Long-term SARS-CoV-2-specific immune and inflammatory responses in individuals recovering from COVID-19 with and without post-acute symptoms

Cell Rep. 2021 Aug 10;36(6):109518. doi: 10.1016/j.celrep.2021.109518. Epub 2021 Aug 6.


We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally in 70 individuals with PCR-confirmed SARS-CoV-2 infection. Participants represent a spectrum of illness and recovery, including some with persistent viral shedding in saliva and many experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). T cell responses remain stable for up to 9 months. Whereas the magnitude of early CD4+ T cell immune responses correlates with severity of initial infection, pre-existing lung disease is independently associated with higher long-term SARS-CoV-2-specific CD8+ T cell responses. Among participants with PASC 4 months following coronavirus disease 2019 (COVID-19) symptom onset, we observe a lower frequency of CD8+ T cells expressing CD107a, a marker of degranulation, in response to Nucleocapsid (N) peptide pool stimulation, and a more rapid decline in the frequency of N-specific interferon-γ-producing CD8+ T cells. Neutralizing antibody levels strongly correlate with SARS-CoV-2-specific CD4+ T cell responses.

Keywords: COVID-19; PASC; SARS-CoV-2; T cell; immunity; long COVID; post-acute sequelae of SARS-CoV-2 infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 / complications*
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Post-Acute COVID-19 Syndrome
  • SARS-CoV-2 / immunology*
  • Severity of Illness Index
  • Virus Shedding / immunology


  • Antibodies, Neutralizing
  • Antibodies, Viral