A Genome-Wide Arrayed CRISPR Screen Reveals PLSCR1 as an Intrinsic Barrier to SARS-CoV-2 Entry (preprint)

Interferons (IFNs) play a crucial role in the regulation and evolution of host-virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence SARS-CoV-2 infection. We then performed an integrated analysis of genes interacting with SARS-CoV-2, drawing from a selection of 67 large-scale studies, including our own. We identified 28 genes of high relevance in both human genetic studies of COVID-19 patients and functional genetic screens in cell culture, with many related to the IFN pathway. Among these was the IFN-stimulated gene PLSCR1. PLSCR1 did not require IFN induction to restrict SARS-CoV-2 and did not contribute to IFN signaling. Instead, PLSCR1 specifically restricted spike-mediated SARS-CoV-2 entry. The PLSCR1-mediated restriction was alleviated by TMPRSS2 over-expression, suggesting that PLSCR1 primarily restricts the endocytic entry route. In addition, recent SARS-CoV-2 variants have adapted to circumvent the PLSCR1 barrier via currently undetermined mechanisms. Our study contributes to understanding the association between PLSCR1 variants and severe COVID-19 cases reported in a recent GWAS.

SARS-CoV-2 Orphan Gene ORF10 Contributes to More Severe COVID-19 Disease (preprint)

The orphan gene of SARS-CoV-2, ORF10, is the least studied gene in the virus responsible for the COVID-19 pandemic. Recent experimentation indicated ORF10 expression moderates innate immunity in vitro. However, whether ORF10 affects COVID-19 in humans remained unknown. We determine that the ORF10 sequence is identical to the Wuhan-Hu-1 ancestral haplotype in 95% of genomes across five variants of concern (VOC). Four ORF10 variants are associated with less virulent clinical outcomes in the human host: three of these affect ORF10 protein structure, one affects ORF10 RNA structural dynamics. RNA-Seq data from 2070 samples from diverse human cells and tissues reveals ORF10 accumulation is conditionally discordant from that of other SARS-CoV-2 transcripts. Expression of ORF10 in A549 and HEK293 cells perturbs immune-related gene expression networks, alters expression of the majority of mitochondrially-encoded genes of oxidative respiration, and leads to large shifts in levels of 14 newly-identified transcripts. We conclude ORF10 contributes to more severe COVID-19 clinical outcomes in the human host.

Identification of the host reservoir of SARS-CoV-2 and determining when it spilled over into humans (preprint)

1Since the emergence of SARS-CoV-2 in Wuhan in 2019 its host reservoir has not been established. Phylogenetic analysis was performed on whole genome sequences (WGS) of 71 coronaviruses and a Breda virus. A subset comprising two SARS-CoV-2 Wuhan viruses and 8 of the most closely related coronavirus sequences were used for host reservoir analysis using Bayesian Evolutionary Analysis Sampling Trees (BEAST). Within these genomes, 20 core genome fragments were combined into 2 groups each with similar clock rates (5.9x10-3 and 1.1x10-3 subs/site/year). Pooling the results from these fragment groups yielded a most recent common ancestor (MRCA) shared between SARS-COV-2 and the bat isolate RaTG13 around 2007 (95% HPD: 2003, 2011). Further, the host of the MRCA was most likely a bat (probability 0.64 - 0.87). Hence, the spillover into humans must have occurred at some point between 2007 and 2019 and bats may have been the most likely host reservoir.

Changes in the epidemiological profile of pituitary stalk thickening among pediatric population in Chile during COVID-19 pandemic (preprint)

Purpose Pituitary stalk thickening (PST) is a rare disease affecting mainly adults. Pediatric cases are infrequent. The aim of this study is to evaluate the frequency of pediatric patients with PST during the pandemic outbreak of COVID-19 in Chile and compare it with previous data. Methods A retrospective chart review was conducted in patients with PST diagnosed during COVID-19 outbreak. Patients <18 years with pituitary stalk width of 3mm or more at pituitary insertion and/or 4mm or more at optic chiasm were included. In order to characterize and compare these cases with those already published, a review of the literature was performed. Results Nine patients were diagnosed with PST. Seven were girls. Mean age at the onset of symptoms was 10.36 years (2.4-17). Germinal cell tumors (GCT) were diagnosed in 8 patients and Langerhans cell histiocytosis in one. All patients had negative tumor markers, arginine-vasopressin deficiency (AVD) and at least one anterior pituitary hormonal deficit at diagnosis. Diagnoses were confirmed histologically in all patients, and four required a second biopsy. We found a frequency of 4 patients per year with PST due to GCT which is twice the one expected in the same population in Chile. Conclusion A surprisingly high frequency of PST presented during the COVID-19 pandemic among Chilean pediatric patients, being GCT the most frequent etiology. The reasons behind this increase in reported cases are still to be elucidated.

