A study of Indian Gen X and Millennials consumers' intention to use FinTech payment services during COVID-19 pandemic

PurposeAmid the COVID-19 contamination, people are bound to use contactless FinTech payment services. Because of restrictions on physical movement and avoidance of touching physical money, people willingly choose mobile payment, resulting in enormous growth in FinTech payment service industries. Because of this, this study aims to examine the effect of factors affecting Gen X and Millennials users to use FinTech payment services.Design/methodology/approachThe authors used 328 responses collected through convenience sampling of Indian users aged between 26 and 57 years in the Delhi-NCR region who are users of FinTech payment services.FindingsThe authors' findings verified that in India, perceived COVID-19 risk, perceived severity for COVID, individual mobility, subjective norms, perceived ease of use and perceived usefulness have statistically significant impacts on FinTech payment services during the COVID-19 pandemic. Structural equation modelling was used to study the proposed research model. Overall, the model predicted 76.9 % of the variation in intention to use FinTech payment services by the abovesaid variables by Indian users during a pandemic.Practical implicationsThis study will provide valuable insight to all FinTech service providers and stakeholders in planning and designing the concerned policy. It will be able to draw the attention of users more.Originality/valueThis research added a valuable theory to the existing technology adoption model (TAM) theory. It demonstrated the utility of the above variables in adopting and using FinTech payment services, which will help service providers to develop future strategies because of the COVID-19 pandemic.

MXene‐Based Aptameric Fluorosensor for Sensitive and Rapid Detection of COVID‐19

MXene‐Based Aptameric FluorosensorsThe aptamer‐functionalized MXene nanosheet acts as an effective bionanosensor for fluorescence‐enhanced detection of COVID‐19 with high sensitivity and specificity. This fluosensor is capable of detecting SARS‐CoV‐2 spike protein (limit of detection: 38.9 fg mL−1) and SARS‐CoV‐2 pseudovirus (limit of detection: 7.2 copies) within 30 min, and can also detect clinical samples. More details can be found in article number 2301146 by Binwu Ying and co‐workers.

SARS-CoV-2 infection disrupts trophoblast function and placental syncytial barrier integrity via its accessory protein, ORF3a

Problem: Although it is rare for a SARS-CoV-2 infection to transmit vertically to the fetus during pregnancy, there is a significantly increased risk of adverse pregnancy outcomes due to maternalCOVID- 19. However, there is a poor understanding of such risks because mechanistic studies on how SARS-CoV-2 infection disrupts placental homeostasis are significantly lacking. The SARS-CoV-2 proteome includes multiple structural and non-structural proteins, including the non-structural accessory proteinORF3a. The roles of these proteins in mediating placental infection remain undefined. We and others have shown that autophagy activity in placental syncytium is essential for barrier function and integrity. Here, we have used clinical samples and cultured trophoblast cells to evaluate syncytial integrity of placenta exposed to SARS-CoV-2. The objective of our study was to investigate potential mechanisms through which SARS-CoV-2 impairs placental homeostasis and causes adverse pregnancy outcomes. We tested the central hypothesis that an essential SARS-CoV-2 non-structural and accessory protein, ORF3a, uniquely (amongst multiple viral proteins tested) with a novel three-dimensional structure andwith no homology to any other proteins is a key modulator of placental trophoblast cell dynamics via autophagy and intracellular trafficking of a tight junction protein (TJP), ZO-1. Method(s): We used clinical samples and cultured trophoblast cells to evaluate syncytial integrity of placentas exposed to SARS-CoV- 2. Autophagic flux was measured in placental villous biopsies from SARS-CoV-2-exposed and unexposed pregnant women by quantifying the expression of autophagy markers, LC3 and P62. Trophoblast cells (JEG-3, Forskolin-treated JEG-3, HTR8/SVneo, or primary human trophoblasts (PHTs)) were transfected with expression plasmids encoding SARS-CoV-2 proteins including ORF3a. Using western blotting, multi-label immunofluorescence, and confocal imaging, we analyzed the effect of ORF3a on the autophagy, differentiation, invasion, and intracellular trafficking of ZO-1 in trophoblasts. Using coimmunoprecipitation assays, we tested ORF3a interactions with host proteins. t-tests and one-way analyses of variance (ANOVAs) with post hoc tests were used to assess the data, with significance set at P < .05. Result(s): We discovered :1) increased activation of autophagy, but incomplete processing of autophagosome-lysosomal degradation;2) accumulation of protein aggregates in placentas exposed to SARS-CoV- 2. Mechanistically, we showed that the SARS-CoV-2 ORF3a protein, uniquely 3) blocks the autophagy-lysosomal degradation process;4) inhibits maturation of cytotrophoblasts into syncytiotrophoblasts (STBs);5) reduces production ofHCG-beta, a key pregnancy hormone that is also essential for STB maturation;and 6) inhibits trophoblast invasive capacity. Furthermore, ORF3a harbors an intrinsically disordered C-terminus withPDZ-bindingmotifs.We show for the first time that, 7) ORF3a binds to and co-localizes with the PDZ domain of ZO-1, a junctional protein that is essential for STB maturation and the integrity of the placental barrier. Conclusion(s): Our work outlines a new molecular and cellular mechanism involving the SARS-CoV-2 accessory protein ORF3a that may drive the virus's ability to infect the placenta and damage placental syncytial integrity. This implies that the mechanisms facilitating viral maturation, such as the interaction of ORF3a with host factors, can be investigated for additional functionality and even targeted for developing new intervention strategies for treatment or prevention of SARS-CoV-2 infection at the maternal-fetal interface.

