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Background: The COVID-19 pandemic disrupted healthcare services usage. We estimated the impact of the COVID-19 pandemic on healthcare services utilization among people living with HIV (PLWH) in Catalonia, Spain., Methods: We accessed public healthcare usage in HIV units, primary care, hospitals, and emergency departments among 17,738 PLWH in the PISCIS cohort from January 1, 2017, to December 31, 2020. We performed an interrupted time series analysis using the autoregressive integrated moving average to estimate the effect of COVID-19 on medical visits and HIV monitoring among PLWH., Results: A non-significant decrease of 17.1% (95% CI: [-29.4, 0.4]) in overall medical visits was observed during the lockdown, followed by a steady resumption until the end of 2020. Three health facilities presented statistically significant declines in visits during the lockdown: HIV units (-44.8% [-56.7, -23.6]), hospitals (-40.4% [-52.8, -18.1]), and emergency departments (-36.9% [-47.0, -21.9]); thereafter, the visits have begun to increase steadily but not to previous levels as of December 2020. In contrast, primary care visits remained unchanged during the lockdown by 1.9% (95% CI: -13.5, 23.9). CD4 cell (54.2% [95% CI: -64.4, -36.0]) and HIV RNA viral load (53.1% [95% CI: -62.9, -36.1]) laboratory monitoring reduced significantly during the lockdown., Conclusion: COVID-19 lockdowns significantly disrupted in-person healthcare services usage among PLWH. The reduction in healthcare utilization however did not affect primary care services. Despite services gradually rebounding to pre-pandemic levels, it is imperative to effectively prepare for future pandemics and implement measures to ensure continuous provision of care to PLWH during pandemic lockdowns., (Copyright © 2023 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Cognitive difficulties are reported as lasting sequelae within post COVID-19 condition. However, the chronicity of these difficulties and related factors of fatigue, mood, and perceived health have yet to be fully determined. To address this, the current longitudinal study aimed to clarify the trends of cognitive test performance and cognitive domain impairment following COVID-19 onset, and whether hospitalization influences outcomes. 57 participants who reported subjective cognitive difficulties after confirmed COVID-19 infection were assessed at baseline (~6 months post COVID-19) and follow-up (~15 months later) visits. Assessments included measures across multiple cognitive domains and self-report questionnaires of fatigue, mood, and overall health. Analyses were conducted in three stages: at the test score level (raw and adjusted scores), at the cognitive domain level, and stratified by hospitalization status during infection. Results at the test-score level indicate that cognitive performance remains relatively stable across assessments at the group level, with no significant improvements in any adjusted test scores at follow-up. Cognitive domain analyses indicate significant reductions in attention and executive functioning impairment, while memory impairment is slower to resolve. On self-report measures, there was a significant improvement in overall health ratings at follow-up. Finally, those hospitalized during infection performed worse on timed cognitive measures across visits and accounted for a larger proportion of cases with short-term and working memory impairment at follow-up. Overall, our findings indicate that cognitive difficulties persist both at test score and cognitive domain levels in many cases of post COVID-19 condition, but evidence suggests some improvement in global measures of attention, executive functioning and overall self-rated health. Furthermore, an effect of hospitalization on cognitive symptoms post COVID-19 may be more discernible over time., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Grunden et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Coronavirus disease 2019 (COVID-19) has been a major public health burden. We hypothesised that circulating extracellular vesicles (cEVs), key players in health and disease, could trace the cell changes during COVID-19 infection and recovery. Therefore, we studied the temporal trend of cEV and inflammatory marker levels in plasma samples of COVID-19 patients that were collected within 24 h of patient admission (baseline, n = 80) and after hospital discharge at day-90 post-admission (n = 59). Inflammatory markers were measured by standard biochemical methods. cEVs were quantitatively and phenotypically characterized by high-sensitivity nano flow cytometry. In patients recovered from COVID-19 lower levels of inflammatory markers were detected. cEVs from vascular (endothelial cells) and blood (platelets, distinct immune subsets) cells were significantly reduced at day-90 compared to admission levels, a pattern also observed for cEVs from progenitor, perivascular and epithelial cells. The best discriminatory power for COVID-19 severity was found for inflammatory markers lactate dehydrogenase and neutrophil-to-lymphocyte ratio and for granulocyte/macrophage-released CD66b + /CD68 + -cEVs. Albeit inflammatory markers were good indicators of systemic inflammatory response and discriminators of COVID-19 remission, they do not completely reveal cell stress and organ damage states. cEVs reaching baseline pre-infection levels at 90 days post-infection in recovered patients discriminate parental cells affected by disease., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Objectives: To assess the effect of COVID-19 on the postacute risk of cardiovascular events (CVEs) among people with HIV (PWH)., Methods: Population-based matched cohort, including all PWH ≥16 years in the Catalan PISCIS HIV cohort. We estimated the incidence rate of the first CVE after COVID-19, analysed it a composite outcome (2020-2022). We adjusted for baseline differences