Persistent hypofibrinolysis in severe COVID-19 associated with elevated fibrinolysis inhibitors activity.

Hypercoagulability and reduced fibrinolysis are well-established complications associated with COVID-19. However, the timelines for the onset and resolution of these complications remain unclear. The aim of this study was to evaluate, in a cohort of COVID-19 patients, changes in coagulation and fibrinolytic activity through ROTEM assay at different time points during the initial 30 days following the onset of symptoms in both mild and severe cases. Blood samples were collected at five intervals after symptoms onset: 6-10 days, 11-15 days, 16-20 days, 21-25 days, and 26-30 days. In addition, fibrinogen, plasminogen, PAI-1, and alpha 2-antiplasmin activities were determined. Out of 85 participants, 71% had mild COVID-19. Twenty uninfected individuals were evaluated as controls. ROTEM parameters showed a hypercoagulable state among mild COVID-19 patients beginning in the second week of symptoms onset, with a trend towards reversal after the third week of symptoms. In severe COVID-19 cases, hypercoagulability was observed since the first few days of symptoms, with a tendency towards reversal after the fourth week of symptoms onset. A hypofibrinolytic state was identified in severe COVID-19 patients from early stages and persisted even after 30 days of symptoms. Elevated activity of PAI-1 and alpha 2-antiplasmin was also detected in severe COVID-19 patients. In conclusion, both mild and severe cases of COVID-19 exhibited transient hypercoagulability, reverted by the end of the first month. However, severe COVID-19 cases sustain hypofibrinolysis throughout the course of the disease, which is associated with elevated activity of fibrinolysis inhibitors. Persistent hypofibrinolysis could contribute to long COVID-19 manifestations.

Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency. Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output. Results: Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19. Discussion: Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.

Extracellular vesicles are a late marker of inflammation, hypercoagulability and COVID-19 severity.

Exacerbated inflammation and coagulation are a hallmark of COVID-19 severity. Extracellular vesicles (EVs) are intercellular transmitters involved in inflammatory conditions, which are capable of triggering prothrombotic mechanisms. Since the release of EVs is potentially associated with COVID-19-induced coagulopathy, the aim of this study was to evaluate changes in inflammation- and hypercoagulability-related EVs during the first month after symptom onset and to determine whether they are associated with disease severity. Blood samples of patients with mild or severe forms of the disease were collected on three occasions: in the second, third and fourth weeks after symptom onset for the quantification by flow cytometry of CD41A (platelet glycoprotein IIb/IIIa), CD162 (PSGL-1), CD31 (PECAM-1) and CD142 cells (tissue factor). Analysis of variance (ANOVA) with repeated measures, Kruskal-Wallis and correlation tests were used. Eighty-five patients were enrolled, 71% of whom had mild disease. Seventeen uninfected individuals served as controls. Compared to controls, both mild and severe COVID-19 were associated with higher EV-CD31+, EV-CD41+ and EV-CD142+ levels. All EV levels were higher in severe than in mild COVID-19 only after the third week from symptom onset, as opposed to C-reactive protein and D-dimer levels, which were higher in severe than in mild COVID-19 earlier during disease progression. EV levels were also associated with C-reactive protein and D-dimer levels only after the third week of symptoms. In conclusion, EVs expressing CD41A, CD31, TF, and CD162 appear as late markers of COVID-19 severity. This finding may contribute to the understanding of the pathogenesis of acute and possibly long COVID-19.

Extracellular vesicles are a late marker of inflammation, hypercoagulability and COVID-19 severity

ABSTRACT Exacerbated inflammation and coagulation are a hallmark of COVID-19 severity. Extracellular vesicles (EVs) are intercellular transmitters involved in inflammatory conditions, which are capable of triggering prothrombotic mechanisms. Since the release of EVs is potentially associated with COVID-19-induced coagulopathy, the aim of this study was to evaluate changes in inflammation- and hypercoagulability-related EVs during the first month after symptom onset and to determine whether they are associated with disease severity. Blood samples of patients with mild or severe forms of the disease were collected on three occasions: in the second, third and fourth weeks after symptom onset for the quantification by flow cytometry of CD41A (platelet glycoprotein IIb/IIIa), CD162 (PSGL-1), CD31 (PECAM-1) and CD142 cells (tissue factor). Analysis of variance (ANOVA) with repeated measures, Kruskal-Wallis and correlation tests were used. Eighty-five patients were enrolled, 71% of whom had mild disease. Seventeen uninfected individuals served as controls. Compared to controls, both mild and severe COVID-19 were associated with higher EV-CD31+, EV-CD41+ and EV-CD142+ levels. All EV levels were higher in severe than in mild COVID-19 only after the third week from symptom onset, as opposed to C-reactive protein and D-dimer levels, which were higher in severe than in mild COVID-19 earlier during disease progression. EV levels were also associated with C-reactive protein and D-dimer levels only after the third week of symptoms. In conclusion, EVs expressing CD41A, CD31, TF, and CD162 appear as late markers of COVID-19 severity. This finding may contribute to the understanding of the pathogenesis of acute and possibly long COVID-19.

Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation.

The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.

Applying mucosal barrier injury laboratory-confirmed bloodstream infection criteria in patients with solid tumors and hematologic malignancies: A retrospective cohort study looking for the real source of infection.

We evaluated the interference of the mucosal barrier injury (MBI) laboratory-confirmed bloodstream infection (MBI-LCBI) criteria on the central-line-associated bloodstream infection (CLABSI) incidence density, and the proportion of catheter-related bloodstream infections (CRBSIs) among those classified as MBI. We detected 339 CLABSIs: 15.0% were classified as MBI-LCBIs, and among these, 19.6% were classified as CRBSIs.

Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation

ABSTRACT The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.

Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.

BACKGROUND: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce. METHODS: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment. RESULTS: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities. CONCLUSIONS: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

Post-acute sequelae of SARS-CoV-2 infection (PASC): a protocol for a multidisciplinary prospective observational evaluation of a cohort of patients surviving hospitalisation in Sao Paulo, Brazil.

INTRODUCTION: COVID-19 may lead to persistent and potentially incapacitating clinical manifestations (post-acute sequelae of SARS-CoV-2 infection (PASC)). Using easy-to-apply questionnaires and scales (often by telephone interviewing), several studies evaluated samples of COVID-19 inpatients from 4 weeks to several months after discharge. However, studies conducting systematic multidisciplinary assessments of PASC manifestations are scarce, with thorough in-person objective evaluations restricted to modestly sized subsamples presenting greatest disease severity. METHODS AND ANALYSES: We will conduct a prospective observational study of surviving individuals (above 18 years of age) from a cohort of over 3000 subjects with laboratory-confirmed COVID-19 who were treated as inpatients at the largest academic health centre in Sao Paulo, Brazil (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo). All eligible subjects will be consecutively invited to undergo a 1-2-day series of multidisciplinary assessments at 2 time-points, respectively, at 6-9 months and 12-15 months after discharge. Assessment schedules will include detailed multidomain questionnaires applied by medical research staff, self-report scales, objective evaluations of cardiopulmonary functioning, physical functionality and olfactory status, standardised neurological, psychiatric and cognitive examinations, as well as diagnostic laboratory, muscle ultrasound and chest imaging exams. Remaining material from blood tests will be incorporated by a local biobank for use in future investigations on inflammatory markers, genomics, transcriptomics, peptidomics and metabolomics. ETHICS AND DISSEMINATION: All components of this programme have been approved by local research ethics committees. We aim to provide insights into the frequency and severity of chronic/post-COVID multiorgan symptoms, as well as their interrelationships and associations with acute disease features, sociodemographic variables and environmental exposures. Findings will be disseminated in peer-reviewed journals and at scientific meetings. Additionally, we aim to provide a data repository to allow future pathophysiological investigations relating clinical PASC features to biomarker data extracted from blood samples. TRIAL REGISTRATION NUMBER: RBR-8z7v5wc; Pre-results.

Detection of HIV-1 infections in blood donors during the pre-seroconversion window period in São Paulo, Brazil.

By decreasing the pre-seroconversion window period, nucleic acid testing (NAT) has improved the safety of blood products and reduced the risk of transfusion-transmitted infections. Between 2011 and 2017, NAT determinations for approximately 898,202 donations were performed at Fundação Pró-Sangue/Hemocentro de São Paulo (FPS-HSP). Three seronegative HIV-viremic donations were detected. The NAT yield rate per million donations was 3.34 for HIV, and the acute HIV-1 infections detected are described, followed by a brief review of the situation in Brazil.

Detection of HIV-1 infections in blood donors during the pre-seroconversion window period in São Paulo, Brazil

Abstract By decreasing the pre-seroconversion window period, nucleic acid testing (NAT) has improved the safety of blood products and reduced the risk of transfusion-transmitted infections. Between 2011 and 2017, NAT determinations for approximately 898,202 donations were performed at Fundação Pró-Sangue/Hemocentro de São Paulo (FPS-HSP). Three seronegative HIV-viremic donations were detected. The NAT yield rate per million donations was 3.34 for HIV, and the acute HIV-1 infections detected are described, followed by a brief review of the situation in Brazil.

Autologous hematopoietic stem cell transplant in a patient with leprosy: Is it safe?

A patient with non-Hodgkin lymphoma, preparing for an autologous hematopoietic stem cell transplant (HSCT), developed leprosy. The patient was successfully treated with rifampicin, ofloxacin, and doxycycline, and the HSCT was performed without complications, being the first report, to our knowledge, of leprosy in an autologous HSCT patient.

Padrozação de estratégia molecular custo-efetiva para rastreamento de fenótipos eritrocitários e plaquetários raros em doadores de sangue visando à organização de banco de doadores raros no estado de São Paulo / Cost-effective molecular strategy standardization for screening of erythrocyte phenotypes and rare platelet in blood donors aiming at the organization of a rare donor bank in the state of São Paulo

OBJETIVOS: 1- Padronizar a genotipagem em larga escala para determinação de antígenos eritrocitários e plaquetários pela plataforma de OpenArray®em doadores de sangue. 2- Elaboração de software para registro destes doadores, com interface com o equipamento de genotipagem. METODOLOGIA: Extração automatizada de DNA e genotipagem através demicroarranjos líquidos (OpenArray®) para 32 alelos codificantes de antígenos eritrocitários e plaquetários. RESULTADOS: Foi realizada a genotipagem de 5487 doadores para os antígenos propostos, de forma completamente interfaceada e automatizada. O ensaio customizado de Open Array® mostrou-se acurado e de rápida execução. Elaborou-se software próprio para interfaceamento dos resultados da genotipagem e busca dos genótipos. CONCLUSÃO: Padronizou-se estratégia efetiva para rastreamento de doadores de sangue com fenótipos raros. A automação de todas as etapas experimentais e o interfaceamento completo dos dados minimizaram os erros humanos e aumentaram a rapidez do processo descrito, que pode ser aplicado como estratégia de genotipagem de doadores de todo o Estado de São Paulo.