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SARS-CoV-2 vaccine induced humoral & cell-mediated immune responses in Indian cohort of rheumatoid arthritis
For correspondence: Dr Bhawna Gupta, School of Biotechnology, Kalinga Institute of Industrial Technology, Deemed to be University, Bhubaneswar 751 024, Odisha, India e-mail: bhawna.gupta@kiitbiotech.ac.in
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Received: ,
Accepted: ,
Abstract
Background & objectives
The COVID-19 pandemic came up with distinct challenges for patients with rheumatoid arthritis indicating higher risk of infection and severity due to SARS-CoV-2. In this study, we performed the immunotyping of humoral and cell-mediated responses in patients with rheumatoid arthritis to assess characteristics and durability of Covid vaccine-induced immune memory.
Methods
We enrolled 50 individuals with rheumatoid arthritis who had received SARS COV-2 vaccine (Covaxin/Covishield). Of these 26 were assessed within six months of the second vaccine dose (T1) and 24 were evaluated 6–9 months after the third dose (T2). Serum IgG titres were measured using chemiluminescent microparticle immunoassay (CLIA), and lymphocyte immunophenotyping. In vitro challenge with the SARS-CoV-2 spike protein was performed using flow cytometry.
Results
Patients vaccinated with Covishield showed significantly higher IgG titres and elevated levels of cytokines such as TNFα and IFNγ compared to those vaccinated with Covaxin. The Covishield group also exhibited a higher percentage of antigen-specific and inflammatory T cell subsets, contributing to the overall cytokine pool in patients with rheumatoid arthritis. In vitro stimulation with the SARS-CoV-2 spike protein further activated lymphocytes in Covishield-vaccinated individuals.
Interpretation & conclusions
Our study presents the increased effectiveness of Covishield in initiating responses compared to Covaxin. Covishield vaccinated patients with rheumatoid arthritis show higher antigen specificity and T cell activation indicating a shift of the immune system towards a Th1 phenotype, which makes it imperative to focus on development of safe and durable vaccines with a continuous follow up for the patients with rheumatoid arthritis to control disease severity.
Keywords
Activation induced marker
CD4+ T cells
CD8+ T cells
Covaxin
Covishield
rheumatoid arthritis
December 2019 marked the beginning of the pandemic era starting with the outbreak of the SARS-CoV-2 in Wuhan, China. The World Health Organization declared COVID-19, a pandemic on March 11, 2020, as it affected people across continents1. Since August 2023, SARS-CoV-2 has affected nearly 770 million people worldwide with over 6.9 million deaths2. Due to the associated fatality, vaccine development against SARS-CoV-2 was pertinent. Indians were mass vaccinated with either of the two vaccines namely Covishield (AZD1222/ChAdOx1 - based on non-replicating virus vector-based vaccine encoding SARS-CoV-2 spike glycoprotein) and Covaxin (BBV152-inactivated whole virus, respectively)3. Rheumatoid arthritis is an autoimmune disorder characterised by inflammation of the synovial membrane lining the joints4. The disease is driven by the hyperactivation of T cells, resulting in the elevated production of immune mediators such as cytokines and cytolytic enzymes. These include TNF-α, IFN-γ, IL-6, IL-1, IL-12, and IL-155. The administration of vaccines comes with side effects, which may induce the overexpression of cytokines in the patient with rheumatoid arthritis.
SARS-CoV-2 infection has been reported to have an interesting relationship with the T cell biology. Reports have shown a change in the T cell subsets in patients with SARS-CoV-2, this phenomenon might serve as a diagnostic/prognostic indicator for the detection of SARS-CoV-2 infection6,7. Studies are needed to document the immune profiles of the CD8+ T and CD4+ T cells post administration of the vaccines. Patients with rheumatoid arthritis experience heightened levels of systemic inflammation, and the potential side effects of vaccines may pose an added burden on their already compromised immune systems. Therefore, it is essential to evaluate both the efficacy and safety of vaccines within this patient cohort. In this study, we performed immunophenotyping of CD4⁺ T cells, CD8⁺ T cells, and B cells in RA patients to assess the characteristics and durability of vaccine-induced immune memory. This was achieved through stimulation with a viral peptide pool challenge.
Materials & Methods
This study was undertaken by the School of Biotechnology, Kalinga Institute of Industrial Technology, Deemed to be University, Bhubneswar, Odisha, India from October 2021 to August 2022, after obtaining the ethical approval from the Institute Ethics Approval Committee.
