ABSTRACT
BACKGROUND: Four EMA-approved vaccines against SARS-CoV-2 are currently available. Data regarding antibody responses to initial vaccination regimens in patients with inflammatory bowel diseases (IBD) are limited. METHODS: We conducted a prospective, controlled, multicenter study in tertiary Greek IBD centers. Participating patients had completed the initial vaccination regimens (1 or 2 doses, depending on the type of COVID-19 vaccine) at least 2 weeks before study enrolment. Anti-S1 IgG antibody levels were measured. Demographic and adverse events data were collected. RESULTS: We tested 403 patients (Crohn's disease, 58.9%; male, 53.4%; median age, 45 years) and 124 healthy controls (HCs). Following full vaccination, 98% of patients seroconverted, with mRNA vaccines inducing higher seroconversion rates than viral vector vaccines (P = .021). In total, IBD patients had lower anti-S1 levels than HCs (P < .001). In the multivariate analysis, viral vector vaccines (P < .001), longer time to antibody testing (P < .001), anti-TNFα treatment (P = .013), and age (P = .016) were independently associated with lower anti-S1 titers. Vedolizumab monotherapy was associated with higher antibody levels than anti-TNFα or anti-interleukin-12/IL-23 monotherapy (P = .023 and P = .032). All anti- SARS-CoV-2 vaccines were safe. CONCLUSIONS: Patients with IBD have impaired antibody responses to anti-SARS-CoV-2 vaccination, particularly those receiving viral vector vaccines and those on anti-TNFα treatment. Older age also hampers antibody production after vaccination. For those low-response groups, administration of accelerated or prioritized booster vaccination may be considered.
Thisis a multicenter study on IBD patients after COVID-19 vaccination and anti-S1 IgG antibody levels measurement. Patients with IBD have lower antibody responses than healthy controls, particularly those receiving viral vector vaccines and those on anti-TNFα or combination treatment.
ABSTRACT
L-Dopa decarboxylase (DDC) is the most significantly co-expressed gene with ACE2, which encodes for the SARS-CoV-2 receptor angiotensin-converting enzyme 2 and the interferon-inducible truncated isoform dACE2. Our group previously showed the importance of DDC in viral infections. We hereby aimed to investigate DDC expression in COVID-19 patients and cultured SARS-CoV-2-infected cells, also in association with ACE2 and dACE2. We concurrently evaluated the expression of the viral infection- and interferon-stimulated gene ISG56 and the immune-modulatory, hypoxia-regulated gene EPO. Viral load and mRNA levels of DDC, ACE2, dACE2, ISG56 and EPO were quantified by RT-qPCR in nasopharyngeal swab samples from COVID-19 patients, showing no or mild symptoms, and from non-infected individuals. Samples from influenza-infected patients were analyzed in comparison. SARS-CoV-2-mediated effects in host gene expression were validated in cultured virus-permissive epithelial cells. We found substantially higher gene expression of DDC in COVID-19 patients (7.6-fold; p = 1.2e-13) but not in influenza-infected ones, compared to non-infected subjects. dACE2 was more elevated (2.9-fold; p = 1.02e-16) than ACE2 (1.7-fold; p = 0.0005) in SARS-CoV-2-infected individuals. ISG56 (2.5-fold; p = 3.01e-6) and EPO (2.6-fold; p = 2.1e-13) were also increased. Detected differences were not attributed to enrichment of specific cell populations in nasopharyngeal tissue. While SARS-CoV-2 virus load was positively associated with ACE2 expression (r≥0.8, p<0.001), it negatively correlated with DDC, dACE2 (r≤-0.7, p<0.001) and EPO (r≤-0.5, p<0.05). Moreover, a statistically significant correlation between DDC and dACE2 expression was observed in nasopharyngeal swab and whole blood samples of both COVID-19 and non-infected individuals (r≥0.7). In VeroE6 cells, SARS-CoV-2 negatively affected DDC, ACE2, dACE2 and EPO mRNA levels, and induced cell death, while ISG56 was enhanced at early hours post-infection. Thus, the regulation of DDC, dACE2 and EPO expression in the SARS-CoV-2-infected nasopharyngeal tissue is possibly related with an orchestrated antiviral response of the infected host as the virus suppresses these genes to favor its propagation.