Establishing clinically meaningful ranges of metal hypersensitivity in orthopaedic patients using COVID-19 vaccine-induced adaptive immune responses from fully vaccinated adults.

Background: This study aimed to assess metal sensitization ranges among orthopaedic patients by comparing adaptive immune responses in all-comer pre- and post-operative orthopaedic adults who were COVID-19 unvaccinated or vaccinated vs patients with a painful aseptic implant by lymphocyte transformation test (LTT) to SARS-CoV-2-Spike-Protein (SP) and implant metal(s), respectively.

Methods: Data were retrospectively reviewed from three independent groups: unvaccinated COVID-19 adults (n = 23); fully COVID-19 vaccinated adults (n = 35); unvaccinated, painful aseptic implant patients with history of metal allergy (n = 98). Standard in vitro LTT for SP and implant metal(s) (nickel, cobalt) were performed and rated as negative (stimulation index [SI]<2), mild (SI ≥ 2), positive (SI ≥ 4-15), and high sensitization (SI > 15) adaptive immune responses to tested antigen.

Results: Overall, 17/23 (74%) of unvaccinated adults showed negative to mild LTT ranges, and 35/35 (100%) of vaccinated showed mild to positive LTT ranges to SP. Vaccinated individuals showed significantly higher median SI (16.1) to SP than unvaccinated (median SI, 1.7;  < 0.0001). Most vaccinated adults (94%) showed a lymphocyte SI > 4 to SP, establishing LTT SI ≥ 4 with >90% sensitivity for diagnosing effective COVID-19 adaptive immune responses. Significantly fewer painful orthopaedic patients (41%) showed comparable elevated levels of lymphocyte metal sensitivity at SI ≥ 4 compared to vaccinated group ( < 0.0001).

Conclusions: Vaccinated adults showed significantly higher lymphocyte SI to SP than unvaccinated indicating that SI ranges ≥4 should be set as unequivocally diagnostic of LTT-positive adaptive immune responses to tested antigen. This analysis supports using higher LTT SI ranges (SI ≥ 4) in diagnosing clinical orthopaedic-related Type IV metal-hypersensitivity responses among orthopaedic patients.