Study design
Patients with rheumatoid arthritis who met the ACR/EULAR classification criteria8 for rheumatoid arthritis were enrolled in the study between October 2021 and August 2022 (Table I). The vaccination campaign by the Government of India included two vaccines: Covishield (AZD1222/ChAdOx1) and Covaxin (BBV152)9. Based on the vaccine received, participants in this study were grouped into: (i) Covaxin-vaccinated (n=10) and (ii) Covishield-vaccinated (n=14). During sample collection, informed consent was obtained, and details, including the disease, demographic data, history of SARS-CoV-2 exposure, and vaccination records were documented (Table I). These patients were also categorized as unvaccinated, within six months of receiving the second dose, and within 6–12 months of receiving the booster (third) dose.
| Clinical and paraclinical variables | Mean±SEM |
|---|---|
| Age (yr) | 52.2±8.1 |
| Gender (Male/Female) | 12/38 |
| Disease duration (yr) | 11.1±3.1 |
| Disease Activity Score 28 (DAS 28) | 8.7±0.3 |
| Vaccine administered (Covaxin/Covishield/not vaccinated) | 18/22/10 |
| Flare up post vaccination | 14/19 |
| Rheumatoid factor positive | 100% |
| ESR (mm/1st h) | 64.2±5.8 |
| Anti- CCP (%) | 100% |
| Therapeutic regimens |
DMARDS: Methotrexate, sulfasalazine Steroid: Prednisolone Supplement: Calcium, Folic acid, & Vitamin D |
SEM, standard error mean
Blood sample collection, peripheral blood mononuclear cells (PBMC) isolation and preservation of serum
Under supervision, 5 mL of blood was collected from each individual with rheumatoid arthritis. Of this, 4 mL was transferred into a K₂EDTA tube (BD Biosciences, New Jersey, USA) for PBMC isolation, and 1 mL was placed into a clot activator tube (BD Biosciences, New Jersey, USA) for serum collection. Peripheral blood mononuclear cells were isolated using density gradient centrifugation with ficoll-Hypaque (Lymphoprep, STEMCELL Technologies, Vancouver, Canada) following the manufacturer’s instructions. The serum was aliquoted and stored at –80°C for analysis.
Chemiluminescent microparticle immunoassay
IgG antibodies specific to the receptor binding domain region of Spike antigen in serum samples were analysed with a chemiluminescent microparticle immunoassay (CLIA) on ARCHITECT i1000SR system of Abbott Diagnostics. Total IgG levels were measured at two time points: 3–6 months after the second dose and 6–12 months after the third dose, using the ARCH SARS-CoV-2 IgG II Quant kit (Abbott Diagnostics, Illinois, USA) following the manufacturer’s instructions. According to the manufacturer’s data, the obtained AU/mL values were standardized to WHO-standardized BAU/mL using the conversion factor: 1 BAU/mL = 0.142 Abbott AU/Ml10. The cut-off value for the analysis was set at 352 BAU/mL.
PBMC stimulation in vitro
Freshly isolated PBMCs were resuspended in RPMI 1640 media (Gibco), which was enriched with 1 per cent Penicillin-Streptomycin solution (Gibco) and 5 per cent heat-inactivated human AB serum (Sigma-Aldrich, Missouri, USA). The cell post washing was stained with Trypan Blue and were counted using haemocytometer, and then were cultured at 1.5x10^6 cells per well, cells were stimulated with 1 µg/mL of wild type (WT)-SARS-CoV-2 peptide pool (MilteyniBiotec) for 24 hours, unstimulated cells were taken as the negative controls. Post stimulation the cells were washed with 1X PBS and were stained with antibodies for Fluorescence Activated Cell Sorting (FACS) analysis. For detection of secretory proteins Brefeldin A (10 µg/mL, eBiosciences) was introduced to the media for the last 10 h of stimulating PBMC with the peptide pool.
Flow cytometry analysis
The expression of the activation-induced markers (AIM) and the cytokines analysis was done with the help of full spectrum flow cytometry (CYTEK Aurora). The cells were harvested after stimulation and were resuspended in 100/µL of FACS buffer (3% FBS in PBS) and were surface stained for CD3, CD8, CD4, CD45RA, CCR7, CD19, CD27, CD38, IgA, IgM, IgD, IgG. The cells were first washed with FACS buffer and are then designated for intracellular staining, which were then fixed with BD Cytofix (BD Biosciences, New Jersey, USA) for 20 min at 4℃. The cells were then permeabilized with BD Cytoperm (BD Biosciences, New Jersey, USA) then stained with CD154, CD137, IFNγ, TNFα and Granzyme B. Expression levels of the markers were measured and the data obtained was analysed using FCS Express 7. Fluorescence minus one (FMO) control was used to accurately set the gates for true expression analysis. The representative images for the gating strategy used for assessing the CD4+, CD8+ T cells and the B cells are shown in supplementary figures 1 and 2, respectively.
