Prospective cohort study to assess clinical, virological and host response aspects in patients with COVID-19

Abstract

We are starting the activities of units (wards and ICU) for the care of patients with COVID-19 at Hospital São Paulo, therefore, with the opportunity to prospectively monitor patients with moderate-to-moderate / severe illness. These patients will be with clinical manifestations between those who will be discharged to the home (mild cases) and those who should be directly admitted to Intensive Care Units (ICU) (severe cases). Thus, their outcome will be hospital discharge or clinical deterioration with the need for vasoactive drugs and ventilatory support, admission to the ICU and eventual death, that is, with improvement or deterioration of the patient. Thus, we will have a unique opportunity to monitor the host's response and describe the altered processes or pathways in the admission and follow-up of patients with different clinical outcomes. The pulmonary involvement of patients with COVID-19 and the data available in series of patients support the involvement of innate and acquired immunity, with profound lymphopenia and high levels of pro-inflammatory cytokines (data previously described for SARS-CoV and MERS -CoV). We have a background of contributions from projects supported by FAPESP (processes 2011 / 20189-5 and 2017 / 21052-0) evaluating the host response in sepsis, which includes the investigation of leukocyte immunophenotyping, plasma and intracellular cytokine research, as well as other cellular functions. More relevant to this proposal, we recently expanded our tools incorporating transcriptomics and proteomics, which has allowed us to comprehensively assess the host's response in the context of sepsis. Our hypothesis is that in patients with COVID-19, in addition to changes in lymphocyte subpopulations, which we will evaluate immunophenotypically, the presence of circulating cytokines, which we will also evaluate, there will be a greater disturbance in the regulation of transcription and gene translation and that this will be captured in the analysis of the mononuclear cell proteome. Taking advantage that we will monitor patients with potential improvement or worsening, we can describe processes related to these outcomes and, eventually, biomarkers that help us to anticipate them. Goals: Main goal: Bearing in mind that we will monitor patients with a potential for improvement or deterioration, we can describe processes or patterns of host response related to these outcomes and, eventually, identify biomarkers that help us to discriminate patients with distinct outcomes. Specific objectives: 1. Clinical-epidemiological: Describe the clinical changes in patients of moderate severity, characterizing aspects that may be related to their outcome. 2. Virological monitoring: Assess the presence of SARS-CoV-2 in nasal and oropharyngeal secretion during patient follow-up.3. Assess the dynamics of changes in peripheral blood cell populations (lymphocytes, monocytes and neutrophils). A. Monitoring of T, TCD4, TCD8, B and NK lymphocyte count. B. Evaluate the expression of cell activation markers (HLA-DR and CD38) in TCD4 + and TCD8 + lymphocytes.4. Determine the plasma level of cytokines and chemokines involved in the pathogenesis of the disease and representative of inflammatory and anti-inflammatory activity, as well as of subpopulations of T lymphocytes. 5. Proteomics of peripheral blood mononuclear cells (PBMC). A. Qualitative and quantitative proteomic analysis (Label-free quantification). B. Functional enrichment. C. Protein-protein interaction networks (PPIN), looking for key proteins and modules. We estimated to include 100 patients, of which 20% might have clinical deterioration and 80% clinical resolution with treatment in the ward. (AU)