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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306918

ABSTRACT

Cancer patients, in particular patients with hematological malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4 + and CD8 + T cell responses in unexposed and SARS-CoV-2-infected cancer patients to characterize SARS-CoV‑2 immunity and to identify immunological parameters contributing to COVID-19 outcome. Unexposed patients with hematological malignancies presented with reduced prevalence of pre-existing SARS-CoV-2 cross-reactive CD4 + T cell responses and signs of T cell exhaustion when compared to solid tumor patients and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between COVID-19 cancer patients and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T cell responses were profoundly reduced in cancer patients, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T cell immunity as determinant for dismal outcome of COVID-19 in cancer patients.

2.
Ultraschall Med ; 2021 Jul 05.
Article in English | MEDLINE | ID: covidwho-1294528

ABSTRACT

PURPOSE: Medical education has been transformed during the COVID-19 pandemic, creating challenges regarding adequate training in ultrasound (US). Due to the discontinuation of traditional classroom teaching, the need to expand digital learning opportunities is undeniable. The aim of our study is to develop a tele-guided US course for undergraduate medical students and test the feasibility and efficacy of this digital US teaching method. MATERIALS AND METHODS: A tele-guided US course was established for medical students. Students underwent seven US organ modules. Each module took place in a flipped classroom concept via the Amboss platform, providing supplementary e-learning material that was optional and included information on each of the US modules. An objective structured assessment of US skills (OSAUS) was implemented as the final exam. US images of the course and exam were rated by the Brightness Mode Quality Ultrasound Imaging Examination Technique (B-QUIET). Achieved points in image rating were compared to the OSAUS exam. RESULTS: A total of 15 medical students were enrolled. Students achieved an average score of 154.5 (SD ±â€Š11.72) out of 175 points (88.29 %) in OSAUS, which corresponded to the image rating using B-QUIET. Interrater analysis of US images showed a favorable agreement with an ICC (2.1) of 0.895 (95 % confidence interval 0.858 < ICC < 0.924). CONCLUSION: US training via teleguidance should be considered in medical education. Our pilot study demonstrates the feasibility of a concept that can be used in the future to improve US training of medical students even during a pandemic.

3.
Cancer Discov ; 11(8): 1982-1995, 2021 08.
Article in English | MEDLINE | ID: covidwho-1236486

ABSTRACT

Patients with cancer, in particular patients with hematologic malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4+ and CD8+ T-cell responses in unexposed and SARS-CoV-2-infected patients with cancer to characterize SARS-CoV-2 immunity and to identify immunologic parameters contributing to COVID-19 outcome. Unexposed patients with hematologic malignancies presented with reduced prevalence of preexisting SARS-CoV-2 cross-reactive CD4+ T-cell responses and signs of T-cell exhaustion compared with patients with solid tumors and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between patients with COVID-19 and cancer and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T-cell responses were profoundly reduced in patients with cancer, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T-cell immunity as a potential determinant for dismal outcome of COVID-19 in patients with cancer. SIGNIFICANCE: This first comprehensive analysis of SARS-CoV-2 immune responses in patients with cancer reports on the potential implications of impaired SARS-CoV-2 T-cell responses for understanding pathophysiology and predicting severity of COVID-19, which in turn might allow for the development of therapeutic measures and vaccines for this vulnerable patient population.See related commentary by Salomé and Horowitz, p. 1877.This article is highlighted in the In This Issue feature, p. 1861.


Subject(s)
COVID-19 , Neoplasms , CD4-Positive T-Lymphocytes , Humans , Immunity , Programmed Cell Death 1 Receptor , SARS-CoV-2
4.
Mol Cancer ; 20(1): 52, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1136226

ABSTRACT

In vitro-transcribed messenger RNA-based therapeutics represent a relatively novel and highly efficient class of drugs. Several recently published studies emphasize the potential efficacy of mRNA vaccines in treating different types of malignant and infectious diseases where conventional vaccine strategies and platforms fail to elicit protective immune responses. mRNA vaccines have lately raised high interest as potent vaccines against SARS-CoV2. Direct application of mRNA or its electroporation into dendritic cells was shown to induce polyclonal CD4+ and CD8+ mediated antigen-specific T cell responses as well as the production of protective antibodies with the ability to eliminate transformed or infected cells. More importantly, the vaccine composition may include two or more mRNAs coding for different proteins or long peptides. This enables the induction of polyclonal immune responses against a broad variety of epitopes within the encoded antigens that are presented on various MHC complexes, thus avoiding the restriction to a certain HLA molecule or possible immune escape due to antigen-loss. The development and design of mRNA therapies was recently boosted by several critical innovations including the development of technologies for the production and delivery of high quality and stable mRNA. Several technical obstacles such as stability, delivery and immunogenicity were addressed in the past and gradually solved in the recent years.This review will summarize the most recent technological developments and application of mRNA vaccines in clinical trials and discusses the results, challenges and future directions with a special focus on the induced innate and adaptive immune responses.


Subject(s)
Cancer Vaccines/genetics , Cancer Vaccines/immunology , Neoplasms/etiology , Neoplasms/therapy , RNA, Messenger/genetics , RNA, Messenger/immunology , Animals , Antigens, Neoplasm/genetics , Antigens, Neoplasm/immunology , Cancer Vaccines/administration & dosage , Drug Delivery Systems , Gene Expression Regulation, Neoplastic , Gene Transfer Techniques , Humans , Immunity , Immunotherapy , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Neoplasms/pathology , RNA Stability , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
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