Active medical recommendation is the best tool for increasing influenza vaccine coverage in healthy adult workers

Introduction In Spain, influenza vaccination is available in companies free of charge for their workers. Despite this, vaccination coverage against influenza is very low in these groups. Objectives The aim of this work is to know the reasons for acceptance of influenza vaccination in a working population. Methods During the 2021–2022 influenza vaccination campaign, we conducted a survey of two groups of workers at the automobile factories of RENAULT ESPAÑA S.A. in the cities of Valladolid and Palencia (Spain). The first group (NV) was formed by 304 (33.5%) workers who did not receive the influenza vaccine in the previous season. The second (V) was formed by 604 workers (66.5%) who had been vaccinated against influenza at least the previous season. In the NV group, they were asked the reasons why they did not get vaccinated the previous season and if they did so in 2021–2022. In group V, only the reasons for continuing to be vaccinated were asked. Results In NV, the main reason for avoiding vaccination in the previous season was the lack of perception of the severity of the influenza infection (74.7%), and 31.6% and 29.0% of them decided to get vaccinated during the 2021–2022 season due to the fear of co-infection of SARS-CoV-2 and influenza and medical recommendations respectively. The 83.5% of group V responded that the reason for getting vaccinated in 2021–2022 was their adherence to vaccination. Conclusions The results show that medical recommendation is the best tool to vaccinate workers against influenza and make them adhere to it. Also, the fear to co-infection of COVID-19 and flu was a frequent reason for getting vaccinated, above all in NV. Resumen Introducción En España la vacunación antigripal está disponible en las empresas de manera gratuita para sus trabajadores. A pesar de esto, las coberturas vacunales frente a la gripe son muy bajas en estos grupos. Objetivos El objetivo es conocer los motivos de aceptación de la vacunación antigripal en la población trabajadora. Métodos Durante la campaña de vacunación de gripe 2021–2022 realizamos una encuesta a dos grupos de trabajadores de las factorías automovilísticas de RENAULT ESPAÑA S.A. en las ciudades de Valladolid y Palencia. El primer grupo (NV) estuvo formado por 304 (33,5%) trabajadores que no recibieron la vacuna antigripal la temporada anterior. El segundo (V) estaba formado por 604 trabajadores (66,5%) que habían sido vacunados contra la gripe al menos la temporada anterior. En el grupo NV se les preguntó las razones de porque no se vacunaron la temporada anterior y si lo hicieron en 2021–2022. En el grupo V se preguntó únicamente las razones para seguirse vacunando. Resultados En NV, la principal razón para evitar la vacunación en la temporada anterior fue la falta de percepción de la gravedad de la gripe (74,7%), y el 31,6% y 29,0% de ellos decidió vacunarse durante la temporada 2021–2022 por el miedo a la co-infección del SARS-Cov-2 y gripe y a las recomendaciones médicas respectivamente. El 83,5% del grupo V respondió que el motivo de vacunarse en el 2021–2022 fue su adherencia a la vacunación. Conclusiones Los resultados muestran que la recomendación médica es la mejor herramienta para vacunar frente a la gripe a los trabajadores y hacerles adherentes a la misma. También, el miedo a la co-infección de COVID-19 y gripe fue una de las razones más frecuentes para vacunarse, sobre todo en NV.

Myocarditis related SARS-CoV-2 infection or vaccination: an expert consensus statement on its diagnosis and management.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has revealed several cardiovascular complications, including myocarditis caused by SARS-CoV-2 infection (COVID-19) or after messenger RNA vaccine administration. Because of the high prevalence of COVID-19, the expansion of vaccination programs, and the appearance of new information on myocarditis in these contexts, there is a need to condense the knowledge acquired since the start of the pandemic. To meet this need, this document was drafted by the Myocarditis Working Group of the Heart Failure Association of the Spanish Society of Cardiology, with the collaboration of the Spanish Agency for Medicines and Health Products (AEMPS). The document aims to address the diagnosis and treatment of cases of myocarditis associated with SARS-CoV-2 infection or messenger RNA vaccine administration.

