Immune responses of critically ill patients with sepsis can be classified into three patterns: macrophage-activation syndrome (MAS) (Kyriazopoulou et al., 2017), sepsis-induced immunoparalysis characterized by low expression of the human leukocyte antigen D related (HLA-DR) on CD14 monocytes (Lukaszewicz et al., 2009), and an intermediate functional state of the immune system lacking obvious dysregulation. We investigated whether this classification might apply to patients with SRF caused by SARS-CoV-2. Results revealed that approximately one fourth of patients with SRF have MAS and that most patients suffer from immune dysregulation dominated by low expression of HLA-DR on CD14 monocytes, which is triggered by monocyte hyperactivation, excessive release of interleukin-6 (IL-6), and profound lymphopenia. This pattern is distinct from the immunoparalysis state reported in either bacterial sepsis or SRF caused by 2009 H1N1 influenza.