On-going impact of the SARS-CoV-2 pandemic on the evolution of carbapenemase-producing Enterobacterales in Ontario, Canada

Background. The spread of carbapenemase-producing Enterobacterales (CPE) is global threat. Numerous outbreaks of CPE have been reported during the COVID-19 pandemic. We describe the impact of of the SARS-CoV-2 pandemic on the emergence of CPE in south-central Ontario, Canada. Incidence of clinical isolates of CPE and isolates with different CPE genes in Toronto/Peel region, 2017-2021. The upper panel shows the incidence of patients with clinical isolates of CPE by year and quarter from q4 2007 to q1 2022. The lower panel shows the incidence of patients with clinical isolates with different carbapenemase genes by fiscal year during the same period. Methods. TIBDN has performed population-based surveillance for CPE in Toronto/Peel region (pop 4.5M) from first identified isolate in 2007. All laboratories test/refer all carbapenem non-susceptible Enterobacterial isolates for identification of CPE. Hospital charts are reviewed and patients/physicians interviewed. Population data are obtained from Statistics Canada. Results. From 10/2007 to 3/31/2022, 1367 persons colonized or infected with CPE were identified. Theirmedian age was 68.7yrs (IQR 54-78yrs);761 (56%) weremale. 772 (56%) were colonized when first identified;115 (8.4%) were bacteremic at identification or subsequently developed bacteremia. The most common organisms were E. coli (651, 48%), K. pneumoniae (436, 32%), Enterobacter spp. (146, 11%), Citrobacter spp (62, 5%);the most common genes were NDM+/-OXA-48 (722, 53%), OXA-48-like (341, 25%), KPC (225, 16%), VIM(44, 3%). The incidence of CPE infections increased steadily until 3/2020 then declined by 61%and remained stable until 3/2022 (Figure, upper panel). The declinewas greater for E. coli (56%decrease), K. pneumoniae (62%) than for Enterobacter spp. (30%) and other species (19%). It occurred in all genes in 2020;however, KPC containing organisms increased again in 2021 (Figure, lower panel). Conclusion. The advent of the COVID-19 pandemic was associated with an immediate, substantial decline in the incidence of patients with CPE in our population area. This decline occurred in both isolates with genes usually occurring in cases imported from other countries, and in those usually occurring in cases associated with transmission within Canadian hospitals. Decreased travel and enhanced infection prevention and control in hospitals may both have contributed to reductions in CPE during the pandemic. (Figure Presented).

Burden of Covid.19 in Long.Term.Care Facilities: Preliminary Results of a Multicentre Cohort.Study from Eastern and Western Switzerland

Background: COVID-19 outbreaks with high mortality rates have been reported from long-term care facilities (LTCFs) worldwide despite infection control and prevention (ICP) measures. However, no systematic data exist on COVID-19 burden and its risk factors in Swiss-LTCFs. Aims: to assess (i) COVID-19 incidence and-related mortality for the year 2020 and their influencing factors, (ii) vaccination rates of residents and health care workers (HCW). Methods: LTCFs from cantons of St Gallen (SG) and Vaud (VD) (Eastern and Western Switzerland) were invited to participate in this cohort study. In May 2021, we collected COVID-19 cases and-related deaths 2020 and their potential risk factors at institutional level (e.g. size, number of single beds, staffing, ICP measures, aggregated resident characteristics) as well as vaccination rates of residents and HCW. Risk factor analysis and prospective surveillance of COVID-19 is ongoing. Results: We enrolled a total of 59 institutions (33 from SG, 26 from VD), with a median of 46 (IQR 33.69) occupied beds. In 2020, median COVID-19 incidence was 38.6 per 100 occupied beds, with higher rates in VD than in SG (48% vs. 29.4%, p = 0.028) (Fig. 1). Rates varied widely among LTCFs, with some institutions reporting no COVID-19 cases. On average (median), one-fifth (20%) of COVID-19 cases died and COVID-19 related deaths accounted for 21.6% of total deaths. Regarding ICP measures, 54/59 institutions (91.5%) recommended using gowns in contact with COVID-19 patients, whilst use of other PPE (i.e. FFP2 masks, glows and googles) was more heterogeneous. Only a few LTCFs reported having ever used regular testing of asymptomatic residents (6/59, 10.2%) or HCW (14/59, 23.7%) as a prevention strategy. Nearly half of them (27/59, 45.8%) never banned visits or only in outbreak situations. Of 2786 residents, a median of 72.2% per facility received ≥1 dose of COVID-19 vaccine. COVID-19 vaccine uptake among HCW was low (28.6%) (Fig. 1). Conclusion: COVID-19 burden was highly heterogeneous in Swiss LTCFs. Further analyses will reveal factors, which could potentially explain these differences. Of note, we found a relatively high COVID-19 vaccine uptake among care home residents, whilst vaccine coverage of HCW is low.

