A bovine antibody possessing an ultralong complementarity-determining region CDRH3 targets a highly conserved epitope in sarbecovirus spike proteins.

Broadly neutralizing antibodies have huge potential as novel antiviral therapeutics due to their ability to recognize highly conserved epitopes that are seldom mutated in viral variants. A subset of bovine antibodies possess an ultralong complementarity-determining region (CDR)H3 that is highly adept at recognizing such conserved epitopes, but their reactivity against Sarbecovirus Spike proteins has not been explored previously. Here, we use a SARS-naïve library to isolate a broadly reactive bovine CDRH3 that binds the receptor-binding domain of SARS-CoV, SARS-CoV-2, and all SARS-CoV-2 variants. We show further that it neutralizes viruses pseudo-typed with SARS-CoV Spike, but this is not by competition with angiotensin-converting enzyme 2 (ACE2) binding. Instead, using differential hydrogen-deuterium exchange mass spectrometry, we demonstrate that it recognizes the major site of vulnerability of Sarbecoviruses. This glycan-shielded cryptic epitope becomes available only transiently via interdomain movements of the Spike protein such that antibody binding triggers destruction of the prefusion complex. This proof of principle study demonstrates the power of in vitro expressed bovine antibodies with ultralong CDRH3s for the isolation of novel, broadly reactive tools to combat emerging pathogens and to identify key epitopes for vaccine development.

How the First Year of the COVID-19 Pandemic Impacted Patients' Hospital Admission and Care in the Vascular Surgery Divisions of the Southern Regions of the Italian Peninsula.

BACKGROUND: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. METHODS: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. RESULTS: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p < 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p < 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). CONCLUSIONS: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia.

Prevalence and impact of dysrhythmias in COVID-19 intensive care patients

Background: The COVID-19 pandemic has had a dramatic impact on clinical practice, amounting to more emergency department and intensive care unit (ICU) admissions. Due to their frequent multiple comorbidities, management in the ICU is challenging. Early studies suggest that cardiac injury is frequent in hospitalized patients with COVID-19, and it is plausible that these patients have a higher risk of cardiac dysrhythmias. Purpose: To determine the prevalence of dysrhythmias in ICU patients with COVID-19 pneumonia, identify major predictors and determine the impact on in-hospital mortality. Methods: A retrospective study of 98 consecutive patients with COVID-19 Pneumonia admitted to the ICU of a tertiary hospital in 2020. The main outcome was dysrhythmias (including significant bradycardia, high/slow ventricular rate or new-onset atrial fibrillation (AF) or atrial flutter, other supraventricular tachycardias, ventricular tachycardia and ventricular fibrillation). Significant bradycardia was defined as heart rate lower than 40 or need of treatment. Sociodemographic variables and clinical data were retrieved for each patient, severity scores at admission (Apache II, SOFA and SAPS II), number of days on mechanical ventilation or high-flow oxygen and placement on Venovenous Extracorporeal Membrane Oxygenation (ECMO) or prone position were recorded. Statistical comparison was made between groups, including logistic regression adjusting for confounding variables. Results: The most frequent arrhythmia was significant sinus bradycardia (28, 28.5%) followed by high ventricular rate AF (14, 14.2%). Patients who had dysrhythmias were older (66.24 ± 10.13 vs 60.85 ± 12.69 years, p 0.024), more severe (SAPS II score 42.55 ± 11.08 vs 35.98 ± 11.26, p 0.006), had more atrial fibrillation (AF) (p 0.022), had higher maximum C-reactive protein (mCRP) (6.56 ± 2.68 vs 6.24 vs 2.86, p 0.009), were mechanically ventilated for a longer time (15.64 ± 13.18 vs 8.92 ± 8.85 days, p 0.004), had longer intubation time (14.52 ± 9.39 vs 8.70 ± 8.21 days, p 0.002) and had higher usage of dexamethasone (p 0.042) and prone position (p 0.016). When adjusted for confounding variables, prone was the most significant predictor (OR 2.800;95% CI 1.203-6.516) followed by use of dexamethasone (OR 2.484;95% CI 1.020-6.050). Days intubated, days on mechanical ventilation, age, mCRP and SAPS II on admission were also predictors of dysrhythmia. Regarding mortality, patients with arrhythmic events had a tendency for greater in-hospital death (OR 2.440;95% CI 0.950-6.310;p 0.065). Conclusions: COVID-19 ICU patients are a subset of patients at risk of cardiac arrhythmias. Use of prone position was the main contributor to these events, but clinical history, severity and treatment may also play an important role. Efforts must be made to optimize ventilatory support and treatment in order to reduce the risk of dysrhythmias. (Figure Presented).

