SARS-CoV-2 Systemic Effects: New Clues.

To date, much discussion has been had on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung infection associated with COVID-19 onset, of which the major manifestation is characterized by a "cytokine storm" [...].

Non-classical HLA class I molecules and their potential role in viral infections.

Human Leukocyte Antigens (HLA) are classified in three different classes I, II and III, and represent the key mediators of immune responses, self-tolerance development and pathogen recognition. Among them, non-classical subtypes (HLA-Ib), e.g. HLA-E and HLA-G, are characterize by tolerogenic functions that are often exploited by viruses to evade the host immune responses. In this perspective, we will review the main current data referred to HLA-G and HLA-E and viral infections, as well as the impact on immune response. Data were selected following eligibility criteria accordingly to the reviewed topic. We used a set of electronic databases (Medline/PubMed, Scopus, Web of Sciences (WOS), Cochrane library) for a systematic search until November 2022 using MeSH keywords/terms (i.e. HLA, HLA-G, HLA-E, viral infection, SARS-CoV-2, etc.…). Recent studies support the involvement of non-classical molecules, such as HLA-E and HLA-G, in the control of viral infection. On one side, viruses exploit HLA-G and HLA-E molecule to control host immune activation. On the other side, the expression of these molecules might control the inflammatory condition generated by viral infections. Hence, this review has the aim to summarize the state of art of literature about the modulation of these non-classical HLA-I molecules, to provide a general overview of the new strategies of viral immune system regulation to counteract immune defenses.

Effect of SARS-CoV-2 infection in pregnancy on CD147, ACE2 and HLA-G expression.

INTRODUCTION: Recent studies reported a differential expression of both ACE2 and CD147 in pregnant women associated to SARS-CoV-2 placental infection. The aim of this study is to further investigate the placental SARS-CoV-2 infection and the potential effect on protein expression (ACE2, CD147, HLA-G and CD56). METHODS: The study was on three subgroups: i) 18 subjects positive for SARS-CoV-2 swab at delivery; ii) 9 subjects that had a positive SARS-CoV-2 swab during pregnancy but resulted negative at delivery; iii) 11 control subjects with physiological pregnancy and with no previous or concomitant SARS-CoV-2 swab positivity. None of the subjects were vaccinated for SARS-CoV-2 infection. The placenta samples were analyzed for SARS-CoV-2 NP (Nucleocapsid protein) positivity and the expression of ACE2, CD147, HLA-G and CD56. RESULTS: We observed a higher percentage of SARS-CoV-2 NP positive placenta samples in the group of SARS-CoV-2 PCR positive at delivery in comparison with SARS-CoV-2 PCR negative at delivery. The localization of SARS-CoV-2 NP positivity in placenta samples was mainly in syncytiotrophoblast (ST) of SARS-CoV-2 PCR positive at delivery group and in extra-villous trophoblast (EVT) of SARS-CoV-2 PCR negative at delivery group. CD147, HLA-G positivity was higher in ST of SARS-CoV-2 PCR positive at delivery group, while CD56-expressing immune cells were decreased in comparison with control subjects. DISCUSSION: We confirmed the ability of SARS-CoV-2 to infect placenta tissues. The simultaneous SARS-CoV-2 swab positivity at delivery and the positivity of the placenta tissue for SARS-CoV-2 NP seems to create an environment that modifies the expression of specific molecules, as CD147 and HLA-G. These data suggest a possible impact of SARS-CoV-2 infection during pregnancy, that might be worthy to be monitored also in vaccinated subjects.

Humoral and adaptive immune responses to the SARS-CoV-2 vaccine.

