Immune determinants of viral clearance in hospitalised COVID-19 patients: reduced circulating naive CD4+T Cell counts correspond with delayed viral clearance

Zlei, M.; Sidorov, I.A.; Joosten, S.A.; Heemskerk, M.H.M.; Myeni, S.K.; Pothast, C.R.; Brouwer, C.S. de; Boomaars-van der Zanden, A.L.; Meijgaarden, K.E. van; Morales, S.T.; Wessels, E.; Janse, J.J.; Goeman, J.J.; Cobbaert, C.M.; Kroes, A.C.M.; Cannegieter, S.C.; Roestenberg, M.; Visser, L.G.; Kikkert, M.; Feltkamp, M.C.W.; Arbous, S.M.; Staal, F.J.T.; Ottenhoff, T.H.M.; Dongen, J.J.M. van; Roukens, A.H.E.; Vries, J.J.C. de; Collaboration BEAT-COVID; Collaboration LUMC COVID

doi:doi:10.3390/cells11172743

Virus-specific cellular and humoral responses are major determinants for protection from critical illness after SARS-CoV-2 infection. However, the magnitude of the contribution of each of the components to viral clearance remains unclear. Here, we studied the timing of viral clearance in relation to 122 immune parameters in 102 hospitalised patients with moderate and severe COVID-19 in a longitudinal design. Delayed viral clearance was associated with more severe disease and was associated with higher levels of SARS-CoV-2-specific (neutralising) antibodies over time, increased numbers of neutrophils, monocytes, basophils, and a range of pro-inflammatory cyto-/chemokines illustrating ongoing, partially Th2 dominating, immune activation. In contrast, early viral clearance and less critical illness correlated with the peak of neutralising antibodies, higher levels of CD4 T cells, and in particular naive CD4+ T cells, suggesting their role in early control of SARS-CoV-2 possibly by...Show moreVirus-specific cellular and humoral responses are major determinants for protection from critical illness after SARS-CoV-2 infection. However, the magnitude of the contribution of each of the components to viral clearance remains unclear. Here, we studied the timing of viral clearance in relation to 122 immune parameters in 102 hospitalised patients with moderate and severe COVID-19 in a longitudinal design. Delayed viral clearance was associated with more severe disease and was associated with higher levels of SARS-CoV-2-specific (neutralising) antibodies over time, increased numbers of neutrophils, monocytes, basophils, and a range of pro-inflammatory cyto-/chemokines illustrating ongoing, partially Th2 dominating, immune activation. In contrast, early viral clearance and less critical illness correlated with the peak of neutralising antibodies, higher levels of CD4 T cells, and in particular naive CD4+ T cells, suggesting their role in early control of SARS-CoV-2 possibly by proving appropriate B cell help. Higher counts of naive CD4+ T cells also correlated with lower levels of MIF, IL-9, and TNF-beta, suggesting an indirect role in averting prolonged virus-induced tissue damage. Collectively, our data show that naive CD4+ T cell play a critical role in rapid viral T cell control, obviating aberrant antibody and cytokine profiles and disease deterioration. These data may help in guiding risk stratification for severe COVID-19.Show less

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Immune determinants of viral clearance in hospitalised COVID-19 patients: reduced circulating naive CD4+T Cell counts correspond with delayed viral clearance