Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19.

MDA5, encoded by the IFIH1gene, is a cytoplasmic sensor of viral RNAs that triggers interferon (IFN) antiviral responses. Common and rare IFIH1 variants have been associated with the risk of type 1 diabetes and other immune-mediated disorders, and with the outcome of viral diseases. Variants associated with reduced IFN expression would increase the risk for severe viral disease. The MDA5/IFN pathway would play a critical role in the response to SARS-CoV-2 infection mediating the extent and severity of COVID-19. Here, we genotyped a cohort of 477 patients with critical ICU COVID-19 (109 death) for three IFIH1 functional variants: rs1990760 (p.Ala946Thr), rs35337543 (splicing variant, intron 8 + 1G > C), and rs35744605 (p.Glu627Stop). The main finding of our study was a significant increased frequency of rs1990760 C-carriers in early-onset patients (< 65 years) (p = 0.01; OR = 1.64, 95%CI = 1.18-2.43). This variant was also increased in critical vs. no-ICU patients and in critical vs. asymptomatic controls. The rs35744605 C variant was associated with increased blood IL6 levels at ICU admission. The rare rs35337543 splicing variant showed a trend toward protection from early-onset critical COVID-19. In conclusion, IFIH1 variants associated with reduced gene expression and lower IFN response might contribute to develop critical COVID-19 with an age-dependent effect.

Re-imagining Early Childhood Education and School Readiness for Children and Families of Color in the Time of COVID-19 and Beyond.

High quality and culturally responsive early childhood education and care (ECEC) for young children before kindergarten is seen as a way to ensure that all children enter school ready to learn. ECEC is even more crucial in the context of recovery from the COVID-19 pandemic and the disproportionate burden of trauma and stress borne by families of color in disinvested neighborhoods. Remote learning and repeated disruptions to in-person instruction as protocols shifted during waves of the pandemic placed an extra strain on families, and may have increased educational disparities in the U.S. Taken together, these challenges have implications for children's school readiness due to their impact on opportunities for learning at home and in the classroom. This paper explores how ECEC programs can be strengthened to better meet children's needs, and ways in which future research can shed light on these important issues.

Multimorbidity Patterns and Their Association with Social Determinants, Mental and Physical Health during the COVID-19 Pandemic.

BACKGROUND: The challenge posed by multimorbidity makes it necessary to look at new forms of prevention, a fact that has become heightened in the context of the pandemic. We designed a questionnaire to detect multimorbidity patterns in people over 50 and to associate these patterns with mental and physical health, COVID-19, and possible social inequalities. METHODS: This was an observational study conducted through a telephone interview. The sample size was 1592 individuals with multimorbidity. We use Latent Class Analysis to detect patterns and SF-12 scale to measure mental and physical quality-of-life health. We introduced the two dimensions of health and other social determinants in a multinomial regression model. RESULTS: We obtained a model with five patterns (entropy = 0.727): 'Relative Healthy', 'Cardiometabolic', 'Musculoskeletal', 'Musculoskeletal and Mental', and 'Complex Multimorbidity'. We found some differences in mental and physical health among patterns and COVID-19 diagnoses, and some social determinants were significant in the multinomial regression. CONCLUSIONS: We identified that prevention requires the location of certain inequalities associated with the multimorbidity patterns and how physical and mental health have been affected not only by the patterns but also by COVID-19. These findings may be critical in future interventions by health services and governments.

Global Emergence of Resistance to Fluconazole and Voriconazole in Candida parapsilosis in Tertiary Hospitals in Spain During the COVID-19 Pandemic.

Background: Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins, and it is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole-nonsusceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last 2 years at the Spanish Mycology Reference Laboratory. Methods: Yeast were identified by molecular biology, and antifungal susceptibility testing was performed using the European Committee on Antimicrobial Susceptibility Testing protocol. The ERG11 gene was sequenced to identify resistance mechanisms, and strain typing was carried out by microsatellite analysis. Results: We examined the susceptibility profile of 1315 C. parapsilosis isolates available at our reference laboratory between 2000 and 2021, noticing an increase in the number of isolates with acquired resistance to fluconazole, and voriconazole has increased in at least 8 different Spanish hospitals in 2020-2021. From 121 recorded clones, 3 were identified as the most prevalent in Spain (clone 10 in Catalonia and clone 96 in Castilla-Leon and Madrid, whereas clone 67 was found in 2 geographically unrelated regions, Cantabria and the Balearic Islands). Conclusions: Our data suggest that concurrently with the coronavirus disease 2019 pandemic, a selection of fluconazole-resistant C. parapsilosis isolates has occurred in Spain, and the expansion of specific clones has been noted across centers. Further research is needed to determine the factors that underlie the successful expansion of these clones and their potential genetic relatedness.

