LIMITED INDUCTION OF LUNG-RESIDENT MEMORY T CELLS BY SARS-CoV-2 mRNA VACCINATION

Background: Resident memory T cells (TRM) present at the respiratory tract may be essential to enhance early SARS-CoV-2 viral clearance, thus limiting viral infection and disease. While long-term antigen-specific TRM are detectable beyond 11 months in the lung of convalescent COVID-19 patients after mild and severe infection, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. Method(s): We obtained cross-sectional paired blood and lung biopsy samples from patients (n=30) undergoing lung resection for various reasons and assigned them to one of four groups: I.) uninfected unvaccinated individuals (n=5), II.) unvaccinated long-term SARS-CoV-2 convalescent individuals (between 6.0-10.5 months post-infection;n=9), III.) uninfected and long-term vaccinated individuals (between 6.0-7.7 months after the second or third dose;n=10), and IV.) uninfected and short-term vaccinated individuals (between 1.3-1.8 months after the third or fourth dose;n=6). We determined the presence of SARS-CoV-2-specific CD4+ and CD8+ T cells in blood and lung samples after exposure of cells to M, N, and S peptide pools, followed by flow cytometry to detect TRM cells expressing interferon (IFN)gamma and/or CD107a, as a degranulation marker. Result(s): We found that the frequency of CD4+ T cells secreting IFNgamma in response to S-peptides was variable but detectable in blood and lung up to 8 months after mRNA vaccination. Moreover, the IFNgamma response of CD4+ T cells in the lung of mRNA-vaccinated patients was similar to the response found in convalescent patients. However, in mRNA-vaccinated patients, lung responses presented less frequently with a TRM phenotype compared to convalescent infected individuals and, strikingly, polyfunctional CD107a+ IFNgamma+ TRM were virtually absent in vaccinated patients. Conclusion(s): mRNA vaccines might induce memory responses within the lung parenchyma in some patients, potentially contributing to the overall disease control. However, the robust and broad TRM response established in convalescent-infected individuals may offer advantages at limiting disease if the virus is not blocked by initial mechanisms of protection, such as neutralization. Our results warrant investigation of mucosal vaccine-induced resident T cell responses in establishing superior site-specific protective immunity.

Application of Project-Based Learning to Improve the Teaching and Learning Outcomes of a Course in Information System Design in a Computer Science Department

A proposal to use the well-known Project-based Learning method together with modern digital tools to improve the learning outcomes of computer science students, considering the COVID-19 pandemic context, is summarized here. The Kruchten's "4 + 1" model of IEEE 1471-2000 standard was used to describe the architecture of the software systems that were developed by the students. The methodology is quantitative with a quasi-experimental design, the population is made up of two groups from the Information Systems Design course, one was the experimental group and the other the control group. The results show a significant improvement in the learning outcomes of the students of the experimental group, in procedural and conceptual dimensions, in relation to the control group.

Oral ivermectin effectiveness in the treatment of permethrin-resistant scabies: a descriptive and retrospective observational study

Background and importanceIvermectin is used as a therapeutic alternative for permethrin-resistant scabies. The recommended treatment consists of administering two single doses (SD) separated by 7–14 days. An increased incidence and resistance to permethrin was observed in late 2020 possibly influenced by the SARS-CoV-2 pandemic.Aim and objectivesTo assess the effectiveness of oral ivermectin as a treatment for topical 5% permethrin-resistant scabies in patients from a tertiary hospital and to analyse the characteristics of the sample and the treatment.Material and methodsAn observational, retrospective and descriptive study was done including patients who collected ivermectin 3 mg tablets in the Hospital Outpatient Pharmaceutical Care Unit between April 2020 and April 2021. All patients were previously treated with topical 5% permethrin and treatment had failed. Ivermectin was considered effective in patients who were discharged from Dermatology Clinics or did not consult for itching or other symptoms in the following 4 weeks after the last dose. Other variables were: number of doses, age, sex and familiar history or cohabiting cases of scabies.ResultsA total of 37 patients were included and 39 applications were made. There were 16 applications from April 2020 to December 2020 (mean of 1.78±1.79 applications/month;95% CI 0.41 to 3.05) and 23 from January to April 2021 (mean of 4.6±2.6 applications/month;95% CI 1.37 to 7.83). Ivermectin was effective in 87.2% (34/39) patients and in the remaining 12.8% (5/39) therapeutic failure occurred, so they required treatment for a second time. A patient was excluded because it was unclear if treatment had been ineffective or reinfestation had occurred. 56.4% (22/39) of patients received two SD separated for 7–14 days. 58.5% (24/39) of patients were women and the mean age of the sample was 31.1±19.3 years (95% CI 26.8 to 37.4). 54.0% (21/39) of the patients were aged between 11 and 30 years, and 74.4% (29/39) had a familiar history or cohabitants within their family nucleus with scabies.Conclusion and relevanceIn our sample, ivermectin effectiveness was greater than 90% in scabies resistant to topical 5% permethrin and seems independent of the number of doses received. Results suggest that scabies mainly affects women and young people. Infections in cohabitants seem to have an increased frequency and may have been influenced by confinement and delays of treatments during the SARS-CoV-2 pandemic.References and/or acknowledgementsConflict of interestNo conflict of interest

Biologic agents for rheumatic diseases in the covid-19 outbreak: Friend or foe?