Alzheimer's disease and COVID-19.

In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.

Sensitizing breast cancers to immune checkpoint inhibitors through CD27 agonism and vaccination against tumor-associated antigen

Project objective: Despite the recent revolution in immune checkpoint inhibitors (ICIs), only modest improvement in overall survival and likely caused by not enough potent cellular immunity among BC patients. Our lab has been focus on inducing cellular immunity against HER2+ BC through vaccination against the tumor-associated antigen HER2. Approximately 20 years ago, we performed an experimental pilot study by administrating HER2 peptide and recombinant protein pulsed dendritic cells (DC vaccine) to six patients with refractory HER2+ advanced or metastatic (stage II (>= 6 +LN), III, or stage IV) BC. We followed the patients on 2019 found that all of the six patients were still alive, 18 years after vaccination. Their blood sample were analyzed with cytometry by time-offlight (CyTOF) and found there is a significantly increased presence of CD27 expressing memory T cells in response to HER2 peptide stimulation. Recent report on the SARS-CoV2 mRNA vaccine also suggested that CD27 expressing memory T cells plays a critical role in long-lasting cellular immunity against SARS-CoV2 infection. Therefore, we hypothesized that CD27 plays a critical role in cellular immunity against BC, and the stimulation of CD27 expressing T cells with mAb targeting CD27 significantly increase the cellular immunity triggered by vaccination against tumor-associated antigen. Result(s): We recapitulate the rise of CD27+ antigen specific T cells among the vaccinated patients using a transgenic mouse model expressing human CD27. When combined the adenoviral-vector based HER2 (Ad-HER2) vaccination with a single dose of human aCD27 antibody (Varlilumab), we found there is a robust increase in the HER2 specific T cells compared to vaccination alone, especially CD27+CD44+ memory CD4 T cells, even after 120 days post vaccination. Using an ICIinsensitive syngeneic HER2+ BC models, we found 50% of mice in the combination group of aCD27 antibody plus Ad-HER2 showed total tumor regression by the end of study. When combined with anti-PD1 antibody, the combination of AdHER2 and Varlilumab leads to total tumor regression in 90% of tumor bearing mice with syngeneic HER2+ BC, indicating that the vaccination against tumor associated antigen HER2 plus anti-CD27 antibody sensitized ICI-insensitive HER2+ BC toward ICI. Conclusion(s): Our data demonstrates that the administration of anti-CD27 antibody significantly increase the long term presence of CD27+ antigen specific memory T cells after vaccination against tumor associated antigen HER2. As consequence, combination of anti-CD27 with HER2 sensitized the immune unresponsive breast cancer toward anti-PD1 antibody. Our study suggests that the vaccination against tumor-associated antigen with mAb targeting CD27 leads to the robust cellular immunity, which is required for successful ICIs against breast cancer.

