https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345889

Immunogenicity of SARS-CoV-2 vaccines in patients with cancer

Immune checkpoint inhibitor (ICI) therapy revolutionized the treatment of multiple solid and hematologic malignancies. Yet, with it came profound inflammatory toxicities that mimic autoimmune diseases, termed immune-related adverse events (irAEs). Prominent among these is gastrointestinal inflammation, including a spectrum of gastritis, enteritis, and colitis. Here we synthesize an approach to immune checkpoint related enterocolitis (irEC) - including diagnostics and therapeutics - underpinned by new insights into the mechanism behind these phenomena.This review presents updated insights on how to approach irEC, including novel approaches to selective immunosuppressive therapy, the role of fecal microbiota transplant, and the underlying cellular mechanisms of irEC. This review provides an update on irEC diagnosis and therapy, with considerations of new therapies and special patient populations. The field of gastrointestinal irAEs requires additional investigation, which will ultimately provide the tools required for patients to continue to receive life-saving ICI therapy. 

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Update on Immune Checkpoint Inhibitor Enterocolitis

Simple Summary The efficacy and safety of the BNT126b2 vaccine against SARS-CoV-2 has not been thoroughly studied in cancer patients treated with immunotherapy. This research aims to investigate the efficacy and safety of the vaccine in patients with melanoma under immunotherapy; at the same time, through the immunophenotyping of T cells and myeloid cells of the peripheral blood, it will be possible to look for changes in the subpopulations of such cells after vaccinations. The results of the study help establish the efficacy and safety of the vaccine in this population, especially since a theoretical concern exists about the vaccine triggering irAEs. Abstract The BNT162b2 vaccine against SARS-CoV-2 has a proven efficacy and a favorable safety profile. In cancer patients under immunotherapy in the form of immune-checkpoint inhibitors (ICIs), the efficacy of the vaccine has not been thoroughly studied, while a theoretical concern has also been raised about triggering immune-related adverse events (irAEs) by the vaccine. We conducted a prospective, non-interventional study on the immunogenicity and safety of the BNT162b2 vaccine in patients with advanced or metastatic melanoma treated with ICIs. Blood samples were obtained 0–4 days before the first dose and 12–21 days after the second dose of the vaccine for the quantification of the SARS-CoV-2 anti-spike antibody using an ELISA and immunophenotyping of the T and myeloid cell subpopulations. The active recording of AEs for a two-month period was conducted. Forty patients were included in the study. All but one (97.3%) achieved seroconversion after two doses of the vaccine and no correlations of the antibody titers with any of the studied parameters (age, gender, stage and duration of the disease, type of ICI, previous treatment, etc.) were found. Moreover, no differences in the subpopulations of the T cells (including the T-regulatory cells) or the myeloid cells were found pre- and post-vaccination. All AEs were low-grade, while one case of arthritis exacerbation was noted. The seroconversion rate in the studied population was high and was comparable to that of healthy subjects, while no major safety issues were raised during the safety follow-up. Finally, no derangements in the subpopulations of T cells or myeloid cells were noted. This is the first study focusing on the immunogenicity, safety, and effect of anti-SARS-CoV-2 vaccines on the blood-cell immunophenotype status of patients with melanoma treated with ICIs.

/pdf/immunogenicity-and-safety-of-the-bnt162b2-mrna-covid-19-w9bgtafn.pdf

Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Melanoma Treated with Immunotherapy

The impact of the coronavirus disease 2019 (COVID-19) pandemic has been immense, and it continues to have lasting repercussions. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus primarily infects the respiratory system, other organ systems are affected, including the liver. Scientific knowledge on the role of SARS-CoV-2 infection and liver injury has evolved rapidly, with recent data suggesting specific hepatotropism of SARS-CoV-2. Moreover, additional concerns have been raised in regard to long-term liver damage, related to emerging cases of post-COVID-19 cholangiopathy and chronic cholestasis. Great effort has also been focused on studying how specific subpopulations with chronic medical conditions might be disproportionately impacted by COVID-19. One such population includes individuals with chronic liver disease (CLD) and cirrhosis, with an expanding body of research indicating these patients being particularly susceptible to adverse outcomes. In this review, we provide an updated summary on the current pathogenesis and mechanism of liver injury in the setting of SARS-CoV-2 infection, the association between health outcomes and SARS-CoV-2 infection in patients with CLD, and the unique consequences of the COVID-19 pandemic on the routine care of patients with CLD.

https://www.gutnliver.org/journal/download_pdf.php?doi=10.5009/gnl220327

SARS-CoV-2 Infection and Liver Disease: A Review of Pathogenesis and Outcomes

Immune-related adverse events and disease outcomes after the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients receiving immune checkpoint inhibitors.

Patients with cancer frequently receive immune-checkpoint inhibitors (ICIs), which may modulate immune responses to COVID-19 vaccines. Recently, cytokine release syndrome (CRS) was observed in a patient with cancer who received BTN162b2 vaccination under ICI treatment. Here, we analyzed adverse events and serum cytokines in patients with 23 different tumors undergoing (n = 64) or not undergoing (n = 26) COVID-19 vaccination under ICI therapy in a prospectively planned German single-center cohort study (n = 220). We did not observe clinically relevant CRS (≥grade 2) after vaccination (95% CI 0-5.6%; Common Terminology of Adverse Events v.5.0) in this small cohort. Within 4 weeks after vaccination, serious adverse events occurred in eight patients (12.5% 95% CI 5.6-23%): six patients were hospitalized due to events common under cancer therapy including immune related adverse events and two patients died due to conditions present before vaccination. Despite absence of CRS symptoms, a set of pairwise-correlated CRS-associated cytokines, including CXCL8 and interleukin-6 was >1.5-fold upregulated in 40% (95% CI 23.9-57.9%) of patients after vaccination. Hence, elevated cytokine levels are common and not sufficient to establish CRS diagnosis. 

/pdf/cytokine-release-syndrome-like-serum-responses-after-covid-17sq5uwx.pdf

Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy

/pdf/author-correction-cytokine-release-syndrome-like-serum-2fea1ola.pdf

Author Correction: Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy

We report the case of a 38-year-old male patient who presented with blanching of the face after strenuous exercise or physical exertion. The symptoms regressed in a relaxed state. Three years before presentation, he underwent botulinum toxin injections in the affected areas of the face. Facial blanching is a rare side effect of botulinum toxin injection. The postulated pathophysiology involves different transmitters mainly acetylcholine as well as co-transmitters implicated in vasodilation. Usually, facial blanching resolves shortly after waning of the botulinum toxin. However, in our case, the symptoms persisted for a longer time. Till date, therapy options for post-botulinum facial blanching are lacking, mainly due to the temporary aspect of the disease.

/pdf/persistent-facial-blanching-after-botulinum-toxin-injection-2hkr8erj.pdf

Katharina A. Kälber

Papers

Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy

Author Correction: Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy

Persistent Facial Blanching after Botulinum Toxin Injection