{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:06:45Z","timestamp":1775002005979,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Background: This proposal aims to explain some of the gaps in scientific knowledge on the natural history of coronavirus disease (COVID-19), with a specific focus on immune, inflammatory, and metabolic markers, in parallel with temporal assessment of clinical and mental health in patients with COVID-19. The study will explore the temporal modulatory effects of physical activity and body composition on individual trajectories. This approach will provide a better understanding of the survival mechanisms provided by the immunomodulatory role of physical fitness. Methods: We will conduct a prospective observational cohort study including adult patients previously infected with the SARS-CoV-2 virus who have expressed a mild to moderate COVID-19 infection. Procedures will be conducted for all participants at baseline, six weeks after vaccination, and again at 12 months. At each visit, a venous blood sample will be collected for immune phenotypic characterization and biochemistry assays (inflammatory and metabolic parameters). Also, body composition, physical activity level, cardiovascular and pulmonary function, peripheral and respiratory muscle strength, functional exercise capacity, and mental health will be evaluated. Using the baseline information, participants will be grouped based on physical activity levels (sedentary versus active), body composition (normal weight versus overweight or obese), and SARS-CoV-2 status (positive versus negative). A sub-study will provide mechanistic evidence using an in-vitro assay based on well-trained individuals and age-matched sedentary controls who are negative for SARS-CoV-2 infection. Whole blood will be stimulated using recombinant human coronavirus to determine the cytokine profile. Peripheral blood mononuclear cells (PBMCs) from healthy well-trained participants will be collected and treated with homologous serum (from the main study; samples collected before and after the vaccine) and recombinant coronavirus (inactive virus). The metabolism of PBMCs will be analyzed using Respirometry (Seahorse). Data will be analyzed using multilevel repeated-measures ANOVA. Conclusions: The data generated will help us answer three main questions: (1) Does the innate immune system of physically active individuals respond better to viral infections compared with that of sedentary people? (2) which functional and metabolic mechanisms explain the differences in responses in participants with different physical fitness levels? and (3) do these mechanisms have long-term positive modulatory effects on mental and cardiovascular health? Trial registration number: Brazilian Registry of Clinical Trials: RBR-5dqvkv3. Registered on 21 September 2021.<\/jats:p>","DOI":"10.3390\/ijerph182413249","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T11:27:36Z","timestamp":1639654056000},"page":"13249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Modulatory Effects of Physical Activity Levels on Immune Responses and General Clinical Functions in Adult Patients with Mild to Moderate SARS-CoV-2 Infections\u2014A Protocol for an Observational Prospective Follow-Up Investigation: Fit-COVID-19 Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9645-1003","authenticated-orcid":false,"given":"F\u00e1bio Santos","family":"Lira","sequence":"first","affiliation":[{"name":"Exercise and Immunometabolism Research Group, Postgraduation Program in Movement Sciences, Department of Physical Education, Universidade Estadual Paulista (UNESP), Presidente Prudente 19060-900, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9119-7774","authenticated-orcid":false,"given":"Telmo","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology, Polytechnic Institute of Coimbra, Coimbra Health School, Rua 5 de Outubro-SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal"},{"name":"Laboratory for Applied Health Research (LabinSa\u00fade), Rua 5 de Outubro-SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9342-5563","authenticated-orcid":false,"given":"Luciele","family":"Guerra Minuzzi","sequence":"additional","affiliation":[{"name":"Exercise and Immunometabolism Research Group, Postgraduation Program in Movement Sciences, Department of Physical Education, Universidade Estadual Paulista (UNESP), Presidente Prudente 19060-900, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2236-2478","authenticated-orcid":false,"given":"Caique","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Exercise and Immunometabolism Research Group, Postgraduation Program in Movement Sciences, Department of Physical Education, Universidade Estadual Paulista (UNESP), Presidente Prudente 19060-900, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1154-740X","authenticated-orcid":false,"given":"Tiago","family":"Olean-Oliveira","sequence":"additional","affiliation":[{"name":"Exercise and Immunometabolism Research Group, Postgraduation Program in Movement Sciences, Department of Physical Education, Universidade Estadual Paulista (UNESP), Presidente Prudente 19060-900, SP, Brazil"}]},{"given":"Ana Paula Coelho","family":"Figueira Freire","sequence":"additional","affiliation":[{"name":"Physiotherapy Department, Universidade do Oeste Paulista (UNOESTE), Presidente Prudente 19050-900, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-7331","authenticated-orcid":false,"given":"Manuel Jo\u00e3o","family":"Coelho-e-Silva","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o do Desporto e da Atividade F\u00edsica, Faculdade de Ci\u00eancias do Desporto e Educa\u00e7\u00e3o F\u00edsica, Universidade de Coimbra, CIDAF, 3030-779 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7844-0506","authenticated-orcid":false,"given":"Armando","family":"Caseiro","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology, Polytechnic Institute of Coimbra, Coimbra Health School, Rua 5 de Outubro-SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal"},{"name":"Laboratory for Applied Health Research (LabinSa\u00fade), Rua 5 de Outubro-SM Bispo, Apartado 7006, 3046-854 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7010-2799","authenticated-orcid":false,"given":"Ronaldo Vagner","family":"Thomatieli-Santos","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Universidade Federal de S\u00e3o Paulo (UNIFESP), Santos 11000-000, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-888X","authenticated-orcid":false,"given":"Vanessa Ribeiro","family":"Dos Santos","sequence":"additional","affiliation":[{"name":"Skeletal Muscle Assessment Laboratory Postgraduation Program in Movement Sciences, Department of Physical Education, Universidade Estadual Paulista (UNESP), Presidente Prudente 19060-900, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4700-0000","authenticated-orcid":false,"given":"Luis Alberto","family":"Gobbo","sequence":"additional","affiliation":[{"name":"Skeletal Muscle Assessment Laboratory Postgraduation Program in Movement Sciences, Department of Physical Education, Universidade Estadual Paulista (UNESP), Presidente Prudente 19060-900, SP, Brazil"}]},{"given":"Mar\u00edlia","family":"Seelaender","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, LIM26-HC, FMUSP, University of S\u00e3o Paulo, S\u00e3o Paulo 11000-000, SP, Brazil"}]},{"given":"Karsten","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Department of Exercise Physiology and Sports Therapy, Institute of Sports Science, Justus-Liebig-University Giessen, 35390 Giessen, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3116-4553","authenticated-orcid":false,"given":"Ricardo Aurino","family":"Pinho","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, School of Medicine, Pontificia Universidade Catolica Do Parana, Curitiba 80000-000, PR, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7019-9762","authenticated-orcid":false,"given":"Jos\u00e9 Cesar","family":"Rosa-Neto","sequence":"additional","affiliation":[{"name":"Immunometabolism Research Group, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, Universidade de S\u00e3o Paulo (USP), S\u00e3o Paulo 01000-000, SP, Brazil"}]},{"given":"Bruna Spolador","family":"de Alencar Silva","sequence":"additional","affiliation":[{"name":"Exercise and Immunometabolism Research Group, Postgraduation Program in Movement Sciences, Department of Physical Education, Universidade Estadual Paulista (UNESP), Presidente Prudente 19060-900, SP, Brazil"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"ref_1","first-page":"00542","article-title":"Persistent symptoms 3 months after a SARS-CoV-2 infection: The post-COVID-19 syndrome?","volume":"6","author":"Delbressine","year":"2020","journal-title":"ERJ Open Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1001\/jama.2020.12603","article-title":"Persistent Symptoms in Patients after Acute 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