Vaccines against SARS-CoV-2 ameliorate infection and adverse outcomes from SARS-CoV-2. Elicitation of high affinity and durable protective antibody responses is a hallmark of a successful humoral immune response to vaccination. To assess the relevance of serum levels of SARS-CoV-2 specific antibodies and to further characterize the immune response to SARS-CoV-2 vaccines, we report i) the levels of spike-binding and neutralizing antibodies to SARS-COV-2 in the sera of 30 healthy volunteers at nine months after the second vaccination dose of mRNA vaccine and one month after the booster dose; ii) the levels of IFN-γ production by blood T cells exposed to SARS-CoV-2 spike antigen (Wuhan, Alpha B.1.1.7, Delta B.1.617.2, and Omicron B1.1.529 variants); and iii) the specific phenotype of T cells related with exposure to SARS-CoV-2 spike antigen. We observed that the booster dose induced increased humoral and adaptive immune responses and led to early activation of the memory CD8+ T subset.

Innate Immune Response in SARS-CoV-2 Infection.

An efficient host immune response is crucial in controlling viral infections. Despite most studies focused on the implication of T and B cell response in COVID-19 (Corona Virus Disease-19) patients or in their activation after vaccination against SARS-CoV-2, host innate immune response has raised even more interest as well. In fact, innate immunity, including Natural Killer (NK) cells, monocytes/macrophages and neutrophils, represent the first line of defense against the virus and it is essential to determine the correct activation of an efficient and specific acquired immune response. In this perspective, we will report an overview on the main findings concerning SARS-CoV-2 interaction with innate host immune system, in correlation with pathogenesis and viral immune escape mechanisms.

Relevance of VEGF and CD147 in different SARS-CoV-2 positive digestive tracts characterized by thrombotic damage.

Several evidence suggests that, in addition to the respiratory tract, also the gastrointestinal tract is a main site of severe acute respiratory syndrome CoronaVirus 2 (SARS-CoV-2) infection, as an example of a multi-organ vascular damage, likely associated with poor prognosis. To assess mechanisms SARS-CoV-2 responsible of tissue infection and vascular injury, correlating with thrombotic damage, specimens of the digestive tract positive for SARS-CoV-2 nucleocapsid protein were analyzed deriving from three patients, negative to naso-oro-pharyngeal swab for SARS-CoV-2. These COVID-19-negative patients came to clinical observation due to urgent abdominal surgery that removed different sections of the digestive tract after thrombotic events. Immunohistochemical for the expression of SARS-CoV-2 combined with a panel of SARS-CoV-2 related proteins angiotensin-converting enzyme 2 receptor, cluster of differentiation 147 (CD147), human leukocyte antigen-G (HLA-G), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 was performed. Tissue samples were also evaluated by electron microscopy for ultrastructural virus localization and cell characterization. The damage of the tissue was assessed by ultrastructural analysis. It has been observed that CD147 expression levels correlate with SARS-CoV-2 infection extent, vascular damage and an increased expression of VEGF and thrombosis. The confirmation of CD147 co-localization with SARS-CoV-2 Spike protein binding on gastrointestinal tissues and the reduction of the infection level in intestinal epithelial cells after CD147 neutralization, suggest CD147 as a possible key factor for viral susceptibility of gastrointestinal tissue. The presence of SARS-CoV-2 infection of gastrointestinal tissue might be consequently implicated in abdominal thrombosis, where VEGF might mediate the vascular damage.

Transparent Polymeric Formulations Effective against SARS-CoV-2 Infection.

The main route of the transmission of the SARS-CoV-2 virus is through airborne small aerosol particles containing viable virus as well as through droplets transmitted between people within close proximity. Transmission via contaminated surfaces has also been recognized as an important route for the spread of SARS-CoV-2 coronavirus. Among a variety of antimicrobial agents currently in use, polymers represent a class of biocides that have become increasingly important as an alternative to existing biocidal approaches. Two transparent polymeric compounds, containing silver and benzalkonium ions electrostatically bound to a polystyrene sulfonate backbone, were synthesized, through simple procedures, and evaluated for their antimicrobial properties against Gram-positive and Gram-negative bacteria and Candida albicans (ISO EN 1276) and for their antiviral activity toward 229E and SARS-CoV-2 coronaviruses (ISO UNI EN 14476:2019). The results showed that the two tested formulations are able to inhibit the growth of (1.5-5.5) × 1011 CFU of Gram-positive bacteria, Gram-negative bacteria, and of the fungal species Candida albicans. Both compounds were able to control the 229E and SARS-CoV-2 infection of a target cell in a time contact of 5 min, with a virucidal effect from 24 to 72 h postinfection, according to the European Medicines Agency (EMA) guidelines, where a product is considered virucidal upon achieving a reduction of 4 logarithms. This study observed a decrease of more than 5 logarithms, which implies that these formulations are likely ideal candidates for the realization of transparent surface coatings that are capable of maintaining remarkable antibacterial activity and SARS-CoV-2 antiviral properties over time.