Tachydysrhythmias in patients admitted with COVID-19 pneumonia: prevalence and impact on in-hospital mortality

Background: The COVID-19 pandemic has shifted tremendously the paradigm of hospital care and treatment of cardiovascular (CV) patients. According to most recent evidence, due to its multisystemic impact, COVID-19 may lead to an increased risk of cardiac arrhythmias with subsequently increased morbimortality. Purpose: Determine the prevalence of tachyarrhythmias in patients admitted with COVID-19, possible predictors and impact on in-hospital mortality. Methods: A retrospective study of 3475 consecutive patients with COVID-19 pneumonia admitted to our hospital between February 2020 and November 2021 were included. The main outcome was tachyarrhythmias (high ventricular rate (HVR) or new-onset atrial fibrillation (AF), HVR or new-onset atrial flutter (AFL), other supraventricular tachycardias (SVT), ventricular tachycardia (VT) and ventricular fibrillation (VF)). Secondary outcome was in-hospital mortality. Sociodemographic variables and clinical data were recorded. Statistical comparison was made between groups, including logistic regression to determine odds ratios (OR). Results: A total of 215 patients presented HVR AF (6.31%), 79 of which with new-onset AF (36.74%). 8 patients had HVR AFL (0.23%), 5 VT (0.15%), 4 VF (0.12%) and only 3 patients had a SVT identified (0.09%). Patients with tachyarrhythmias were significantly older (77. 74 ± 11.25 68.94 ± 17.51 years, p <0.001) and had more hypertension (p 0.034), heart failure (HF) (p <0.001), severe valvular heart disease (VHD) (p 0.007), coronary artery disease (CAD) (p 0.031), chronic kidney disease (CKD) (p 0.048) and paroxysmal AF (if previously diagnosed (p 0.001). There were no significant differences regarding gender, dyslipidemia, diabetes, cerebrovascular disease and obstructive sleep apnoea (OSA). Patients with HF had the highest risk of tachyarrhythmia (OR 3.539;95% CI 2.666-4.698;p <0.001), followed by severe VHD (OR 1.990;95% CI 1.192-3.365;p 0.009) and CAD (OR 1.575;95% CI 1.040-2.386;p 0.032). Older patients or patients with hypertension or CKD were also at an increased risk. Also of note, patients previously diagnosed with paroxysmal AF were more likely to have episodes of HVR AF than the ones with persistent or permanent AF (OR 1.819;95% CI 1.272-2.602;p 0.001) Regarding the secondary outcome, patients with tachyarrhythmias during hospital stay had an odd almost 3 times higher of death (OR 2.820;95% CI 2.151-3.695;p <0.001). Conclusions: Tachyarrhythmias is a common complication in COVID-19 patients during hospital stay that is significantly linked to higher in-hospital mortality. Patients presenting with high CV disease burden are at particularly significant risk and should be carefully managed. Odds-ratio of tachyarrhythmias (Figure Presented).

