Introduction

Since World Health Organization (WHO) called the outbreak a “pandemic” on 11 March, 2020, despite significant movement restrictions, social distancing measures, and stay-at-home orders endorsed in many countries, the COVID-19 pandemic has caused overwhelming morbidity and mortality.\cite{Hanaei_2020} To mitigate the escalating encumbrance of COVID-19, vaccine development had taken place at a phenomenal speed and has spawned a slew of vaccines of different platforms and varying degrees of effectiveness and protection; most using the SARS-CoV-2 surface spike as the main antigenic target for the generation of binding and neutralizing antibodies and T cells, as well as an antigen coding sequence based on the Wuhan lineage virus that was first described (Gen Bank accession number M908947).\cite{Moghadas_2021,Emary_2021}
SARS-CoV-2 infection has a wide clinical spectrum, ranging from asymptomatic to severe and deadly diseases, especially in case of co-morbidities.\cite{Garc_a_2020} Diabetes is undoubtedly one of the most important comorbidities of COVID-19 and the prevalence of SARS-CoV-2 infections range from 5% to 36% among the diabetic patients globally.\cite{Ali_2021,Corrao_2021} The intricate interaction between COVID-19 infection and diabetes get worse significantly with increasing age of patients and longer period of uncontrolled diabetes.\cite{Baidya_2020} Diabetes causes intensification of the severity of COVID-19 disease by compromising innate immunity, triggering an enhanced pro-inflammatory response, and lowering angiotensin-converting enzyme 2 (ACE2) expressions.\cite{Pal_2020} Diabetes patients have been reported to have a lower clearance of SARS-CoV-2 from their bloodstream, which along with poor T cell activity, and associated cardiovascular illness lead to the vulnerability of diabetic individuals to COVID-19 infections.\cite{Daryabor_2020} Furthermore, dysregulation in immune response is also aided by an adverse hormonal environment in Type 2 diabetes mellitus (T2DM) patients.\cite{Guest_2008} Hence, T2DM patients are among the priority group to receive vaccination against SARS-CoV-2 worldwide as per recommendation from WHO.\cite{covid-19}
Immunocompromised patients have demonstrated decreased immune response compared to the healthy group. While in prior studies the humoral response (IgG) in healthy control was found to be > 99% against BNT162b2 (Pfizer-BioNTech), Bergman et al. showed that only 72.2% of the patients (solid organ recipients and patients living with the human immunodeficiency virus) had seroconverted 2 weeks after administrating the 2nd dose of the BNT162b2 (Pfizer-BioNTech) vaccine.\cite{Mariani_2021,Bertram_2022,Bergman_2021} In the case of diabetes, the evidences regarding immune responses are mixed worldwide.\cite{Schillie_2012,Huijts_2017,Verstraeten_2020} However, the paucity of data on cell-mediated response to the SARS-CoV-2 vaccine in T2DM patients and data on the immunological vaccine responses related to glycemic control in participants with T2DM in the hitherto available clinical trials of COVID-19 vaccines, calls for more research in this subgroup.\cite{Soetedjo_2022} Moreover, no study on a comprehensive and integrated analysis of immune parameters with response kinetics to SARS-CoV-2 vaccination in correlation with glycemic control in type 2 diabetic patients has ever been conducted in Bangladesh. In Bangladesh, with more than 13.1 million people living with diabetes,  the question regarding the effect of glycemic control over immune response following vaccination against SARS-CoV-2 remains.\cite{factsheet} In these circumstances, this study aimed to assess and compare IFN-\(\gamma\) and IL-2 secreting peripheral blood cells (PBMCs) against the SARS-CoV-2 BNT162b2 (Pfizer-BioNTech) mRNA vaccine in type 2 diabetic individuals attending a tertiary care hospital in Bangladesh.

Materials and Methods

Study design

This is a longitudinal observational study to evaluate the humoral and T-cell mediated immune response against SARS-CoV-2 mRNA vaccine in individuals at or above 30 years of age with type 2 diabetes mellitus attending a tertiary care hospital of Bangladesh. A total of 19 adults with pre-diagnosed type 2 diabetes mellitus and 16 apparently healthy individuals were included in this study as type 2 diabetic group and healthy control group respectively. Participants were studied before 1st dose (T1), 4 weeks after 1stdose (T2) and 2-4 weeks after 2nd dose (T3) of BNT162b2 mRNA (Pfizer-BioNTech) vaccination. Study participants were selected from November 2021 to April 2022 by purposive sampling method from the Endocrinology outpatient department and COVID-19 Vaccine Centre of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. All laboratory procedures were performed in the Department of Virology, BSMMU. For the purpose of this study, the cut-off value of HbA1c was set at 7% and participants were categorized as follows: type 2 diabetes mellitus patients with HbA1c >7% as good glycemic control and type 2 diabetes mellitus patients with HbA1c \(\le\)7% as inadequate or poor glycemic control.\cite{2014} Body Mass Index (BMI) (kg/m2) was measured and categorized as BMI <25 kg/m2 and BMI \(\ge\)25 kg/m2. Hypertension was defined by either a documented diagnosis of hypertension, the patient taking antihypertensive medications, or the latest (within three months) blood pressure readings (either systolic \(\ge\)140 or diastolic \(\ge\)90).