COVID-19 vaccination humoral immune response in individuals with diabetes

The prevalence of diabetes is as high as 20% in individuals hospitalized for coronavirus disease 2019 (COVID-19), and a large number of patients who experience a severe disease course of COVID-19 are diabetic. The in-hospital mortality of COVID-19 patients with diabetes mellitus (DM) is as high as 25%.

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

Chronic, systemic low-grade inflammation is characteristic of metabolic diseases like type 2 diabetes (T2D). This causes exaggerated cytokine release, inflammation, impaired phagocytosis, or glycation of immunoglobulins. This alters the outcome of individuals with diabetes mellitus who are exposed to infection. Additionally, individuals with T2D have pre-existing alterations in the adaptive immune system (B and T lymphocytes), including T cells expressing lower levels of co-stimulatory molecules or interleukin (IL)-12 receptors. Furthermore, clearing of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) requires an effective response of the adaptive immune system.

Hence, individuals with diabetes are considered a high-risk population for experiencing adverse COVID-19 outcomes. COVID-19 vaccination is highly recommended in this population; this has led to prioritization in the current vaccination strategies of most countries. However, whether individuals with diabetes also face a reduced immune response following SARS-CoV2 vaccinations remains doubtful.

The study

A new study published in medRxiv* preprint server investigated the humoral immune response and side effects related to COVID-19 vaccines in individuals with type 1 diabetes (T1D) and T2D to elucidate impacts of the type of diabetes and glycemic control on the antibody response following COVID-19 vaccinations.

This study aimed to compare SARS-CoV-2 antibody levels after COVID-19 vaccination in individuals with diabetes to healthy, non-diabetes controls.

The “Immune response to Covid-19 vaccination in individuals with Diabetes Mellitus – COVAC-DM” study was a prospective, multicenter, real-world, cohort study that included 161 individuals with DM at two centers in Austria – Medical University of Graz and Medical University of Innsbruck, and one center in Germany – University of Bayreuth.

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

Overall, 161 patients were enrolled between April and June 2021 of whom 150 were included in the final analysis.

The findings

Seventy-five participants had T1D, of which 49 belonged to the well-controlled group—having a mean HbA1c of 6.6 ± 0.6 %, and 26 were insufficiently controlled—with a mean HbA1c of 8.4 ± 0.9%. Meanwhile, 75 participants had T2D, of whom 37 had well-controlled diabetes—having a mean HbA1c 6.5 ± 0.6% and 38 insufficiently controlled diabetes—with a mean HbA1c 8.4 ± 0.9%.

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

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

The results revealed that 10-14 days after the first vaccination dose, 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 findings showed that those with T1D and T2D display a humoral immune response to COVID-19 vaccines—measured by anti-receptor binding domain SARS-CoV-2 S antibodies—comparable to healthy controls.

Higher antibody levels were detected in individuals with well-controlled T1D; however, this difference does not persist after adjustment for age, sex, and multiple comparisons. The findings 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 findings contradicted a recent observational study from Italy (CAVEAT study) that demonstrated a lower antibody response to COVID-19 vaccination in individuals with T2D having an HbA1c above 7.0%. This was accompanied by a reduced CD4pos T cell response measured by tumor necrosis factor (TNF)-α, IL-2, or interferon (IFN)-γ response.

Age was found to be a major determinant of humoral immune response to a COVID-19 vaccination. Previous data have confirmed that elderly individuals exhibit a lower antibody response to these vaccines and display a more rapid waning of antibodies.

Other clinical features that predict antibody response are – kidney function or eGFR. This data suggested that re-vaccination intervals in individuals with diabetes and advanced diabetic kidney disease should be shorter.


In this study, a correlation between anti-SARS-CoV-2 S antibodies and diabetes duration could not be found. Meanwhile, the correlation of these antibodies with patients’ body mass index was rather weak.

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

*Important notice

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

Journal reference:
Nidhi Saha

Written by

Nidhi Saha

I am a medical content writer and editor. My interests lie in public health awareness and medical communication. I have worked as a clinical dentist and as a consultant research writer in an Indian medical publishing house. It is my constant endeavor is to update knowledge on newer treatment modalities relating to various medical fields. I have also aided in proofreading and publication of manuscripts in accredited medical journals. I like to sketch, read and listen to music in my leisure time.


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