Multi-objective Evolutionary Discretization of Gene Expression Profiles: Application to COVID-19 Severity Prediction

Machine learning models can use information from gene expressions in patients to efficiently predict the severity of symptoms for several diseases. Medical experts, however, still need to understand the reasoning behind the predictions before trusting them. In their day-to-day practice, physicians prefer using gene expression profiles, consisting of a discretized subset of all data from gene expressions: in these profiles, genes are typically reported as either over-expressed or under-expressed, using discretization thresholds computed on data from a healthy control group. A discretized profile allows medical experts to quickly categorize patients at a glance. Building on previous works related to the automatic discretization of patient profiles, we present a novel approach that frames the problem as a multi-objective optimization task: on the one hand, after discretization, the medical expert would prefer to have as few different profiles as possible, to be able to classify patients in an intuitive way;on the other hand, the loss of information has to be minimized. Loss of information can be estimated using the performance of a classifier trained on the discretized gene expression levels. We apply one common state-of-the-art evolutionary multi-objective algorithm, NSGA-II, to the discretization of a dataset of COVID-19 patients that developed either mild or severe symptoms. The results show not only that the solutions found by the approach dominate traditional discretization based on statistical analysis and are more generally valid than those obtained through single-objective optimization, but that the candidate Pareto-optimal solutions preserve the sense-making that practitioners find necessary to trust the results. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Health Economic Evaluation of COVID-19 Vaccines: A Systematic Literature Review

Objectives: The COVID19 pandemic caused over six million deaths worldwide as of 2022 and made necessary the rapid development of vaccines. The objective of this Systematic Literature Review is to summarise the main evidence from economic evaluations of vaccines against COVID19. Method(s): Searches were conducted on PubMed on July 13th 2022. The selected papers considered COVID19 vaccination scenarios without population limits. The types of study design examined were cost-benefit and cost-effectiveness analyses. Result(s): Overall, 16 articles from an initial list of 1842 were included in this review. Out of the 16 models, there were five Markov cohort models (three of them were combined with a decision tree model), four dynamic transmission models, three microsimulation models, three epidemiological models (without further information on the model structure) and one decision tree model. Model characteristics were considerably consistent between high-, middle- or low-income countries. Five studies considered both the healthcare and societal perspective, while seven studies reported only the former, and one only the latter. Two studied did not specify the study perspective. Ten of the studies did not consider any level of herd immunity, and no study considered cross-protection. Although eight studies used "naive" comparisons between vaccines, none of the studies conducted thorough indirect treatment comparison. All the models suggest that vaccines are cost-effective as they prevent death and transmission, and reduce the severity of cases. Although the sources of effectiveness estimates were always stated, the details of those studies were rarely reported. Nevertheless, the outcome measures and the key parameters used in the models were generally clearly stated and justified. Conclusion(s): This SLR highlights several challenges for conducting Health Economic evaluations of COVID19 vaccines. The quality of the models and their estimates suffered from the very fast pace of COVID19 research. Therefore, economic evidence on vaccination programs requires additional rigorous research.Copyright © 2023

Training the Armed Forces personnel in COVID-19 contact tracing: a Portuguese case study : Sofia Carmezim Pereira

