Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity.

BACKGROUND: Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely. OBJECTIVE: Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs). METHODS: Patients with severe asthma or atopic dermatitis who were taking benralizumab, dupilumab, or mepolizumab and had received the initial dose of the 2-dose adult SARS-CoV-2 mRNA vaccine were enrolled in a prospective, observational study. As our control group, we used a cohort of immunologically healthy subjects (with no significant immunosuppression) who were not taking biologics (NBs). We used a multiplexed immunoassay to measure antibody levels, neutralization assays to assess antibody function, and flow cytometry to quantitate Spike-specific lymphocytes. RESULTS: We analyzed blood from 57 patients in the PoB group and 46 control subjects from the NB group. The patients in the PoB group had lower levels of SARS-CoV-2 antibodies, pseudovirus neutralization, live virus neutralization, and frequencies of Spike-specific B and CD8 T cells at 6 months after vaccination. In subgroup analyses, patients with asthma who were taking biologics had significantly lower pseudovirus neutralization than did subjects with asthma who were not taking biologics. CONCLUSION: The patients in the PoB group had reduced SARS-CoV-2-specific antibody titers, neutralizing activity, and virus-specific B- and CD8 T-cell counts. These results have implications when considering development of a more individualized immunization strategy in patients who receive biologic medications blocking IL-4 or IL-5 pathways.

Neuropathic pain and itch mechanisms underlying allergic conjunctivitis

OBJECTIVE: Among the constellation of symptoms that characterizes allergic conjunctivitis, many (eg, burning and stinging) can be attributed to chronic neuropathic pain. Cumulative data support that these hallmark symptoms might be linked to the effects of allergen-induced neuromodulation. This review investigates the key characteristics of neuropathic itch and pain in allergic conjunctivitis and their underlying pathogenic mechanisms. METHODS: A literature review was conducted using a PubMed search focusing on allergic conjunctivitis, neurogenic inflammation, neuropathic itch, and neuropathic pain. Articles were reviewed, and those discussing clinical course, pathophysiology, and neuronal regulation of chronic neuropathic symptoms as related to allergic disease were summarized. RESULTS: Recent evidence suggests that some symptoms of allergic conjunctivitis may be better represented as a chronic neuropathic disorder. We found that neurogenic mechanisms may have a significant role in chronic ocular surface inflammation from allergic inflammation. Manifestations may be associated with repeated ocular sensory nerve injury leading to an acute-to-chronic transition, which is in turn associated with neuropathologic changes (peripheral and central sensitization), neuronal dysfunction, and spontaneous ocular pain. CONCLUSION: Current goals in the management of allergic conjunctivitis aim to minimize the inflammatory cascade associated with the allergic response in the initial stages of the pathogenic mechanism. Based on the mechanistic data reviewed herein, the recognition that neuronal inflammation explains many of the symptoms in allergic conjunctivitis opens new frontiers for drug discovery

OBJETIVO: Entre la constelación de síntomas que caracteriza la conjuntivitis alérgica, muchos, como la sensación de ardor y escozor, pueden ser fundamentados en el dolor neuropático crónico. Cada vez disponemos de más datos para respaldar que estos síntomas característicos podrían estar relacionados con los efectos de la neuromodulación inducida por alérgenos. En esta revisión se enfatizarán las características clave del dolor y el prurito neuropático en la conjuntivitis alérgica y sus mecanismos patológicos. MÉTODOS: Se realizó una revisión de la literatura realizando una búsqueda bibliográfica en la base PubMed utilizando, como palabras clave, conjuntivitis alérgica, inflamación neurogénica, prurito neuropático, dolor neuropático. Se revisaron los artículos y se resumieron aquellos que se centraban en el curso clínico, la fisiopatología y la regulación neuronal de los síntomas neuropáticos crónicos en relación con la enfermedad alérgica. RESULTADOS: La literatura científica reciente sugiere que algunos síntomas de la conjuntivitis alérgica se representan mejor como un trastorno neuropático crónico. Los mecanismos neurogénicos parecen tener un papel significativo en la inflamación crónica de la superficie ocular inducida por las reacciones alérgicas. Las manifestaciones pueden estar asociadas con la lesión del nervio sensorial ocular repetida que conlleva una transición de aguda a crónica y se asocia con cambios neuropatológicos (sensibilización periférica y central), disfunción neuronal y dolor ocular espontáneo. CONCLUSIÓN: Los objetivos actuales de manejo de la conjuntivitis alérgica se centran en minimizar la cascada inflamatoria asociada con la respuesta alérgica en los estadíos iniciales fisiopatológicos. Sin embargo, y en relación con los datos mecanísticos revisados en este documento, el reconocimiento de que la inflamación neuronal explica muchos de los síntomas en la conjuntivitis alérgica abre nuevas fronteras para el descubrimiento de nuevas opciones terapéuticas