Investigation of a Prolonged and Large Outbreak of Healthcare-Associated Mucormycosis Cases in an Acute Care Hospital-Arkansas, June 2019-May 2021.

Background: Outbreaks of healthcare-associated mucormycosis (HCM), a life-threatening fungal infection, have been attributed to multiple sources, including contaminated healthcare linens. In 2020, staff at Hospital A in Arkansas alerted public health officials of a potential HCM outbreak. Methods: We collected data on patients at Hospital A who had invasive mucormycosis during January 2017-June 2021 and calculated annual incidence of HCM (defined as mucormycosis diagnosed within ≥7 days after hospital admission). We performed targeted environmental assessments, including linen sampling at the hospital, to identify potential sources of infection. Results: During the outbreak period (June 2019-June 2021), 16 patients had HCM; clinical features were similar between HCM patients and non-HCM patients. Hospital-wide HCM incidence (per 100 000 patient-days) increased from 0 in 2018 to 3 in 2019 and 6 in 2020. For the 16 HCM patients, the most common underlying medical conditions were hematologic malignancy (56%) and recent traumatic injury (38%); 38% of HCM patients died in-hospital. Healthcare-associated mucormycosis cases were not epidemiologically linked by common procedures, products, units, or rooms. At Hospital A and its contracted offsite laundry provider, suboptimal handling of laundered linens and inadequate environmental controls to prevent mucormycete contamination were observed. We detected Rhizopus on 9 (9%) of 98 linens sampled at the hospital, including on linens that had just arrived from the laundry facility. Conclusions: We describe the largest, single-center, HCM outbreak reported to date. Our findings underscore the importance of hospital-based monitoring for HCM and increased attention to the safe handling of laundered linens.

Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases.

INTRODUCTION: Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses. METHODS: Prospective cohort study including adults with chronic pulmonary diseases and healthcare personnel as controls (1:1). Blood was sampled at inclusion, 3 weeks, 2 and 6 months after first vaccination. We reported antibody concentrations as geometric means with 95% CI of receptor binding domain (RBD)-IgG and neutralising antibody index of inhibition of ACE-2/RBD interaction (%). A low responder was defined as neutralising index in the lowest quartile (primary outcome) or RBD-IgG <225 AU/mL plus neutralising index <25% (secondary outcome), measured at 2 months. We tested associations using Poisson regression. RESULTS: We included 593 patients and 593 controls, 75% of all had neutralising index ≥97% at 2 months. For the primary outcome, 34.7% of patients (n=157/453) and 12.9% of controls (n=46/359) were low responders (p<0.0001). For the secondary outcome, 8.6% of patients (n=39/453) and 1.4% of controls (n=5/359) were low responders (p<0.001). Risk factors associated with low responder included increasing age (per decade, adjusted risk ratio (aRR) 1.17, 95% CI 1.03 to 1.32), Charlson Comorbidity Index (per point) (aRR 1.15, 95% CI 1.05 to 1.26), use of prednisolone (aRR 2.08, 95% CI 1.55 to 2.77) and other immunosuppressives (aRR 2.21, 95% CI 1.65 to 2.97). DISCUSSION: Patients with chronic pulmonary diseases established functional humoral responses to vaccination, however lower than controls. Age, comorbidities and immunosuppression were associated with poor immunological responses.

The Impact of Social Distancing in 2020 on Admission Rates for Exacerbations in Asthma: A Nationwide Cohort Study.

BACKGROUND: Social distancing measures introduced during the coronavirus disease 2019 pandemic have reduced admission rates for various infectious and noninfectious respiratory diseases. We hypothesized that rates of asthma exacerbations would decline following the national lockdown in Denmark. OBJECTIVE: To determine weekly rates of in- and out-of-hospital asthma exacerbations before and during the social distancing intervention implemented on March 12, 2020. METHODS: All individuals older than 18 years with at least 1 outpatient hospital contact with asthma as the main diagnosis from January 1, 2013, to December 31, 2017, were included. Weekly asthma exacerbation rates from January 1, 2018, to May 22, 2020, were calculated. An interrupted time-series model with the lockdown on March 12, 2020, as the point of interruption was used. RESULTS: A total of 38,225 patients with asthma were identified. The interrupted time-series model showed no immediate fall in exacerbation rates during the first week after March 12, 2020. However, there was a significant decline in weekly exacerbation rates in the following 10 weeks (change in trend for exacerbations requiring hospitalization: -0.75 [95% CI, -1.39 to -0.12]; P < .02 and in all asthma exacerbations: -12.2 [95% CI, -19.1 to -5.4; P < .001), amounting to a reduction of approximately 1 and 16.5 exacerbations per year per 100 patients in the cohort, respectively. CONCLUSIONS: The introduction of the social distancing measures in Denmark did not lead to an immediate reduction in asthma exacerbation rates; however, a gradual decline in exacerbation rates during the following 10-week period was observed.

Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19: a randomised double-blinded placebo-controlled trial.

