Nausea Predicts Bacteremia in Immunocompetent Patients with Pneumococcal Community-Acquired Pneumonia: Secondary Data Analysis from a Prospective Cohort.

BACKGROUND: In pneumococcal community-acquired pneumonia (CAP), bacteremia is associated with increased mortality, but initial clinical severity scores frequently fail to identify bacteremic patients at risk. We have previously shown that gastrointestinal symptoms are common among patients admitted to the hospital with pneumococcal bacteremia. The aim of this study was to examine gastrointestinal symptoms and inflammatory responses in bacteremic and non-bacteremic pneumococcal CAP in a prospective cohort of immunocompromised and immunocompetent patients hospitalized with CAP. METHODS: Logistic regression analysis was used to estimate the predictive value of gastrointestinal symptoms for pneumococcal bacteremia in patients with CAP. The Mann-Whitney test was used to compare inflammatory responses in patients with bacteremic vs. non-bacteremic pneumococcal CAP. RESULTS: Eighty-one patients with pneumococcal CAP were included, of whom 21 (26%) had bacteremia. Immunocompetent patients with pneumococcal CAP had an odds ratio of 16.5 (95% CI 3.0-90.9, p = 0.001) for bacteremia if nausea was present, whereas no such association was found in the immunocompromised patients (OR 0.22, 95% CI 0.02-2.05, p = 0.18). The serum levels of C-reactive protein, procalcitonin and interleukin 6 were significantly higher in the patients with bacteremic pneumococcal CAP compared to non-bacteremic pneumococcal CAP patients (p < 0.001, p = 0.005, and p = 0.019, respectively). CONCLUSIONS: In immunocompetent patients hospitalized with pneumococcal CAP, nausea may be a predictor of bacteremia. Bacteremic pneumococcal CAP patients display an increased inflammatory response compared to non-bacteremic pneumococcal CAP patients.

Development and scaling of a sequencing pipeline for genomic surveillance of SARS-CoV-2 in New York City

In the ongoing COVID-19 pandemic, detecting the appearance and spread of variants of concern (VOC) is a critical capability in the fight to quell the virus and return to normalcy. Genomic surveillance of the emergence, propagation, and geographical spread of VOCs is thus an important tool for public health officials and government leaders to make policy decisions and advise the public. As part of our role as a major SARS-CoV-2 diagnostic testing facility in New York City, the Pandemic Response Lab (PRL) has been performing genomic surveillance on the large number of positive samples processed by the facility on a daily basis from throughout the New York metropolitan area. Here we describe the development and optimization of a high-throughput SARS-CoV-2 genome sequencing facility at PRL serving New York City.

Hepcidin predicts 5-year mortality after community-acquired pneumonia.

BACKGROUND: Virtually all living organisms, including microbes and humans, depend on iron to survive and grow. During an infection, the plasma level of iron and several iron-related proteins change substantially. We hypothesized that iron and iron-related proteins could predict short- and long-term outcomes in community-acquired pneumonia. METHODS: Blood samples from a prospective cohort of 267 in-patients with community-acquired pneumonia were analysed for hepcidin, ferritin, iron, transferrin, transferrin saturation, and soluble transferrin receptor at admission and 6-weeks post-discharge. Adverse short-term outcome was defined as admission to intensive care unit or death within 30 days, and long-term outcome was assessed as 5-year overall mortality. Logistic regression, Kaplan Meier survival curves, and Cox regression models with cut-offs at median for the potential biomarkers were used for statistical evaluation. RESULTS: Low admission levels of hepcidin predicted 5-year overall mortality, independently of age, sex, comorbid conditions, and anaemia. Low levels of ferritin at admission as well as low levels of iron and transferrin saturation and high levels of soluble transferrin receptor at the 6-week follow-up were predictors of 5-year overall mortality in univariable, but not in multivariable analyses. Neither of these potential biomarkers predicted adverse short-term outcomes. CONCLUSIONS: In hospitalized patients with community-acquired pneumonia, low levels of hepcidin at admission predicted 5-year overall mortality, but not short-term adverse outcome.