PROTOCOLO TRANSDIAGNÓSTICO PSICAP DE ENTRENAMIENTO COGNITIVO-CONDUCTUAL EN GRUPO PARA TRASTORNOS EMOCIONALES

The PsicAP clinical trial showed that adding 7 sessions of group cognitive-behavioural training with a transdiagnostic approach to the usual treatment of emotional disorders in adult primary care patients increased efficacy and cost-effectiveness in reducing symptom levels, reduced disability and improved quality of life. In this work, these seven sessions of the PsicAP protocol of transdiagnostic treatment are described, aimed at intervening on the factors common to the different disorders: cognitive distortions and emotional regulation strategies. En España, las comunidades autónomas que están tratando a pacientes de atención primaria con trastornos de ansiedad y depresión aplicando el protocolo PsicAP, objetivo de esta publicación, en su práctica clínica habitual (Madrid y Navarra) están obteniendo resultados similares a los obtenidos en el ensayo clínico y están atendiendo cada año a un mayor número de personas (Vázquez, 2019). Con el tiempo, han ido centrando cada vez más su atención en problemas que son interpretados como amenaza, magnificándolos, activándose de manera creciente a nivel fisiológico, llegando a un mayor grado de malestar y descontrol, que muchas veces dificulta la conducta adaptativa. En cambio, el aprendizaje de información y habilidades cognitivas, emocionales y conductuales para manejar los problemas de la vida parece estar en la base de las técnicas cognitivo-conductuales, que han obtenido mayor evidencia empírica a favor del tratamiento de diferentes trastornos emocionales, como los trastornos de ansiedad y del estado de ánimo (González-Blanch, et al., 2021a;Priede-Díaz et al., 2021).

Structure-Based Discovery of Inhibitors of the SARS-CoV-2 Nsp14 N7-Methyltransferase.

An under-explored target for SARS-CoV-2 is the S-adenosyl methionine (SAM)-dependent methyltransferase Nsp14, which methylates the N7-guanosine of viral RNA at the 5'-end, allowing the virus to evade host immune response. We sought new Nsp14 inhibitors with three large library docking strategies. First, up to 1.1 billion lead-like molecules were docked against the enzyme's SAM site, leading to three inhibitors with IC50 values from 6 to 50 µM. Second, docking a library of 16 million fragments revealed 9 new inhibitors with IC50 values from 12 to 341 µM. Third, docking a library of 25 million electrophiles to covalently modify Cys387 revealed 7 inhibitors with IC50 values from 3.5 to 39 µM. Overall, 32 inhibitors encompassing 11 chemotypes had IC50 values < 50 µM and 5 inhibitors in 4 chemotypes had IC50 values < 10 µM. These molecules are among the first non-SAM-like inhibitors of Nsp14, providing starting points for future optimization.

Progress in the Typhoid Conjugate Vaccine Program Rollout Supported by Gavi During the COVID-19 Pandemic and the Path Forward.

Gavi supports countries to introduce typhoid conjugate vaccine (TCV) with catch-up campaigns. Available TCVs are highly efficacious, equity-focused, and critical to curbing the expansion of antimicrobial resistance. Four Gavi-supported countries have introduced TCVs since 2018. In the wake of the COVID-19 emergency, momentum is building to scale up TCV introduction worldwide, supported by global partners and Gavi's funding for improved typhoid diagnostics.

Hydroxytyrosol and Arginine as Antioxidant, Anti-Inflammatory and Immunostimulant Dietary Supplements for COVID-19 and Long COVID.