using inverse probability weighting and used competing risk analysis., Results: We included 4199 PWH with and 14 004 PWH without COVID-19. The median follow-up was 243 days (interquartile range [IQR]: 93-455), 82% (14 941/18 203) were men, with a median age of 47 years. Overall, 211 PWH with COVID-19 and 621 without developed CVE, with an incidence rate of 70.2 and 56.8/1000 person-years, respectively. During COVID-19 infection, 7.6% (320/4199) required hospitalization and 0.6% (25/4199) intensive care unit admission, 97% (4079/4199) had CD4 + T-cell ≥200 cells/μL, 90% (3791/4199) had HIV-RNA<50 copies/mL and 11.8% (496/4199) had previous CVE at baseline. The cumulative CVE incidence was higher among PWH after COVID-19 compared with PWH without COVID-19 during the first year (log-rank p=0.011). The multivariable analysis identified significantly increased CVE risk with age, heterosexual men, previous cardiovascular disease (CVD), and chronic kidney or liver disease. COVID-19 was associated with increased subsequent risk of CVE (adjusted hazard ratio 1.30 [95% CI, 1.09-1.55]), also when only including individuals without previous CVD (1.60 [95% CI, 1.11-2.29]) or nonhospitalized patients (1.34 [95% CI, 1.11-1.62])., Discussion: COVID-19 was associated with a 30% increased risk of major CVE in PWH during the subsequent year, suggesting that COVID-19 should be considered an additional CVD risk in PWH in the short term., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: People living with HIV who are lost to follow-up have a greater risk of health deterioration, mortality, and community transmission., Objective: Our aim was to analyse both how rates of loss to follow-up (LTFU) changed between 2006 and 2020 and how the COVID-19 pandemic affected these rates in the PISCIS cohort study of Catalonia and the Balearic Islands., Methods: We analysed socio-demographic and clinical characteristics of LTFU yearly and with adjusted odds ratios to assess the impact of these determinants on LTFU in 2020 (the year of COVID-19). We used latent class analysis to categorize classes of LTFU based on their socio-demographic and clinical characteristics at each year., Results: In total, 16.7% of the cohort were lost to follow-up at any time in the 15 years (n = 19 417). Of people living with HIV who were receiving follow-up, 81.5% were male and 19.5% were female; of those who were lost to follow-up, 79.6% and 20.4% were male and female, respectively (p < 0.001). Although rates of LTFU increased during COVID-19 (1.11% vs. 0.86%, p = 0.024), socio-demographic and clinical factors were similar. Eight classes of people living with HIV who were lost to follow-up were identified: six for men and two for women. Classes of men (n = 3) differed in terms of their country of birth, viral load (VL), and antiretroviral therapy (ART); classes of people who inject drugs (n = 2) differed in terms of VL, AIDS diagnosis, and ART. Changes in rates of LTFU included higher CD4 cell count and undetectable VL., Conclusions: The socio-demographic and clinical characteristics of people living with HIV changed over time. Although the circumstances of the COVID-19 pandemic increased the rates of LTFU, the characteristics of these people were similar. Epidemiological trends among people who were lost to follow-up can be used to prevent new losses of care and to reduce barriers to achieve Joint United Nations Programme on HIV/AIDS 95-95-95 targets., (© 2023 British HIV Association.)

Background: It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19., Methods: We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020-October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis., Results: Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83-2.45 with an I 2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29-1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31-0.75], I 2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40-0.68], I 2 37%) were significantly lower for people with previous macrovascular disease., Conclusions: This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup., (© 2022. The Author(s).)

Fatigue in its many forms of physical, mental, and psychosocial exhaustion is a common symptom of post-COVID-19 condition, also known as "Long COVID." Persistent fatigue in COVID-19 patients is frequently accompanied by cognitive dysfunction and neuropsychiatric symptoms; however, less is known about the relationships between these components of post-COVID-19 condition and fatigue itself. Consequently, the present study sought to (1) distinguish the types of fatigue experienced by participants, and (2) investigate whether cognitive deficits across various domains and neuropsychiatric conditions predicted these different types of fatigue. The study included 136 COVID-19 patients referred for neuropsychological evaluation due to cognitive complaints 8 months on average after SARS-CoV-2 infection. Measures included self-reported fatigue (physical, cognitive, and psychosocial), neuropsychiatric questionnaires (assessing symptoms of depression, anxiety, apathy, and executive functioning), a comprehensive neuropsychological assessment, and self-reported quality of life and everyday functioning. Results showed that reports of clinical significant fatigue were pervasive in our sample (82.3% of participants), with physical fatigue rated highest on average relative to the subscale maximum. Elevated levels of apathy, anxiety, and executive dysfunction in neuropsychiatric measures along with executive and attentional difficulties on cognitive tests were found to be consistently important predictors among different types of fatigue. This implicates both cognitive and neuropsychiatric symptoms as predictors of fatigue in post-COVID-19 condition, and stresses the importance of a holistic approach in assessing and considering potential treatment for COVID-19 patients experiencing fatigue., (© 2022. The Author(s).)

