Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients.
Samuele NotarbartoloValeria RanzaniAlessandra BanderaPaola GruarinValeria BevilacquaAnna Rita PutignanoAndrea GobbiniEugenia GaleotaCristina ManaraMauro BombaciElisa PesceElena ZagatoAndrea FavalliMaria Lucia SarnicolaSerena CurtiMariacristina CrostiMartina MartinovicTanya FabbrisFederico MariniLorena DonniciMariangela LorenzoMarilena MancinoRiccardo UngaroAndrea LombardiDavide MangioniAntonio MuscatelloStefano AlibertiFrancesco BlasiT Maria DeFeoDaniele PratiLara ManganaroFrancesca GranucciAntonio LanzavecchiaRaffaele de FrancescoAndrea GoriRenata GrifantiniSergio AbrignaniPublished in: Science immunology (2021)
To understand how a protective immune response against SARS-CoV-2 develops over time, we integrated phenotypic, transcriptional and repertoire analyses on PBMCs from mild and severe COVID-19 patients during and after infection, and compared them to healthy donors (HD). A type I IFN-response signature marked all the immune populations from severe patients during the infection. Humoral immunity was dominated by IgG production primarily against the RBD and N proteins, with neutralizing antibody titers increasing post infection and with disease severity. Memory B cells, including an atypical FCRL5+ T-BET+ memory subset, increased during the infection, especially in patients with mild disease. A significant reduction of effector memory, CD8+ T cells frequency characterized patients with severe disease. Despite such impairment, we observed robust clonal expansion of CD8+ T lymphocytes, while CD4+ T cells were less expanded and skewed toward TCM and TH2-like phenotypes. MAIT cells were also expanded, but only in patients with mild disease. Terminally differentiated CD8+ GZMB+ effector cells were clonally expanded both during the infection and post-infection, while CD8+ GZMK+ lymphocytes were more expanded post-infection and represented bona fide memory precursor effector cells. TCR repertoire analysis revealed that only highly proliferating T cell clonotypes, which included SARS-CoV-2-specific cells, were maintained post-infection and shared between the CD8+ GZMB+ and GZMK+ subsets. Overall, this study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8+ T cell population with memory precursor-like features.
Keyphrases
- sars cov
- immune response
- induced apoptosis
- dendritic cells
- cell cycle arrest
- working memory
- regulatory t cells
- transcription factor
- respiratory syndrome coronavirus
- newly diagnosed
- gene expression
- cell death
- oxidative stress
- cross sectional
- single cell
- dna methylation
- genome wide
- toll like receptor
- cell proliferation
- peritoneal dialysis
- peripheral blood