Updated project metadata. The majority of those infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the first wave did not require hospitalisation. Most had a short-lived mild or asymptomatic infection, while others had symptoms that persisted for weeks or months. We performed a longitudinal targeted analysis of the plasma proteome of 156 healthcare workers (HCW) with and without lab confirmed SARS-CoV-2 infection. We hypothesized that the plasma proteome would reflect differences in the inflammatory response that linked to symptom severity and duration. We showed that perturbation of the proteome persisted for over six weeks, tracking symptom severity and antibody responses. Additionally, we identified a prognostic signature at the time of seroconversion that identified individuals likely to suffer from persistent symptoms related to SARS-CoV-2 infection.