Robust SARS-CoV-2 antibody and T cell immunity following three COVID-19 vaccine doses in inflammatory bowel disease patients receiving anti-TNF or alternative treatments (preprint)

BACKGROUND AND AIMS: Vaccine-mediated immune responses in patients with inflammatory bowel disease (IBD) may be influenced by IBD therapies. We investigated in-depth humoral and T-cell responses to SARS-CoV-2 vaccination in IBD patients following three COVID-19 vaccine doses. METHODS: Immune responses of 100 SARS-CoV-2-uninfected IBD patients on varying treatments were compared to healthy controls (n=35). Anti-S1/2 and anti-RBD SARS-CoV-2-specific antibodies, CD4+ and CD8+ T-cell responses were measured at baseline and at five time-points after COVID-19 vaccination. RESULTS: Anti-S1/2 and anti-RBD antibody concentrations at ~1 month after second dose vaccination were significantly lower in anti-TNF-treated patients compared to non-TNF IBD patients and healthy controls (126.4 vs 262.1 and 295.5, p<0.0001). Anti-S1/2 antibodies remained reduced in anti-TNF treated patients before and after the third dose (285.7 vs 365.3, p=0.03), although anti-RBD antibodies reached comparable titres to non-TNF patients. Anti-RBD antibodies were higher in the vedolizumab group than controls after second dose (4.2 vs 3.6, p=0.003). Anti-TNF monotherapy was associated with increased CD4+ and CD8+ T-cell activation compared to combination anti-TNF patients after second dose, but comparable after third dose. Overall, IBD patients demonstrated similar CD4+/CD8+ T-cell responses compared to healthy controls regardless of treatment regimen. CONCLUSIONS: Anti-TNFs impaired antibody concentrations when compared to non-TNF patients and controls after two vaccine doses. These differences were not observed after the third vaccine dose. However, vaccine induced SARS-CoV-2-specific T cell responses are robust in anti-TNF-treated patients. Our study supports the need for timely booster vaccination particularly in anti-TNF treated patients to minimise the risk of severe SARS-CoV-2 infection.

Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19 (preprint)

In 2015, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) reached the Republic of Korea through nosocomial transmission and was the largest epidemic outside of the Arabian Peninsula. To date, despite various strategies to identify CoV interventions, only limited therapeutic options are available. To address these unmet medical needs, we used a South Korean MERS-CoV clinical isolate and screened 5,406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactive molecules, for their activity against the isolate. The primary assay confirmed 221 hits by dose-response curve analysis and identified 54 hits with a therapeutic index (TI) greater than 6. Time-of-addition studies with 12 FDA-approved drugs demonstrated that 8 and 4 therapeutics act on the early and late stages of the viral life cycle, respectively. Among the drugs were e.g., three cardiotonic agents (ouabain, digitoxin, digoxin) with a TI greater than 100, an anti-malaria drug (atovaquone; TI >34), an inhalable corticosteroid (ciclesonide; TI >6), etc. Together, our results identify potential therapeutic options for treating MERS-CoV infections and could provide a basis for agents against a wider range of coronavirus-related illnesses, including the currently emerging Coronavirus Disease 2019 (COVID-19) outbreak.