Phytochemicals from plant extracts are becoming increasingly popular in the world of food science and technology because they have positive effects on human health. In particular, several bioactive foods and dietary supplements are being investigated as potential treatments for chronic COVID. Hydroxytyrosol (HXT) is a natural antioxidant, found in olive oil, with antioxidant anti-inflammatory properties that has been consumed by humans for centuries without reported adverse effects. Its use was approved by the European Food Safety Authority as a protective agent for the cardiovascular system. Similarly, arginine is a natural amino acid with anti-inflammatory properties that can modulate the activity of immune cells, reducing the production of pro-inflammatory cytokines such as IL-6 and TNF-α. The properties of both substances may be particularly beneficial in the context of COVID-19 and long COVID, which are characterised by inflammation and oxidative stress. While l-arginine promotes the formation of •NO, HXT prevents oxidative stress and inflammation in infected cells. This combination could prevent the formation of harmful peroxynitrite, a potent pro-inflammatory substance implicated in pneumonia and COVID-19-associated organ dysfunction, as well as reduce inflammation, improve immune function, protect against free radical damage and prevent blood vessel injury. Further research is needed to fully understand the potential benefits of HXT and arginine in the context of COVID-19.

RNA Regulatory Networks 2.0.

The central role of RNA molecules in cell biology has been an expanding subject of study since the proposal of the "RNA world" hypothesis 60 years ago [...].

The Omicron Sub-Variant BA.4 Displays a Remarkable Lack of Clinical Signs in a Golden Syrian Hamster Model of SARS-CoV-2 Infection.

The ongoing emergence of SARS-CoV-2 virus variants remains a source of concern because it is accompanied by the potential for increased virulence as well as evasion of immunity. Here we show that, although having an almost identical spike gene sequence as another Omicron variant (BA.5.2.1), a BA.4 isolate lacked all the typical disease characteristics of other isolates seen in the Golden Syrian hamster model despite replicating almost as effectively. Animals infected with BA.4 had similar viral shedding profiles to those seen with BA.5.2.1 (up to day 6 post-infection), but they all failed to lose weight or present with any other significant clinical signs. We hypothesize that this lack of detectable signs of disease during infection with BA.4 was due to a small (nine nucleotide) deletion (∆686-694) in the viral genome (ORF1ab) responsible for the production of non-structural protein 1, which resulted in the loss of three amino acids (aa 141-143).

Effect of COVID-19 pandemic on municipal solid waste generation: a case study in Granada city (Spain).

The 2020 coronavirus pandemic has involved a series of political and social measures that have been adapted to the spread of the disease. Apart from the severe effects on health sector, the most effects of the pandemic have been felt in households and day-to-day life. Consequently, COVID-19 has had a significant impact on the generation of not only medical and health care waste but also of municipal solid waste production and composition. In this context, this work studied the implications of COVID-19 for municipal solid waste generation in Granada, Spain. Granada is a city where the economy is based mainly on the services sector, tourism and the University. Therefore, the impact of COVID-19 pandemic has greatly affected the city and it can be analyzed through the municipal solid waste generation. For the study of the incidence of COVID-19 in the generation of waste a period that goes from March 2019 to February 2021 has been chosen. The results show that, in the global calculation, a decrease in the generation of waste in the city is observed in this last year, reaching - 13.8%. Regarding the organic-rest fraction, the decrease in the COVID year represents - 11.7%. However, bulky waste has shown an increase in the COVID year which may be related to higher home furnishings renovation rates than in other years. Finally, glass is the waste flow that best indicates the effect of COVID in the service sector. In leisure areas, a significant reduction in the collection of glass is observed (- 45%). Supplementary Information: The online version contains supplementary material available at 10.1007/s10163-023-01671-2.

COVID vaccine evaluation of barriers and resources among families of children with diagnosed allergies.

Background: We aimed to determine vaccine hesitancy and the main barriers associated with the 2019 novel coronavirus, SARS-CoV-2 (COVID-19) vaccination among families of children diagnosed with food/drug/environmental allergies. Methods: Between May and June 2021, we approached 146 families seen at the outpatient allergy clinic at the Montreal Children's Hospital and a community allergy practice were invited to complete an anonymous online survey on COVID-19 and vaccination attitudes and behaviour. Uni and multivariable logistic regressions were compared to estimate factors associated with vaccine hesitancy. Results: Among all patients, 24.1% reported vaccine hesitancy. The large majority of parents (95.2%) believed that vaccines work. The most common barrier to vaccination was fear of adverse side effects (57.0%). One-third of participants (31.5%) reported that a history of food, venom and drug allergy was a contraindication for COVID-19 vaccination. Fifty-nine (60.8%) participants stated that the dissemination of additional information would increase their willingness to be vaccinated. Most (96.9%) parents reported that their children's vaccinations were up to date. Hesitant families were more likely to be parents of children aged 6-10 years, be of Asian descent, report that mRNA vaccines are riskier than traditional vaccines, and report that the vaccine should not be given if the child has a history of allergic reaction to vaccines. Conclusion: Vaccine hesitancy exists mainly among certain ethnic groups and families with young children. Allergies to food, venom and drug allergy are commonly perceived as contraindications for COVID-19 vaccination. Knowledge translation activities addressing parental concerns will help increase vaccination rates.

