First confirmation of importation and transmission in Spain of the newly identified SARS-CoV-2 B.1.1.7 variant.

INTRODUCTION: A newly identified SARS-CoV-2 variant, VOC202012/01 originating lineage B.1.1.7, recently emerged in the United Kingdom. The rapid spread in the UK of this new variant has caused other countries to be vigilant. MATERIAL AND METHODS: We based our initial screening of B.1.1.7 on the dropout of the S gene signal in the TaqPath assay, caused by the 69/70 deletion. Subsequently, we confirmed the B.1.1.7 candidates by whole genome sequencing. RESULTS: We describe the first three imported cases of this variant from London to Madrid, subsequent post-arrival household transmission to three relatives, and the two first cases without epidemiological links to UK. One case required hospitalization. In all cases, drop-out of gene S was correctly associated to the B.1.1.7 variant, as all the corresponding sequences carried the 17 lineage-marker mutations. CONCLUSION: The first identifications of the SARS-CoV-2 B.1.1.7 variant in Spain indicate the role of independent introductions from the UK coexisting with post-arrival transmission in the community, since the early steps of this new variant in our country.

Potent Neutralizing Activity of Polyclonal Equine Antibodies against SARS-CoV-2 Variants of Concern.

Several monoclonal anti-SARS-CoV-2 antibodies (mAbs) have received emergency authorization for COVID-19 treatment. However, most of these mAbs are not active against the highly mutated Omicron SARS-CoV-2 subvariants. We have tested a polyclonal approach of equine anti-SARS-CoV-2 F(ab')2 antibodies that achieved a high level of neutralizing potency against all SARS-CoV-2 VoCs tested including Omicron BA.1, BA.2, BA.2.12 and BA.4/5. A repertoire of antibodies targeting conserved epitopes in different regions of the spike protein could plausibly account for this remarkable breadth of neutralization. These results warrant the clinical investigation of equine polyclonal F(ab')2 antibodies as a novel therapeutic strategy against COVID-19.

Disasters in Spain from 1950 - 2020: Impact on Public Health.

OBJECTIVE: The aim of this study was to establish the frequency and profile of disasters and to analyze trends in disasters and their impact on Spanish public health. METHODS: Retrospective observational study of disasters that occurred in Spain from 1950 through 2020 was conducted. The variables studied for each episode were number of people affected, number of injured/sick, and number of deaths. Absolute and relative frequencies, population rates, mean, median, standard error of the mean (SEM), and 95% confidence intervals (CI) were used, and trend analysis was performed using exponential smoothing and linear regression. RESULTS: A total of 491 disasters were identified in Spain. Of these, 255 (51.9%) were natural disasters, 224 (45.7%) technological disasters, and 12 (2.4%) man-made disasters. The average number of disasters per year was 7.01 (95% CI, 5.99-9.34). These disasters affected a total of 820,489 people, with an average of 3,491 people (SEM = 2.18) per episode. There was a significant increase (P <.001) in the total frequency of disasters in Spain during the period studied. CONCLUSIONS: Spain has a disaster profile of mixed type, combining natural with technological disasters. From 1950 through 2020, there was a significant increase in the number of disasters, with an overall profile similar to that of Europe, with climatological disasters being the most frequent type.

Cross neutralization of SARS-CoV-2 omicron subvariants after repeated doses of COVID-19 mRNA vaccines.

We have measured the humoral response to messenger RNA (mRNA) vaccines in COVID-19 naïve and convalescent individuals. Third doses of mRNA COVID-19 vaccines induced a significant increase in potency and breadth of neutralization against SARS-CoV-2 variants of concern (VoC) including Omicron subvariants BA.1, BA.2, and BA.2.12.1, that were cross-neutralized at comparable levels and less for BA.4/5. This booster effect was especially important in naïve individuals that only after the third dose achieved a level that was comparable with that of vaccinated COVID-19 convalescents except for BA.4/5. Avidity of RBD-binding antibodies was also significantly increased in naïve individuals after the third dose, indicating an association between affinity maturation and cross neutralization of VoC. These results suggest that at least three antigenic stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences are required to induce high avidity cross-neutralizing antibodies. Nevertheless, the circulation of new subvariants such as BA.4/5 with partial resistance to neutralization will have to be closely monitored and eventually consider for future vaccine developments.

