A second key observation from these studies was the robust PB response. Some patients had PB frequencies rivaling those found in acute Ebola or Dengue infection (34, 42, 43, 55). Furthermore, blood PB frequencies are typically correlated with blood activated cTfh responses (40). However, in COVID-19 patients, this relationship between PB and activated cTfh was weak. The lack of relationship between these two cell types in this disease could be due to T cell-independent B cell responses, lack of activated cTfh in peripheral blood at this time point, or lower CXCR5 expression observed across lymphocyte populations, making it more difficult to identify cTfh. Indeed, activated (CD38+HLA-DR+) CD4 T cells could play a role in providing B cell help, perhaps as part of an extrafollicular response, but such a connection was also not robust in the current data. Most ICU patients made SARS-CoV2-specific antibodies, suggesting that at least part of the PB response was antigen-specific. Indeed, the cTfh response did correlate with antibodies suggesting that at least some of the humoral response is targeted against the virus. Future studies will be needed to address the antigen specificity, ontogeny, and role in pathogenesis for these robust PB responses.