Background: Reports on the impact of some antiretrovirals against SARS-CoV-2 infection and disease severity are conflicting., Objectives: We evaluated the effect of tenofovir as either tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with HIV (PLWH)., Methods: We conducted a propensity score-matched analysis in the prospective PISCIS cohort of PLWH (n = 14 978) in Catalonia, Spain. We used adjusted Cox regression models to assess the association between tenofovir and SARS-CoV-2 outcomes., Results: After propensity score-matching, SARS-CoV-2 diagnosis rates were similar in TAF/FTC versus ABC/3TC recipients (11.6% versus 12.5%, P = 0.256); lower among TDF/FTC versus ABC/3TC recipients (9.6% versus 12.8%, P = 0.021); and lower among TDF/FTC versus TAF/FTC recipients (9.6% versus 12.1%, P = 0.012). In well-adjusted logistic regression models, TAF/FTC was no longer associated with reduced SARS-CoV-2 diagnosis [adjusted odds ratio (aOR) 0.90; 95% confidence interval (CI), 0.78-1.04] or hospitalization (aOR 0.93; 95% CI, 0.60-1.43). When compared with ABC/3TC, TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or hospitalization (aOR 0.51; 95% CI, 0.15-1.70). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or associated hospitalization (aOR 0.33; 95% CI, 0.10-1.07) compared with TAF/FTC., Conclusions: TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalizations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure should not modify any preventive or therapeutic SARS-CoV-2 infection management., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The study reports our experience with paired inspiration/expiration thin-section computed tomographic (CT) scans in the follow-up of COVID-19 patients with persistent respiratory symptoms., Methods: From August 13, 2020, to May 31, 2021, 48 long-COVID patients with respiratory symptoms (27 men and 21 women; median age, 62.0 years; interquartile range: 54.0-69.0 years) underwent follow-up paired inspiration-expiration thin-section CT scans. Patient demographics, length of hospital stay, intensive care unit admission rate, and clinical and laboratory features of acute infection were also included. The scans were obtained on a median of 72.5 days after onset of symptoms (interquartile range: 58.5-86.5) and at least 30 days after hospital discharge. Thin-section CT findings included ground-glass opacity, mosaic attenuation pattern, consolidation, traction bronchiectasis, reticulation, parenchymal bands, bronchial wall thickening, and air trapping. We used a quantitative score to determine the degree of air trapping in the expiratory scans., Results: Parenchymal abnormality was found in 50% (24/48) of patients and included air trapping (37/48, 77%), ground-glass opacities (19/48, 40%), reticulation (18/48, 38%), parenchymal bands (15/48, 31%), traction bronchiectasis (9/48, 19%), mosaic attenuation pattern (9/48, 19%), bronchial wall thickening (6/48, 13%), and consolidation (2/48, 4%). The absence of air trapping was observed in 11/48 (23%), mild air trapping in 20/48 (42%), moderate in 13/48 (27%), and severe in 4/48 (8%). Independent predictors of air trapping were, in decreasing order of importance, gender (p = 0.0085), and age (p = 0.0182)., Conclusions: Our results, in a limited number of patients, suggest that follow-up with paired inspiratory/expiratory CT in long-COVID patients with persistent respiratory symptoms commonly displays air trapping., Key Points: • Our experience indicates that paired inspiratory/expiratory CT in long-COVID patients with persistent respiratory symptoms commonly displays air trapping. • Iterative reconstruction and dose-reduction options are recommended for demonstrating air trapping in long-COVID patients., (© 2022. The Author(s).)

Two years after the appearance of the SARS-CoV-2 virus, the causal agent of the current global pandemic, it is time to analyze the evolution of the immune protection that infection and vaccination provide. Cellular immunity plays an important role in limiting disease severity and the resolution of infection. The early appearance, breadth and magnitude of SARS-CoV-2 specific T cell response has been correlated with disease severity and it has been thought that T cell responses may be sufficient to clear infection with minimal disease in COVID-19 patients with X-linked or autosomal recessive agammaglobulinemia. However, our knowledge of the phenotypic and functional diversity of CD8+ cytotoxic lymphocytes, CD4+ T helper cells, mucosal-associated invariant T (MAIT) cells and CD4+ T follicular helper (Tfh), which play a critical role in infection control as well as long-term protection, is still evolving. It has been described how CD8+ cytotoxic lymphocytes interrupt viral replication by secreting antiviral cytokines (IFN-γ and TNF-α) and directly killing infected cells, negatively correlating with stages of disease progression. In addition, CD4+ T helper cells have been reported to be key pieces, leading, coordinating and ultimately regulating antiviral immunity. For instance, in some more severe COVID-19 cases a dysregulated CD4+ T cell signature may contribute to the greater production of pro-inflammatory cytokines responsible for pathogenic inflammation. Here we discuss how cellular immunity is the axis around which the rest of the immune system components revolve, since it orchestrates and leads antiviral response by regulating the inflammatory cascade and, as a consequence, the innate immune system, as well as promoting a correct humoral response through CD4+ Tfh cells. This review also analyses the critical role of cellular immunity in modulating the development of high-affinity neutralizing antibodies and germinal center B cell differentiation in memory and long-lived antibody secreting cells. Finally, since there is currently a high percentage of vaccinated population and, in some cases, vaccine booster doses are even being administered in certain countries, we have also summarized newer approaches to long-lasting protective immunity and the cross-protection of cellular immune response against SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moga, Lynton-Pons and Domingo.)