COVID-19 Infection in Vaccinated Adult Patients with Hematological Malignancies. Preliminary Results from Epicovideha (Epidemiology of COVID-19 infection in patients with hematological malignancies: A European Haematology Association Survey)

Introduction Coronavirus disease 2019 (COVID-19) is a life-threatening condition of high relevance for co-morbid patients, such as those with baseline hematological malignancies (HM). One year after the diagnosis of the first COVID-19 case, at the end of 2020, the first vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were administered to the population, starting with individuals at highest risk of infection. EPICOVIDEHA aims to describe the epidemiology, vaccination strategies and mortality rates from HM patients at risk. Methods We collected clinical and epidemiological data from patients with laboratory-based diagnosis of SARS-CoV-2 infection after partial or complete vaccination. The study was sponsored by the European Hematology Association - Infectious Diseases Working Party. Patients were registered in the EPICOVIDEHA online survey between January 1, 2021 and July 31, 2021 from Europe and United States. Data captured included underlying conditions prior to SARS-CoV-2, HM status and management prior to SARS-CoV-2, SARS-CoV-2 vaccination and infection details and mortality. The survey will continue until December 31, 2021. Results Overall, 40 patients have been so far registered, 24 male and 16 females, the vast majority of them aged over 50 years (N=38, 95%). Three quarters of patients were affected by lymphoproliferative malignancies (chronic lymphoid leukemia [CLL] N=14 and non-Hodgkin lymphoma [NHL] and multiple myeloma [MM] N=8, each), followed by myelodysplastic syndrome (MDS) (N=4), acute myeloid leukemia (AML) (N=2) and others (chronic myeloid leukemia [CML], acute lymphoid leukemia [ALL], polycythemia vera [PV] and aggressive mastocytosis one of each). Thirty-one patients (77.5%) were receiving active treatment for underlying HM at the time of SARS-CoV-2 infection, with 16 of them being on chemotherapy in the month prior to infection. All patients were vaccinated with a median time from vaccine to SARS-CoV-2 infection of 45.5 days (IRQ 19-67.5). Twenty-nine patients received a mRNA vaccine (BioNTech/Pfizer N=28, Moderna COVE N=1), whereas the remaining 11 an inactivated vaccine (Sinovac CoronaVac N=6) and vector-based vaccine (AstraZeneca Oxford N=5). Twenty-three patients were completely vaccinated, of which 22 (97.5%) patients were immunized (a minimum of 15 days following second dose). On the contrary, among 17 patients partially vaccinated, none was immunized. In 9 cases, viral genomes were analyzed (English variant N=7, South Africa variant N=1, Indian variant N=1). Overall, 25/40 patients presented with a severe/critical infection (62.5%), 13 of which (52%) were fully vaccinated and immunized, whereas only 15 (37.5%) were asymptomatic or mildly symptomatic. Twenty-seven (92.5%) patients were admitted to hospital, 5/27 (18.5%) to ICU, all requiring mechanical ventilation. After a follow-up of 30 day from SARS-CoV-2 infection, 8 patients died (20%), with 7/8 deaths (87.5%) attributable to SARS-CoV-2. There was no difference in overall survival between those patients that received 2 doses of vaccine or 1 dose (figure 1a), as well as no difference being observed between patients with and without lymphoproliferative malignancies (figure 1b), patients that receiving/not receiving active treatment in the last month (figure 1c), or the type of vaccine injected (figure 1d). Conclusions Our survey, involving over 150 Hematology Departments around the world, provides some preliminary insights. The majority of patients who do not respond to vaccination are patients with lymphoproliferative diseases, as can also be observed for other types of vaccination (e.g., flu-vaccination). Dramatically the mortality observed in all patients, although lower than that observed in the pre-vaccination period which in our experience was around 31%, still remains high (20%). Recruitment to this survey continues, and we hope that with larger numbers of cases, more definitive conclusions can be drawn to develop strategies to keep these complex patients safe. [Formula presented] Disclosures: Lop z-Garcia: Celgene: Other: Speaker Honoraria;Abbvie: Other: Speaker Honoraria, Advisor, Travel and accommodation grants;Janssen: Other: Speaker Honoraria, Advisor, Travel and accommodation grants, Research Funding;Roche: Other: Speaker Honoraria, Travel and accommodation grants;Novonordisk: Other: Speaker Honoraria;Fresenius: Other: Speaker Honoraria. Glenthoej: Novo Nordisk: Honoraria;Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;bluebird bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Alexion: Research Funding. Mikulska: Biotest: Speakers Bureau;Janssen: Speakers Bureau;MSD: Speakers Bureau;Gilead: Speakers Bureau;Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Busca: Gilead Sciences: Other: Lecture Honoraria;Merck: Other: Lecture Honoraria;Pfizer Pharmaceuticals: Other: Lecture Honoraria;Basilea: Other: Lecture Honoraria;Biotest: Other: Lecture Honoraria;Jazz Pharmaceuticals: Other: Lecture Honoraria;Takeda: Membership on an entity's Board of Directors or advisory committees. Corradini: KiowaKirin;Incyte;Daiichi Sankyo;Janssen;F. Hoffman-La Roche;Kite;Servier: Consultancy;AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Honoraria;AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Consultancy;Amgen;Takeda;AbbVie: Consultancy, Honoraria, Other: Travel and accommodations;Novartis;Gilead;Celgene: Consultancy, Other: Travel and accommodations;BMS: Other: Travel and accommodation;Sanofi: Consultancy, Honoraria;Incyte: Consultancy;Novartis, Janssen, Celgene, BMS, Takeda, Gilead/Kite, Amgen, AbbVie: Other: travel and accomodations. Hoenigl: Gilead, Pfizer, Astellas, Scynexis, and NIH: Research Funding. Klimko: Gilead Science, MSD, Pfizer: Membership on an entity's Board of Directors or advisory committees;Gilead Sciences, MSD, Pfizer Pharmaceuticals, and Astellas Pharma: Speakers Bureau. Pagliuca: Gentium/Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Gilead, Pfizer, and MSD: Research Funding. Passamonti: Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AbbVie: Speakers Bureau;BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Köhler: German Federal Ministry of Research and Education and the State of North Rhine-Westphalia, Germany: Other: Support;Miltenyi Biotec GmbH, Bergisch Gladbach, Germany, and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany: Other: Non-financial grants;Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, MSD Sharp & Dohme GmbH, Noxxon N.V., and University Hospital, LMU Munich: Consultancy, Honoraria. Cornely: Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis: Other: Grants or Contracts. Pagano: Gilead Science, MSD, Pfizer, Basilea, Janssen, Novartis, Jazz Pharmaceutical, Cidara: Membership on an entity's Board of Directors or advisory committees;Gilead Sciences, MSD, Pfizer Pharmaceuticals, Astellas Pharma: Speakers Bureau;Menarini: Consultancy.

