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Breast Cancer (BC) is the most common cancer in women in the United States. The COVID-19 pandemic affected healthcare delivery throughout North America. Breast cancer diagnosis and management was similarly affected.We conducted a scoping review to determine the impact of COVID-19 on BC care and the impact on patients' well-being.Our review found that the pandemic led to changes in screenings, biopsies, medical therapy, and surgery. Constraints of the pandemic left patients without resources to navigate the emotional toll from social distancing. There was a disparity in patients' perceptions of the impact of the pandemic on BC care.Although the pandemic altered medical care in general, we found that the impact on breast cancer care was counterintuitively not as significant as predicted. However, the pandemic did impact breast cancer patients' mental well-being. This highlights the importance of properly communicating, in real-time, guidelines on breast cancer management to allay the fears of the general public.

Objetivos: El estudio MEMOGAL (NCT04319081) está dirigido a evaluar cambios en la función cognitiva en pacientes tratados con inhibidores de la PCSK9 (iPCSK9). Se realiza primer análisis: 1) Discutir el papel de los farmacéuticos hospitalarios durante de la pandemia, así como evaluar el impacto de la misma en el control lipídico. 2) Análisis descriptivo; 3) Eficacia en reducción de colesterol-LDL (c-LDL) de alirocumab y evolocumab; 4) Reportar seguridad de los iPCSK9. Material y Métodos: Se trata de un análisis prospectivo en vida real de pacientes tratados por primera vez con iPCSK9 en la práctica clínica habitual e incluidos en su primera dispensación en las consultas de Farmacia de 12 Hospitales de Galicia desde mayo 2020-abril 2021. Los valores basales de c-LDL son los previos al inicio del tratamiento con iPCSK9 y como seguimiento los valores a los 6 meses. Resultados: Se incluyeron 89 pacientes. El 86,5% con enfermedad cardiovascular y un 53,9% intolerancia a estatinas. Un 78,8% de los pacientes tratados con estatinas de alta intensidad. Las estatinas más usadas fueron rosuvastatina (34,1%) y atorvastatina (20,5%). El nivel basal de c-LDL fue 148 mg/dL y de 71 mg/dL al seguimiento. Los pacientes tratados con alirocumab (N=43) presentaban valores basales de 144 mg/dL y de 73 mg/dL al seguimiento y con evolocumab (N=46) de 151 mg/dL basal y 69 mg/dL al seguimiento. La reducción de c-LDL fue para evolocumab 51,21% y alirocumab 51,05%. El 43,1% presentaban a los 6 meses valores > 70mg/dL, el 19,4% entre 55 y 69 mg/dl y el 37,5% < 55 mg/dL. Los pacientes que obtuvieron una reducción >50% de c-LDL fueron el 58,3%. Los eventos adversos presentados fueron: Reacción en el lugar de inyección (N=2), mialgias (N=1), síntomas pseudogripales (N=1) y deterioro neurocognitivo (N=1). Conclusiones: 1) A pesar de haber disminuido el número de prescripciones de iPCSK9 durante la pandemia, el control lipídico de estos pacientes no se ha visto afectado. 2) La mitad de los pacientes tratados con iPSCK9 se debe a intolerancia a estatinas y el 86% es en prevención secundaria; 3) Se presentaron valores de reducción similares a los ensayos clínicos pivotales. A pesar de esto, un 39% del total y un 60% en doble terapia no alcanzaron las recomendaciones de las guías ESC/EAS (50%). No hubo diferencias significativas entre evolocumab y alirocumab: 51,21% vs 51,05% (p=,972); 4) No se observaron eventos de especial interés con el uso de estos fármacos. El posible deterioro cognitivo será analizado como variable principal una vez completado el estudio MEMOGAL.

Behavioral and medical control measures have not been effective in containing the spread of SARS-CoV-2 in large part due to the unwillingness of populations to adhere to "best practices". Ultraviolet light with wavelengths of between 200 and 280 nm (UV-C) and, in particular, germicidal ultraviolet light, which refers to wavelengths around 254 nm, have the potential to unobtrusively reduce the risk of SARS-CoV-2 transmission in enclosed spaces. We investigated the effectiveness of a strategy using UV-C light to prevent airborne transmission of the virus in a hamster model. Treatment of environmental air with 254 nm UV-C light prevented transmission of SARS-CoV-2 between individuals in a model using highly susceptible Syrian golden hamsters. The prevention of transmission of SARS-CoV-2 in a natural system by treating elements of the surrounding environment is one more weapon in the arsenal to combat COVID. The results presented indicate that coupling mitigation strategies utilizing UV-C light, along with current methods to reduce transmission risk, have the potential to allow a return to normal indoor activities.

Background Coronavirus disease (COVID-19) continues to lead to worldwide morbidity and mortality. This study examined the association between blood type and clinical outcomes in patients with COVID-19 measured by a calculated morbidity score and mortality rates. The secondary aim was to investigate the relationship between patient characteristics and COVID-19 associated clinical outcomes and mortality. Methods Logistic regression was used to determine what factors were associated with death. A total morbidity score was constructed based on overall patient's COVID-19 clinical course. This score was modeled using Quasi-Poisson regression. Bayesian variable selection was used for the logistic regression to obtain a posterior probability that blood type is important in predicting worsened clinical outcomes and death. Results Neither blood type nor Rh+ status was a significant moderator of death or morbidity score in regression analyses. Increased age (adjusted Odds Ratio=3.37, 95% CI=2.44–4.67), male gender (aOR=1.35, 95% CI=1.08-1.69), and number of comorbid conditions (aOR=1.28, 95% CI=1.01-1.63) were significantly associated with death. Significant factors in predicting total morbidity score were age (adjusted Multiplicative Effect=1.45; 95% CI=1.349-1.555) and gender (aME=1.17; 95% CI=1.109-1.243). The posterior probability that blood type influenced death was only 10%. Conclusions There is strong evidence that blood type was not a significant predictor of clinical course or death in patients hospitalized with COVID-19. Older age and male gender led to worse clinical outcomes and higher rates of death; older age, male gender, and comorbidities predicted a worse clinical course and higher morbidity score. Race was not a significant predictor of death in our population and was associated with an increased, albeit not significant, morbidity score.

Modulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID-19). The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others.We report the preliminary results from the Vall d'Hebron cohort study at Vall d'Hebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed SARS-CoV-2 infection and who were treated with tocilizumab until March 25th.82 patients with COVID-19 received at least one dose of tocilizumab. The mean (± SD) age was 59.1 (19.8) years, 63% were male, 22% were of non-Spanish ancestry, and the median (IQR) age-adjusted Charlson index at baseline was 3 (1-4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5-11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3-8.5 (age-adjusted hazard ratio for mortality 2.1; 95% CI, 0.8-5.8) if tocilizumab was administered after the onset of ARDS.Early administration of tocilizumab in patients needing oxygen supplementation may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data regarding the precise timing in of initiation of the treatment with tocilizumab.Los tratamientos inmunomoduladores para la prevención del daño pulmonar están siendo ampliamente estudiados contra la COVID-19. El objetivo primario es evaluar la mortalidad a los 7 días después de la administración de tocilizumab. El objetivo secundario es el ingreso en UCI, el desarrollo de distrés respiratorio agudo e insuficiencia respiratoria aguda entre otros.Informamos sobre los resultados preliminares de la cohorte del Hospital Universitario Vall d’Hebron en Barcelona (España), que incluye todos los pacientes consecutivos con infección confirmada por SARS-CoV-2 y que recibieron tratamiento con tocilizumab hasta el 25 de marzo 2020.Ochenta y dos pacientes con COVID-19 recibieron al menos una dosis de tocilizumab. La edad media (±DE) fue de 59,1 (±19,8) años, el 63% eran hombres, 22% correspondía a paciente nacidos fuera de España, y la mediana (RIC) del índice de Charlson ajustado por edad en el momento basal fue de 3 (1-4) puntos. Sesenta y dos pacientes (75,6%) y 45 pacientes (54,9%) desarrollaron insuficiencia respiratoria y distrés respiratorio agudo respectivamente. La mediana de tiempo desde el inicio de los síntomas hasta el desarrollo de ditrés fue de 8 días (5-11). La mortalidad a los 7 días fue del 26,8% La hazard ratio de mortalidad fue del 3,3; IC 95% 1,3-8,5 (la hazard ratio de mortalidad ajustada por edad fue de 2,1; IC 95% 0,8-5,8) si el tocilizumab se administraba después del inicio del distrés respiratorio.La administración precoz de tocilizumab en pacientes con suplementos de oxígeno podría ser crítica para la recuperación de los pacientes. Nuestros datos podrían ayudar a tomar decisiones clínicas hasta que se disponga de más información sobre el momento adecuado para iniciar el tratamiento con tocilizumab.

BackgroundThe risks and impact of COVID19 disease and vaccination in patients with Immune Mediated Inflammatory Diseases (IMID) remain incompletely understood. IMID patients and particularly patients receiving immunosuppressive treatment were excluded from the original, registrational phase-3 COVID19 vaccination efficacy and safety trials. Real-world observational data can help to fill this gap in knowledge. The BELCOMID study aims to explore the interaction between IMIDs, immune-modulating treatment modalities and SARS-CoV-2 infection and vaccination in a real-life patient cohort.MethodsA multidisciplinary, prospective, observational cohort study was set up. Consecutive patients with IMIDs of the gut, joints and skin followed at two high-volume referral centers were invited. Both patients under conventional treatment or targeted immune modulating therapies were included. Patient data and serological samples were collected at 3 predefined periods (before COVID19 vaccination, before booster vaccination, after booster vaccination). Primary endpoints were positive PCR-test and SARS-CoV-2 serology reflecting previous SARS-CoV-2 infection or vaccination. Associations with IMID treatment modality and IMID disease activity were assessed. Results of the first two inclusion periods (before booster vaccination) are reported.ResultsAt the first inclusion period data was assessed of 2165 IMID-patients before COVID19 vaccination. At the second inclusion period, data of 2065 patients was collected of whom 1547 had received complete baseline COVID19 vaccination and 222 were partially vaccinated. SARS-CoV-2 infection rate remained low in both groups. No significant increase in IMID flare-up rate was noted in patients with prior SARS-CoV-2 infection. Multiple logistic regression analyses did not show a significant influence of IMID-treatment modality or IMID activity on SARS-CoV-2 infection risk (based on PCR positivity or N-serology). Patients treated with conventional immunomodulators, systemic steroids, and patients on advanced therapies such as biologics or small molecules, had reduced S-antibody seroconversion. S-antibody response was also lower in patients without prior SARS-CoV-2 infection and in active smokers. A subset of patients (4.1%) had no S- nor N-antibody seroconversion following complete baseline vaccination.ConclusionThe BELCOMID study results confirm the benign course of COVID19 infection and vaccination in a large real-life IMID-population. However, our results underscore the need for repeated vaccination and smoking cessation in patients with IMIDs treated with immune-modulating therapies or systemic steroids during the pandemic.

Objetivo: Determinar el impacto que ha tenido la pandemia COVID-19 en profesionales sanitarios, en términos de cambios laborales y de salud mental. Método: 1-Estudio transversal y 2-Estudio longitudinal prospectivo sobre profesionales de la salud que trabajaron de forma directa con pacientes afectados por la pandemia COVID-19 durante el periodo comprendido entre marzo-junio de 2020 en un hospital de tercer nivel de Barcelona. Se recogieron datos basales (julio-noviembre de 2020) y de seguimiento (noviembre de 2020-marzo de 2021). Se recogieron datos relacionados con el puesto de trabajo y hábitos tóxicos con cuestionarios ad hoc, y de estrés percibido, estrés postraumático, depresión y ansiedad mediante cuestionarios validados. Resultados: En el grupo basal (estudio transversal) participaron 90 profesionales, 76% enfermeras. Más de un tercio estuvo de baja o tomó fármacos para gestionar el estrés. La mitad de los fumadores aumentó el consumo de tabaco, y uno de cada 5 aumentó el consumo de alcohol. Se asocia de forma significativa el cambio de turno habitual con la depresión, el perfil profesional con la ansiedad, y el estrés percibido con la edad. En el estudio longitudinal, el grupo de seguimiento (n=64) muestra niveles elevados de estrés y ansiedad, que se mantienen o incluso aumentan en el tiempo de forma significativa. Conclusiones: Los cambios estructurales acontecidos en el hospital durante la primera ola de la pandemia COVID-19 tuvieron un fuerte impacto en los profesionales, presentando muchos de ellos un aumento en los hábitos tóxicos, así como una salud mental alterada que se mantiene en el tiempo.

We evaluated rotational thromboelastometry tracings in 44 critically ill coronavirus disease 2019 patients, to determine whether there is a viscoelastic fingerprint and to test the hypothesis that the diagnosis and prediction of venous thromboembolism would be enhanced by the addition of rotational thromboelastometry testing.Rotational thromboelastometry values reflected an increase in clot strength for the EXTEM, INTEM, and FIBTEM assays beyond the reference range. No hyperfibrinolysis was noted. Fibrinolysis shutdown was present but did not correlate with thrombosis; 32% (14/44) of patients experienced a thrombotic episode. For every 1 mm increase of FIBTEM maximum clot formation, the odds of developing thrombosis increased 20% (95% confidence interval, 0-40%, P = .043), whereas for every 1,000 ng/mL increase in D-dimer, the odds of thrombosis increased by 70% (95% confidence interval, 20%-150%, P = .004), after adjustment for age and sex (AUC 0.96, 95% confidence interval, 0.90-1.00). There was a slight but significant improvement in model performance after adding FIBTEM maximum clot formation and EXTEM clot formation time to D-dimer in a multivariable model (P = .04).D-dimer concentrations were more predictive of thrombosis in our patient population than any other parameter. Rotational thromboelastometry confirmed the hypercoagulable state of coronavirus disease 2019 intensive care unit patients. FIBTEM maximum clot formation and EXTEM clot formation time increased the predictability for thrombosis compared with only using D-dimer. Rotational thromboelastometry analysis is most useful in augmenting the information provided by the D-dimer concentration for venous thromboembolism risk assessment when the D-dimer concentration is between 1,625 and 6,900 ng/dL, but the enhancement is modest. Fibrinolysis shutdown did not correlate with thrombosis.

