Sera from the cohort of convalescent individuals following mild disease did not have elevated DSG2 autoantibody levels (median OD = 0.37 [0.19–0.58], n = 40, P > 0.9999), nor did sera from a non-COVID-19 cohort of ITU patients (median OD = 0.35 [0.16–0.71], n = 16, P>0.9999), nor sera from a cohort of patients in convalescence after influenza infection (median OD = 0.35 [0.23–0.56], n = 48, P > 0.9999). Here, DSG2 is linked to COVID-19.