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Association of Surgeons in Training Surgical Summit, online, 17 Oct 2020 - 17 Oct 2020 2021 Virtual Annual Meeting / Surgical Research Society, online, 24 Mar 2021 - 25 Mar 2021, National Research Collaborative Meeting, online, 10 Dec 2020 - 10 Dec 2020, Royal Australasian College of Surgeons Annual Academic Surgery Conference, online, 5 Nov 2020 - 5 Nov 2020; The British journal of surgery : BJS 108(12), 1448-1464 (2021). doi:10.1093/bjs/znab336 Published by Wiley, New York, NY [u.a.]

The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants and breakthrough infections despite available coronavirus disease 2019 (COVID-19) vaccines calls for antiviral therapeutics. The application of soluble angiotensin converting enzyme 2 (ACE2) as a SARS-CoV-2 decoy that reduces cell bound ACE2-mediated virus entry is limited by a short plasma half-life. This work presents a recombinant human albumin ACE2 genetic fusion (rHA-ACE2) to increase the plasma half-life by an FcRn-driven cellular recycling mechanism, investigated using a wild type (WT) albumin sequence and sequence engineered with null FcRn binding (NB). Binding of rHA-ACE2 fusions to SARS-CoV-2 spike protein subdomain 1 (S1) was demonstrated (WT-ACE2 KD = 32.8 nM and NB-ACE2 KD = 31.7 nM) using Bio-Layer Interferometry and dose-dependent in vitro inhibition of host cell infection of pseudotyped viruses displaying surface SARS-CoV-2 spike (S) protein. FcRn-mediated in vitro recycling was translated to a five times greater plasma half-life of WT-ACE2 (t½ β = 13.5 h) than soluble ACE2 (t½ β = 2.8 h) in humanised FcRn/albumin double transgenic mice. The rHA-ACE2-based SARS-CoV-2 decoy system exhibiting FcRn-driven circulatory half-life extension introduced in this work offers the potential to expand and improve the anti-COVID-19 anti-viral drug armoury. Statement of significance: The COVID-19 pandemic has highlighted the need for rapid development of efficient antiviral therapeutics to combat SARS-CoV-2 and new mutants to lower morbidity and mortality in severe cases, and for people that are unable to receive a vaccine. Here we report a therapeutic albumin ACE2 fusion protein (rHA-ACE2), that can bind SARS-CoV-2 S protein decorated virus-like particles to inhibit viral infection, and exhibits extended in vivo half-life compared to ACE2 alone. Employing ACE2 as a binding decoy for the virus is expected to efficiently inhibit all SARS-CoV-2 mutants as they all rely on binding with endogenous ACE2 for viral cell entry and, therefore, rHA-ACE2 constitutes a versatile addition to the therapeutic arsenal for combatting COVID-19.

The purpose of this report is to outline the evaluation and comparison approach and the knowledge obtained through a detailed data collection process, in order to examine the implementation and application of the Half Double Methodology (HDM) at Forsvarsministeriets Material- og Indkøbsstyrelse (FMI), as well as compare and contrast pilot and reference projects. State-owned FMI is the Danish Ministry of Defence Acquisition and Logistics Organization (English abbreviation: DALO), and thus a unit under the Ministry of Defence and the Danish public sector. It is likely that the Half Double Methodology has had a positive impact on FMI and their team collaboration. The procurement process is faster, which especially is evident in pilot case 3, but also the initial versions of pilot case 1 and 2. However, here, the cases were subject to external conditions which increased the duration. FMI experiences satisfaction from stakeholders involved in the procurement. This satisfaction is also present in most of the team members engaging with the methodology. Hence overall, integrating the Half Double Methodology in FMI’s team collaboration is perceived as a success in FMI and continues to be applied. However, there is still room for improvements in the procurement process and team configuration. This relates to the application of HDM, but also other constraints in FMI, which is related to a lack of resources to develop interdisciplinary teams, as well as challenges from covid-19 restrictions. The purpose of this report is to outline the evaluation and comparison approach and the knowledge obtained through a detailed data collection process, in order to examine the implementation and application of the Half Double Methodology (HDM) at Forsvarsministeriets Material- og Indkøbsstyrelse (FMI), as well as compare and contrast pilot and reference projects. State-owned FMI is the Danish Ministry of Defence Acquisition and Logistics Organization (English abbreviation: DALO), and thus a unit under the Ministry of Defence and the Danish public sector. It is likely that the Half Double Methodology has had a positive impact on FMI and their team collaboration. The procurement process is faster, which especially is evident in pilot case 3, but also the initial versions of pilot case 1 and 2. However, here, the cases were subject to external conditions which increased the duration. FMI experiences satisfaction from stakeholders involved in the procurement. This satisfaction is also present in most of the team members engaging with the methodology. Hence overall, integrating the Half Double Methodology in FMI’s team collaboration is perceived as a success in FMI and continues to be applied. However, there is still room for improvements in the procurement process and team configuration. This relates to the application of HDM, but also other constraints in FMI, which is related to a lack of resources to develop interdisciplinary teams, as well as challenges from covid-19 restrictions.