To analyse susceptibility/risk of suffering COVID-19 among adults with distinct underlying medical conditions.Population-based cohort study involving 79,083 individuals ≥50 years old in Tarragona (Southern Catalonia, Spain). Baseline cohort characteristics (demographic, pre-existing comorbidities, chronic medications and vaccinations history) were established at study start (01/03/2020) and primary outcome was laboratory-confirmed COVID-19 occurred among cohort members throughout 01/03/2020-30/06/2020. Risk of suffering COVID-19 was evaluated by Cox regression, estimating multivariable hazard ratios (HRs) adjusted for age/sex and pre-existing comorbidities.Across study period, 536 laboratory-confirmed COVID-19 cases were observed (mean incidence: 39.5 cases per 100,000 persons-week). In multivariable-analysis, increasing age/years (HR: 1.01; 95% CI: 1.00-1.02), nursing-home (HR: 20.19; 95% CI: 15.98-25.51), neurological disease (HR: 1.35; 95% CI: 1.03-1.77), taking diuretics (HR: 1.39; 95% CI: 1.10-1.75), antiplatelet (HR: 1.36; 95% CI: 1.05-1.76) and benzodiazepines (HR: 1.24; 95% CI: 1.00-1.53) increased risk; conversely, taking angiotensin-converting-enzyme inhibitors (HR: 0.78; 95% CI: 0.61-1.00), angiotensin-receptor-blockers (HR: 0.70; 95%CI: 0.51-0.96) and statins (HR: 0.75; 95% CI: 0.58-0.96) were associated with reduced risk. Among community-dwelling individuals, pre-existing cancer, renal and cardiac disease appeared also related with an increased risk, whereas influenza vaccination was associated with reduced risk.In a setting with relatively low incidence of COVID-19 across the first wave of pandemic period, increasing age, nursing-home residence and multiple comorbidities appear predisposing for COVID-19 among middle-aged/older adults. Conversely, statins, angiotensin-receptor blockers/inhibitors and influenza vaccination were related with decreased risk.Analizar incidencia y riesgo/susceptibilidad de sufrir la COVID-19 en adultos según distintas condiciones médicas preexistentes.Cohorte de base poblacional que incluyó 79.083 personas ≥50 años en Tarragona. Características basales de la cohorte (edad/sexo, comorbilidades, medicaciones crónicas) se establecieron a 01-03-2020 y se registraron todos los casos de COVID-19 confirmada ocurridos en miembros de la cohorte hasta el 30-06-2020. Para estimación de riesgos se realizó regresión de Cox, con cálculo de hazard ratio (HR) ajustados por edad, sexo y comorbilidad.Se observaron 536 casos confirmados de COVID-19 (incidencia media: 39,5 casos por 100.000 personas-semana). En análisis multivariante, edad/años (HR: 1,01; IC el 95%: 1,00-1,02; p = 0,050), estar institucionalizado/residencia (HR: 20,19; IC 95%: 15,98-25,51; p0,001), enfermedad neurológica (HR: 1,35; IC el 95%: 1,03-1,77), diuréticos (HR: 1,39; IC 95%: 1,10-1,75), antiagregantes plaquetarios (HR: 1,36; IC 95%: 1,05-1,76) y benzodiacepinas (HR: 1,24; IC 95%: 1,00-1,53) se asociaron con un riesgo aumentado de la COVID-19 analizando la totalidad de la cohorte; contrariamente, medicación IECA (HR: 0,78; IC el 95%: 0,61-1,00), ARA-II (HR: 0,70; IC el 95%: 0,51-0,96) y estatinas (HR: 0,75; IC el 95%: 0,58-0,96) se asociaron con menor riesgo. Entre personas no institucionalizadas, cáncer, nefropatía y cardiopatía se asociaron con mayor riesgo y vacunación antigripal con menor riesgo.En un área con relativamente baja incidencia de COVID-19, edad, institucionalización y múltiples comorbilidades aumentaron el riesgo/susceptibilidad de sufrir la COVID-19. Contrariamente, estatinas, inhibidores del sistema renina-angiotensina y vacunación antigripal se asociaron con menor riesgo.

Background : Israel began a mass vaccination program with the rapid rollout of the Pfizer-BioNTech COVID-19 BNT162b2 vaccine for adults. At the same time, government stringency measures in terms of closing public life were decreased. Our objective was to estimate the total number of Covid-19 deaths avoided due to the massive vaccination campaign in the elderly Israeli population. Methods : We examined the effect of vaccination on mortality when at least 90% of the population over age 70 were vaccinated for less than seven months. Projected deaths as expected from vaccine efficacy and actual mortality data were compared for the study population to account for potential confounding effects of government stringency. The average Oxford Stringency Index was calculated in the study period and the preceding period of the pandemic. Potential confounding effects of an age shift in the distribution of deaths were examined by analyzing the distributions before and after the study period. Results : Confirmed deaths from COVID-19 in the population over 70 after mass vaccination were recorded as 370, versus 5,120 estimated without vaccinations. Conclusions : Vaccines against COVID-19 saved more lives than expected by simply applying individual vaccine efficacy to the vaccinated population in Israel, despite a loosening of government stringency. Our findings support the worldwide efforts of governments to improve vaccination rates, especially in the elderly population.

Purpose To explore siblings' perceptions of having a brother or sister with congenital heart disease in the UK during the COVID-19 pandemic. Design and methods Siblings of children with congenital heart disease aged 8–17 years old were interviewed via video call technology between September 2020 and February 2021. We conducted reflexive thematic analysis of these interviews to generate themes. Findings Interviews took place with 17 siblings, predominantly of white ethnicity n = 15 (86%). Most siblings interviewed were first born in the family n = 15 (88%), and most children with CHD were the youngest n = 15(88%). Four themes were generated; My sibling is vulnerable, what does this mean for my family, I have a responsibility to protect my brother or sister, our family time during the pandemic and adjustment and adaptations to pandemic life. Conclusions Siblings identified difficult aspects of the pandemic and these related to concerns about their brother's or sister's vulnerability, family impact, and keeping their sibling safe. They also identified adjustments they made to keep their family functioning throughout the COVID-19 pandemic. Despite the worry and uncertainty siblings experienced, they valued increased family cohesion which helped to mitigate some challenges of the restrictions imposed in the UK. Practice implications Honest and open communication is valued by siblings. It is vital to ensure siblings receive the support they need to ensure they keep up with their schooling and social commitments as pandemic related restrictions ease.

