The impact of SARS-CoV-2 variants on IBD management

The COVID-19 pandemic has revealed several challenges in inflammatory bowel disease (IBD) management. One of the initial key considerations was the effect of immunosuppression on COVID-19 incidence and outcomes, as well as on immunity after infection or vaccination.1, 2 With a rise in cases due to the emergence of SARS-CoV-2 variants, the question now is whether this information still applies.

A SARS-CoV-2 variant called B.1.1.7 was first identified in the UK, where it has now become the dominant strain; the variant has spread to more than 70 countries.² Another variant, B.1.351, emerged independently in South Africa, and the Brazil variant, P.1, was identified in January, 2021. The UK and South Africa variants have a mutation (N501Y) in the receptor-binding domain of the spike protein that is reported to be linked to a 40–70% higher transmission rate.³ Some early studies have suggested a higher incidence of death with B.1.1.7 than the original strain.2, 4 Variable protection is provided by the current licensed SARS-CoV-2 vaccines against these emergent variants.3, 5 Consequently, many countries have imposed further lockdowns, travel bans, and strict quarantine rules for those that have visited these areas where the variants are endemic.

The new variants share the same symptomatology with the initial strain; however, loss of taste or smell were observed slightly less often with B.1.1.7.⁶ Despite evidence of increased transmissibility, it is important to note that, as yet, there remains little evidence that this variant is associated with a more severe phenotype or an increase in mortality,⁴ although such observations might be confounded by advances in testing and therapeutic strategies against COVID-19 since SARS-CoV-2 first emerged.

The emergence of SARS-CoV-2 variants poses several questions for the IBD community. Our initial experience of COVID-19 has suggested that the medications used for patients with IBD do not seem to confer an increased risk of infection, severity, or poorer outcomes.⁷ It might not be possible to currently confirm that the same is true for the new variants. Moreover, further mutations of SARS-CoV-2 are likely to develop in the future, which might lead to altered infectivity, virulence, and severity. What effect this will have on patients with IBD remains to be seen.

A notable additional consideration is whether immunosuppression affects antiviral⁸ and immune responses⁹ for patients with IBD. The combination of viral mutation plus immunosuppression might be enough to weaken anti-vaccine responses to the point that available vaccines no longer confer meaningful anti-SARS-CoV-2 immunity, at least with respect to the mutant viral forms.

Therefore, we suggest that patients with IBD should still proceed with caution in the current pandemic. Furthermore, we suggest that vaccine efficacy in the general population should be extrapolated to the immunosuppressed population very cautiously. Considering there is already evidence for a lower immunogenic response to the new variants with the currently licensed vaccines,⁴ the fact that immunosuppression can further reduce immunogenicity is cause for concern for patients with IBD.

Despite a plethora of research into the effects of the primary sequenced SARS-CoV-2, there is now a need to develop observational prospective studies to evaluate the effect of new variants on patients with IBD. It is essential that the health-care community promotes ongoing research into the efficacy of available and new vaccines as they become available. An exemplar model has been the UK CLARITY IBD initiative to assess seroconversion after SARS-CoV-2 infection in patients with IBD receiving systemic anti-tumour necrosis factor therapy (infliximab) or gut-selective anti-α4β7 integrin therapy (vedolizumab). Promoting such research will ensure adaptable and resilient future strategies to enable rapid evidence-based adaptations to vaccination strategies, which might include vaccine selection, combination vaccines, or use of boosters to confer optimal immunity to patients with IBD.