[Assessment of Direct (COVID-19-Related) and Collateral, Psychosocial Pandemic Consequences for Vulnerable Groups by the Example of Serious Mental Illness]. / Erfassung direkter (COVID-19-bezogener) und kollateraler, psychosozialer Folgen für vulnerable Gruppen am Beispiel schwerer psychischer Erkrankungen.

The indirect pandemic consequences could by far exceed the direct effects of SARS-CoV-2 in terms of costs, morbidity, and mortality. This essay includes a proposed method (matrix) to visualize virus-related and psychosocial risks for different populations side by side in a systematic and concise manner. COVID-19-related and psychosocial vulnerability, stressors, direct and indirect consequences are derived on a theoretical and empirical basis. An exemplary quantification of the matrix for the vulnerable group of people with severe mental illness revealed a very high risk for severe COVID-19 consequences, as well as a pronounced risk for psychosocial collateral effects. The proposed approach could be further discussed for a risk-graded pandemic management, crisis recovery, and future preparedness to adequately address psychosocial collateral effects and better identify and protect vulnerable groups in this regard.

[Differences due to socio-economic status, genetic background and sex in cancer and precision medicine - An intersectional approach to close the care gap for marginalized groups]. / Unterschiede durch sozioökomische Benachteiligung, genetischen Hintergrund und Geschlecht bei Tumorerkrankungen.

Malignant tumor diseases constitute the 2nd most common cause of death and due to our extended life expectancy cancer per se has substantially increased, being highly prevalent after cardiovascular diseases. Evidence also generated from the COVID-19 pandemic, that defined gender differences exist in symptom and disease courses, and have advocated the need to assess gender, ethnic/racial and minority differences in cancer care and treatment more meticulously. It is becoming increasingly evident that in novel cancer care/precision oncology, representation of minorities, elderly and frail patients in clinical trials remains largely unbalanced, thus distribution of cancer success is iniquitous. This article focusses on these aspects and suggests solutions, how this can be improved.

AGIHO guideline on evidence-based management of COVID-19 in cancer patients: 2022 update on vaccination, pharmacological prophylaxis and therapy in light of the omicron variants.

The novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 pose a significant challenge to healthcare systems worldwide. Patients with cancer have been identified as a high-risk population for severe infections, rendering prophylaxis and treatment strategies for these patients particularly important. Rapidly evolving clinical research, resulting in the recent advent of various vaccines and therapeutic agents against COVID-19, offers new options to improve care and protection of cancer patients. However, ongoing epidemiological changes and rise of new virus variants require repeated revisions and adaptations of prophylaxis and treatment strategies to meet these new challenges. Therefore, this guideline provides an update on evidence-based recommendations with regard to vaccination, pharmacological prophylaxis and treatment of COVID-19 in cancer patients in light of the currently dominant omicron variants. It was developed by an expert panel of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) based on a critical review of the most recent available data.

The TLR-NF-kB axis contributes to the monocytic inflammatory response against a virulent strain of Lichtheimia corymbifera, a causative agent of invasive mucormycosis.

