Association of Human Leukocyte Antigen Genotypes with Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine-Induced Subacute Thyroiditis.

Despite mass vaccination, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) is rarely seen as a complication. The reason why some individuals are susceptible to developing vaccine-induced SAT is not known. SAT develops in genetically predisposed individuals who carry specific human leukocyte antigen (HLA) haplotypes. It is unknown whether specific HLA alleles are associated with SARS-CoV-2 vaccine-induced SAT. This study compared the HLA profiles of patients with SARS-CoV-2 vaccine-induced SAT to controls, to assess whether there is an association between specific HLA genotypes and development of SAT. The relationship between HLA genotypes and the clinical course of SARS-CoV-2 vaccine-induced SAT was also evaluated. A case-control study was conducted in a Turkish tertiary care center. Fourteen patients with SARS-CoV-2 vaccine-induced SAT and 100 healthy controls were included. , and frequencies were analyzed by next-generation sequencing. The frequencies of alleles were significantly higher in SARS-CoV-2 vaccine-induced SAT cohort when compared with controls (: 13 [93%] vs. 40 [40%],  < 0.001; : 13 [93%] vs. 43 [43%],  < 0.001, respectively). More severe thyrotoxicosis was seen in patients having and homozygous alleles (free thyroxine: 4.47 ng/dL [3.77-5.18] vs. 1.41 ng/dL [1.22-2.63],  = 0.048). Inflammation tended to be more severe in homozygous patients (C-reactive protein: 28.2 mg/dL [13.6-42.9] vs. 4.8 [1.2-10.5],  = 0.07). The frequencies of and alleles were higher in SARS-CoV-2 vaccine-induced SAT compared with controls. Homozygosity for and was associated with thyrotoxicosis and a greater inflammatory reaction. Our findings should be confirmed in studies of other populations.