Background Local contact tracing teams needed to be reinforced in preparation for a peak in Covid-19 cases. The Portuguese Armed Forces showed availability and their members initiated a formal training facilitated by the Public Health Unit (PHU) of Amadora. Health systems must be prepared to respond to all threats, as the COVID-19 pandemic showed us the need for quick task shifting and the training of non-experts’ workers. Objectives The aim of the project was to develop contact tracing skills by non-health professionals, in the context of the COVID-19 pandemic. The training program was held online, with a total duration of 48 hours, distributed by the topics described: introduction to health and epidemiology concepts, the national guidelines, and the information systems (13h). We privileged demonstrative and participatory training methods, followed by continuous supervision of each contact tracing survey and constant feedback (35h). Learning support materials were sent out to assist the trainees, including written and video support. Results More than 200 personnel - sailors, soldiers and airmen - were trained. Each Lisbon and Tagus Valley area PHU was reinforced with a team of military professionals in order to support the contact tracing process, with an increase in the number of surveys completed. We highlight as positive aspects: increased number of contact tracing surveys carried out;growth of inter-institutional partnerships;freeing up of specialized PHU resources to other important tasks. As for negative aspects we focus on the complexity in health communication, the limited time for training, and the lack of specific health knowledge of the trainees. Conclusions This pandemic revealed the Portuguese need for a transdisciplinary approach in the provision of care, specially at a Public Health level. Training programs like these highlight the vital role of reshaping and reorganizing the healthcare workforce answering Public Health necessities. Key messages • Training programs for non-health workers must be prepared to reinforce health systems when necessary. The reinforcement of contact tracing teams by the Portuguese Armed Forces was a great example. • A transdisciplinary approach in the provision of care was essential during the COVID-19 pandemic. Specific training of non-health workers can be planned in time to respond to health threats.

An evolutionary approach to the discretization of gene expression profiles to predict the severity of COVID-19

In this work, we propose to use a state-of-the-art evolutionary algorithm to set the discretization thresholds for gene expression profiles, using feedback from a classifier in order to maximize the accuracy of the predictions based on the discretized gene expression levels, while at the same time minimizing the number of different profiles obtained, to ease the understanding of the expert. The methodology is applied to a dataset containing COVID-19 patients that developed either mild or severe symptoms. The results show that the evolutionary approach performs better than a traditional discretization based on statistical analysis, and that it does preserve the sense-making necessary for practitioners to trust the results. © 2022 Owner/Author.

Prospective, non-interventional study with a cohort to assess real-world effectiveness (RWE) and safety of emicizumab in persons with hemophilia A (PWHA) without inhibitors in Spain, hemolution cohort

Background : Haemophilia A (HA) is a disorder characterized by deficiency in clotting FVIII that affects daily lives of patients and caregivers. Emicizumab is a humanized, bispecific, monoclonal antibody, which substitutes missing activated FVIII. Aims : Effectiveness and safety on emicizumab in clinical practice. Methods : Hemolife study initiated in March 2020, describes the socio-occupational impact of HA without inhibitors in patients and caregivers, in terms of quality of life, activity, and productivity/absenteeism, among others. At that time, both COVID-19 pandemic and emicizumab approval for PwHA without inhibitors happened. A multidisciplinary Scientific Committee of experts in HA, rethought Hemolife study to include a cohort of patients treated with emicizumab (Hemolution), resulting in a more complete and stronger RWE study, and avoiding logistical duplications that a separate study would mean to centers and patients. 2020 has been a year for adaptation, efficiency and re-design;also, in RWE context. 100 PwHA will be followed for 12 months within Hemolife. At any time, a patient prescribed with emicizumab may be enrolled in Hemolution cohort, followed for at least 8 months after initiation of emicizumab to collect efficiency and safety data (Figure 1). Finally, Hemolife involves telemedicine;in a pandemic setting, Hemolution could also benefit from this live data collection and may shape a new and more dynamic form of care in HA that avoids being in the hospital. Results : Ongoing study. Protocol was submitted and approved by authorities/ethics committee's (Table 1). Conclusions : By this novel approach we will gather information on emicizumab in clinical practice and provide relevant information to the Haemophilia community, contributing to improve patient care in HA.

