Impact of Omicron Variant Infection on Assessment of Spike-Specific Immune Responses Using the EUROIMMUN Quan-T-Cell SARS-CoV-2 Assay and Roche Elecsys Anti-SARS-CoV-2-S.

The currently prevailing variants of SARS-CoV-2 are subvariants of the Omicron variant. The aim of this study was to analyze the effect of mutations in the Spike protein of Omicron on the results Quan-T-Cell SARS-CoV-2 assays and Roche Elecsys anti-SARS-CoV-2 anti-S1. Omicron infected subjects ((n = 37), vaccinated (n = 20) and unvaccinated (n = 17)) were recruited approximately 3 weeks after a positive PCR test. The Quan-T-Cell SARS-CoV-2 assays (EUROIMMUN) using Wuhan and the Omicron adapted antigen assay and a serological test (Roche Elecsys anti-SARS-CoV-2 anti-S1) were performed. Using the original Wuhan SARS-CoV-2 IGRA TUBE, in 19 of 21 tested Omicron infected subjects, a positive IFNy response was detected, while 2 non-vaccinated but infected subjects did not respond. The Omicron adapted antigen tube resulted in comparable results. In contrast, the serological assay detected a factor 100-fold lower median Spike-specific RBD antibody concentration in non-vaccinated Omicron infected patients (n = 12) compared to patients from the pre Omicron era (n = 12) at matched time points, and eight individuals remained below the detection threshold for positivity. For vaccinated subjects, the Roche assay detected antibodies in all subjects and showed a 400 times higher median specific antibody concentration compared to non-vaccinated infected subjects in the pre-Omicron era. Our results suggest that Omicron antigen adapted IGRA stimulator tubes did not improve detection of SARS-CoV-2-specific T-cell responses in the Quant-T-Cell-SARS-CoV-2 assay. In non-vaccinated Omicron infected individuals, the Wuhan based Elecsys anti-SARS-CoV-2 anti-S1 serological assay results in many negative results at 3 weeks after diagnosis.

Application of mRNA Technology in Cancer Therapeutics.

mRNA-based therapeutics pose as promising treatment strategies for cancer immunotherapy. Improvements in materials and technology of delivery systems have helped to overcome major obstacles in generating a sufficient immune response required to fight a specific type of cancer. Several in vivo models and early clinical studies have suggested that various mRNA treatment platforms can induce cancer-specific cytolytic activity, leading to numerous clinical trials to determine the optimal method of combinations and sequencing with already established agents in cancer treatment. Nevertheless, further research is required to optimize RNA stabilization, delivery platforms, and improve clinical efficacy by interacting with the tumor microenvironment to induce a long-term antitumor response. This review provides a comprehensive summary of the available evidence on the recent advances and efforts to overcome existing challenges of mRNA-based treatment strategies, and how these efforts play key roles in offering perceptive insights into future considerations for clinical application.

[Long-term follow-up study of post-COVID-19 patients].

AIM: To evaluate dynamic changes in the lungs, hemostasis system, immune system in different terms after coronavirus pneumonia. MATERIALS AND METHODS: Ventilation-perfusion single-photon emission computed tomography/computed tomography (CT), functional methods of lung investigation, evaluation of hemostasis system, immune status and specific humoral immune response were performed and evaluated in different terms after coronavirus pneumonia. A total of 71 patients were examined according to this protocol. We examined patients with the lesion volume not less than 50% according to chest CT. All patients were divided into 2 groups depending on the distance from the acute stage of coronavirus pneumonia. Group 1 included patients who were examined early (3060 days after hospital discharge), group 2 included patients who were examined later (61180 days after hospital discharge). RESULTS: We obtained gradual regression of pathologically-modified tissue from 67.3% during the inpatient phase to 30.9% during the early period and to 19.7% during the late period of examination, according to CT scan of the chest organs. The same tendency was demonstrated by diffusion capacity of the lungs. Perfusion scintigraphy data showed a decrease in perfusion deficit from 26.012.8% during the early period of examination to 19.46.2% during the late period of examination. On the contrary, ventilatory scintigraphy demonstrates the increase of isotope passage time through the alveolar-capillary membrane over time (from 48.231.3 minutes in the early period to 83.637.2 minutes in the late period). An increase in D-dimer was detected in 24% of patients in the early group. The levels of inflammatory markers, indices of immune status, and specific humoral immune response did not differ in the two described groups. CONCLUSION: The results demonstrate gradual regression of pathological changes caused by coronavirus infection.

In-vitro evaluation of the immunomodulatory effects of Baricitinib: Implication for COVID-19 therapy.

OBJECTIVE: Baricitinib seems a promising therapy for COVID-19. To fully-investigate its effects, we in-vitro evaluated the impact of baricitinib on the SARS-CoV-2-specific-response using the whole-blood platform. METHODS: We evaluated baricitinib effect on the IFN-γ-release and on a panel of soluble factors by multiplex-technology after stimulating whole-blood from 39 COVID-19 patients with SARS-CoV-2 antigens. Staphylococcal Enterotoxin B (SEB) antigen was used as a positive control. RESULTS: In-vitro exogenous addition of baricitinib significantly decreased IFN-γ response to spike- (median: 0.21, IQR: 0.01-1; spike+baricitinib 1000 nM median: 0.05, IQR: 0-0.18; p < 0.0001) and to the remainder-antigens (median: 0.08 IQR: 0-0.55; remainder-antigens+baricitinib 1000 nM median: 0.03, IQR: 0-0.14; p = 0.0013). Moreover, baricitinib significantly decreased SEB-induced response (median: 12.52, IQR: 9.7-15.2; SEB+baricitinib 1000 nM median: 8, IQR: 1.44-12.16; p < 0.0001). Baricitinib did modulate other soluble factors besides IFN-γ, significantly decreasing the spike-specific-response mediated by IL-17, IL-1ß, IL-6, TNF-α, IL-4, IL-13, IL-1ra, IL-10, GM-CSF, FGF, IP-10, MCP-1, MIP-1ß (p ≤ 0.0156). The baricitinib-decreased SARS-CoV-2-specific-response was observed mainly in mild/moderate COVID-19 and in those with lymphocyte count ≥1 × 103/µl. CONCLUSIONS: Exogenous addition of baricitinib decreases the in-vitro SARS-CoV-2-specific response in COVID-19 patients using a whole-blood platform. These results are the first to show the effects of this therapy on the immune-specific viral response.