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. 2023 Nov 19:48:89-95.
doi: 10.1016/j.jor.2023.11.041. eCollection 2024 Feb.

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

Marco S Caicedo  1   2 , Vianey Flores  1 , Rochelle Siapno  1 , Michael Crosby  2 , Lauryn A Samelko  1   2 , Joshua J Jacobs  2 , Nadim J Hallab  1   2
Affiliations

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

Marco S Caicedo et al. J Orthop. .

Abstract

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; P < 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 (P < 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.

Keywords: Antibodies; COVID-19; LTT; Lymphocytes; Metal sensitivity; Pain; Stimulation index; Total joint arthroplasty.

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Conflict of interest statement

MSC, VF, RS, MC, and LS are employees of Orthopedic Analysis, LLC. NJH is an employee of Orthopedic Analysis, LLC; has stock or stock options in Orthopedic Analysis, LLC.

Figures

Fig. 1
Fig. 1
A. Rate of positive COVID-19 IgG antibody titers. B. Median COVID-19 IgG antibody titers.
Fig. 2
Fig. 2
A. Patient-Specific Lymphocyte Stimulation Index to SARS-CoV-2-Spike-Protein or Implant Metal(s) by LTT. B. Median Lymphocyte Stimulation Index Response to SARS-CoV-2-Spike-Protein or Implant Metal(s) by LTT per Patient Group. C, challenge agent; G, group; LTT, lymphocyte transformation test.
Fig. 3
Fig. 3
Mean Lymphocyte Stimulation Index Response to the Original Strain of COVID-19, SARS-CoV-2-Spike-Protein, or the COVID-19 Omicron Variant Among Unvaccinated and Vaccinated Adults by LTT. C, challenge agent; G, group; LTT, lymphocyte transformation test.
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