A bidirectional relationship of association has been highlighted in a number of recent studies and underscores the need for further prospective studies to address the potential indirect effects of alloreactivity induced by CDI. Summary CDI has emerged as one of the most common infections in the early transplant period. Recent studies have begun to address the epidemiology of disease, risk factors for, and outcomes after infection in the stem cell transplant. However, more research is needed to unravel the observed relationship between CDI and GVHD.

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