Consenso de expertos sobre el diagnóstico y el tratamiento de la miocarditis asociada con infección o vacunación contra el SARS-CoV-2 Myocarditis related SARS-CoV-2 infection or vaccination: an expert consensus statement on its diagnosis and management

La pandemia causada por el coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2) ha puesto de manifiesto una serie de complicaciones cardiovasculares, entre las que destaca la miocarditis ocasionada tanto por la propia infección por SARS-CoV-2 (COVID-19) como por la administración de vacunas de ARN mensajero. La elevada prevalencia de primoinfección, la difusión universal de los programas de vacunación y la constante aparición de nueva información sobre la miocarditis en estos contextos, hace necesario condensar el conocimiento adquirido desde el inicio de la pandemia. Con este objetivo, el Grupo de Trabajo Miocarditis de la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología, con la colaboración de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), ha elaborado el presente documento que pretende abordar el diagnóstico y el tratamiento de los casos de miocarditis asociados con la infección por SARS-CoV-2 o la vacuna de ARN mensajero.

[Myocarditis related SARS-CoV-2 infection or vaccination: an expert consensus statement on its diagnosis and management]. / Consenso de expertos sobre el diagnóstico y el tratamiento de la miocarditis asociada con infección o vacunación contra el SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has revealed several cardiovascular complications, including myocarditis caused by SARS-CoV-2 infection (COVID-19) or after messenger RNA vaccine administration. Because of the high prevalence of COVID-19, the expansion of vaccination programs, and the appearance of new information on myocarditis in these contexts, there is a need to condense the knowledge acquired since the start of the pandemic. To meet this need, this document was drafted by the Myocarditis Working Group of the Heart Failure Association of the Spanish Society of Cardiology, with the collaboration of the Spanish Agency for Medicines and Health Products (AEMPS). The document aims to address the diagnosis and treatment of cases of myocarditis associated with SARS-CoV-2 infection or messenger RNA vaccine administration.

Optimal position of air purifiers in elevator cabins for the improvement of their ventilation effectiveness

Ventilation in confined spaces is essential to reduce the airborne transmission of viruses responsible for respiratory diseases such as COVID-19. Mechanical ventilation using purifiers is an interesting solution for elevator cabins to reduce the risk of infection and improve the air quality. In this work, the optimal position and blowing direction of these devices to maximize ventilation and minimize the residence time of the air inside two cabins (large and small) is studied. Special attention is devoted to idle periods when the cabin is not used by the passengers, in order to keep the cabin ambient safe and clean, avoiding that the trapped air in the cabin (after its use) could suppose a reservoir for contaminants. CFD numerical models of two typical cabin geometries, including the discretization of small slots and grilles for infiltration, have been developed. A full 3D URANS approach with a k-epsilon RNG turbulence model and a non-reactive scalar to compute the mean age of air (MAA) was employed. The CFD results have been also validated with experimental measurements from a home-made 1:4 small-scale mock-up. The optimal position of the purifier is on the larger sidewall of the cabins for a downward blowing direction (case 1 of the database). Flow rates in the range of 0.4–0.6 m3/min, depending on the size of the cabin, are sufficient to assure a correct ventilation. Upward blowing may be preferable only if interaction of the jet core with the ceiling or other flow deflecting elements are found. In general, the contribution of infiltrations (reaching values of up to 10%), and how these secondary flows interact with the main flow pattern driven by the purifier, is relevant and not considered previously in the literature. Though an optimal position can improve ventilation considerably, it has been proven that a good choice of the purification flow rate is more critical to ensure an adequate air renewal.

Nanobodies Protecting From Lethal SARS-CoV-2 Infection Target Receptor Binding Epitopes Preserved in Virus Variants Other Than Omicron.