Computer vision syndrome-related symptoms in presbyopic computer workers.

PURPOSE: To evaluate the prevalence of computer vision syndrome (CVS)-related symptoms in a presbyopic population using the computer as the main work tool, as well as the relationship of CVS with the electronic device use habits and the ergonomic factors. METHODS: A sample of 198 presbyopic participants (aged 45-65 years) who regularly work with a computer completed a customised questionnaire divided into: general demographics, optical correction commonly used and for work, habits of electronic devices use, ergonomic conditions during the working hours and CVS-related symptoms during work performance. A total of 10 CVS-related symptoms were questioned indicating the severity with which they occurred (0-4) and the median total symptom score (MTSS) was calculated as the sum of the symptoms. RESULTS: The MTSS in this presbyopic population is 7 ± 5 symptoms. The most common symptoms reported by participants are dry eyes, tired eyes and difficulties in refocusing. MTSS is higher in women (p < 0.05), in laptop computer users (p < 0.05) and in teleworkers compared to office workers (p < 0.05). Regarding ergonomic conditions, MTSS is higher in participants who do not take breaks while working (p < 0.05), who have an inadequately lighting in the workspace (p < 0.05) and in the participants reporting neck (p < 0.01) or back pain (p < 0.001). CONCLUSION: There is a relationship between CVS-related symptoms, the use of electronic devices and the ergonomic factors, which indicates the importance of adapting workplaces, especially for home-based teleworkers, and following basic visual ergonomics rules.

Gastrointestinal symptoms and complications in patients hospitalized due to COVID-19, an international multicentre prospective cohort study (TIVURON project).

BACKGROUND: Retrospective studies suggest that coronavirus disease (COVID-19) commonly involves gastrointestinal (GI) symptoms and complications. Our aim was to prospectively evaluate GI manifestations in patients hospitalized for COVID-19. METHODS: This international multicentre prospective cohort study recruited COVID-19 patients hospitalized at 31 centres in Spain, Mexico, Chile, and Poland, between May and September 2020. Patients were followed-up until 15 days post-discharge and completed comprehensive questionnaires assessing GI symptoms and complications. A descriptive analysis as well as a bivariate and multivariate analysis were performer using binary logistic regression. p<0.05 was considered significant. RESULTS: Eight hundred twenty-nine patients were enrolled; 129 (15.6%) had severe COVID-19, 113 (13.7%) required ICU admission, and 43 (5.2%) died. Upon admission, the most prevalent GI symptoms were anorexia (n=413; 49.8%), diarrhoea (n=327; 39.4%), nausea/vomiting (n=227; 27.4%), and abdominal pain (n=172; 20.7%), which were mild/moderate throughout the disease and resolved during follow-up. One-third of patients exhibited liver injury. Non-severe COVID-19 was associated with ≥2 GI symptoms upon admission (OR 0.679; 95% CI 0.464-0.995; p=0.046) or diarrhoea during hospitalization (OR 0.531; 95% CI 0.328-0.860; p=0.009). Multivariate analysis revealed that worse hospital outcomes were not independently associated with liver injury or GI symptoms. CONCLUSION: GI symptoms were more common than previously documented, and were mild, rapidly resolved, and not independently associated with COVID-19 severity. Liver injury was a frequent complication in hospitalized patients not independently associated with COVID-19 severity.

