A Comparison of Retrieved Respiratory Viral load emitted by infected SARS-CoV-2 patients

Viral RNA in fine (< 5 µm) aerosols from 13 patients infected by the SARS-CoV-2 virus were obtained using the Gesundheit-II (G-II) equipment which collects respiratory emissions. The collection was performed in isolation wards of the National Centre for Infectious Diseases of Singapore under an approved protocol. The patients breathed normally for 30 minutes, talk, and sing for 15 minutes each (with 30 minutes rest in between activity) into a specially designed aerosol collector in two size fractions. The coarse fraction (> 5 µm) and the fine aerosols (< 5 µm) are subsequently collected and subjected to PCR analysis for their viral load quantification. Viral RNA detected from 59% of the patients showed that patients earlier in illness were more likely to emit detectable RNA, and loads differed significantly between breathing, talking, and singing. © 2022 17th International Conference on Indoor Air Quality and Climate, INDOOR AIR 2022. All rights reserved.

Uncovering The Science Of Covid-19

The COVID-19 pandemic has disrupted lives and livelihoods all over the world by its myriad of twists and turns. The causative SARS coronavirus 2 continues to defy the imagination by its rapid evolution from the Alpha to Delta to Omicron variants. This book by an international and multi-disciplinary team of virologists, infectious diseases and public health physicians aims to uncover the scientific basis underpinning the virus characteristics, as well as the clinical and public health management of COVID-19. The ten chapters address and discuss a broad range of key topics including viral evolution, clinical management, diagnostic methodologies, aerosol transmission, public health containment measures, vaccination, pathophysiology, and omics analyses. More generally, the book can serve as a useful reference guide on many future scientific issues and questions that will continue to arise as humanity learns to confront and co-exist with COVID-19. © 2023 by World Scientific Publishing Co. Pte. Ltd.

The Novel SARS-CoV-2: An Overview on its Detection, Prevention and Control

On 30 January 2020, the World Health Organization (WHO) characterized the novel severe acute respiratory syndrome Coronavirus 2 (SARSCoV- 2) outbreak as a Public Health Emergency of International Concern. Subsequently, on 11 March 2020, WHO declared the global spread of Coronavirus disease 2019 (COVID-19) as a pandemic triggered by this causative virus. This COVID-19 pandemic has impacted lives and livelihoods worldwide, resulting in unprecedented social disruption and economic losses. In order to design and develop effective diagnostics, vaccines and therapeutic interventions against SARS-CoV-2, it is imperative to understand the molecular and cellular mechanisms underpinning the complex interactions between this virus, its variants, and its infected hosts. This chapter provides an overview on the classification, genomic organization and evolution of SARS-CoV-2 (including the emergence of variants from Alpha to Omicron), and summarizes existing and emerging testing strategies. With unprecedented speed, an array of conventional and new COVID-19 vaccines has been developed, evaluated in clinical trials, and administered to billions worldwide. Current and novel antiviral drugs and immunomodulatory approaches are discussed for the therapeutic and prophylactic management of SARS-CoV-2 infections. Finally, much remains for humanity to discover and learn as the world must continue to adapt and live with endemic COVID-19 and SARSCoV- 2 evolution. © 2023 by World Scientific Publishing Co. Pte. Ltd.

Analysis of Outcomes and Predictors of Response in Patients with Relapsed Mantle Cell Lymphoma Treated with Brexucabtagene Autoleucel