Inflammatory bowel disease (IBD) and immunosuppression do not worsen the prognosis of COVID-19. Results from the eneida project of Geteccu

Introduction: The exhaustive registry of COVID-19 cases in patients with IBD is a unique opportunity to learn how to deal with this infection, especially in reference to the management of immunosuppressive treatment, isolation measures or if the disease is more severe in IBD patients due to immunosuppression. Aims & Methods: Aims: The aims of this study were to know the incidence and characteristics of COVID-19 in the ENEIDA cohort during the first wave of the pandemic;the outcomes among those under immunosuppressants/ biologics for IBD;the risk factors for contracting the infection and poor outcomes;and the impact of the infection after three-month followup. Methods: Prospective observational cohort study of all IBD patients with COVID-19 included in the ENEIDA registry (with 60.512 patients in that period) between March and July 2020, with at least 3 months of follow-up. Any patient with a confirmed (by PCR or SARS-CoV-2 serology) or probable (suggestive clinical picture) infection was considered as a case. Results: A total of 482 patients with COVID-19 from 63 centres were included: 247 Crohn's disease, 221 ulcerative colitis and 14 unclassified colitis;median age 52 years (IQR: 42-61), 48% women and 44% 1 comorbidity. Diagnosis was made by PCR: 62% and serology: 35%. The most frequent symptoms: fever (69%), followed by cough (63%) and asthenia (38%). During lockdown 78% followed strict isolation. 35% required hospital admission (ICU: 2.7%) and 12% fulfilled criteria for SIRS upon admission. 18 patients died from COVID-19 (mortality:3.7%). 12% stop IBD medication during COVID-19. At 3 months, taken into account all included cases, 76% were in remission of IBD. Age 50 years (OR 2.09;95% CI:1.27-3.4;p=0.004), 1 comorbidities (OR 2.28;95% CI:1.4-3.6;p=0.001), and systemic steroids <3 months before infection (OR 1.3;95%CI:1-1.6;p= 0.003), were risk factors for hospitalisation due to COVID-19. A Charlson score 2 (OR 5.4;95%CI:1.5-20.1;p=0.01) was associated with ICU admission. Age 60 years (OR 7.1;95%CI:1.8-27.4;p=0.004) and having 2 comorbidities (OR 3.9;95% CI:1.3-11.6;p=0.01) were risk factors for COVID- 19 related death. Conclusion: IBD does not seem to worsen the prognosis of COVID-19, even when immunosuppressants and biological drugs are used. Age and comorbidity are the most important prognostic factors for more severe COVID-19 in IBD patients.

Comorbidities and epidemiological risk factor but not immunosuppressive therapies increase the risk of COVID-19 in inflammatory bowel disease (IBD): An ENEIDA-based, casecontrol study

Introduction: The information regarding IBD patients with COVID-19 suggests that the factors related to bad outcome are older age and comorbidity whereas immunosuppressants do not have a significant impact worsening the disease evolution. Aims & Methods: Aims: To assess if there are differences in epidemiological, demographical, and clinical characteristics between infected and non-infected IBD patients. Methods: Case-control study in IBD patients with COVID-19 (cases) compared to IBD without COVID-19 (controls) in the period March-July/2020 within the ENEIDA registry (promoted by GETECCU and with more than 60.000 IBD patients included). Cases were matched 1:2 by age (±5y), type of disease (CD/UC), gender, and centre. All controls were selected from only one investigator blind to other clinical characteristics of the patients to avoid selection bias. Results: 482 cases and 964 controls from 63 Spanish centres were included. No differences were found within the basal characteristics including CD location, CD behaviour, extraintestinal manifestations, family history of IBD or smoking habits. Cases had ≥ 1 comorbidities (cases:43%vs. controls: 35%, p=0.01) and occupational risk (cases:27% vs. controls:10.6%, p<0.0001) in a higher proportion. Strict lock-down was the only measure demonstrating protection against COVID-19 (cases:49% vs. controls:70%, p<0.0001). There were no differences in the use of systemic steroids (p=0.19), immunosuppressants (p=0.39) or biologics (p=0.28) between cases and controls. Cases were more often treated with aminosalycilates (42% vs.34%, p=0.003). Having ≥ 1 comorbidities (OR:1.6, 95%CI: 1.2-2.1), occupational risk (OR:1.95, 95%CI:1.39-2.7) and the use of aminosalycilates (OR:1.4, 95%CI: 1-1.8) were risk factors for COVID-19. On the other hand, strict lockdown was a protective factor (OR:0.38, CI:0.29-0.49). Conclusion: Comorbidities and epidemiological risk factors are the most relevant aspects for the risk of COVID-19 in IBD patients. This risk of COVID- 19 seems to be increased by aminosalycilates but not by immunosuppressants or biologics. The attitude regarding treating IBD patients with aminosalicylates during COVID-19 pandemic deserves a deeper analysis. (Table Presented).