Background Coronavirus disease 2019 (COVID-19) has affected more than 210 million people worldwide. An optimal therapeutic approach for COVID-19 remains uncertain, to date. Since the history of cancer was linked to higher mortality rates due to COVID-19, the establishment of a safe and effective vaccine coverage is crucial in these patients. However, patients with cancer were mostly excluded from vaccine candidates’ clinical trials. This systematic review aims to investigate the current available evidence about the immunogenicity of COVID-19 vaccines in patients with cancer (PsC). Patients and methods All prospective studies that evaluated safety and efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included, with immunogenicity after the first and the second dose as the primary endpoint, when available. Results Vaccination against COVID-19 for PsC seems overall safe and immunogenic after well-conducted vaccinations schedules. Yet, the seroconversion rate remains lower, lagged or both compared to the general population. Patients with hematologic malignancies, especially those receiving B cell depleting agents in the last 12 months are the most at risk of poor seroconversion. Conclusion A tailored approach to vaccination may be proposed to PsC, especially on the basis of the type of malignancy and of the specific oncologic treatments received.

Graphical abstract Several existing drugs have gained initial consideration due to their therapeutic characteristics against COVID-19 (Corona Virus Disease 2019). Hydroxychloroquine (HCQ) was proposed as possible therapy for shortening the duration of COVID-19, but soon after this, it was discarded. Similarly, known antiviral compounds were also proposed and investigated to treat COVID-19. We report a pharmacophore screening using essential chemical groups derived from HCQ and known antivirals to search a natural compound chemical space. Molecular docking of HCQ under physiological condition with spike protein, 3C-like protease (3CLpro), and RNA-dependent RNA polymerase (RdRp) of SARS-CoV2 showed − 8.52 kcal/mole binding score with RdRp, while the other two proteins showed relatively weaker binding affinity. Docked complex of RdRp-HCQ is further examined using 100 ns molecular dynamic simulation. Docking and simulation study confirmed active chemical moieties of HCQ, treated as 6-point pharmacophore to screen ZINC natural compound database. Pharmacophore screening resulted in the identification of potent hit molecule [(3S,3aR,6R,6aS)-3-(5-phenylsulfanyltetrazol-1-yl)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]N-naphthalen-ylcarbamate from natural compound library. Additionally, a set of antiviral compounds with similar chemical scaffolds are also used to design a separate ligand-based pharmacophore screening. Antiviral pharmacophore screening produced a potent hit 4-[(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)-(2-hydroxyphenyl)methyl]-1,5-dimethyl-2-phenylpyrazol-3-one containing essential moieties that showed affinity towards RdRp. Further, both these screened compounds are docked (− 8.69 and − 8.86 kcal/mol) and simulated with RdRp protein for 100 ns in explicit solvent medium. They bind at the active site of RdRp and form direct/indirect interaction with ASP618, ASP760, and ASP761 catalytic residues of the protein. Successively, their molecular mechanics Poisson Boltzmann surface area (MMPBSA) binding energies are calculated over the simulation trajectory to determine the dynamic atomistic interaction details. Overall, this study proposes two key natural chemical moieties: (a) tetrazol and (b) phenylpyrazol that can be investigated as a potential chemical group to design inhibitors against SARS-CoV2 RdRp. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-021-10358-5.

Background: The World Health Organization declared COVID-19 a pandemic in March 2020. The first vaccine became available in December, with practically no post-marketing data. Methods: An analytical cross-sectional survey-based study was conducted in a third-level hospital in Spain between March and April 2021 to describe the difference in adverse events with the BNT162b2 and mRNA-1273 COVID-19 vaccines. The participants were hospital workers who completed a survey voluntarily at least 14 days after the last vaccine. The STROBE checklist was followed. Results: One thousand two hundred and forty-nine respondents completed the survey; 48% (599) received mRNA-1273 and 52% (650) BNT162b2. Fourteen thousand four hundred and two adverse reactions were recorded, 6896 local (3939 with mRNA-1273 and 2957 with BNT162b2 (6.6 vs 4.4 reactions per patient)) and 7506 systemic (4460 with mRNA-1273 and 3046 with BNT162b2 (7.4 vs 4.7 per patient)). Local reactions were more frequent after the first dose, while systemic reactions were higher after the second, for both vaccines and in a higher percentage with mRNA-1273 compared to BNT162b2 (p-value

Motivation With the coronavirus pandemic still raging, prophylactic-nasal and early-treatment throat-sprays could help prevent infection and reduce viral load. Niclosamide has the potential to treat a broad-range of viral infections if local bioavailability is optimized as mucin-penetrating solutions that can reach the underlying epithelial cells. Experimental pH-dependence of supernatant concentrations and dissolution rates of niclosamide were measured in buffered solutions by UV/Vis-spectroscopy for niclosamide from different suppliers (AK Sci and Sigma), as precipitated material, and as cosolvates. Data was compared to predictions from Henderson-Hasselbalch and precipitation-pH models. Optical-microscopy was used to observe the morphologies of original, converted and precipitated niclosamide. Results Niclosamide from the two suppliers had different polymorphs resulting in different dissolution behavior. Supernatant concentrations of the “AKSci-polymorph” increased with increasing pH, from 2.53μM at pH 3.66 to 300μM at pH 9.2, reaching 703μM at pH 9.63. However, the “Sigma-polymorph” equilibrated to much lower final supernatant concentrations, reflective of more stable polymorphs at each pH. Similarly, when precipitated from supersaturated solution, or as cosolvates, niclosamide also equilibrated to lower final supernatant concentrations. Polymorph equilibration though was avoided by using a solvent-exchange technique to make the solutions. Conclusions Given niclosamide’s activity as a host cell modulator, optimized niclosamide solutions could represent universal prophylactic nasal and early treatment throat sprays against COVID19, its more contagious variants, and other respiratory viral infections. They are the simplest and potentially most effective formulations from both an efficacy standpoint as well as manufacturing and distribution, (no cold chain). They now just need testing. Supplementary Information The online version contains supplementary material available at 10.1007/s11095-021-03112-x.

