Neutralizing monoclonal antibodies in haematological patients paucisymptomatic for COVID-19: The GIMEMA EMATO-0321 study.

COVID-19 continues to be a relevant issue among patients with haematological malignancies (HM). Vaccines are frequently not effective in subjects on active treatment. In this multicentre retrospective study of Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA), we collected data from 91 paucisymptomatic HM patients treated with anti-spike neutralizing monoclonal antibodies (nMoAbs) to determine time to viral clearance, referencing it to the expected value of 28 days from an historical group of untreated paucisymptomatic patients. Secondary endpoints included rate of hospitalization, intensive care unit (ICU) admission, COVID-19 related death and safety. SARS-CoV-2 molecular swab negativity was obtained in 86 patients (95%), with a median time of 18 days (IQR 13-26; p < 0.0001). We did not find significant variations according to age, diagnosis, treatment type, vaccination status or nMoAbs type. Rate of hospitalization due to COVID-19 progression was 12% (11/91), with 2 patients (2.2%) requiring ICU admission. With a median follow-up of 2.33 months, the overall mortality was 5.5% (5/91), with 3 deaths due to COVID-19. Side effects were rare and self-limiting. Our data suggest that nMoAbs can limit the detrimental effect of immunosuppressive treatments on COVID-19 clinical progression and time to viral clearance. The original trial was registered at www.clinicaltrials.gov as #NCT04932967.

Immune Response Failure in Paucisymptomatic Long-Standing SARS-CoV-2 Spreaders.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. This disease has a spectrum of different clinical pictures with different outcomes. Herein, we report all the data from three paucisymptomatic patients during a hospital stay that might represent a paradigmatic example of the method by which SARS-CoV-2 is shed. We demonstrated the lack of an adequate qualitative and quantitative immune response by multiparametric flow cytometry analysis. Our data can provide a new perspective about the method by which SARS-CoV-2 is shed and the clinical weight of viral persistence. In all three cases, the long persistence of the virus and the consistent reduction in both innate and adaptative immune cells are not associated with greater disease severity. These patients might represent at least part of the population. In particular, one patient oscillated between positive and negative swab tests several times without presenting any immune response. In all three cases, the immune response failure was not associated with a clinically significant involvement, indicating that it is not the virus's ability to impair the immune system, as well as its presence and persistence the fundamental mechanism that might causally lead to death. Finally, this kind of immune response in paucisymptomatic patients could pose a considerable danger to public health that questions the quarantine period. It is urgent to quantify the phenomenon with a large sample study.