Increased sHLA-G Is Associated with Improved COVID-19 Outcome and Reduced Neutrophil Adhesion.

Human leukocyte antigen (HLA) is a group of molecules involved in inflammatory and infective responses. We evaluated blood sHLA-E and sHLA-G levels in hospitalized COVID-19 patients with respiratory failure and their relationship with clinical evolution, changes in endothelial activation biomarker profile, and neutrophil adhesion. sHLA-E, sHLA-G, and endothelial activation biomarkers were quantified by ELISA assay in plasma samples. Neutrophil adhesion to endothelium was assessed in the presence/absence of patients' plasma samples. At admission, plasma levels of sHLA-G and sHLA-E were significantly higher in COVID-19 patients with respiratory failure compared to controls. COVID-19 clinical improvement was associated with increased sHLA-G plasma levels. In COVID-19, but not in control patients, an inverse correlation was found between serum sICAM-1 and E-selectin levels and plasma sHLA-G values. The in vitro analysis of activated endothelial cells confirmed the ability of HLA-G molecules to control sICAM-1 and sE-selectin expression via CD160 interaction and FGF2 induction and consequently neutrophil adhesion. We suggest a potential role for sHLA-G in improving COVID-19 patients' clinical condition related to the control of neutrophil adhesion to activated endothelium.

Depression at the time of the COVID-19 pandemic: A CES-D survey before and during the lockdown

On January 31, 2020, the first two cases of COVID-19 were detected in Italy;the extent and the rapidity of virus spread forced the Italian Government to take extraordinary measures to prevent contagion. In this study, we aimed to compare data collected before and during the COVID-19 pandemic on the depression symptomatology in a sample from the general population. We used archival data from a previous dataset we had access to, which included Center for Epidemiologic Studies-Depression scale (CES-D) data from non-clinical volunteers collected before (n = 151;Pre-COVID-19 group) and during (n = 352;COVID group) the pandemic. Statistical analyses compared CES-D scores yielded by the Pre-COVID-19 sample against those yielded by the COVID-19 sample. Additionally, the possible impact of demographic variables on CES-D scores before and during COVID-19 was tested. Moreover, in the COVID-19 group we found a statistically significant difference on the CES-D scores between men and women and a nearly significant relationship between age and CES-D scores. This study showed that the lockdown measures and the pandemic itself might have led to an increasing of the depressive symptoms in a non-clinical sample (and maybe in the Italian population), especially in women and youths. (English) [ABSTRACT FROM AUTHOR] Il 31 gennaio del 2020, in Italia, furono registrati i primi due casi di COVID-19;la portata e la rapidità della diffusione del virus costrinsero il governo italiano ad adottare delle misure di emergenza straordinarie per rallentare il contagio. L'obiettivo del presente studio è stato quello di indagare la sintomatologia depressiva sperimentata da un campione proveniente dalla popolazione generale, confrontando i dati raccolti prima e durante il lockdown da COVID-19. Sono stati utilizzati dati d'archivio che includevano dati relativi alla Center for Epidemiologic Studies-Depression scale (CES-D) somministrata prima (n = 151;gruppo Pre-COVID-19) e durante (n = 352;gruppo COVID-19) il primo lockdown italiano a un campione non-clinico. Le analisi si sono focalizzare sul confronto dei punteggi ottenuti alla CES-D nel gruppo Pre-COVID-19 e nel gruppo COVID-19. Inoltre, è stata valutata la possibile influenza di alcune variabili demografiche sui punteggi ottenuti alla CES-D prima e durante la pandemia da COVID-19. Inoltre, all'interno del gruppo COVID-19, sono state osservate delle differenze statisticamente significative tra i punteggi alla CES-D ottenuti da uomini e donne e una correlazione quasi significativa tra l'età dei partecipanti e i punteggi ottenuti alla CES-D. Lo studio ha rivelato che le misure restrittive e la pandemia stessa possono aver contribuito ad un incremento dei sintomi depressivi in un campione di individui non-clinici (e probabilmente nella popolazione generale italiana), specialmente nei giovani e nelle donne. (Italian) [ABSTRACT FROM AUTHOR] Copyright of BPA - Applied Psychology Bulletin (Bollettino di Psicologia Applicata) is the property of Giunti O.S. Organizzazioni Speciali and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection.

