The biology driving individual patient responses to SARS-CoV-2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year post-disease onset, from 215 SARS-CoV-2 infected subjects with differing disease severities. Our analyses revealed distinct “systemic recovery” profiles, with specific progression and resolution of the inflammatory, immune, metabolic and clinical responses. In particular, we found a strong inter- and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery at the patient level, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc- bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app, designed to test our findings prospectively.