An Ultralong Bovine CDRH3 that Targets a Conserved, Cryptic Epitope on SARS-CoV and SARS-CoV-2 (preprint)

The ability of broadly neutralising antibodies to target conserved epitopes gives them huge potential as antibody-based therapeutics, particularly in the face of constant viral antigen evolution. Certain bovine antibodies are highly adept at binding conserved, glycosylated epitopes, courtesy of their ultralong complementarity determining region (CDR)H3. Here, we used a SARS-naive, bovine ultralong CDRH3 library and mammalian cell display, to isolate a bovine paratope that engages the SARS-CoV and SARS-CoV-2 receptor-binding domain (RBD). This neutralises viruses pseudo-typed with SARS-CoV Spike protein but not by competition with RBD binding to ACE2. Instead, using differential hydrogen-deuterium exchange mass spectrometry and site-directed mutagenesis, we demonstrate that this ultralong CDRH3 recognises a rarely identified, conserved, cryptic epitope that overlaps the target of pan-sarbecovirus antibodies (7D6/6D6). The epitope is glycan-shielded and becomes accessible only transiently via inter-domain movements. This represents the first bovine anti-sarbecovirus paratope and highlights the power of this approach in identifying novel tools to combat emerging pathogens.

Impact of the COVID-19 pandemic on emergent pacemaker implantation during lockdown and its aftermath

Background: COVID-19 was first considered a pandemic on the 11th of March of 2020 by the World Health Organization. Its impact comprised not only the direct consequences of the disease but a decrease in the follow-up and interventions of patients with cardiovascular (CV) disease. In Portugal and the World, the consequences of this complex paradigm shift on emergent pacemaker implantation rates during and after this pandemic is largely unknown. Purpose: We sought to analyse the impact of COVID-19 pandemic on emergent pacemaker implantation rate and patient profile in a tertiary hospital during the first Portuguese lockdown and subsequent post-lockdown period. Methods: We retrospectively reviewed the clinical profile of patients who had pacemakers implanted in our hospital in an urgent/emergent setting from March 18, 2020 to May 17, 2020 (lockdown) and May 19 to July 17, 2020 (post-lockdown). This data was then directly compared to the homologous periods from the year before (H1 and H2, respectively). Results: A total of 180 patients submitted to emergent pacemaker implantation were included. The cohort was comprised of 29 patients who had a pacemaker implanted during lockdown, 60 post-lockdown, 38 in H1 (+31% vs lockdown) and 53 in H2. Average age and gender proportion were similar for all groups. When comparing lockdown and post-lockdown periods, the number of cases significantly increased in the second period (+106.9%) and there was a tendency for a higher number of temporary pacemaker use (3.4% vs 16.7%;p=0.076). Patients admitted during lockdown were 7.57 times more likely to present with hypotension/shock (odds ratio (OR) 7.57;p=0.013). Regarding lockdown and its homologous 2019 period, there was a decrease in the number of patients admitted (-23.7%). Again, there was a higher tendency for hypotension on presentation during lockdown (p=0.054). In comparison to its homologous 2019 period, post-lockdown saw a slight increase in the number of patients (+13.2%) and more patients presented with bradycardia (16.7% vs 3.8%;p=0.026). Also of note, no patients were admitted to the emergency department during lockdown for anomalies detected on ambulatory tests (Holter, electrocardiogram or implanted loop recorder). Conclusion: During lockdown, clinical presentation was generally more severe, with a greater number of patients presenting with hypotension/ shock. In addition, there appears to be a lockdown effect on emergent bradyarrhtmias admissions in the post-lockdown period with a profound impact: higher admission rates and more severe presentations including a higher need of temporary pacemaker. Patients with symptoms suggestive of bradyarrhythmias should be advised to present promptly regardless of the pandemic. (Figure Presented).

Energy Efficiency and Life Cycle Assessment with System Dynamics of Electricity Production from Rice Straw Using a Combined Gasification and Internal Combustion Engine