(1) Background: Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the coronavirus disease (COVID-19) that has led to a pandemic that began in March 2020. The role of the SARS-CoV-2 components on innate and adaptive immunity is still unknown. We investigated the possible implication of pathogen-associated molecular patterns (PAMPs)-pattern recognition receptors (PRRs) interaction. (2) Methods: We infected Calu-3/MRC-5 multicellular spheroids (MTCSs) with a SARS-CoV-2 clinical strain and evaluated the activation of RNA sensors, transcription factors, and cytokines/interferons (IFN) secretion, by quantitative real-time PCR, immunofluorescence, and ELISA. (3) Results: Our results showed that the SARS-CoV-2 infection of Calu-3/MRC-5 multicellular spheroids induced the activation of the TLR3 and TLR7 RNA sensor pathways. In particular, TLR3 might act via IRF3, producing interleukin (IL)-1α, IL-1ß, IL-4, IL-6, and IFN-α and IFN-ß, during the first 24 h post-infection. Then, TLR3 activates the NFκB transduction pathway, leading to pro-inflammatory cytokine secretion. Conversely, TLR7 seems to mainly act via NFκB, inducing type 1 IFN, IFN-γ, and IFN-λ3, starting from the 48 h post-infection. (4) Conclusion: We showed that both TLR3 and TLR7 are involved in the control of innate immunity during lung SARS-CoV-2 infection. The activation of TLRs induced pro-inflammatory cytokines, such as IL-1α, IL-1ß, IL-4, and IL-6, as well as interferons. TLRs could be a potential target in controlling the infection in the early stages of the disease.

SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the HLA-E/NKG2A Pathway.

Natural killer cells are important in the control of viral infections. However, the role of NK cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has previously not been identified. Peripheral blood NK cells from SARS-CoV and SARS-CoV-2 naïve subjects were evaluated for their activation, degranulation, and interferon-gamma expression in the presence of SARS-CoV and SARS-CoV-2 spike proteins. K562 and lung epithelial cells were transfected with spike proteins and co-cultured with NK cells. The analysis was performed by flow cytometry and immune fluorescence. SARS-CoV and SARS-CoV-2 spike proteins did not alter NK cell activation in a K562 in vitro model. On the contrary, SARS-CoV-2 spike 1 protein (SP1) intracellular expression by lung epithelial cells resulted in NK cell-reduced degranulation. Further experiments revealed a concomitant induction of HLA-E expression on the surface of lung epithelial cells and the recognition of an SP1-derived HLA-E-binding peptide. Simultaneously, there was increased modulation of the inhibitory receptor NKG2A/CD94 on NK cells when SP1 was expressed in lung epithelial cells. We ruled out the GATA3 transcription factor as being responsible for HLA-E increased levels and HLA-E/NKG2A interaction as implicated in NK cell exhaustion. We show for the first time that NK cells are affected by SP1 expression in lung epithelial cells via HLA-E/NKG2A interaction. The resulting NK cells' exhaustion might contribute to immunopathogenesis in SARS-CoV-2 infection.