Psychosocial impact of the COVID-19 pandemic on patients with inflammatory bowel disease in spain

Introduction: Few studies have examined the effects of COVID-19 on the mental health of patients with inflammatory bowel disease (IBD), who are already at higher risk of depression, anxiety and stress than the general population. Aims & Methods: This cross-sectional study was conducted to assess the psychosocial impact of COVID-19 on patients with IBD in Spain during lockdown and the first wave of the pandemic. A self-report questionnaire that integrated the Spanish version of the Depression, Anxiety and Stress Scale-21 items (DASS-21) and the Perceived Stress Questionnaire (PSS) was designed to gather sociodemographic data and information related to the effects of COVID-19 on the lives of IBD patients. Twelve IBD units invited their patients to answer the anonymous online survey via email or by using a QR code displayed at the unit. A link to the survey was also published on the GETECCU (Spanish IBD group) website and social media account. The survey was conducted between the 1st July and the 25th August 2020. Results: Of the 693 survey participants with IBD, 67% were female, mean age 43 (12y SD). 61% had ulcerative colitis, 36% Crohn's disease 3% indeterminate colitis. Only 15 participants were diagnosed with COVID-19: 3 of them required hospital admission and none required ICU admission. Physical activity levels and sleep habits were adversely affected for 79% and 67% of respondents, respectively. In addition, 39% reported a decrease in income due to the pandemic. 95% report having complied with IBD treatment during the COVID-19 pandemic, despite over 50% of them feeling that they were more at risk of infection due to their medication. DASS-21 scores indicate that during the lockdown the estimated prevalence of depression was 10.5% [95% CI 8.2-13%], anxiety 20% [95% CI -17- 23%] and stress 18% [95% CI 8.2-13%]. Conclusion: In the short-term, lockdown during the COVID-19 pandemic has had a considerable impact on the mental health of IBD patients in Spain. Further follow-up studies should be carried out to determine the real long-term impact.

Incidence, clinical presentation, and severity of SARS-CoV-2 infection in inflammatory bowel disease patients in the “second and the third wave” of infection

Introduction: Data about the SARS-CoV-2 infection in inflammatory bowel disease patients (IBD) are scarce so, there is a need for more data about the risk, clinical characteristics, and evolution of this patients. Aims & Methods: Our aim was to analyse the incidence, clinical presentation, and severity of SARS-CoV-2 infection in IBD patients in the “second and the third wave” of infection. We design a cross-sectional, observational study in IBD patients follwed in our IBD Unit with confirmed SARSCoV- 2 infection by PCR and/or antigen tests from 01 July 2020 to 01 March 2021. All data were collected by telephone interview and reviewing the electronical medical records. Results: Fifty-one of 805 IBD patients followed in our Unit were diagnosed of SARS-CoV-2 infection in this period (6.3%;95% CI 4.6-8.0). Mean age: 45±13 years;56.9% female, 23.5% smokers, 56.9% Crohn's disease, 29.4% comorbidities and 17.6% asymptomatic. Digestive symptoms were reported in 22 patients (43.1%), with diarrhoea as the most common (39.2%, median duration: 4 days;IQR 1-7). The most frequent symptoms other than diarrhoea were low-grade fever/fever in 43.1% (median duration: 3 days;IQR 1-6.5) and dysosmia/dysgeusia in 39.2% (median duration: 15 days;IQR 7-30). Only one patient (2%) was diagnosed with IBD flare-up during infection. Six patients (11.8%) temporarily withdrew their IBD treatment because of COVID-19. Most of the patients had a mild disease (88.2%), no patient had to be admitted in the intensive care unit. Only one patient died (2%) due to SARS-CoV-2 infection and multiple previous comorbidities, 52 years old male with ulcerative colitis in treatment with Mesalazine and dendritic cell sarcoma, common variable inmunodefiency, and primary sclerosing cholangitis progressing to cirrhosis. In the multivariate analysis, the presence of dyspnoea was associated with more severe infection (p=0.007;OR:25.7;95% CI 2.4-277.8). Patients on immunomodulators and/or biological therapy did not have more severe disease compared to non-immunosuppressed patients (p>0.05). Conclusion: SARS-CoV-2 infection was relatively frequent is our series. Dyspnoea was associated with a more severe infection. Severity of SARSCoV- 2 infection was not related to immunosuppression or development of IBD flare-ups and only a small percentage of patient needed to modify IBD medication during infection.