Joint Transmission Scheme and Coded Content Placement in Cluster-Centric UAV-Aided Cellular Networks

Recently, as a consequence of the COVID-19 pandemic, dependence on telecommunication for remote learning/working and telemedicine has significantly increased. In this context, preserving high Quality of Service (QoS) and maintaining low-latency communication are of paramount importance. In cellular networks, the incorporation of unmanned aerial vehicles (UAVs) can result in enhanced connectivity for outdoor users due to the high probability of establishing Line of Sight (LoS) links. The UAV's limited battery life and its signal attenuation in indoor areas, however, make it inefficient to manage users' requests in indoor environments. Referred to as the cluster-centric and coded UAV-aided femtocaching (CCUF) framework, the network's coverage in both indoor and outdoor environments increases by considering a two-phase clustering framework for Femto access points (FAPs)' formation and UAVs' deployment. Our first objective is to increase the content diversity. In this context, we propose a coded content placement in a cluster-centric cellular network, which is integrated with the coordinated multipoint (CoMP) approach to mitigate the intercell interference in edge areas. Then, we compute, experimentally, the number of coded contents to be stored in each caching node to increase the cache-hit-ratio, signal-to-interference-plus-noise ratio (SINR), and cache diversity and decrease the users' access delay and cache redundancy for different content popularity profiles. Capitalizing on clustering, our second objective is to assign the best caching node to indoor/outdoor users for managing their requests. In this regard, we define the movement speed of ground users as the decision metric of the transmission scheme for serving outdoor users' requests to avoid frequent handovers between FAPs and increase the battery life of UAVs. Simulation results illustrate that the proposed CCUF implementation increases the cache-hit-ratio, SINR, and cache diversity and decrease the users' access delay, cache redundancy, and UAVs' energy consumption.

Trace Elements Zinc and Selenium: Their Significance in the Conditions of the Covid-19 Pandemic

Within the conditions of the ongoing COVID-19 pandemic, when many questions regarding prevention and treatment strategies remain unsolved and the search for the best antiviral agents is underway, attention should be paid to the role of trace elements zinc and selenium in increasing the body's resistance to viral infections and their direct antiviral activity against SARS-CoV-2. Experimental data show that trace elements zinc and selenium not only actthrough regulating the immune response at all levels of humoral and cellular immunity, but also can play a significant role in adjuvant therapy for viral diseases. This is especially relevant in the case of COVID-19. Studies of the direct antiviral effect of these micro-elements testify to its 3 main ways to SARS-Cov-2: I - counteraction to virus replication and its transcription through: (i) their covalent binding to the SH-group of the cysteine of the main protease M(Pro) of the virus;(ii) inhibition of its RNA polymerase activity by zinc;II - preventing the penetration of the virus into cells due to blocking SH-groups of protein disulfide isomerase (RDI) of the protein of its spikes (peplomers);III - decreasing the adsorption capacity of the virus due to the blocking of the electrostatic interaction of SARS-CoV-2 peplomers and angiotensin-converting enzyme (ACE-2) in ultra-low, uncharacteristic oxidation states (Zn+1and Se-2). The intensity of the antiviral action of these trace elements may depend on their chemical form. It was found that zinc citrate (a five-membered complex of zinc with citric acid) and monoselenium citric acid obtained with the help of nanotechnology have a greater intensity of action and higher chemical purity. Taking into account the immunostimulating and direct antiviral effect of zinc and selenium, their use in the form of pharmaceuticals and dietary supplements should be considered as adjunctive therapy for SARS-CoV-2 in patients, or as a preventive strategy for uninfected people from risk groups during the spread of COVID-19.Copyright © Publisher PH <<Akademperiodyka>> of the NAS of Ukraine, 2023.