Management of the COVID-19 Pandemic: Analysis of the Perception of Professionals of Emergency Medical Systems in Spain after the First Wave.

OBJECTIVE: The objective of this study was to identify the perceived problems by medical and nursing professionals that have arisen in the Spanish Emergency Medical Services (EMS) as a consequence of the first wave of the severe acute respiratory syndrome-coronavirus-2/SARS-CoV-2 pandemic, as well as the measures or solutions adopted to manage those problems and improve response. METHOD: This was a cross-sectional study of quantitative and qualitative methodology ("mixed methods") using a self-administered questionnaire in 23 key informants of EMS of Spain selected by purposeful sampling, followed by the statistical analysis of both types of variables and an integration of the results in the discussion. RESULTS: Common problems had been identified in many EMS, as well as similar solutions in some of them. Among the former, the following had been found: lack of leadership and support from managers, initial shortage of personal protective equipment (PPE), lack of participation in decision making, initial lack of clinical protocols, and slowness and/or lack of adaptability of the system, among others. Among the solutions adopted: reinforcement of emergency call centers, development of specific coronavirus disease 2019 (COVID-19) telephone lines and new resources, personal effort of professionals, new functions of EMS, support to other structures, and reinforcement of the role of nursing. CONCLUSION: The general perception among the respondents was that there was a lack of support and communication with health care managers and that the staff expertise was not used by policy makers to make decisions adapted to reality, also expressing the need to improve the capacity for analysis of the EMS response. Few respondents reported good overall satisfaction with their EMS response. The EMS adopted different types of measures to adapt to the COVID-19 pandemic.

First confirmation of importation and transmission in Spain of the newly identified SARS-CoV-2 B.1.1.7 variant Primera confirmación de importación y transmisión en España de la variante B.1.1.7 del SARS-CoV-2 recientemente identificada

Introduction A newly identified SARS-CoV-2 variant, VOC202012/01 originating lineage B.1.1.7, recently emerged in the United Kingdom. The rapid spread in the UK of this new variant has caused other countries to be vigilant. Material and methods We based our initial screening of B.1.1.7 on the dropout of the S gene signal in the TaqPath assay, caused by the 69/70 deletion. Subsequently, we confirmed the B.1.1.7 candidates by whole genome sequencing. Results We describe the first three imported cases of this variant from London to Madrid, subsequent post-arrival household transmission to three relatives, and the two first cases without epidemiological links to UK. One case required hospitalization. In all cases, drop-out of gene S was correctly associated to the B.1.1.7 variant, as all the corresponding sequences carried the 17 lineage-marker mutations. Conclusion The first identifications of the SARS-CoV-2 B.1.1.7 variant in Spain indicate the role of independent introductions from the UK coexisting with post-arrival transmission in the community, since the early steps of this new variant in our country.

Stress and Burnout Levels among Emergency Medical Technicians Working during COVID-19 Pandemic: A Cross-Sectional Study in Spain

