Incidence and prevalence of headache in influenza: A 2010-2021 surveillance-based study.

BACKGROUND AND PURPOSE: Influenza is a common cause of acute respiratory infection, with headache being one of the symptoms included in the European Commission case definition. The prevalence of headache as a symptom of influenza remains unknown. We aimed to describe the incidence and prevalence of headache in patients with influenza. METHODS: All consecutive patients who met the definition criteria of influenza-like illness during the influenza seasons 2010-2011 through 2021-2022 were included. The seasonal cumulative incidence of influenza per 1000 patients at risk and the prevalence of headache as an influenza symptom were calculated, including the 95% confidence intervals (CIs). Subgroup analyses were done based on patients' sex, age group, microbiological confirmation, vaccination status, and influenza type/subtype/lineage. RESULTS: During the study period, 8171 patients were eligible. The incidence of headache in the context of influenza varied between 0.24 cases per 1000 patients (season 2020-2021) and 21.69 cases per 1000 patients (season 2017-2018). The prevalence of headache was 66.1% (95% CI = 65.1%-67.1%), varying between 49.6% (season 2021-2022) and 80.1% (season 2010-2011). The prevalence of headache was higher in women (67.9% vs. 65.7%, p = 0.03) and higher in patients between 15 and 65 years old. Headache was more prevalent in patients infected with B subtypes than A subtypes (68.7% vs. 56.9%, p < 0.001). There were no notable differences regarding vaccination status or microbiological confirmation of the infection. CONCLUSIONS: Headache is a common symptom in patients with influenza, with a prevalence higher than that observed in other viral infections.

Potential Effects on Elderly People From Nirsevimab Use in Infants.

Nirsevimab therapy has the potential to revolutionize infant respiratory syncytial virus (RSV) prophylaxis. But other populations suffering RSV, such the elderly or those over 60, may also be protected by using this novel antibody in the infant group. It is true that some studies link the use of nirsevimab to a reduction in the virus's ability to spread by lowering the viral load in infants as a result of the drug's long half-life. However, this protective effect may not be very significant because RSV transmission in the elderly typically comes from other elderly people or from school-aged children. Furthermore, RSV may be transmitted at any time of the year and not just during the period of nirsevimab protection due to its existence in human reservoirs. The reasons made here show that, even though nirsevimab treatment in infants may protect the elderly, this benefit would be limited and testimonial. Therefore, immunizing the elderly with currently licensed and developing vaccines should be a priority.

El uso de nirsevimab puede suponer una revolución en la prevención del virus respiratorio sincitial (VRS) en lactantes. Sin embargo, el uso de este nuevo anticuerpo en dicho grupo de edad podría proteger también a otros grupos que conviven con ellos, como por ejemplo las personas de edad avanzada o grupo de personas mayores de 60 años. Si bien es cierto que algunos estudios sugieren una disminución en la propagación del virus con el uso de nirsevimab, al reducir la carga viral en lactantes como consecuencia de la prolongada vida media del fármaco, este efecto protector podría ser de escasa relevancia, ya que la transmisión del VRS en personas de edad avanzada sucede en la mayor parte de los casos desde personas de la misma edad o desde niños en edad escolar. Adicionalmente, la presencia de VRS en reservorios humanos puede permitir que el VRS se transmita en cualquier época del año, no limitándose únicamente al periodo de protección de nirsevimab. Los argumentos aquí expuestos demuestran que, si bien el uso de nirsevimab en lactantes podría tener un efecto protector en las personas de edad avanzada, este solo sería testimonial y limitado. En consecuencia, debe priorizarse la inmunización de los pacientes de edad avanzada con las vacunas actualmente autorizadas y en desarrollo.

Association of viral loads of influenza A (H3N2) with age and care setting on presentation-a prospective study during the 2022-2023 influenza season in Spain.

