ABSTRACT
While several studies have been conducted on HLA and Covid-19 infection, few investigated the role of HLA polymorphism on vaccination response. We previously analyzed the HLA allele and haplotype frequencies in a hundred weak responders (antibody levels <5th percentile) after mRNA anti-Covid vaccine and found some suggestions about specific alleles and one haplotype. We moved on typing individuals enrolled in the same cohort study ("RENAISSANCE") with antibody titers above the 95th percentile at six months after vaccination, in order to search for any alleles predictive of strong humoral response. Individuals with clinical history of COVID-19 or positive anti-nucleocapsid antibodies were excluded. Allelic frequencies were compared with those of weak responders and of the general population, taken from the national bone marrow donor registry, IBMDR. N = 123 evaluable individuals presented with >95th percentile antibody titers at six months after BNT162b2 vaccine. One-third of them had >2080 BAU/mL, lowest value was 1261 BAU/mL. Comparison of allelic frequencies with weak responders showed a significant different proportion of individuals carrying A*03:01, A*24:02 and DRB1*16:01 (21.5% vs. 3.6%, 7.7% vs. 14.9% and 3.2% vs. 8.1% respectively). Moreover, when looking at alleles of the ancestral haplotype A3-B35-C4-DR1, we observed frequencies of 4.47%, 0.84% and 0% in the present cohort, IBMDR and weak responders, respectively. After adjusting for age, gender and BMI, the presence of A*03:01 confirmed to be statistically significant (p<0.0001) and was predictive of high antibody titers at six months with an odds ratio of 12.5 with respect to weak antibody levels. Age was the only other significant variable, with an odds ratio of 0.96. Clinical collection data is underway to correlate Covid-19 infection rates in both cohorts, in an attempt to find a definite correlation between HLA and vaccine protection.
ABSTRACT
OBJECTIVE: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic disease (Covid-19) affects thyroid function via multiple mechanisms. We described painless atypical thyroiditis coexisting with non-thyroidal illness syndrome in patients hospitalized for severe Covid-19 disease. We aimed to better characterize it and to follow its evolution over time. METHOD(S): Baseline (at hospital admittance) and longitudinal study of consecutive patients hospitalized for severe Covid-19 disease, without known history of thyroid disfunction, assessing serum thyroid function and autoantibodies, inflammatory markers and thyroid ultrasound scan (US). Patients showing US focal hypoechoic areas suggestive for thyroiditis (thyroiditis-areas) also underwent thyroid 99mTc or I123 uptake scan and thyroid US-guided fine needle aspiration (US-FNA) for lymphocyte and SARS-CoV-2 RNA analysis. RESULT(S): Among 183 patients, thyroid US was performed at the earliest possible time (2-3 months post infection) in 65 (35%) and showed thyroiditis-areas in 18/65 (28%) patients;thyroid 99mTc/I123 uptake was reduced in 14/17 (82%). Thyroiditis-areas were present in 6/10 (60%) patients with baseline low TSH (versus 10/40, 25%, normal TSH, p = 0.034). Patients with thyroiditis-areas also had higher baseline FT4 (p = 0.018) and IL-6 (p = 0.016) compared with normal thyroid US. Thyroid US-FNA showed CD4+CD8+CD103+CD69+ tissue resident memory T-cells, a recently identified lymphocyte lineage that occupies tissues without recirculating, in 7/8 (87%) patients. Preliminary findings using MHC I and II dextramers also identified SARS-CoV-2-specific T-cells, but no viral RNA. Follow-up analysis, conducted in 75/183 (41%) patients, showed thyroid function and inflammatory markers normalized at all time-points and no increase of thyroid autoantibodies positivity. The thyroiditis-areas, often reduced in size, were still present after 6 and 12 months in 13/15 (87%) and 6/12 (50%) patients, respectively. After 9 months the thyroid uptake at 99mTc/I123 scintigraphy was still reduced in 4/6 (67%) patients, even if partially recovered (mean +28%) compared with baseline. CONCLUSION(S): Thyroid dysfunction during moderate-to-severe Covid-19 disease is mild and transient. Thyroiditis-areas occur frequently and may persist after one year, even if reduced in size. The association of thyroiditis-areas with low TSH and high FT4 and IL-6 serum concentrations, and the preliminary finding of intra-thyroid SARS-CoV-2-specific T-cells, support the hypothesis of a direct thyroid gland involvement in SARS-CoV-2 infection.