BACKGROUND: Combining the antibiotic azithromycin and hydroxychloroquine induces airway immunomodulatory effects, with the latter also having in vitro antiviral properties. This may improve outcomes in patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: Placebo-controlled double-blind randomised multicentre trial. Patients aged ≥18 years, admitted to hospital for ≤48 h (not intensive care) with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR test were recruited. The intervention was 500 mg daily azithromycin for 3 days followed by 250 mg daily azithromycin for 12 days combined with 200 mg twice-daily hydroxychloroquine for all 15 days. The control group received placebo/placebo. The primary outcome was days alive and discharged from hospital within 14 days (DAOH14). RESULTS: After randomisation of 117 patients, at the first planned interim analysis, the data and safety monitoring board recommended stopping enrolment due to futility, based on pre-specified criteria. Consequently, the trial was terminated on 1 February 2021. 61 patients received the combined intervention and 56 patients received placebo. In the intervention group, patients had a median (interquartile range) 9.0 (3-11) DAOH14 versus 9.0 (7-10) DAOH14 in the placebo group (p=0.90). The primary safety outcome, death from all causes on day 30, occurred for one patient in the intervention group versus two patients receiving placebo (p=0.52), and readmittance or death within 30 days occurred for nine patients in the intervention group versus six patients receiving placebo (p=0.57). CONCLUSIONS: The combination of azithromycin and hydroxychloroquine did not improve survival or length of hospitalisation in patients with COVID-19.

COVID-19 outcomes in hospitalized patients with active cancer: Experiences from a major New York City health care system.

BACKGROUND: The authors sought to study the risk factors associated with severe outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients with cancer. METHODS: The authors queried the New York University Langone Medical Center's records for hospitalized patients who were polymerase chain reaction-positive for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and performed chart reviews on patients with cancer diagnoses to identify patients with active cancer and patients with a history of cancer. Descriptive statistics were calculated and multivariable logistic regression was used to determine associations between clinical, demographic, and laboratory characteristics with outcomes, including death and admission to the intensive care unit. RESULTS: A total of 4184 hospitalized SARS CoV-2+ patients, including 233 with active cancer, were identified. Patients with active cancer were more likely to die than those with a history of cancer and those without any cancer history (34.3% vs 27.6% vs 20%, respectively; P < .01). In multivariable regression among all patients, active cancer (odds ratio [OR], 1.89; CI, 1.34-2.67; P < .01), older age (OR, 1.06; CI, 1.05-1.06; P < .01), male sex (OR for female vs male, 0.70; CI, 0.58-0.84; P < .01), diabetes (OR, 1.26; CI, 1.04-1.53; P = .02), morbidly obese body mass index (OR, 1.87; CI, 1.24-2.81; P < .01), and elevated D-dimer (OR, 6.41 for value >2300; CI, 4.75-8.66; P < .01) were associated with increased mortality. Recent cancer-directed medical therapy was not associated with death in multivariable analysis. Among patients with active cancer, those with a hematologic malignancy had the highest mortality rate in comparison with other cancer types (47.83% vs 28.66%; P < .01). CONCLUSIONS: The authors found that patients with an active cancer diagnosis were more likely to die from COVID-19. Those with hematologic malignancies were at the highest risk of death. Patients receiving cancer-directed therapy within 3 months before hospitalization had no overall increased risk of death. LAY SUMMARY: Our investigators found that hospitalized patients with active cancer were more likely to die from coronavirus disease 2019 (COVID-19) than those with a history of cancer and those without any cancer history. Patients with hematologic cancers were the most likely among patients with cancer to die from COVID-19. Patients who received cancer therapy within 3 months before hospitalization did not have an increased risk of death.

From spontaneous to strategic natural window ventilation: Improving indoor air quality in Swiss schools.

Natural window ventilation is frequently employed in schools in Europe and often leads to inadequate levels of human bioeffluents. However, intervention studies that verify whether recommended ventilation targets can be achieved in practice with reasonable ventilation regimes and that are also suitable for countries with cold winters are practically non-existent. To explore the initial situation in Switzerland we carried out carbon dioxide (CO2) measurements during the winter in 100 classrooms, most of which (94%) had natural window ventilation. In more than two thirds of those, the hygienic limit value of 2000 ppm specified for CO2 in the Swiss Standard SN 520180 (2014) was exceeded. To improve ventilation behavior, an intervention was implemented in 23 classrooms during the heating season. Ventilation was performed exclusively during breaks (to avoid discomfort from cold and drafts), efficiently, and only for as long as was necessary to achieve the ventilation objective of compliance with the hygienic limit value (strategic ventilation). The intervention included verbal and written instructions, awareness-raising via a school lesson and an interactive tool for students, which was also used to estimate the required duration of ventilation. CO2 exposure was significantly reduced in pilot classes (Wilcoxon signed-rank test, p = 3.815e-06). Median CO2 levels decreased from 1600 ppm (control group) to 1097 ppm (intervention group), and the average proportion of teaching time at 400-1400 ppm CO2 increased from 40% to 70%. The duration of ventilation was similar to spontaneous natural window ventilation (+5.8%). Stricter ventilation targets are possible. The concept of the intervention is suitable for immediate adoption in schools with natural window ventilation for a limited period, pending the installation of a mechanical ventilation system. The easy integration of this intervention into everyday school life promotes compliance, which is particularly important during the COVID-19 pandemic.

Does inhaled corticosteroid use affect the risk of COVID-19-related death?

ICS does not seem to protect against COVID-19-related mortality, but more data is needed to determine whether it is harmful. Due to its known and important benefits ICS should be prescribed as usual for both asthma and COPD. https://bit.ly/3pWVimX.