The emergence of SARS-CoV-2 variants that escape from immune neutralization are challenging vaccines and antibodies developed to stop the COVID-19 pandemic. Thus, it is important to establish therapeutics directed toward multiple or specific SARS-CoV-2 variants. The envelope spike (S) glycoprotein of SARS-CoV-2 is the key target of neutralizing antibodies (Abs). We selected a panel of nine nanobodies (Nbs) from dromedary camels immunized with the receptor-binding domain (RBD) of the S, and engineered Nb fusions as humanized heavy chain Abs (hcAbs). Nbs and derived hcAbs bound with subnanomolar or picomolar affinities to the S and its RBD, and S-binding cross-competition clustered them in two different groups. Most of the hcAbs hindered RBD binding to its human ACE2 (hACE2) receptor, blocked cell entry of viruses pseudotyped with the S protein and neutralized SARS-CoV-2 infection in cell cultures. Four potent neutralizing hcAbs prevented the progression to lethal SARS-CoV-2 infection in hACE2-transgenic mice, demonstrating their therapeutic potential. Cryo-electron microscopy identified Nb binding epitopes in and out the receptor binding motif (RBM), and showed different ways to prevent virus binding to its cell entry receptor. The Nb binding modes were consistent with its recognition of SARS-CoV-2 RBD variants; mono and bispecific hcAbs efficiently bound all variants of concern except omicron, which emphasized the immune escape capacity of this latest variant.

Patient’s preferences on the use of Telemedicine during the Coronavirus disease 2019 (COVID-19) Pandemic. ONCOTELEMED study (preprint)

BACKGROUND Since the beginning of the COVID-19 pandemic, the use of telehealth for cancer care was rapidly implemented without previous experience. Afterwards, few published studies have assessed patient’s perception with the use of telemedicine during this period. The main objective of ONCOTELEMD study was to evaluate the opinion of patients attended via telemedicine during the first quarter of 2020 in the Medical Oncology Service of Hospital Parc Taulí, Sabadell. METHODS 646 patients were visited via telephone between March 13 and April 30 2020. A 12-question survey was presented to them between February 4 and April 19 2021. Statistical analysis was carried out using Chi-square test. RESULTS 487 patients responded. Median age was 68 years [27–90]. 90% of patients were satisfied with the telephone visit and 60% would agree to switch some in-person to virtual visits in the future. In general, patients agreed to be informed via telehealth of radiological/analytical results but not of new oral or endovenous treatments. 75% of patients had a medium or low-null knowledge of new technologies. However, statistical significant differences were found according to age groups. 60% of patients younger than 50 years would prefer to have different technological tools to contact their oncologist whereas 58% of patients older than 70 years would prefer only telephone or video-calls. CONCLUSIONS In global, patients surveyed were satisfied with the virtual visit and believe that telehealth could have a role following COVID-19 pandemic. Nevertheless, it is necessary to individualize its use according to patient’s preferences and conditions.

ABO blood group is involved in the quality of the specific immune response anti-SARS-CoV-2.

Since December 2019, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. To eradicate it, it is crucial to acquire a strong and long-lasting anti-SARS-CoV-2 immunity, by either natural infection or vaccination. We collected blood samples 12-305 days after positive polymerase chain reactions (PCRs) from 35 recovered individuals infected by SARS-CoV-2. Peripheral blood mononuclear cells were stimulated with SARS-CoV-2-derived peptide pools, such as the spike (S), nucleocapsid (N) and membrane (M) proteins, and we quantified anti-S immunoglobulins in plasma. After 10 months post-infection, we observed a sustained SARS-CoV-2-specific CD4+ T-cell response directed against M-protein, but responses against S- or N-proteins were lost over time. Besides, we demonstrated that O-group individuals presented significantly lower frequencies of specific CD4+ T-cell responses against Pep-M than non O-group individuals. The non O-group subjects also needed longer to clear the virus, and they lost cellular immune responses over time, compared to the O-group individuals, who showed a persistent specific immune response against SARS-CoV-2. Therefore, the S-specific immune response was lost over time, and individual factors might determine the sustainability of the body's defenses, which must be considered in the future design of vaccines to achieve continuous anti-SARS-CoV-2 immunity.

Neonatal Infection Due to SARS-CoV-2: An Epidemiological Study in Spain.

