COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma.

The clinical and immunological impact of B-cell depletion in the context of coronavirus disease 2019 (COVID-19) is unclear. We conducted a prospectively planned analysis of COVID-19 in patients who received B-cell depleting anti-CD20 antibodies and chemotherapy for B-cell lymphomas. The control cohort consisted of age- and sex-matched patients without lymphoma who were hospitalized because of COVID-19. We performed detailed clinical analyses, in-depth cellular and molecular immune profiling, and comprehensive virological studies in 12 patients with available biospecimens. B-cell depleted lymphoma patients had more severe and protracted clinical course (median hospitalization 88 versus 17 d). All patients actively receiving immunochemotherapy (n = 5) required ICU support including long-term mechanical ventilation. Neutrophil recovery following granulocyte colony stimulating factor stimulation coincided with hyperinflammation and clinical deterioration in 4 of the 5 patients. Immune cell profiling and gene expression analysis of peripheral blood mononuclear cells revealed early activation of monocytes/macrophages, neutrophils, and the complement system in B-cell depleted lymphoma patients, with subsequent exacerbation of the inflammatory response and dysfunctional interferon signaling at the time of clinical deterioration of COVID-19. Longitudinal immune cell profiling and functional in vitro assays showed SARS-CoV-2-specific CD8+ and CD4+ T-effector cell responses. Finally, we observed long-term detection of SARS-CoV-2 in respiratory specimens (median 84 versus 12 d) and an inability to mount lasting SARS-CoV-2 antibody responses in B-cell depleted lymphoma patients. In summary, we identified clinically relevant particularities of COVID-19 in lymphoma patients receiving B-cell depleting immunochemotherapies.

Acute liver failure, rupture and hemorrhagic shock as primary manifestation of advanced metastatic disease.

BACKGROUND: Malignancies rarely cause of acute liver failure, the presence of which have to be ruled-out during transplant evaluation. Tumor-related liver ruptures sporadically occur and might further complicate patient management. CASE REPORT: We report the case of a previously healthy 56-year-old male with complaints of abdominal pain. Initially, levels of liver enzymes were elevated, however, comprehensive imaging examinations revealed no gross abnormalities. As acute liver failure developed, transplantation was evaluated. Sudden liver rupture and hemorrhage forced the performance of an emergency laparotomy. Hepatectomy was planned, until a donor organ was allocated. Intraoperatively, the liver unexpectedly revealed diffuse tumor infiltration. Without further therapeutical options, the patient died. Immunohistochemistry showed metastatic infiltration of a carcinoma of unknown primary. CONCLUSION: Even in previously healthy patients suffering from acute liver failure, exclusion of malignancies is mandatory before transplantation. As imaging might be misleading, a biopsy should be considered early in unresolved cases.