Data analysis
Statistical analyses were carried out with the help of Graph Pad Prism 9. The significant differences were determined using Student’s T-test and one way ANOVA. The results were shown as the mean±SEM, with a P value <0.05 indicating statistical significance.
Results
Estimating anti-RBD IgG antibody titre in patients vaccinated with Covaxin (BBV152) and Covishield (ChAdOx1)
Serum samples were collected from 26 individuals with rheumatoid arthritis within six months of the 2nd dose of vaccination (T1), segregated into not vaccinated (n=10), vaccinated with Covaxin (n=8) and vaccinated with Covishield (n=8); and from 24 individuals with rheumatoid arthritis within 6-9 months of the 3rd dose of vaccination (T2), categorized into vaccinated with Covaxin (n=10) and vaccinated with Covishield (n=14). The serum samples were subjected to CLIA-based estimation of Anti-RBD IgG for WT-SARS-CoV-2 variant. The analysis revealed that the antibody titre levels were significantly higher (P<0.001) in the Covishield vaccinated individuals with rheumatoid arthritis (16647.5±10831.6 BAU/mL) however Covaxin vaccination (2549.3±2385.1 BAU/mL) did not induce a sustained antibody titres in study participants at time point T1 (Fig. 1). Analysis at time point T2 (Fig. 1) also reflected a higher concentration (P<0.001) of serum Anti-RBD IgG in the samples from the Covishield vaccinated group (28638.2±5871.05 BAU/mL) in comparison to the Covaxin vaccinated group (15505.1±9260.3 BAU/mL).
- Anti-RBD IgG antibody titres in individuals with rheumatoid arthritis vaccinated with Covaxin (BBV152) or Covishield (ChAdOx1). Vaccine-induced IgG production in the non-vaccinated (n=10), Covaxin vaccinated (n=8) and Covishield vaccinated individuals (n=8) at time point T1 (post 2nd dose) and Covaxin vaccinated (n=10) and Covishield vaccinated individuals (n=14) at time point T2 (post 3rd dose). The triangle represents the individuals with rheumatoid arthritis administered with Covishield and the closed circle represents those administered with Covaxin. The significance between the differential expression was tested by performing a one-way ANOVA with Turkey’s multiple comparison test. Bars are represented as mean+SEM., P ***<0.001.
Covishield vaccination induces abundant CD4+ T cell activation in individuals with rheumatoid arthritis
The PBMCs were stimulated with WT-Spike peptivator for 24 h and then analysed for the expression of activation-induced markers, memory subsets (effector memory, central memory, naive, and terminally differentiated effector memory cells), and cytokine expression (Fig. 2). After challenge with the WT-peptivator, the expression patterns of AIM+ (CD137+CD154+) (Fig. 2A), TNFα (CD4+) (Fig. 2B), and IFNγ (CD4+IFNγ+) (Fig. 2C) were evaluated. The AIM+ cells were further analysed for AIM+TEMRA+ (CD45RA+CCR7-) (Fig. 2D), AIM+Naive+ (CD45RA+CCR7+) (Fig. 2E, AIM+EM+ (CD45RA-, CCR7-) (Fig. 2F), and AIM+CM+ (CD45RA-CCR7+) (Fig. 2G). The graph represents the percent positive population in the stimulated cells of Covishield or Covaxin vaccinated individuals and their respective unstimulated controls.
- Covishield vaccination induces abundant CD4+ T cell activation in individuals with rheumatoid arthritis. The scattor dot plot represent the percentage positive cells expressing (A) CD4+AIM+, (B) CD4+TNFα+, (C) CD4+IFNγ+, (D) CD4+TEMRA+, (E) CD4+Naive+, (F) CD4+EM+ and (G) CD4+CM+ after stimulation with WT(wildtype)-spike peptivator for 24 h followed by antibody staining and flow cytometry analysis. The black lines in the plots represent the quartiles and the lines represent the median for n=24 participants samples. Covishield vaccinated (n= 14), Covaxin vaccinated (n= 10). The participants were categorized into unstimulated (UNS) and spike challenged groups for Covishield and Covaxin. The significance was measured by performing a one-way ANOVA, with Turkey’s multiple comparison test. P *<0.05, **<0.01,***<0.001.
