Treatment with the anti-TNF agent infliximab blunts the body's immune response to SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD), which may boost susceptibility to recurrent infection and contribute to the evolution of SARS-CoV-2 variants, caution researchers from the U.K. "Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy," advise Dr. Tariq Ahmad of Royal Devon and Exeter NHS Trust and colleagues in the journal Gut. Infliximab and other anti-TNF agents are known to impair protective immunity following vaccination against pneumonia, influenza and viral hepatitis, as well as increase risk of serious infection, particularly respiratory infections. Dr. Ahman and colleagues sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infection. They compared antibody responses to SARS-CoV-2 in 4,685 IBD patients treated with infliximab and 2,250 IBD patients treated with another biologic, vedolizumab, which is not associated with increased susceptibility to infection or blunted immune responses to vaccines. Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups; 389 (8.3%) patients on infliximab and 201 (8.9%) on vedolizumab had symptoms indicative of infection; 89 of 1,712 patients (5.2%) on infliximab had a positive SARS-CoV-2 test as did 38 of 877 (4.3%) patients on vedolizumab. However, significantly fewer patients taking infliximab than vedolizumab had detectable antibodies to the virus in blood (3.4% vs. 6.0%; P<0.0001). Multivariate analysis confirmed that infliximab therapy was independently associated with lower seropositivity (odds ratio, 0.66; P=0.0027). Concomitant immunomodulator use with a thiopurine or methotrexate was also independently associated with blunted serological responses to SARS-CoV-2 (OR, 0.70; P=0.012). In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab- than vedolizumab-treated patients (48% vs. 83%; P=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median cut-off index, 0.8 vs. 37.0; P<0.0001). Based on their finding, the authors say, "infliximab seems to be directly influencing the serological response to infection," which has important implications. "From a public health perspective, impaired serological responses might lead to chronic nasopharyngeal colonization that may act as a reservoir to drive persistent transmission and the evolution of new SARS-CoV-2 variants," they explain. "For the individual anti-TNF treated patient, lower rates of seroconversion and reduced anti-SARS-CoV-2 antibody reactivity levels may ultimately increase their susceptibility to recurrent COVID-19," they add. "Accepting that vaccination is critical to suppress transmission, serology testing should be considered to detect suboptimal vaccine responses to inform the need for the most restrictive social distancing measures to protect patients and public health. If attenuated serological responses following vaccination are observed, then modified vaccination schedules given in combination might need to be considered in these patients," Dr. Ahmad and colleagues conclude. This study was funded by F. Hoffmann-La Roche, Hull University Teaching Hospital NHS Trust, Biogen GmbH (Switzerland), Celltrion Healthcare, Galapagos NV, Royal Devon and Exeter NHS Foundation Trust. Dr. Ahmad reports grants and non-financial support from F. Hoffmann-La Roche AG and grants from Biogen Inc, Celltrion Healthcare and Galapagos NV. —Reuters Staff Source