Background/Introduction:Among all health care workers, EMTs have played a notable role during COVID-19;working as a frontline, they faced many challenges, including working overload and an extremely cautious environment that requires a rapid and precise response, which led to experiencing higher severity of mental health symptoms.Objectives:To explore the association between stress and burnout among EMTs while working during the COVID-19 pandemic.Method/Description:A cross-sectional quantitative study with a descriptive design. It was conducted from March-April 2021 on 280 Spanish EMTs, using an online survey of 42 items about workload and working conditions during COVID-19 and other variables specific to COVID-19. The Perceived Stress Scale (PSS), Maslach Burnout Inventory (MBI), and Pearson’s correlation coefficient were used to determine the relationships between the variables.Results/Outcomes:The study revealed a moderate positive correlation between the perceived level of stress and burnout among the EMTs. Specifically, findings showed a strong positive correlation between stress and EE (0.62) and a moderate positive correlation with DP (0.48). However, it found a moderate negative correlation between the level of stress and the third subdimension of burnout, PA (0.45), where the increase in the stress level correlated with a decrease in PA of the EMTs.Conclusion:Burnout might be related to the persistent stress of the EMTs working during the COVID-19 pandemic, considering their work conditions and the socio-demographic variables. The mental health of the first responders is crucial, as it influences their achievement and works satisfaction, and it might affect the quality of the service they provide.Tables and Figures (optional)Table 1.Pearson Correlation: Correlation between the Stress and Burnout among the Emergency Medical Technicians (n = 280)

First confirmation of importation and transmission in Spain of the newly identified SARS-CoV-2 B.1.1.7 variant.

INTRODUCTION: A newly identified SARS-CoV-2 variant, VOC202012/01 originating lineage B.1.1.7, recently emerged in the United Kingdom. The rapid spread in the UK of this new variant has caused other countries to be vigilant. MATERIAL AND METHODS: We based our initial screening of B.1.1.7 on the dropout of the S gene signal in the TaqPath assay, caused by the 69/70 deletion. Subsequently, we confirmed the B.1.1.7 candidates by whole genome sequencing. RESULTS: We describe the first three imported cases of this variant from London to Madrid, subsequent post-arrival household transmission to three relatives, and the two first cases without epidemiological links to UK. One case required hospitalization. In all cases, drop-out of gene S was correctly associated to the B.1.1.7 variant, as all the corresponding sequences carried the 17 lineage-marker mutations. CONCLUSION: The first identifications of the SARS-CoV-2 B.1.1.7 variant in Spain indicate the role of independent introductions from the UK coexisting with post-arrival transmission in the community, since the early steps of this new variant in our country.

Impact of COVID-19 Pandemic on Stress and Burnout Levels amongst Emergency Medical Technicians: A Cross-Sectional Study in Spain.

BACKGROUND: Emergency medical technicians (EMTs) are essential health care workers (HCWs). Although they play an extraordinary role during the COVID-19 pandemic, they are mostly exposed to various occupational health and safety risks that have significantly impacted their mental health, giving rise to symptoms, such as stress and burnout. AIM: This study aimed to assess the perceived levels of stress and burnout amongst EMTs in relation to their socio-demographic characteristics and to explore the associations between their stress and burnout levels during the COVID-19 pandemic. METHODS: This work is an observational cross-sectional design study conducted between 29 March and 30 April 2021, with a convenience sample of 280 Spanish EMTs yielding a response rate of 28%. The online survey had 42 items that aimed to determine participants' socio-demographic characteristics, the Perceived Stress Scale (PSS) and the Maslach Burnout Inventory (MBI). RESULTS: The results showed that more than half of the EMTs (53%) perceived a moderate stress level, 37% perceived moderate levels of emotional exhaustion (EE) and 40% had moderate levels of depersonalization (DP). Furthermore, 48% had low levels of personal accomplishment (PA). Gender, age, having personal protective equipment (PPE) and experiencing fear of infection were statistically significant areas where participants experienced greater stress (p < 0.05). A positive correlation between stress, EE and DP and a negative correlation between stress and the PA subdimension of burnout were found. CONCLUSIONS: The COVID-19 pandemic had a tremendous impact on the mental health of ambulance EMTs. Further studies building on this study and others on the psychological status of EMTs before the pandemic and follow-up during the pandemic, as well as deeper investigations on their work conditions, are needed to facilitate the implementation of various interventions. Such efforts can mitigate the negative impacts of the pandemic on their mental health, and prepare them for future disasters.KEY MESSAGEThe COVID-19 pandemic has affected the lives of the majority of the world's population. In particular, it has impacted the mental health of various communities, including HCWs. Highly stressful and insecure work conditions have placed frontline HCWs at a high risk of psychological distress, making them victims and service providers simultaneously.