Objectives: To estimate COVID-19 infection rate in patients treated with bDMARDS due to rheumatic inflammatory diseases, determine the influence of the treatment as a risk or protective factor and studying the prognosis of rheumatic patients receiving biologic agents compared to general population in a third level Hospital setting in León, Spain. Methods: We performed an observational study including patients who received bD MARDs due to rheumatic diseases between December 1st 2019 and December 1st 2020 and examined the COVID-19 infection rate. We performed a multivariate logistic regression model to assess risk factors of COVID-19 infection Results: There was a total of 3711 patients with COVID-19 requiring hospitalization. 40 patients out of a total of 820 patients with rheumatic diseases (4.8%) receiving bD MARDs were infected witth COVID-19 and four required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 2.75%, and it was 0.48% among the group with underlying rheumatic diseases. Out of the 3711 patients, 423 patients died, 2 of which received treatment with biologic agents. Patients with rheumatic diseases who tested positive for COVID-19 were older (female: median age 60.8 IQR 46-74;male: median age 61.9 IQR 52-70.3) than those who were negative for COVID-19 (female: median age 58.3 IQR 48-69;male: median age 56.2 IQR 47-66), more likely to have hypertension (45% vs 26%, OR 2.25 (95%CI 1.14-4.27), p = 0.02), cardiovascular disease (23 % vs 9%, OR 2.85 (95%CI 1.31-6.23), p = 0.01), be smokers (13% vs 4.6%, OR 2.95 (95%CI 1.09-7.98), p = 0.04), receiving treatment with rituximab (20%vs 8%, 2.28 (CI 1.24-6.32), p = 0.02) and a higher dosage of glucocorticoids (OR 2.2 (1.2-10.23), p 0.02) and were less likely to be receiving treatment with IL-6 inhibitors (0.03% vs 14%, OR 0.16, (95%CI 0.10-0.97), p = 0.03). Patients who tested negative for COVID-19 were more likely to be treated with bDMARDs for a longer period (in months) than patients with a positive result (OR 0.54 (95%CI 0.22-0.87), p = 0.04).We found no differences in sex or rheumatological disease between patients who tested positive for COVID-19 and patients who tested negative. Conclusion: Overall, the use of bD MARDs was not associated with severe manifestations of COVID-19. Patients with rheumatic disease diagnosed with COVID-19 were more likely to be receiving a higher dose of glucocorticoids and treatment with rituximab. IL-6 inhibitors may have a protective effect.

How Spanish biobanks have adapted the informed consent process during the Covid-19 pandemic

Due to the situation caused by the Covid-19 pandemic, biobanks have adapted, among other processes, the obtaining of informed consents (IC). This paper details the most relevant elements of the applicable regulations, describes the adaptations done by some of the biobanks of the Spanish Biobank Network to manage the IC process, which have been approved by their Ethics Committees, and draws some conclusions from the results obtained from the survey carried out on these biobanks. © 2021

Characterization and Outcomes of SARS-CoV-2 Infection in Patients with Sarcoidosis.

To analyze the clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with sarcoidosis from a large multicenter cohort from Southern Europe and to identify the risk factors associated with a more complicated infection. We searched for patients with sarcoidosis presenting with SARS-CoV-2 infection (defined according to the European Centre for Disease Prevention and Control guidelines) among those included in the SarcoGEAS Registry, a nationwide, multicenter registry of patients fulfilling the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders 1999 classification criteria for sarcoidosis. A 2:1 age-sex-matched subset of patients with sarcoidosis without SARS-CoV-2 infection was selected as control population. Forty-five patients with SARS-CoV-2 infection were identified (28 women, mean age 55 years). Thirty-six patients presented a symptomatic SARS-CoV-2 infection and 14 were hospitalized (12 required supplemental oxygen, 2 intensive care unit admission and 1 mechanical ventilation). Four patients died due to progressive respiratory failure. Patients who required hospital admission had an older mean age (64.9 vs. 51.0 years, p = 0.006), a higher frequency of baseline comorbidities including cardiovascular disease (64% vs. 23%, p = 0.016), diabetes mellitus (43% vs. 13%, p = 0.049) and chronic liver/kidney diseases (36% vs. 0%, p = 0.002) and presented more frequently fever (79% vs. 35%, p = 0.011) and dyspnea (50% vs. 3%, p = 0.001) in comparison with patients managed at home. Age- and sex-adjusted multivariate analysis identified the age at diagnosis of SARS-Cov-2 infection as the only independent variable associated with hospitalization (adjusted odds ratio 1.18, 95% conficence interval 1.04-1.35). A baseline moderate/severe pulmonary impairment in function tests was associated with a higher rate of hospitalization but the difference was not statistically significant (50% vs. 23%, p = 0.219). A close monitoring of SARS-CoV-2 infection in elderly patients with sarcoidosis, especially in those with baseline cardiopulmonary diseases and chronic liver or renal failure, is recommended. The low frequency of severe pulmonary involvement in patients with sarcoidosis from Southern Europe may explain the weak prognostic role of baseline lung impairment in our study, in contrast to studies from other geographical areas.

