There is growing evidence that the humoral immune response plays a significant role in the resolution of SARS-CoV-2. Patients with inherited or acquired immunoglobulin deficiencies have a higher risk of mortality, delayed viral clearance, and prolonged symptomatic infection, and this contributes to viral evolution. Case reports/series have implied a therapeutic role of monoclonal antibodies and convalescent plasma (CCP) as well as antivirals in the management of seronegative, symptomatic patients with SARS-CoV-2. In this review, we discuss the existing evidence supporting the efficacy of the above-mentioned treatment options and provide suggestions for management.