Background and Objectives: Evidence regarding the safety and efficacy of messenger RNA (mRNA) vaccines in patients with myasthenia gravis (MG) after immunosuppressive therapies is scarce. Our aim is to determine whether the mRNA-1273 vaccine is safe and able to induce humoral and cellular responses in patients with MG., Methods: We performed an observational, longitudinal, prospective study including 100 patients with MG of a referral center for MG in our country, conducted from April 2021 to November 2021 during the vaccination campaign. The mRNA-1273 vaccine was scheduled for all participants. Blood samples were collected before vaccination and 3 months after a second dose. Clinical changes in MG were measured using the MG activities of daily life score at baseline and 1 week after the first and second doses. A surveillance of all symptoms of coronavirus disease 2019 (COVID-19) was conducted throughout the study. Humoral and cellular immune responses after vaccination were assessed using a spike-antibody ELISA and interferon gamma release assay in plasma. The primary outcomes were clinically significant changes in MG symptoms after vaccination, adverse events (AEs), and seroconversion and T-cell immune response rates., Results: Ninety-nine patients completed the full vaccination schedule, and 98 had 2 blood samples taken. A statistically significant worsening of symptoms was identified after the first and second doses of the mRNA-1273 vaccine, but this was not clinically relevant. Mild AEs occurred in 14 patients after the first dose and in 21 patients after the second dose. Eighty-seven patients developed a humoral response and 72 patients showed a T-cell response after vaccination. A combined therapy with prednisone and other immunosuppressive drugs correlated with a lower seroconversion ratio (OR = 5.97, 95% CI 1.46-24.09, p = 0.015) and a lower T-cell response ratio (OR = 2.83, 95% CI 1.13-7.13, p = 0.024)., Discussion: Our findings indicate that the mRNA vaccination against COVID-19 is safe in patients with MG and show no negative impact on the disease course. Patients achieved high humoral and cellular immune response levels., Classification of Evidence: This study provides Class IV evidence that patients with MG receiving the mRNA-1273 vaccine did not show clinical worsening after vaccination and that most of the patients achieved high cellular or immune response levels., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Despite the development of combination antiretroviral therapy (cART) infections continue to cause significant morbidity and mortality among people living with HIV (PLWH). Pulmonary infections with Streptococcus pneumoniae, Haemophilus influenza, and Staphylococcus aureus remain common. One-third of PLWH worldwide are infected with tuberculosis and the infection manifests at any stage of HIV infection. Fungal infection is usually confined to PLWH unaware of their HIV infection until immunosuppression is advanced or those choosing to discontinue cART. The importance of viral infections has diminished since wide availability of cART; however, mortality from COVID-19 in PLWH may remain greater than in the non-HIV population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: While much of the scientific focus thus far has been on cognitive sequelae in patients with severe COVID-19, subjective cognitive complaints are being reported across the spectrum of disease severity, with recent studies beginning to corroborate patients' perceived deficits. In response to this, the aims of this study were to (1) explore the frequency of impaired performance across cognitive domains in post-COVID patients with subjective complaints and (2) uncover whether impairment existed within a single domain or across multiple., Methods: Sixty-three patients with subjective cognitive complaints post-COVID were assessed with a comprehensive protocol consisting of various neuropsychological tests and mood measures. Cognitive test performance was transformed into T scores and classified based on recommended guidelines. After performing a principal component analysis to define cognitive domain factors, distributions of test scores within and across domains were analyzed., Results: Results revealed pervasive impact on attention abilities, both as the singularly affected domain (19% of single-domain impairment) as well as coupled with decreased performance in executive functions, learning, and long-term memory. These salient attentional and associated executive deficits were largely unrelated to clinical factors such as hospitalization, disease duration, biomarkers, or affective measures., Discussion: These findings stress the importance of comprehensive evaluation and intervention to address cognitive sequelae in post-COVID patients of varying disease courses, not just those who were hospitalized or experienced severe symptoms. Future studies should investigate to what extent these cognitive abilities are recuperated over time as well as employ neuroimaging techniques to uncover underlying mechanisms of neural damage., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

COVID-19 pathophysiology is currently not fully understood, reliable prognostic factors remain elusive, and few specific therapeutic strategies have been proposed. In this scenario, availability of biomarkers is a priority. MS-based Proteomics techniques were used to profile the proteome of 81 plasma samples extracted in four consecutive days from 23 hospitalized COVID-19 associated pneumonia patients. Samples from 10 subjects that reached a critical condition during their hospital stay and 10 matched non-severe controls were drawn before the administration of any COVID-19 specific treatment and used to identify potential biomarkers of COVID-19 prognosis. Additionally, we compared the proteome of five patients before and after glucocorticoids and tocilizumab treatment, to assess the changes induced by the therapy on our selected candidates. Forty-two proteins were differentially expressed between patients' evolution groups at 10% FDR. Twelve proteins showed lower levels in critical patients (fold-changes 1.20-3.58), of which OAS3 and COG5 found their expression increased after COVID-19 specific therapy. Most of the 30 proteins over-expressed in critical patients (fold-changes 1.17-4.43) were linked to inflammation, coagulation, lipids metabolism, complement or immunoglobulins, and a third of them decreased their expression after treatment. We propose a set of candidate proteins for biomarkers of COVID-19 prognosis at the time of hospital admission. The study design employed is distinctive from previous works and aimed to optimize the chances of the candidates to be validated in confirmatory studies and, eventually, to play a useful role in the clinical practice., (© 2022. The Author(s).)