Psychiatric disorders during acute hospital treatment of COVID-19 - a case series

IntroductionCoronavirus disease (COVID-19) has been associated with the development mental and behavioural symptoms and psychiatric disorders. This association is stronger in severe cases of the disease and in those needing inpatient treatment, particularly in intensive care units (ICU).ObjectivesTo determine the incidence of psychiatric disorders in a Portuguese hospital-based sample of patients with COVID-19. To describe relevant demographic and clinical data.MethodsWe reviewed all COVID-19 inpatients assessed by liaison psychiatry at our hospital between April and September 2020. Patients admitted due to a psychiatric disorder were excluded from the analysis. We reviewed medical records and retrieved relevant clinical data. ICD-10 was used to classify diagnoses.ResultsWe identified 36 cases with a mean age of 62.64 years-old (SD 19.23). The most common disorder was delirium, which occurred in 41.7% of our sample (15 patients), followed by adjustment disorder (22.2%, n=8), and depressive episode (16.7%, n=8). Most patients had no personal (61.1%, n=22) nor family (75%, n=27) history of a psychiatric disorder. Mean length of admission was 36.89 days (SD 28.91). Seventeen cases (47.22%) had at least one risk factor for severe COVID-19 disease and 14 (38.89%) were admitted at some point to the ICU.ConclusionsIn our sample, delirium was the main cause for mental or behavioural symptoms in COVID-19 patients. However, we observed a wide array of presentations in our center. A larger sample would allow to better characterize this often-overlooked symptoms and identify risk factors to psychiatric syndromes.DisclosureNo significant relationships.

The impact of measures recommended by the government to limit the spread of coronavirus (COVID-19) on physical activity levels, quality of life, and mental health of Brazilians

To reduce transmission of the coronavirus, the Brazilian government adopted containment measures to control the virus' spread, including limitations to the practice of physical activity. It was aimed to analyze the effects of COVID-19 quarantine on physical activity levels, energy expenditure, quality of life, and level of stress in a sample of the Brazilian population. The sample included 426 participants (7 to 80 years). The International Physical Activity Questionnaire, Short form survey-36 (SF-36), and Stress Perception Scale, were used to assess the level of physical activity, quality of life and stress, respectively. The anthropometric data was used to the assessment of body mass index and basal metabolic rate. Body weight increased significantly in all sample (p < 0.05). During the pandemic, 84% of the sample indicated a low level of physical activity. Furthermore, weekly energy expenditure decreased significantly in all age groups during the pandemic (children p < 0.0001;adolescents: p < 0.0001;adults p < 0.001, and elderly p < 0.0001). All aspects of quality of life, significantly reduced in both sexes in all age groups (p < 0.05). With the exception of children, stress levels increased significantly during the pandemic (adolescents: male: p=0.003, female: p < 0.05;adults: male: p=0.003, female: p=0.01, and elderly: male: p=0.02, female: p=0.03). Findings from the present study suggests that COVID-19 social isolation has negatively affected Brazilian' physical activity and quality of life.