Early Introduction and Community Transmission of SARS-CoV-2 Omicron Variant, New York, New York, USA.

The Omicron variant of SARS-CoV-2 has become dominant in most countries and has raised significant global health concerns. As a global commerce center, New York, New York, USA, constantly faces the risk for multiple variant introductions of SARS-CoV-2. To elucidate the introduction and transmission of the Omicron variant in the city of New York, we created a comprehensive genomic and epidemiologic analysis of 392 Omicron virus specimens collected during November 25-December 11, 2021. We found evidence of 4 independent introductions of Omicron subclades, including the Omicron subclade BA.1.1 with defining substitution of R346K in the spike protein. The continuous genetic divergence within each Omicron subclade revealed their local community transmission and co-circulation in New York, including both household and workplace transmissions supported by epidemiologic evidence. Our study highlights the urgent need for enhanced genomic surveillance and effective response planning for better prevention and management of emerging SARS-CoV-2 variants.

SARS-CoV-2 Continuous Genetic Divergence and Changes in Multiplex RT-PCR Detection Pattern on Positive Retesting Median 150 Days after Initial Infection.

Being in the epicenter of the COVID-19 pandemic, our lab tested 193,054 specimens for SARS-CoV-2 RNA by diagnostic multiplex reverse transcription polymerase chain reaction (mRT-PCR) starting in March 2020, of which 17,196 specimens resulted positive. To investigate the dynamics of virus molecular evolution and epidemiology, whole genome amplification (WGA) and Next Generation Sequencing (NGS) were performed on 9516 isolates. 7586 isolates with a high quality were further analyzed for the mutation frequency and spectrum. Lastly, we evaluated the utility of the mRT-PCR detection pattern among 26 reinfected patients with repeat positive testing three months after testing negative from the initial infection. Our results show a continuation of the genetic divergence in viral genomes. Furthermore, our results indicate that independent mutations in the primer and probe regions of the nucleocapsid gene amplicon and envelope gene amplicon accumulate over time. Some of these mutations correlate with the changes of detection pattern of viral targets of mRT-PCR. Our data highlight the significance of a continuous genetic divergence on a gene amplification-based assay, the value of the mRT-PCR detection pattern for complementing the clinical diagnosis of reinfection, and the potential for WGA and NGS to identify mutation hotspots throughout the entire viral genome to optimize the design of the PCR-based gene amplification assay.

Co-Infection with 4 Species of Mycobacteria Identified by Using Next-Generation Sequencing.

We identified co-infection with 4 species of mycobacteria in a woman in New York, New York, USA, by using next-generation sequencing. This procedure is useful for identifying co-infections with multiple mycobacteria, tracing the geographic origin of strains, investigating transmission dynamics in susceptible populations, and gaining insight into prevention and control.

Detection and Genetic Characterization of Community-Based SARS-CoV-2 Infections - New York City, March 2020.

To limit introduction of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), the United States restricted travel from China on February 2, 2020, and from Europe on March 13. To determine whether local transmission of SARS-CoV-2 could be detected, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) conducted deidentified sentinel surveillance at six NYC hospital emergency departments (EDs) during March 1-20. On March 8, while testing availability for SARS-CoV-2 was still limited, DOHMH announced sustained community transmission of SARS-CoV-2 (1). At this time, twenty-six NYC residents had confirmed COVID-19, and ED visits for influenza-like illness* increased, despite decreased influenza virus circulation.† The following week, on March 15, when only seven of the 56 (13%) patients with known exposure histories had exposure outside of NYC, the level of community SARS-CoV-2 transmission status was elevated from sustained community transmission to widespread community transmission (2). Through sentinel surveillance during March 1-20, DOHMH collected 544 specimens from patients with influenza-like symptoms (ILS)§ who had negative test results for influenza and, in some instances, other respiratory pathogens.¶ All 544 specimens were tested for SARS-CoV-2 at CDC; 36 (6.6%) tested positive. Using genetic sequencing, CDC determined that the sequences of most SARS-CoV-2-positive specimens resembled those circulating in Europe, suggesting probable introductions of SARS-CoV-2 from Europe, from other U.S. locations, and local introductions from within New York. These findings demonstrate that partnering with health care facilities and developing the systems needed for rapid implementation of sentinel surveillance, coupled with capacity for genetic sequencing before an outbreak, can help inform timely containment and mitigation strategies.

COVID-19 in obstetrics 2020: the experience at a New York City medical center.