Severe coronavirus disease 2019 (COVID-19) manifests as a life-threatening microvascular syndrome. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the Spike (S) protein to engage with its receptors and infect host cells. To date, it is still not known whether heart vascular pericytes (PCs) are infected by SARS-CoV-2, and if the S protein alone provokes PC dysfunction. Here, we aimed to investigate the effects of the S protein on primary human cardiac PC signalling and function. Results show, for the first time, that cardiac PCs are not permissive to SARS-CoV-2 infection in vitro, whilst a recombinant S protein alone elicits functional alterations in PCs. This was documented as: (1) increased migration, (2) reduced ability to support endothelial cell (EC) network formation on Matrigel, (3) secretion of pro-inflammatory molecules typically involved in the cytokine storm, and (4) production of pro-apoptotic factors responsible for EC death. Next, adopting a blocking strategy against the S protein receptors angiotensin-converting enzyme 2 (ACE2) and CD147, we discovered that the S protein stimulates the phosphorylation/activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) through the CD147 receptor, but not ACE2, in PCs. The neutralisation of CD147, either using a blocking antibody or mRNA silencing, reduced ERK1/2 activation and rescued PC function in the presence of the S protein. In conclusion, our findings suggest that circulating S protein prompts vascular PC dysfunction, potentially contributing to establishing microvascular injury in organs distant from the site of infection. This mechanism may have clinical and therapeutic implications.Clinical perspectiveSevere COVID-19 manifests as a microvascular syndrome, but whether SARS-CoV-2 infects and damages heart vascular pericytes (PCs) remains unknown.We provide evidence that cardiac PCs are not infected by SARS-CoV-2. Importantly, we show that the recombinant S protein alone elicits cellular signalling through the CD147 receptor in cardiac PCs, thereby inducing cell dysfunction and microvascular disruption in vitro.This study suggests that soluble S protein can potentially propagate damage to organs distant from sites of infection, promoting microvascular injury. Blocking the CD147 receptor in patients may help protect the vasculature not only from infection, but also from the collateral damage caused by the S protein.

Fast and reliable detection of infectious SARS-CoV-2 virus loads is an important issue. Fluorescence spectroscopy is a sensitive tool to do so in clean environments. This presumes a comprehensive knowledge of fluorescence data.We aim at providing fully featured information on wavelength and time-dependent data of the fluorescence of the SARS-CoV-2 spike protein S1 subunit, its receptor-binding domain (RBD), and the human angiotensin-converting enzyme 2, especially with respect to possible optical detection schemes.Spectrally resolved excitation-emission maps of the involved proteins and measurements of fluorescence lifetimes were recorded for excitations from 220 to 295 nm. The fluorescence decay times were extracted by using a biexponential kinetic approach. The binding process in the SARS-CoV-2 RBD was likewise examined for spectroscopic changes.Distinct spectral features for each protein are pointed out in relevant spectra extracted from the excitation-emission maps. We also identify minor spectroscopic changes under the binding process. The decay times in the biexponential model are found to be ( 2.0 ± 0.1 ) ns and ( 8.6 ± 1.4 ) ns.Specific material data serve as an important background information for the design of optical detection and testing methods for SARS-CoV-2 loaded media.

Intestinal bacteria may influence lung homeostasis via the gut-lung axis. We conducted a single-center, quadruple-blinded, randomized trial in adult symptomatic Coronavirus Disease 2019 (Covid19) outpatients. Subjects were allocated 1:1 to probiotic formula (strains Lactiplantibacillus plantarum KABP022, KABP023, and KAPB033, plus strain Pediococcus acidilactici KABP021, totaling 2 × 109 colony-forming units (CFU)) or placebo, for 30 days. Co-primary endpoints included: i) proportion of patients in complete symptomatic and viral remission; ii) proportion progressing to moderate or severe disease with hospitalization, or death; and iii) days on Intensive Care Unit (ICU). Three hundred subjects were randomized (median age 37.0 years [range 18 to 60], 161 [53.7%] women, 126 [42.0%] having known metabolic risk factors), and 293 completed the study (97.7%). Complete remission was achieved by 78 of 147 (53.1%) in probiotic group compared to 41 of 146 (28.1%) in placebo (RR: 1.89 [95 CI 1.40–2.55]; P

Purpose The aim of this study was to assess the emotional intelligence of nurses caring for COVID-19 patients. Methods This was a descriptive cross-sectional study that was conducted from May to July 2020 in Tehran, Iran. Nurses caring for patients with COVID-19 were requested to fill in Bradbury and Graves's questionnaire online using a questionnaire in electronic format. Results Finally 211 nurses completed the questionnaires. Most of the nurses were working in critical care wards and caring for critical patients (61.6). Nurses' emotional intelligence was reported to be 63.19 (8.22). In general, the nurses' emotional intelligence was moderate. Between the dimensions, self-awareness and self-management had the highest scores. Also, the lowest score was related to self-management. The ward type and complexity of care had no effect on the scores of emotional intelligence. Nurses caring for patients with moderate disease severity had a higher relationship management score than nurses caring for critically ill patients (P Conclusion The total score of emotional intelligence was moderate. Due to the continuation of the COVID-19 pandemic and the possibility of mental and physical fatigue of health care workers, improving emotional intelligence can be effective in resilience and stability of the psychological status of employees.

PurposeTo date, over 4.2 million Germans and over 235 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Uro-oncology (UO) patients are particularly vulnerable but in urgent need of life-saving systemic treatments. Our multicentric study examined the impact of the COVID-19 crisis on the medical care of UO patients in German university hospitals receiving ongoing systemic anti-cancer treatment and to detect the delay of medical care, defined as deferred medical treatment or deviation of the pre-defined follow-up assessment.MethodsData of 162 UO patients with metastatic disease undergoing systemic cancer treatment at five university hospitals in Germany were included in our analyses. The focus of interest was any delay or change in treatment between February 2020 and May 2020 (first wave of the COVID-19 crisis in Germany). Statistical analysis of contingency tables were performed using Pearson’s chi-squared and Fisher’s exact tests, respectively. Effect size was determined using Cramér’s V (V).ResultsTwenty-four of the 162 patients (14.8%) experienced a delay in systemic treatment of more than 2 weeks. Most of these received immuno-oncologic (IO) treatments (13/24, 54.2%,p = 0.746). Blood tests were delayed or canceled significantly more often in IO patients but with a small effect size (21.1%,p = 0.042,V = 0.230). Treatment of patients with renal cell carcinoma (12/73, 16.4%) and urothelial carcinoma (7/32, 21.9%) was affected the most.ConclusionsOur data show that the COVID-19 pandemic impacted the medical care of UO patients, but deferment remained modest. There was a tendency towards delays in IO and ADT treatments in particular.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the causative agent of coronavirus disease‐2019 (COVID‐19), a respiratory disease that varies in severity from mild to severe/fatal. Several risk factors for severe disease have been identified, notably age, male sex, and pre‐existing conditions such as diabetes, obesity, and hypertension. Several advancements in clinical care have been achieved over the past year, including the use of corticosteroids (e.g., corticosteroids) and other immune‐modulatory treatments that have now become standard of care for patients with acute severe COVID‐19. While the understanding of the mechanisms that underlie increased disease severity with age has improved over the past few months, it remains incomplete. Furthermore, the molecular impact of corticosteroid treatment on host response to acute SARS‐CoV‐2 infection has not been investigated. In this study, a cross‐sectional and longitudinal analysis of Ab, soluble immune mediators, and transcriptional responses in young (65 ≤ years) and aged (≥ 65 years) diabetic males with obesity hospitalized with acute severe COVID‐19 was conducted. Additionally, the transcriptional profiles in samples obtained before and after corticosteroids became standard of care were compared. The analysis indicates that severe COVID‐19 is characterized by robust Ab responses, heightened systemic inflammation, increased expression of genes related to inflammatory and pro‐apoptotic processes, and reduced expression of those important for adaptive immunity regardless of age. In contrast, COVID‐19 patients receiving steroids did not show high levels of systemic immune mediators and lacked transcriptional indicators of heightened inflammatory and apoptotic responses. Overall, these data suggest that inflammation and cell death are key drivers of severe COVID‐19 pathogenesis in the absence of corticosteroid therapy., Graphical Abstract Corticosteroids treatment significantly dampens the dysregulated inflammatory and apoptotic responses seen in acute severe COVID‐19

Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine1,2, European health authorities have recommended that patients under the age of 55 who received one dose of ChAdOx1-S-nCoV-19 vaccine receive a second dose of Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here, we show that the heterologous ChAdOx1-S-nCoV-19/BNT162b2 combination confers better protection against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection than the homologous BNT162b2/BNT162b2 combination in a real-world observational study of healthcare workers (n=13121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody (Ab) responses but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity, regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential was correlated with increased frequencies of switched and activated memory B cells recognizing the SARS-CoV-2 Receptor Binding Domain (RBD). The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immune compromised individuals.

Purpose The COVID-19 pandemic has led to global changes in healthcare systems. The purpose of this study was to investigate the effects on surgical care of patients. Methods We performed a retrospective analysis of routine data from the largest hospital group in Germany (68 acute hospitals). Included were inpatients who underwent cholecystectomy between March 19, 2020 (beginning of the first lockdown in Germany) and September 22, 2020. These patients were compared with those treated in the same interval in 2019. Results In the 2020 study period, 4035 patients met the inclusion criteria (2019: 4526 patients). During the first lockdown, there was a significant reduction in the number of cholecystectomies performed (51.1% decrease). More patients with a higher risk profile underwent urgent operations, which were accompanied by a significant increase in conversion from laparoscopic to open cholecystectomy. The patients were treated as inpatients for a longer duration than 2019, and the mortality rate increased significantly to 1.3% (2019: 0.1%). The complication rate also showed a significant increase. After the end of the first lockdown, daily admission rates normalized very quickly. However, it was not possible to fully address the backlog of operations. Conclusion There is still a “patient stagnation” 6 months after the first German lockdown. Extrapolated to the national level, this corresponds to almost 21,000 fewer cholecystectomies performed in Germany in 2020. It remains to be seen whether surgical rates will return to pre-pandemic levels and whether complications will arise in the future due to the lack of operations.

It is well accepted that environmental stressors experienced over a one’s life, from microbial infections to chemical toxicants to even psychological stressors, ultimately shape central nervous system (CNS) functioning but can also contribute to its eventual breakdown. The severity, timing and type of such environmental “hits”, woven together with genetic factors, likely determine what CNS outcomes become apparent. This focused review assesses the current COVID-19 pandemic through the lens of a multi-hit framework and disuses how the SARS-COV-2 virus (causative agent) might impact the brain and potentially interact with other environmental insults. What the long-term consequences of SAR2 COV-2 upon neuronal processes is yet unclear, but emerging evidence is suggesting the possibility of microglial or other inflammatory factors as potentially contributing to neurodegenerative illnesses. Finally, it is critical to consider the impact of the virus in the context of the substantial psychosocial stress that has been associated with the global pandemic. Indeed, the loneliness, fear to the future and loss of social support alone has exerted a massive impact upon individuals, especially the vulnerable very young and the elderly. The substantial upswing in depression, anxiety and eating disorders is evidence of this and in the years to come, this might be matched by a similar spike in dementia, as well as motor and cognitive neurodegenerative diseases.

This review aimed to study molecular mechanisms for high incidence of life-threatening mucormycosis infection in COVID19 cases during second wave of SARS CoV2 pandemic in India. Hyperglycaemia, impaired immunity, acidosis, raised ferritin, glucocorticoid therapy, and COVID19 specific other factors have been implicated in pathogenesis of COVID19 associated mucormycosis (CAMM). Endoplasmic reticulum chaperone 'Glucose Related Protein 78' (GRP78), also involved in SARS CoV2 entry, is the host receptor for invasion by Mucorales. GRP78 is over-expressed by SARS CoV2, hyperglycaemia and ferritin. Delta variant of SARS CoV2 and indiscriminate use of steroids were distinguishing features of second wave and appear to upregulate GRP78 through intricate interplay between internal and external milieu. Common invasive fungal infections like candidiasis and aspergillosis, not utilizing GRP78 as receptor, were inconspicuous. Further molecular research to unravel mechanisms involved in the pathogenesis of CAMM shall effectively complement existing strategies for its prevention and treatment.

Objectives The study purpose was to evaluate the effects of the COVID-19 pandemic on the rate and disease profile of orofacial and respiratory infections in oral and maxillofacial surgery (OMFS) and ear, nose, and throat (ENT) emergency units. Materials and methods Records of patients with orofacial or respiratory infection, or infectious symptoms, diagnosed in the OMFS or ENT Emergency Departments of the Helsinki University Hospital, Helsinki, Finland between 1st March and 30th October 2020 and the corresponding periods in 2018 and 2019 were reviewed. The main outcome variable was the occurrence of studied infections during the evaluated periods. Other study variables were age, gender, residence area, speciality, specific cause for the emergency department visit and admission to ward. Results There was a significant 37% decrease in the number of infection patients in 2020 compared to the years 2019 and 2018 (1894 vs. 2929 and 3077, respectively, p p = .013). Conclusion A significant decrease was observed in the volume of emergency department visits for orofacial and respiratory infections during the COVID-19-pandemic in 2020 compared to the non-COVID periods. Clinical relevance It seems that social distancing, facial mask wearing, and other infection prevention precautions have changed the accustomed patient profile in orofacial and respiratory infections.

