SARS-CoV-2 infection has caused a lasting global pandemic costing millions of lives and untold additional costs . Understanding the immune response to SARS-CoV-2 has been one of the main challenges in the past year in order to decipher mechanisms of host responses and interpret disease pathogenesis . Comparatively little is known in regard to how the immune response against SARS-CoV-2 differs from other respiratory infections . In our study, we compare the peripheral blood immune signature from SARS-CoV-2 infected patients to patients hospitalized pre-pandemic with Influenza Virus or Respiratory Syncytial Virus (RSV). Our in-depth profiling indicates that the immune landscape in patients infected by SARS-CoV-2 is largely similar to patients hospitalized with Flu or RSV . Similarly, serum cytokine and chemokine expression patterns were largely overlapping . Unique to patients infected with SARS-CoV-2 who had the most critical clinical disease state were changes in the regulatory T cell (Treg) compartment . A Treg signature including increased frequency, activation status, and migration markers was correlated with the severity of COVID-19 disease . These findings are particularly relevant as Tregs are being discussed as a therapy to combat the severe inflammation seen in COVID-19 patients. Likewise, having defined the overlapping immune landscapes in SARS-CoV-2, existing knowledge of Flu and RSV infections could be leveraged to identify common treatment strategies.