Nosocomial COVID-19 at a comprehensive cancer center during the first year of the pandemic: Lessons learned.

BACKGROUND: The spread of coronavirus disease 2019 (COVID-19) in health care settings endangers patients with cancer. As knowledge of the transmission of COVID-19 emerged, strategies for preventing nosocomial COVID-19 were updated. We describe our early experience with nosocomial respiratory viral infections (RVIs) at a cancer center in the first year of the pandemic (March 2020-March 2021). METHODS: Nosocomial RVIs were identified through our infection control prospective surveillance program, which conducted epidemiologic investigations of all microbiologically documented RVIs. Data was presented as frequencies and percentages or medians and ranges. RESULTS: A total of 35 of 3944 (0.9%) documented RVIs were determined to have been nosocomial acquired. Majority of RVIs were due to SARS CoV-2 (13/35; 37%) or by rhinovirus/enterovirus (12/35; 34%). A cluster investigation of the first 3 patients with nosocomial COVID-19 determined that transmission most likely occurred from employees to patients. Five patients (38%) required mechanical ventilation and 4 (31%) died during the same hospital encounter. CONCLUSIONS: Our investigation of the cluster led to enhancement of our infection control measures. The implications of COVID-19 vaccination on infection control policies is still unclear and further studies are needed to delineate its impact on the transmission of COVID-19 in a hospital setting.

Surveillance and identification of clusters of healthcare workers with coronavirus disease 2019 (COVID-19): Multidimensional interventions at a comprehensive cancer center.

BACKGROUND: Cases of novel coronavirus disease 2019 (COVID-19) were first reported in Wuhan, China, in December 2019. In this report, we describe 3 clusters of COVID-19 infections among healthcare workers (HCWs), not associated with patient exposure, and the interventions undertaken to halt ongoing exposure and transmission at our cancer center. METHODS: A cluster of cases was defined as 2 or more cases of severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-positive COVID-19 among HCWs who work in the same unit area at the same time. Cases were identified by real-time reverse transcription polymerase chain reaction testing. Contact tracing, facility observations, and infection prevention assessments were performed to investigate the 3 clusters between March 1 and April 30, 2020, with subsequent implementation of containment strategies. RESULTS: The initial cluster involved HCWs from an ancillary services unit, with contacts traced back to a gathering in a break room in which 1 employee was symptomatic, although not yet diagnosed with COVID-19, with subsequent transmission to 7 employees. The second cluster involved 4 employees and was community related. The third cluster involved only 2 employees with possible transmission while working in the same office at the same time. A step-up approach was implemented to control the spread of infection among employees, including universal masking, enhanced cleaning, increase awareness, and surveillance testing. No nosocomial transmission to patients transpired. CONCLUSIONS: To our knowledge, this is the first report of a hospital-based cluster of COVID-19 infections among HCWs in a cancer hospital describing our steps to mitigate further transmission.

Association of increased influenza vaccination in health care workers with a reduction in nosocomial influenza infections in cancer patients.

BACKGROUND: Vaccination of health care workers (HCWs) remains a key strategy to reduce the burden of influenza infections in cancer patients. METHODS: In this 8-year study, we evaluated the effect of a multifaceted approach, including a mandatory influenza vaccination program, on HCW vaccination rates and its effect on nosocomial influenza infections in cancer patients. RESULTS: The influenza vaccination rate of all employees significantly increased from 56% (8,762/15,693) in 2006-2007 to 94% (17,927/19,114) in 2013-2014 (P < .0001). The 2009 mandatory participation program increased HCW vaccination rates in the targeted groups (P < .0001), and the addition of an institutional policy in 2012 requiring influenza vaccination or surgical mask use with each patient contact further increased vaccination rates by 10%-18% for all groups in 1 year. The proportion of nosocomial influenza infections significantly decreased (P = .045) during the study period and was significantly associated with increased HCW vaccination rates in the nursing staff (P = .043) and in personnel working in high-risk areas (P = .0497). CONCLUSIONS: Multifaceted influenza vaccination programs supported by institutional policy effectively increased HCW vaccination rates. Increased HCW vaccination rates were associated with a reduction in the proportion of nosocomial influenza infections in immunocompromised cancer patients.