Competing Interests: Declaration of Competing Interest NdB does not have any relevant conflict of interest to declare. PD reports grants or contracts from Gilead, Janssen and ViiV Healthcare paid to the institution, as well as consulting fees and payments for lectures, speakers bureaus, educational events from Gilead, Janssen, ViiV Healthcare, MSD, Roche and Teravechnologies.

Background: Factors affecting outcomes of SARS-CoV-2 infection in people living with HIV are unclear. We assessed the factors associated with SARS-CoV-2 diagnosis and severe outcomes among people living with HIV., Methods: We did a retrospective cohort study using data from the PISCIS cohort of people with HIV in Catalonia (Spain) between March 1 and Dec 15, 2020. We linked PISCIS data with integrated health-care, clinical, and surveillance registries through the Public Data Analysis for Health Research and Innovation Program of Catalonia (PADRIS) to obtain data on SARS-CoV-2 diagnosis, chronic comorbidities, as well as clinical and mortality outcomes. Participants were aged at least 16 years in care at 16 hospitals in Catalonia. Factors associated with SARS-CoV-2 diagnoses and severe outcomes were assessed using univariable and multivariable Cox regression models. We estimated the effect of immunosuppression on severe outcomes (hospital admission for >24 h with dyspnoea, tachypnoea, hypoxaemia, asphyxia, or hyperventilation; or death) using Kaplan-Meier survival analysis., Findings: We linked 20 847 (72·8%) of 28 666 participants in the PISCIS cohort with PADRIS data; 13 142 people had HIV. 749 (5·7%) people with HIV were diagnosed with SARS-CoV-2: their median age was 43·5 years (IQR 37·0-52·7), 131 (17·5%) were female, and 618 (82·5%) were male. 103 people with HIV (13·8%) were hospitalised, seven (0·9%) admitted to intensive care, and 13 (1·7%) died. SARS-CoV-2 diagnosis was more common among migrants (adjusted hazard ratio 1·55, 95% CI 1·31-1·83), men who have sex with men (1·42, 1·09-1·86), and those with four or more chronic comorbidities (1·46, 1·09-1·97). Age at least 75 years (5·2, 1·8-15·3), non-Spanish origin (2·1, 1·3-3·4), and neuropsychiatric (1·69, 1·07-2·69), autoimmune disease (1·92, 1·14-3·23), respiratory disease (1·84, 1·09-3·09), and metabolic disease (2·59, 1·59-4·23) chronic comorbidities were associated with increased risk of severe outcomes. A Kaplan-Meier estimator showed differences in the risk of severe outcomes according to CD4 cell count in patients with detectable HIV RNA (p=0·039) but no differences were observed in patients with undetectable HIV RNA (p=0·15)., Interpretation: People living with HIV with detectable HIV viraemia, chronic comorbidities, and some subpopulations could be at increased risk of severe outcomes from COVID-19. These groups should be prioritised in clinical management and SARS-CoV-2 vaccination programmes., Funding: Fundació "la Caixa"., Translations: For the Catalan, Spanish and Russian translations of the Summary see Supplementary Materials section., Competing Interests: Declaration of interests JMM reports receiving a personal 80:20 research grant from Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain, during 2017–21. EL reports receiving honoraria for lectures and presentations from ViiV Healthcare, Gilead Sciences, and Jansen Therapeutics; travel support for attending meetings from ViiV Healthcare and Jansen Therapeutics; payments for participating in the data safety monitoring and advisory board of ViiV Healthcare; being a full time employee of ViiV Healthcare since May 3, 2020; and payments made from Juan Rodés to the Spanish Government on his behalf. PD reports that his institution received grants from Gilead Sciences, Janssen-Cilag, and ViiV Healthcare; and he personally received honoraria from Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, ViiV Healthcare, Roche, and Thera Technologies. AI reports that his institution received grants from Gilead Sciences and Merck Sharp & Dohme; and he personally received consultation fees from Gilead Sciences, ViiV Healthcare, and Thera Technologies; honoraria for lectures and presentations from Gilead Sciences, Merck Sharp & Dohme, Jansen Therapeutics, and ViiV Healthcare; and travel support for attending meetings from Gilead Sciences, Jansen, and ViiV Healthcare. VF reports that his institution received grants from Gilead Sciences, ViiV Healthcare, and Merck Sharp & Dohme; and he personally received consultation fees from ViiV Healthcare; honoraria for lectures and presentations from ViiV Healthcare, Gilead Sciences, Jansen Therapeutics, and Merck Sharp & Dohme; and travel support for attending meetings from Gilead Sciences. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim: The study aim was to assess the association of vitamin D supplementation before hospital admission and severe outcomes in subjects admitted for COVID-19. Methods: We performed a cross-sectional analysis of pseudonymised medical record data from subjects admitted to the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) for COVID-19 during March and April 2020. The composite primary study outcome was defined as death and/or invasive mechanical ventilation (IMV). Association between risk factors and study outcomes was evaluated by bivariate analysis, followed by logistic regression analysis. Results: In total, 1,267 persons were hospitalised during the observation period. Overall, 14.9% of the subjects were on active vitamin D supplementation treatment before admission. The subjects in the vitamin D group were significantly older than subjects without vitamin D supplementation. We observed higher rates of the primary outcome (death and/or IMV) among the persons with previous use of vitamin D (30.1 vs. 22.9% in those not receiving treatment). In the bivariate analysis, previous use of vitamin D was positively associated with death and/or IMV [odds ratio (OR): 1.45 95% CI: 1.03; 2.04]; however, after adjustment for other risk factors this association disappeared (OR: 1.09 95%CI: 0.65; 1.81). Conclusion: We did not find an association between vitamin D supplementation before hospital admission and death and/or IMV in subjects admitted for COVID-19. The age and the burden of age-associated comorbidities were independently associated with the in-hospital events., Competing Interests: RC has received advisory and/or speaking fees from Abbott, Ascensia, Lilly, MSD, Novo Nordisk and Sanofi. JF-N has received advisory and or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; they received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, and Boehringer. PD has received lecture and Advisory Board fees from Gilead Sciences, Roche, Merck, Sharp and Dohme, ViiV Healthcare, Janssen and Cilag, Theratechnologies, Boehringer Ingelheim, and Ferrer International. PD has received research grants from Gilead Sciences, ViiV Healthcare, GSK, Janssen and Cilag, and Boehringer Ingelheim. DM has received advisory and/or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; they received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, and Boehringer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Arroyo-Díaz, Julve, Vlacho, Corcoy, Ponte, Román, Navas-Méndez, Llauradó, Franch-Nadal, Domingo and Mauricio.)