We observed a significant increase in the expression of AIM+CD4+ T cells in the stimulated and unstimulated groups. This was also confirmed by the interquartile range (IQR) analysis (Table II), the Covishield group treated with spike peptivator had the highest IQR. Post challenge with the spike peptivator there was an increase in the levels of TNFα and IFNγ in the Covishield stimulated group in comparison to the Covaxin groups.
| Antigen induced marker | Covishield unstimulated | Covishield spike | Covaxin unstimulated | Covaxin spike |
|---|---|---|---|---|
| CD4 AIM+ | n=14 | n=14 | n=10 | n=10 |
| Median | 0.13 | 0.46 | 0.03 | 0.14 |
| IQR | 0.0825-0.5775 | 0.2275-1.9075 | 0.025-0.13 | 0.06-0.31 |
|
<0.0525 0.0525<Ab<0.16 0.16<Ab<0.46 >0.46 |
0 6 2 4 |
1 2 3 6 |
7 0 2 1 |
2 4 3 1 |
| CD8 AIM+ | n=14 | n=14 | n=10 | n=10 |
| Median | 17.325 | 21.79 | 0.055 | 0.4 |
| IQR | 9.38-20.90 | 16.28-31.30 | 0.0375-0.2075 | 0.05-0.87 |
|
<0.17 0.17<Ab<10.05 10.05<Ab<20.03 >20.03 |
0 3 6 5 |
0 1 6 7 |
8 2 0 0 |
4 6 0 0 |
IQR, inter-quartile range; Ab, antibody; CD8, CD8 T cells; AIM, activation induced marker
Analysis of the memory subsets within the AIM+CD4+ T cell population revealed an increased expression of TEMRA+CD4+ T cells in the Spike peptivator-stimulated PBMCs of Covishield-vaccinated patients only. The Naive+CD4+ T cell population decreased significantly in the Covishield-vaccinated group compared to the Covaxin-vaccinated group, suggesting that these cells have been exposed to an antigen, consistent with our AIM data. No significant changes were observed in the AIM+EM+CD4+ T cells or AIM+CM+CD4+ T cells.
Spike challenge activates CD8+ T cell mediated immune response in Covishield vaccinated individuals
To assess the response of cytotoxic T cells in vaccinated individuals with rheumatoid arthritis following a 24 h challenge with the spike peptivator, we analysed CD8+ T cells for the presence of AIM+ (CD8+ CD137+) (Fig. 3A), CD8+ TNFα+ (Fig. 3B), and CD8+ Granzyme B+ (Fig. 3C). The AIM+ T cells were further analysed for memory subsets: AIM+Naive+ (CD45RA+CCR7+) (Fig. 3D), AIM+TEMRA+ (CD45RA+CCR7-) (Fig. 3E), AIM+CM+ (CD45RA-CCR7+) (Fig. 3F), and AIM+EM+ (CD45RA-, CCR7-) (Fig. 3G).
- Spike challenge in Covishield vaccinated individuals with rheumatoid arthritis activates CD8+ T cell-mediated immune response. The scattor plots represent the percentage positive cells expressing (A) CD8+AIM+, (B) CD8+TNFα+, (C) CD8+Granzyme B+, (D) CD8+Naive+, (E) CD8+TEMRA+, (F) CD8+CM+ and (G) CD8+EM+ after stimulation with WT(wildtype)-spike peptivator for 24 h followed by antibody staining and flow cytometry analysis. The black lines in the plots represent the quartiles and the lines represent the median for n=24 participants samples. Covishield vaccinated (n=14), Covaxin vaccinated (n= 10). The participants were categorized into unstimulated (UNS) and spike challenged groups for Covishield and Covaxin. The significance was measured by performing a one-way ANOVA, with Turkey’s multiple comparison test. P *<0.05, **<0.01,***<0.001, ****<0.0001.
The results showed an increased expression of activation-induced markers in the CD8+ T cells of Covishield-vaccinated individuals challenged with the WT-spike peptivator, compared to their unstimulated control. This was further supported by the IQR analysis (Table II), which also highlighted differences between the stimulated and unstimulated groups of Covaxin-vaccinated individuals. The CD8+ T cells of Covishield vaccinated individuals showed an inherent accumulation of TNFα which further elevated post WT-spike peptivator demonstrating that Covishield vaccination imparts a robust CD8+ T cell activation. This was not observed in individuals vaccinated with Covaxin.