N-Glycans differentially regulate eosinophil and neutrophil recruitment during allergic airway inflammation.

Allergic airway inflammation, including asthma, is usually characterized by the predominant recruitment of eosinophils. However, neutrophilia is also prominent during severe exacerbations. Cell surface-expressed glycans play a role in leukocyte trafficking and recruitment during inflammation. Here, the involvement of UDP-N-acetylglucosamine:α-6-D-mannoside ß1,6-N-acetylglucosaminyltransferase V (MGAT5)-modified N-glycans in eosinophil and neutrophil recruitment during allergic airway inflammation was investigated. Allergen-challenged Mgat5-deficient (Mgat5(-/-)) mice exhibited significantly attenuated airway eosinophilia and inflammation (decreased Th2 cytokines, mucus production) compared with WT counterparts, attributable to decreased rolling, adhesion, and survival of Mgat5(-/-) eosinophils. Interestingly, allergen-challenged Mgat5(-/-) mice developed airway neutrophilia and increased airway reactivity with persistent elevated levels of proinflammatory cytokines (IL-17A, TNFα, IFNγ)). This increased neutrophil recruitment was also observed in LPS- and thioglycollate (TG)-induced inflammation in Mgat5(-/-) mice. Furthermore, there was significantly increased recruitment of infused Mgat5(-/-) neutrophils compared with WT neutrophils in the peritoneal cavity of TG-exposed WT mice. Mgat5(-/-) neutrophils demonstrated enhanced adhesion to P-selectin as well as increased migration toward keratinocyte-derived chemokine compared with WT neutrophils in vitro along with increased calcium mobilization upon activation and expression of elevated levels of CXCR2, which may contribute to the increased neutrophil recruitment. These data indicate an important role for MGAT5-modified N-glycans in differential regulation of eosinophil and neutrophil recruitment during allergic airway inflammation.

Outbreak of community-acquired methicillin-resistant Staphylococcus aureus skin infections among health care workers in a cancer center.

BACKGROUND: The incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) soft tissue infections is rising. However, CA-MRSA outbreaks among health care workers (HCWs) are rarely reported. We describe 3 clusters of CA-MRSA soft tissue infections among HCWs and the subsequent transmission to a patient. METHODS: The first cluster of boils occurred in 4 employees who worked in the ambulatory treatment clinic (area A) and 1 patient (PA1) who frequently visited area A. Three employees (EA1, EA2, and EA3) and PA1 had positive cultures. Twelve employees in 2 geographically separate diagnostic imaging areas (areas B and C) reported recent or current boils of whom EB1, EB2, EB3, and EC1 had positive cultures. Molecular subtyping using pulse-field gel electrophoresis (PFGE) was performed on all 8 isolates and confirmed by the Centers for Disease Control and Prevention laboratory. RESULTS: Relatedness of the MRSA strain was confirmed by PFGE in 7 of 8 isolates. Only EB3 was not related to the prototype CA-MRSA strain. All 7 related MRSA strains contained the typical genetic organization of staphylococcal cassette chromosome (SCC)-mec type IVa plus genes encoding Panton-Valentine Leukocidin. EB3's strain contained SCC-mec type II and was Panton-Valentine Leukocidin negative. A total of 171 questionnaires was sent. Nine of the 85 HCWs who responded reported a recent or current history of boils. Infection control conducted an education program for employees in areas A, B, and C. CONCLUSION: Early identification and control of CA-MRSA infections among HCWs is important to limit horizontal transmission to patients. Future efforts should include educational programs and guidelines for reporting and treating HCWs with MRSA infections.

Allergen-induced airway remodeling is impaired in galectin-3-deficient mice.

