Alterations in the Plasma Proteome Persist Ten Months after Recovery from SARS-CoV-2 Infection

Using a high density aptamer-based proteomic assay that measures more than 7000 proteins per sample, we evaluated the acute and long-term effects of SARS-CoV-2 breakthrough infections on the plasma proteome. During the acute phase of the infection, unvaccinated persons have a marked innate immune response while vaccinated patients manifested an adaptive immune response. However, at three and ten months after the onset of infection, the proteomes of both vaccinated and unvaccinated persons had not returned to normal. The dichotomy of vaccination status does not fully account for the heterogeneity of the host proteome response. Additional analyses identified clinical factors that influence changes in the plasma proteome. Protein biomarkers that predicted persistent lung disease and post-acute sequelae of SARS-CoV-2 at 10 months were identified. The persistence of alterations in the plasma proteome as late as 10 months after the onset of symptoms in both vaccinated and unvaccinated persons, prompts questions about long-term altered immune responses. These observations have implications for post-acute sequelae of SARS-CoV-2.