OBJECTIVES: The aim of this study was to analyze the viral load (VL) using cycle threshold (Ct) in patients infected with influenza A (H3N2). METHODS: This prospective study was conducted during the 2022-2023 influenza season in sentinel, non-sentinel, and hospitalized patients of Castilla y León (Spain). Respiratory samples were obtained from nasopharyngeal swabs and analyzed by quantitative reverse transcription-polymerase chain reaction specific for influenza A (H3N2) to obtain the Ct value. RESULTS: A total of 1047 individuals were enrolled (174 [16.6%] sentinel, 200 [19.1%] non-sentinel, 673 [64.3%] hospitalized). The mean Ct value was lower in infants, young children, and in the elderly, with a sharp increase in the last from 65 years until 90 years. In addition, the lower Ct values were observed in non-sentinel patients and then in hospitalized patients, probably because non-sentinel are outpatients in the acute phase of the influenza infection. CONCLUSIONS: A higher VL (lower Ct value) is related to the extreme ages of life: children and the elderly. Furthermore, a higher VL is related with the care setting, being probably higher in outpatients because they are in the acute phase of the disease and slightly lower in hospitalized patients because they are attended during the post-acute phase.

Factors associated to the presence of headache in patients with influenza infection and its consequences: a 2010-2020 surveillance-based study.

Headache is a common symptom of influenza infection; however, its causes and consequences remain uncertain. In this manuscript, we analyzed which demographic and clinical factors were associated with the presence of headache during the course of influenza infection and whether patients with headache had a different prognosis, evaluated by need of hospitalization, sick leave or school absenteeism. The influence study (NCT05704335) was an observational study that analyzed data routinely collected from the Health Sentinel Network between 2010 and 2020. During the study period, 7832 cases were considered, among which, 5275 (67.4%) reported headache. The presence of headache was independently associated with myalgia (2.753; 95%CI: 2.456-3.087, P < 0.001), asthenia (OR: 1.958; 95%CI: 1.732-2.214, P < 0.001), shivering (OR: 1.925; 95%CI: 1.718-2.156, P < 0.001), nasopharyngeal erythema (OR: 1.505; 95%CI: 1.293-1.753, P < 0.001), fever (OR: 1.469; 95%CI: 1.159-1.861; P = 0.001), sudden onset of symptoms (OR: 1.380; 95%CI: 1.120-1.702, p = 0.004), female sex (OR: 1.134; 95%CI: 1.023-1.257, P = 0.018), and gastrointestinal symptoms (OR: 1.169; 95%CI: 1.039-1.315; P = 0.01). Patients with headache had a sex and age adjusted lower odds of being referred to the hospital (OR: 0.463; 95%CI: 0.264-0.812, P = 0.007) and a higher odd of having a sick leave and/or school absenteeism (absenteeism (OR: 1.342; 95%CI: 1.190-1.514, P < 0.001). In conclusion, the presence of headache seems associated with symptoms caused by the innate immune response. These findings support a headache pathophysiology linked with the innate immune response. Due to the potential negative consequences and its treatable nature, clinicians should systematically evaluate it and, whenever necessary, treat it too.

Impact on the time elapsed since SARS-CoV-2 infection, vaccination history, and number of doses, on protection against reinfection.

SARS-CoV-2 reinfections have been frequent, even among those vaccinated. The aim of this study is to know if hybrid immunity (infection + vaccination) is affected by the moment of vaccination and number of doses received. We conducted a retrospective study in 746 patients with a history of COVID-19 reinfection and recovered the dates of infection and reinfection and vaccination status (date and number of doses). To assess differences in the time to reinfection(tRI) between unvaccinated, vaccinated before 6 months, and later; and comparing one, two or three doses (incomplete, complete and booster regime) we performed the log-rank test of the cumulative incidence calculated as 1 minus the Kaplan-Meier estimator. Also, an adjusted Cox-regression was performed to evaluate the risk of reinfection in all groups. The tRI was significantly higher in those vaccinated vs. non-vaccinated (p < 0.001). However, an early incomplete regime protects similar time than not receiving a vaccine. Vaccination before 6 months after infection showed a lower tRI compared to those vaccinated later with the same regime (adj-p < 0.001). Actually, early vaccination with complete and booster regimes provided lower length of protection compared to vaccinating later with incomplete and complete regime, respectively. Vaccination with complete and booster regimes significantly increases the tRI (adj-p < 0.001). Vaccination increases the time it takes for a person to become reinfected with SARS-CoV-2. Increasing the time from infection to vaccination increases the time in which a person could be reinfected and reduces the risk of reinfection, especially in complete and booster regimes. Those results emphasize the role of vaccines and boosters during the pandemic and can guide strategies on future vaccination policy.