Aim: This study's objective was to assess the risk of severe in-hospital complications of patients admitted for COVID-19 and diabetes mellitus (DM)., Design: This was a cross-sectional study., Settings: We used pseudonymised medical record data provided by six general hospitals from the HM Hospitales group in Spain., Outcome Measures: Multiple logistic regression analyses were used to identify variables associated with mortality and the composite of mortality or invasive mechanical ventilation (IMV) in the overall population, and stratified for the presence or absence of DM. Spline analysis was conducted on the entire population to investigate the relationship between glucose levels at admission and outcomes., Results: Overall, 1621 individuals without DM and 448 with DM were identified in the database. Patients with DM were on average 5.1 years older than those without. The overall in-hospital mortality was 18.6% (N=301), and was higher among patients with DM than those without (26.3% vs 11.3%; p<0.001). DM was independently associated with death, and death or IMV (OR=2.33, 95% CI: 1.7 to 3.1 and OR=2.11, 95% CI: 1.6 to 2.8, respectively; p<0.001). In subjects with DM, the only variables independently associated with both outcomes were age >65 years, male sex and pre-existing chronic kidney disease. We observed a non-linear relationship between blood glucose levels at admission and risk of in-hospital mortality and death or IMV. The highest probability for each outcome (around 50%) was at random glucose of around 550 mg/dL (30.6 mmol/L), and the risks flattened above this value., Conclusion: The results confirm the high burden associated with DM in patients hospitalised with COVID-19 infection, particularly among men, the elderly and those with impaired kidney function. Moreover, hyperglycaemia on admission was strongly associated with poor outcomes, suggesting that personalised optimisation could help to improve outcome during the hospital stay., Competing Interests: Competing interests: EO has received advisory and or speaking fees from AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, Sanofi and Amgen; he received research grants to the institution from MSD and Amgen. RC has received advisory and/or speaking fees from Abbott, Ascensia, Lilly, MSD, Novo Nordisk and Sanofi. MM-C has received advisory honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi; he received speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, Menarini, MSD, Novartis, Novo Nordisk and Sanofi; he received research grants to the institution from AstraZeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi. JF-N has received advisory and or speaking fees from AstraZeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi; he received research grants to the institution from AstraZeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi and Boehringer. KK has acted as a consultant, speaker or received grants for investigator-initiated studies for AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG/Menarini Group, Janssen and Napp. DM has received advisory and/or speaking fees from AstraZeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi; he received research grants to the institution from AstraZeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi and Boehringer. PD has received lecture and Advisory Board fees from Gilead Sciences, Roche, Merck, Sharp & Dohme, ViiV Healthcare, Janssen & Cilag, Theratechnologies, Boehringer Ingelheim and Ferrer International. PD has received research grants from Gilead Sciences, ViiV Healthcare, GSK, Janssen & Cilag and Boehringer Ingelheim. BV, FXCC, JR, RP-T, MG and EC have no conflict of interest to declare., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We aimed to assess differences in patients' profiles in the first two surges of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Barcelona, Spain., Methods: We prospectively collected data from all adult patients with SARS-CoV-2 infection diagnosed at the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. All the patients were diagnosed through nasopharyngeal swab PCR. The first surge spanned from 1st March to 13th August 2020, while surge two spanned from 14th August to 8th December 2020., Results: There were 2479 and 852 patients with microbiologically proven SARS-CoV-2 infection in surges one and two, respectively. Patients from surge two were significantly younger (median age 52 (IQR 35) versus 59 (40) years, respectively, p < 0.001), had fewer comorbidities (379/852, 44.5% versus 1237/2479, 49.9%, p 0.007), and there was a shorter interval between onset of symptoms and diagnosis (median 3 (5) versus 4 (5) days, p < 0.001). All-cause in-hospital mortality significantly decreased for both the whole population (24/852, 2.8% versus 218/2479, 8.8%, p < 0.001) and hospitalized patients (20/302, 6.6% versus 206/1570, 13.1%, p 0.012). At adjusted logistic regression analysis, predictors of in-hospital mortality were older age (per year, adjusted odds ratio (aOR) 1.079, 95%CI 1.063-1.094), male sex (aOR 1.476, 95%CI 1.079-2.018), having comorbidities (aOR 1.414, 95%CI 0.934-2.141), ICU admission (aOR 3.812, 95%CI 1.875-7.751), mechanical ventilation (aOR 2.076, 95%CI 0.968-4.454), and coronavirus disease 2019 (COVID-19) during surge one (with respect to surge two) (aOR 2.176, 95%CI 1.286-3.680)., Conclusions: First-wave SARS-CoV-2-infected patients had a more than two-fold higher