Intranasal administration of a single dose of MVA-based vaccine candidates against COVID-19 induced local and systemic immune responses and protects mice from a lethal SARS-CoV-2 infection.

Current coronavirus disease-19 (COVID-19) vaccines are administered by the intramuscular route, but this vaccine administration failed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection in the upper respiratory tract, mainly due to the absence of virus-specific mucosal immune responses. It is hypothesized that intranasal (IN) vaccination could induce both mucosal and systemic immune responses that blocked SARS-CoV-2 transmission and COVID-19 progression. Here, we evaluated in mice IN administration of three modified vaccinia virus Ankara (MVA)-based vaccine candidates expressing the SARS-CoV-2 spike (S) protein, either the full-length native S or a prefusion-stabilized [S(3P)] protein; SARS-CoV-2-specific immune responses and efficacy were determined after a single IN vaccine application. Results showed that in C57BL/6 mice, MVA-based vaccine candidates elicited S-specific IgG and IgA antibodies in serum and bronchoalveolar lavages, respectively, and neutralizing antibodies against parental and SARS-CoV-2 variants of concern (VoC), with MVA-S(3P) being the most immunogenic vaccine candidate. IN vaccine administration also induced polyfunctional S-specific Th1-skewed CD4+ and cytotoxic CD8+ T-cell immune responses locally (in lungs and bronchoalveolar lymph nodes) or systemically (in spleen). Remarkably, a single IN vaccine dose protected susceptible K18-hACE2 transgenic mice from morbidity and mortality caused by SARS-CoV-2 infection, with MVA-S(3P) being the most effective candidate. Infectious SARS-CoV-2 viruses were undetectable in lungs and nasal washes, correlating with high titers of S-specific IgGs and neutralizing antibodies against parental SARS-CoV-2 and several VoC. Moreover, low histopathological lung lesions and low levels of pro-inflammatory cytokines in lungs and nasal washes were detected in vaccinated animals. These results demonstrated that a single IN inoculation of our MVA-based vaccine candidates induced potent immune responses, either locally or systemically, and protected animal models from COVID-19. These results also identified an effective vaccine administration route to induce mucosal immunity that should prevent SARS-CoV-2 host-to-host transmission.

Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses.

Background: SARS-CoV-2 vaccination has proven the most effective measure to control the COVID-19 pandemic. Booster doses are being administered with limited knowledge on their need and effect on immunity. Objective: To determine the duration of specific T cells, antibodies and neutralization after 2-dose vaccination, to assess the effect of a third dose on adaptive immunity and to explore correlates of protection against breakthrough infection. Methods: 12-month longitudinal assessment of SARS-CoV-2-specific T cells, IgG and neutralizing antibodies triggered by 2 BNT162b2 doses followed by a third mRNA-1273 dose in a cohort of 77 healthcare workers: 17 with SARS-CoV-2 infection prior to vaccination (recovered) and 60 naïve. Results: Peak levels of cellular and humoral response were achieved 2 weeks after the second dose. Antibodies declined thereafter while T cells reached a plateau 3 months after vaccination. The decline in neutralization was specially marked in naïve individuals and it was this group who benefited most from the third dose, which resulted in a 20.9-fold increase in neutralization. Overall, recovered individuals maintained higher levels of T cells, antibodies and neutralization 1 to 6 months post-vaccination than naïve. Seventeen asymptomatic or mild SARS-CoV-2 breakthrough infections were reported during follow-up, only in naïve individuals. This viral exposure boosted adaptive immunity. High peak levels of T cells and neutralizing antibodies 15 days post-vaccination associated with protection from breakthrough infections. Conclusion: Booster vaccination in naïve individuals and the inclusion of viral antigens other than spike in future vaccine formulations could be useful strategies to prevent SARS-CoV-2 breakthrough infections.

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers.

