Clinical efficacy of different monoclonal antibody regimens among non-hospitalised patients with mild to moderate COVID-19 at high risk for disease progression: a prospective cohort study.

This study aimed to compare the clinical progression of COVID-19 in high-risk outpatients treated with the monoclonal antibodies (mAb) bamlanivimab, bamlanivimab-etesevimab and casirivimab-imdevimab. This is an observational, multi-centre, prospective study conducted from 18 March to 15 July 2021 in eight Italian tertiary-care hospitals including mild-to-moderate COVID-19 outpatients receiving bamlanivimab (700 mg), bamlanivimab-etesevimab (700-1400 mg) or casirivimab-imdevimab (1200-1200 mg). All patients were at high risk of COVID-19 progression according to Italian Medicines Agency definitions. In a patient subgroup, SARS-CoV-2 variant and anti-SARS-CoV-2 serology were analysed at baseline. Factors associated with 28-day all-cause hospitalisation were identified using multivariable multilevel logistic regression (MMLR) and summarised with adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 635 outpatients received mAb: 161 (25.4%) bamlanivimab, 396 (62.4%) bamlanivimab-etesevimab and 78 (12.2%) casirivimab-imdevimab. Ninety-five (15%) patients received full or partial SARS-CoV-2 vaccination. The B.1.1.7 (Alpha) variant was detected in 99% of patients. Baseline serology showed no significant differences among the three mAb regimen groups. Twenty-eight-day all-cause hospitalisation was 11.3%, with a significantly higher proportion (p 0.001) in the bamlanivimab group (18.6%), compared to the bamlanivimab-etesevimab (10.1%) and casirivimab-imdevimab (2.6%) groups. On MMLR, aORs for 28-day all-cause hospitalisation were significantly lower in patients receiving bamlanivimab-etesevimab (aOR 0.51, 95% CI 0.30-0.88 p 0.015) and casirivimab-imdevimab (aOR 0.14, 95% CI 0.03-0.61, p 0.009) compared to those receiving bamlanivimab. No patients with a history of vaccination were hospitalised. The study suggests differences in clinical outcomes among the first available mAb regimens for treating high-risk COVID-19 outpatients. Randomised trials are needed to compare efficacy of mAb combination regimens in high-risk populations and according to circulating variants.

Prompt Hematological Recovery in Response to a Combination of Pegylated Interferon α-2a and Rituximab in a Profoundly Immuno-Suppressed Hairy Cell Leukemia Patient with a Mycobacterial Infection at Onset: Benefits and Drawbacks of Rapid Immune Reconstitution.

The present paper reports, to the best of our knowledge for the first time, the efficacy and tolerability of the combination of interferon (IFN)α-2a in pegylated formulation and rituximab after a "priming" phase with IFN in the frontline treatment of hairy cell leukemia (HCL) in a profoundly immunosuppressed patient with a Mycobacterium abscessus infection at onset. This immunotherapy combination may represent a potential therapeutic option in patients with active severe infection and for whom the use of purine nucleoside analogues (PNA) is contraindicated. The benefits and drawbacks of remarkably rapid immune reconstitution in the context of opportunistic infections are highlighted as well, as the potentially paradoxical effects of immune recovery as a result of effective immunotherapy strategies, known as immune reconstitution inflammatory syndrome (IRIS), have to be taken into account when dealing with patients with opportunistic infections.

COVID-19 in B Cell-Depleted Patients After Rituximab: A Diagnostic and Therapeutic Challenge.

B cell-targeting strategies such as rituximab are widely used in B cell hematologic malignancies, rheumatologic and musculoskeletal diseases and a variety of autoimmune disorders. The purpose of this paper is to illustrate how exposure to anti-CD20 treatment profoundly affects B cell functions involved in anti-SARS-CoV-2 immunity and significantly impacts on the clinical and serological course of SARS-CoV-2 infection, long term immunity and vaccine responses. The data presented here suggest that the effects of B cell-depleting agents on adaptive immunity should be taken into account for the proper selection and interpretation of SARS-CoV-2 diagnostics and to guide appropriate therapeutic approaches and protective measures. Combination therapeutic strategies including immunotherapy in association with prolonged antiviral treatment may play a decisive role in the setting of B cell immune deficiencies.

Suppression of Covid-19 outbreak among healthcare workers at the Treviso Regional Hospital, Italy and lessons for ophthalmologists.

PURPOSE: To describe a strategy to reduce Covid-19 spread among healthcare workers and provide ophthalmologists with recommendations useful for a possible second wave of Covid-19 in Autumn. METHODS: Epidemiological surveillance at the Cà Foncello Hospital (Veneto, Italy) since 24 February 2020 to 24 April 2020 when the municipality of Treviso was hit by the Covid-19 outbreak. The number of naso-pharigeal (NP) swabs performed was 7010. RESULTS: The number of infected among healthcare workers was 209/ 3924 (5.32%): medical doctors: 28 cases / 498 (5.6%). None among ophthalmologists; specialized nurses: 86/1294 (6.4%) None in the ophthalmic unit; intermediate care technicians: 68/463 (14.7%). The 46% of the positive tested were asymptomatic. We share key suggested actions for the reorganization in ophthalmological services: be part of a global epidemiological local strategy of containment (Testing, Tracing, Treating); protect your department: Keep on screening patients by telephone interview before entering the hospital; promote continuous and appropriate use of PPE both for doctors and for patients; make any effort to obtain a continuous flow of patients in every line of the ophthalmic service; treat appropriately any single patient with vision threatening condition; avoid unnecessary or futile testings and examinations. CONCLUSION: The Treviso model shows that it is possible and safe to keep on performing high risk hospital activities like ophthalmology, even in the epicenter of covid outbreak, if adequate actions are performed. We discuss about the value of NP swabs and serological tests as a strategy in case of a second wave of infections.