Background: Brexucabtagene autoleucel (brexu-cel) is the first CD19 chimeric antigen receptor T-cell (CAR T) therapy approved for use in patients (pts) with relapsed mantle cell lymphoma (MCL). The ZUMA-2 trial demonstrated that brexu-cel induces durable remissions in these pts with an ORR of 85% (59% CR), estimated 12-month PFS rate of 61%, and similar toxicity profile to other CAR T therapies (Wang et al, NEJM 2020). We conducted a multicenter, retrospective study of pts treated with commercial brexu-cel to evaluate its safety and efficacy in the non-trial setting. Methods: We reviewed records of pts with relapsed MCL across 12 US academic medical centers. Pts who underwent leukapheresis between July 2020 and June 2021 with the intent to proceed to commercial brexu-cel were included. Baseline demographic and clinical characteristics were summarized using descriptive statistics. Survival curves were generated using the Kaplan-Meier method, and univariate models were fit to identify predictors of post-CAR T outcomes. Results: Fifty-five pts underwent leukapheresis. There were 3 manufacturing failures. Baseline characteristics of the 52 pts who received brexu-cel are summarized in Table 1. Median age was 66 yrs (range: 47-79 yrs) and 82% were male. Twenty of 29 (69%) pts with known baseline MIPI were intermediate or high risk. Seven pts had a history of CNS involvement. The median number of prior therapies was 3 (range: 2-8), including prior autologous stem cell transplant (ASCT) in 21 (40%) and prior allogeneic transplant in 2 pts (1 with prior ASCT and 1 without). Fifty percent had relapsed within 24 months of their initial therapy. All pts had previously received a Bruton's tyrosine kinase inhibitor (BTKi), including 29 (56%) with disease progression on a BTKi. Forty (77%) pts received bridging therapy (17 BTKi, 10 BTKi + venetoclax, 6 chemo, 3 venetoclax, 2 XRT only, 1 steroids only, 1 lenalidomide + rituximab). The ORR was 88% (CR 69%) among patients who received brexu-cel. Two pts had PD on initial restaging and 3 died prior to first response assessment (without evidence of relapse). Seven pts have not completed restaging due to limited follow-up (< 3 months) and were not included in the response assessment. Five pts have progressed, including 2 with CR and 1 with PR on initial restaging. With a median follow-up of 4.2 months, the estimated 6-month PFS and OS rates were 82.7% and 89.0%, respectively. All 7 pts with prior CNS involvement were alive without relapse at last follow-up. The incidence of cytokine release syndrome (CRS) was 84% (10% grade ≥ 3) with a median time to max grade of 5 days (range: 0-10 days). There were no cases of grade 5 CRS. The incidence of neurotoxicity (NT) was 57% (31% grade ≥ 3) with a median time to onset of 7 days (range: 4-15 days). NT occurred in 4/7 pts with prior CNS involvement (3 grade 3, 1 grade 4). Grade 5 NT occurred in 1 pt who developed cerebral edema and died 8 days after infusion. Thirty-five pts received tocilizumab, 33 received steroids, 7 received anakinra, and 1 received siltuximab for management of CRS and/or NT. Post-CAR T infections occurred in 8 pts, including two grade 5 infectious AEs (covid19 on day +80 and septic shock on day +40 after infusion). Rates of grade ≥ 3 neutropenia and thrombocytopenia were 38% and 37%, respectively. Among pts with at least 100 days of follow-up and lab data available, 5/34 (15%) had persistent grade ≥ 3 neutropenia and 4/34 (12%) had persistent grade ≥ 3 thrombocytopenia at day +100. Five pts have died, with causes of death being disease progression (2), septic shock (1), NT (1), and covid19 (1). Univariate analysis did not reveal any significant associations between survival and baseline/pre-CAR T MIPI, tumor pathologic or cytogenetic features, prior therapies, receipt of steroids/tocilizumab, or pre-CAR T tumor bulk. Conclusions: This analysis of relapsed MCL pts treated with commercial brexu-cel reveals nearly identical response and toxicity rates compared to those reported on ZUMA-2. Longer follow-up is require to confirm durability of response, but these results corroborate the efficacy of brexu-cel in a population of older adults with high-risk disease features. While all 7 pts with prior CNS involvement are alive and in remission, strategies to mitigate the risk of NT in this setting need to be evaluated. Further studies to define the optimal timing of CAR T, bridging strategies, and salvage therapies for post-CAR T relapse in MCL are warranted. [Formula presented] Disclosures: Gerson: TG Therapeutics: Consultancy;Kite: Consultancy;Abbvie: Consultancy;Pharmacyclics: Consultancy. Sawalha: TG Therapeutics: Consultancy, Research Funding;Celgene/BMS: Research Funding;BeiGene: Research Funding;Epizyme: Consultancy. Bond: Kite/Gilead: Honoraria. Karmali: Janssen/Pharmacyclics: Consultancy;BeiGene: Consultancy, Speakers Bureau;Morphosys: Consultancy, Speakers Bureau;Takeda: Research Funding;Genentech: Consultancy;AstraZeneca: Speakers Bureau;Roche: Consultancy;Karyopharm: Consultancy;Epizyme: Consultancy;Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau;BMS/Celgene/Juno: Consultancy, Research Funding;EUSA: Consultancy. Torka: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Chow: ADC Therapeutics: Current holder of individual stocks in a privately-held company, Research Funding;AstraZeneca: Research Funding. Shadman: Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune, Mustang Bio and Atara Biotherapeutics: Consultancy;Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding. Ghosh: Genentech: Research Funding;Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau;Karyopharma: Consultancy, Honoraria;Seattle Genetics: Consultancy, Honoraria, Speakers Bureau;Janssen: Consultancy, Honoraria, Speakers Bureau;TG Therapeutics: Consultancy, Honoraria, Research Funding;Incyte: Consultancy, Honoraria;Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau;Genmab: Consultancy, Honoraria;Epizyme: Honoraria, Speakers Bureau;Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau;AstraZeneca: Consultancy, Honoraria, Speakers Bureau;ADC Therapeutics: Consultancy, Honoraria;Adaptive Biotech: Consultancy, Honoraria;AbbVie: Honoraria, Speakers Bureau. Moyo: Seattle Genetics: Consultancy. Fenske: TG Therapeutics: Consultancy, Speakers Bureau;Servier Pharmaceuticals: Consultancy;Seattle Genetics: Speakers Bureau;Sanofi: Speakers Bureau;Pharmacyclics: Consultancy;MorphoSys: Consultancy;Kite (Gilead): Speakers Bureau;KaryoPharm: Consultancy;CSL Therapeutics: Consultancy;Bristol-Myers Squibb: Speakers Bureau;Biogen: Consultancy;Beigene: Consultancy;AstraZeneca: Speakers Bureau;ADC Therapeutics: Consultancy;Adaptive Biotechnologies: Consultancy;AbbVie: Consultancy. Grover: Genentech: Research Funding;Novartis: Consultancy;ADC: Other: Advisory Board;Kite: Other: Advisory Board;Tessa: Consultancy. Maddocks: Seattle Genetics: Divested equity in a private or publicly-traded company in the past 24 months;BMS: Divested equity in a private or publicly-traded company in the past 24 months;Pharmacyclics: Divested equity in a private or publicly-traded company in the past 24 months;Novatis: Divested equity in a private or publicly-traded company in the past 24 months;Janssen: Divested equity in a private or publicly-traded company in the past 24 months;Morphosys: Divested equity in a private or publicly-traded company in the past 24 months;ADC Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months;Karyopharm: Divested equity in a private or publicly-traded company in the past 24 months;Beigene: Divested equity in a private or publicly-traded company in the past 24 months;Merck: Divested equity in a private or publicly-traded company in the past 24 months;KITE: Divested equity in a private or publicly-traded company in the past 24 months;Celgene: Divested equity in a private or publicly-traded company in the past 24 months. Jacobson: Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support;Humanigen: Consultancy, Honoraria, Other: Travel support;Celgene: Consultancy, Honoraria, Other: Travel support;Pfizer: Consultancy, Honoraria, Other: Travel support, Research Funding;Lonza: Consultancy, Honoraria, Other: Travel support;AbbVie: Consultancy, Honoraria;Precision Biosciences: Consultancy, Honoraria, Other: Travel support;Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Other: Travel support;Nkarta: Consultancy, Honoraria;Axis: Speakers Bureau;Clinical Care Options: Speakers Bureau. Cohen: Janssen, Adaptive, Aptitude Health, BeiGene, Cellectar, Adicet, Loxo/Lilly, AStra ZenecaKite/Gilead: Consultancy;Genentech, Takeda, BMS/Celgene, BioInvent, LAM, Astra Zeneca, Novartis, Loxo/Lilly: Research Funding.