The global spread of the SARS-CoV-2 virus during the early months of 2020 was rapid and exposed vulnerabilities in health systems throughout the world. Obstetric SARS-CoV-2 disease was discovered to be largely asymptomatic carriage but included a small rate of severe disease with rapid decompensation in otherwise healthy women. Higher rates of hospitalization, Intensive Care Unit (ICU) admission and intubation, along with higher infection rates in minority and disadvantaged populations have been documented across regions. The operational gymnastics that occurred daily during the Covid-19 emergency needed to be translated to the obstetrics realm, both inpatient and ambulatory. Resources for adaptation to the public health crisis included workforce flexibility, frequent communication of operational and protocol changes for evaluation and management, and application of innovative ideas to meet the demand.

Risk factors for nephrotoxicity onset associated with polymyxin B therapy.

OBJECTIVES: Polymyxin B is an active agent against many MDR Gram-negative bacteria, but nephrotoxicity is a major hindrance to its widespread use. To guide its optimal use, we determined the risk factors for nephrotoxicity onset associated with polymyxin B. METHODS: In a multicentre, retrospective, cohort study, we evaluated adult patients with normal renal function who received ≥72 h of polymyxin B therapy. Pertinent information was retrieved from medical records; patients were followed for up to 30 days after therapy was started. The primary endpoint of this study was the onset of nephrotoxicity. A Cox proportional hazards model was used for analysis. RESULTS: A total of 192 patients (52.1% male, 67.7% Caucasian) were evaluated. The mean ±â€ŠSD age, actual body weight (ABW) and daily dose by ABW were 68.3 ±â€Š17.2 years, 71.5 ±â€Š20.4 kg and 1.5 ±â€Š0.5 mg/kg, respectively. The median duration of therapy was 9.5 days. The overall prevalence rate of nephrotoxicity was 45.8% and the median onset of nephrotoxicity was 9 days. Independent risk factors for the onset of nephrotoxicity included daily dose by ABW (HR = 1.73; P = 0.022), concurrent use of vancomycin (HR = 1.89; P = 0.005) and contrast media (HR = 1.79; P = 0.009). Nephrotoxicity was seen earlier in the high-risk group (P = 0.003). CONCLUSIONS: Risk factors for nephrotoxicity onset associated with polymyxin B were identified. In conjunction with susceptibility and other pharmacokinetic/pharmacodynamic data, our results can be used to optimize treatment for MDR Gram-negative infections.

In vitro assessment and multicenter cohort study of comparative nephrotoxicity rates associated with colistimethate versus polymyxin B therapy.

Despite concerns of nephrotoxicity, polymyxin antibiotics often remain the only susceptible agents for multidrug-resistant (MDR) Gram-negative bacteria. Colistin has been more commonly used clinically due to a perceived safety benefit. We compared the nephrotoxicity of colistin to polymyxin B. The in vitro cytotoxicity of colistin was compared to polymyxin B in two mammalian renal cell lines. To validate the clinical relevance of the findings, we evaluated adult patients with normal renal function who received a minimum of 72 h of polymyxin therapy in a multicenter study. The primary outcome was the prevalence of nephrotoxicity, as defined by the RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria. Colistin exhibited an in vitro cytotoxicity profile similar to polymyxin B. A total of 225 patients (121 receiving colistimethate, 104 receiving polymyxin B) were evaluated. Independent risk factors for colistimethate-associated nephrotoxicity included age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00 to 1.07; P = 0.03), duration of therapy (OR 1.08; 95% CI, 1.02 to 1.15; P = 0.02), and daily dose by ideal body weight (OR 1.40; 95% CI, 1.05 to 1.88; P = 0.02). In contrast, cystic fibrosis was found to be a protective factor in patients who received colistimethate (OR, 0.03; 95% CI, 0.001 to 0.79; P = 0.04). In a matched analysis based on the risk factors identified (n = 76), the prevalence of nephrotoxicity was higher with colistimethate than with polymyxin B (55.3% versus 21.1%; P = 0.004). Polymyxin B was not found to be more nephrotoxic than colistin and may be the preferred polymyxin for MDR infections. A prospective study comparing the two polymyxins directly is warranted.

A case of Lactobacillus jensenii associated native valve endocarditis.

Lactobacillus jensenii is rarely reported as a cause of endocarditis in immunocompetent patients. We describe a case of Lactobacillus jensenii associated native valve endocarditis that was identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) technology. While most Lactobacillus species are generally resistant to vancomycin, Lactobacillus jensenii is frequently susceptible, but treatment requires accurate susceptibility results followed by timely medical and surgical intervention. Probiotic use in patients can be a risk factor for infection with Lactobacillus species.

Fatal case of disseminated cryptococcal infection and meningoencephalitis in the setting of prolonged glucocorticoid use in a Covid-19 positive patient.