Cellular and humoral immune responses after SARS-CoV-2 vaccination in pediatric kidney recipients

Objective: Humoral and cellular immune responses to SARS-CoV-2 vaccination are reduced in adult kidney recipients. After pediatric kidney transplantation there are only few data available - mostly limited to monitoring of SARS-CoV-2 antibodies. Method(s): Cellular and humoral immune responses have been monitored before and after SARS-CoV-2 vaccination in pediatric kidney recipients. After in vitro stimulation with SARS-CoV-2 antigen (spike glycoprotein) virus-specific CD4 and CD8 T cells (SARS-CoV-2-Tvis) have been identified by cytokine flow cytometry. SARS-CoV-2 IgG was measured by CMIA. Result(s): Immune response after SARS-CoV-2 vaccination was analyzed in a total of 30 pediatric kidney recipients (age at 1st vaccine dose 5.2 - 17.8 years, median 14.8 years;43% male;30/30 2 vaccine doses;23/30 3 vaccine doses). At time of vaccination 22 patients (73%) received a tacrolimus (Tac)-based immunosuppression combined with mycophenolate mofetil (MMF;n = 15) or everolimus (n = 6) or neither of them (n = 1);3 patients were exposed to cyclosporine A and 5 patients to a calcineurin inhibitor (CNI)- free immunosuppression. MMF was used in 18/30 patients. After 1st dose of mRNA vaccine SARS-CoV-2 antibodies were detectable in 50% of pediatric kidney recipients, after 2nd dose in 78% and after 3rd dose in 88%. After the 2nd vaccine dose absence of humoral immune response (< 33.8 BAU/ml) was only found in case of MMF use (predominately combined with Tac). Peak IgG values (> 2,080 BAU/ml) were only detected in MMF-free regimens (6/7). Cellmediated response partially differed from humoral response, e. g., in some patients SARS-CoV2-Tvis were found despite lack of virus-specific antibodies. After 1st vaccine dose SARS-CoV-2-Tvis were detectable in 50% of pediatric kidney recipients, after 2nd dose in 92%. After 2nd vaccine dose absence or very low levels of SARS-CoV-2-Tvis (< 0.3 cells/mul) were only found in Tac-based immunosuppressive regimens, whereas higher levels (> 1.3 cells/mul) were exclusively detected in patients with MMFfree medication. Conclusion(s): After pediatric kidney transplantation humoral and cellular immune responses to SARS-CoV-2 vaccination were suboptimal, but more pronounced than in adult kidney recipients. Use of Tac and MMF was associated with impaired immune response to vaccination. SARS-CoV-2-specific humoral response corresponded only partially to cell-mediated response. Additional monitoring of SARS-CoV- 2-Tvis might be recommendable to improve assessment of the individual vaccine response and thereby to personalize the decision on the necessity of further vaccine doses.

Predominantly defective CD8+ T cell immunity to SARS-CoV-2 mRNA vaccination in lung transplant recipients.

BACKGROUND: Although mRNA vaccines have overall efficacy preventing morbidity/mortality from SARS-CoV-2 infection, immunocompromised persons remain at risk. Antibodies mostly prevent early symptomatic infection, but cellular immunity, particularly the virus-specific CD8+ T cell response, is protective against disease. Defects in T cell responses to vaccination have not been well characterized in immunocompromised hosts; persons with lung transplantation are particularly vulnerable to vaccine failure with severe illness. METHODS: Comparison groups included persons with lung transplantation and no history of COVID-19 (21 and 19 persons after initial mRNA vaccination and a third booster vaccination respectively), 8 lung transplantation participants recovered from COVID-19, and 22 non-immunocompromised healthy control individuals after initial mRNA vaccination (without history of COVID-19). Anti-spike T cell responses were assayed by stimulating peripheral blood mononuclear cells (PBMCs) with pooled small overlapping peptides spanning the SARS-CoV-2 spike protein, followed by intracellular cytokine staining (ICS) and flow cytometry for release of cytokines in response to stimulation, including negative controls (no peptide stimulation) and positive controls (phorbol myristate acetate [PMA] and ionomycin stimulation). To evaluate for low frequency memory responses, PBMCs were cultured in the presence of the mRNA-1273 vaccine for 14 days before this evaluation. RESULTS: Ionophore stimulation of PBMCs revealed a less inflammatory milieu in terms of interleukin (IL)-2, IL-4, and IL-10 profiling in lung transplantation individuals, reflecting the effect of immunosuppressive treatments. Similar to what we previously reported in healthy vaccinees, spike-specific responses in lung transplantation recipients were undetectable (< 0.01%) when tested 2 weeks after vaccination or later, but were detectable after in vitro culture of PBMCs with mRNA-1273 vaccine to enrich memory T cell responses. This was also seen in COVID-19-recovered lung transplantation recipients. Comparison of their enriched memory responses to controls revealed relatively similar CD4+ T cell memory, but markedly reduced CD8+ T cell memory both after primary vaccination or a booster dose. These responses were not correlated to age or time after transplantation. The vaccine-induced CD4+ and CD8+ responses correlated well in the healthy control group, but poorly in the transplantation groups. CONCLUSIONS: These results reveal a specific defect in CD8+ T cells, which have key roles both in transplanted organ rejection but also antiviral effector responses. Overcoming this defect will require strategies to enhance vaccine immunogenicity in immunocompromised persons.

