RESUMO
BACKGROUND: Patients with antibody deficiency respond poorly to coronavirus disease 2019 (COVID-19) vaccination and are at risk of severe or prolonged infection. They are given long-term immunoglobulin replacement therapy (IRT) prepared from healthy donor plasma to confer passive immunity against infection. Following widespread COVID-19 vaccination alongside natural exposure, we hypothesized that immunoglobulin preparations will now contain neutralizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibodies, which confer protection against COVID-19 disease and may help to treat chronic infection. METHODS: We evaluated anti-SARS-CoV-2 spike antibody in a cohort of patients before and after immunoglobulin infusion. Neutralizing capacity of patient samples and immunoglobulin products was assessed using in vitro pseudovirus and live-virus neutralization assays, the latter investigating multiple batches against current circulating Omicron variants. We describe the clinical course of 9 patients started on IRT during treatment of COVID-19. RESULTS: In 35 individuals with antibody deficiency established on IRT, median anti-spike antibody titer increased from 2123 to 10 600 U/mL postinfusion, with corresponding increase in pseudovirus neutralization titers to levels comparable to healthy donors. Testing immunoglobulin products directly in the live-virus assay confirmed neutralization, including of BQ1.1 and XBB variants, but with variation between immunoglobulin products and batches.Initiation of IRT alongside remdesivir in patients with antibody deficiency and prolonged COVID-19 infection (median 189 days, maximum >900 days with an ancestral viral strain) resulted in clearance of SARS-CoV-2 at a median of 20 days. CONCLUSIONS: Immunoglobulin preparations now contain neutralizing anti-SARS-CoV-2 antibodies that are transmitted to patients and help to treat COVID-19 in individuals with failure of humoral immunity.
Assuntos
Anticorpos Neutralizantes , COVID-19 , Humanos , Glicoproteína da Espícula de Coronavírus , Vacinas contra COVID-19 , SARS-CoV-2 , Anticorpos AntiviraisAssuntos
Angioedema , Angioedemas Hereditários , Humanos , Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/epidemiologia , Angioedemas Hereditários/prevenção & controle , Pirazóis/uso terapêutico , Angioedema/tratamento farmacológico , Reino Unido/epidemiologia , Proteína Inibidora do Complemento C1/uso terapêuticoRESUMO
We describe a rare case of a 54-year-old female with hairy cell leukemia, who following treatment for neutropenic sepsis, developed an extensive severe maculopapular exanthema with perifollicular hemorrhage. Cladribine, cotrimoxazole, allopurinol, domperidone, amikacin, piperacillin/tazobactam, and meropenem had all been given in the 9 days prior to eruption onset. Three months later, drug patch testing/delayed intradermal testing was positive to cotrimoxazole, trimethoprim, amikacin, piperacillin/tazobactam, and meropenem, with additional evidence of penicillin cross-reactivity. Drug challenge tests were negative to allopurinol and domperidone. She was diagnosed with multiple drug hypersensitivity to cotrimoxazole, amikacin, piperacillin/tazobactam, and meropenem. Multiple drug hypersensitivity is a novel syndrome mainly seen with severe delayed type IV drug eruptions, involving long-lasting strong T-cell reactivity to two or more structurally unrelated drugs.