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

Peluso, Michael J.; Deitchman, Amelia N.; Torres, Leonel; Iyer, Nikita S.; Munter, Sadie E.; Nixon, Christopher C.; Donatelli, Joanna; Thanh, Cassandra; Takahashi, Saki; Hakim, Jill; Turcios, Keirstinne; Janson, Owen; Hoh, Rebecca; Tai, Viva; Hernandez, Yanel; Fehrman, Emily A.; Spinelli, Matthew A.; Gandhi, Monica; Trinh, Lan; Wrin, Terri; Petropoulos, Christos J.; Aweeka, Francesca T.; Rodriguez-Barraquer, Isabel; Kelly, J. Daniel; Martin, Jeffrey N.; Deeks, Steven G.; Greenhouse, Bryan; Rutishauser, Rachel L.; Henrich, Timothy J.

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.