denotes emergency department, and IQR interquartile range. † Race was determined by the clinical team. ‡ Obesity was defined as a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher.

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Background Patients hospitalized with coronavirus disease 2019 (COVID-19) frequently require mechanical ventilation and have high mortality rates, but the impact of viral burden on these outcomes is unknown. Methods We conducted a retrospective cohort study of patients hospitalized with COVID-19 from March 30 to April 30, 2020 at two hospitals in New York City. SARS-CoV-2 viral load was assessed using cycle threshold (Ct) values from a reverse transcription-polymerase chain reaction assay applied to nasopharyngeal swab samples. We compared patient characteristics and outcomes among patients with high, medium, and low admission viral loads and assessed whether viral load was independently associated with risk of intubation and in-hospital mortality. Results We evaluated 678 patients with COVID-19. Higher viral load was associated with increased age, comorbidities, smoking status, and recent chemotherapy. In-hospital mortality was 35.0% with a high viral load (Ct<25; n=220), 17.6% with a medium viral load (Ct 25-30; n=216), and 6.2% with a low viral load (Ct>30; n=242; P<0.001). The risk of intubation was also higher in patients with a high viral load (29.1%), compared to those with a medium (20.8%) or low viral load (14.9%; P<0.001). High viral load was independently associated with mortality (adjusted odds ratio [aOR] 6.05; 95% confidence interval [CI]: 2.92-12.52; P<0.001) and intubation (aOR 2.73; 95% CI: 1.68-4.44; P<0.001) in multivariate models. Conclusions Admission SARS-CoV-2 viral load among hospitalized patients with COVID-19 independently correlates with the risk of intubation and in-hospital mortality. Providing this information to clinicians could potentially be used to guide patient care.

Patients with cancer may be at increased risk of severe coronavirus disease 2019 (COVID-19), but the role of viral load on this risk is unknown. We measured SARS-CoV-2 viral load using cycle threshold (C T ) values from reverse transcription-polymerase chain reaction assays applied to nasopharyngeal swab specimens in 100 patients with cancer and 2914 without cancer who were admitted to three New York City hospitals. Overall, the in-hospital mortality rate was 38.8% among patients with a high viral load, 24.1% among patients with a medium viral load, and 15.3% among patients with a low viral load ( P <0.001). Similar findings were observed in patients with cancer (high, 45.2% mortality; medium, 28.0%; low, 12.1%; P =0.008). Patients with hematologic malignancies had higher median viral loads (C T =25.0) than patients without cancer (C T =29.2; P =0.0039). SARS-CoV-2 viral load results may offer vital prognostic information for patients with and without cancer who are hospitalized with COVID-19.

Carbapenem-resistant Enterobacteriaceae (CRE) are emerging global pathogens. The spread of CRE to transplant recipients and patients with hematologic malignancies has ominous implications. These patients rely on timely, active antibacterial therapy to combat gram-negative infections; however, recommended empirical regimens are not active against CRE. Approximately 3%-10% of solid organ transplant (SOT) recipients in CRE-endemic areas develop CRE infection, and the infection site correlates with the transplanted organ. Mortality rates associated with CRE infections approach 40% in SOT recipients and 65% in patients with hematologic malignancies. Given that the current antimicrobial armamentarium to combat CRE is extremely limited, a multifaceted approach that includes antimicrobial stewardship and active surveillance is needed to prevent CRE infections in immunocompromised hosts. Improving outcomes of established infections will require the use of risk factor-based prediction tools and molecular assays to more rapidly administer CRE-active therapy and the development of new antimicrobial agents with activity against CRE.

Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of Ն4/4 g/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P ϭ 0.045), cancer (aOR, 3.61, P ϭ 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P ϭ 0.03) were independently associated with mortality. Active empirical ther-

IMPORTANCEHerpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster.OBJECTIVE To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients.DESIGN, SETTING, AND PARTICIPANTS Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT.INTERVENTIONS Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. MAIN OUTCOMES AND MEASURESThe primary end point was occurrence of confirmed herpes zoster cases. RESULTS Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P < .001), equivalent to 68.2% vaccine efficacy. Of 8 secondary end points, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; 95% CI, 0.00-0.78; P = .02) and of other prespecified herpes zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst herpes zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .01). Five secondary objectives were descriptive. Injection site reactions were recorded in 86% of vaccine and 10% of placebo recipients, of which pain was the most common, occurring in 84% of vaccine recipients (grade 3: 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points. CONCLUSIONS AND RELEVANCE Among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine compared with placebo significantly reduced the incidence of herpes zoster over a median follow-up of 21 months.

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