BACKGROUND: There is widespread concern over the impact of public health measures, such as lockdowns, associated with COVID-19 on mental health, including suicide. High-quality evidence from low-income and middle-income countries, where the burden of suicide and self-harm is greatest, is scarce. We aimed to determine the effect of the pandemic on hospital presentations for self-poisoning. METHODS: In this interrupted time-series analysis, we established a new self-poisoning register at the tertiary care Teaching Hospital Peradeniya in Sri Lanka, a lower-middle-income country. Using a standard extraction sheet, data were gathered for all patients admitted to the Toxicology Unit with self-poisoning between Jan 1, 2019, and Aug 31, 2020. Only patients classified by the treating clinician as having intentionally self-poisoned were included. Data on date of admission, age or date of birth, sex, and poisoning method were collected. No data on ethnicity were available. We used interrupted time-series analysis to calculate weekly hospital admissions for self-poisoning before (Jan 1, 2019-March 19, 2020) and during (March 20-Aug 31, 2020) the pandemic, overall and by age (age

Background: COVID-19 is newly emerging infectious disease that spread globally at unpredictable and unique pattern to the extent that the World Health Organization announced COVID-19 as a pandemic in the first couple months of 2020. This study aims to describe clinical and demographic features of COVID-19 patients and the influence of various risk factors on the severity of disease. Methods: This research is a retrospective study based on Saudi Arabia's ministry of health's Covid-19 data. The analysis relies on data of all COVID-19 patients recorded in Riyadh between 1st, March 2020 and 30th, July 2020. Statistical analyses were performed to investigate the effect of demographic characteristic, clinical presentation, and comorbidities on infection severity. Results: A total number of 1026 COVID-19 patients were identified based on the demographic data as follows: 709 cases (69% of cases) were males and 559 cases (54% of cases) were Saudi. Most of patients were diagnosed with mild signs and symptoms 697 (68% of cases), while 164 patient (16% of cases) demonstrated moderate signs and symptoms, and 103 cases (10%) were severe and 62 (6%) had critical febrile illness. Fever, cough, sore throat, and shortness of breath were the most common symptoms among patients with COVID-19. Among studied comorbidities in COVID-19 patients, diabetes mellitus and hypertension were the most prevalent. The results from the bivariate logistic regression analysis revealed that older age, diabetes mellitus, asthma, smoking, and fever are associated with severe or critically ill cases. Conclusion: The findings of this study show that old age, fever, and comorbidities involving diabetes mellitus, asthma, and smoking were significantly associated with infection severity. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

SARS-CoV-2 is the etiological agent of COVID19. There are currently several licensed vaccines approved for human use and most of them are targeting the spike protein (or virion) in the virion envelope to induce protective immunity. Recently, variants that spread more quickly have emerged. There is evidence that some of these variants are less sensitive to neutralization in vitro, but it is not clear whether they can evade vaccine induced protection. In this study, we tested the utility of SARS-CoV-2 spike RBD as a vaccine antigen and explore the effect of formulation with Alum/MPLA or AddaS03 adjuvants. Our results indicate RBD induces high titers of neutralizing antibodies and activates strong cellular immune responses. There is also significant cross-neutralisation of variants B1.1.7 and B.1.351 and to a lesser extent, SARS-CoV-1. These results indicate that recombinant RBD can be a viable candidate as a stand-alone vaccine or as a booster shot to diversify our strategy for COVID19 protection.

Background Healthcare emergency can increase work-related stress and reduce nurses’ job satisfaction and quality of life. Managerial decisions and proactive interventions implemented to react to the emergency ensure the best patient outcomes. Purpose The purpose of this study was to verify whether a proactive organizational approach can limit nurses’ work-related stress and help preserve their job satisfaction and quality of life during a health emergency. Methods A longitudinal mixed methods study was conducted. Data were collected before and after the transformation into a SARS-CoV-2 Hospital and the implementation of organizational interventions. Focus groups were conducted to investigate quantitative data. Findings After the implementation of interventions and as the pandemic progressed, work-related stress decreased and job satisfaction and quality of life increased. Discussion Through proactive organization, even during an emergency, nurses are prepared for working, and work-related stress due to changes is reduced. Nurses are motivated and satisfied with their organization and management, and quality of life increases.

Aim Patients with cancer are at an increased risk for severe coronavirus disease of 2019, thus data on the safety and efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted this prospective study of patients with cancer vaccinated with BNT162b2 and monitored for antibody response and safety. The aim was to evaluate the rate of seropositivity and define predictors for non-reactive immune response. Furthermore, we evaluated the frequency and the severity of adverse events. Methods The study included patients with solid tumours undergoing anticancer treatment and immunocompetent health-care workers serving as controls. Serum titres of the receptor-binding domain (RBD) immunoglobulin G (IgG) and neutralising antibodies were measured 2–4 weeks after each vaccine dose. Results The analysis included 129 patients, of which 70.5% patients were metastatic. Patients were treated with chemotherapy (55%), immunotherapy (34.1%), biological agents (24.8%), hormonal treatment (8.5%) and radiotherapy (4.6%), that were given either alone or in combinations. The seropositivity rate among patients with cancer and controls was 32.4% versus 59.8% (p

Background One major challenge for detecting the virus that causes COVID-19 is commercial SARS-CoV-2 testing kit or reagent availability. To allow every laboratory or hospital access to an in-house assay, we developed a low-cost SARS-CoV-2 detection assay protocol using in-house primers and reagents/equipment on hand in most biology or diagnostic laboratories: a SYBR Green-based RT-PCR. RNA extraction has also become a major bottleneck due to limited supplies and the required labor. Thus, we validated an alternative RNA extraction protocol. Methods We designed and synthesized in-house primers according to SARS-CoV-2 genome sequences retrieved from GISAID database. One hundred and ninety patient samples were collected by nasopharyngeal swab, coded, and used to develop and validate the assay protocol. RNA extraction was performed using TRI reagent-based RNA protocol to inactivate the virus; thus, testing was conducted in a conventional biosafety level 2 laboratory. Results The sensitivity and specificity of the primers were evaluated using 190 patient samples previously tested for SARS-CoV-2. The positive amplicons were sequenced to confirm the results. The assay protocol was developed, and the specificity of each RT-PCR product was confirmed using melting curve analyses. Of 190 samples, the SYBR Green-based RT-PCR assay detected SARS-CoV-2 target genes in 88 samples, with no false-positive results. These findings indicate that the sensitivity of our assay was 97.7% and specificity of 100% with those of the diagnostic laboratory that tested the same samples using a Rotor-Gene PCR cycler with an Altona Diagnostics SARS-CoV-2 kit (R2 = 0.89). Conclusions These approaches are reliable, repeatable, specific, sensitive, simple, and low-cost tools for the detection of SARS-CoV-2 in a conventional biosafety level 2 laboratory, offering alternative approaches when commercial kits are unavailable or not affordable.

Background SARS-CoV-2 has been detected in stool samples of COVID-19 patients, with potential implications for faecal-oral transmission. Compared to nasopharyngeal swab samples, the complexity of the stool matrix poses a challenge in the detection of the virus that has not yet been solved. However, robust and reliable methods are needed to estimate the prevalence and persistence of SARS-CoV-2 in the gut and to ensure the safety of microbiome-based procedures such as faecal microbiota transplant (FMT). The aim of this study was to establish a sensitive and reliable method for detecting SARS-CoV-2 in stool samples. Results Stool samples from individuals free of SARS-CoV-2 were homogenised in saline buffer and spiked with a known titre of inactivated virus ranging from 50 to 750 viral particles per 100 mg stool. Viral particles were concentrated by ultrafiltration, RNA was extracted, and SARS-CoV-2 was detected via real-time reverse-transcription polymerase chain reaction (RT-qPCR) using the CDC primers and probes. The RNA extraction procedure we used allowed for the detection of SARS-CoV-2 via RT-qPCR in most of the stool samples tested. We could detect as few as 50 viral particles per 100 mg of stool. However, high variability was observed across samples at low viral titres. The primer set targeting the N1 region provided more reliable and precise results and for this primer set our method had a limit of detection of 1 viral particle per mg of stool. Conclusions Here we describe a sensitive method for detecting SARS-CoV-2 in stool samples. This method can be used to establish the persistence of SARS-CoV-2 in stool and ensure the safety of clinical practices such as FMT.

