Molecular and Clinical Epidemiology of SARS-CoV-2 Infection among Vaccinated and Unvaccinated Individuals in a Large Healthcare Organization from New Jersey.

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations, from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOCs) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOCs, including Alpha (n = 714), Delta (n = 1877), and Omicron (n = 1802). Omicron isolates were further sub-typed as BA.1 (n = 899), BA.2 (n = 853), or BA.4/BA.5 (n = 50); the remaining 614 isolates were classified as "Other". Approximately 31.5% (1577/5007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p < 0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p < 0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p < 0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

Genomic Epidemiology and Serology Associated with a SARS-CoV-2 R.1 Variant Outbreak in New Jersey.

Examining the neutralizing capacity of monoclonal antibodies (MAbs) used to treat COVID-19, as well as antibodies recovered from unvaccinated, previously vaccinated, and infected individuals, against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) remains critical to study. Here, we report on a SARS-CoV-2 nosocomial outbreak caused by the SARS-CoV-2 R.1 variant harboring the E484K mutation in a 281-bed psychiatric facility in New Jersey among unvaccinated inpatients and health care professionals (HCPs). A total of 81 inpatients and HCPs tested positive for SARS-Cov-2 by reverse transcription (RT)-PCR from 29 October 9 to 30 November 2020. The R.1 variant exhibits partial or complete resistance to two MAbs in clinical use, as well as 2 receptor binding domain MAbs and 4 N-terminal domain (NTD) MAbs. NTD MAbs against pseudovirus harboring single characteristic R.1 mutations highlight the role of S255F in loss of activity. Additionally, we note dampened neutralization capacity by plasma from individuals with previous SARS-CoV-2 infection or sera from vaccinated individuals. The relative resistance of the R.1 variant is likely lower than that of B.1.351 and closer to that of P.1 and B.1.526. The R.1 lineage has been reported in 47 states in the United States and 40 countries. Although high proportions exhibited symptoms (26% and 61% among patients and HCPs, respectively) and relative antibody resistance, we detected only 10 R.1 variants from over 2,900 samples (~0.34%) collected from January to October 2021. Among 3 vaccinated individuals previously infected with R.1, we observed robust neutralizing antibody responses against SARS-CoV-2 wild type and VOCs. IMPORTANCE The neutralizing capacities of monoclonal antibodies used to treat COVID-19 and of those recovered from previously infected and vaccinated individuals against SARS-CoV-2 variants of concern (VOCs) remain important questions. We report on a nosocomial outbreak caused by a SARS-CoV-2 R.1 variant harboring an E484K mutation among 81 unvaccinated inpatients and health care professionals. We note high attack rates with symptoms in nearly 50% of infected individuals, in sharp contrast to an unrelated institutional outbreak caused by the R.1 variant among a vaccinated population. We found little evidence of significant community spillover. This variant exhibits partial or complete resistance to two monoclonal antibodies in clinical use and dampened the neutralization capacity of convalescent-phase plasma from individuals with previous infection or sera from vaccinated individuals. Among three vaccinated individuals previously infected with R.1, we observed robust neutralizing antibody responses against SARS-CoV-2 wild type and VOCs. These findings underscore the importance of vaccination for prevention of symptomatic COVID-19 disease.

A multiphase intervention of novel color additive for bleach disinfectant wipes improves thoroughness of cleaning in an academic medical center.

Surface disinfection is critical for preventing health care-associated infections; however, sustaining high-quality cleaning technique is challenging without constant feedback and training of staff. A novel color additive to bleach wipes, Highlight, indicates where surfaces have been wiped and fades to colorless to provide real-time visual feedback of cleaning. In a multiphase interventional study, Highlight reduced failure rates of cleaning based on fluorescent marker removal (15.0%-4.5%) and adenosine triphosphate bioluminescence assay (3.6%-2.5%).

At the vanguard: Leaders' perspectives on establishing healthcare system infection prevention programs.

Hospitals are increasingly consolidating into health systems. Some systems have appointed healthcare epidemiologists to lead system-level infection prevention programs. Ideal program infrastructure and support resources have not been described. We informally surveyed 7 healthcare epidemiologists with recent experience building and leading system-level infection prevention programs. Key facilitators and barriers for program structure and implementation are described.

Prevention of Mycobacterium tuberculosis Transmission in Health Care Settings.

Patients with tuberculosis (TB) pose a risk to other patients and health care workers, and outbreaks in health care settings occur when appropriate infection control measures are not used. This article discusses strategies to prevent transmission of Mycobacterium tuberculosis within health care settings. All health care facilities should have an operational TB infection control plan that emphasizes the use of a hierarchy of controls (administrative, environmental, and personal respiratory protection). Resources available to clinicians who work in the prevention and investigation of nosocomial transmission of M tuberculosis also are discussed.

Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study.

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.

Preventing Transmission of Mycobacterium tuberculosis in Health Care Settings.

Patients with tuberculosis (TB) pose a risk to other patients and health care workers, and outbreaks in health care settings occur when appropriate infection control measures are not used. In this article, we discuss strategies to prevent transmission of Mycobacterium tuberculosis within health care settings. All health care facilities should have an operational TB infection control plan that emphasizes the use of a hierarchy of controls (administrative, environmental, and personal respiratory protection). We also discuss resources available to clinicians who work in the prevention and investigation of nosocomial transmission of M tuberculosis.

Contact precautions: more is not necessarily better.

OBJECTIVE: To determine whether increases in contact isolation precautions are associated with decreased adherence to isolation practices among healthcare workers (HCWs). DESIGN: Prospective cohort study from February 2009 to October 2009. SETTING: Eleven teaching hospitals. PARTICIPANTS: HCWs. METHODS: One thousand thirteen observations conducted on HCWs. Additional data included the number of persons in isolation, types of HCWs, and hospital-specific contact precaution practices. Main outcome measures included compliance with individual components of contact isolation precautions (hand hygiene before and after patient encounter, donning of gown and glove upon entering a patient room, and doffing upon exiting) and overall compliance (all 5 measures together) during varying burdens of isolation. RESULTS: Compliance with hand hygiene was as follows: prior to donning gowns/gloves, 37.2%; gowning, 74.3%; gloving, 80.1%; doffing of gowns/gloves, 80.1%; after gown/glove removal, 61%. Compliance with all components was 28.9%. As the burden of isolation increased (20% or less to greater than 60%), a decrease in compliance with hand hygiene (43.6%-4.9%) and with all 5 components (31.5%-6.5%) was observed. In multivariable analysis, there was an increase in noncompliance with all 5 components of the contact isolation precautions bundle (odds ratio [OR], 6.6 [95% confidence interval (CI), 1.15-37.44]; P = .03) and in noncompliance with hand hygiene prior to donning gowns and gloves (OR, 10.1 [95% CI, 1.84-55.54]; P = .008) associated with increasing burden of isolation. CONCLUSIONS: As the proportion of patients in contact isolation increases, compliance with contact isolation precautions decreases. Placing 40% of patients under contact precautions represents a tipping point for noncompliance with contact isolation precautions measures.

Review of macrolides (azithromycin, clarithromycin), ketolids (telithromycin) and glycylcyclines (tigecycline).

The advanced macrolides, azithromycin and clarithromycin, and the ketolide, telithromycin, are structural analogs of erythromycin. They have several distinct advantages when compared with erythromycin, including enhanced spectrum of activity, more favorable pharmacokinetics and pharmacodynamics, once-daily administration, and improved tolerability. Clarithromycin and azithromycin are used extensively for the treatment of respiratory tract infections, sexually transmitted diseases, and Helicobacter pylori-associated peptic ulcer disease. Telithromycin is approved for the treatment of community-acquired pneumonia. Severe hepatotoxicity has been reported with the use of telithromycin.

Prevention of health care-acquired pneumonia and transmission of Mycobacterium tuberculosis in health care settings.

Health care-acquired pneumonia (HAP) is associated with significant morbidity and mortality. These infections most frequently arise from a patient's indigenous flora, although occasionally they result from exposure to environmental pathogens such as Legionella and Aspergillus. This article reviews infection prevention strategies to reduce the incidence of HAP. Successful implementation of these prevention strategies usually requires a multidisciplinary approach and standardization of protocols. This article also discusses strategies to prevent transmission of Mycobacterium tuberculosis within health care settings.

Macrolides, ketolides, and glycylcyclines: azithromycin, clarithromycin, telithromycin, tigecycline.

The advanced macrolides, azithromycin and clarithromycin, and the ketolide, telithromycin, are structural analogs of erythromycin. They have several distinct advantages when compared with erythromycin, including enhanced spectrum of activity, more favorable pharmacokinetics and pharmacodynamics, once-daily administration, and improved tolerability. Clarithromycin and azithromycin are used extensively for the treatment of respiratory tract infections, sexually transmitted diseases, and Helicobacter pylori-associated peptic ulcer disease. Telithromycin is approved for the treatment of community-acquired pneumonia. Severe hepatotoxicity has been reported with the use of telithromycin.

Macrolides and ketolides: azithromycin, clarithromycin, telithromycin.

The advanced macrolides, azithromycin and clarithromycin, and the ketolide telithromycin are structural analogues of erythromycin. They have several distinct advantages when compared with erythromycin including enhanced spectrum of activity, more favorable pharmacokinetics and pharmacodynamics, once daily administration, and improved tolerability. This article reviews the pharmacokinetics, antimicrobial activity, clinical use, and adverse effects of these antimicrobial agents.