SARS-CoV-2 neutralizing antibodies decline over one year and patients with severe COVID-19 pneumonia display a unique cytokine profile.

OBJECTIVES: As coronavirus disease 2019 (COVID-19) rages on worldwide, there is an urgent need to characterize immune correlates of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify immune determinants of COVID-19 severity. METHODS: This study examined the longitudinal profiles of neutralizing antibody (NAb) titers in hospitalized COVID-19 patients clinically diagnosed with mild symptoms, pneumonia, or severe pneumonia, up to 12 months after illness onset, using live-virus neutralization. Multiplex, correlation, and network analyses were used to characterize serum-derived inflammatory cytokine profiles in all severity groups. RESULTS: Peak NAb titers correlated with disease severity, and NAb titers declined over the course of 12 months regardless of severity. Multiplex analyses revealed that IP-10, IL-6, IL-7, and VEGF-α were significantly elevated in severe pneumonia cases compared to those with mild symptoms and pneumonia cases. Correlation and network analyses further suggested that cytokine network formation was distinct in different COVID-19 severity groups. CONCLUSIONS: The study findings inform on the long-term kinetics of naturally acquired serological immunity against SARS-CoV-2 and highlight the importance of identifying key cytokine networks for potential therapeutic immunomodulation.

Novel salivary gland allergens from tropical mosquito species and IgE reactivity in allergic patients.

BACKGROUND: Mosquito allergy is common in tropical countries but remains under-diagnosed. This may be due to the lack of knowledge and diagnostic tools for tropical mosquito allergens. OBJECTIVE: We aimed to characterize allergens from tropical mosquito species and investigate IgE reactivity in mosquito-allergic patients to the salivary gland proteins from these mosquitoes. METHODS: Salivary gland extract (SGE) from 4 mosquito species, highly distributed in the tropics, including Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Anopheles dirus b, were studied. SGE-specific IgE and IgG ELISA were developed, and serum from 64 mosquito-allergic and 22 non-allergic healthy control subjects was assayed. Further investigations using IgE-immunoblots followed by mass spectrometry analysis were performed to identify and characterize allergens from each species. RESULTS: Mosquito-allergic subjects have detectable serum IgE to SGE derived from local mosquito species, while the IgE levels to Aedes communis using commercially available ELISA were mostly minimal. IgE-immunoblot analysis and mass spectrometry identified 5 novel mosquito allergens from A. albopictus (Aed al 2, Aed al 3), C. quinquefasciatus (Cul q 2.01, Cul q 3), and A. dirus b (Ano d 2). Interestingly, 4 of the 5 new allergens belong to the D7 protein family. CONCLUSIONS & CLINICAL RELEVANCE: Five novel allergens from 3 tropical mosquito species were characterized. The majority of mosquito-allergic subjects who live in the tropics have IgE reactivity to these allergens. Our study paves the way for the development of diagnostic tests, component-resolved diagnostics, and future immunotherapy for mosquito allergy in tropical countries.