ASSESSMENT OF POTENTIAL SARS-CoV-2 VIRUS N GENE INTEGRATION INTO HUMAN GENOME REVEALS NO SIGNIFICANT IMPACT ON RT-qPCR COVID-19 DIAGNOSTIC TESTING

The SARS Coronavirus 2 (SARS-CoV-2) pandemic presents new scientific and scale-up challenges for diagnostic capabilities worldwide. The gold standard diagnostic for SARS-CoV-2 infection is a reverse transcription/quantitative PCR (RT-qPCR) which targets the viral genome, an assay that has now been performed on millions of patient specimens worldwide regardless of symptomatic status. Recently Zhang et al. suggested the possibility that the SARS-CoV-2 N gene could integrate into host cell DNA through the action of the LINE-1 retrotransposon, a mobile element that is potentially active in human somatic cells, thereby calling into question the veracity of N-gene based RT-qPCR for detection of SARS-CoV-2 infection. Accordingly, we assessed the potential impact of these purported integration events on nasal swab specimens tested at our clinical laboratory. Using an N-gene based RT-qPCR assay, we tested 768 arbitrarily selected specimens and identified 2 samples which resulted in a positive detection of viral sequence in the absence of reverse transcriptase, a necessary but not sufficient signal consistent with possible integration of the SARS-CoV-2 N gene into the host genome. Regardless of possible viral N gene integration into the genome, in this small subset of samples, all patients were still positive for SARS-CoV-2 infection, as indicated by a much lower Ct value for reactions performed in the presence of reverse transcriptase (RT) versus reactions performed without RT. Moreover, one of the two positives observed in the absence of RT also tested positive when using primers targeting ORF1ab, a gene closer to the 5 end of the genome. These data are inconsistent with the N gene integration hypothesis suggested by the studies by Zhang et al., and importantly, our results suggest little to no practical impact of possible SARS-CoV-2 genome integration events on RT-qPCR testing. COMPETING INTEREST STATEMENTThe authors of this study are employees of the Pandemic Response Lab (PRL)/ReOpen Diagnostics, a private company performing SARS-CoV-2 RT-qPCR based testing, an area of interest of this study.

Hepcidin and Ferritin Predict Microbial Etiology in Community-Acquired Pneumonia.

BACKGROUND: Iron is crucial for survival and growth of microbes. Consequently, limiting iron availability is a human antimicrobial defense mechanism. We explored iron and iron-related proteins as potential biomarkers in community-acquired pneumonia and hypothesized that infection-induced changes in these potential biomarkers differ between groups of pathogens and could predict microbial etiology. METHODS: Blood samples from a prospective cohort of 267 patients with community-acquired pneumonia were analyzed for hepcidin, ferritin, iron, transferrin, and soluble transferrin receptor at admission, clinical stabilization, and a 6-week follow-up. A total of 111 patients with an established microbiological diagnosis confined to 1 microbial group (atypical bacterial, typical bacterial, or viral) were included in predictive analyses. RESULTS: High admission levels of ferritin predicted atypical bacterial versus typical bacterial etiology (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.18-4.32; P = .014). Furthermore, hepcidin and ferritin predicted atypical bacterial versus viral etiology (hepcidin: OR = 3.12, 95% CI = 1.34-7.28, P = .008; ferritin: OR = 2.38, 95% CI = 1.28-4.45, P = .006). The findings were independent of C-reactive protein and procalcitonin. CONCLUSIONS: Hepcidin and ferritin are potential biomarkers of microbial etiology in community-acquired pneumonia.

Progress and Challenges in "Getting to Zero" New HIV Infections in Miami, Florida.

OBJECTIVES: Miami has the highest rate of new HIV diagnoses in the United States. We examined the early successes and challenges in fulfilling recommendations made by the Miami-Dade County HIV/AIDS Getting to Zero Task Force, formed by local experts in 2016. METHODS: We used a host of surveillance data, published empirical studies, public reports, and unpublished data from partners of the Task Force to evaluate progress and challenges in meeting the recommendations. RESULTS: Improvements in prevention and care included routinized HIV testing in emergency departments, moving the linkage-to-care benchmark from 90 to 30 days, increased viral suppression, and awareness of pre-exposure prophylaxis. However, treatment enrollment, viral suppression, and pre-exposure prophylaxis uptake remained low. CONCLUSIONS: Recommendations from the Task Force provide excellent guidance for implementing evidence-based HIV prevention in Miami, yet success in achieving the recommendations will require continued or increased support in many public health sectors in South Florida.

The seamless transfer of care: a pilot study assessing the usability of an electronic transfer of care communication tool.

The purpose of this pilot study was to explore the feasibility of implementing a new electronic transfer of care (TOC) tool. The study was conducted in a Canadian tertiary care center. Brief survey instruments were completed by acute care physicians, community-based physicians, and patients to assess providers' perspectives on the usability of the novel electronic tool. The units of analysis were physician and patient perceptions. Mixed methods were used including descriptive statistical analyses and qualitative thematic analysis. Twenty-eight unique acute care physicians completed 100 electronic TOC summaries, and 44 unique community-based physicians rated quality and pertinence of the summaries. Twenty-two patients responded to a follow-up telephone call. The novel TOC communication tool was generally well received by physicians and patients, and it is now being evaluated in a large-scale clinical trial assessing hard clinical outcomes. The information presented herein provides a template for assessment of such information system innovations.