Review of Immunologic Manifestations of COVID-19 Infection and Vaccination.

We herein summarize currently available and clinically relevant information regarding the human immune responses to SARS-CoV-2 infection and vaccination, in relation to COVID-19 outcomes with a focus on acute respiratory distress syndrome (ARDS) and myocarditis.

Symptomology following mRNA vaccination against SARS-CoV-2.

Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P < 0.001), with >80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19-2.51) and dose 2 (1.76, 1.28-2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last <2 days. Appreciable post-vaccine symptoms are associated with female sex, prior COVID-19, younger age, and hypertension. This information can aid clinicians in advising patients on the safety and expected symptomatology associated with vaccination.

Clinical predictors of early and late endoscopic recurrence following ileocolonic resection in Crohn's disease.

BACKGROUND AND AIM: Multiple factors are suggested to place Crohn's disease patients at risk of recurrence after ileocolic resection with conflicting associations. We aimed to identify clinical predictors of recurrence at first (early) and further (late) postoperative colonoscopy. METHODS: Crohn's disease patients undergoing ileocolic resection were prospectively recruited at six North American centers. Clinical data was collected and endoscopic recurrence was defined as Rutgeerts score ≥i2. A multivariable model was fitted to analyze variables independently associated with recurrence. RESULTS: A total of 365 patients undergoing 674 postoperative colonoscopies were included with a median age of 32 years, 189 (51.8%) were male and 37 (10.1%) non-Whites. Postoperatively, 133 (36.4%) used anti-TNF and 30 (8.2%) were smokers. At first colonoscopy, 109 (29.9%) had recurrence. Male gender (OR = 1.95, 95% CI 1.12 - 3.40), non-White ethnicity (OR = 2.48, 95% CI 1.09 - 5.63), longer interval between surgery and colonoscopy (OR = 1.09, 95% CI 1.002 - 1.18), and postoperative smoking (OR = 2.78, 95% CI 1.16 - 6.67) were associated with recurrence, while prophylactic anti-TNF reduced the risk (OR = 0.28, 95% CI 0.14 - 0.55). Postoperative anti-TNF prophylaxis had a protective effect on anti-TNF experienced patients but not on anti-TNF naïve patients. Among patients without recurrence at first colonoscopy, Rutgeerts score i1 was associated with subsequent recurrence (OR = 4.43, 95% CI 1.73 - 11.35). CONCLUSIONS: We identified independent clinical predictors of early and late Crohn's disease postoperative endoscopic recurrence. Clinical factors traditionally used for risk stratification failed to predict recurrence and need to be revised.

Review of Immunologic Manifestations of COVID-19 Infection and Vaccination.

We herein summarize currently available and clinically relevant information regarding the human immune responses to SARS-CoV-2 infection and vaccination, in relation to COVID-19 outcomes with a focus on acute respiratory distress syndrome (ARDS) and myocarditis.

Differences in SARS-CoV-2 Vaccine Response Dynamics Between Class-I- and Class-II-Specific T-Cell Receptors in Inflammatory Bowel Disease.

T-cells specifically bind antigens to induce adaptive immune responses using highly specific molecular recognition, and a diverse T-cell repertoire with expansion of antigen-specific clones can indicate robust immune responses after infection or vaccination. For patients with inflammatory bowel disease (IBD), a spectrum of chronic intestinal inflammatory diseases usually requiring immunomodulatory treatment, the T-cell response has not been well characterized. Understanding the patient factors that result in strong vaccination responses is critical to guiding vaccination schedules and identifying mechanisms of T-cell responses in IBD and other immune-mediated conditions. Here we used T-cell receptor sequencing to show that T-cell responses in an IBD cohort were influenced by demographic and immune factors, relative to a control cohort of health care workers (HCWs). Subjects were sampled at the time of SARS-CoV-2 vaccination, and longitudinally afterwards; TCR Vß gene repertoires were sequenced and analyzed for COVID-19-specific clones. We observed significant differences in the overall strength of the T-cell response by age and vaccine type. We further stratified the T-cell response into Class-I- and Class-II-specific responses, showing that Ad26.COV2.S vector vaccine induced Class-I-biased T-cell responses, whereas mRNA vaccine types led to different responses, with mRNA-1273 vaccine inducing a more Class-I-deficient T-cell response compared to BNT162b2. Finally, we showed that these T-cell patterns were consistent with antibody levels from the same patients. Our results account for the surprising success of vaccination in nominally immuno-compromised IBD patients, while suggesting that a subset of IBD patients prone to deficiencies in T-cell response may warrant enhanced booster protocols.

The T-cell clonal response to SARS-CoV-2 vaccination in inflammatory bowel disease patients is augmented by anti-TNF therapy and often deficient in antibody-responders.

BACKGROUND: Vaccination against SARS-CoV-2 is a highly effective strategy to protect against infection, which is predominantly mediated by vaccine-induced antibodies. Postvaccination antibodies are robustly produced by those with inflammatory bowel disease (IBD) even on immune-modifying therapies but are blunted by anti-TNF therapy. In contrast, T-cell response which primarily determines long-term efficacy against disease progression,, is less well understood. We aimed to assess the post-vaccination T-cell response and its relationship to antibody responses in patients with inflammatory bowel disease (IBD) on immune-modifying therapies. METHODS: We evaluated IBD patients who completed SARS-CoV-2 vaccination using samples collected at four time points (dose 1, dose 2, 2 weeks after dose 2, 8 weeks after dose 2). T-cell clonal analysis was performed by T-cell Receptor (TCR) immunosequencing. The breadth (number of unique sequences to a given protein) and depth (relative abundance of all the unique sequences to a given protein) of the T-cell clonal response were quantified using reference datasets and were compared to antibody responses. RESULTS: Overall, 303 subjects were included (55% female; 5% with prior COVID) (Table). 53% received BNT262b (Pfizer), 42% mRNA-1273 (Moderna) and 5% Ad26CoV2 (J&J). The Spike-specific clonal response peaked 2 weeks after completion of the vaccine regimen (3- and 5-fold for breadth and depth, respectively); no changes were seen for non-Spike clones, suggesting vaccine specificity. Reduced T-cell clonal depth was associated with chronologic age, male sex, and immunomodulator treatment. It was preserved by non-anti-TNF biologic therapies, and augmented clonal depth was associated with anti-TNF treatment. TCR depth and breadth were associated with vaccine type; after adjusting for age and gender, Ad26CoV2 (J&J) exhibited weaker metrics than mRNA-1273 (Moderna) (p=0.01 for each) or BNT262b (Pfizer) (p=0.056 for depth). Antibody and T-cell responses were only modestly correlated. While those with robust humoral responses also had robust TCR clonal expansion, a substantial fraction of patients with high antibody levels had only a minimal T-cell clonal response. CONCLUSION: Age, sex and select immunotherapies are associated with the T-cell clonal response to SARS-CoV-2 vaccines, and T-cell responses are low in many patients despite high antibody levels. These factors, as well as differences seen by vaccine type may help guide reimmunization vaccine strategy in immune-impaired populations. Further study of the effects of anti-TNF therapy on vaccine responses are warranted.

The T-Cell Response to SARS-CoV-2 Vaccination in Inflammatory Bowel Disease is Augmented with Anti-TNF Therapy.

T-cell and antibody responses to severe acute respiratory syndrome coronavirus 2 vaccination in inflammatory bowel disease patients are poorly correlated. T-cell responses are preserved by most biologic therapies, but augmented by anti-tumor necrosis factor (anti-TNF) treatment. While anti-TNF therapy blunts the antibody response, cellular immunity after vaccination is robust.