UNIVERSAL SCREENING OF COVID-19 IN ASYMPTOMATIC PATIENTS STARTING FERTILITY TREATMENT IN NEW YORK CITY

Objective: To evaluate a protocol of universal symptom and viral screening prior to initiation of controlled ovarian hyperstimulation among patients receiving care in New York City. Design: Prospective cohort study. Materials and Methods: Prior to initiation of controlled ovarian hyperstimulation for oocyte cryopreservation or in vitro fertilization cycles, patients were screened by phone for symptoms of fever, cough, sore throat, recent travel or contact with confirmed COVID cases. If negative, patients were scheduled for nasopharyngeal swabs at our center the following day, with visits spaced at 15 minute intervals to avoid crowding. Upon presentation for swab testing, patients were again screened for symptoms and fever. Nasopharyngeal swabs were collected in accordance with the Center for Disease Control (CDC) guidelines, and delivered to the university’s clinical microbiology laboratory. The swabs were tested using the Roche Cobas 6800 SARS-CoV-2 test, a qualitative assay, using real-time reverse transcriptase polymerase chain reaction (RT-PCR) test (Roche Diagnostics, USA), with results delivered in the same day. A negative test result was required prior to patients' baseline ultrasound and bloodwork the following morning. This study was conducted from April 21- May 21, 2020, Results: The study sample included 151 asymptomatic patients who were tested for SARS-CoV-2 via nasopharyngeal swab. Overall, 149 (98.68%) tested negative for COVID-19, 1 (0.66%) tested indeterminate, 2 (1.32%) tested invalid, and 0 (0%) tested positive for COVID-19. Of the 149 patients who have tested negative, 81 have successfully undergone oocyte retrieval without complications. One patient screened positive for symptoms at the time of swab presentation and was instructed to return for testing in 2 weeks. Conclusions: The incidence of COVID-19 infection among asymptomatic patients seeking fertility treatment in NYC is low. We have demonstrated that fertility care can safely resume in a way to limit risk to our patients, staff, and our physicians working in the epicenter of infection.

THE EMOTIONAL IMPACT OF THE ASRM GUIDELINES ON FERTILITY PATIENTS DURING THE COVID-19 PANDEMIC

Objective: To survey fertility patients’ agreement with ASRM recommendations during the COVID-19 pandemic and the emotional impact on them. Design: An online survey was sent to current fertility patients at a New York City academic fertility practice at the epicenter of the COVID-19 pandemic. Materials and Methods: Patient agreement with the ASRM recommendations during the COVID-19 pandemic and the emotional impact rated on a Likert scale. Ordinal data such as responses rated on a Likert scale were analyzed using Mann-Whitney Wilcoxon testing and responses were compared using Fisher exact or chi-square test as appropriate, with significance at p<0.05. Results: A total of 518 patients completed the survey for a response rate of 17%. Fifty percent of respondents had a cycle canceled due to the COVID-19 pandemic. Of those who had a cycle cancelled, 85% of respondents found it to be moderately to extremely upsetting with 22% rating it to be equivalent to the loss of a child. There was no difference on the emotional impact based on the type of cycle cancelled. Fifty-five percent of patients agreed that diagnostic procedures such as hysterosalpingograms should be cancelled while 36% of patients agreed all fertility cycles should be cancelled (22% unsure, 43% disagreed). Patients were slightly more likely to agree with the ASRM guidelines if they have an upcoming cycle cancelled (p = 0.041). Of all respondents 82% would have preferred to have the option to start a treatment cycle in consultation with their doctor. Conclusions: Given the severity of the COVID-19 pandemic, the physical, financial and emotional impact of this unprecedented threat cannot be underestimated in our fertility patients.

