Pandemic, power and paradox: Improvising as the New Normal during the COVID-19 crisis

The global COVID-19 pandemic made salient various paradoxical tensions, such as the trade-offs between individual freedom and collective safety, between short term and long-term consequences of adaptation to the new conditions, the power implications of sameness (COVID-19 was non-discriminatory in that all were affected in one way or another) and difference (yet not all were affected equally due to social differences), whereas most businesses became poorer under lockdown, others flourished;while significant numbers of workers were confined to home, some could not return home;some thrived while working from home as others were challenged by the erosion of barriers between their private and working lives. Rapid improvisational responding and learning at all levels of society presented itself as a naturally occurring research opportunity for improvisation scholars. This improvisation saw the arrival of a 'New Normal', eventually defined as 'learning to live with COVID-19'. The five articles in this special issue capture critical aspects of improvisation, paradoxes and power made salient by the COVID-19 pandemic in contexts ranging from higher-education, to leadership, to medical care and virtue ethics. In their own ways, each breaks new ground by contributing novel insights into improvisation scholarship.

Architects’ ‘enforced togetherness’: new design affordances of the home

Lockdown impositions have impacted people’s lives, their health and wellbeing, changing the ways in which dwellings are used and occupied. Spaces within the home have had to be rapidly renegotiated, redesigned and resynchronised in ways not yet fully explored or understood. Social relationships in the home have shifted and adapted as a result of ‘enforced togetherness’. This study presents a rich snapshot of 23 UK designer-architects’ transformative lived experiences of lockdown, using an interpretative phenomenological approach. It identifies four critical socio-spatial affordances that are rooted in the physical and mental wellbeing of the architects/designers. ‘Individuality’ suggests the need for increased physical separation to be alone. ‘Communality’ denotes a need for household members to be together. Both individuality and communality are seen as two opposite dimensions of the socio-spatial affordance of the home. ‘Adaptability’ points to requirements for flexible, decluttered and versatile spaces to enable ‘vibrancy’ not ‘suffocation’. Finally, ‘connectivity’ encompasses the need for a strong connection between the indoors and outdoors. These dimensions must be considered in housing design, so new housing models can emerge. The use of interpretative phenomenological analysis, employing the architectural tool of drawing, is shown to be a useful approach for housing research. PRACTICE RELEVANCE The impact on households’ wellbeing as a consequence of Covid-19 lockdowns has led to new considerations for future housing design. In a post-Covid environment, the particular needs for housing have been transformed. The findings and insights from this study will help to reframe the existing conventions of housing design criteria (e.g. a reliance on defining space functions) toward a clearer set of qualities for inhabitant and household wellbeing. New housing criteria involving socio-spatial affordances of individuality, communality, adaptability, and connectivity are shown to be viable and highly appropriate. These new dimensions highlight how inhabitants’ wellbeing can be included in viable and affordable housing. © 2022 The Author(s).

Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases.

Despite the fast development of vaccines, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still circulates through variants of concern (VoC) and escape the humoral immune response. SARS-CoV-2 has provoked over 200,000 deaths/months since its emergence and only a few antiviral drugs showed clinical benefit up to this moment. Thus, chemical structures endowed with anti-SARS-CoV-2 activity are important for continuous antiviral development and natural products represent a fruitful source of substances with biological activity. In the present study, agathisflavone (AGT), a biflavonoid from Anacardium occidentale was investigated as a candidate anti-SARS-CoV-2 compound. In silico and enzymatic analysis indicated that AGT may target mainly the viral main protease (Mpro) and not the papain-like protease (PLpro) in a non-competitive way. Cell-based assays in type II pneumocytes cell lineage (Calu-3) showed that SARS-CoV-2 is more susceptible to AGT than to apigenin (APG, monomer of AGT), in a dose-dependent manner, with an EC50 of 4.23 ± 0.21 µM and CC50 of 61.3 ± 0.1 µM and with a capacity to inhibit the level of pro-inflammatory mediator tumor necrosis factor-alpha (TNF-α). These results configure AGT as an interesting chemical scaffold for the development of novel semisynthetic antivirals against SARS-CoV-2.

Transport and evaporation of virus-containing droplets exhaled by men and women in typical cough events.