Based on the RECOVERY trial, glucocorticoids have become the mainstay of treatment for COVID-19, thus increasing the risk of opportunistic infections. We report a case of disseminated Cryptococcus neoformans with documented meningoencephalitis in a patient with severe COVID-19 in the setting of prolonged glucocorticoid administration with poor outcome likely due to adrenal involvement.

Combination antibiotic therapy for treatment of a patient with infected prosthesis and peri-prosthetic abscess due to Klebsiella pneumoniae harboring New Delhi Metallo (NDM) beta-lactamase.

Treatment options for patients infected with multi-drug resistant gram-negative bacteria harboring metallo-beta-lactamases (MBLs) requires precision therapy. We present the case of a 20 year-old male with a right distal femoral peri-prosthetic abscess with presumed infected hardware and osteomyelitis in whom four multi-drug resistant gram negative bacteria were isolated. The rapid identification of an MBL producing organism, novel combination of therapy, and prompt infection prevention enforcement and education led to appropriate treatment of our patient as well as prevention of spread of organisms during and after hospitalization. This case illustrated successful management of multiple challenges faced by patients infected and/or harboring extensively resistant bacteria.

Implementation of a Collaborated Antimicrobial Stewardship Program and Outpatient Parenteral Antimicrobial Therapy (OPAT) Unit-driven Monoclonal Antibody Therapy Program for COVID-19 at an NYC Hospital.

OBJECTIVES: This study aimed to assess the processes and clinical outcomes of a joint collaboration between Antimicrobial Stewardship Program (ASP) and the outpatient parenteral antimicrobial therapy (OPAT) unit for delivery of monoclonal antibody therapy for mild-to-moderate COVID-19. METHODS: We carried out a retrospective, interim analysis of our COVID-19 monoclonal antibody therapy program. Outcomes included clinical response, incidence of hospitalization, and adverse events. RESULTS: A total of 175 patients (casirivimab-imdevimab, n = 130; bamlanivimab, n = 45) were treated between December 2020 and March 1, 2021. The median time from symptom onset was 6 (IQR 4, 8) days at time of treatment. Of 135 patients available for follow-up, 71.9% and 85.9% of patients reported symptom improvement within 3 and 7 days of treatment, respectively. A total of 9 (6.7%) patients required COVID-19-related hospitalization for progression of symptoms, all within 14 days of treatment. A total of 7 (4%) patients experienced an infusion-related reaction. CONCLUSIONS: ASP-OPAT collaboration is a novel approach to implement an efficient and safe monoclonal antibody therapy program for the treatment of mild-to-moderate COVID-19.

Parental Coronavirus Disease 2019 Testing of Hospitalized Children: Rethinking Infection Control in a Pandemic.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) poses a challenge to infection control within hospital systems. Asymptomatic children and their caretakers carry the risk of silently spreading infection in pediatric emergency departments and hospital units. Our current knowledge is evolving, and infection control measures are frequently changing depending on new emerging data. METHODS: We conducted a point-prevalence study to assess SARS-CoV-2 Real-Time Polymerase Chain Reaction (SARS-CoV-2 RT-PCR) results of hospitalized children, their asymptomatic caretakers, and caretaker-child test concordance at a major community hospital in New York City. We screened Children and caretakers with temperature measurements and the presence of COVID-19 symptoms before pediatric emergency department evaluation. Children requiring hospitalization and their caretakers had nasopharyngeal swabs for SARS-CoV-2 RT-PCR. The paired results are used to identify the infection control level at the appropriate pediatric unit. RESULTS: Forty consecutive asymptomatic caretaker-child pairs had SARS-CoV-2 RT-PCR testing between May 28th to June 22nd, 2020. The rate of asymptomatic COVID-19 was 2.5% in hospitalized children and 7.5% in caretakers. The caretaker-child SARS-CoV-2 RT-PCR test concordance was evident in 95% of the cohort. CONCLUSION: This cohort had a low asymptomatic SARS-CoV-2 PCR positive rate in children and their caretakers with a high concordance rate of paired test results. It suggests that children's SARS-CoV-2 PCR test result will likely correspond to their accompanying caretaker at healthcare facilities where admission screening is performed.

Streptococcus pseudoporcinus: Case Reports and Review of the Literature.

Streptococcus pseudoporcinus is a beta-hemolytic Gram-positive, catalase-negative, nonmotile coccus arranged in short chains, usually found in the female genitourinary tract and differentiated from Streptococcus porcinus in 2006. Only two human infections associated with this organism have been reported to date: one in a patient with a first digit wound infection and another with lower extremity cellulitis. We describe two novel cases of Streptococcus pseudoporcinus causing endocarditis in one and pneumonia with empyema in another, illustrating the potential of these bacteria to cause severe invasive and life-threatening disease.

