Case report: SARS-CoV-2 specific T-cells are associated with myocarditis after COVID-19 vaccination with mRNA-1273

Vaccination of SARS-CoV-2 with BNT162b2 or mRNA-1273 both have a low incidence of induction of myocarditis. Here we report on utilizing adaptive immune receptor repertoire sequencing (AIRR-Seq) as a way to assess the specificity of tissue infiltrating immune cells.

Case report: SARS-CoV-2 specific T-cells are associated with myocarditis after COVID-19 vaccination with mRNA-1273.

Vaccination of SARS-CoV-2 with BNT162b2 or mRNA-1273 both have a low incidence of induction of myocarditis. Here we report on utilizing adaptive immune receptor repertoire sequencing (AIRR-Seq) as a way to assess the specificity of tissue infiltrating immune cells.

Urinary biomarkers to predict acute kidney damage and mortality in COVID-19.

INTRODUCTION: Acute kidney injury (AKI) is a frequent condition in patients hospitalized for COVID-19. There are only a few reports on the use of urinary biomarkers in COVID-19 and no data so far comparing the prognostic use of individual biomarkers in the prediction of adverse outcomes. MATERIALS AND METHODS: We performed a prospective mono-centric study on the value of urinary biomarkers in predicting the composite endpoint of a transfer to the intensive care unit, the need for renal replacement therapy, mechanical ventilation, and in-hospital mortality. 41 patients hospitalized for COVID-19 were enrolled in this study. Urine samples were obtained shortly after admission to assess neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin, and vascular non-inflammatory molecule-1 (vanin-1). RESULTS: We identified calprotectin as a predictor of a severe course of the disease requiring intensive care treatment (AUC 0.728, p = 0.016). Positive and negative predictive values were 78.6% and 76.9%, respectively, using a cut-off concentration of 127.8 ng/mL. NGAL tended to predict COVID-19-associated AKI without reaching statistical significance (AUC 0.669, p = 0.053). The best parameter in the prediction of in-hospital mortality was NGAL as well (AUC 0.674, p = 0.077). KIM-1 and vanin-1 did not reach significance for any of the investigated endpoints. CONCLUSION: While KIM-1 and vanin-1 did not provide prognostic clinical information in the context of COVID-19, the present study shows that urinary calprotectin is moderately predictive of the need for intensive care unit (ICU) admission, and NGAL may be modestly predictive of AKI in COVID-19. Calprotectin and NGAL show promise as potential helpful adjuncts in the identification of patients at increased risk of poor outcomes or complications in COVID-19.

Superior humoral immunity in vaccinated SARS-CoV-2 convalescence as compared to SARS-COV-2 infection or vaccination.

Emerging variants of concern (VOC) raise obstacles in shaping vaccination strategies and ending the pandemic. Vaccinated SARS-CoV-2 convalescence shapes the current immune dynamics. We analyzed the SARS-CoV-2 VOC-specific cellular and humoral response of 57 adults: 42 convalescent mRNA vaccinated patients (C+V+), 8 uninfected mRNA vaccinated (C-V+) and 7 unvaccinated convalescent individuals (C+V-). While C+V+ demonstrated a superior humoral SARS-CoV-2 response against all analyzed VOC (alpha, delta, omicron) compared to C-V+ and C+V-, SARS-CoV-2 reactive CD4+ and CD8+ T cells, which can cross-recognize the alpha, delta and omicron VOC after infection and/or vaccination were observed in all there groups without significant differences between the groups. We observed a preserved cross-reactive C+V+ and C-V+ T cell memory. An inferior humoral response but preserved cross-reactive T cell memory in C+V- compared to C+V+ was observed, as well as an inferior humoral response but preserved cross-reactive T cell memory in C+V- compared to C-V+. Adaptive immunity generated after SARS-CoV-2 infection and vaccination leads to superior humoral immune response against VOC compared to isolated infection or vaccination. Despite the apparent loss of neutralization potential caused by viral evolution, a preserved SARS-CoV-2 reactive T cell response with a robust potential for cross-recognition of the alpha, delta and omicron VOC was detected in all studied cohorts. Our results may have implications on current vaccination strategies.

Vaccination in patients with kidney failure: lessons from COVID-19.

Infection is the second leading cause of death in patients with chronic kidney disease (CKD). Adequate humoral (antibody) and cellular (T cell-driven) immunity are required to minimize pathogen entry and promote pathogen clearance to enable infection control. Vaccination can generate cellular and humoral immunity against specific pathogens and is used to prevent many life-threatening infectious diseases. However, vaccination efficacy is diminished in patients with CKD. Premature ageing of the immune system and chronic systemic low-grade inflammation are the main causes of immune alteration in these patients. In the case of SARS-CoV-2 infection, COVID-19 can have considerable detrimental effects in patients with CKD, especially in those with kidney failure. COVID-19 prevention through successful vaccination is therefore paramount in this vulnerable population. Although patients receiving dialysis have seroconversion rates comparable to those of patients with normal kidney function, most kidney transplant recipients could not generate humoral immunity after two doses of the COVID-19 vaccine. Importantly, some patients who were not able to produce antibodies still had a detectable vaccine-specific T cell response, which might be sufficient to prevent severe COVID-19. Correlates of protection against SARS-CoV-2 have not been established for patients with kidney failure, but they are urgently needed to enable personalized vaccination regimens.

Predictors of impaired SARS-CoV-2 immunity in healthcare workers after vaccination with BNT162b2.

Healthcare workers are at substantially increased risk for infection with SARS-CoV-2. Successful vaccination constitutes a crucial prerequisite to protect this group during the pandemic. Since post vaccination antibody monitoring is not standard of care in all healthcare institutions, data on risk factors of impaired vaccine induced immune response are urgently required. Moreover, there are no data on cellular immune responses in humoral low responders so far. Anti-SARS-CoV-2 spike IgG was assessed after vaccination with BNT162b2 in 1386 employees of three hospitals of a German healthcare provider. Concentrations were compared to those of 45 convalescent employees. Vaccine-induced cellular immunity was measured in employees with reduced humoral response by assessment of frequencies of SARS-CoV-2-reactive CD4+ and CD8+ T cell. Anti-SARS-CoV-2 spike IgG were detected in 99.9% of 1386 healthcare workers after completed vaccination. The median antibody concentration was significantly higher after vaccination than after infection with SARS-CoV-2 (p = 0.0001). 10 subjects (0.7%) generated an IgG concentration < 100 IU/ml, and only two persons (0.1%, solid organ recipients) did not produce detectable antibodies at all. T cell responses of those subjects with submaximal or lacking humoral response were comparable to employees with maximal antibody titers. 50% of those individuals with impaired or lacking humoral immune response were on immunosuppression. Vaccination to SARS-CoV-2 with BNT162b2 is very effective in healthcare workers yielding a seroconversion rate of 99.9%. Immunosuppression is the most important risk factor of an impaired immune response. There was no case of vaccination failure without immunosuppression. Thus, post vaccination antibody monitoring is highly recommendable in those employees with immunosuppression.

Severe Acute Respiratory Syndrome Coronavirus 2 Cross-Reactive B and T Cell Responses in Kidney Transplant Patients.

BACKGROUND: Immune responses to seasonal endemic coronaviruses might have a pivotal role in protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Those SARS-CoV-2-crossreactive T cells were recently described in immunocompetent individuals. Still, data on cross-reactive humoral and cellular immunity in kidney transplant recipients is currently lacking. METHODS: The pre-existing, cross-reactive antibody B and T cell immune responses against SARS-CoV-2 in unexposed adults with kidney transplantation (Tx, n = 14) and without (non-Tx, n = 12) sampled before the pandemic were compared with 22 convalescent patients with COVID-19 (Cp) applying enzyme-linked immunosorbent assay and flow cytometry. RESULTS: In both unexposed groups, SARS-CoV-2 IgG antibodies were not detectable. Memory B cells binding spike (S) protein SARS-CoV-2 were detected in unexposed individuals (64% among Tx; 50% among non-Tx) and higher frequencies after infection (80% Cp). The numbers of SARS-CoV-2-reactive T cells were comparable between patients who had undergone Tx and those who had not. SARS-CoV-2-reactive follicular T helper cells were present in 61% of the unexposed cohort in both patients who had undergone Tx and those who had not. CONCLUSIONS: Cross-reactive memory B and T cells against SARS-CoV-2 exist also in transplanted adults, suggesting a primed adaptive immunity. The effect on the disease course may depend on the concomitant immunosuppressive drugs.

Low-density lipoprotein apheresis is associated with removal of SARS-CoV-2 antibodies.

BACKGROUND: Low-density lipoprotein apheresis is not specific to lipoproteins but removes immunoglobulins as well. It remains elusive, whether protective SARS-CoV-2 antibodies after vaccination from COVID-19 are eliminated as well. METHODS: A cross-sectional case-control study on 55 patients undergoing weekly lipoprotein apheresis and 21 patients with comparable comorbidities and epidemiology not undergoing apheresis. SARS-CoV-2 IgG was assessed in all patients prior to apheresis and in 38 patients both before and after apheresis. RESULTS: SARS-CoV-2 IgG concentrations before a session of lipoprotein apheresis were comparable to control patients not undergoing apheresis(1727 IU/ml, IQR 365-2500) vs. 1652 IU/ml,(IQR408.8-2500), p = 0.78). SARS-CoV-2 IgG concentrations were reduced by lipoprotein apheresis from 1656 IU/ml(IQR 540.5-2500) prior to 1305 IU/ml (IQR 449-2500) afterwards(p < 0.0001). CONCLUSION: Lipoprotein apheresis removes SARS-CoV-2 IgG. The average elimination rate was 21.2%. In the present population of patients undergoing apheresis once weekly, however, the elimination did not lead to inferior concentrations compared to patients not undergoing lipoprotein apheresis.

Immune Response in Moderate to Critical Breakthrough COVID-19 Infection After mRNA Vaccination.

SARS-CoV-2 variants of concern (VOCs) can trigger severe endemic waves and vaccine breakthrough infections (VBI). We analyzed the cellular and humoral immune response in 8 patients infected with the alpha variant, resulting in moderate to fatal COVID-19 disease manifestation, after double mRNA-based anti-SARS-CoV-2 vaccination. In contrast to the uninfected vaccinated control cohort, the diseased individuals had no detectable high-avidity spike (S)-reactive CD4+ and CD8+ T cells against the alpha variant and wild type (WT) at disease onset, whereas a robust CD4+ T-cell response against the N- and M-proteins was generated. Furthermore, a delayed alpha S-reactive high-avidity CD4+ T-cell response was mounted during disease progression. Compared to the vaccinated control donors, these patients also had lower neutralizing antibody titers against the alpha variant at disease onset. The delayed development of alpha S-specific cellular and humoral immunity upon VBI indicates reduced immunogenicity against the S-protein of the alpha VOC, while there was a higher and earlier N- and M-reactive T-cell response. Our findings do not undermine the current vaccination strategies but underline a potential need for the inclusion of VBI patients in alternative vaccination strategies and additional antigenic targets in next-generation SARS-CoV-2 vaccines.