Outbreak report of SARS-CoV-2 infection by airborne transmission: Epidemiologic and molecular evidence. / Reporte de un brote de infección por SARS-CoV-2 por transmisión aérea: evidencia epidemiológica y molecular

INTRODUCTION: It has been shown that the transmission of SARS-CoV-2 occurs mainly by air, and the risk of infection is greater in closed spaces. OBJECTIVE: To describe the epidemiology, virology and molecular characterization of a COVID-19 outbreak at a closed vaccination point during the third wave of SARS-CoV-2 in Colombia. MATERIALS AND METHODS: Diagnostic tests, interviews, sampling, cell cultures and viral sequencing were carried out, the latter being molecular characterization and lineage identification. RESULTS: Seven workers were positive for SARS-CoV-2; among these, 3 samples were analyzed, plus an additional sample belonging to the mother of the presumed index case; all samples were identified with lineage B.1.625, with a maximum of 2 nucleotides difference between them. CONCLUSIONS: Variant B.1.625 was identified as the cause of the COVID-19 outbreak, and a co-worker was also identified as the index case. Unexpectedly, attending a vaccination day became a risk factor for acquiring the infection.

Introducción. Se ha demostrado que la transmisión de SARS-CoV-2 se produce principalmente por vía aérea y el riesgo de infección es mayor en espacios cerrados con alta concentración de personas; este último factor se presentó en algunos de los puestos de vacunación de la ciudad de Medellín. Objetivo. Describir la epidemiología, virología y caracterización molecular de un brote de COVID-19 en un punto de vacunación cerrado durante la tercera ola de SARS-CoV-2 en Colombia. Materiales y métodos. Se realizaron test diagnósticos, entrevistas, toma de muestras, aislamiento viral y secuenciación genómica. Con esta última, se hizo la caracterización molecular y se identificó el linaje. Resultados. Siete trabajadores fueron positivos para SARS-CoV-2, y de estos, tres muestras fueron secuenciadas, más una muestra adicional perteneciente a la madre del presunto caso índice. Todas las muestras fueron identificadas con el linaje B.1.625, con un máximo de dos nucleótidos de diferencia entre ellas. Conclusiones. Se identificó la variante B.1.625 como la causante del brote de COVID-19, y también un compañero de trabajo fue identificado como el caso índice. De forma imprevista, asistir a una jornada de vacunación se convirtió en un factor de riesgo para adquirir la infección.

Assessment of SARS-CoV-2 neutralizing antibody titers in breastmilk from convalescent and vaccinated mothers.

Breastmilk contains antibodies that could protect breastfed infants from infections. In this work, we examined if antibodies in breastmilk could neutralize SARS-CoV-2 in 84 breastmilk samples from women that were either vaccinated (Comirnaty, mRNA-1273, or ChAdOx1), infected with SARS-CoV-2, or both infected and vaccinated. The neutralization capacity of these sera was tested using pseudotyped vesicular stomatitis virus carrying either the Wuhan-Hu-1, Delta, or BA.1 Omicron spike proteins. We found that natural infection resulted in higher neutralizing titers and that neutralization correlated positively with levels of immunoglobulin A in breastmilk. In addition, significant differences in the capacity to produce neutralizing antibodies were observed between both mRNA-based vaccines and the adenovirus-vectored ChAdOx1 COVID-19 vaccine. Overall, our results indicate that breastmilk from naturally infected women or those vaccinated with mRNA-based vaccines contains SARS-CoV-2 neutralizing antibodies that could potentially provide protection to breastfed infants from infection.

Digital Transformation and Local Government Response to the COVID-19 Pandemic: An Assessment of Its Impact on the Sustainable Development Goals.

This paper analyzes how Digital Transformation (DT) processes have influenced the Attitude of local governments (LGs) toward the COVID-19 pandemic and their effect on achieving the United Nations' Sustainable Development Goals (SDGs). The data were collected from LGs in Spain (n = 124) through a questionnaire in which the IT skills of their workers, the DT processes, budgets, degree of regulatory compliance, and implementation of trust seals were measured, together with the IT security measures adopted. The contrast between the proposed model and the results showed that the direct influence of IT security influences the government's attitude toward COVID-19 and DT implementing actions to achieve SDGs. The findings of this work are of great value both for the actors involved in the design and implementation of public policies and for those responsible for local governance in their objective to improve citizens' experience of the services provided and in exceptional situations such as the one experienced as a result, of-COVID-19.

Inborn Error of STAT2-Dependent IFN-I Immunity in a Patient Presented with Hemophagocytic Lymphohistiocytosis and Multisystem Inflammatory Syndrome in Children.