Asymptomatic rectal colonization with carbapenem-resistant Enterobacteriaceae and Clostridium difficile among residents of a long-term care facility in New York City.

BACKGROUND: Residents of long-term care facilities (LTCFs) are at increased risk for colonization and development of infections with multidrug-resistant organisms. This study was undertaken to determine prevalence of asymptomatic rectal colonization with Clostridium difficile (and proportion of 027/NAP1/BI ribotype) or carbapenem-resistant Enterobacteriaceae (CRE) in an LTCF population. METHODS: Active surveillance was performed for C difficile and CRE rectal colonization of 301 residents in a 320-bed (80-bed ventilator unit), hospital-affiliated LTCF with retrospective chart review for patient demographics and potential risk factors. RESULTS: Over 40% of patients had airway ventilation and received enteral feeding. One-third of these patients had prior C difficile-associated infection (CDI). Asymptomatic rectal colonization with C difficile occurred in 58 patients (19.3%, one-half with NAP1+), CRE occurred in 57 patients (18.9%), and both occurred in 17 patients (5.7%). Recent CDI was significantly associated with increased risk of C difficile ± CRE colonization. Multivariate logistic regression analysis revealed presence of tracheostomy collar to be significant for C difficile colonization, mechanical ventilation to be significant for CRE colonization, and prior CDI to be significant for both C difficile and CRE colonization. CONCLUSIONS: The strong association of C difficile or CRE colonization with disruption of normal flora by mechanical ventilation, enteral feeds, and prior CDI carries important implications for infection control intervention in this population.

Mixing with herringbone-inspired microstructures: overcoming the diffusion limit in co-laminar microfluidic devices.

Enhancing mixing is of uttermost importance in many laminar microfluidic devices, aiming at overcoming the severe performance limitation of species transport by diffusion alone. Here we focus on the significant category of microscale co-laminar flows encountered in membraneless redox flow cells for power delivery. The grand challenge is to achieve simultaneously convective mixing within each individual reactant, to thin the reaction depletion boundary layers, while maintaining separation of the co-flowing reactants, despite the absence of a membrane. The concept presented here achieves this goal with the help of optimized herringbone flow promoting microstructures with an integrated separation zone. Our electrochemical experiments using a model redox couple show that symmetric flow promoter designs exhibit laminar to turbulent flow behavior, the latter at elevated flow rates. This change in flow regime is accompanied by a significant change in scaling of the Sherwood number with respect to the Reynolds number from Sh ~ Re(0.29) to Sh ~ Re(0.58). The stabilized continuous laminar flow zone along the centerline of the channel allows operation in a co-laminar flow regime up to Re ~325 as we demonstrate by micro laser-induced fluorescence (µLIF) measurements. Micro particle image velocimetry (µPIV) proves the maintenance of a stratified flow along the centerline, mitigating reactant cross-over effectively. The present work paves the way toward improved performance in membraneless microfluidic flow cells for electrochemical energy conversion.

Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis.

OBJECTIVES: The goal of this study was to assess the prognostic significance of midwall and infarct patterns of late gadolinium enhancement (LGE) in aortic stenosis. BACKGROUND: Myocardial fibrosis occurs in aortic stenosis as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in a range of other cardiac conditions. METHODS: Between January 2003 and October 2008, consecutive patients with moderate or severe aortic stenosis undergoing cardiovascular magnetic resonance with administration of gadolinium contrast were enrolled into a registry. Patients were categorized into absent, midwall, or infarct patterns of LGE by blinded independent observers. Patient follow-up was completed using patient questionnaires, source record data, and the National Strategic Tracing Service. RESULTS: A total of 143 patients (age 68 ± 14 years; 97 male) were followed up for 2.0 ± 1.4 years. Seventy-two underwent aortic valve replacement, and 27 died (24 cardiac, 3 sudden cardiac deaths). Compared with those with no LGE (n = 49), univariate analysis revealed that patients with midwall fibrosis (n = 54) had an 8-fold increase in all-cause mortality despite similar aortic stenosis severity and coronary artery disease burden. Patients with an infarct pattern (n = 40) had a 6-fold increase. Midwall fibrosis (hazard ratio: 5.35; 95% confidence interval: 1.16 to 24.56; p = 0.03) and ejection fraction (hazard ratio: 0.96; 95% confidence interval: 0.94 to 0.99; p = 0.01) were independent predictors of all-cause mortality by multivariate analysis. CONCLUSIONS: Midwall fibrosis was an independent predictor of mortality in patients with moderate and severe aortic stenosis. It has incremental prognostic value to ejection fraction and may provide a useful method of risk stratification.