Varying Cellular Immune Response against SARS-CoV-2 after the Booster Vaccination: A Cohort Study from Fukushima Vaccination Community Survey, Japan.

Booster vaccination reduces the incidence of severe cases and mortality related to COVID-19, with cellular immunity playing an important role. However, little is known about the proportion of the population that has achieved cellular immunity after booster vaccination. Thus, we conducted a Fukushima cohort database and assessed humoral and cellular immunity in 2526 residents and healthcare workers in Fukushima Prefecture in Japan through continuous blood collection every 3 months from September 2021. We identified the proportion of people with induced cellular immunity after booster vaccination using the T-SPOT.COVID test, and analyzed their background characteristics. Among 1089 participants, 64.3% (700/1089) had reactive cellular immunity after booster vaccination. Multivariable analysis revealed the following independent predictors of reactive cellular immunity: age < 40 years (adjusted odds ratio: 1.81; 95% confidence interval: 1.19-2.75; p-value: 0.005) and adverse reactions after vaccination (1.92, 1.19-3.09, 0.007). Notably, despite IgG(S) and neutralizing antibody titers of ≥500 AU/mL, 33.9% (349/1031) and 33.5% (341/1017) of participants, respectively, did not have reactive cellular immunity. In summary, this is the first study to evaluate cellular immunity at the population level after booster vaccination using the T-SPOT.COVID test, albeit with several limitations. Future studies will need to evaluate previously infected subjects and their T-cell subsets.

Clinical characteristics and host immunity responses of SARS-CoV-2 Omicron variant BA.2 with deletion of ORF7a, ORF7b and ORF8.

BACKGROUND: The pathogenicity and virulence of the Omicron strain have weakened significantly pathogenesis of Omicron variants. Accumulating data indicated accessory proteins play crucial roles in host immune evasion and virus pathogenesis of SARS-CoV-2. Therefore, the impact of simultaneous deletion of accessory protein ORF7a, ORF7b and ORF8 on the clinical characteristics and specific immunity in Omicron breakthrough infected patients (BIPs) need to be verified. METHODS: Herein, plasma cytokines were identified using a commercial Multi-cytokine detection kit. Enzyme-linked immunosorbent assay and pseudovirus neutralization assays were utilized to determine the titers of SARS-CoV-2 specific binding antibodies and neutralizing antibodies, respectively. In addition, an enzyme-linked immunospot assay was used to quantify SARS-CoV-2 specific T cells and memory B cells. RESULTS: A local COVID-19 outbreak was caused by the Omicron BA.2 variant, which featured a deletion of 871 base pairs (∆871 BA.2), resulting in the removal of ORF7a, ORF7b, and ORF8. We found that hospitalized patients with ∆871 BA.2 had significantly shorter hospital stays than those with wild-type (WT) BA.2. Plasma cytokine levels in both ∆871 BA.2 and WT BA.2 patients were within the normal range of reference, and there was no notable difference in the titers of SARS-CoV-2 ancestor or Omicron-specific binding IgG antibodies, neutralizing antibody titers, effector T cells, and memory B cells frequencies between ∆871 BA.2 and WT BA.2 infected adult patients. However, antibody titers in ∆871 BA.2 infected adolescents were higher than in adults. CONCLUSIONS: The simultaneous deletion of ORF7a, ORF7b, and ORF8 facilitates the rapid clearance of the BA.2 variant, without impacting cytokine levels or affecting SARS-CoV-2 specific humoral and cellular immunity in Omicron-infected individuals.