Telephone Monitoring of Isolated Patients With Suspected COVID-19 Disease in Primary Care: Prospective Cohort Study.

Objective: Isolation of suspected cases of COVID-19 has been shown effective in reducing disease transmission and monitoring these patients from primary care allows to detect complications. The objective of this study is to determine the evolution of a cohort of patients with suspected COVID-19, and to analyse the factors associated with hospital admissions due to their unfavourable evolution. Methods: Prospective cohort study. A cohort of 166 patients with COVID-19 symptoms was selected and was followed-up by telephone calls during 14 days of home isolation. Results: By the end of the follow-up, a hospital admission had taken place in 14.7% of patients. The mean survival time until admission among diabetics was 12.6, 10.9 days for chronic kidney diseases, and 9.3 days in immunocompromised patients. Immunosuppression was a risk factor for admission over 50 years of age. Conclusion: Hospital admissions for suspected cases of COVID-19 are associated with diabetes, chronic kidney disease, and immunosuppression. Telephone monitoring of these patients from primary care allows for home isolation and early detection of disease complications.

Frontline Physician Perspectives on Their Experiences Working During the First Wave of the COVID-19 Pandemic.

BACKGROUND: During the first wave of the COVID-19 pandemic physicians worked on the front lines, immersed in uncertainty. Research into perspectives of frontline physicians has lagged behind clinical innovation throughout the pandemic. OBJECTIVE: To inform ongoing and future efforts in the COVID-19 pandemic, we conducted a qualitative exploration of physician perspectives of the effects of policies and procedures as well as lessons learned while caring for patients during the height of the first wave in the spring of 2020. DESIGN: A confidential survey was emailed to a convenience sample. Survey questions included demographic data, participant role in the pandemic, and geographic location. Eleven open-ended questions explored their perspectives and advice they would give going forward. Broad areas covered included COVID-19-specific education, discharge planning, unintended consequences for patient care, mental health conditions to anticipate, and personal/institutional factors influencing workforce well-being amid the crisis. PARTICIPANTS: We received fifty-five surveys from May through July 2020. Demographic data demonstrated sampling of frontline physicians working in various epicenters in the USA, and diversity in gender, race/ethnicity, and clinical specialty. APPROACH: Inductive thematic analysis. KEY RESULTS: Four themes emerged through data analysis: (1) Leadership can make or break morale; (2) Leadership should engage frontline workers throughout decision-making processes; (3) Novelty of COVID-19 led to unintended consequences in care delivery; and (4) Mental health sequelae will be profound and pervasive. CONCLUSIONS: Our participants demonstrated the benefit of engaging frontline physicians as important stakeholders in policy generation, evaluation, and revision; they highlighted challenges, successes, unintended consequences, and lessons learned from various epicenters in the first wave of the COVID-19 pandemic. There is much to be learned from the early COVID-19 pandemic crisis; our participants' insights elucidate opportunities to examine institutional performance, effect policy change, and improve crisis management in order to better prepare for this and future pandemics.

IGHG3 hinge length variation was associated with the risk of critical disease and death in a Spanish COVID-19 cohort.

IgG3 would play an important role in the immune adaptive response against SARS-CoV-2, and low plasma levels might increase the risk of COVID-19 severity and mortality. The IgG3 hinge sequence has a variable repeat of a 15 amino acid exon with common 4-repeats (M) and 3-repeats (S). This length IGHG3 polymorphism might affect the IgG3 effector functions. The short hinge length would reduce the IgG3 flexibility and impairs the neutralization and phagocytosis compared to larger length-isoforms. We genotyped the IGHG3 length polymorphism in patients with critical COVID-19 (N = 516; 107 death) and 152 moderate-severe but no-critical cases. Carriers of the S allele had an increased risk of critical ICU and mortality (p < 0.001, OR = 2.79, 95% CI = 1.66-4.65). This adverse effect might be explained by a less flexibility and reduced ability to induce phagocytosis or viral neutralization for the short length allele. We concluded that the IgG3 hinge length polymorphism could be a predictor of critical COVID-19 and the risk of death. This study was based on a limited number of patients from a single population, and requires validation in larger cohorts.