InfluenCEF study: Clinical phenotype and duration of headache attributed to influenza infection.

INTRODUCTION: Headache is a frequent symptom of infections. We aimed to characterize the clinical phenotype and duration of headache attributed to influenza infection. METHODS: Prospective cohort study done in 53 primary care centers between January and April 2023. Patients were included if they had a confirmed influenza diagnosis, were older than 15 years and had a new-onset headache. Patients' demographics, prior medical history, headache phenotype and duration, associated symptoms and patients' outcomes were assessed. The International Classification of Headache Disorders criteria for headache attributed to a systemic viral infection, migraine and tension-type headache were assessed. RESULTS: Of the 478 patients 75 fulfilled eligibility criteria. The mean age was 43, 56% were men, and 27% had a prior headache history. The headache phenotype was a bilateral headache (52%), with frontal topography (48%), pressing quality (61%), moderate intensity, rhinorrhea (79%), nasal congestion (76%), and photophobia (59%). All patients fulfilled headache attributed to acute systemic viral infection criteria, 43% fulfilled migraine criteria and 31% tension-type headache criteria. The median duration of the headache was four (Inter-quartile range: two-six) days. CONCLUSION: The clinical phenotype of headache attributed to influenza infection was similar to other infections, with more pronounced cranial autonomic symptoms. The headache was an early symptom and was self-limited within a few days.Trial Registration: The study protocol is registered in ClinicalTrial.gov (NCT05704335).

The Impact of the COVID-19 Pandemic on Influenza Vaccination Attitudes and Actions in Spain's Adult Population.

Seasonal influenza is an acute respiratory infection caused by the influenza virus which constitutes a significant public health issue associated with high morbidity and mortality. The aim of this study was to investigate changes in attitudes, perceptions, and practices regarding influenza vaccination in the Spanish adult population during the COVID-19 pandemic, as well as their vaccination intentions, with special attention paid to those over 65 years old and in high-risk groups. To this end, a cross-sectional study was conducted through 2219 telephone interviews, and the results were compared with results obtained a year earlier. Regarding the reasons for deciding to get vaccinated in the 2022/23 season, a significant increase was observed in vaccine confidence (36.7% vs. 42.8%), social responsibility (32.5% vs. 43.8%), and in awareness of the importance of vaccination due to COVID-19 (21.7% vs. 25.4%). Advanced age (OR 2.8, 95% CI 2.0-3.9), belonging to high-risk groups (OR 2.7, 95% CI 2.0-3.7), and prior vaccination (OR 25.3, 95% CI 19.5-32.7) emerged as significant predictors for the intent to receive the influenza vaccine in the 2022/23 season. Continuously observing shifts in perceptions and behaviors related to influenza immunization is crucial to pinpoint factors that may influence the willingness to receive the vaccine and, in this way, design public health strategies that achieve a greater acceptance of it.

Long-term influenza antibodies profiles in previously vaccinated and non-vaccinated adults.

The aim of this work is to describe the dynamics of influenza antibodies after vaccination in adults. We conducted a case-cohort serological study in the automobile manufacturing plants of the Renault España S.A. group in Valladolid and Palencia (Spain), including 550 workers (66.9%) previously vaccinated against influenza (group V), and 272 (33.1%) never vaccinated (group NV). A pre-vaccination serum sample was collected, another after 30-40 days and another after 6 months. The dynamics of antibodies were analyzed. A lower seroprotection of NV before vaccination was observed, but an antibody response between 2 and 4 times higher than in V was assessed. After 6 months, antibodies declined in both groups until equalize. Antibodies titers decrease with age, and no differences were found among underlying pathologies. Adults never vaccinated against influenza had lower seroprotection than those previously vaccinated, but influenza vaccination produces a more intense serological response in them, acquiring significantly higher antibody titers than those previously vaccinated. The antibodies, although in lower titers, persist and equalize among both groups at least 6 months after vaccination, which allows the individual to be protected during the entire circulation of the influenza virus in the same season.

