Treatment of SARS-CoV-2 relapse with remdesivir and neutralizing antibodies cocktail in a patient with X-linked agammaglobulinaemia

Palomba, Emanuele; Carrabba, Maria; Zuglian, Gianluca; Alagna, Laura; Saltini, Paola; Fortina, Valeria; Hu, Cinzia; Bandera, Alessandra; Fabio, Giovanna; Gori, Andrea; Muscatello, Antonio

doi:10.1016/j.ijid.2021.07.064

Cited by 18 publications

(14 citation statements)

References 14 publications

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“…Of note, 4 patients with XLA showed longer durations of testing positive for SARS-CoV-2 (30 to 64 days), and 4 additional cases had reports of rehospitalization or of testing positive, then negative, then positive again. As most people with XLA have no or very few B cells and thus produce no or few antibodies, this finding supports the importance of antibodies in clearing SARS-CoV-2 [ 20 , 24 , 33 , 35 , 49 , 55 , 58 ]]. No case reports included information on whole viral genome sequencing for SARS-CoV-2 to allow for evaluation of the impact of PI on the emergence of variants of concern.…”

Section: Resultssupporting

confidence: 59%

“…A total of 459 people with PI and COVID-19 are described from 54 of the 68 studies [ 12 , 13 , 16 , [18] , [19] , [20] , [21] , 24 , 26 , 27 , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] ] (Table 2). These cases came from case reports as well as cohort studies with information available for individual patients.…”

Section: Resultsmentioning

confidence: 99%

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COVID-19-related health outcomes in people with primary immunodeficiency: A systematic review

Drzymalla

Green

Knuth

et al. 2022

Clinical Immunology

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Section: Resultssupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

COVID-19-related health outcomes in people with primary immunodeficiency: A systematic review

Drzymalla

Green

Knuth

et al. 2022

Clinical Immunology

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“…Up to now, data on effects of COVID-19 treatments in IEI patients have been described ( 14 – 16 ). Recently, our group demonstrated that, during the second year of the pandemic, mabs administration had a beneficial effect on the likelihood of hospitalization and development of severe disease confirming previous data observed in a lower number of patients ( 17 , 18 ). Poor data in IEI are available regarding antiviral therapy, except for some case reports describing remdesivir as effective for viral clearance in XLA patients and in severely immunocompromised patients ( 19 , 20 ).…”

Section: Introductionsupporting

confidence: 86%

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

et al. 2022

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BackgroundSince 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.MethodsLongitudinal, 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.ResultsThe 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.ConclusionsThe 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.

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“…It is unknown, whether a lack of specific humoral immunity to SARS-CoV-2 per se leads to an increased risk of RNAemia. Based on numerous mild COVID-19 cases in XLA patients (2,(15)(16)(17)(18)(19)(20), at least generally persisting and high viral loads seem unlikely.…”

Section: Discussionmentioning

confidence: 99%

“…With regard to humoral immunity, early clinical data from XLA patients suggested that lack of SARS-CoV-2 humoral immunity may be sufficiently compensated by innate and T cell immunity in order to prevent severe COVID-19 (2,(15)(16)(17)(18)(19)(20). On the other hand, patients with Good's syndrome, a thymoma-associated hypogammaglobulinemia with B and/or T cell deficiency and lack of specific humoral immune response, were reported to be at significantly increased risk for severe COVID-19 and a high case fatality rate (12).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

et al. 2022

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Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous. Despite extensive clinical reports, underlying immunological mechanisms are poorly characterized and levels of T cellular and innate immunity in severe cases remain to be determined. In the present study, we report clinical and immunological findings of 5 PAD patients with severe and fatal COVID-19 and undetectable specific humoral immune response to SARS-CoV-2. Reactive T cells to SARS-CoV-2 spike (S) and nucleocapsid (NCAP) peptide pools were analyzed comparatively by flow cytometry in PAD patients, convalescents and naïve healthy individuals. All examined PAD patients developed a robust T cell response. The presence of polyfunctional cytokine producing activated CD4+ T cells indicates a memory-like phenotype. An analysis of innate immune response revealed elevated CD169 (SIGLEC1) expression on monocytes, a surrogate marker for type I interferon response, and presence of type I interferon autoantibodies was excluded. SARS-CoV-2 RNA was detectable in peripheral blood in three severe COVID-19 patients with PAD. Viral clearance in blood was observed after treatment with COVID-19 convalescent plasma/monoclonal antibody administration. However, prolonged mucosal viral shedding was observed in all patients (median 67 days) with maximum duration of 127 days. PAD patients without specific humoral SARS-CoV-2 immunity may suffer from severe or fatal COVID-19 despite robust T cell and normal innate immune response. Intensified monitoring for long persistence of SARS-CoV-2 viral shedding and (prophylactic) convalescent plasma/specific IgG as beneficial treatment option in severe cases with RNAemia should be considered in seronegative PAD patients.

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Treatment of SARS-CoV-2 relapse with remdesivir and neutralizing antibodies cocktail in a patient with X-linked agammaglobulinaemia

Cited by 18 publications

References 14 publications

COVID-19-related health outcomes in people with primary immunodeficiency: A systematic review

COVID-19-related health outcomes in people with primary immunodeficiency: A systematic review

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

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

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