The role played by the beta-galactoside-binding lectin galectin-3 (Gal-3) in airway remodeling, a characteristic feature of asthma that leads to airway dysfunction and poor clinical outcome in humans, was investigated in a murine model of chronic allergic airway inflammation. Wild-type (WT) and Gal-3 knockout (KO) mice were subjected to repetitive allergen challenge with OVA up to 12 wk, and bronchoalveolar lavage fluid (BALF) and lung tissue collected after the last challenge were evaluated for cellular features associated with airway remodeling. Compared to WT mice, chronic OVA challenge in Gal-3 KO mice resulted in diminished remodeling of the airways with significantly reduced mucus secretion, subepithelial fibrosis, smooth muscle thickness, and peribronchial angiogenesis. The higher degree of airway remodeling in WT mice was associated with higher Gal-3 expression in the BALF as well as lung tissue. Cell counts in BALF and lung immunohistology demonstrated that eosinophil infiltration in OVA-challenged Gal-3 KO mice was significantly reduced compared with that WT mice. Evaluation of cellular mediators associated with eosinophil recruitment and airway remodeling revealed that levels of eotaxin-1, IL-5, IL-13, found in inflammatory zone 1, and TGF-beta were substantially lower in Gal-3 KO mice. Finally, leukocytes from Gal-3 KO mice demonstrated decreased trafficking (rolling) on vascular endothelial adhesion molecules compared with that of WT cells. Overall, these studies demonstrate that Gal-3 is an important lectin that promotes airway remodeling via airway recruitment of inflammatory cells, specifically eosinophils, and the development of a Th2 phenotype as well as increased expression of eosinophil-specific chemokines and profibrogenic and angiogenic mediators.

Deficiency of endothelial heparan sulfates attenuates allergic airway inflammation.

The effect of targeted inactivation of the gene encoding N-deacetylase/N-sulfotransferase-1 (Ndst1), a key enzyme involved in the biosynthesis of heparan sulfate (HS) chains, on the inflammatory response associated with allergic inflammation in a murine model of OVA-induced acute airway inflammation was investigated. OVA-exposed Ndst1(f/f)TekCre(+) (mutant) mice deficient in endothelial and leukocyte Ndst1 demonstrated significantly decreased allergen-induced airway hyperresponsiveness and inflammation characterized by a significant reduction in airway recruitment of inflammatory cells (eosinophils, macrophages, neutrophils, and lymphocytes), diminished IL-5, IL-2, TGF-beta1, and eotaxin levels, as well as decreased expression of TGF-beta1 and the angiogenic protein FIZZ1 (found in inflammatory zone 1) in lung tissue compared with OVA-exposed Ndst1(f/f)TekCre(-) wild-type littermates. Furthermore, murine eosinophils demonstrated significantly decreased rolling on lung endothelial cells (ECs) from mutant mice compared with wild-type ECs under conditions of flow in vitro. Treatment of wild-type ECs, but not eosinophils, with anti-HS Abs significantly inhibited eosinophil rolling, mimicking that observed with Ndst1-deficient ECs. In vivo, trafficking of circulating leukocytes in lung microvessels of allergen-challenged Ndst1-deficient mice was significantly lower than that observed in corresponding WT littermates. Endothelial-expressed HS plays an important role in allergic airway inflammation through the regulation of recruitment of inflammatory cells to the airways by mediating interaction of leukocytes with the vascular endothelium. Furthermore, HS may also participate by sequestering and modulating the activity of allergic asthma-relevant mediators such as IL-5, IL-2, and TGF-beta1.

The importance of two-step tuberculin skin testing for newly employed healthcare workers.

At the time of hire, 4059 of 6522 healthcare workers required a 2-step tuberculin skin test; 114 workers (2.8%) demonstrated a boosted reaction after the second step. Boosted reactions were significantly associated with male sex and older age. A verbal history of previous tuberculin skin test results was not a reliable indicator of baseline tuberculin skin test status at the time of hire.

Smallpox vaccine: "non-take" responses in previously vaccinated adults.

This small, retrospective study of laboratory workers who received smallpox vaccine showed a strong correlation between "non-take" reactions and the presence of prior vaccination scars. Although we cannot exclude technique and vaccine potency as causes, the association we observed may indicate that these workers are displaying residual immunity to smallpox.