Rheumatoid arthritis and older age are associated with lower humoral and cellular immune response to primary series COVID-19 mRNA vaccine.

OBJECTIVE: People with autoimmune disease have worse COVID-19 infection-related outcomes, lower antibody responses to COVID-19 vaccine, and higher rates of breakthrough infection. Immunosuppressive medications used to treat rheumatoid arthritis (RA) are associated with lower COVID-19 vaccine responses, though independent contributions of comorbidities, T-cell immunity, and age are less clear. We sought to test the hypothesis that RA, immunosuppressive medications used to treat RA, and older age, contribute to reduced B and T cell response to COVID-19 vaccine. METHODS: We evaluated serum samples, taken the day of 1st vaccine dose, the day of 2nd dose, 2-6 weeks after 2nd dose, 7-12 weeks after 2nd dose, 13-24 weeks after 2nd dose, and 2-6 weeks after the 3rd dose, for anti-spike IgG and neutralizing antibody levels to Wuhan and Omicron BA.1 and peripheral blood mononuclear cells (PBMC) for spike-specific IFN-γ and IL-2 production by ELISPOT assay in 46 RA and 101 non-autoimmune control participants before and after the primary series COVID-19 mRNA vaccination. RESULTS: RA participants had lower spike-specific IgG and Wuhan-strain neutralizing antibody levels 2-6 weeks compared to controls after the second dose of primary vaccine series. Neutralizing antibody levels against Omicron BA.1 were low in both groups. IFN-γ production correlated with Wuhan neutralizing antibody levels, while older age negatively correlated with spike-specific IL-2, IFN-γ and IgG. Lower antibody levels were associated with older age, RA status, and medication usage, while lower T cell responses were associated primarily with older age. CONCLUSIONS: These data indicate lower COVID-19 mRNA vaccine-induced antibody levels in persons with RA compared to individuals without RA, likely partially attributable to immune suppressive medications. At the same time, older age is associated with lower antibody and cellular immune response to COVID-19 vaccines.

Oral Glucose Tolerance Test-based Measures of Insulin Secretory Response in Pregnancy.

BACKGROUND: Oral glucose tolerance test (OGTT)-based measures of insulin secretory response have not been validated in pregnancy. METHODS: In a secondary analysis of a longitudinal study, participants were studied prepregnancy (n = 40), in early pregnancy (n = 36; 12-14 weeks' gestation), and in late pregnancy (n = 36; 34-36 weeks' gestation). Participants underwent an OGTT, an intravenous glucose tolerance test (IVGTT), and a hyperinsulinemic-euglycemic clamp at each timepoint. We calculated homeostatic model assessment of beta-cell function (HOMA-2B), insulinogenic index (IGI), corrected insulin response (CIR), ratio of the area under the insulin curve and the area under the glucose curve (AUCins/AUCglu), and Stumvoll first-phase estimate (Stumvoll) from OGTT insulin and glucose levels. We used Pearson correlation to compare measures from OGTT and IVGTT. We used mixed effects models to examine longitudinal changes in insulin secretory response. RESULTS: Stumvoll was the only OGTT-based measure that was significantly correlated with first-phase insulin response prior to and across gestation (prepregnancy: r = 0.44, P = 0.01; early pregnancy: r = 0.67, P = 0.0001; late pregnancy: r = 0.67, P = 0.0001). In early and late pregnancy, AUCins/AUCglu had the strongest correlation with first-phase insulin response (early pregnancy: r = 0.79, P < 0.0001; late pregnancy: r = 0.69, P < 0.0001) but was not significantly correlated prepregnancy. IGI and CIR were significantly correlated with first-phase insulin response prepregnancy (IGI: r = 0.50, P = 0.005; CIR r = 0.47, P = 0.008) and in late pregnancy (IGI: r = 0.68, P = 0.0001; CIR r = 0.57, P = 0.002) but not in early pregnancy. HOMA-2B was the weakest correlate of first-phase insulin response. Stumvoll and AUCins/AUCglu recapitulated the longitudinal changes in insulin secretory response observed by IVGTT. CONCLUSIONS: Stumvoll and AUCins/AUCglu are valid OGTT-based insulin secretory response measures for pregnancy studies.

Longitudinal Assessment of Relationships Between Health Behaviors and IL-6 in Overweight and Obese Pregnancy.

BACKGROUND: Inflammation is a common factor in adverse pregnancy outcomes (APOs). Behavioral factors influence inflammatory markers and APOs but rarely have been investigated simultaneously in pregnancy. Our purpose was to determine how diet, physical activity, and obesity are associated with interleukin (IL)-6 in early and late pregnancy. METHODS: We conducted a secondary analysis of 49 overweight/obese pregnant women. Health behavior data, including diet quality using the Dietary Inflammatory Index (DII®); physical activity (Leisure Time Physical Activity scale); body mass index (BMI); and plasma IL-6 concentrations were collected at 13-16 weeks (early pregnancy) and 34-36 weeks (late pregnancy) gestation. Multiple linear regression analyses were used to determine the amount of variance explained in early and late pregnancy IL-6 concentrations by early and late pregnancy diet, physical activity, and BMI. RESULTS: Early diet and early BMI were the strongest predictors of early IL-6 concentrations (R2 = 0.43; p < .001) and late IL-6 concentrations (R2 = 0.30; p < .001). Late BMI predicted late IL-6 (R2 = .11; p = .02). Change in diet over pregnancy predicted late IL-6 (R2 = 0.17; p = .03). CONCLUSION: These findings suggest that maternal diet and BMI in early pregnancy, which likely reflects prepregnancy status, may have a greater impact on inflammatory processes than factors later in pregnancy. Future work should assess if behavioral factors before pregnancy produce similar relationships to those reported here, which may clarify the timing and type of lifestyle interventions to effectively reduce APOs.