The spreading of the virus-containing droplets exhaled during respiratory events, e.g., cough, is an issue of paramount importance for the prevention of many infections such as COVID-19. According to the scientific literature, remarkable differences can be ascribed to several parameters that govern such complex and multiphysical problem. Among these, a particular influence appears associated with the different airflows typical of male and female subjects. Focusing on a typical cough event, we investigate this aspect by means of highly-resolved direct numerical simulations of the turbulent airflow in combination with a comprehensive Lagrangian particle tracking model for the droplet motion and evaporation. We observe and quantify major differences between the case of male and female subjects, both in terms of the droplet final reach and evaporation time. Our results can be associated with the different characteristics in the released airflow and thus confirm the influence of the subject gender (or other physical properties providing different exhalation profiles) on both short-range and long-range airborne transmission.

Application of recommended preventive measures against COVID-19 could help mitigate the risk of SARS-CoV-2 infection during dental practice: Results from a follow-up survey of French dentists.

BACKGROUND: During the first-wave of the COVID-19 pandemic, dentists were considered at high-risk of infection. In France, to stop the spread of SARS-CoV-2, a nationwide lockdown was enforced, during which dentists suspended their routine clinical activities, working solely on dental emergencies. This measure has had an indisputable mitigating effect on the pandemic. To continue protecting dentists after suspension of nationwide lockdown, implementation of preventive measures was recommended, including adequate personal protective equipment (PPE) and room aeration between patients. No study has explored whether implementation of such preventive measures since the end of the first-wave has had an impact on the contamination of dentists. METHODS: An online survey was conducted within a French dentist population between July and September 2020. To explore risk factors associated with COVID-19, univariate and multivariate logistic regression analyses were performed. RESULTS: The results showed that COVID-19 prevalence among the 3497 respondents was 3.6%. Wearing surgical masks during non-aerosol generating procedures was a risk factor of COVID-19, whereas reducing the number of patients was a protective factor. CONCLUSIONS: Considering the similar COVID-19 prevalence between dentists and the general population, such data suggest that dentists are not overexposed in their work environment when adequate preventive measures are applied. IMPACT: Dentists should wear specific PPE (FFP2, FFP3 or (K)N95 masks) including during non-aerosol generating procedures and reduce the number of patients to allow proper implementation of disinfection and aeration procedures. Considering the similarities between COVID-19 and other viral respiratory infections, such preventive measures may also be of interest to limit emerging variants spread as well as seasonal viral outbreaks.

Added to pre-existing inflammation, mRNA-lipid nanoparticles induce inflammation exacerbation (IE).

Current nucleoside-modified RNA lipid nanoparticle (modmRNA-LNP) technology has successfully paved the way for the highest clinical efficacy data from next-generation vaccinations against SARS-CoV-2 during the COVID-19 pandemic. However, such modmRNA-LNP technology has not been characterized in common pre-existing inflammatory or immune-challenged conditions, raising the risk of adverse clinical effects when administering modmRNA-LNPs in such cases. Herein, we induce an acute-inflammation model in mice with lipopolysaccharide (LPS) intratracheally (IT), 1 mg kg-1, or intravenously (IV), 2 mg kg-1, and then IV administer modmRNA-LNP, 0.32 mg kg-1, after 4 h, and screen for inflammatory markers, such as pro-inflammatory cytokines. ModmRNA-LNP at this dose caused no significant elevation of cytokine levels in naive mice. In contrast, shortly after LPS immune stimulation, modmRNA-LNP enhanced inflammatory cytokine responses, Interleukin-6 (IL-6) in serum and Macrophage Inflammatory Protein 2 (MIP-2) in liver significantly. Our report identifies this phenomenon as inflammation exacerbation (IE), which was proven to be specific to the LNP, acting independent of mRNA cargo, and was demonstrated to be time- and dose-dependent. Macrophage depletion as well as TLR3 -/- and TLR4-/- knockout mouse studies revealed macrophages were the immune cells involved or responsible for IE. Finally, we show that pretreatment with anti-inflammatory drugs, such as corticosteroids, can partially alleviate IE response in mice. Our findings characterize the importance of LNP-mediated IE phenomena in gram negative bacterial inflammation, however, the generalizability of modmRNA-LNP in other forms of chronic or acute inflammatory and immune contexts needs to be addressed.

