With more than 5 million proven infections and more than 300,000 associated deaths worldwide [1], the SARS-CoV-2 pandemic poses unprecedented challenges to health-care professionals and especially those treating and caring for patients with malignant hematological diseases. These patients often have multiple different risk factors for severe infections [2]. Chronic lymphocytic leukemia (CLL) is the most common form of leukemia and infections are a known contributor to morbidity and mortality due to a disease-inherent immunodeficiency [3, 4]. Considering this multifactorial immune defect, it appears conceivable that patients with CLL are more susceptible to infections with SARS-CoV-2 and more likely to develop severe courses of the associated respiratory disease COVID-19, especially when under additional immunosuppression by chemoimmunotherapy (CIT). Few case reports on COVID-19 in CLL patients from countries with suspected different prevalence rates of COVID-19 have been published so far. The publications report a patient after first-line treatment with single-agent chlorambucil, a case series with four treatment-naive CLL patients, a case series of eight patients on Bruton tyrosine kinase (BTK) inhibitors and most recently a heterogeneously treated population of four patients from the Hospital Clinic of Barcelona [5,6,7,8]. While it has been hypothesized that the BTK inhibitor ibrutinib might have protective effects against COVID-19 by attenuating hyperinflammatory responses, there is currently no data on COVID-19 in patients receiving venetoclax-based treatments [7, 9]. A recent study has suggested a reduction of CLL-inherent immunosuppression after successful treatment with venetoclax-based regimens [10]. In light of these data we sought to determine the incidence, severity, and possible risk factors of COVID-19 cases in a well-defined cohort of patients with CLL receiving venetoclax-based combination treatments as first-line therapy in a prospective clinical trial.