Abstract COVID-19 infection is greatly heterogenous. Individuals with underlying immune dysregulation, will have abnormal responses to COVID-19, thereby accounting for different short-term outcomes and memory formation. Specifically, emerging evidence indicates poor outcomes in autoimmune and cancer patients. We propose that autoimmune patients and severe COVID-19 infection will share an exacerbated pathological response while cancer patients with disease-associated or treatment-induced immune deficiency, will fail to mount a protective anti-viral response. Here, we shall interrogate the effector B cell response to SARS-CoV-2 to identify determinants of protective and pathogenic responses in HC and autoimmune subjects.