The COVID-19 pandemic resulted in an unprecedented reduction in the delivery of surgical services worldwide, especially in non-urgent, non-cancer procedures. A prolonged period without operating (or 'layoff period') can result in surgeons experiencing skill fade (both technical and non-technical) and a loss of confidence. While senior surgeons in the UK may be General Medical Council (GMC) validated and capable of performing a procedure, a loss of 'currency' may increase the risk of error and intraoperative patient harm, particularly if unexpected or adverse events are encountered. Dual surgeon operating may mitigate risks to patient safety as surgeons regain currency while returning to non-urgent operating and may also be beneficial after the greatly reduced activity observed during the COVID-19 pandemic for low-volume complex operations. In addition, it could be a useful tool for annual appraisal, sharing updated surgical techniques and helping team cohesion. This paper explores lessons from aviation, a leading industry in human factors principles, for regaining surgical skills currency. We discuss real and perceived barriers to dual surgeon operating including finance, training, substantial patient waiting lists, and intraoperative power dynamics.

Background Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca). Methods Com-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020–005085–33). Findings Between Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77–89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2–ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second dose, with geometric mean ratios of 1·4 (95% CI 1·1–1·8) for homologous BNT162b2, 1·5 (1·2–1·9) for ChAdOx1 nCoV-19–BNT162b2, 1·6 (1·3–2·1) for BNT162b2–ChAdOx1 nCoV-19, and 2·4 (1·7–3·2) for homologous ChAdOx1 nCoV-19. At 6 months post-second dose, anti-spike IgG geometric mean concentrations fell to 0·17–0·24 of the 28-day post-second dose value across all eight study groups, with only homologous BNT162b2 showing a slightly slower decay for the 12-week versus 4-week interval in the adjusted analysis. The rank order of schedules by humoral response was unaffected by interval, with homologous BNT162b2 remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals compared with their 4-week counterparts. 12-week schedules for homologous BNT162b2 and ChAdOx1 nCoV-19–BNT162b2 were up to 80% less reactogenic than 4-week schedules. Interpretation These data support flexibility in priming interval in all studied COVID-19 vaccine schedules. Longer priming intervals might result in lower reactogenicity in schedules with BNT162b2 as a second dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines using these novel platforms might benefit from schedules with long intervals. Funding UK Vaccine Taskforce and National Institute for Health and Care Research.

In the UK, during the study period (April to July, 2021), all contacts of people with COVID-19 were required to self-isolate for 10 days, which had adverse impacts on individuals and society. Avoiding the need to self-isolate for those who remain uninfected would be beneficial. We investigated whether daily use of lateral flow devices (LFDs) to test for SARS-CoV-2, with removal of self-isolation for 24 h if negative, could be a safe alternative to self-isolation as a means to minimise onward transmission of the virus.We conducted a randomised, controlled, non-inferiority trial in adult contacts identified by COVID-19 contact tracing in England. Consenting participants were randomly assigned to self-isolation (single PCR test, 10-day isolation) or daily contact testing (DCT; seven LFD tests, two PCR tests, no isolation if negative on LFD); participants from a single household were assigned to the same group. Participants were prospectively followed up, with the effect of each intervention on onward transmission established from routinely collected NHS Test and Trace contact tracing data for participants who tested PCR-positive for SARS-CoV-2 during the study period and tertiary cases arising from their contacts (ie, secondary contacts). The primary outcome of the study was the attack rate, the percentage of secondary contacts (close contacts of SARS-CoV-2-positive study participants) who became COVID-19 cases (tertiary cases) in each group. Attack rates were derived from Bernoulli regression models using Huber-White (robust) sandwich estimator clustered standard errors. Attack rates were adjusted for household exposure, vaccination status, and ability to work from home. The non-inferiority margin was 1·9%. The primary analysis was a modified intention-to-treat analysis excluding those who actively withdrew from the study as data from these participants were no longer held. This study is registered with the Research Registry (number 6809). Data collection is complete; analysis is ongoing.Between April 29 and July 28, 2021, 54 923 eligible individuals were enrolled in the study, with final group allocations (following withdrawals) of 26 123 (52·6%) participants in the DCT group and 23 500 (47·4%) in the self-isolation group. Overall, 4694 participants tested positive for SARS-CoV-2 by PCR (secondary cases), 2364 (10·1%) in the self-isolation group and 2330 (8·9%) in the DCT group. Adjusted attack rates (among secondary contacts) were 7·5% in the self-isolation group and 6·3% in the DCT group (difference of -1·2% [95% CI -2·3 to -0·2]; significantly lower than the non-inferiority margin of 1·9%).DCT with 24 h exemption from self-isolation for essential activities appears to be non-inferior to self-isolation. This study, which provided evidence for the UK Government's daily lateral flow testing policy for vaccinated contacts of COVID-19 cases, indicated that daily testing with LFDs could allow individuals to reduce the risk of onward transmission while minimising the adverse effects of self-isolation. Although contacts in England are no longer required to isolate, the findings will be relevant for future policy decisions around COVID-19 or other communicable infections.UK Government Department of Health and Social Care.

The COVID-19 pandemic continues to impact people worldwide–steadily depleting scarce resources in healthcare. Medical Artificial Intelligence (AI) promises a much-needed relief but only if the technology gets adopted at scale. The present research investigates people’s intention to adopt medical AI as well as the drivers of this adoption in a representative study of two European countries (Denmark and France,N= 1068) during the initial phase of the COVID-19 pandemic. Results reveal AI aversion; only 1 of 10 individuals choose medical AI over human physicians in a hypothetical triage-phase of COVID-19 pre-hospital entrance. Key predictors of medical AI adoption are people’s trust in medical AI and, to a lesser extent, the trait of open-mindedness. More importantly, our results reveal that mistrust and perceived uniqueness neglect from human physicians, as well as a lack of social belonging significantly increase people’s medical AI adoption. These results suggest that for medical AI to be widely adopted, people may need to express less confidence in human physicians and to even feel disconnected from humanity. We discuss the social implications of these findings and propose that successful medical AI adoption policy should focus on trust building measures–without eroding trust in human physicians.

ObjectivesWe aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001.MethodsWe conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017.ResultsBetween December 16, 2020, and June 3, 2021, 153 healthy adults aged 18–55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralizing antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.5, 825.1). Seroconversion rates of neutralizing antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific IFN-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively.ConclusionsVLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development.