Old and new aspects of influenza. / Nuevos y viejos aspectos de la gripe.

Influenza is a classic infectious disease that, through the continuous variation of the viruses that produce it, imposes new challenges that we must solve as quickly as possible. The COVID-19 pandemic has substantially modified the behavior of influenza and other respiratory viruses, and in the coming years we will have to coexist with a new pathogen that will probably interact with existing pathogens in a way that we cannot yet glimpse. However, knowledge prior to the pandemic allows us to focus on the aspects that must be modified to make influenza an acceptable challenge for the future. In this review, emphasis is placed on the most relevant aspects of epidemiology, disease burden, diagnosis, and vaccine prevention, and how scientific and clinical trends in these aspects flow from the previously known to future challenges.

Impact of COVID-19 on Adherence to Treatment in Patients with HIV.

In patients with human immunodeficiency virus (HIV), adherence to treatment is affected by the adverse effects of treatment, the presence of additional comorbidities, the complexity of dosage, and family and community support. However, one recent circumstance that was likely to have influenced therapeutic adherence was the COVID-19 pandemic and the applied containment measures. An observational retrospective study of a sample of patients with HIV was conducted to establish the relationship between sociodemographic, clinical, and pharmacological variables and therapeutic adherence before and after the pandemic. Adherence was measured using the validated simplified medication adherence questionnaire (SMAQ) and medication possession rate. A statistical analysis was performed to determine the mean, standard deviation, and median of the quantitative variables and the frequencies of the qualitative variables, and the relationship between the dependent and independent variables was analysed using the chi-squared test and Student's t-test. No statistically significant differences were found between treatment adherence measured before and 22 months after the start of the pandemic. Sex, occupation, treatment regimen, viral load levels, and COVID-19 disease status did not influence adherence during either period. However, the age of patients with HIV had an impact on adherence during both periods (p = 0.008 and p = 0.002, respectively), with the age group under 45 years being less adherent. In addition, experiencing adverse drug reactions (ADRs) was shown to have an impact on adherence before the pandemic (p = 0.006) but not afterwards. The COVID-19 pandemic was not shown to have an impact on the degree of adherence to antiretroviral treatment in patients with HIV. Instead, adherence was influenced by patient age and ADR occurrence; therefore, measures must be taken in this regard. The SMAQ demonstrated sensitivity in assessing adherence.

Adjuvants for COVID-19 Vaccines.

In recent decades, the improvement of traditional vaccines has meant that we have moved from inactivated whole virus vaccines, which provoke a moderate immune response but notable adverse effects, to much more processed vaccines such as protein subunit vaccines, which despite being less immunogenic have better tolerability profiles. This reduction in immunogenicity is detrimental to the prevention of people at risk. For this reason, adjuvants are a good solution to improve the immunogenicity of this type of vaccine, with much better tolerability profiles and a low prevalence of side effects. During the COVID-19 pandemic, vaccination focused on mRNA-type and viral vector vaccines. However, during the years 2022 and 2023, the first protein-based vaccines began to be approved. Adjuvanted vaccines are capable of inducing potent responses, not only humoral but also cellular, in populations whose immune systems are weak or do not respond properly, such as the elderly. Therefore, this type of vaccine should complete the portfolio of existing vaccines, and could help to complete vaccination against COVID-19 worldwide now and over the coming years. In this review we analyze the advantages and disadvantages of adjuvants, as well as their use in current and future vaccines against COVID-19.

Lactate/albumin ratio prognostic value for mortality in patients older than 65 years with complicated urinary tract infection.