in-hospital mortality than second-wave patients. The causes are likely multifactorial., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: When coronavirus infectious disease-2019 (COVID-19) blew up, ill-fated auguries on the collision between COVID-19 and the human immunodeficiency virus (HIV) epidemics loomed., Areas Covered: Data from observational studies suggest similar incidence attacks of SARS-CoV-2 infection in people living with HIV (PLWH) and HIV-uninfected populations. The mortality rate of COVID-19 is similar in both populations too. The authors discuss the role of combination antiretroviral therapy (cART) in preventing infection or reducing COVID-19 severity. They also discuss the pharmacological interventions for COVID-19 in PLWH., Expert Opinion: Management of COVID-19 in PLWH is no different from the general population. It should be based on careful supportive care, emphasizing lung-protective ventilation, and wise pharmacological interventions. The antiviral drug remdesivir and dexamethasone are the only pharmacological interventions with clinical benefit for COVID-19, whereas anticoagulation may prevent thrombotic complications. The experience with using these drugs in PLWH is limited, which prevents from rendering well-founded conclusions. Until more data on COVID-19 in PLWH become available, the best weapons within our reach are sound supportive care and sensible use of RDV and dexamethasone, bearing in mind the potential for drug-drug interactions of most corticosteroids and antiretroviral drugs.

Coronavirus disease 2019 (COVID‐19) has been a major public health burden. We hypothesised that circulating extracellular vesicles (cEVs), key players in health and disease, could trace the cell changes during COVID‐19 infection and recovery. Therefore, we studied the temporal trend of cEV and inflammatory marker levels in plasma samples of COVID‐19 patients that were collected within 24 h of patient admission (baseline, n = 80) and after hospital discharge at day‐90 post‐admission (n = 59). Inflammatory markers were measured by standard biochemical methods. cEVs were quantitatively and phenotypically characterized by high‐sensitivity nano flow cytometry. In patients recovered from COVID‐19 lower levels of inflammatory markers were detected. cEVs from vascular (endothelial cells) and blood (platelets, distinct immune subsets) cells were significantly reduced at day‐90 compared to admission levels, a pattern also observed for cEVs from progenitor, perivascular and epithelial cells. The best discriminatory power for COVID‐19 severity was found for inflammatory markers lactate dehydrogenase and neutrophil‐to‐lymphocyte ratio and for granulocyte/macrophage‐released CD66b+/CD68+‐cEVs. Albeit inflammatory markers were good indicators of systemic inflammatory response and discriminators of COVID‐19 remission, they do not completely reveal cell stress and organ damage states. cEVs reaching baseline pre‐infection levels at 90 days post‐infection in recovered patients discriminate parental cells affected by disease. [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19) disproportionately affects migrants and ethnic minorities, including those with human immunodeficiency virus (HIV). Comprehensive studies are needed to understand the impact and risk factors. Methods Using data from the PISCIS cohort of people with HIV (PWH) in Catalonia, Spain, we investigated COVID-19 outcomes and vaccination coverage. Among 10 640 PWH we compared migrants and non-migrants assessing rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, diagnosis, and associated clinical outcomes through propensity score matching and multivariable Cox regression. Results The cohort (mean age, 43 years; 83.5% male) included 57.4% (3053) Latin American migrants. Migrants with HIV (MWH) had fewer SARS-CoV-2 tests (67.8% vs 72.1%, P <.0001) but similar COVID-19 diagnoses (29.2% vs 29.4%, P =.847) compared to Spanish natives. Migrants had lower complete vaccination (78.9% vs 85.1%, P <.0001) and booster doses (63.0% vs 65.5%, P =.027). COVID-19 hospitalizations (8.1% vs 5.1%, P <.0001) and intensive care unit (ICU) admissions (2.9% vs 1.2%, P <.0001) were higher among migrants, with similar hospitalization duration (5.5 vs 4.0 days, P =.098) and mortality (3 [0.2%] vs 6 [0.4%], P =.510). Age ≥40 years, CD4 counts <200 cells/μL, ≥2 comorbidities, and incomplete/nonreception of the SARS-CoV-2 vaccine increased the risk of severe COVID-19 among migrants. Conclusions MWH had lower rates of SARS-CoV-2 testing and vaccination coverage, although the rates of COVID-19 diagnosis were similar between migrants and non-migrants. Rates of COVID-19–associated hospitalizations and ICU admissions were higher among migrants in comparison with non-migrants, with similar hospitalization duration and mortality. These findings can inform policies to address disparities in future pandemic responses for MWH. [ABSTRACT FROM AUTHOR]

