More than 450 million individuals have recovered from COVID-19, but little is known about the host responses to long COVID. We performed proteomic and metabolomic analyses of 991 blood and urine specimens from 144 COVID-19 patients with comprehensive clinical data and up to 763 days of follow up. Our data showed that the lungs and kidneys are the most vulnerable organs in long COVID patients. Pulmonary and renal long COVID of one-year revisit can be predicted by a machine learning model based on clinical and multi-omics data collected during the first month from the disease onset with an ACC of 87.5%. Serum protein SFTPB and ATR were associated with pulmonary long COVID and might be potential therapeutic targets. Notably, our data show that all the patients with persistent pulmonary ground glass opacity or patchy opacity lesions developed into pulmonary fibrosis at two-year revisit. Together, this study depicts the longitudinal clinical and molecular landscape of COVID-19 with up to two-year follow-up and presents a method to predict pulmonary and renal long COVID.

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