Real-life data on monoclonal antibodies and antiviral drugs in Italian inborn errors of immunity patients during COVID-19 pandemic

Abstract

Background: Since the beginning of the COVID-19 pandemic, patients with Inborn Errors of Immunity have been infected by SARS-CoV-2 virus showing a spectrum of disease ranging from asymptomatic to severe COVID-19. A fair number of patients did not respond adequately to SARS-CoV-2 vaccinations, thus early therapeutic or prophylactic measures were needed to prevent severe or fatal course or COVID-19 and to reduce the burden of hospitalizations.

Methods: Longitudinal, multicentric study on patients with Inborn Errors of Immunity immunized with mRNA vaccines treated with monoclonal antibodies and/or antiviral agents at the first infection and at reinfection by SARS-CoV-2. Analyses of efficacy were performed according to the different circulating SARS-CoV-2 strains.

Results: The analysis of the cohort of 192 SARS-CoV-2 infected patients, across 26 months, showed the efficacy of antivirals on the risk of hospitalization, while mabs offered a positive effect on hospitalization, and COVID-19 severity. This protection was consistent across the alpha, delta and early omicron waves, although the emergence of BA.2 reduced the effect of available mabs. Hospitalized patients treated with mabs and antivirals had a lower risk of ICU admission. We reported 16 re-infections with a length of SARS-CoV-2 positivity at second infection shorter among patients treated with mabs. Treatment with antivirals and mabs was safe.

Conclusions: The widespread use of specific therapy, vaccination and better access to care might have contributed to mitigate risk of mortality, hospital admission, and severe disease. However, the rapid spread of new viral strains underlines that mabs and antiviral beneficial effects should be re- evaluated over time.

Keywords: COVID-19; antiviral drugs; disease severity; duration of viral shedding; hospitalization-risk; inborn errors of immunity; monoclonal antibodies; reinfection.

Figure 1

Graphical design of the study. Patients infected in the entire period and during each wave are grouped on the basis of the treatment received, taking into account age and sex representation for each group.

Figure 2

Analysis of viral shedding (SARS-CoV-2 rt-PCR in naso-pharyngeal swab) duration in days in different subsets of IEI patients. (A) viral shedding duration at first infection among IEI patients not vaccinated or immunized with 1 or 2 mRNA vaccine doses and IEI patients who had received 3 or 4 vaccine doses, during the entire examined period (median: 14 days, IQR 9.7-24.3 days vs 21 days, IQR 14-31 days; p=0.0009). (B) comparison of the viral shedding duration in IEI hospitalized (median: 34 days; IQR 22-51 days) and non-hospitalized patients (median: 16 days; IQR 10-23.75 days, p < 0.001), during the entire examined period. (C) comparison of the viral shedding duration among IEI patients treated at home with mabs or antivirals at the first infection, during the Omicron wave (median 11 days, range 7-15.7 vs 19.5 range 7-26 days, p=0.0054) (D) comparison of viral shedding in patients vaccinated with at least 3 doses receiving treatment with antivirals or mabs (11.0 days, IQR 7.0-14.8 vs 18.5 days, IQR 10.0-25.1; p=0.010).