COVID-19 clinical features in primary care: COVIDPAP study⋆ Expresión clínica de la COVID-19 en pediatría de atención primaria: estudio COVIDPAP

Graphical Objectives In Spain, the tools to diagnose COVID-19 were available in primary care from May 2020. Previously most studies described inpatients or patients in A&E departments, and fever and cough were the most frequent symptoms. This study aims to define the clinical picture of the pediatric COVID-19 in the community. Methods A descriptive and analytical observational study was performed including pediatric cases (0−14 years) from 255 pediatricians, proportionally distributed to its population, from primary health centers in Spain, from 12th May 2020 to 30th April 2021. Diagnostics were made by PCR detection of viral RNA, rapid antigen detection test or positive IgG serology. Results There were 10,021 positive children included, 48.4% women, mean age 8,04 ± 4.17 years. Infection was detected due to contact tracing (70.9%), compatible symptoms (18.8%). Household was the main source of transmission (64.9%), followed by school setting (10%) or unknown (9.9%). We did not find any significant differences in the incidence between holidays and school terms. 43.2% of the children were asymptomatic. Most frequent symptoms are rhinorrhea in <2 years, fever in 3−8years and headache in >9 years. An exhaustive description of objective and subjective symptoms by age is made. 18 patients were hospitalized, one with multisystem inflammatory syndrome in children. There were no deaths. Conclusions pediatric COVID-19 is a mild disease, with a large number of asymptomatic cases, with very few hospital admissions and deaths. The main setting for transmission is the household, and school closures should be a last resource measure during the COVID-19 pandemic. A specific clinical picture of pediatric COVID-19 was not found.

COVID-19 clinical features in primary care: COVIDPAP study.

OBJECTIVES: In Spain, the tools to diagnose COVID-19 were available in primary care from May 2020. Previously most studies described inpatients or patients in A&E departments, and fever and cough were the most frequent symptoms. This study aims to define the clinical picture of the pediatric COVID-19 in the community. METHODS: A descriptive and analytical observational study was performed including pediatric cases (0-14years) from 255 pediatricians, proportionally distributed to its population, from primary health centers in Spain, from 12th May 2020 to 30th April 2021. Diagnostics were made by PCR detection of viral RNA, rapid antigen detection test or positive IgG serology. RESULTS: There were 10,021 positive children included, 48.4% women, mean age 8,04±4.17years. Infection was detected due to contact tracing (70.9%), compatible symptoms (18.8%). Household was the main source of transmission (64.9%), followed by school setting (10%) or unknown (9.9%). We did not find any significant differences in the incidence between holidays and school terms. 43.2% of the children were asymptomatic. Most frequent symptoms are rhinorrhea in <2years, fever in 3-8years and headache in >9years. An exhaustive description of objective and subjective symptoms by age is made. 18 patients were hospitalized, one with multisystem inflammatory syndrome in children. There were no deaths. CONCLUSIONS: pediatric COVID-19 is a mild disease, with a large number of asymptomatic cases, with very few hospital admissions and deaths. The main setting for transmission is the household, and school closures should be a last resource measure during the COVID-19 pandemic. A specific clinical picture of pediatric COVID-19 was not found.

Impact of SARS-Cov-2 infection in patients with hypertrophic cardiomyopathy: results of an international multicentre registry.

AIMS: To describe the natural history of SARS-CoV-2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events. METHODS AND RESULTS: Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS-Cov-2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS-CoV-2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty-nine (22.9%) HCM patients were hospitalized for non-ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS-CoV-2-related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12-4.51], P = 0.0229}, baseline New York Heart Association class [OR per one-unit increase 4.01 (95%CI: 1.75-9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16-26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20-49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community-based SARS-CoV-2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98-2.91, P = 0.0600). CONCLUSIONS: Over one-fourth of HCM patients infected with SARS-Cov-2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality.

