Investigating the impact of COVID-19 vaccinations in immunocompromised adult patients

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

In a recent study posted to the medRxiv* preprint server, researchers assessed the impact of third and fourth coronavirus disease 2019 (COVID-19) vaccination doses on immunity against COVID-19 among immunocompromised adult patients.

Background

Prior investigations have revealed reduced humoral responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid (mRNA) vaccination among immunocompromised individuals with immune-mediated inflammatory disorders (IMID), especially those treated with anti-tumor necrosis factor (TNF) therapies. IMID patients have previously displayed higher levels of waning of the antibody (Ab) as well as T-cell responses in comparison to healthy controls after the second vaccination. However, further research is essential to understand the impacts of the third and fourth dosages.

About the study

In the present study, researchers assessed the immunogenicity of the third and fourth COVID-19 vaccine doses in immunocompromised patients.

A total of 161 participants provided 607 samples throughout eight time points commencing 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 suppurativa, 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.

The team defined patients treated with anti-TNF+MTX/AZA therapy or anti-TNF monotherapy as “TNF IMID” while IMID patients who were not treated with anti-TNF medication as “non-TNF IMID.” Cellular and humoral responses observed after vaccination in treated and untreated IMID patients were compared to that in healthy controls by employing linear regression models constructed at each timepoint after the first three vaccinations.

To resolve the impacts of the third and fourth COVID-19 vaccine doses as per the extent of Ab responses, the team built mixed-effects linear regression models that predicted the average anti-receptor-binding domain (RBD) and anti-spike immunoglobulin (Ig)-G responses at all assessed time points.

Results

The most prevalent diagnosis was IBD while the most commonly employed treatments included anti-TNF-, anti-IL-12/23-, and anti-TNF+MTZ/AZA-therapy. Healthy controls were a part of the study for only up to three months after the third vaccination. Most study participants were vaccinated with the BNT162b2 COVID-19 vaccine. The team noted that age did not have any significant impact on responses to immunization among IMID patients. Furthermore, there were no significant variations between vaccine intervals between the first and the second doses or the second and the third dose amongst all treatment groups. However, anti-TNF-treated patients reported slightly shorter intervals between their third and fourth vaccinations in comparison to that corresponding to anti-IL-23- and anti-IL-12/23-treated patients.

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Anti-IL-23-, anti-TNF-, and anti-TNF+MTX/AZA-treated patients demonstrated lower RBD- or spike-specific Ab levels compared to healthy controls almost two to four weeks after the first vaccination. However, most deficiencies were resolved by a second dose. By three to four months following the second dosage, anti-TNF- and anti-TNF+MTX/AZA-treated patients demonstrated significantly lower SARS-CoV-2-specific Ab responses while other IMID patients had comparable levels to that in healthy controls.

All IMID patients reported a lower capability to neutralize SARS-CoV-2 wild-type compared to healthy controls following the second dose in a spike-pseudotyped lentiviral test. A third dose of vaccination addressed deficiencies in spike- and RBD-specific Ab levels and neutralizing reactions reported in IMID patients. Additionally, three to four months following the third vaccination, only anti-TNF- and anti-TNF+MTX/AZA-treated patients demonstrated diminished antigen (Ag)-specific Ab as well as lowered neutralization responses relative to healthy controls.

Concerning memory T cell responses against SARS-CoV-2, one vaccination dose resulted in lower interferon (IFN)-γ generation among IMID untreated, anti-IL-12/23-, anti-IL-23-, and MTX/AZA-treated patients in comparison to healthy controls. These deficits were restored by the second vaccination. Also, IL-2 and/or IL-4 production was lowered in many treated IMID groups following the second dose. Almost three to four months after the second dose, all IMID patients demonstrated significantly lower IL-2 and IL-4 production with respect to healthy controls along with decreased IFNγ production reported in anti-IL-17A- and anti-IL-23-treated individuals. No deficits were noted in cytokine responses in comparison to healthy controls following the third dose.

All groups revealed significant declines in anti-spike and anti-RBD levels by three to four months after the second dose, with the highest decreases found in TNF IMID patients. Also, the magnitude of waning between anti-spike and anti-RBD IgG after the third and fourth vaccinations revealed unique kinetics. All the research groups demonstrated waning responses for anti-RBD IgG at three to four months following the third dose, which was of a lower level relative to that reported after the second vaccination. On the other hand, no significant differences were observed in waning responses between the third and fourth vaccinations.

Conclusion

The study findings presented the course of adaptive immunity induced by COVID-19 vaccinations among IMID patients treated with targeted or systemic immune-modifying medications. The study demonstrated that repeated vaccination doses extend and widen immune responses against SARS-CoV-2, supporting the administration of three and four vaccinations in immunocompromised patients.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.