The study investigates the persistence of SARS-CoV-2 antigens in plasma from 171 adults at various time points up to 14 months after RNA-confirmed infection, primarily focusing on those who were not vaccinated or reinfected during the pandemic. The findings, using the Simoa® single molecule array detection platform, show that 9.2% of pandemic-era participants had detectable SARS-CoV-2 antigens, significantly higher than the 2% positivity rate in pre-pandemic participants. The prevalence of detectable antigens increased over time, with a notable difference in the post-acute phase. Hospitalized participants and those with worse self-reported health during acute infection had higher antigen detection rates. The study suggests that SARS-CoV-2 may persist in some form or location for up to 14 months, influenced by the acute infection's severity. However, the specificity of the Simoa® assay is high but not perfect, and the study was conducted before the emergence of Delta and Omicron variants, which could affect results. The findings highlight the need for further research on the clinical implications of SARS-CoV-2 persistence.The study investigates the persistence of SARS-CoV-2 antigens in plasma from 171 adults at various time points up to 14 months after RNA-confirmed infection, primarily focusing on those who were not vaccinated or reinfected during the pandemic. The findings, using the Simoa® single molecule array detection platform, show that 9.2% of pandemic-era participants had detectable SARS-CoV-2 antigens, significantly higher than the 2% positivity rate in pre-pandemic participants. The prevalence of detectable antigens increased over time, with a notable difference in the post-acute phase. Hospitalized participants and those with worse self-reported health during acute infection had higher antigen detection rates. The study suggests that SARS-CoV-2 may persist in some form or location for up to 14 months, influenced by the acute infection's severity. However, the specificity of the Simoa® assay is high but not perfect, and the study was conducted before the emergence of Delta and Omicron variants, which could affect results. The findings highlight the need for further research on the clinical implications of SARS-CoV-2 persistence.