Invasive mucormycosis (IM) is a life-threatening infection caused by the fungal order Mucorales, its diagnosis is often delayed, and mortality rates range from 40-80% due to its rapid progression. Individuals suffering from hematological malignancies, diabetes mellitus, organ transplantations, and most recently COVID-19 are particularly susceptible to infection by Mucorales. Given the increase in the occurrence of these diseases, mucormycosis has emerged as one of the most common fungal infections in the last years. However, little is known about the host immune response to Mucorales. Therefore, we characterized the interaction among L. corymbifera-one of the most common causative agents of IM-and human monocytes, which are specialized phagocytes that play an instrumental role in the modulation of the inflammatory response against several pathogenic fungi. This study covered four relevant aspects of the host-pathogen interaction: i) The recognition of L. corymbifera by human monocytes. ii) The intracellular fate of L. corymbifera. iii) The inflammatory response by human monocytes against the most common causative agents of mucormycosis. iv) The main activated Pattern-Recognition Receptors (PRRs) inflammatory signaling cascades in response to L. corymbifera. Here, we demonstrate that L. corymbifera exhibits resistance to intracellular killing over 24 hours, does not germinate, and inflicts minimal damage to the host cell. Nonetheless, viable fungal spores of L. corymbifera induced early production of the pro-inflammatory cytokine IL-1ß, and late release of TNF-α and IL-6 by human monocytes. Moreover, we revealed that IL-1ß production predominantly depends on Toll-like receptors (TLRs) priming, especially via TLR4, while TNF-α is secreted via C-type lectin receptors (CTLs), and IL-6 is produced by synergistic activation of TLRs and CTLs. All these signaling pathways lead to the activation of NF-kB, a transcription factor that not only regulates the inflammatory response but also the apoptotic fate of monocytes during infection with L. corymbifera. Collectively, our findings provide new insights into the host-pathogen interactions, which may serve for future therapies to enhance the host inflammatory response to L. corymbifera.

Sozioökonomische Benachteiligung als Risikofaktor für Krebserkrankungen – „closing the care gap“ Socioeconomic deprivation as a risk factor for cancer—closing the care gap

Armut ist ein Risikofaktor für Krebs. Menschen aus sozioökonomisch benachteiligten Gesellschaftsschichten erkranken häufiger und früher an Krebs, haben nach Diagnosestellung oftmals eine kürzere Lebenserwartung und profitieren hinsichtlich des Gesamtüberlebens weniger von der Therapie. Diese Beobachtung hat sich im Zuge der COVID-19-Pandemie weiter verschärft. Im vorliegenden Beitrag stellen wir zusammengefasst Ergebnisse für Deutschland dar, die diesen Zusammenhang illustrieren. Methodisch greifen wir dazu auf Erkenntnisse zurück, die sich auf individuelle Marker wie das individuelle Einkommen oder auf regionale Indizes sozialer Deprivation wie den German Index of Multiple Deprivation (GIMD) konzentrieren. Das Konzept der Klassenmedizin hinterfragt strukturelle Bedingungen, die dazu führen, dass das Versorgungssystem und die Behandler*innen selbst bestehende Unterschiede weiter fördern, anstatt diese auszugleichen. Faktoren der Ungleichheit in der Versorgung von Menschen gerade mit onkologischen Erkrankungen, seien sie sozioökonomischer, geschlechtsspezifischer oder ethnischer Art, müssen besser erfasst werden, um eine gerechte und gleichwertige Behandlung aller Menschen zu gewährleisten. Zusatzmaterial online Die Online-Version dieses Beitrags (10.1007/s12312-022-01113-4) enthält weitere Informationen aus der Literatur für interessierte Leser*innen.

COVID-19 and Cancer: Special Considerations for Patients Receiving Immunotherapy and Immunosuppressive Cancer Therapies.

Patients with cancer generally have a higher risk of adverse outcomes from COVID-19, with higher age, male sex, poor performance status, cancer type, and uncontrolled malignant disease as the main risk factors. However, the influence of specific cancer therapies varies and raises concerns during the pandemic. In patients undergoing cancer immunotherapy or other immunosuppressive cancer treatments, we summarize the evidence on outcomes from COVID-19; address the safety, immunogenicity, and efficacy of COVID-19 vaccination; and review COVID-19 antiviral therapeutics for the patient with cancer. Despite higher mortality for patients with cancer, treatment with immune checkpoint inhibitors does not seem to increase mortality risk based on observational evidence. Inhibitory therapies directed toward B-cell lineages, including monoclonal antibodies against CD20 and CAR T-cell therapies, are associated with poor outcomes in COVID-19; however, the data are sparse. Regarding vaccination in patients receiving immune checkpoint inhibitors, clinical efficacy comparable to that in the general population can be expected. In patients undergoing B-cell-depleting therapy, immunogenicity and clinical efficacy are curtailed, but vaccination is not futile, which is thought to be due to the cellular response. Vaccine reactogenicity and toxicity in all groups of patients with cancer are comparable to that of the general population. Preexposure prophylaxis with monoclonal antibodies directed against the viral spike may provide passive immunity for those not likely to mount an adequate vaccine response. If infected, prompt treatment with monoclonal antibodies or oral small molecule antivirals is beneficial, though with oral antiviral therapies, care must be taken to avoid drug interactions in patients with cancer.

Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9).

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel virus that spread worldwide from 2019 causing the Coronavirus disease 19 (COVID-19) pandemic. SARS-CoV-2 infection is characterised by an initial viral phase followed in some patients by a severe inflammatory phase. Importantly, immunocompromised patients may have a prolonged viral phase, shedding infectious viral particles for months, and absent or dysfunctional inflammatory phase. Among haematological patients, COVID-19 has been associated with high mortality rate in acute leukaemia, high risk-myelodysplastic syndromes, and after haematopoietic cell transplant and chimeric-antigen-receptor-T therapies. The clinical symptoms and signs were similar to that reported for the overall population, but the severity and outcome were worse. The deferral of immunodepleting cellular therapy treatments is recommended for SARS-CoV-2 positive patient, while in the other at-risk cases, the haematological treatment decisions must be weighed between individual risks and benefits. The gold standard for the diagnosis is the detection of viral RNA by nucleic acid testing on nasopharyngeal-swabbed sample, which provides high sensitivity and specificity; while rapid antigen tests have a lower sensitivity, especially in asymptomatic patients. The prevention of SARS-CoV-2 infection is based on strict infection control measures recommended for aerosol-droplet-and-contact transmission. Vaccinations against SARS-CoV-2 has shown high efficacy in reducing community transmission, hospitalisation and deaths due to severe COVID-19 disease in the general population, but immunosuppressed/haematology patients may have lower sero-responsiveness to vaccinations. Moreover, the recent emergence of new variants may require vaccine modifications and strategies to improve efficacy in these vulnerable patients. Beyond supportive care, the specific treatment is directed at viral replication control (antivirals, anti-spike monoclonal antibodies) and, in patients who need it, to the control of inflammation (dexamethasone, anti-Il-6 agents, and others). However, the benefit of all these various prophylactic and therapeutic treatments in haematology patients deserves further studies.

COVID-19 vaccines in patients with cancer: immunogenicity, efficacy and safety.

Patients with cancer have a higher risk of severe coronavirus disease (COVID-19) and associated mortality than the general population. Owing to this increased risk, patients with cancer have been prioritized for COVID-19 vaccination globally, for both primary and booster vaccinations. However, given that these patients were not included in the pivotal clinical trials, considerable uncertainty remains regarding vaccine efficacy, and the extent of humoral and cellular immune responses in these patients, as well as the risks of vaccine-related adverse events. In this Review, we summarize the current knowledge generated in studies conducted since COVID-19 vaccines first became available. We also highlight critical points that might affect vaccine efficacy in patients with cancer in the future.

Cellular Immune Response after Vaccination in Patients with Cancer-Review on Past and Present Experiences.

Patients with cancer are at particular risk for infection but also have diminished vaccine responses, usually quantified by the level of specific antibodies. Nonetheless, vaccines are specifically recommended in this vulnerable patient group. Here, we discuss the cellular part of the vaccine response in patients with cancer. We summarize the experience with vaccines prior to and during the SARS-CoV-2 pandemic in different subgroups, and we discuss why, especially in patients with cancer, T cells may be the more reliable correlate of protection. Finally, we provide a brief outlook on options to improve the cellular response to vaccines.