Objective: Coronavirus disease 2019 (COVID-19) cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to increase worldwide. Although some data from pediatric series are available, more evidence is required, especially in neonates, a group with specific characteristics that deserve special attention. This study aimed to describe general and clinical characteristics, management, and treatment of postnatal-acquired (community and nosocomial/hospital-acquired) COVID-19 neonatal cases in Spain. Methods: This was a national prospective epidemiological study that included cases from a National Registry supported by the Spanish Society of Neonatology. Neonates with postnatal SARS-CoV-2 infection were included in this study. General data and infection-related information (mode and source of transmission, age at diagnosis, clinical manifestations, need for hospitalization, admission unit, treatment administered, and complementary studies performed, hospital stay associated with the infection) were collected. Results: A total of 40 cases, 26 community-acquired and 14 nosocomial were registered. Ten were preterm newborns (2 community-acquired and 8 nosocomial COVID-19 cases). Mothers (in both groups) and healthcare workers (in nosocomial cases) were the main source of infection. Hospital admission was required in 22 community-acquired cases [18 admitted to the neonatal intermediate care unit (NIMCU) and 4 to the neonatal intensive care unit (NICU)]. Among nosocomial COVID-19 cases (n = 14), previously admitted for other reasons, 4 were admitted to the NIMCU and 10 to the NICU. Ten asymptomatic patients were registered (5 in each group). In the remaining cases, clinical manifestations were generally mild in both groups, including upper respiratory airways infection, febrile syndrome or acute gastroenteritis with good overall health. In both groups, most severe cases occurred in preterm neonates or neonates with concomitant pathologies. Most of the cases did not require respiratory support. Hydroxychloroquine was administered to 4 patients in the community-acquired group and to 2 patients in the nosocomial group. Follow-up after hospital discharge was performed in most patients. Conclusions: This is the largest series of COVID-19 neonatal cases in Spain published to date. Although clinical manifestations were generally mild, prevention, treatment, and management in this group are essential.

Induction of High Levels of Specific Humoral and Cellular Responses to SARS-CoV-2 After the Administration of Covid-19 mRNA Vaccines Requires Several Days.

Objectives: In the context of the Covid-19 pandemic, the fast development of vaccines with efficacy of around 95% preventing Covid-19 illness provides a unique opportunity to reduce the mortality associated with the pandemic. However, in the absence of efficacious prophylactic medications and few treatments for this infection, the induction of a fast and robust protective immunity is required for effective disease control, not only to prevent the disease but also the infection and shedding/transmission. The objective of our study was to analyze the level of specific humoral and cellular T-cell responses against the spike protein of SARS-CoV-2 induced by two mRNA-based vaccines (BNT162b2 and mRNA-1273), but also how long it takes after vaccination to induce these protective humoral and cellular immune responses. Methods: We studied in 40 healthy (not previously infected) volunteers vaccinated with BNT162b2 or mRNA-1273 vaccines the presence of spike-specific IgG antibodies and SARS-CoV-2-specific T cells at 3, 7 and 14 days after receiving the second dose of the vaccine. The specific T-cell response was analyzed stimulating fresh whole blood from vaccinated volunteers with SARS-CoV-2 peptides and measuring the release of cytokines secreted by T cells in response to SARS-CoV-2 stimulation. Results: Our results indicate that the immunization capacity of both vaccines is comparable. However, although both BNT162b2 and mRNA-1273 vaccines can induce early B-cell and T-cell responses, these vaccine-mediated immune responses do not reach their maximum values until 14 days after completing the vaccination schedule. Conclusion: This refractory period in the induction of specific immunity observed after completing the vaccination could constitute a window of higher infection risk, which could explain some emerging cases of SARS-CoV-2 infection in vaccinated people.

DEAE-chitosan nanoparticles as a pneumococcus-biomimetic material for the development of antipneumococcal therapeutics.

Advanced biomaterials provide an interesting and versatile platform to implement new and more effective strategies to fight bacterial infections. Chitosan is one of these biopolymers and possesses relevant features for biomedical applications. Here we synthesized nanoparticles of chitosan derivatized with diethylaminoethyl groups (ChiDENPs) to emulate the choline residues in the pneumococcal cell wall and act as ligands for choline-binding proteins (CBPs). Firstly, we assessed the ability of diethylaminoethyl (DEAE) to sequester the CBPs present in the bacterial surface, thus promoting chain formation. Secondly, the CBP-binding ability of ChiDENPs was purposed to encapsulate a bio-active molecule, the antimicrobial enzyme Cpl-711 (ChiDENPs-711), with improved stability over non-derivatized chitosan. The enzyme-loaded system released more than 90% of the active enzybiotic in ≈ 2 h, above the usual in vivo half-life of this kind of enzymes. Therefore, ChiDENPs provide a promising platform for the controlled release of CBP-enzybiotics in biological contexts.