BACKGROUND: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers. METHODS: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social-demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion). RESULTS: Among 64,172 health workers from 12 European health centers, 797 breakthrough infections were observed (cumulative incidence of 1.2%). The primary analysis using individual data on 8 out of 12 centers showed that age and previous infection significantly modified breakthrough infection rates. In the meta-analysis of aggregated data from all centers, previous SARS-CoV-2 infection and the standardized antibody titer were inversely related to the risk of breakthrough infection (p = 0.008 and p = 0.007, respectively). CONCLUSION: The inverse correlation of antibody titer with the risk of breakthrough infection supports the evidence that vaccination plays a primary role in infection prevention, especially in health workers. Cellular immunity, previous clinical conditions, and vaccination timing should be further investigated.

The Impact of COVID-19 Pandemic Lockdown on Routine Immunization in the Province of Laghman, Afghanistan.

Background: The COVID-19 pandemic, declared by the World Health Organization as a public health international emergency concern in March 2020, has caused serious impacts on individuals, families, communities, and societies across the globe. The COVID-19 pandemic not only disrupted the health systems and the economy, but also significantly impacted routine immunization programs. Aim: To study the impact of the COVID-19 pandemic lockdown on the routine immunization coverage program in the province of Laghman, Afghanistan. Methods: A comparative cross-sectional quantitative study was conducted to understand the impact of COVID-19 on routine childhood immunization during the study period. Secondary data was used from the Ministry of Health from April to July 2020 and compared with the historical data of the same period in 2019. Student t-test was used to test the association between the mean changes in the daily immunization coverage. A p-value<0.05 was considered as statistically significant with 95% confidence interval. Results: There was a 21.4% significant (p<0.01) decline in the total immunization coverage during April-July 2020 compared to April-July 2019. This reduction was diverse across all districts and all vaccine antigens. The most affected district was Alingar, and the most affected vaccines were measles and OPV4, with 28% declines, followed by PCV3 at 26%, and DPT3, IPV, OPV3, PCV2 and rotavirus at 23%. The outreach vaccination coverage declined by 56.1% compared to the fixed, at 13.4%. Conclusion: The COVID-19 pandemic seriously affected the routine immunization in Afghanistan. On average, 325 children per day missed out on a lifesaving vaccine in Laghman province which put them at risk of getting preventable diseases. To provide access to routine immunization during pandemics, the study suggests a set of customized interventions to strengthen and sustain routine immunization.

Topological and Multivalent Effects in Glycofullerene Oligomers as EBOLA Virus Inhibitors

The synthesis of new biocompatible antiviral materials to fight against the development of multidrug resistance is being widely explored. Due to their unique globular structure and excellent properties, [60]fullerene-based antivirals are very promising bioconjugates. In this work, fullerene derivatives with different topologies and number of glycofullerene units were synthesized by using a SPAAC copper free strategy. This procedure allowed the synthesis of compounds 1–3, containing from 20 to 40 mannose units, in a very efficient manner and in short reaction times under MW irradiation. The glycoderivatives were studied in an infection assay by a pseudotyped viral particle with Ebola virus GP1. The results obtained show that these glycofullerene oligomers are efficient inhibitors of EBOV infection with IC50s in the nanomolar range. In particular, compound 3, with four glycofullerene moieties, presents an outstanding relative inhibitory potency (RIP). We propose that this high RIP value stems from the appropriate topological features that efficiently interact with DC-SIGN.

Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2.

Novel safe, immunogenic, and effective vaccines are needed to control the COVID-19 pandemic, caused by SARS-CoV-2. Here, we describe the safety, robust immunogenicity, and potent efficacy elicited in rhesus macaques by a modified vaccinia virus Ankara (MVA) vector expressing a full-length SARS-CoV-2 spike (S) protein (MVA-S). MVA-S vaccination was well tolerated and induced S and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against SARS-CoV-2 and several variants of concern. S-specific IFNγ, but not IL-4, -producing cells were also elicited. After SARS-CoV-2 challenge, vaccinated animals showed a significant strong reduction of virus loads in bronchoalveolar lavages (BAL) and decreased levels in throat and nasal mucosa. Remarkably, MVA-S also protected macaques from fever and infection-induced cytokine storm. Computed tomography and histological examination of the lungs showed reduced lung pathology in MVA-S-vaccinated animals. These findings favor the use of MVA-S as a potential vaccine for SARS-CoV-2 in clinical trials.