Evaluation of ward-level risk factors for nosocomial COVID-19 outbreaks: A matched case-control study

Introduction: The prevention of SARS-CoV-2 outbreaks in acute care hospitals is a major challenge. In the second wave of the pandemic, we observed several wards with outbreaks whereas others were spared. Objectives: We aimed to investigate risk factors for nosocomial COVID-19 outbreaks on a ward level. Methods: We conducted a matched case-control study in our tertiary care centre with over 700 beds by defining outbreak (≥ 2 nosocomial patients infected within a 14-day period) and control wards. Nosocomial infection was defined if a patient tested positive for COVID-19 on day 5 or later of hospitalisation. Matching was done 1:1 for approximate number of beds (± 10) and the time of the outbreak. The beginning of the outbreak was defined as the day of the first positively tested nosocomial COVID-19 case on the ward. Intensive care units and designated COVID- 19 wards were excluded. Presumed ward-, patient- and staff-specific variables were investigated. Paired Wilcoxon signed-rank test was used to compare variables between outbreak- and control wards. Results: From July to December 2020, we observed 9 outbreak wards (surgical and medical, range of beds 17 - 31, range nurses 19 - 41 per ward) with a total of 40 patients infected (range 2-7 per ward). The percentage of healthcare workers (HCW) tested positive within a period of 14 days prior until 2 days after the start of the outbreak was the only significant risk factor (9.7% vs 2.7%, p = 0.04). No difference in the percentage of infected HCW was observed in a time period further preceding the start of the outbreak (3 months to 2 weeks). Outbreak wards trended towards a higher number of beds per room (2.22 vs 1.97, p = 0.09) and a younger HCW age (33.3 vs 36.2 years, p = 0.17) compared to control wards. No association was found for factors reflecting work-load, patient turnover, or work experience of HCW (Table). Conclusion: Increased numbers of infected HCW shortly before the outbreak seem to be a risk factor for nosocomial SARS-CoV-2 outbreaks. This supports the notion that infected HCW are an important source of nosocomial COVID-19 and underscores the importance of adequate infection control- and prevention measures of HCW in- and outside the hospital. (Figure Presented).

