Glycaemic control is associated with SARS-CoV-2 breakthrough infections in vaccinated patients with type 2 diabetes

Abstract

Patients with type 2 diabetes (T2D) are characterized by blunted immune responses, which are affected by glycaemic control. Whether glycaemic control influences the response to COVID-19 vaccines and the incidence of SARS-CoV-2 breakthrough infections is unknown. Here we show that poor glycaemic control, assessed as mean HbA1c in the post-vaccination period, is associated with lower immune responses and an increased incidence of SARS-CoV-2 breakthrough infections in T2D patients vaccinated with mRNA-BNT162b2. We report data from a prospective observational study enroling healthcare and educator workers with T2D receiving the mRNA-BNT162b2 vaccine in Campania (Italy) and followed for one year (5 visits, follow-up 346 ± 49 days) after one full vaccination cycle. Considering the 494 subjects completing the study, patients with good glycaemic control (HbA1c one-year mean < 7%) show a higher virus-neutralizing antibody capacity and a better CD4 + T/cytokine response, compared with those with poor control (HbA1c one-year mean ≥ 7%). The one-year mean of HbA1c is linearly associated with the incidence of breakthrough infections (Beta = 0.068; 95% confidence interval [CI], 0.032-0.103; p < 0.001). The comparison of patients with poor and good glycaemic control through Cox regression also show an increased risk for patients with poor control (adjusted hazard ratio [HR], 0.261; 95% CI, 0.097-0.700; p = 0.008). Among other factors, only smoking (HR = 0.290, CI 0.146-0.576 for non-smokers; p < 0.001) and sex (HR = 0.105, CI 0.035-0.317 for females; p < 0.001) are significantly associated with the incidence of breakthrough infections.

Comparing the B and T cell-mediated immune responses in patients with type 2 diabetes receiving mRNA or inactivated COVID-19 vaccines

“…Van Praet et al showed that peripheral blood mononuclear cells (PBMCs) from patients with diabetes produced less interferon gamma (IFNg) upon SARS-CoV2 glycoprotein stimulation (22). Marfella et al showed that CD4 + T cell responses were impaired in patients with type 2 diabetes who had poor glycaemic control (20,23). Notably, T cell biology is complex with distinct effector and memory T cell subsets performing discrete roles in immunity (24).…”

A personalized antibody score for predicting individual COVID-19 vaccine-elicited antibody levels from basic demographic and health information

“…These positive and negative factors are consistent with previous studies (22, 25-28). In addition, diabetes and autoimmune diseases have been reported to be risk factors for breakthrough infections (29, 30). Considering that individual antibody titers are partially predictive of the likelihood of breakthrough infections (31, 32), this suggests that our antibody score could also be used as a risk score for breakthrough infections.…”

Repurposing SGLT-2 Inhibitors to Target Aging: Available Evidence and Molecular Mechanisms

“…Older age, male sex, and the presence of age-related diseases are the strongest risk factors for severe outcomes in patients with coronavirus disease (COVID)-19, the disease driven by the infection of SARS-CoV-2 [ 98 ]. All three of these conditions are characterized by a more pervasive status of inflammaging, which predisposes patients with these features to develop excessive inflammation coupled with an inefficient immune-mediated viral neutralization, two phenomena held to drive severe COVID-19 outcomes [ 99 , 100 , 101 ].…”