A Dual-Approach Strategy to Optimize the Safety and Efficacy of Anti-Zika Virus Monoclonal Antibody Therapeutics.

Antibody-dependent enhancement of infection (ADE) is clinically relevant to Dengue virus (DENV) infection and poses a major risk to the application of monoclonal antibody (mAb)-based therapeutics against related flaviviruses such as the Zika virus (ZIKV). Here, we tested a two-tier approach for selecting non-cross-reactive mAbs combined with modulating Fc glycosylation as a strategy to doubly secure the elimination of ADE while preserving Fc effector functions. To this end, we selected a ZIKV-specific mAb (ZV54) and generated three ZV54 variants using Chinese hamster ovary cells and wild-type (WT) and glycoengineered ΔXF Nicotiana benthamiana plants as production hosts (ZV54CHO, ZV54WT, and ZV54ΔXF). The three ZV54 variants shared an identical polypeptide backbone, but each exhibited a distinct Fc N-glycosylation profile. All three ZV54 variants showed similar neutralization potency against ZIKV but no ADE activity for DENV infection, validating the importance of selecting the virus/serotype-specific mAbs for avoiding ADE by related flaviviruses. For ZIKV infection, however, ZV54CHO and ZV54ΔXF showed significant ADE activity while ZV54WT completely forwent ADE, suggesting that Fc glycan modulation may yield mAb glycoforms that abrogate ADE even for homologous viruses. In contrast to the current strategies for Fc mutations that abrogate all effector functions along with ADE, our approach allowed the preservation of effector functions as all ZV54 glycovariants retained antibody-dependent cellular cytotoxicity (ADCC) against the ZIKV-infected cells. Furthermore, the ADE-free ZV54WT demonstrated in vivo efficacy in a ZIKV-infection mouse model. Collectively, our study provides further support for the hypothesis that antibody-viral surface antigen and Fc-mediated host cell interactions are both prerequisites for ADE, and that a dual-approach strategy, as shown herein, contributes to the development of highly safe and efficacious anti-ZIKV mAb therapeutics. Our findings may be impactful to other ADE-prone viruses, including SARS-CoV-2.

SARS-CoV2 infection induce miR-155 expression and skewed Th17/Treg balance by changing SOCS1 level: A clinical study.

BACKGROUND: One of the regulators in severe acute respiratory syndrome coronavirus2 (SARS-CoV2) infection is miRNAs. In COVID-19 patients, immunological responses to SARS-CoV2 infection may be impacted by miR-155, a miRNA associated to inflammation. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) of 50 confirmed COVID-19 patients /Healthy Controls (HCs) was isolated by Ficoll. The frequency of T helper 17 and regulatory T cells was analyzed by flowcytometry. The RNA was extracted from each sample and after synthesis of c-DNA, the relative expression of miR-155, suppressor of cytokine signaling (SOCS-1), Signal transducer and activator of transcription 3(STAT3), and Fork Head Box Protein 3 (FoxP3) was evaluated by real-time PCR. The protein level of STAT3, FoxP3 and RORγT in the isolated PBMCs measured by western blotting. The serum level of IL-10, TGF-ß, IL-17 and IL21 was assessed by ELISA method. RESULTS: The population of Th17 cells showed a significant rise, whereas Treg cells reduced in COVID-19 cases. The master transcription factor of Treg (FoxP3) and Th17 (RORγT) relative expression showed the same pattern as flowcytometry. STAT3 level of expression at RNA and protein level increased in COVID-19 cases. FOXP3 and SOCS-1 proteins were down-regulated. The relative expression of miR-155, up-regulated in PBMC of COVID-19 patients and revealed a negative correlation with SOCS-1. The serum cytokine profile showed a reduction in TGF-ß, on the other hand an increase was seen in IL-17, IL-21 and IL-10 in COVID-19 cases toward control group. CONCLUSION: Based on the studies conducted in this field, it can be suggested that Th17/Treg in covid-19 patients can be affected by miR-155 and it can be considered a valuable diagnostic and prognostic factor in this disease.