Educational Impact on Ecuadorian University Students Due to the COVID-19 Context

The mobility restrictions imposed in different countries due to the pandemic of Sars-CoV2 has hugely impacted different areas in the world. In this work, impacts on the social areas of Ecuadorian university students such as education, economy, physical and mental health, and access to telecommunications are analyzed. For this work, in a snapshot between May to September 2020, 1841 students from 6 public and 5 private universities from Ecuador were surveyed through 47 questions, which were grouped into 7 mutually exclusive dimensions. The Partial Least Squares Structural Equation Model (PLS-SEM) was used to analyze the correlations between the responses of the questions and the relations between dimensions. Dimensional relations were used to analyze how students perceive online classes, teachers’preparation, mood, and the impact on their learning process due to their decreasing family income. Among the most important results, we found that 63.78% of students want to return to on-site classes regardless of their conditions of Internet connection and their available learning tools (computers, tablets, or cellphones). The results also show that family income has influenced how students access the Internet, Internet connection, technological resources for online learning, and mood. Regarding the relations between variables, we found that older students and students from higher semesters think that online classes are better than face-to-face classes and want to continue in online education.

CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study.

BACKGROUND: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. METHODS: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. RESULTS: Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233-0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547-0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. CONCLUSIONS: CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.

Cutaneous reactions after SARS-CoV-2 vaccination: a cross-sectional Spanish nationwide study of 405 cases.

BACKGROUND: Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized. OBJECTIVE: To describe and classify cutaneous reactions after SARS-CoV-2 vaccination. METHODS: A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification. RESULTS: From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment. CONCLUSIONS: Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.

The Retornus-2 study: impact of respiratory muscle training in subacute stroke patients with dysphagia, study protocol of a double-blind randomized controlled trial.

BACKGROUND: Stroke can lead to varying degrees of oropharyngeal dysphagia, respiratory muscle dysfunction and even increase medical complications such as aspiration, malnutrition and death. Recent studies suggest that inspiratory and expiratory respiratory muscle training (IEMT) can improve swallowing efficacy and may reduce aspiration events. The main purpose of this study is to examine whether an 8-week IEMT programme can improve respiratory muscle strength and swallow dysfunction severity in subacute stroke patients with dysphagia. METHODS: Retornus-2 is a two-arm, prospectively registered, randomized controlled study with blinded assessors and the participation of fifty individuals who have suffered a stroke. The intervention group undergoes IEMT training consisting of 5 sets of 10 repetitions, three times a day for 8 weeks. Training loads increase weekly. The control group undergoes a sham-IEMT protocol. The primary outcome examines the efficacy of the IEMT protocol to increase respiratory muscle strength and reduce dysphagia severity. The secondary outcome assesses the longitudinal impact of dysphagia on body composition and nutritional assessment over a 6-month follow-up. DISCUSSION: IEMT induces an improvement in respiratory muscle strength and might be associated with relevant benefits in dysphagia patterns, as well as a reduction in the number of aspiration events confirmed by videofluoroscopy or fiberoptic endoscopic evaluation of swallowing. The description of the impact of swallowing impairment on nutritional status will help develop new strategies to face this known side-effect. TRIAL REGISTRATION: Clinicaltrials.gov NCT03021252. Registered on 10 January 2017. https://clinicaltrials.gov/ct2/results?cond=retornus+2&term=&cntry=ES&state=&city=&dist= WHO trial Registration data set: Due to heavy traffic generated by the COVID-19 outbreak, the ICTRP Search Portal does not respond. The portal recommends other registries such as clinicaltrials.gov. Protocol version: RETORNUS 2_ PROTOCOL_2.

Covid-19 older hospitalized patients: Three clinical-psychological patterns

Background and aims. The COVID-19 outbreak is a far-reaching health crisis and a significant psychological stressor. COVID-19 patients experience an unknown and life-threatening condition that ex-poses them to strict social distancing, physical discomfort, medication side effects, long hospitalization, stigmatization and fear of death. Older people seem to be particularly vulnerable to the current pandemic from both a physical and a psychological point of view. The present article aims to describe different psychological reactions in older hospitalized COVID-19 patients encountered by the clinical psychology Unit of one of northern Italy most hit hospitals. Three prototypical clinical cases will be described and discussed. Insights about different attitudes towards the illness will be offered. Conclusions. Auto-biographical narration among older hospitalized COVID-19 patients has positive effect. Hospital psychologist can support patients in the process of disease acceptance.