Casas tomadas: Habitabilidad, comunidad y espacios públicos en tiempos de pandemia

Reflexiones en torno a la pandemia que se suscitó desde marzo de 2020. Si bien las transformaciones ocurridas en este contexto pandémico son amplias y remiten a procesos sociales, subjetivos, familiares, laborales, económicos, nos detenemos en los cambios sucedidos en el espacio público y en la comunidad. Trabajamos estas categorías a partir de la habitabilidad (la casa), del exterior como amenaza, del contagio, de la inmunidad y del otro, y reflexionamos desde una aproximación conceptual, con testimonios y experiencias. Damos cuenta también de la dinámica de un capitalismo que no descansa y de la clase social en esta problemática.Alternate :Reflections on the pandemic that arose since March 2020. Although the transformations that have occurred in this pandemic context are extensive and refer to social, subjective, family, work, and economic processes, we will focus on the changes that occurred in the public space and in the community. We work on these categories based on habitability (the house), from the outside as a threat, from contagion, from immunity and from the other, and we reflect from a conceptual approach, with testimonies and experiences. We also realize the dynamics of a capitalism that does not rest and of the social class in this problem.

A Single Dose of an MVA Vaccine Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Protein Neutralizes Variants of Concern and Protects Mice From a Lethal SARS-CoV-2 Infection.

We generated an optimized COVID-19 vaccine candidate based on the modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, termed MVA-CoV2-S(3P). The S(3P) protein was expressed at higher levels (2-fold) than the non-stabilized S in cells infected with the corresponding recombinant MVA viruses. One single dose of MVA-CoV2-S(3P) induced higher IgG and neutralizing antibody titers against parental SARS-CoV-2 and variants of concern than MVA-CoV2-S in wild-type C57BL/6 and in transgenic K18-hACE2 mice. In immunized C57BL/6 mice, two doses of MVA-CoV2-S or MVA-CoV2-S(3P) induced similar levels of SARS-CoV-2-specific B- and T-cell immune responses. Remarkably, a single administration of MVA-CoV2-S(3P) protected all K18-hACE2 mice from morbidity and mortality caused by SARS-CoV-2 infection, reducing SARS-CoV-2 viral loads, histopathological lesions, and levels of pro-inflammatory cytokines in the lungs. These results demonstrated that expression of a novel full-length prefusion-stabilized SARS-CoV-2 S protein by the MVA poxvirus vector enhanced immunogenicity and efficacy against SARS-CoV-2 in animal models, further supporting MVA-CoV2-S(3P) as an optimized vaccine candidate for clinical trials.

Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice.

Two doses of the MVA-CoV2-S vaccine candidate expressing the SARS-CoV-2 spike (S) protein protected K18-hACE2 transgenic mice from a lethal dose of SARS-CoV-2. This vaccination regimen prevented virus replication in the lungs, reduced lung pathology, and diminished levels of pro-inflammatory cytokines. High titers of IgG antibodies against S and receptor-binding domain (RBD) proteins and of neutralizing antibodies were induced against parental virus and variants of concern, markers that correlated with protection. Similar SARS-CoV-2-specific antibody responses were observed at prechallenge and postchallenge in the two-dose regimen, while the single-dose treatment does not avoid vaccine breakthrough infection. All vaccinated animals survived infection and were also protected to SARS-CoV-2 reinfection. Furthermore, two MVA-CoV2-S doses induced long-term memory S-specific humoral and cellular immune responses in C57BL/6 mice, 6 months after immunization. The efficacy and immunological benefits of the MVA-CoV2-S vaccine candidate against COVID-19 supports its consideration for human clinical trials.