RESUMEN
We report SARS-CoV-2 vaccine-induced immunity and risk of breakthrough infections in patients with inflammatory bowel disease treated with infliximab, a commonly used anti-TNF drug and those treated with vedolizumab, a gut-specific antibody targeting integrin a4b7 that does not impact systemic immunity. In infliximab-treated patients, the magnitude of anti-SARS-CoV2 antibodies was reduced 4-6-fold. One fifth of both infliximab- and vedolizumab-treated patients did not mount a T cell response. Antibody half-life was shorter in infliximab-treated patients. Breakthrough SARS-CoV-2 infections occurred more frequently in infliximab-treated patients and the risk was predicted by the level of antibody response after second vaccine dose. Overall, recipients of two doses of the BNT162b2 vaccine had higher anti-SARS-CoV-2 antibody concentrations, higher seroconversion rates, shorter antibody half-life and less breakthrough infections compared to ChAdOx1 nCoV-19 vaccine recipients. Irrespective of biologic treatment, higher, more sustained antibody levels were observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Patients treated with anti-TNF therapy should be offered third vaccine doses.
RESUMEN
Studies of adaptive immunity to SARS-CoV-2 include characterisation of lethal, severe and mild cases1-8. Understanding how long immunity lasts in people who have had mild or asymptomatic infection is crucial. Healthcare worker (HCW) cohorts exposed to and infected by SARS-CoV-2 during the early stages of the pandemic are an invaluable resource to study this question9-14. The UK COVIDsortium is a longitudinal, London hospital HCW cohort, followed from the time of UK lockdown9,10 ; weekly PCR, serology and symptom diaries allowed capture of asymptomatic infection around the time of onset, so duration of immunity could be tracked. Here, we conduct a cross-sectional, case-control, sub-study of 136 HCW at 16-18 weeks after UK lockdown, with 76 having had laboratory-confirmed SARS-CoV-2 mild or asymptomatic infection. Neutralising antibodies (nAb) were present in 90% of infected HCW sampled after the first wave; titres, likely to correlate with functional protection, were present in 66% at 16-18 weeks. T cell responses tended to be lower in asymptomatic infected HCW than those reporting case-definition symptoms of COVID-19, while nAb titres were maintained irrespective of symptoms. T cell and antibody responses were discordant. HCW lacking nAb also showed undetectable T cells to Spike protein but had T cells of other specificities. Our findings suggest that the majority of HCW with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multi-specific T cell responses for at least 4 months after mild or asymptomatic SARS-CoV-2 infection.
