Graft vs. associated with the presence of hypogammaglobulinemia. It appears that patients with CLL have the worst outcomes amongst patients with malignant hemopathies and SARS-CoV-2 infection. Bruton tyrosine kinase inhibitors reduce the hyperinflammatory status of patients with CLL with COVID-19, which is accompanied by decreased levels of serum inflammatory markers, ferritin and D-dimer, and serum levels of pro-inflammatory cytokines, but they increase the risk of infections and impaired humoral immunity. An abrupt discontinuation of these may promote the rapid FMK decompensation of CLL, which may even mimic the clinical manifestations of COVID-I9, including a significant increase in cytokine release. In conclusion, therapeutic decisions must be personalized to each patient with CLL and each at risk patient must be quarantined during the SARS-CoV-2 pandemic to reduce their risk of contraction. Keywords: chronic lymphocytic leukemia, coronavirus disease-2019, ibrutinib, monoclonal antibodies, severe acute respiratory syndrome coronavirus 2, venetoclax 1.?Introduction Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western countries (1), with an incidence of 4.2 new cases per 100,000 individuals per year (2). The median age at diagnosis of CLL is estimated to be ~72 years (2) and several patients will have other associated diseases (3,4). Patients often have inadequate humoral and cellular immune responses to various infections and vaccinations due to the induction of immunosuppression (5). In total, ~70% of patients with CLL develop infections, of which 30% require hospitalization or intravenous antimicrobial treatment (6,7), and this is reflected in the increased morbidity and mortality rates (6). ATF1 The pathophysiology of complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is complex and not fully understood. Patients with severe forms of coronavirus disease-2019 (COVID-19) have inadequate immune responses to the virus, or otherwise the clinical manifestations FMK are the result of an exaggerated adaptive immune response. Thus, the clinical impact of this infection on patients with CLL has not been fully elucidated (5). The current strategy for monitoring and treating patients with CLL includes a watch and wait policy that applies to several patients. Untreated patients with CLL are considered to have a lower risk of infection than those who have undergone therapeutic interventions, but a higher risk compared with age-matched controls (5). Indeed, patients with CLL have a high risk of developing a severe form of COVID-19 (3,4), particularly if they are undergoing chemotherapy, due FMK to the immunosuppressive effects of these regimens (4,8) and a result of hematological malignancy. Immunomodulatory agents also increase the risk of this viral infection and alter the response to treatment (9). Hematologists in Birmingham have published a report on the evolution of 4 treatment-na?ve patients with CLL who became infected with SARS-CoV-2. Lymphocytosis increased on average by 3-fold during infection with SARS-CoV-2, compared with the baseline levels (5). Unlike lymphopenia, which correlates with severe forms of COVID-19 and has an unfavorable evolution in the general population (5,8), the clinical form was severe, and the mortality rates were high. One of the mechanisms that may explain lymphocytosis in patients with CLL infected with SARS-CoV-2 may be related to the high levels of endogenous steroids during the intense inflammatory process (5). Patients with CLL must be quarantined during the pandemic due to the risk of infection and of exhibiting a severe response, the likelihood of which is higher than that of FMK the general population, even if they are not undergoing immunochemotherapy (5,10). An excessive immune response, similar to cytokine release syndrome, is present in severe forms of COVID-19. The patients have high serum levels of pro-inflammatory cytokines, which leads to increased morbidity and mortality (11). Indeed, patients with CLL had the worst outcome in a group.