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There is a lack of predictive markers for early and rapid identification of disease progression in COVID-19 patients. Our study aims at identifying microRNAs (miRNAs)/small nucleolar RNAs (snoRNAs) as potential biomarkers of COVID-19 severity. Using differential expression analysis of microarray data (n = 29), we identified hsa-miR-1246, ACA40, hsa-miR-4532, hsa-miR-145-5p, and ACA18 as the top five differentially expressed transcripts in severe versus asymptomatic, and ACA40, hsa-miR-3609, ENSG00000212378 (SNORD78), hsa-miR-1231, hsa-miR-885-3p as the most significant five in severe versus mild cases. Moreover, we found that white blood cell (WBC) count, absolute neutrophil count (ANC), neutrophil (%), lymphocyte (%), red blood cell (RBC) count, hemoglobin, hematocrit, D-Dimer, and albumin are significantly correlated with the identified differentially expressed miRNAs and snoRNAs. We report a unique miRNA and snoRNA profile that is associated with a higher risk of severity in a cohort of SARS-CoV-2 infected patients. Altogether, we present a differential expression analysis of COVID-19-associated microRNA (miRNA)/small nucleolar RNA (snoRNA) signature, highlighting their importance in SARS-CoV-2 infection. Qatar University QUST-1-CMED-2021-2 (FC). We gratefully acknowledge Hashim Alhussain for providing support in the BSL-3 laboratory at Qatar University. Scopus

The use of T cell–based adoptive immunotherapeutic strategies is emerging as an attractive alternative to currently used antiinfectious protocols in at-risk patients, such as those undergoing hematopoietic stem cells transplantation [1]. As more extensively tested in oncologic patients, two main strategies may be used: firstly, the infusion of autologous or donorderived total or pathogen-specific T cells, and secondly, the use of pathogen-specific engineered T cells. In the latest approach, it is included the redirection of T cells by using the so-called chimeric antigen receptors (CARs). CARs were firstly described in the late 1980s [2], and after design and technical improvements have recently reached the clinics with several ongoing clinical trials. In 2013, they were considered by Science magazine as important turning points in cancer immunotherapy—the major scientific breakthrough of that year [3]. In brief, CARs are artificial receptors constituted by a specific antigen-binding domain (usually, but not necessarily, represented by a single chain antibody fragment—scFv), an extracellular hinge region, a transmembrane domain, and a T cell receptor–derived intracellular signaling domain capable of triggering T cell activation [4]. This construct is used to transduce T cells which can therefore acquire a definite antigen specificity. Put simply, CARs may be considered as featuring the binding specificity of a monoclonal antibody (mAb) associated with the effector functions of a T cell. The main potential advantages of CARs are related to their capacity of recognizing antigens in a major histocompatibility complex (MHC)-independent manner, making them attractive immunotherapeutic tools. Ideally, the same CAR construct may be used effectively in different MHC-unrelated patients, one of the main limitations in the actual use of T cell–based therapy. Another important potential advantage is the capability of bypassing escape mechanisms based on MHC down-regulation, which may be put in practice by both neoplastic cells and infectious agents [5,6]. On the other hand, the lack of MHC control in T cell activation is the main theoretical risk

Viral infections and opportunistic fungal pathogens represent a major menace for immunocompromised patients. Despite the availability of antifungal and antiviral drugs, mortality in these patients remains high, underlining the need of novel therapeutic options based on completely different strategies. This review describes the potential of several T-cell-based therapeutic approaches in the prophylaxis and treatment of infectious diseases with a particular focus on persistent viral infections and opportunistic fungal infections, as these mostly affect immunocompromised patients. © 2015 Future Medicine Ltd. Viral infections and opportunistic fungal pathogens represent a major menace for immunocompromised patients. Despite the availability of antifungal and antiviral drugs, mortality in these patients remains high, underlining the need of novel therapeutic options based on completely different strategies. This review describes the potential of several T-cell-based therapeutic approaches in the prophylaxis and treatment of infectious diseases with a particular focus on persistent viral infections and opportunistic fungal infections, as these mostly affect immunocompromised patients.