The AIM+ CD8+ T cell population in Covishield-vaccinated individuals showed a low frequency of naive cells but a higher prevalence of effector CD8+ T cells. Interestingly, there was an increased expression of the AIM+ CM+ CD8+ T cell subset, which supports the elevated TNFα expression observed post-stimulation with the WT-spike peptivator. No significant changes were seen in the levels of AIM+ TEMRA+ and AIM+ EM+ CD8+ T cells.
Covaxin and Covishield booster dose (3rd dose) administration induced B cell responses in individuals with rheumatoid arthritis
After assessing the immune profiles of CD4⁺ and CD8⁺ T cells following stimulation with the WT-spike peptivator, we subsequently examined the humoral immune response in vaccinated individuals. The analysis focused on IgA (Fig. 4A), IgG (Fig. 4B), IgM (Fig. 4C), memory B cells (Fig. 4D), and class-switched CD27⁺ B cells (Fig. 4E). A total of nine study participants were included in this study, with six from the Covishield-vaccinated group and three from the Covaxin-vaccinated group. The analysis revealed that both Covishield and Covaxin were able to produce similar B cell responses post booster dose (3rd dose) of the vaccine. The levels of IgG, IgM and IgA as well as the percentage of CD27+ memory+ B cells were similar in both the vaccine groups. The expression of CD38+ CD27+ activated switch memory B cells also showed similar expression pattern for both the vaccines.
- Covaxin and Covishield booster dose (3rd dose) administration induced B cell responses in individuals with rheumatoid arthritis. The percentage of cells analysed for B cell responses have been represented (A) IgA, (B) IgG, (C) IgM, (D) Memory B cells, and (E) class switched B cells expressing CD27 in individuals with rheumatoid arthritis vaccinated with Covishield and Covaxin six months post administration of the 3rd dose of vaccine. The data is represented as mean±SEM. The significance was tested by performing a student’s t test.
Discussion
The SARS-CoV-2 pandemic made development of vaccines imperative to restrain the spread of virus and severity of the infection. Hence, two vaccines were manufactured to immunize Indian population: Covishield a non-replicating virus vector-based vaccine encoding SARS-CoV-2 spike glycoprotein and Covaxin – an inactivated whole virus11-13. One of the major implications of SARS-CoV-2 infection is the onset of cytokine storm post infection, which may be mimicked by the vaccination as well14,15. In patients with rheumatoid arthritis the cytokine levels are already higher due to the pathophysiology of the disease16. This makes it pertinent to understand the effect, safety and efficacy of these virus-based vaccines in pathology and disease progression of rheumatoid arthritis.
In the present study, we observed an increased serum levels for anti-RBD spike IgG antibody in individuals vaccinated with the first dose of Covishield during the first wave of the SARS-CoV-2 infection making it substantial to hypothesize that Covishield administration may increase the cell mediated and humoral immune responses in individuals with rheumatoid arthritis. Post 3rd dose analysis showed higher serum anti-RBD IgG levels in Covishield vaccinated individuals, supporting our hypothesis and highlighting the need to study lymphocyte responses after vaccination and WT-Spike exposure in rheumatoid arthritis.
CD4+ T cells from Covishield vaccinated individuals with rheumatoid arthritis showed higher expression of AIM markers, TNFα, and IFNγ upon WT-spike stimulation, with IQR analysis placing them in a higher range than Covaxin recipients. The subset analysis reflected an increase in the TEMRA+AIM+CD4+ T cells, which are effective immune responders in case of any viral infection. The expression of TEMRA+AIM+ CD4+ T cells also supports the activation state of the CD4+ T cells upon challenge with the WT-spike peptivator. The reduced naive+AIM+ CD4+ T cell population in both treated and untreated Covishield vaccinated groups suggests a higher presence of antigen-experienced CD4+ T cells capable of recognizing the viral peptide upon challenge. However, the expression of effector memory and central memory subsets was similar across all four groups.