Use of respirator vs. surgical masks in healthcare personnel and its impact on SARS-COV-2 acquisition-a prospective multicentre cohort study

Introduction: There is insufficient evidence regarding the role of respirators in the prevention of SARS-CoV-2 infection. Objectives: We analysed the impact of filtering facepiece class 2 (FFP2) vs. surgical masks on the risk of SARS-CoV-2 acquisition in Swiss healthcare workers (HCW). Methods: Our prospective multicentre cohort enrolled HCW from June to August 2020, who were asked about COVID-19 risk exposures/behaviours, including preferred mask type when caring for COVID-19 patients outside of aerosol-generating procedures (AGP). HCW performing AGP were also asked about universal FFP2 use (i.e. irrespective of patients' COVID-19 status). We assessed the impact of FFP2 on i) self-reported SARS-CoV- 2-positive nasopharyngeal PCR/rapid antigen tests (weekly surveys), and ii) SARS-CoV-2 seroconversion (baseline to January/February 2021). Results: We enrolled 3'259 participants from nine healthcare institutions, whereof 716 (22%) preferentially used FFP2 respirators. Among these, 81/716 (11%) reported a SARS-CoV-2-positive swab, compared to 352/2543 (14%) surgical mask users (median follow-up 242 days);seroconversion was documented in 85/656 (13%) FFP2 and 426/2255 (19%) surgical mask users. Adjusted for baseline characteristics, COVID-19 exposure, and risk behaviour, FFP2 use was marginally associated with a decreased risk for SARS-CoV-2-positive swab (aHR 0.8, p = 0.052) and seroconversion (aOR 0.7, p = 0.053);household exposure was the strongest risk factor (aHR for positive swab 10.1, p < 0.001;aOR for seroconversion 5.0, p < 0.001). In subgroup analysis, FFP2 use was clearly protective among HCW with frequent (> 20 patients) COVID-19 exposure (aHR 0.7, p < 0.001;aOR 0.6, p = 0.036). Universal FFP2 use during AGP showed no additional protective effect (aHR 1.1, p = 0.7;aOR 0.9, p = 0.53). Conclusion: FFP2 compared to surgical masks may convey additional protection from SARS-CoV-2 for HCW with frequent exposure to COVID-19 patients. (Figure Presented).

COVID-19 in cancer patients: clinical characteristics and outcome-an analysis of the LEOSS registry.

INTRODUCTION: Since the early SARS-CoV-2 pandemic, cancer patients have been assumed to be at higher risk for severe COVID-19. Here, we present an analysis of cancer patients from the LEOSS (Lean European Open Survey on SARS-CoV-2 Infected Patients) registry to determine whether cancer patients are at higher risk. PATIENTS AND METHODS: We retrospectively analyzed a cohort of 435 cancer patients and 2636 non-cancer patients with confirmed SARS-CoV-2 infection, enrolled between March 16 and August 31, 2020. Data on socio-demographics, comorbidities, cancer-related features and infection course were collected. Age-, sex- and comorbidity-adjusted analysis was performed. Primary endpoint was COVID-19-related mortality. RESULTS: In total, 435 cancer patients were included in our analysis. Commonest age category was 76-85 years (36.5%), and 40.5% were female. Solid tumors were seen in 59% and lymphoma and leukemia in 17.5% and 11% of patients. Of these, 54% had an active malignancy, and 22% had recently received anti-cancer treatments. At detection of SARS-CoV-2, the majority (62.5%) presented with mild symptoms. Progression to severe COVID-19 was seen in 55% and ICU admission in 27.5%. COVID-19-related mortality rate was 22.5%. Male sex, advanced age, and active malignancy were associated with higher death rates. Comparing cancer and non-cancer patients, age distribution and comorbidity differed significantly, as did mortality (14% vs 22.5%, p value < 0.001). After adjustments for other risk factors, mortality was comparable. CONCLUSION: Comparing cancer and non-cancer patients, outcome of COVID-19 was comparable after adjusting for age, sex, and comorbidity. However, our results emphasize that cancer patients as a group are at higher risk due to advanced age and pre-existing conditions.

Stroke in a young adult with mild COVID-19 suggesting endotheliitis.

We present the case of a young adult with stroke and very mild coronavirus disease 2019 (COVID-19). Results of hematologic work-up suggest SARS-CoV-2-induced endotheliitis. No concurrent etiology for stroke was detected. This case illustrates the possibility of stroke in healthy SARS-CoV-2-infected patients without hyperinflammatory state or excessive systemic coagulation activation.