Editorial: immunosuppression and SARS‐CoV‐2 vaccination—where do we stand?

LINKED CONTENT

This article is linked to Woelfel et al papers. To view these articles, visit https://doi.org/10.1111/apt.17264

With the coronavirus pandemic waning but still very much present, whether the degree of protection conferred by the SARS‐CoV‐2 vaccines is similar to those on immunosuppression remains unclear. Woelfel and colleagues examined the impact of biologics on humoral and T‐cell associated responses to the third dose of an mRNA SARS‐CoV‐2 vaccine among 139 patients with IBD on biologics (81 on tumour necrosis factor α antagonists [anti‐TNF], 58 treated with vedolizumab or ustekinumab) and 110 controls. ¹ Humoral immune responses were quantified by anti‐spike protein IgG concentrations. Cellular immunity was defined by T‐cell‐mediated interferon‐γ release after stimulation of whole blood with SARS‐CoV‐2 antigens. Patients with IBD on anti‐TNF therapy (but not non‐TNF biologic users) had lower anti‐spike IgG concentrations than controls. However, antibody concentrations met the threshold for seropositivity in all patients except for one on a non‐TNF biologic. Antibody titres were lower at a longer time interval after the booster dose and higher in those who received the mRNA‐1273 vaccine (NIH‐Moderna) or who had prior SARS‐CoV‐2 infection. A greater proportion of anti‐TNF‐treated patients also had inadequate T‐cell responses (20.5%) than non‐TNF biologic users (9.6%) or healthy controls (2%). T‐cell responses did not correlate with anti‐spike protein antibody titres (p = 0.88), suggesting that cellular and humoral immune response to vaccination was discordant. Importantly, lower concentrations of anti‐spike antibodies were not associated with a higher risk of breakthrough infections during the SARS‐CoV‐2 B1.1.1.529 (Omicron) wave.

Literature on the impact of immunosuppression on SARS‐CoV‐2 vaccine responses in IBD has been mixed. Studies from the United Kingdom, Israel and the United States demonstrated a weaker humoral immune response to SARS‐CoV‐2 vaccines among patients on anti‐TNF agents, consistent with the present study. ² , ³ , ⁴ , ⁵ In contrast, other multi‐centre cohorts demonstrated a high degree of seropositivity to vaccination irrespective of immunosuppression status. ⁶ , ⁷ While one study suggested a two‐fold increase in the risk of breakthrough infections as a result of the weaker serologic response in patients on infliximab compared to vedolizumab, ⁸ others found a low rate of breakthrough independent of systemic immunosuppression at vaccination. ⁴ , ⁶ Importantly, none of the studies demonstrated an increase in either serious infections or mortality.

To translate these findings into clinical practice today, one can conclude that there may be a modest impairment of the humoral immune response to the SARS‐CoV‐2 vaccine in patients on systemic anti‐TNF therapy. However, it should be emphasised that equally high‐quality studies have suggested no impairment of immune response to vaccination. It is reasonable to prioritise patients with IBD on anti‐TNF (or immunomodulator) therapy to additional booster doses as data emerge on the value of such a practice in the general population. However, both patients and physicians should be reassured that a weaker humoral immune response has not translated into a significant increase in risk for severe COVID‐19 or mortality. This emphasises the importance of continuing treatment of underlying IBD without interruption to prevent IBD‐related morbidity.

FUNDING INFORMATION

None.

CONFLICTS OF INTEREST

Ananthakrishnan has received consulting fees from Ikena Oncology and Menten AI, and an honorarium for a lecture from Pfizer.