Lung resident dendritic cells majorly have a protective role during the early onset of the disease by activating the adaptive immune cell response. Under the influence of PAMPs, DAMPs, and inflammatory cytokine signaling, lung resident dendritic cells are conditioned and migrate to the draining lymph node under the influence of CCR7 where they prime naïve CD4+ and CD8+ T cells (Braun et al., 2011; Thaiss et al., 2011). In contrast, monocyte-derived dendritic cells generate under the influence of GM-CSF, IFN-γ, and IL-4, along with other proinflammatory signals (Qu et al., 2014). Previous studies have shown elevated secretions of CCL3, CCL5, MCP-1, IP-10, TNF-α, and IL-6 by activated inflammatory dendritic cells (DCs) in response to SARS-CoV (Law et al., 2005). Recent reports also suggest the presence of activated dendritic cells in COVID-19 patients. Notably, meta-transcriptomic sequencing of BALF obtained from 8 COVID-19 patients revealed an activated status of these cells along with neutrophils, as compared to other innate and adaptive immune cells (Yang A.P. et al., 2020; Zhou Z. et al., 2020). Thus, based on previous clinical studies on SARS-CoV infection and recent emerging studies on SARS-CoV-2, it is evident that hyperinflammatory immune response in severe and critically ill COVID-19 patients is mainly mounted by infiltrated innate immune cells at the site of infection with a substantial contribution by the adaptive immune cells as discussed below in the section on the dysfunctional adaptive immune response.