AbstractMost children have a mild course of acute COVID-19. Only few mainly non-controlled studies with small sample size have evaluated long-term recovery from SARS-CoV-2 infection in children. The aim of this study was to evaluate symptoms and duration of ‘long COVID’ in children. A nationwide cohort study of 37,522 children aged 0–17 years with RT-PCR verified SARS-CoV-2 infection (response rate 44.9%) and a control group of 78,037 children (response rate 21.3%). An electronic questionnaire was sent to all children from March 24th until May 9th, 2021. Symptoms lasting > 4 weeks were common among both SARS-CoV-2 children and controls. However, SARS-CoV-2 children aged 6–17 years reported symptoms more frequently than the control group (percent difference 0.8%). The most reported symptoms among pre-school children were fatigue Risk Difference (RD) 0.05 (CI 0.04–0.06), loss of smell RD 0.01 (CI 0.01–0.01), loss of taste RD 0.01 (CI 0.01–0.02) and muscle weakness RD 0.01 (CI 0.00–0.01). Among school children the most significant symptoms were loss of smell RD 0.12 (CI 0.12–0.13), loss of taste RD 0.10 (CI 0.09–0.10), fatigue RD 0.05 (CI 0.05–0.06), respiratory problems RD 0.03 (CI 0.03–0.04), dizziness RD 0.02 (CI 0.02–0.03), muscle weakness RD 0.02 (CI 0.01–0.02) and chest pain RD 0.01 (CI 0.01–0.01). Children in the control group experienced significantly more concentration difficulties, headache, muscle and joint pain, cough, nausea, diarrhea and fever than SARS-CoV-2 infected. In most children ‘long COVID’ symptoms resolved within 1–5 months.Conclusions: Long COVID in children is rare and mainly of short duration. What is Known:• There are increasing reports on ‘long COVID’ in adults.• Only few studies have evaluated the long-term recovery from COVID-19 in children, and common for all studies is a small sample size (median number of children included 330), and most lack a control group. What is New:• 0.8% of SARS-CoV-2 positive children reported symptoms lasting >4 weeks (‘long COVID’), when compared to a control group.• The most common ‘long COVID’ symptoms were fatigue, loss of smell and loss of taste, dizziness, muscle weakness, chest pain and respiratory problems.• These ‘long COVID’ symptoms cannot be assigned to psychological sequelae of social restrictions.• Symptoms such as concentration difficulties, headache, muscle- and joint pain as well as nausea are not ‘long COVID’ symptoms.• In most cases ‘long COVID’ symptoms resolve within 1-5 months.

The COVID-19 pandemic has led governments to instate a large number of restrictions on and recommendations for citizens’ behavior. One widely used tool for measuring compliance with these strictures are nationally representative surveys that ask citizens to self-report their behavior. But if respondents avoid disclosing socially undesirable behaviors, such as not complying with government strictures in a public health crisis, estimates of compliance will be biased upwards. To assess the magnitude of this problem, this study compares measures of compliance from direct questions to those estimated from list-experiments - a response technique that allows respondents to report illicit behaviors without individual-level detection. Implementing the list-experiment in two separate surveys of Danish citizens (n>5,000), we find no evidence that citizens under-report non-compliant behavior. We therefore conclude that survey estimates of compliance with COVID-19 regulations do not suffer from social desirability bias.

AbstractFew data are available on the incidence of deep vein thrombosis (DVT) in critically ill COVID-19 with thrombosis prophylaxis. This study retrospectively included 88 patients in the ICU with critically ill COVID-19 at Jinyintan Hospital in Wuhan, China. All patients underwent compression ultrasonography for identifying DVT. Firth logistic regression was used to examine the association of DVT with sex, age, hypoalbuminemia, D-dimer, and SOFA score. The median (interquartile range [IQR]) age and SOFA score of 88 patients were 63 (55–71) years old and 5 (4–6), respectively. Despite all patients receiving guideline-recommended low-molecular-weight heparin (LMWH) thromboprophylaxis, the incidence of DVT was 46% (95% CI 35–56%). Proximal DVT was recognized in 9% (95% CI 3–15%) of the patients, while 46% (95% CI 35–56%) of patients had distal DVT. All of the proximal DVT combined with distal DVT. Risk factors of DVT extension occurred in all distal DVT patients. As Padua score ≥ 4 or IMPROVE score ≥ 2, 53% and 46% of patients had DVT, respectively. Mortality was higher in patients with acute DVT (30%) compared with non-DVT (17%), but did not reach statistical significance. Hypoalbuminemia (odds ratio [OR], 0.17; 95% CI 0.06–0.05, P = 0.001), higher SOFA score (OR per IQR, 2.07; 95% CI 1.38–3.39, P = 0.001), and elevated D-dimer (OR per IQR, 1.04; 95% CI 1.03–1.84, P = 0.029) were significant DVT risk factors in multivariable analyses. High incidence of DVT was identified in patients with critically ill COVID-19, despite the use of guideline-recommended pharmacologic thromboprophylaxis. The presence of hypoalbuminemia, higher SOFA score, and elevated D-dimer were significantly independent risk factors of DVT. More effective VTE prevention and management strategies may need to be addressed.