The delayed generation of functional virus-specific cTfh cells in severe patients observed in our study may reflect the delayed germinal center reaction in severe compared with mild patients, which supports and potentially explains the observation from other labs that patients with mild COVID-19 displayed substantial affinity maturation for antibodies binding to the prefusion spike much earlier than patients with severe COVID-1939, and blunted affinity maturation against the SARS-CoV-2 prefusion spike protein may predict worse outcome for hospitalized patients40. This evidence concerns the gene CHMP5 and COVID-19.