Intensity & Longevity of SARS-CoV-2 Vaccination Response in Patients with Immune-Mediated Inflammatory Disease

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In a preprint version of a study posted on medRxiv*, researchers investigated the longevity and intensity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immune response in patients suffering from immune-mediated inflammatory diseases (IMIDs).


SARS-CoV-2, since its emergence, has infected millions of people and led to severe health complications. It has been observed that SARS-CoV-2 poses a huge threat to patients suffering from immune-mediated inflammatory diseases (IMIDs).

Owing to the compromised immune system and use of immunomodulatory drugs, the humoral immune response towards SARS-CoV-2 in these patients is altered.

Studies on the durability and intensity of antibody responses after vaccination in IMID patients are limited. Therefore, a large study concerning vaccination schedules in these high-risk patients is crucial considering the emerging novel SARS-CoV-2 variants.

About the Study

In this large prospective study, patients who attended or were admitted to the registered centers, receiving either no treatment or treatment with immunomodulatory agents, were recruited between December 2020 and 2021.

About 5,076 participants were registered, from which 3,733 individuals, including 2,535 IMID patients (41% males, 58.9% females) and 1198 healthy controls (HC) (53.8% males, 46.2%females), were selected. The mean age of IMID participants was 55.0 years, greater than the HC group (40.7 years).

IMID patients diagnosed with spondyloarthritis, rheumatoid arthritis, systemic autoimmune diseases, inflammatory bowel diseases, vasculitis, and psoriasis were included. Moreover, those having at least one blood sample starting four weeks before their first vaccine were also included. Patients with unclear diagnosis, organ-specific autoimmunity, immunodeficiency, and malignancy were excluded. A total of two vaccination doses were provided. Those who showed poor response to two doses were given a third dose.

A total of 5564 samples were collected from these participants. Follow-up of the patients was done right from the first vaccination dose till December 1st, 2021. Treatment of IMID was classified at sampling time-points into cytokine, signaling, adhesion molecule, T cell, B cell inhibitors, conventional immune modulators, other drugs, and combined drugs.

IgG antibodies raised against the SARS-CoV-2 spike proteins (S1 domain) were measured by enzyme-linked immunosorbent assay (ELISA). The optical density (OD) value between more than or equal to 0.8 and less than 1.1 (OD450 nm) was considered borderline, whereas a value more than or equal to 1.1 was considered positive.

Study Findings

After the first vaccination, the mean IgG antibody levels were recorded at different time points. The highest OD levels were found at around 8-10 weeks after the vaccination in both HC and IMID. However, levels of antibodies were attained earlier in the HCs than in the IMID participants.

When adjusted with age and sex, the marginal mean antibodies were higher in HCs than IMIDs after eight weeks. The peak marginal mean antibody levels were also twice higher at week 10 (12.48, 95%CI) in HCs than with the IMIDs (5.71, 95%CI), thus displaying a larger mean difference of 6.98. However, at week 40, the difference was not significant, with an antibody level of 3.31 compared to IMIDs (2.40). Moreover, HC showed a biphasic decline of antibodies after week 20, whereas IMIDs showed monophasic.

Poor antibody response with OD less than 1.1 was observed among HC participants (0 to 2.32%) and IMIDs (7.4 to 17.8%), which rose after the 8- to 10-weeks. The marginal poor-antibody response was always high in the IMID patients compared to the HCs. Researchers also found that age and gender contributed to the risk of poor vaccination response. At age 35, the risk of poor response was 17.87% for IMIDs (week 40), whereas at 65 years of age, it was 35.83%. Sex-wise, male participants in IMIDs showed poorer (28.62%) response at week 40 than females (23.69 %).

Further, a blunted peak response of marginal mean antibody levels by diagnosis was observed in IMID patients than in HC. Untreated IMID participants also showed lower responses compared to HCs. Higher mean differences in both the diagnosis groups were found around week 10 for psoriasis and other diagnoses, whereas the lowest was found with rheumatoid arthritis (RA), vasculitis, and other diagnoses patients.

In IMIDs, autoantibodies were lower in vasculitis and other diagnoses than in systemic autoimmune diseases, inflammatory bowel diseases, polymyalgia rheumatica, psoriasis, and spondyloarthritis. The mean antibody levels for RA were significantly lower than only that of psoriasis among all IMID groups. However, at week 40, the differences in antibody levels between HC and IMID groups were low except for RA and spondyloarthritis.

The mean antibody levels were similar between untreated IMIDs and patients treated with other drugs such as antimalarials or sulfasalazine or glucocorticoids. However, these levels were low in those treated with B- or T-cell inhibitor drugs. The largest mean differences were found in HCs and other treatment groups at week 10, specifically with the B-cell agents.

When compared between the treatment groups, B-cell showed a lower response than all the groups, except the T-cell. The T-cell inhibitors also showed lower peak response with cytokine and signaling inhibitors, immune modulators, and other drugs. At week 40, HC showed higher antibodies compared to conventional immune modulators, cytokine inhibitors, B-cell, and T-cell inhibitors.

In the case of IMIDs, untreated patients demonstrated higher mean antibody levels than cytokine inhibitors, B cell inhibitors, and T-cell inhibitors. Monotherapy with cytokines, T-cells, or immunomodulators showed a higher antibody response than the combination therapy. After the third dose, the IMID patients showed higher antibody levels than those who received only two doses at 40 weeks.


Overall, the study indicates that patients suffering from IMID show reduced intensity and longevity of antibody response even after two doses of vaccination. The antibody levels also frequently dropped compared to the HCs over the course. However, with the booster dose, the antibody levels were higher. When treated with B or T cell inhibitors, the response was poor. However, peak response was observed when treated with cytokines. The researchers, however, highlight a few limitations which need to be addressed.

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