Clinical performance of the Elecsys® anti-SARS-CoV-2 combined in an algorithm with two specific anti-IgG immunoassays for the evaluation of the serological response of patients with COVID-19 in a population with a high prevalence of infection.

BACKGROUND: Anti-SARS-CoV-2 antibodies have been used in the study of the immune response in infected patients. However, differences in sensitivity and specificity have been reported, depending on the method of analysis. The aim of the present study was to evaluate the diagnostic accuracy of an algorithm in which a high-throughput automated assay for total antibodies was used for screening and two semi-automated IgG-specific methods were used to confirm the results, and also to correlate the analytical results with the clinical data and the time elapsed since infection. METHODS: We studied 306 patients, some hospitalized and some outpatients, belonging to a population with a high prevalence of COVID-19. One-hundred and ten patients were classified as SARS-CoV-2 negative and 196 as positive by polymerase chain reaction. RESULTS: The algorithm and automated assay alone had a specificity and a positive predictive value of 100%, although the sensitivity and negative predictive value of the algorithm was higher. Both methods showed a good sensitivity from day 11 of the onset of symptoms in asymptomatic and symptomatic patients. The absorbance of the total antibodies was significantly higher in severely symptomatic than in asymptomatic or mildly symptomatic patients, which suggests the antibody level was higher. We found 15 patients who did not present seroconversion at 12 days from the onset of symptoms or the first polymerase chain reaction test. CONCLUSION: This study highlights the proper functioning of algorithms in the diagnosis of the immune response to COVID-19, which can help to define testing strategies against this disease.

The age again in the eye of the COVID-19 storm: evidence-based decision making.

BACKGROUND: One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data. RESULTS: Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/µL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve. CONCLUSION: Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results.

Symptomatic Common Carotid Free-Floating Thrombus in a COVID-19 Patient, Case Report and Literature Review.

Carotid free-floating thrombus is an uncommon entity that usually presents with neurologic symptoms. Crescendo transient ischemic attack is an accepted indication for urgent carotid endarterectomy. COVID-19 is associated with severe thromboembolic complications. We report the case of a 61-year-old man who developed, 2 weeks after the diagnosis of COVID-19, crescendo transient ischemic attack, complicating a large intraluminal floating thrombus within the right common carotid artery. A carotid thromboendarterectomy under local anesthesia, with patch closure was immediately performed without complications. We conducted a literature review to identify cases of common carotid artery thrombus related to COVID-19. Carotid free-floating thrombus in the common carotid artery is exceptional. However, since the beginning of the COVID-19 pandemic, 15 cases have been published.

Potent neutralization of clinical isolates of SARS-CoV-2 D614 and G614 variants by a monomeric, sub-nanomolar affinity nanobody.

Despite unprecedented global efforts to rapidly develop SARS-CoV-2 treatments, in order to reduce the burden placed on health systems, the situation remains critical. Effective diagnosis, treatment, and prophylactic measures are urgently required to meet global demand: recombinant antibodies fulfill these requirements and have marked clinical potential. Here, we describe the fast-tracked development of an alpaca Nanobody specific for the receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein with potential therapeutic applicability. We present a rapid method for nanobody isolation that includes an optimized immunization regimen coupled with VHH library E. coli surface display, which allows single-step selection of Nanobodies using a simple density gradient centrifugation of the bacterial library. The selected single and monomeric Nanobody, W25, binds to the SARS-CoV-2 S RBD with sub-nanomolar affinity and efficiently competes with ACE-2 receptor binding. Furthermore, W25 potently neutralizes SARS-CoV-2 wild type and the D614G variant with IC50 values in the nanomolar range, demonstrating its potential as antiviral agent.

COVID-19: age, Interleukin-6, C-reactive protein, and lymphocytes as key clues from a multicentre retrospective study.

BACKGROUND: The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor. RESULTS: In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course. CONCLUSIONS: Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease.