The COVID-19 pandemic has led to widespread mental health problems, necessitating the investigation of lon-gitudinal mental health changes, associated risk factors, and neural mechanisms in survivors. We recorded de-mographics, mental health, social support, and potential exposures in survivors at 3 months (n = 189), 6 months (n = 47), and 2 years (n = 69) post-discharge and collected brain imaging data at the second timepoint. Control groups included non-COVID-19 locals (3 months: n = 188, 6 months: n = 42, 2 years: n = 71). Results indicated that female survivors exhibited higher post-traumatic stress symptoms (PTSS) and depression levels than female controls for up to 2 years, along with higher anxiety level for up to 6 months. Male survivors had higher PTSS, depression, and anxiety levels than male controls at 2 months. Moreover, COVID-related trauma and low social support were risk factors for PTSS and negative emotions in survivors. Neuroimaging revealed increased amygdala activity in male survivors and correlations between hippocampus activity and depression symptoms as well as between right hippocampus activity and social support. Our study emphasized the importance of monitoring mental wellness in COVID-19 survivors and underscored the crucial role of social support in miti-gating mental health problems.