Adapting to COVID-19 on construction sites: what are the lessons for long-term improvements in safety and worker effectiveness?

Purpose: Substantial changes were made on many UK construction projects in response to the COVID-19 pandemic. The purpose of this paper is to explore the unanticipated positive consequences of these and the scope for longer-term learning and developments within the sector. Design/methodology/approach: A qualitative approach was used, semi-structured interviews were conducted across six major project sites. Interviewees (n = 33) included site and senior managers, supply chain representatives and occupational safety and health (OSH) professionals. The interviews explored their experiences of working on site during the pandemic, the changes made to work practices and their perceived impacts of these changes. Findings: Improved planning and work sequencing were part of the revised process to make sites COVID-secure. This increased worker effectiveness and housekeeping/tidiness. The view on some sites was that this would improve OSH performance. The changes were perceived to be beneficial but may not be accepted by clients in the long term, as they could result in projects taking longer to complete. The ways in which COVID-19 risk has been communicated and perceived also provides longer-term lessons for the sector’s OSH management and training. Originality/value: Construction has adapted rapidly and effectively to new ways of working during the pandemic. This research captured in real time some of the changes made and presents an argument for embedding and adopting the changes to improve working arrangements and OSH within the construction sector. © 2021, Emerald Publishing Limited.

Liver enzyme elevation and acute liver injury are independently associated with adverse clinical outcomes in patients with COVID-19: A territory-wide cohort study of 1,040 patients in Hong Kong

Background: Different degrees of liver injury were reported in patients infected by Coronavirus disease 2019 (COVID-19) It is possibly caused by systemic inflammation and adverse drug reactions in severe COVID-19 patients under different medical treatments However, the impact of liver injury on adverse clinical outcomes remains unclear We aimed to examine the impact of liver injury on clinical outcomes in COVID-19 patients Methods: All COVID-19 patients reported to the Department of Health between 23 January 2020 and 1 May 2020 in Hong Kong were identified using an electronic database managed by Hospital Authority, Hong Kong, and retrospectively studied Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) elevation was defined as ALT/AST ≥2x upper limit of normal (ULN) (i.e. 80 U/L) Acute liver injury was defined as ALT and/or AST ≥2xULN, with total bilirubin ≥2xULN (i.e. 38 μmol/L) and/or international normalized ratio (INR) ≥1.7. The primary endpoint was a composite of intensive care unit (ICU) admission, use of invasive mechanical ventilation, and/or death Results: 1,040 COVID-19 patients were identified. Their mean age was 38±18 years, 560 (53 8%) were male, 4 1% and 0 3% had hepatitis B and C virus infection, respectively;53 (5 1%) were admitted to ICU, 22 (2 1%) received invasive mechanical ventilation, and 4 (0 4%) died Among 816 COVID-19 patients who had serial measurement of liver biochemistries, 184 (22 5%) had ALT/ AST elevation and 15 (1 8%) had acute liver injury Acute liver injury was more common in patients who had hepatitis B/C virus infection than those who did not have (9 4% vs. 1 8%, P=0 026) ALT/AST elevation (adjusted odds ratio [aOR] 7 92, 95% CI 4 14-15 14, P<0 001) and acute liver injury (aOR 6 40, 95% CI 1 78-23 07, P=0 005) were independently associated with development of primary endpoint (Table) Use of lopinavirritonavir ± ribavirin + interferon beta (aOR 1 94, 95% CI 1 20- 3 13, P=0 006) and corticosteroids (aOR 3 92, 95% CI 2 14- 7 16, P<0 001) were independently associated with ALT/AST elevation Use of corticosteroids was associated with acute liver injury (aOR 4 76, 95% CI 1 56-14 50, P=0 006), while all 15 patients who developed acute liver injury also usedlopinavir-ritonavir ± ribavirin ± interferon beta Conclusion: ALT/AST elevation and acute liver injury were independently associated with adverse clinical outcomes in COVID-19 patients Use of lopinavir-ritonavir, with or without ribavirin, interferon beta and/or corticosteroids were associated with ALT/AST elevation and acute liver injury in COVID-19 patients.