BACKGROUND: Lactate to albumin ratio (LAR) is an emerging sepsis biomarker that has been tested for mortality in patients with sepsis of different focus. Our goal is to evaluate the prognostic value of LAR in patients admitted to the hospital due to complicated urinary tract infections. METHODS: Prospective observational study of patients older than 65 years diagnosed with UTI. Area under the ROC curve, sensibility, and specificity to predict 30-day mortality were calculated for LAR, qSOFA and SOFA. RESULTS: 341 UTI cases were analyzed. 30-day mortality (20.2% vs. 6.7%, p < 0.001) and longer hospital stay (5 [4-8] vs. 4 [3-7], p 0.018) were associated with LAR ≥ 0.708. LAR has no statistically significant differences compared to qSOFA and SOFA for predicting 30-day mortality (AUROC 0.737 vs. 0.832 and 0.777 respectively, p 0.119 and p 0.496). The sensitivity of LAR was similar to the sensitivity of qSOFA and SOFA (60.8% vs. 84.4% and 82.2, respectively, p 0.746 and 0.837). However, its specificity was lower than the specificity of qSOFA (60.8% vs. 75%, p 0.003), but similar to the specificity of SOFA (60.8% vs. 57.8%, p 0.787). CONCLUSION: LAR has no significant differences with other well-stablished scores in sepsis, such as qSOFA and SOFA, to predict 30-day mortality in patients with complicated UTI.

Attitudes, Perceptions and Practices of Influenza Vaccination in the Adult Population: Results of a Cross-Sectional Survey in Spain.

In Spain, the 2021/22 influenza season overlapped with the sixth wave of the 2019 coronavirus disease pandemic (COVID-19). Influenza is a major public health problem associated with high morbidity and mortality. The objectives of this study were to determine the knowledge, perceptions and practices of influenza vaccination in the Spanish population, coinciding with the COVID-19 pandemic, with special attention paid to people over 65 years of age. A cross-sectional study was carried out by conducting 2211 telephone interviews. It was observed that 81.6% of people ≥ 65 years were vaccinated annually or with some frequency compared to 35.5% of those under 65 years (p < 0.001). Fifty percent of Spaniards showed an intention to be vaccinated in the 2021/22 campaign, during the SARS-CoV2 pandemic. In the case of people ≥ 65 years old, this figure was 83% compared to 42% of those under 65 years old (p < 0.001). Significant predictors of intention to be vaccinated were age of 65 years or older (OR 1.8, 95% CI 1.3-2.5), female sex (OR 1.9, 95% CI 1.5-2.4), belonging to risk groups (OR 2.2, 95% CI 1.6-3.1) and having been previously vaccinated (OR 29.7, 95% CI 22.5-39.2). The main reasons for deciding to be vaccinated were the need to be protected against the virus and to be vaccinated annually. On the other hand, lack of recommendation and considering the influenza vaccine as not necessary were the main reasons for not getting vaccinated. In addition, health personnel stood out as the main source of information (32.9%) compared to traditional media (26.9%) and public administration (12.3%). This study aimed to assess and analyse the factors influencing willingness to receive influenza vaccines in the COVID-19 era among Spanish adults, as well as the main information channels and strategies to encourage vaccination.

Putative Secondary Structure at 5’UTR as a Potential Antiviral Target against SARS-CoV-2 / Estructura secundaria en 5’UTR como diana antiviral contra el SARS-CoV-2

SARS-CoV-2 is an enveloped positive-sense single-stranded RNA coronavirus that causes COVID-19, ofwhich the current outbreak has resulted in a high number ofcases and fatalities throughout the world, even vaccine dosesare being administered. The aim of this work was to scan theSARS-CoV-2 genome in search for therapeutic targets. Wefound a sequence in the 5’UTR (NC\_045512:74-130), consisting of a typical heptamer next to a structured region thatmay cause ribosomal frameshifting. The potential biologicalvalue of this region is relevant through its low similarity withother viruses, including coronaviruses related to SARS-CoV,and its high sequence conservation within multiple SARSCoV-2 isolates. We have predicted the secondary structure ofthe region by means of different bioinformatic tools. We havesuggested a most probable secondary structure to proceedwith a 3D reconstruction of the structured segment. Finally,we carried out virtual docking on the 3D structure to look fora binding site and then for drug ligands from a database oflead compounds. Several molecules that could be probablyadministered as oral drugs show promising binding affinitywithin the structured region, and so it could be possible interfere its potential regulatory role (AU)