Previous reports have shown activation of T cells and increased expression of IFNγ by CD8+ T cells in the Indian population post vaccination with Covishield and Covaxin17,18. Activated AIM+CD8+ T cells in individuals with rheumatoid arthritis vaccinated with Covishield and stimulated with the spike peptivator showed a significant increase, while no significant AIM expression was observed in Covaxin vaccinated individuals with rheumatoid arthritis. TNFα secretion was significantly higher in the Covishield vaccinated and challenged group compared to the Covaxin vaccinated group, indicating that CD8+ T cells challenged with the WT-spike peptivator were already in an activated state. Upon analysing the memory subsets of the AIM+CD8+ T cell population, we found an increased presence of CM+AIM+CD8+ T cells, the expression of naive CD8+ T cells was lower in the Covishield vaccinated group and Covaxin vaccinated challenged with WT-spike peptivator. The unchallenged Covaxin vaccinated group had high levels of naive CD8+ T cells, which seconds the lower levels of activation markers in case of the Covaxin vaccinated group. The percentage of positive cells in case of AIM+TEMRA+ and AIM+EM+ CD8+ T cells remained unchanged in all the four groups.
The study of the immune status of the CD4+ and CD8+ T cells becomes very crucial post administration of vaccine. Rheumatoid arthritis is an autoimmune disease that is driven by Th1 and Th17 driven responses19. The activity of the CD8+ T cells has been well studied in rheumatoid arthritis20,21, cytokines released by the activation drive the severity of the disease. We and others have previously showed that activation of CD8+ T cells leads to increased levels of granzyme B, perforin, TNFα and IFNγ22,23 associated with disease progression.
The cells expressing B cells memory markers were similar in both Covishield and Covaxin vaccinated individuals; however, the cells expressing IgG, IgM and IgA did not differ in both the groups. The expression of CD27 in the class switched memory B cells also did not vary between the two vaccinated cohorts demonstrating the effector function of the antibodies produced by the activated B cells and their ability to clear out any infection induced by the viral infection post vaccination24. Thus, in the present study the B cell immunophenotyping reveals that post vaccination (post 6 months of booster/3rd dose administration) the efficacy of the B cell responses remains similar in both the vaccinated patient groups. Earlier studies undertaken with respect to the B cell responses have also reported similar results25.
Participants in this study were selected within 6 to 12 months of the administration of the 3rd dose, to look for the response induced by the administration of the vaccines we had performed a limit of stimulation index analysis for the number of responders in our population26. This study aimed to understand the immune responses exhibited by individuals with rheumatoid arthritis following vaccination. The onset of inflammation of the synovial membrane lining the body’s joints is a characteristic of rheumatoid arthritis27. The main feature of SARS-CoV-2 infection is the onset of cytokine storm with the progression of the disease28. The cytokines are the major players when it comes to the disease progression in case of rheumatoid arthritis29. These cytokines contribute to inflammation in rheumatoid arthritis-affected joints.
Administration of the SARS-CoV-2 spike protein-based vaccine Covishield elevates baseline levels of TNFα and IFNγ in individuals with rheumatoid arthritis. This finding is important to consider when planning treatment and management of rheumatoid arthritis. The therapeutic regimen of rheumatoid arthritis patients includes treatment with DMARDs and NSAIDs, which are immune modulators that lower the levels of proinflammatory cytokines30. Given the increased expression of TNFα and IFNγ in patients vaccinated with Covishield, it is essential to adjust their treatment regimens accordingly. This immune activation may be linked to heightened disease severity or potential relapse following vaccination. In most cases of rheumatoid arthritis, the treatment regimen consists of anti-TNFα therapy as well, which alleviates the inflammatory effect. Continuing the same therapy in Covishield-vaccinated individuals may elevate inflammation due to increased TNFα expression. In contrast, anti-TNFα therapy might be reduced in Covaxin vaccinated individuals, given their already lower TNFα levels.
Developing a vaccine for a deadly virus like SARS-CoV-2 is inherently challenging, and even more so when administered to individuals with inflammatory autoimmune conditions such as rheumatoid arthritis. While side effects are common, in individuals with rheumatoid arthritis they can be more critical, potentially worsening the disease. The vaccines used showed limited or no long-term impact on T cell-mediated protective immunity. Although T cells recognized the viral peptide, they failed to induce TNFα expression, a key factor in viral clearance. Therefore, it is essential that vaccines strike a careful balance between safety and long-term efficacy, especially in the context of viral pandemics and emerging variants.
Financial support & sponsorship
The study received funding support as Senior Research Fellowship (Ref No. 420/(CSIR- UGC NET DEC. 2017) awarded to first author (NS).
Conflicts of Interest
None.
Use of Artificial Intelligence (AI)-Assisted Technology for manuscript preparation
The authors confirm that there was no use of AI-assisted technology for assisting in the writing of the manuscript and no images were manipulated using AI.
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