Mesenchymal Stem Cells: Case Report of an Adjuvant Ambulatory Therapy for a COVID-19 High-Risk and steroid-hypersensitive Patient.

INTRODUCTION: Due to the rapid progression of COVID-19 to severe and critical stages, thousands of patients have required the use of intensive care unit (ICU) treatment, placing an excessive strain on health systems. Immunomodulatory effects of Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs) have shown promising results on the treatment of patients with COVID-19. However, the effect of promptly applied cell therapy on ambulatory patient prognosis has not been described. This case report presents the clinical outcome of a multimorbid, steroid-hypersensitive, COVID-19 patient treated with WJ-MSCs transplantation. CASE PRESENTATION: A 67-year-old woman with Type 2 diabetes, overweight (82 kg, 168 cm, BMI = 29.053), hypertension (60/190 mmHg) and steroid-hypersensitivity, tested positive for COVID-19 after presenting typical symptoms such as fatigue, chest pain, myalgia, nasal congestion, dysgeusia, anosmia and oxygen saturation (SpO2) 94% - 96%, with normal body temperature (36°C). The patient received pharmacologic treatment but, when symptoms worsened, WJ-MSCs were transplanted to modulate the suspected onset of the cytokine release syndrome. Significant improvement of symptoms and clinical parameters (inflammatory markers and CT score) were observed, and the patient fully recovered within a short period of time. CONCLUSION: The present case report exhibits the favorable outcome of using Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs) as an ambulatory and adjuvant therapy for COVID-19. Prompt WJ-MSCs infusion can be a safe ambulatory adjuvant therapy in COVID-19 infection care, preventing disease progression to critical stages and avoiding hospital overcrowding.

Cellular and humoral immune response to SARS-CoV-2 mRNA vaccines in patients treated with either Ibrutinib or Rituximab.

Patients treated with B-cell-targeting therapies like Rituximab or Ibrutinib have decreased serological response to various vaccines. In this study, we tested serological and cellular response to SARS-CoV-2 mRNA vaccines in 16 patients treated with Ibrutinib, 16 treated with maintenance Rituximab, 18 patients with chronic lymphocytic leukaemia (CLL) with watch and wait status and 21 healthy volunteers. In comparison with the healthy volunteers, where serological response was achieved by 100% subjects, patients on B-cell-targeting therapy (Ibrutinib and Rituximab) had their response dramatically impaired. The serological response was achieved in 0% of Rituximab treated, 18% of Ibrutinib treated and 50% of untreated CLL patients. Cell-mediated immunity analysed by the whole blood Interferon-γ Release immune Assay developed in 80% of healthy controls, 62% of Rituximab treated, 75% of Ibrutinib treated and 55% of untreated CLL patients. The probability of cell-mediated immune response development negatively correlates with disease burden mainly in CLL patients. Our study shows that even though the serological response to SARS-CoV-2 vaccine is severely impaired in patients treated with B-cell-targeting therapy, the majority of these patients develop sufficient cell-mediated immunity. The vaccination of these patients therefore might be meaningful in terms of protection against SARS-CoV-2 infection.

Adenovirus vector and mRNA vaccines: Mechanisms regulating their immunogenicity.

Replication-incompetent adenovirus (Ad) vector and mRNA-lipid nanoparticle (LNP) constructs represent two modular vaccine platforms that have attracted substantial interest over the past two decades. Due to the COVID-19 pandemic and the rapid development of multiple successful vaccines based on these technologies, there is now clear real-world evidence of the utility and efficacy of these platforms. Considerable optimization and refinement efforts underpin the successful application of these technologies. Despite this, our understanding of the specific pathways and processes engaged by these vaccines to stimulate the immune response remains incomplete. This review will synthesize our current knowledge of the specific mechanisms by which CD8+ T cell and antibody responses are induced by each of these vaccine platforms, and how this can be impacted by specific vaccine construction techniques. Key gaps in our knowledge are also highlighted, which can hopefully focus future studies.

