Japan is currently suffering the fourth wave of the COVID-19 pandemic, with the dominant type being SARS-CoV-2 alpha variant. Patients with COVID-19 variant types show more aggressive symptoms. In the present study, three patients developed a red face during treatment. Two of them suddenly worsened shortly after. We assumed that the red face reflected a cytokine storm and conjectured that it may be a specific sign of variant type COVID-19, because we have never seen it in patients with non-variant type. Moreover, we believe that red face may be predictive of a sudden deterioration.