Human inborn errors of immunity (IEI) affecting the type I interferon (IFN-I) induction pathway have been associated with predisposition to severe viral infections. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome that has been increasingly associated with inborn errors of IFN-I-mediated innate immunity. Here is reported a novel case of complete deficiency of STAT2 in a 3-year-old child that presented with typical features of HLH after mumps, measles, and rubella vaccination at the age of 12 months. Due to the life-threatening risk of viral infection, she received SARS-CoV-2 mRNA vaccination. Unfortunately, she developed multisystem inflammatory syndrome in children (MIS-C) after SARS-CoV-2 infection, 4 months after the last dose. Functional studies showed an impaired IFN-I-induced response and a defective IFNα expression at later stages of STAT2 pathway induction. These results suggest a possible more complex mechanism for hyperinflammatory reactions in this type of patients involving a possible defect in the IFN-I production. Understanding the cellular and molecular links between IFN-I-induced signaling and hyperinflammatory syndromes can be critical for the diagnosis and tailored management of these patients with predisposition to severe viral infection.

"Acute kidney injury in critically ill patients with COVID-19: The AKICOV multicenter study in Catalonia".

This study describes the incidence, evolution and prognosis of acute kidney injury (AKI) in critical COVID-19 during the first pandemic wave. We performed a prospective, observational, multicenter study of confirmed COVID-19 patients admitted to 19 intensive care units (ICUs) in Catalonia (Spain). Data regarding demographics, comorbidities, drug and medical treatment, physiological and laboratory results, AKI development, need for renal replacement therapy (RRT) and clinical outcomes were collected. Descriptive statistics and logistic regression analysis for AKI development and mortality were used. A total of 1,642 patients were enrolled (mean age 63 (15.95) years, 67.5% male). Mechanical ventilation (MV) was required for 80.8% and 64.4% of these patients, who were in prone position, while 67.7% received vasopressors. AKI at ICU admission was 28.4% and increased to 40.1% during ICU stay. A total of 172 (10.9%) patients required RRT, which represents 27.8% of the patients who developed AKI. AKI was more frequent in severe acute respiratory distress syndrome (ARDS) ARDS patients (68% vs 53.6%, p<0.001) and in MV patients (91.9% vs 77.7%, p<0.001), who required the prone position more frequently (74.8 vs 61%, p<0.001) and developed more infections. ICU and hospital mortality were increased in AKI patients (48.2% vs 17.7% and 51.1% vs 19%, p <0.001) respectively). AKI was an independent factor associated with mortality (IC 1.587-3.190). Mortality was higher in AKI patients who required RRT (55.8% vs 48.2%, p <0.04). Conclusions There is a high incidence of AKI in critically ill patients with COVID-19 disease and it is associated with higher mortality, increased organ failure, nosocomial infections and prolonged ICU stay.

The impact of government actions and risk perception on the promotion of self-protective behaviors during the COVID-19 pandemic.

INTRODUCTION: We aim to understand the factors that drive citizens of different countries to adhere to recommended self-protective behaviors during the COVID-19 pandemic. METHODS: Survey data was obtained through the COVID-19 Impact project. We selected countries that presented a sufficiently complete time series and a statistically relevant sample for running the analysis: Cyprus, Germany, Greece, Ireland, Latvia, Spain, Switzerland, the United Kingdom, and the United States of America. To identify country-specific differences in self-protective behaviors, we used previous evidence and change-point detection analysis to establish variations across participating countries whose effect was then assessed by means of interrupted series analysis. RESULTS: A high level of compliance with health and governmental authorities' recommendations were generally observed in all included countries. The level of stress decreased near the period when countries such as Cyprus, Greece or the United Kingdom relaxed their prevention behavior recommendations. However, this relaxation of behaviors did not occur in countries such as Germany, Ireland, or the United States. As observed in the change-point detection analysis, when the daily number of recorded COVID-19 cases decreased, people relaxed their protective behaviors (Cyprus, Greece, Ireland), although the opposite trend was observed in Switzerland. DISCUSSION: COVID-19 self-protective behaviors were heterogeneous across countries examined. Our findings show that there is probably no single winning strategy for exiting future health crises, as similar interventions, aimed to promote self-protective behaviors, may be received differently depending on the specific population groups and on the particular geographical context in which they are implemented.