Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2 specific CD8 T cell responses following COVID-19

Roukens, A. H. E.; Konig, M.; Dalebout, T.; Tak, T.; Azimi, S.; Kruize, Y.; Pothast, C. R.; Hagedoorn, R. S.; Arbous, S. M.; Zhang, J. L. H.; Verheij, M.; Prins, C.; Does, A. M.; Hiemstra, P. S.; Vries, J. J. C.; Janse, J. J.; Roestenberg, M.; Myeni, S. K.; Kikkert, M.; Heemskerk, M. H. M.; Yazdanbakhsh, M.; Smits, H. H.; Jochems, S. P.; BEAT-COVID group,; group, COVID-19 LUMC

The immune system plays a major role in Coronavirus Disease 2019 (COVID-19) pathogenesis, viral clearance and protection against re-infection. Immune cell dynamics during COVID-19 have been extensively documented in peripheral blood, but remain elusive in the respiratory tract. We performed minimally-invasive nasal curettage and mass cytometry to characterize nasal immune cells of COVID-19 patients during and 5-6 weeks after hospitalization. Contrary to observations in blood, no general T cell depletion at the nasal mucosa could be detected. Instead, we observed increased numbers of nasal granulocytes, monocytes, CD11c+ NK cells and exhausted CD4+ T effector memory cells during acute COVID-19 compared to age-matched healthy controls. These pro-inflammatory responses were found associated with viral load, while neutrophils also negatively correlated with oxygen saturation levels. Cell numbers mostly normalized following convalescence, except for persisting CD127+ granulocytes and activated T cells, including CD38+ CD8+ tissue-resident memory T cells. Moreover, we identified SARS-CoV-2 specific CD8+ T cells in the nasal mucosa in convalescent patients. Thus, COVID-19 has both transient and long-term effects on the immune system in the upper airway.