Expresión Clínica De La Covid-19 En Pediatría De Atención Primaria: Estudio Covidpap Covid-19 Clinical Features In Primary Care: Covidpap Study

Objectives: In Spain, the tools to diagnose COVID-19 were available in primary care from May 2020. Previously most studies described inpatients or patients in A&E departments, and fever and cough were the most frequent symptoms. This study aims to define the clinical picture of the pediatric COVID-19 in the community. Methods: A descriptive and analytical observational study was performed including pediatric cases (0-14y) from 255 pediatricians, proportionally distributed to its population, from primary health centers in Spain, from 12th May 2020 to 30th April 2021. Diagnostics were made by PCR detection of viral RNA, rapid antigen detection test or positive IgG serology. Results: There were 10,021 positive children included, 48.4% women, mean age 8,04±4.17y. Infection was detected due to contact tracing (70.9%), compatible symptoms (18.8%). Household was the main source of transmission (64.9%), followed by school setting (10%) or unknown (9.9%). We did not find any significant differences in the incidence between holidays and school terms. 43.2% of the children were asymptomatic. Most frequent symptoms are rhinorrhea in < 2y, fever in 3-8y and headache in >9y. An exhaustive description of objective and subjective symptoms by age is made. 18 patients were hospitalized, one with multisystem inflammatory syndrome in children. There were no deaths. Conclusions: Pediatric COVID-19 is a mild disease, with a large number of asymptomatic cases, with very few hospital admissions and deaths. The main setting for transmission is the household, and school closures should be a last resource measure during the COVID-19 pandemic. A specific clinical picture of pediatric COVID-19 was not found.

Relationships of People with Intellectual Disabilities in Times of Pandemic: An Inclusive Study

(1) Background: Since 2012, our Inclusive Research Team has developed several studies on various topics that interest the co-researchers with intellectual disabilities. In 2021, throughout the COVID-19 pandemic, the co-researchers decided to investigate the impact of the pandemic on the relationships of people with intellectual disabilities. The aim of this article is to disseminate how this inclusive study was developed and to explain its results;(2) Methods: Co-researchers and academic researchers met six times to make different decisions: decide on the research topic;discuss the topic;prepare an interview script for people with intellectual disabilities;analyse the data obtained;and decide how to disseminate the results of the research. The co-researchers interviewed 10 people with intellectual disabilities and participated as facilitators in 3 focus groups;(3) Results: During the pandemic, digital devices have enabled people with intellectual disabilities to maintain their social relationships. However, the lack of access or support in using them, as well as the restrictions imposed on people with intellectual disabilities living in institutions, have presented significant barriers to maintaining their social relationships;(4) Conclusions: This article shows the difficulties people with intellectual disabilities face in maintaining successful social relationships in times of pandemic, and how we undertook research in an inclusive, virtual manner.

The Effects of Covid-19 on Science Education: A Thematic Review of International Research

The health emergency caused by the COVID-19 pandemic has transformed and decisively affected the entire education system, which has resulted in an urgent need to adapt it to an online scenario. Science education is an area that has been highly affected by and, as a consequence, science teachers were forced to make an extra effort to create virtual learning environments accessible for all students. This study offers a systematic review to synthesize how the COVID-19 pandemic has influenced science teachers’ educational practices and adaptations. To this end, Web of Science, ERIC and Scopus databases used to explore the virtual educational practices, e.g., teaching-learning processes, during the pandemic. The purpose of this study is to analyze the main bibliographic characteristics of the collected literature (research purpose, methodological design, geographical and temporal distribution, central themes) via thematic analysis. The findings offered a synthesis of studies that explain innovative practices, tools, and strategies that were very useful for teachers and students in the STEM area. We believe that future lines of research should be oriented towards broadening the analysis of different pedagogical approaches developed in the teaching of STEM areas during the health crisis by COVID-19. This could be useful for guiding professional and educational actions.

Association between the interferon-induced transmembrane protein 3 gene (IFITM3) rs34481144 / rs12252 haplotypes and COVID-19.

The interferon induced transmembrane-protein 3 (IFITM3) plays an important role in the defence against viral infection. IFITM3 gene variants have been linked to differences in expression and associated with the risk of severe influenza by some authors. More recently, these variants have been associated with the risk of COVID-19 after SARS-CoV-2 infection. We determined the effect of two common IFITM3 polymorphisms (rs34481144 â€‹C/T and rs12252 A/G) on the risk of hospitalization due to COVID-19 by comparing 484 patients (152 required support in thr intensive care unit, ICU) and 182 age and sex matched controls (no disease symptoms). We found significantly higher frequencies of rs34481144 â€‹T and rs12252 â€‹G carriers among the patients (OR â€‹= â€‹2.02 and OR â€‹= â€‹1.51, respectively). None of the two variants were associated with ICU-admission or death. We found a significantly higher frequency of rs34481144 CC â€‹+ â€‹rs12252 AA genotype carriers among the controls, suggesting a protective effect (p = 0.001, OR = 0.56, 95%CI = 0.40-0.80). Moreover, haplotype rs34481144 â€‹C - rs12252 A was significantly increased in the controls (p â€‹= â€‹0.008, OR â€‹= â€‹0.71, 95%CI â€‹= â€‹0.55-0.91). Our results showed a significant effect of the IFITM3 variants in the risk for hospitalization after SARS-CoV-2 infection.