Prevalence and risk indicators of first-wave COVID-19 among oral health-care workers: A French epidemiological survey.

BACKGROUND: Previous studies have highlighted the increased risk of contracting the COVID-19 for health-care workers and suggest that oral health-care workers may carry the greatest risk. Considering the transmission route of the SARS-CoV-2 infection, a similar increased risk can be hypothesized for other respiratory infections. However, no study has specifically assessed the risk of contracting COVID-19 within the dental profession. METHODS: An online survey was conducted within a population of French dental professionals between April 1 and April 29, 2020. Univariable and multivariable logistic regression analyses were performed to explore risk indicators associated with laboratory-confirmed COVID-19 and COVID-19-related clinical phenotypes (i.e. phenotypes present in 15% or more of SARS-CoV-2-positive cases). RESULTS: 4172 dentists and 1868 dental assistants responded to the survey, representing approximately 10% of French oral health-care workers. The prevalence of laboratory-confirmed COVID-19 was 1.9% for dentists and 0.8% for dental assistants. Higher prevalence was found for COVID-19-related clinical phenotypes both in dentists (15.0%) and dental assistants (11.8%). Chronic kidney disease and obesity were associated with increased odds of laboratory-confirmed COVID-19, whereas working in a practice limited to endodontics was associated with decreased odds. Chronic obstructive pulmonary disease, use of public transportation and having a practice limited to periodontology were associated with increased odds of presenting a COVID-19-related clinical phenotype. Moreover, changes in work rhythm or clinical practice were associated with decreased odds of both outcomes. CONCLUSIONS: Although oral health-care professionals were surprisingly not at higher risk of COVID-19 than the general population, specific risk indicators could exist, notably among high aerosol-generating dental subspecialties such as periodontology. Considering the similarities between COVID-19-related clinical phenotypes other viral respiratory infections, lessons can be learned from the COVID-19 pandemic regarding the usefulness of equipping and protecting oral health-care workers, notably during seasonal viral outbreaks, to limit infection spread. IMPACT: Results from this study may provide important insights for relevant health authorities regarding the overall infection status of oral health-care workers in the current pandemic and draw attention to particular at-risk groups, as illustrated in the present study. Protecting oral health-care workers could be an interesting public health strategy to prevent the resurgence of COVID-19 and/or the emergence of new pandemics.

Turbulence dictates the fate of virus-containing liquid droplets in violent expiratory events (preprint)

Violent expiratory events, such as coughing and sneezing, are highly nontrivial examples of two-phase mixture of liquid droplets dispersed into an unsteady humid turbulent fluid phase. Understanding the physical mechanisms determining the fate of droplets is becoming a priority given the global COVID-19 emergency caused by the SARS-CoV-2 infection. By means of state-of-the-art fully resolved direct numerical simulations we contribute to solve this issue by identifying the key role of turbulence on the fate of exhaled droplets. Our results impact the current notion of social distance.

Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment (preprint)

Acute lung inflammation has severe morbidity, as seen in COVID-19 patients. Lung inflammation is accompanied or led by massive accumulation of neutrophils in pulmonary capillaries ("margination"). We sought to identify nanostructural properties that predispose nanoparticles to accumulate in pulmonary marginated neutrophils, and therefore to target severely inflamed lungs. We designed a library of nanoparticles and conducted an in vivo screen of biodistributions in naive mice and mice treated with lipopolysaccharides. We found that supramolecular organization of protein in nanoparticles predicts uptake in inflamed lungs. Specifically, nanoparticles with agglutinated protein (NAPs) efficiently home to pulmonary neutrophils, while protein nanoparticles with symmetric structure (e.g. viral capsids) are ignored by pulmonary neutrophils. We validated this finding by engineering protein-conjugated liposomes that recapitulate NAP targeting to neutrophils in inflamed lungs. We show that NAPs can diagnose acute lung injury in SPECT imaging and that NAP-like liposomes can mitigate neutrophil extravasation and pulmonary edema arising in lung inflammation. Finally, we demonstrate that ischemic ex vivo human lungs selectively take up NAPs, illustrating translational potential. This work demonstrates that structure-dependent interactions with neutrophils can dramatically alter the biodistribution of nanoparticles, and NAPs have significant potential in detecting and treating respiratory conditions arising from injury or infections.