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Gastroenterology ; 162(7):S-1008, 2022.
Article in English | EMBASE | ID: covidwho-1967396


BACKGROUND: Immune-modulating medications for inflammatory bowel diseases (IBD) have been associated with suboptimal vaccine responses. There is conflicting data with SARS-CoV-2 vaccination. METHODS: We measured SARS-CoV-2 vaccine immunogenicity at 2 weeks post 2nd mRNA vaccine in IBD patients as compared to normal healthy donors (NHD). We measured humoral immune responses to SARS-CoV-2: anti-spike Immunoglobulin G (IgG) and anti-receptor binding domain (RBD) IgG were measured by ELISA, and neutralizing antibody titers were measured using recombinant, reporter SARS-CoV-2. Antigen specific memory B cells were measured using recombinant SARS-CoV-2 proteins. Activation induced marker T cell (AIM) assays were performed using SARS-CoV-2 spike megapools. Immunophenotyping was performed by flow cytometry. RESULTS: We enrolled 29 patients with IBD (19 with Crohn's disease, 10 with ulcerative colitis) on infliximab (IFX) monotherapy (N=9), IFX combination therapy with a thiopurine (N=9), vedolizumab monotherapy (N= 11) as compared to matched NHD (N=12). At 2 weeks post vaccination, all subjects made detectable anti-spike IgG and anti-RBD IgG. There were no differences in anti-spike IgG titers among the different groups. IBD patients on IFX monotherapy, but not IBD patients on IFX combination therapy or vedolizumab monotherapy, had lower anti-RBD and neutralization titers as compared to NHD (p-value: 0.041 and 0.023, respectively) (Fig. 1). There were no significant differences in the percentage of spike-specific or RBD-specific memory B cells in IBD patients as compared to NHD (Fig. 1). There were no differences in the percentage of spike-specific CD4+ or CD8+ T cells in all IBD patients as compared to NHDs (Fig. 2). CONCLUSIONS: We demonstrate overall comparable and perserved cell-mediated immunity to SARS-CoV-2 vaccination in a small cohort of IBD patients treated with a range of different immune-modulating medications as compared to healthy controls. Larger numbers of patients are needed to validate these findings.

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation ; 41(4):S399-S399, 2022.
Article in English | EuropePMC | ID: covidwho-1781950


Introduction Solid organ transplant recipients (SOTR) have lower SARS-CoV-2 spike seroconversion than healthy subjects (HS) following vaccination. A breakthrough (BT) infection is defined as the detection of SARS-CoV-2 in a respiratory specimen after a person is ≥14 days after completing the recommended doses for a vaccine. We report a case of SARS-CoV-2 BT infection in a SOTR who was immunologically followed longitudinally following vaccination. Case Report A 44-year-old man with a history of non-ischemic cardiomyopathy (NICM) and end stage renal disease had undergone heart and kidney transplantation in December 2017 with thymoglobulin induction. His NICM was secondary to radiation for non-Hodgkin's lymphoma treated with autologous bone marrow transplant in 2001. Maintenance immunosuppression consisted of sirolimus 2mg daily, tacrolimus 2mg twice daily (BID), and prednisone 5mg daily at his 1st Moderna vaccine in April 2021. In anticipation of surgery, sirolimus was stopped and mycophenolate mofetil (MMF) 500mg BID was started. He was on this regimen at the time of his 2nd Moderna vaccine. Sirolimus was restarted in July and increased to 1mg daily while continuing MMF 500mg BID, tacrolimus, and prednisone. At the end of July, the patient was exposed to several family members with COVID-19. He tested positive 89 days after his 2nd Moderna vaccine (cycle threshold of 33.5). He was asymptomatic at the time, but later developed fever, myalgias, headache, and loss of taste and smell and was treated with casirivimab and imdevimab monoclonal antibody (mAb) infusion. We assessed the patient's immunologic response 14 days post 2nd Moderna vaccination and at BT infection prior to mAb infusion and compared this to HS. The patient developed SARS-CoV-2 spike-specific CD4+ T cells at 14 days post 2nd mRNA vaccine at a frequency below the average frequency for HS. At BT infection, the patient did not have SARS-CoV-2 spike-specific CD4+ T cells, partly due to virus induced lymphopenia. The patient did not develop spike-specific CD8+ T cells, spike IgG or neutralizing antibodies at 14 days post 2nd Moderna vaccination or at BT infection. Summary The patient developed SARS-CoV-2-specific CD4+ T cells following vaccination. His uneventful recovery may be secondary to these SARS-CoV-2 specific CD4+ T cells post vaccination as well as receiving mAb therapy 8 days post infection.

Preprint in English | EMBASE | ID: ppcovidwho-327028


We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, NVX-CoV2373) cross-recognize SARS-CoV-2 variants. Preservation of at least 83% and 85% for CD4+ and CD8+ T cell responses was found, respectively, regardless of vaccine platform or variants analyzed. By contrast, highly significant decreases were observed for memory B cell and neutralizing antibody recognition of variants. Bioinformatic analyses showed full conservation of 91% and 94% of class II and class I spike epitopes. For Omicron, 72% of class II and 86% of class I epitopes were fully conserved, and 84% and 85% of CD4+ and CD8+ T cell responses were preserved. In-depth epitope repertoire analysis showed a median of 11 and 10 spike epitopes recognized by CD4+ and CD8+ T cells from vaccinees. Functional preservation of the majority of the T cell responses may play an important role as a second-level defense against diverse variants.

Preprint in English | EMBASE | ID: ppcovidwho-326837


SARS-CoV-2 infection and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of two new pools of Experimentally-defined T cell epitopes derived from the non-spike Remainder of the SARS-CoV-2 proteome (CD4RE and CD8RE). The combination of T cell responses to these new pools and Spike (S) were used to discriminate four groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status: non-infected, non-vaccinated (I-V-);infected and non-vaccinated (I+V-);infected and then vaccinated (I+V+);and non-infected and vaccinated (I-V+). The overall classification accuracy based on 30 subjects/group was 89.2% in the original cohort and 88.5% in a validation cohort of 96 subjects. The T cell classification scheme was applicable to different mRNA vaccines, and different lengths of time post-infection/post-vaccination. T cell responses from breakthrough infections (infected vaccinees, V+I+) were also effectively segregated from the responses of vaccinated subjects using the same classification tool system. When all five groups where combined, for a total of 239 different subjects, the classification scheme performance was 86.6%. We anticipate that a T cell-based immunodiagnostic scheme able to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccination and aid in establishing SARS-CoV-2 correlates of protection.