Plant-wide modelling in wastewater treatment: showcasing experiences using the Biological Nutrient Removal Model

Plant-wide modelling can be considered an appropriate approach to represent the current complexity in water resource recovery facilities, reproducing all known phenomena in the different process units. Nonetheless, novel processes and new treatment schemes are still being developed and need to be fully incorporated in these models. This work presents a short chronological overview of some of the most relevant plant-wide models for wastewater treatment, as well as the authors'experience in plant-wide modelling using the general model BNRM (Biological Nutrient Removal Model), illustrating the key role of general models (also known as supermodels) in the field of wastewater treatment, both for engineering and research.

Determinants of COVID-19 disease severity in patients with underlying rheumatic disease.

BACKGROUND: Over the month of April, Spain has become the European country with more confirmed cases of COVID-19 infection, after surpassing Italy on April 2nd. The community of Castile and León in Spain is one of the most affected by COVID-19 infection and the province of León has a total of 3711 cases and 425 deaths so far. Rheumatic patients should be given special attention regarding COVID-19 infection due to their immunocompromised state resulting from their underlying immune conditions and use of targeted immune-modulating therapies. Studying epidemiological and clinical characteristics of patients with rheumatic diseases infected with SARS-CoV2 is pivotal to clarify determinants of COVID-19 disease severity in patients with underlying rheumatic disease. OBJECTIVES: To describe epidemiological characteristics of patients with rheumatic diseases hospitalized with COVID-19 and determine risk factors associated with mortality in a third level Hospital setting in León, Spain. METHODS: We performed a prospective observational study, from 1st March 2020 until the 1st of June including adults with rheumatic diseases hospitalized with COVID-19 and performed a univariate and multivariate logistic regression model to estimate ORs and 95% CIs of mortality. Age, sex, comorbidities, rheumatic disease diagnosis and treatment, disease activity prior to infection, radiographic and laboratorial results at arrival were analysed. RESULTS: During the study period, 3711 patients with COVID-19 were admitted to our hospital, of whom 38 (10%) had a rheumatic or musculoskeletal disease. Fifty-three percent were women, with a mean age at hospital admission of 75.3 (IQR 68-83) years. The median length of stay was 11 days. A total of 10 patients died (26%) during their hospital admission. Patients who died from COVID-19 were older (median age 78.4 IQR 74.5-83.5) than those who survived COVID-19 (median age 75.1 IQR 69.3-75.8) and more likely to have arterial hypertension (9 [90%] vs 14 [50%] patients; OR 9 (95% CI 1.0-80.8), p 0.049), dyslipidaemia (9 (90%) vs 12 (43%); OR 12 (95% CI 1.33-108), p 0.03), diabetes ((9 (90%) vs 6 (28%) patients; OR 33, p 0.002), interstitial lung disease (6 (60%) vs 6 (21%); OR 5.5 (95% CI 1.16-26), p 0.03), cardiovascular disease (8 (80%) vs 11 (39%); OR 6.18 (95% IC 1.10-34.7, p 0.04) and a moderate/high index of rheumatic disease activity (7 (25%) vs 6(60%); OR 41.4 (4.23-405.23), p 0.04). In univariate analyses, we also found that patients who died from COVID-19 had higher hyperinflammation markers than patients who survived: C-reactive protein (181 (IQR 120-220) vs 107.4 (IQR 30-150; p 0.05); lactate dehydrogenase (641.8 (IQR 465.75-853.5) vs 361 (IQR 250-450), p 0.03); serum ferritin (1026 (IQR 228.3-1536.3) vs 861.3 (IQR 389-1490.5), p 0.04); D-dimer (12,019.8 (IQR 843.5-25,790.5) vs 1544.3 (IQR 619-1622), p 0.04). No differences in sex, radiological abnormalities, rheumatological disease, background therapy or symptoms before admission between deceased patients and survivors were found. In the multivariate analysis, the following risk factors were associated with mortality: rheumatic disease activity (p = 0.003), dyslipidaemia (p = 0.01), cardiovascular disease (p = 0.02) and interstitial lung disease (p = 0.02). Age, hypertension and diabetes were significant predictors in univariate but not in multivariate analysis. Rheumatic disease activity was significantly associated with fever (p = 0.05), interstitial lung disease (p = 0.03), cardiovascular disease (p = 0.03) and dyslipidaemia (p = 0.01). CONCLUSIONS: Our results suggest that comorbidities, rheumatic disease activity and laboratorial abnormalities such as C-reactive protein (CRP), D-Dimer, lactate dehydrogenase (LDH), serum ferritin elevation significantly associated with mortality whereas previous use of rheumatic medication did not. Inflammation is closely related to severity of COVID-19. Key Points • Most patients recover from COVID-19. • The use of DMARDs, corticosteroids and biologic agents did not increase the odds of mortality in our study. • Rheumatic disease activity might be associated with mortality.