Legionella pneumophila occurrence in reduced-occupancy buildings in 11 cities during the COVID-19 pandemic (preprint)

In spring 2020, reduced water demand was an unintended consequence of COVID-19 pandemic-related building closures. Concerns arose that contaminants associated with water stagnation, such as Legionella pneumophila , could become prevalent. To investigate this potential public health risk, samples from 26 reduced-occupancy buildings across 11 cities in the United States, Canada, and Switzerland were analyzed for L. pneumophila using liquid culture (Legiolert, n=258) and DNA-based methods (qPCR/ddPCR, n=138). L. pneumophila culture-positivity was largely associated with just five buildings, each of which had specific design or operational deficiencies commonly associated with L. pneumophila occurrence. Samples from free chlorine buildings had higher culture-positivity (37%) than chloramine buildings (1%), and 78% of culture-positive samples occurred when the residual was ≤0.1 mg/L Cl 2 . Although overall sample positivities using culture- and DNA-based methods were equivalent (34% vs. 35%), there was disagreement between the methods in 13% of paired samples. Few buildings reported any water management activities, and L. pneumophila concentrations in flushed samples were occasionally greater than in first-draw samples. This study provides insight into how building plumbing characteristics and management practices contribute to L. pneumophila occurrence during low water use periods and can inform targeted prevention and mitigation efforts. Synopsis Statement Legionella pneumophila occurrence was evaluated in reduced-occupancy buildings during the COVID-19 pandemic across multiple cities. Graphic for Table of Contents (TOC)

Cytosorb® Rescue for COVID-19 Patients with Vasoplegic Shock (CytoResc): A Prospective, Open-Label, Randomised Controlled Pilot Study (preprint)

Background: Several observations indicate a hyperinflammatory state in severely ill COVID-19 patients. The aim of this study was to investigate the effect of extracorporeal cytokine elimination by CytoSorb® on COVID-19 associated vasoplegic shock.Methods: In this prospective randomised pilot study COVID-19 patients with vasoplegic shock requiring norepinephrine >0·2 µg/kg/min, CRP >100 mg/L and indication for hemodialysis were randomised 1:1 to receive CytoSorb® treatment for 3-7 days or standard of care. The primary endpoint was time until resolution of vasoplegic shock, estimated by a Cox-regression model. Secondary endpoints included mortality, serum interleukin-6 concentrations, and catecholamine requirements. The study was registered in the German Registry of Clinical Trials (DRKS00021447).Findings: From November 2020 to March 2021, 50 patients were enrolled of which 23 patients were randomised to receive CytoSorb® treatment and 26 patients to receive standard of care. One patient randomised to cytokine adsorption was excluded due to withdrawal of informed consent. Resolution of vasoplegic shock was observed in 13 (56·5%) of 23 patients in the CytoSorb® and 12 (46·2%) of 26 patients in the control group after a median of 5 (IQR 4-5) and 4 (IQR 3-5) days, respectively. The hazard ratio (HR) for the primary endpoint, adjusted for the predefined variables age, gender, ECMO-therapy, or time from shock onset to study inclusion was HR 1·23 (95%CI: 0·54-2·79), p=0·63). The mortality rate was 78% in the CytoSorb® and 73% in the control group (unadjusted HR 1·17 (95%CI: 0·61-2.23), p=0·64). The effects on inflammatory markers and catecholamine requirements and the type and rates of adverse events were similar in the two groups.Interpretation: In this pilot trial in severely ill COVID-19 patients CytoSorb® treatment did not improve resolution of vasoplegic shock as compared to standard treatment. Mortality rates, catecholamine requirements, inflammatory markers and adverse events did not differ between the two groups.Trial Registration: The study was registered in the German Registry of Clinical Trials (DRKS00021447Funding: Internal university fundsDeclaration of Interest: HS, LJL, MP, TK, PT, FS, KUE, SK, JVK, MO, AKrü, A Kra, KB declare no conflicts of interest. PE received honoraria from GSK and AstraZeneca and filed two patents for novel urinary biomarkers outside the submitted work. ST received research funding and honoraria for workshops and lectures from Orionpharma. He additionally received honoraria for workshops and lectures from Edwards and honoraria for lectures from Amomed and Smith&Nephews. CS received grants from: Drägerwerk AG& Co.KGaA; German Reseach Society; German Aerospace Center; Einstein Foundation Berlin; Federal Joint Committee (G-BA); Inner University grants; Project Management Agency; Non-Profit Promoting Science and Education; European Society of Anesthesiology and Intensive Care; Baxter Deutschland GmbH; Cytosorbents Europe GmbH; Edwards Lifsciences Germany GmbH; Fresenius Medical Care; Grünenthal GmbH; Massimo Europe Ltd.; Pfizer Pharma PFE GmbH; Georg Thieme Verlag, Dr. F Köhler Chemie GmbH; Sintetica GmbH; Stifterverband für die deutsche Wissenschaft e.V./Philips; Stiftung Charié; AGUETTANT Deutschland GmbH; AbbVie Deutschland GmbH & Co.KG; Amomed Pharma GmbH; InTouch Health; Copra System GmbH; Correvio GmbH; Max Plank Gesellschaft zur Förderung der Wissenschaften e.V.; Deutsche Gesellschaft für Anästhesiologie & Intensivmedizin (DGAI); Stifterverband für die Deutsche Wissenschaft e.V./Medtronic; Philipps ElectronicsNederland BV; BMG, BMBF, German Research Society all outside the submitted work. In addition, CS has different patents. DK received fees for speaking at a symposia organized on behalf of Fresenius Medical Care AG, Germany.Ethical Approval: The original protocol and the changes were approved by the local ethicscommittee (EA1/069/20).

