ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to variants associated with milder disease. We employed the k18-hACE2 mouse model to study how differences in the course of infection by SARS-CoV-2 variants alpha, delta, and omicron relate to tissue pathology and the immune response triggered. We documented a variant-specific pattern of infection severity, inducing discrete lung and blood immune responses and differentially impacting primary lymphoid organs. Infections with variants alpha and delta promoted bone marrow (BM) emergency myelopoiesis, with blood and lung neutrophilia. The defects in the BM hematopoietic compartment extended to the thymus, with the infection by the alpha variant provoking a marked thymic atrophy. Importantly, the changes in the immune responses correlated with the severity of infection. Our study provides a comprehensive platform to investigate the modulation of disease by SARS-CoV-2 variants and underscores the impact of this infection on the function of primary lymphoid organs.
ABSTRACT
Background: Patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 may be at risk to develop a severe course of COVID-19 due to the immune dysregulation or the influence of immunomodulating drugs on the course of the infection. For a better understanding of SARS-CoV-2 infections in patients with IRD and due to the high incidence of COVID-19 in Madrid from the beginning of this pandemic infection in Spain, the Society of Rheumatology from Madrid (SORCOM) established a registry (REUMA-COVID SORCOM) shortly after the beginning of the pandemic in Spain. Objectives: To determine factors associated with severity of infection with SARS-CoV-2 in patients with inflammatory rheumatic diseases in Madrid Methods: The REUMA-COVID SORCOM registry is a multicenter, retrospective, observational cohort study conducted in Madrid, a SORCOM initiative. All rheumatology departments from Madrid were invited to participate. The study includes patients with IRD presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and November 10, 2020. We consider severe infection death or need of hospitalization. Inclusion criteria was having an IRD and at least 1 of the following 4 criteria: (1) a biologically confirmed COVID-19 diagnosis based on a positive result of a SARS-CoV-2 polymerase chain reaction (PCR) test on a nasopharyngeal swab;(2) Detection of IgM or IgG anti SARSCoV2 in a symptomatic or asymptomatic patients (3)typical thoracic computed tomography (CT) abnormalities (ground-glass opacities) in epidemic areas;(4) COVID19-typical symptoms in an epidemic zone of COVID-19. Results: As of November 10, 2020, 417 patients with IRD were included in the REUMA-COVID SORCOM registry. 5 patients were discharged for incomplete data. Of 412 patients (mean age 57 years, 87.4% Caucasian race, 66.3% female) 174 need hospitalization (42.2%) and 33 patients died (18.4% mortality in hospitalized patients). 82.3% had comorbidities. 234 (56.8%) patients were classified as inflammatory arthropathy, 133 (32.3%) had connective tissue diseases (CTD). 41.1% of the patients had a large history of IRD (≥ 10 years). 10.4% of patients had previously pulmonary involvement. The study includes 143 patients taking Methotrexate, 89 patients taking anti-TNFα therapy and 27 Rituximab. In the univariant analysis, no differences were seen in the severity of COVID-19 infection in patients taking methotrexate. 63% of the all patients taking Rituximab included in the registry need hospitalization and 22% of them died. Hypertension, COPD or cardiovascular disease was associated with hospitalization. Independent factors associated with COVID-19 hospitalization in the multivariate analysis was: age (≥62 years), male sex, IMC ≥30, previous cardiovascular comorbidities and the IRD disease duration (≥ 10 years). Independent factors associated with COVID-19 related death was: age (≥ 62 years), having a CTD diagnose, pulmonary involvement before infection and chronical GC treatment. Conclusion: Patients with IRD represent a population of particular interest in the pandemic context because the baseline immunological alteration and the treated with immunosuppressants agents they receive, comorbidities and the well-known risk of severe infection. Older age, male sex, cardiovascular comorbidities were factors associated with high risk of hospitalization in IRD patients. CTD diseases, previously pulmonary involvement and chronical GC treatment with more than 10mg/day were associated with high risk of death. Neither anti TNF-α treatment nor Methotrexate were risk factor for hospitalization or death COVID-19 related in IRD patients.
ABSTRACT
BACKGROUND: Individuals with Substance Use Disorders (SUD), are vulnerable to the psychological consequences of the COVID-19 pandemic. This is the first study to assess risk factors of adverse mental health outcomes during lockdown in a SUD population. METHODS: This was a cross-sectional study, conducted through an online survey that was completed by 303 individuals with SUD, attended in the Addiction Unit of University of Barcelona Clínic Hospital. Sociodemographic and clinical data were collected and descriptive analyses were carried out. Depending on whether individuals reported a worsening or no change/improvement in anxiety and depression symptoms during lockdown, the sample was divided in two groups. A logistic regression was then carried out to identify risk factors associated with adverse mental health outcomes. RESULTS: Overall, frequency of use for the majority of individuals with SUD remained stable during lockdown in comparison to the pre-lockdown era, although a reduction was found in frequency of tobacco, alcohol, cannabis and cocaine use in a small fraction of individuals with SUD. Symptoms of clinical anxiety were found in 58.7% of the sample while 48.2% of participants scored above the clinical threshold for depression. In addition, 50.3% of the sample reported a deterioration in depression and anxiety symptoms during lockdown that was associated with the following risk factors: previous trauma-exposure, female gender, distress and isolation, income reduction and alcohol use. CONCLUSION: A high percentage of patients with SUD experienced adverse mental health outcomes during lockdown that were associated with several risk factors, which should be taken into account in policy making and prevention strategies, as well as in clinical practice, in order to provide personalized care to SUD patients during the time of the pandemic.