SARS-CoV-2 could be spread through hospital medication dispensed to patients: A prospective observational study.

ABSTRACT: Our objective was to analyze in vitro the persistence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the packaging material of the drugs dispensed to hospital wards. Additionally, to evaluate if the protection with a double plastic bag prevents the contamination of the medication dispensed to an intensive care unit (ICU).On the first part, different materials containing different drugs within an ICU were sampled to confirm the lack of contamination by SARS-CoV-2. The confirmation of the virus was performed using real time reverse transcription polymerase chain reaction. As a control group, in the microbiology laboratory we inoculated the virus into the different surfaces containing the same drugs included in the first part. Samples were obtained with a sterile swab at 3, 6, 8, 10, 14, 21, and 30 days after inoculation and analyzed through real time reverse transcription polymerase chain reaction.None of the studied materials containing the drugs within an ICU was contaminated by SARS-CoV-2. In the second part, SARS-CoV-2 was found in all surfaces for up to 30 days.The use of double-bag unit-dose system to deliver medication in a pandemic seems effective to prevent the potential transmission of SARS-CoV-2. A striking SARS-CoV-2 RNA stability of up to 30 days was found in the surfaces containing the drugs.

Real-Life Impact of Glucocorticoid Treatment in COVID-19 Mortality: A Multicenter Retrospective Study.

We aimed to determine the impact of steroid use in COVID-19 in-hospital mortality, in a retrospective cohort study of the SEMICOVID19 database of admitted patients with SARS-CoV-2 laboratory-confirmed pneumonia from 131 Spanish hospitals. Patients treated with corticosteroids were compared to patients not treated with corticosteroids; and adjusted using a propensity-score for steroid treatment. From March-July 2020, 5.262 (35.26%) were treated with corticosteroids and 9.659 (64.73%) were not. In-hospital mortality overall was 20.50%; it was higher in patients treated with corticosteroids than in controls (28.5% versus 16.2%, OR 2.068 [95% confidence interval; 1.908 to 2.242]; p = 0.0001); however, when adjusting by occurrence of ARDS, mortality was significantly lower in the steroid group (43.4% versus 57.6%; OR 0.564 [95% confidence interval; 0.503 to 0.633]; p = 0.0001). Moreover, the greater the respiratory failure, the greater the impact on mortality of the steroid treatment. When adjusting these results including the propensity score as a covariate, in-hospital mortality remained significantly lower in the steroid group (OR 0.774 [0.660 to 0.907], p = 0.002). Steroid treatment reduced mortality by 24% relative to no steroid treatment (RRR 0.24). These results support the use of glucocorticoids in COVID-19 in this subgroup of patients.

Variant-genetic and transcript-expression analysis showed a role for the chemokine-receptor CCR5 in COVID-19 severity.

The chemokine receptor CCR5 has been implicated in COVID-19. CCR5 and its ligands are overexpressed in patients. The pharmacological targeting of CCR5 would improve the COVID-19 severity. We sought to investigate the role of the CCR5-Δ32 variant (rs333) in COVID-19. The CCR5-Δ32 was genotyped in 801 patients (353 in the intensive care unit, ICU) and 660 healthy controls, and the deletion was significantly less frequent in hospitalysed COVID-19 than in healthy controls (p = 0.01, OR = 0.66, 95%CI = 0.49-0.88). Of note, we did not find homozygotes among the patients, compared to 1% of the controls. The CCR5 transcript was measured in leukocytes from 85 patients and 40 controls. We found a significantly higher expression of the CCR5 transcript among the patients, with significant difference when comparing the non-deletion carriers (controls = 35; patients = 81; p = 0.01). ICU-patients showed non-significantly higher expression than no-ICU cases. Our study points to CCR5 as a genetic marker for COVID-19. The pharmacological targeting of CCR5 should be a promising treatment for COVID-19.