This study assessed the environmental performance and energy efficiency of electricity generation from rice straw using a combined gasification and internal combustion engine (G/ICE). A life cycle assessment (LCA) was performed to consider the conversion to electricity of rice straw, the production of which was based on the Philippine farming practice. Rice straw is treated as a milled rice coproduct and assumes an environmental burden which is allocated by mass. The results of an impact assessment for climate change was used directly in a system dynamic model to plot the accumulated greenhouse gas emissions from the system and compare with various cases in order to perform sensitivity analyses. At a productivity of 334 kWh/t, the global warming potential (GWP) of the system is equal to 0.642 kg CO2-eq/MJ, which is 27% lower than the GWP of rice straw on-site burning. Mitigating biogenic methane emissions from flooded rice fields could reduce the GWP of the system by 34%, while zero net carbon emissions can be achieved at 2.78 kg CO2/kg of milled rice carbon sequestration. Other sources of greenhouse gas (GHG) emissions are the use of fossil fuels and production of chemicals for agricultural use. The use of agricultural machinery and transport lorries has the highest impact on eutrophication potential and human toxicity, while the application of pesticides and fertilizers has the highest impact on ecotoxicity. The biomass energy ratio (BER) and net energy ratio (NER) of the system is 0.065 and 1.64, respectively. The BER and NER can be improved at a higher engine efficiency from 22% to 50%. The use of electricity produced by the G/ICE system to supply farm and plant operations could reduce the environmental impact and efficiency of the process.

COVID 19: The catalyst for digital transformation in the hospitality industry?

Despite its benefits related to efficiency, creating better customer experiences, increasing revenue, and supporting decision-making, until the outbreak of COVID-19 digital transformation was not on many hotels' strategic plans. However, like in many other industries, the COVID-19 physical distancing good practices and governments' restrictions acted as catalysts and promoted hotel digitalization. To this end, a questionnaire was administered to 51 hotel managers to verify if that happened in Portuguese hotels and what processes were most impacted. Results showed that 92% of the hotel managers agreed that COVID-19 promoted the digitalization of processes, with most organizations considering that online meetings and technology productivity tools are here to stay. Hotels' digitalization has the potential to generate high-efficiency gains both in public-facing operations and back-office operations. This study highlights these implications and intends to spur researchers to investigate the practical impact of these implications on business efficiency and social theory.

COVID-19 seroprevalence in military police force, Southern Brazil.

BACKGROUND: Limited data is available regarding the frequency of COVID-19 in populations that are highly exposed to SARS-CoV-2. In this cross-section study we evaluated COVID-19 seroprevalence in military police forces of 10 major cities in Rio Grande do Sul, South of Brazil. METHODS: Sampling was randomly performed in clusters, in respect to the number of professionals at service per city and military unit. Research subjects were evaluated on July 23, 2020 (first wave peak in Brazil). Clinical information was obtained, and venous blood was taken for ELISA testing (IgA, and IgG antibodies). Sample size consisted of 1,592 military workers (33.6% of study population). They were mostly man (81.2%) and young (median 34 years-old). Most had been asymptomatic (75.3%) during pandemic, and 27.5% reported close contact with COVID-19 cases (after a median time of 21 days). Antibodies were detected in 3.3% of the participants, mostly IgA (2.7%), and IgG (1.7%). After 3 weeks, 66.7% of IgA and IgG results turned negative, in addition to 78.3% and 100% of borderline IgA and IgG results, respectively. CONCLUSION: The seroprevalence of COVID-19 amongst military police was at least 3.4 higher than the findings of other studies performed in the general population, in the same cities and dates. Most detectable antibodies were of IgA class, which implies recent exposure. Asymptomatic people were more prone to have negative antibody titters in the second run.

March 2020: 31 days that will reshape tourism

Lessons from previous endemics/pandemics show which type/timing of public health measures had a significant influence on the impact of diseases. However, those show that public health measures and travel restrictions represent a significant burden on countries’ economies, especially in the tourism industry. This study aims to investigate whether a country’s dependence on tourism might influence the time/nature of pandemic mitigation measures and the impact of the pandemic on tourism, particularly in the hospitality sector. To achieve a comprehensive/multidimensional perspective, 12 European countries were studied based on the collection of data from 6 different sources: cases/deaths caused by the disease, economic indicators, public health measures, rooms supply/demand, reservation/cancellation rates, demographic and healthcare system characteristics. Using data science techniques/methods allowed to verify that the dependence of some countries on tourism did not make them to have a different behaviour in terms of the application of measures. Despite the differences in the timings/types of measures implemented, tourism was highly affected in all countries. © 2020 Informa UK Limited, trading as Taylor & Francis Group.