El SARS-CoV-2 es un coronavirus de ARN monocatenariode sentido positivo envuelto que causa COVID-19, del cual elbrote actual ha provocado una gran cantidad de casos y muertes en todo el mundo, incluso cuando se están administrandodosis de vacunas. En este trabajo hemos escaneado el genomadel SARS-CoV-2 en busca de dianas terapéuticas. Encontramosuna secuencia en el 5’UTR (NC \ _045512: 74-130), que consiste en un heptámero típico junto a una región estructurada quepuede causar cambios en la pauta de lectura. El valor biológicopotencial de esta región es relevante debido a su baja similitud con otros virus, incluidos los coronavirus relacionados conel SARS-CoV, y su alta conservación de secuencia dentro demúltiples aislados de SARS-CoV-2. Hemos predicho la estructura secundaria de la región mediante diferentes herramientasbioinformáticas. Hemos sugerido una estructura secundariamás probable para así proceder al acoplamiento virtual en laestructura 3D para buscar un sitio de unión y luego ligandosde fármacos. Hemos encontrado varias moléculas que probablemente podrían administrarse como fármacos orales muestran una afinidad de unión prometedora dentro de la regiónestructurada, por lo que es posible que interfieran en su posiblefunción reguladora de la replicación viral. (AU)

A new MALDI-TOF approach for the quick sequence type identification of Legionella pneumophila.

BACKGROUND: Recently, MALDI-TOF has emerged as a quick tool for bacterial typing. The aim was to evaluate if MALDI-TOF based typing of Legionella pneumophila can achieve the same discriminatory power as that of the Sequence Based Typing (SBT) method. METHODS: The Sequence Type (ST) was obtained from the 90 strains included in the training set and an in-house MALDI-TOF library based on the Main Spectra Profile (MSP) was generated for the identification of such ST. Then, our library was validated by three procedures: a) creating a dendrogram, b) searching for specific peaks present exclusively in each MSP entry, and c) analysing a validation set composed of 14 strains with known ST. Fully characterized L. pneumophila ATCC 33152, which belongs to ST 36, was used as a control strain. RESULTS: In the training set, 17 strains belonged to ST 1, 1 to ST 20, 63 to ST 22, 1 to ST 146, 6 to ST 578, and 2 to ST 1086. Specific peaks present in each MSPs spectrum, which are considered type-specific biomarkers, ranged from 2 to 11; more concretely, MSP for ST 1 identification shows 2 specific peaks; MSP for ST 20 identification: 9 specific peaks; MSP for ST 22 and ST 36 identification: 11 specific peaks; MSP for ST 146 identification: 5 specific peaks; and MSP for ST 578 and ST 1086 identification: 3 specific peaks. Using the validation set (nine strains belonging to ST 22 and five to ST 1), MALDI-TOF assigned accurately the ST in 30 min per tested strain with a full match. CONCLUSIONS: The ST of L. pneumophila can be identified and reported in few minutes directly from colonies grown on BCYE agar using MALDI-TOF.

COVID-19 Comes 40 Years After AIDS - Any Lesson?

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has hit health-care systems and societies in an unprecedented manner. In 1981, the first cases of AIDS were reported and wide diagnostic testing helped to characterize high-risk groups and the global burden of the epidemic. With Coronavirus Disease (COVID)-19, everything has happened too fast and both cases and fatalities are huge but still uncertain in most places. Diagnostic testing of active and past SARS-CoV-2 infections needs to expand rapidly, ideally using rapid tests. COVID-19 deaths are highly concentrated in the elderly population, with a large proportion of fatalities being "with" rather than "by" SARS-CoV-2 infection. They are often the result of inadequate health care due to overwhelming demands. To date, there is no specific therapy for SARS-CoV-2 infection. Several antivirals are being tested clinically, including remdesivir, at this time the most promising. For others such as lopinavir/ritonavir, neither significant virological nor clinical benefit has been shown. Given the characteristic pulmonary cytokine storm underlying the pathogenic mechanism of severe COVID-19 pneumonia and acute respiratory distress, antiinflammatory agents are being investigated. The benefit of orticosteroids, hydroxychloroquine, etc., is limited. Monoclonal antibodies targeting different pro-inflammatory cytokines, such as tocilizumab, an anti-interleukin 6 agent, are being tried with encouraging results. Ultimately a protective vaccine will be the best response for controlling the COVID-19 pandemic.