[Vaccination against SARS-CoV-2 in cancer patients]. / Impfung gegen SARS-CoV-2 bei Krebspatienten.

Patients with cancer are at an increased risk to suffer severe coronavirus disease 2019 (COVID-19). Therefore, specific preventative measures including COVID-19 vaccines are especially important. Both anticancer therapies and the underlying malignancy itself can lead to significant immunosuppression posing a particular challenge for vaccination strategies in these patients. At the moment, four COVID-19 vaccines are European Medicines Agency (EMA) approved in Germany: two mRNA and two viral vector-based vaccines. All four vaccines show excellent protection against severe COVID-19. Their mechanism of action relies on the induction of the production of virus-specific proteins by human cells and the following activation of a specific adaptive immune response. Vaccination against COVID-19 has been prioritized for cancer patients and medical personnel in Germany. Regarding timing of vaccination, vaccination prior to initiation of anticancer therapy seems ideal in newly diagnosed disease. However, due to the significant risk of severe COVID-19 in cancer patients, vaccination is also strongly recommended for patients already undergoing anticancer therapy. In these patients, immune response might be reduced. In two particular patient cohorts, namely stem cell transplant recipients and patients treated with B­cell depleting agents, an interval of several months following therapy is recommended because otherwise the response to vaccination will most likely be severely reduced. Preliminary data suggest only low rates of seroconversion following a single shot of vaccine in cancer patients. Therefore, on the long run, repeat vaccination regimens might be preferable in cancer patients.

2021 update of the AGIHO guideline on evidence-based management of COVID-19 in patients with cancer regarding diagnostics, viral shedding, vaccination and therapy.

The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated infectious coronavirus disease (COVID-19) has posed a unique challenge to medical staff, patients and their families. Patients with cancer, particularly those with haematologic malignancies, have been identified to be at high risk to develop severe COVID-19. Since publication of our previous guideline on evidence-based management of COVID-19 in patients with cancer, research efforts have continued and new relevant data has come to light, maybe most importantly in the field of vaccination studies. Therefore, an update of our guideline on several clinically important topics is warranted. Here, we provide a concise update of evidence-based recommendations for rapid diagnostics, viral shedding, vaccination and therapy of COVID-19 in patients with cancer. This guideline update was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology by critically reviewing the currently available data on these topics applying evidence-based medicine criteria.

Evidence-based management of COVID-19 in cancer patients: Guideline by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO).

Since its first detection in China in late 2019 the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated infectious disease COVID-19 continue to have a major impact on global healthcare and clinical practice. Cancer patients, in particular those with haematological malignancies, seem to be at an increased risk for a severe course of infection. Deliberations to avoid or defer potentially immunosuppressive therapies in these patients need to be balanced against the overarching goal of providing optimal antineoplastic treatment. This poses a unique challenge to treating physicians. This guideline provides evidence-based recommendations regarding prevention, diagnostics and treatment of SARS-CoV-2 infection and COVID-19 as well as strategies towards safe antineoplastic care during the COVID-19 pandemic. It was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO) by critically reviewing the currently available data on SARS-CoV-2 and COVID-19 in cancer patients applying evidence-based medicine criteria.

Frequently asked questions regarding SARS-CoV-2 in cancer patients-recommendations for clinicians caring for patients with malignant diseases.

Since early 2020, the SARS-CoV-2 pandemic has a massive impact on health care systems worldwide. Patients with malignant diseases are assumed to be at increased risk for a worse outcome of SARS-CoV-2 infection, and therefore, guidance regarding prevention and management of the infection as well as safe administration of cancer-therapy is required. Here, we provide recommendations for the management of patients with malignant disease in the times of COVID-19. These recommendations were prepared by an international panel of experts and then consented by the EHA Scientific Working Group on Infection in Hematology. The primary aim is to enable clinicians to provide optimal cancer care as safely as possible, since the most important protection for patients with malignant disease is the best-possible control of the underlying disease.