Discussion
Since the emergency approval, vaccination against SARS-CoV-2 remained the mainstay for preventing COVID-19 notably severe disease, along with social distancing, application of personal protective equipment (e.g., face mask) and maintenance of proper hygiene. The immune response after vaccination, developed by both innate and adaptive immune systems, were found to be slowed and delayed in immunocompromised groups.\cite{Soetedjo_2022} However, the immunological reactions to COVID-19 vaccinations in type 2 diabetic individuals were little understood up to this point.\cite{Marfella_2021}
In the present study, IFN-\(\gamma\) and IL-2 secreting PBMCs were evaluated in known cases of type 2 diabetes and healthy individuals aged 53.2±9.12 years and 50.4±11.4 years respectively. Through purposive sampling an approximately equivalent distribution of both male and female gender was also taken with a minute female predominance. Most of the participants in this study had a BMI <25 kg/m2. A major percentage of participants in the type 2 diabetic group had inadequate or poor (HbA1c\(\ge\)7.0%) glycemic control. Poor glycemic control was an effective indicator of disease severity and mortality in patients with COVID-19.\cite{ergenc2022} Participants were studied at 3 time points, baseline (T1) being at the day of 1st dose of vaccination, at the day of 2nd dose of vaccination (T2) which was 4 weeks after 1st dose and lastly between the time period of 2-4 weeks after the 2nd dose (T3) with a mean duration of 24.2±3.39 days.
All participants had negative IgG titer at the baseline time point before 1st dose (T1). SARS-CoV-2 specific IgG antibody was assessed in this study to perceive any differences in seroconversion rate between T2DM participants and the healthy control group, and both groups showed a 100% seroconversion rate at 4 weeks after 1st dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine. The participants in both type 2 diabetic group and healthy control group had a significant rise in both IFN-\(\gamma\) and IL-2 secreting PBMCs counts from T1 to T3. However, the type 2 diabetic groups showed a lower IFN-\(\gamma\) secreting PBMCs counts after 1st dose (T2) than healthy control group indicating a lower IFN-\(\gamma\) response which was also demonstrated in a study where Van Praet et al. showed the association of diabetes with a lower cellular response against BNT162b2 (Pfizer-BioNTech) mRNA vaccine.\cite{Van_Praet_2021} Prior studies showed that diabetic subjects display a delayed adaptive immune response to pathogen.\cite{Vallerskog_2010} Dysfunction of both innate immune response (including dysfunction of neutrophils and macrophages) and adaptive immune response (including T cells) are supposed to be accountable for the feeble immune system against invading pathogens in diabetic subjects.\cite{Berbudi_2020}
In this study, significant negative correlation of HbA1c (%) to IFN-\(\gamma\) secreting PBMCs count at T3 were observed in type 2 diabetic group which coincides with the CAVEAT study by Marfella et al., in which authors demonstrated significantly reduced immune response, particularly neutralizing antibody, in T2DM patients with HbA1c >7% than normoglycemic subjects and T2DM patients with good glycemic control.\cite{Marfella_2021} Reduced lymphocyte proliferative responses CD4+ to CD8+ lymphocyte ratio, decreased macrophage or monocyte function, and abnormalities with antigen presentation were seen in patients with hyperglycemia and insulin resistance and may resulted in this delayed immune response.\cite{Schillie_2012,Marseglia_2000} However, Sourij et al. demonstrated that HbA1c (%) levels did not have significant impact on antibody levels after COVID-19 vaccination from which the present study differs.\cite{Sourij_2022} In the present study, robust rise of IFN-\(\gamma\) and IL-2 secreting PBMCs counts were observed from T1 to T3, irrespective of hypertension status, BMI level and age of the type 2 diabetic participants. Also, similar to the findings by Van Praet et al., there was no discernible difference in IFN-\(\gamma\) and IL-2 secreting PBMCs counts from ELISpot assays between the genders in present study, however, Schwarz et al. detected delayed and reduced antibody and T-cell responses in elderly people, to which the present study differs.\cite{Van_Praet_2021,Schwarz_2021}
The present study had quite a few limitations, too. Firstly, due to restrictive recruitment along with financial and time constraints, this study was relatively small and was complicated by low statistical power. Larger prospective studies are required to confirm the findings of this study. This study was performed in a single center and only BNT162b2 (Pfizer-BioNTech) mRNA vaccinees were included in this study. A further difficulty was the high individual variability, inherent to human studies. To account for this, very robust statistics, e.g., median value, two-sided Mann-Whitney-U test, etc. were used.
Conclusion
The present study demonstrated that BNT162b2 (Pfizer-BioNTech) mRNA vaccine induces robust T-cell mediated immune response in both type 2 diabetic participants and healthy individuals. However, type 2 diabetic group showed lower immunological responses specially after 1st dose when compared with healthy control. This study also demonstrated that hypertension, gender and age did not affect the cellular immune response in type 2 diabetic participants.
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors upon request.
Ethics statement
This study was reviewed and approved by the Institutional Review Board of Bangabandhu Sheikh Mujib Medical University (reference: BSMMU/2021/10168, Registration number: 3692). The patients/participants provided their written informed consent to participate in this study.
Author contributions
The manuscript of this paper was prepared by SH. F TA and AN were responsible for revising the article critically. All authors contributed to the article and approved the submitted version.
Funding
This study was funded by research grant of Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh.