Humoral immune response to COVID-19 vaccination in people with diabetes

The prevalence of diabetes reaches up to 20% among people hospitalized with coronavirus disease 2019 (COVID-19), and a large number of patients who experience severe disease from COVID-19 are diabetic. Hospital mortality of COVID-19 patients with diabetes mellitus (DM) reaches up to 25%.

To study: Humoral immune response to Covid-19 vaccination in diabetes: dependent on age but independent of type of diabetes and glycemic control – the prospective cohort study COVAC-DM. Image Credit: Gecko Studio / Shutterstock

Chronic, low-grade systemic inflammation is characteristic of metabolic diseases such as type 2 diabetes (T2DM). This causes exaggerated release of cytokines, inflammation, altered phagocytosis, or glycation of immunoglobulins. This changes the results of people with diabetes mellitus who are at risk of infection. In addition, people with T2DM have pre-existing alterations in the adaptive immune system (B and T cells), including T cells expressing lower levels of costimulatory molecules or interleukin (IL) -12 receptors. In addition, elimination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires an effective adaptive immune system response.

Therefore, people with diabetes are considered a high risk population for experiencing adverse effects from COVID-19. COVID-19 vaccination is strongly recommended in this population; this has led to prioritization in current immunization strategies in most countries. However, it remains doubtful whether people with diabetes will also face a reduced immune response following SARS-CoV2 vaccinations.

The study

A new study published in medRxiv* The preprint server studied the humoral immune response and side effects of COVID-19 vaccines in people with type 1 diabetes (T1D) and T2D to elucidate the impacts of diabetes type and glycemic control on response into antibodies after COVID-19 vaccinations.

This study aimed to compare the levels of SARS-CoV-2 antibodies after COVID-19 vaccination in people with diabetes to healthy and non-diabetic controls.

The study “Immune response to vaccination against Covid-19 in people with diabetes mellitus – COVAC-DM” was a prospective, multicenter and real cohort study that included 161 people with DM in two centers in Austria – Medical University of Graz and Medical University of Innsbruck, and a center in Germany – University of Bayreuth.

Participants with T1D or T2D, aged 18 to 80, diagnosed with diabetes before receiving a COVID-19 vaccine were recruited from outpatient clinics at participating sites. Participants were then enrolled based on their glycated hemoglobin (HbA1c) and diabetes type in one of four predefined groups – well-controlled T1D with HbA1c ≤7.5%; Insufficiently controlled T1D with an HbA1c> 7.5%; Well-controlled T2DM with an HbA1c ≤7.5%; and insufficiently controlled T2DM with HbA1c> 7.5%.

A total of 161 patients were included between April and June 2021, of which 150 were included in the final analysis.

The results

Seventy-five participants had T1D, of which 49 were in the well-controlled group with a mean HbA1c of 6.6 ± 0.6% and 26 were insufficiently controlled with a mean HbA1c of 8.4 ± 0.9%. During this time, 75 participants had T2DM, 37 of whom had well-controlled diabetes, with an average HbA1c of 6.5 ± 0.6% and 38 had insufficiently controlled diabetes, with an average HbA1c of 8.4 ± 0.9. %.

The control group consisted of 86 healthy participants. Of these, 49 (57%) were women with a mean age of 48 ± 11.6 years, and 96.5% received the Moderna vaccine and 3.5% the BioNTech / Pfizer vaccine.

Three cases of hospitalization were recorded after vaccination. One occurred 24 days after the first dose of vaccination due to peripheral edema and chronic heart failure. 12 days after the second dose of vaccination for grade 3 atrioventricular block. The third hospitalization was due to a miscarriage after ten weeks of pregnancy.

The results revealed that 10 to 14 days after the first dose of vaccination, 52.7% of the patients with T1D and 48.0% of the patients with T2D had anti-SARS-CoV2-S antibodies above the detection limit of 0.8, with low median levels.

The results showed that people with T1D and T2DM show a humoral immune response to COVID-19 vaccines – measured by SARS-CoV-2 S antibodies in the anti-receptor binding domain – comparable to healthy controls.

Higher antibody levels have been detected in individuals with well-controlled T1D; however, this difference does not persist after adjusting for age, sex and multiple comparisons. The results also indicated that age and estimated glomerular filtration rate (eGFR) predict antibody levels after COVID-19 vaccination, while HbA1c levels are not.

It was noted that the results contradicted a recent observational study from Italy (CAVEAT study) which demonstrated a weaker antibody response to COVID-19 vaccination in people with T2DM with HbA1c greater than 7.0%. This was accompanied by a reduction in the response of CD4pos T cells as measured by tumor necrosis factor (TNF) -α, IL-2 or the response to interferon (IFN) -γ.

Age has been shown to be a major determinant of the humoral immune response to a COVID-19 vaccination. Previous data has confirmed that older people have a weaker antibody response to these vaccines and have a faster decrease in antibodies.

Other clinical features that predict antibody response are – renal function or eGFR. These data suggest that revaccination intervals in people with diabetes and advanced diabetic kidney disease should be shorter.

Conclusion

In this study, no correlation between anti-SARS-CoV-2 S antibodies and duration of diabetes could be found. During this time, the correlation of these antibodies with the body mass index of the patients was rather weak.

As a result, anti-SARS-CoV-2 S antibody levels after the second dose of COVID-19 vaccine were comparable in healthy controls and individuals with T1D and T2D, regardless of glycemic control. While age and renal function were significantly correlated with the extent of antibody levels.

*Important Notice

medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.