The coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posts a challenge for the understanding of factors affecting disease severity and the identification of prognostic biomarkers and physiological processes relevant for the development of new diagnostic and therapeutic interventions to contribute to the control of this pandemic. To address this challenge, in this study we used a quantitative proteomics together with multiple data analysis algorithms to characterize serum protein profiles in five cohorts from healthy to SARS-CoV-2-infected asymptomatic, recovered, nonsevere and severe individuals. The results corroborated previous findings, but the analysis was focused on novel disease processes and biomarkers. Our results contributed to the characterization of SARS-CoV-2-host molecular interactions and provided protein prognostic biomarkers and physiological disorders associated with COVID-19 with potential implications for the development of new diagnostic and therapeutic interventions to contribute to the control of this pandemic.