No abstract

Highlights d high SARS-CoV-2 IgG but overall reduced T cell immunity in active COVID-19 patients d PD-1, Tim-3, and active caspases in T cells result in impaired T cell function d stable SARS-CoV-2 T cell repertoire yet declining humoral responses during recovery d potentially protective role of pre-existing anti-huCoV CD4 + and CD8 + T cell immunity

Background: It has been reported that both sublingual (SLIT) and subcutaneous (SCIT) allergen-specific immunotherapy have clinical efficacy, yet there are rather few comparative placebo studies of children. We aimed to investigate the clinical and immunological efficacy of mite-specific SLIT and SCIT versus a placebo in rhinitis and asthma in children. Methods: The outcomes of this 1-year, randomized, placebo-controlled, double-blind, double-dummy study were symptom and medication scores, visual analog scores (VAS), titrated skin prick tests, nasal and bronchial allergen provocation doses, serum house dust mite-specific immunglobulin E (HDM-sIgE), sIgG4, IL-10 and IFN-γ levels. Results: Clinical and laboratory parameters were evaluated in 30 patients. SCIT significantly diminished symptom and medication scores for rhinitis and asthma (p = 0.03 and p = 0.05 for rhinitis; p = 0.01 and p = 0.05 for asthma) and VAS. SLIT also reduced VAS, symptoms associated with rhinitis and asthma as well as medication usage for rhinitis, but this reduction was not significant when compared with the placebo. Skin reactivitiy to HDM and HDM-sIgE levels was reduced significantly in both immunotherapy groups. Serum IL-10 levels and nasal provocative doses increased significantly with both SCIT and SLIT. Nasal eosinophil increments after nasal challenge decreased with two treatment modes, but bronchial provocative doses and sputum eosinophil increments after bronchial challenge were reduced only with SCIT. In both treatment arms, there was no change in IFN-γ levels. Serum sIgG4 levels increased significantly only in the SCIT group. Conclusion: Based on the limited number of patients at the end of the 1-year immunotherapy, the clinical efficacy of SCIT on rhinitis and asthma symptoms was more evident when compared with the placebo.

Neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells via surface-expressed angiotensin-converting enzyme 2 (ACE2). We used a surrogate virus neutralization test (sVNT) and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus (VSV) vector-based neutralization assay (pVNT) to assess the degree to which serum antibodies from coronavirus disease 2019 (COVID-19) convalescent patients interfere with the binding of SARS-CoV-2 S to ACE2. Both tests revealed neutralizing anti-SARS-CoV-2 S antibodies in the sera of ~90% of mildly and 100% of severely affected COVID-19 convalescent patients. Importantly, sVNT and pVNT results correlated strongly with each other and to the levels of anti-SARS-CoV-2 S1 IgG and IgA antibodies. Moreover, levels of neutralizing antibodies correlated with the duration and severity of clinical symptoms but not with patient age. Compared to pVNT, sVNT is less sophisticated and does not require any biosafety labs. Since this assay is also much faster and cheaper, sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.

The family of IL-10-related cytokines includes several human members, , and a series of herpesviral and poxviral paralogs. Some of these cytokines share common receptor subunits. In this study, we investigated the effects of these cytokines on naive T cell differentiation, antigen-specific T cell suppression, survival and expression of surface markers in comparison to IL-10 and cytomegalovirus (CMV)-IL-10. Human CD45RA + T cells were stimulated in the presence of IL-10-family cytokines in sequential 12-day cycles.