The lack of structural information on hepatitis C virus (HCV) surface proteins has so far hampered the development of effective vaccines. Recently, two crystallographic structures have described the core portion (E2c) of E2 surface glycoprotein, the primary mediator of HCV entry. Despite the importance of these studies, the E2 overall structure is still unknown and, most importantly, several biochemical and functional studies are in disagreement with E2c structures. Here, the main literature will be discussed and an alternative disulfide bridge pattern will be proposed, based on unpublished human monoclonal antibody reactivity. A modeling strategy aiming at recapitulating the available structural and functional studies of E2 will also be proposed. © 2014 Elsevier Ltd. The lack of structural information on hepatitis C virus (HCV) surface proteins has so far hampered the development of effective vaccines. Recently, two crystallographic structures have described the core portion (E2c) of E2 surface glycoprotein, the primary mediator of HCV entry. Despite the importance of these studies, the E2 overall structure is still unknown and, most importantly, several biochemical and functional studies are in disagreement with E2c structures. Here, the main literature will be discussed and an alternative disulfide bridge pattern will be proposed, based on unpublished human monoclonal antibody reactivity. A modeling strategy aiming at recapitulating the available structural and functional studies of E2 will also be proposed.

The hepatitis C virus (HCV) adopts several escape mechanisms and is able to evade the host immune response in the majority of patients. During primary infection, HCV is not cleared in 80% of cases resulting in chronic infection. The current treatment for HCV infection is mainly represented by the administration of a combined therapy (IFN-α, ribavirin) and by the use of new anti-viral drugs (protease inhibitors). Unfortunately, only 50% of the infected patients respond completely to these therapies. It has been demonstrated how a neutralizing antibody response is correlated with lower HCV titer in acute infection. Moreover, it is also demonstrated how a rapid induction of neutralizing antibodies can be correlated with the viral clearance. Under these purposes, results clear how neutralizing antibodies can be important for the HCV infection control. In addition, they can represent good candidates for passive immunotherapy. They also can be applied both in diagnosis, as useful tools for the evaluation of the presence of cross-neutralizing antibodies in patients sera, and in research studies to better understand the virus–host interplay, an aspect that can be crucial in predicting the infection clinical outcome. In this study, we characterized the synergistic neutralization of HCV by two broadly neutralizing human monoclonal antibodies directed against HCV/E2 glycoprotein, named e20 and e137.

Hepatitis C virus (HCV) is the major cause of chronic liver disease worldwide. There is evidence that neutralizing anti-HCV antibodies may find potential applications in novel prophylactic and therapeutic strategies. This paper describes the very high neutralization activity and unique biological features of two broadly cross-reactive and cross-neutralizing anti-HCV human monoclonal IgG1 derived from human monoclonal recombinant Fab fragments.

A novel phagemid vector, named pCM, was optimized for the cloning and display of antibody fragment (Fab) libraries on the surface of filamentous phage. This vector contains two long DNA "stuffer" fragments for easier differentiation of the correctly cut forms of the vector. Moreover, in pCM the fragment at the heavy-chain cloning site contains an acid phosphatase-encoding gene allowing an easy distinction of the Escherichia coli cells containing the unmodified form of the phagemid versus the heavy-chain fragment coding cDNA. In pCM transcription of heavy-chain Fd/gene III and light chain is driven by a single lacZ promoter. The light chain is directed to the periplasm by the ompA signal peptide, whereas the heavy-chain Fd/coat protein III is trafficked by the pelB signal peptide. The phagemid pCM was used to generate a human combinatorial phage display antibody library that allowed the selection of a monoclonal Fab fragment antibody directed against the nucleoprotein (NP) of Influenza A virus.