Risk factors and its effects on the clinical outcomes of COVID-19 in children: systematic review and metanalysis (preprint)

Objectives: To determine which risk factors contribute to worse COVID-19 outcome in children. Methods: Data sources: The review was conducted in Medline, CINAHL, Pubmed, Scopus, Web of Science, and LILACS. Study selection and data extraction: Articles published in the last year, written in Portuguese, English, and Spanish were included. Duplicates, editorials, letters to the editor, theses, dissertations, review articles, reports, case studies, and studies not addressing the theme were excluded. Controlled terms in Portuguese and English indexed in (DeCS) and (MeSH), and the Boolean operators “AND” and “OR” were used. Synthesis: The risk of bias was calculated using the R software, analysed by the GRADE system and using a funnel plot. All effects were analysed and calculated at a 95% confidence interval. The evidence level was analysed using Stillwell and collaborators’ proposal. Results: A total of 1,628 articles were found. All articles were written in English, one was published in 2019, and 10 in 2020. Six studies were descriptive, two were multicentric cohort studies, two were retrospective cohort studies, one was observational-retrospective, and most were evidence level VI. In essence, all studies pointed out that children with underlying diseases tend to develop more severe COVID-19 illnesses and more hospitalization than children without these diseases. Conclusion: The knowledge of the risk factors related to worse COVID-19 outcomes by professionals allow a better assessment of patients and make them able to act with greater precision in the promotion, prevention, and rehabilitation of these children.

Echocardiographic patterns in critically ill COVID-19 patients. (preprint)

Background: Need for catecholamines is frequent in COVID-19 patients, but the main echocardiographic patterns are unknown. The objective was to report the main echo patterns in critically-ill COVID-19 patients. Methods: Observational and descriptive study in consecutive COVID-19 patients admitted to the ICU between March 12 and May 8, 2020. Systematic critical care echocardiography (CCE) was performed and retrospectively analyzed off-line. Echo values are reported in the overall population and in patients who required catecholamine infusion during the first 2 days following admission (D1-2) or afterwards until day 7 (D3-7). Results: Of the 79 patients (78% male; median age 63 [56-71]; body mass index 29 [26-30]) included, 90% had at least 1 comorbidity. PaO2/FiO2 at admission was 85 [67-162] mmHg. 53% of patients were mechanically ventilated. ICU length of stay was 9 [5-16] days and mortality 34%. 134 echocardiographic studies were performed during the first week in 65 patients. Pulmonary artery acceleration time was decreased (77 [65-97] ms), suggesting pulmonary hypertension. All 39 patients (49%) who required catecholamine infusion underwent CCE and 25.6% had left ventricular (LV) systolic dysfunction, 28.2% acute cor pulmonale (ACP), 7.7% hypovolemia, and 38.5% vasoplegia. Modification of echo patterns was observed at D3-7, with less LV systolic dysfunction and more ACP, which was the most frequent pattern. Computed tomography pulmonary angiography in 6 patients with ACP indicated intrapulmonary thrombus in 4. Conclusion: Different echocardiographic patterns were observed during the first week following ICU admission in COVID-19 patients. ACP was frequent and often related to thrombus in the pulmonary circulation. 

Surgical Management of Bladder Cancer During First Month of COVID-19 Outbreak: Lessons Learned Across Italy (preprint)

Objectives: Real-life overview of bladder cancer (BC) surgical management in Italy during the first month of COVID-19 pandemic (March 2020) with head to head comparison of the data from March 2019, considered “usual activity” period. The aim is to confront performance of Academic Centers (AC) vs Non Academic Centers (NAC) as well as non-COVID Centers (nCC) and COVID Centers (CC). Patients and methods: During April 2020, an e-mail survey was sent to 32 Sections of Urology across Italy. It contained 14 multiple-choice questions focused on activities during March 2019 and March 2020. Statistical analysis was performed using IBM SPSS Statistics (v26) software. Results28 centers answered to survey. AC and NAC showed statistically significant differences (chi-square test p<0.05) about number of physicians assigned to Covid wards (p=0.001), Trans-Urethral Resection of Bladder Tumour (TURBT) (p=0.046) and cystectomies (p=0.037) performed in March 2020 (p=0.037). In 2020, AC performed more surgical procedures compared to NAC. In 2019, AC had more procedures per Operating Block (OB) (p=0.015) and greater number of emergent Trans-Urethral Resections (TUR) (p=0.014), while NAC had more TURBTs. CC had more patients (pts) both evaluated for gross hematuria (p=0.017) and requiring haemostatic Trans-Urethral Resection (hTUR) in 2019. In 2020 nCC had more surgeries per OB (p=0.001), TURBTs (p=0.030) and cystectomies (p=0.034) than CC. ConclusionThe COVID-19 pandemic represents an important challenge for cancer centers, in the context of an extremely dynamic clinical and political situation which requires maximum flexibility to be appropriately managed.