Omics and systems view of innate immune pathways.

Multiomics approaches to studying systems biology are very powerful techniques that can elucidate changes in the genomic, transcriptomic, proteomic, and metabolomic levels within a cell type in response to an infection. These approaches are valuable for understanding the mechanisms behind disease pathogenesis and how the immune system responds to being challenged. With the emergence of the COVID-19 pandemic, the importance and utility of these tools have become evident in garnering a better understanding of the systems biology within the innate and adaptive immune response and for developing treatments and preventative measures for new and emerging pathogens that pose a threat to human health. In this review, we focus on state-of-the-art omics technologies within the scope of innate immunity.

Long term follow-up of humoral and cellular response to mRNA-based vaccines for SARS-CoV-2 in patients with active multiple myeloma.

Long-term kinetics of antibody (Ab) and cell-mediated immune (CMI) response to full anti-SARS-CoV-2 vaccine schedule and booster doses in Multiple Myeloma (MM) patients remain unclear. We prospectively evaluated Ab and CMI response to mRNA vaccines in 103 SARS-CoV-2-naïve MM patients (median age 66, 1 median prior line of therapy) and 63 health-workers. Anti-S-RBD IgG (Elecsys®assay) were measured before vaccination and after 1 (T1), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months from second dose (D2) and 1 month after the introduction of the booster dose (T1D3). CMI response (IGRA test) was evaluated at T3 and T12. Fully vaccinated MM patients displayed high seropositivity rate (88.2%), but low CMI response (36.2%). At T6 the median serological titer was halved (p=0.0391) in MM patients and 35% reduced (p=0.0026) in controls. D3 (94 patients) increased the seroconversion rate to 99% in MM patients and the median IgG titer in both groups (up to 2500 U/mL), maintained at T12. 47% of MM patients displayed a positive CMI at T12 and double-negativity for humoral and CMI (9.6% at T3) decreased to 1%. Anti-S-RBD IgG level ≥346 U/mL showed 20-times higher probability of positive CMI response (OR 20.6, p<0.0001). Hematological response ≥CR and ongoing lenalidomide maintenance enhanced response to vaccination, hindered by proteasome inhibitors/anti-CD38 monoclonal antibodies. In conclusion, MM elicited excellent humoral, but insufficient cellular responses to anti-SARS-CoV-2 mRNA vaccines. Third dose improved immunogenicity renewal, even when undetectable after D2. Hematological response and ongoing treatment at vaccination were the main predictive factors of vaccine immunogenicity, emphasizing the role of vaccine response assessment to identify patients requiring salvage approaches.

Improved Performance of the QuantiFERON-SARS-CoV-2 Assay with the Extended Set.

Multiple assays have been developed for the characterization of the functional activation of SARS-CoV-2 specific T-cells. This study was conducted to assess the post-vaccination and post-infection T cell response, as detected by the QuantiFERON-SARS-CoV-2 assay using the combination of three SARS-CoV-2 specific antigens (Ag1, Ag2 and Ag3). An amount of 75 participants with different infection and vaccination backgrounds were recruited for the evaluation of humoral and cellular immune responses. An elevated IFN-γ response in at least one Ag tube was observed in 69.2% of convalescent subjects and 63.9% of vaccinated ones. Interestingly, in a healthy unvaccinated case and three convalescents with negative IgG-RBD, we detected a positive QuantiFERON test after stimulation with Ag3. The majority of the T cell responders reacted simultaneously to the three SARS-CoV-2 specific antigens, and Ag3 demonstrated the highest rate of reactivity. At univariable analysis, the only factor that was associated with an absence of a cellular response was time from blood collection, being less than 30 days (OR:3.5, CI95% [1.15-10.50], p = 0.028). Overall, the inclusion of Ag3 improved the performance of the QuantiFERON-SARS-CoV-2 and showed a particular interest among subjects who fail to achieve a measurable antibody response after infection or vaccination.