Researchers investigated the influence of third and fourth coronavirus disease 2019 (COVID-19) vaccination doses on immunity against COVID-19 in immunocompromised adult patients in a recent study published on the medRxiv* preprint server.
Background
Previous research has found that immunocompromised patients with immune-mediated inflammatory diseases (IMID), particularly those treated with anti-tumor necrosis factor (TNF) medications, have lower humoral responses following SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccination. After the second vaccination, IMID patients had higher levels of fading of the antibody (Ab) as well as T-cell responses than healthy controls. However, more research is needed to fully understand the effects of the third and fourth dosages.
Concerning the research
The immunogenicity of the third and fourth COVID-19 vaccination doses in immunocompromised patients was examined in the current investigation.
A total of 161 participants contributed 607 samples over eight time periods beginning in January 2021. The eligible participants were adult patients who were diagnosed with one or more IMIDs such as inflammatory bowel disease (IBD), psoriatic arthritis, rheumatoid arthritis, psoriasis, hidradenitis suppurative, or ankylosing spondylitis, treated or untreated with maintenance immunosuppressive therapy including anti-interleukin (IL)-12/23, anti-IL-23, anti-IL-17, methotrexate/azathioprine (MTX/AZA), anti-TNF, or antiTNF+MTX/AZA; and SARS-CoV-2 mRNA-vaccinated.
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Patients who received anti-TNF+MTX/AZA therapy or anti-TNF monotherapy were labeled as “TNF IMID,” while IMID patients who did not get anti-TNF medicine were labeled as “non-TNF IMID.” Using linear regression models built at each time point following the first three vaccines, cellular and humoral responses in treated and untreated IMID patients were compared to those in healthy controls.
To determine the effects of the third and fourth COVID-19 vaccine doses on the degree of Ab responses, the researchers used mixed-effects linear regression models that predicted the average anti-RBD and anti-spike immunoglobulin (Ig)-G responses at all time points.
Results
IBD was the most common diagnosis, and the most widely used therapies were anti-TNF-, anti-IL-12/23-, and anti-TNF+MTZ/AZA therapy. The study only included healthy controls for three months after the third vaccine. The majority of research participants received the BNT162b2 COVID-19 vaccination. The researchers discovered that age had no effect on IMID patients’ responses to immunization. Additionally, there were no significant differences in vaccination intervals between the first and second doses or between the second and third doses across the treatment groups. Anti-TNF-treated individuals, on the other hand, reported slightly shorter intervals between their third and fourth vaccines than anti-IL-23- and anti-IL-12/23-treated patients.
Patients treated with anti-IL-23, anti-TNF, or anti-TNF+MTX/AZA had lower RBD- or spike-specific Ab levels than healthy controls two to four weeks after the first immunization. A second dose, however, corrected the majority of defects. Anti-TNF- and anti-TNF+MTX/AZA-treated patients showed considerably decreased SARS-CoV-2-specific Ab responses three to four months after the second dose, but other IMID patients had levels comparable to healthy controls.
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Following the second dosage of a spike-pseudotyped lentiviral test, all IMID patients reported a reduced ability to neutralize SARS-CoV-2 wild-type compared to healthy controls. A third vaccination dose corrected impairments in spike- and RBD-specific Ab levels as well as neutralizing reactions observed in IMID patients. Furthermore, three to four months after the third vaccination, only anti-TNF- and anti-TNF+MTX/AZA-treated patients had decreased antigen (Ag)-specific Ab as well as neutralization reactions compared to healthy controls.
In terms of memory T cell responses to SARS-CoV-2, a single vaccine dose resulted in reduced interferon (IFN)-generation among IMID untreated, anti-IL-12/23-, anti-IL-23-, and MTX/AZA-treated patients compared to healthy controls. The second immunization corrected these deficiencies. Following the second dose, several treated IMID groups produced less IL-2 and/or IL-4. About three to four months after the second dose, all IMID patients had considerably lower IL-2 and IL-4 production in comparison to healthy controls, as well as lower IFN production reported in anti-IL-17A and anti-IL-23-treated persons. Following the third dose, no differences in cytokine responses were seen as compared to healthy controls.
By three to four months following the second dose, all groups had significant decreases in anti-spike and anti-RBD levels, with TNF IMID patients having the greatest drops. Furthermore, the amount of waning of anti-spike and anti-RBD IgG after the third and fourth vaccines indicated distinct kinetics. All of the research groups showed diminishing anti-RBD IgG responses three to four months after the third dosage, which were lower than those recorded after the second immunization. However, no significant variations in declining responses were seen between the third and fourth vaccines.
Conclusion
The outcomes of the study demonstrated the progression of adaptive immunity induced by COVID-19 vaccines in IMID patients receiving targeted or systemic immune-modifying drugs. The study found that repeated vaccine doses broaden and extend immune responses against SARS-CoV-2, arguing for three or four vaccinations in impaired patients.