Background: Valproic acid (VPA) has shown beneficial effects in vitro against SARS-CoV-2 infection, but no study has analyzed its efficacy in the clinical setting. Methods: This multicenter, retrospective study included 165 adult patients receiving VPA at the time of admission to hospital, and 330 controls matched for sex, age and date of admission. A number of clinical, outcome and laboratory parameters were recorded to evaluate differences between the two groups. Four major clinical endpoints were considered: development of lung infiltrates, in-hospital respiratory worsening, ICU admissions and death. Results: VPA-treated patients had higher lymphocyte (P<0.0001) and monocyte (P = 0.0002) counts, and lower levels of diverse inflammatory parameters, including a composite biochemical severity score (P = 0.016). VPA patients had shorter duration of symptoms (P<0.0001), were more commonly asymptomatic (P = 0.016), and developed less commonly lung infiltrates (65.8%/88.2%, P<0.0001), respiratory worsening (20.6%/30.6%, P = 0.019) and ICU admissions (6.1%/13.0%, P = 0.018). There was no difference in survival (84.8%/88.8%, P = 0.2), although death was more commonly related to non-COVID-19 causes in the VPA group (36.0%/10.8%, P = 0.017). The cumulative hazard for developing adverse clinical endpoints was higher in controls than in the VPA group for infiltrates (P<0.0001), respiratory worsening (P<0.0001), and ICU admissions (P = 0.001), but not for death (0.6). Multivariate analysis revealed that VPA treatment was independently protective for the development of the first three clinical endpoints (P = 0.0002, P = 0.03, and P = 0.025, respectively), but not for death (P = 0.2). Conclusions: VPA-treated patients seem to develop less serious COVID-19 than control patients, according to diverse clinical endpoints and laboratory markers. [ABSTRACT FROM AUTHOR]

Importance: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.Objective: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.Data Sources: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.Study Selection: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.Data Extraction and Synthesis: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.Main Outcomes and Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.Results: A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16).Conclusions and Relevance: In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.Trial Registration: PROSPERO Identifier: CRD42021230155. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The global pandemic of coronavirus disease 2019 (COVID‐19) represented a major public health concern. Growing evidence shows that plasma of COVID‐19 patients contains large numbers of circulating extracellular vesicles (cEVs) that correlate with disease severity and recovery. In this study, we sought to characterize the longitudinal cEV signature in critically ill COVID‐19 patients during hospitalization and its relation to mortality risk.cEVs were quantitatively and phenotypically analysed in hospitalized non‐surviving COVID‐19 patients at baseline (n = 42) and before exitus (n = 40) and in 40 healthy volunteers as a reference group by high sensitivity nano flow cytometry using specific markers for parental cell sources and activation.Levels of cEV subtypes differed between patients with severe COVID‐19 and healthy subjects, specifically those from platelets and endothelial, inflammatory and viral infected cells, which associate to high mortality risk. In the longitudinal analysis from baseline to the time point immediately preceding death, no changes were found for platelet, pan‐leukocyte, and lung epithelial cell‐shed cEVs, while endothelial cell releases of EVs (eEVs) significantly differed. Vascular endothelial growth factor receptor 2‐positive eEVs were significantly increased before death compared to admission whereas endoglin and E‐selectin‐containing eEVs did not change. Conversely, lymphocyte (ℓEV), monocyte, macrophage, pericyte and progenitor cell‐derived cEVs displayed significant reductions before exitus. Noteworthy, levels of CD45+/CD3+‐ℓEVs were significantly associated to the patient's survival time.An evolving cEV profile able to discriminate prompt risk of death during hospitalization has been defined suggesting a role for circulating and vascular cell‐derived EVs in COVID‐19 pathogenesis. [ABSTRACT FROM AUTHOR]

Although the starting event in COVID-19 is a viral infection some patients present with an over-exuberant inflammatory response, leading to acute lung injury (ALI) and adult respiratory distress syndrome (ARDS). Since IL-6 plays a critical role in the inflammatory response, we assessed the efficacy and safety of tocilizumab (TCZ) in this single-centre, observational study in all Covid-19 in-patient with a proven SARS-CoV-2 rapidly progressing infection to prevent ALI and ARDS. 104 patients with COVID-19 treated with TCZ had a lower mortality rate (5·8%) compared with the regional mortality rate (11%), hospitalized patient's mortality (10%), and slightly lower than hospitalized patients treated with our standard of care alone (6%). We found that TCZ rapidly decreased acute phase reactants, ferritin and liver release of proteins. D-Dimer decreased slowly. We did not observe specific safety concerns. Early administration of IL6-R antagonists in COVID-19 patients with impending hyperinflammatory response, may be safe and effective treatment to prevent, ICU admission and further complications. Unlabelled Image • Early administration of IL6-R antagonist tocilizumab, may be an effective and safe treatment for moderate to severe SARS-CoV2 positive patients. • Tocilizumab may prevent irreversible cytokine release syndrome CRS. • Tocilizumab reduced intubation, ICU admission, and decreased the risk of mortality. • Future prospective RCT will give answer about which are the first line drugs to treat COVID-19. [ABSTRACT FROM AUTHOR]