Resident memory T cells (T-RM) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, T-RM are mostly non-recirculating, which reduces the window of opportunity to examine these cells in the blood as they move to the lung parenchyma. Here, we identify circulating virus-specific T cell responses during acute infection with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Disease severity is associated predominantly with IFN gamma and IL-4 responses, increased responses against S peptides and apoptosis, whereas non-hospitalized patients have increased IL-12p70 levels, degranulation in response to N peptides and SARS-CoV-2-specific CCR7(+) T cells secreting IL-10. In convalescent patients, lung-T-RM are frequently detected even 10 months after initial infection, in which contemporaneous blood does not reflect tissue-resident profiles. Our study highlights a balanced anti-inflammatory antiviral response associated with a better outcome and persisting T-RM cells as important for future protection against SARS-CoV-2 infection. Lung resident memory T (T-RM) cells are important for protection from viral infection in the lungs. Here the authors use paired lung biopsy material and blood to characterize T cell responses in patients with COVID-19 over time and find persistence of antiviral lung T-RM cells that might be important to limit reinfection.