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10. Modulation of Human Macrophages by Plasma from COVID-19 Patients Following BCG Vaccination: BATTLE Trial

Author

Buosi K, Jalalizadeh M, Maia AR, Morari J, Velloso LA, and Reis LO

Subjects
covid, bcg, trained immunity, gender, age, healthcare worker, ifns, ace2., Medicine (General), R5-920
Abstract

Keini Buosi,1,* Mehrsa Jalalizadeh,1,* Aline Rosa Maia,2 Joseane Morari,2 Licio Augusto Velloso,2 Leonardo Oliveira Reis1,3 1Uroscience, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, Sao Paulo, 13083-872, Brazil; 2Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas, Campinas, 13083-864, Brazil; 3Immunoncology, Pontifical Catholic University of Campinas, PUC-Campinas, Campinas, Sao Paulo, 13087-571, Brazil*These authors contributed equally to this workCorrespondence: Leonardo Oliveira Reis, PUC-Campinas, Pontifical Catholic University of Campinas, ImmunOncology, Av. John Boyd Dunlop - Jardim Ipaussurama, Campinas, Sao Paulo, 13034-685, Brazil, Tel/Fax +55 019 35217481, Email Reisleo@unicamp.brPurpose: To analyze the interfering effect of plasma from COVID-19 convalescent adults vaccinated or not with intradermal Bacillus Calmette-Guérin (BCG) on human macrophages.Methods: The BATTLE clinical trial (NCT04369794) was initiated in the 2020 SARS-CoV-2 pandemic to study the safety and efficacy of BCG revaccination of COVID-19 convalescent adults. We measured the expression induction of eleven COVID-19-related genes in human macrophages cultured in plasma taken from 22 BCG vaccinated and 17 placebo patients at baseline and 45 days post-intervention. Subgroup analysis was based on gender, age, job type (healthcare worker [HCW] vs non-HCW), and the presence of anosmia/dysgeusia.Results: Compared to plasma from placebo counterparts, the plasma of BCG vaccinated patients increased the expression induction of interferon (IFN)β-1b (p = 0.042) in human macrophages. This increase was more pronounced in females and in healthcare workers (HCW) (p = 0.007 and 0.001, respectively). Interferon-induced transmembrane protein 3 (IFITM3) expression induction was increased by plasma from BCG vaccinated females, young age group, and HCWs (p = 0.004, 0.011, and 0.040, respectively). Interleukin (IL)-10 induction increased by the plasma of young BCG recipients (p = 0.008). Induction of IL-6 expression increased by non-HCW BCG recipients plasma but decreased by HCW BCG recipients plasma (p = 0.005). Baseline plasma of patients who presented with anosmia/dysgeusia at the time of admission induced lower angiotensin-converting enzyme 2 (ACE2) compared to those without the symptom (0.76 vs 0.97, p = 0.004). ACE2 expression induction significantly increased by plasma of BCG recipients if they had anosmia/dysgeusia on admission (p = 0.028).Conclusion: The expressions of IFNβ-1b, IFITM3, IL-6, and IL-10 in human macrophages incubated with the plasma of COVID-19 convalescent patients were modulated by BCG. These modulations depended on subject-specific characteristics, including gender, age, clinical presentation (anosmia/dysgeusia), job type, and previous exposure to mycobacteria.Keywords: COVID, BCG, trained immunity, gender, age, healthcare worker, IFNs, ACE2

Published
2024

45. Referral pattern of leptospirosis cases during a large urban epidemic of dengue

Author

Lee W. Riley, Brendan Flannery, Martha Maria Pereira, Cibele Maria Ribeiro Dourado, F Velloso L de, Mitermayer Galvão dos Reis, L G De Codes, Albert I. Ko, C Carvalho C de, and S Orrico G de

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Referral, law.invention, Dengue fever, Dengue, law, Virology, Humans, Medicine, Leptospirosis, Child, Intensive care medicine, Referral and Consultation, Aged, business.industry, Odds ratio, Middle Aged, medicine.disease, Intensive care unit, Infectious Diseases, Infectious disease (medical specialty), Child, Preschool, Ambulatory, Female, Parasitology, Viral disease, business
Abstract

During heavy seasonal rainfall in 1996, concurrent epidemics of dengue and leptospirosis occurred in an urban center in northeastern Brazil. We interviewed 110 cases of leptospirosis hospitalized a median of seven days after the onset of illness to evaluate the impact of the dengue epidemic on the triage of suspected leptospirosis from ambulatory clinics to the infectious disease reference hospital. Within the first three days of illness, 46 (42%) cases sought their first medical evaluation, and 28 (61% of 46) received a diagnosis of dengue. Dengue diagnoses were associated with a median of five days delay in referral to the infectious disease hospital. Patients who reported initial diagnoses of dengue were more likely than other patients to have required admission to the intensive care unit (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 0.8-9.5) and to have died during hospitalization (OR = 5.1, 95% CI = 0.8-55.0). These findings indicate that diagnostic confusion between the early symptoms of leptospirosis and dengue may have contributed to the high mortality observed during the leptospirosis epidemic.

Published
2001
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50. Type 2 diabetes mellitus - an autoimmune disease?

Author

Velloso, L Augusto, Eizirik, Decio L., Cnop, Miriam, Velloso, L Augusto, Eizirik, Decio L., and Cnop, Miriam

Abstract

Inflammation-induced inhibition of the insulin signalling pathway can lead to insulin resistance and contribute to the development of type 2 diabetes mellitus (T2DM). Obesity and insulin resistance are associated with a chronic but subclinical inflammatory process that impairs insulin action in most tissues and could also hamper pancreatic β-cell function. The involvement of monocytic cells and the profiles of the chemokines and cytokines induced by this inflammation suggest an innate immune response. However, emerging data indicate that elements of the adaptive immune system could also be involved. As activation of an adaptive response requires antigen specificity, some researchers have hypothesized that T2DM evolves from an innate immune response to an autoimmune condition. In this Perspectives article, we present the arguments for and against this hypothesis and discuss which mechanisms could be involved in a putative switch from innate immunity to autoimmunity. © 2013 Macmillan Publishers Limited., SCOPUS: re.j, info:eu-repo/semantics/published

Published
2013

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