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

• Published in: Nature communications Vol. 13; no. 1; pp. 2318 - 7
• Main Authors: Marfella, Raffaele, Sardu, Celestino, D’Onofrio, Nunzia, Prattichizzo, Francesco, Scisciola, Lucia, Messina, Vincenzo, La Grotta, Rosalba, Balestrieri, Maria Luisa, Maggi, Paolo, Napoli, Claudio, Ceriello, Antonio, Paolisso, Giuseppe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.04.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/31; 631/326/596/4130; 692/163/2743/137/773; 82/1; Antibodies; BNT162 Vaccine; CD4 antigen; Confidence intervals; Coronaviruses; COVID-19; COVID-19 - epidemiology; COVID-19 - prevention & control; COVID-19 Vaccines; Cytokines; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - epidemiology; Female; Glycated Hemoglobin A; Glycemic Control; Humanities and Social Sciences; Humans; Immune response; Immunization; Infections; Medical personnel; mRNA; multidisciplinary; Observational studies; Patients; Risk analysis; Risk factors; RNA, Messenger; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Sex; Smoking; Statistical analysis; Vaccines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30068-2

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. In this study, Marfella et al. show that patients with diabetes and poor glycaemic control have a blunted response to COVID-19 vaccine and are more prone to develop breakthrough infections, with further analysis suggesting smoking and male sex as potential risk factors to get COVID-19 despite vaccination.