Since 2020, our clinic has observed a notable increase in primary immunodeficiency (PI) patients presenting with antibody deficiencies, despite previously reporting minimal illness or being clinically stable prior to the COVID-19 pandemic. Concurrently, we’ve documented a rapid rise in cases of Postural Orthostatic Tachycardia Syndrome (POTS) and related dysautonomia. Whereas only a handful of POTS patients were seen before 2020, our current clinic population exceeds 40, with roughly 80% also demonstrating antibody deficiency, most commonly Specific Antibody Deficiency (SAD). We conducted a retrospective review of five patients with SAD and POTS receiving intravenous immunoglobulin (IVIg) therapy in either the home infusion setting or our clinic. Comorbidities included other dysautonomia conditions, Lyme disease, and orthostatic hypotension. The cohort was all female, White, median age 25 years, and dosing of 0.62 g/kg/Q4Weeks over 10 months. Reported Adverse Drug Reactions (ADRs) were primarily headaches and fatigue, with one patient discontinuing IVIg due to aseptic meningitis. Functional impact was substantial, with missed school, impaired work capacity, and reliance on online education. IgG levels improved in most patients. Patient-reported outcomes varied. Two described clear improvement in syncope, dizziness, and activity tolerance and one noted improved energy but no change in core POTS symptoms, one reported diminishing benefit over time, and one discontinued due to severe ADRs. Compared with other POTS treatments, IVIg was perceived superior by two patients, neutral by two, and intolerable by one. This review highlights a post-COVID-19 increase in patients presenting with both PI and POTS, with a notable overlap of SAD. While IVIg was associated with improved IgG levels and, in some cases, reduced syncope and fatigue, responses were heterogeneous. These findings suggest a possible immunologic contribution to POTS in the context of SAD, but the small sample size limits definitive conclusions. Future research should investigate correlations between new onset PI/SAD and POTS, the role of COVID-19 in triggering dysautonomia, and whether IVIg can be systematically evaluated as a therapeutic option. Larger, prospective studies are needed to clarify whether recurrent infections and immune dysfunction exacerbate POTS symptoms and to determine if IVIg can meaningfully improve quality of life.
