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

Endocrine Disruptors, Epigenetic Changes, and Transgenerational Transmission

Recent discoveries in the field of molecular biology are focused on phenomena like chromatin condensation, histone (H) modification, and deoxyribonucleic acid (DNA) methylation, as well as the action of small non-coding ribonucleic acid (RNA), which together belong to the branch of epigenetics. The term “epigenetics” was coined in 1940 by Conrad Waddington [1] who described it as “the branch of biology which studies the causal interactions between genes and their product which bring phenotypes into being.” In fact, epigenetics includes all those mechanisms that are able to regulate DNA expression without modifying nucleotide sequence. Among the main epigenetic mechanisms mentioned earlier, DNA methylation is the most widely known and most studied modification (Table 3.1). The process of DNA methylation constitutes a postreplicative modification, in which a methyl group is added covalently to a DNA residue [10]. The methylation occurs at the carbon 5 of the cytosine ring in 5′-3′-oriented CG dinucleotides (named as CpGs), and it is catalyzed by the action of DNA methyltransferases (DNMTs)[11]. Furthermore, recent evidences have shown that also RNA factors, such as small RNAs (small interfering RNA [siRNA] and microRNA [miRNA]), have the ability to direct DNA methylation through a mechanism called RNA-directed DNA methylation (RdDM), performed by double-stranded RNA (dsRNA), which may be produced after the transcription of inverted repeats [12]

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

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" [...]

Role of KIR Receptor in NK Regulation during Viral Infections

Natural Killer (NK) cells are key effectors of the innate immune system which represent the first line of defense against viral infections. NK cell activation depends on the engagement of a complex receptor repertoire expressed on their surface, consisting of both activating and inhibitory receptors. Among the known NK cell receptors, the family of killer Ig-like receptors (KIRs) consists in activating/inhibitory receptors that interact with specific human leukocyte antigen (HLA) molecules expressed on target cells. In particular, the expression of peculiar KIRs have been reported to be associated to viral infection susceptibility. Interestingly, a significant association between the development and onset of different human pathologies, such as tumors, neurodegeneration and infertility, and a clonal KIRs expression on NK cells has been described in presence of viral infections, supporting the crucial role of KIRs in defining the effect of viral infections in different tissues and organs. This review aims to report the state of art about the role of KIRs receptors in NK cell activation and viral infection control

Gestational Viral Infections: Role of Host Immune System

Viral infections in pregnancy are major causes of maternal and fetal morbidity and mortality. Infections can develop in the neonate transplacentally, perinatally, or postnatally (from breast milk or other sources) and lead to different clinical manifestations, depending on the viral agent and the gestational age at exposure. Viewing the peculiar tolerogenic status which characterizes pregnancy, viruses could exploit this peculiar immunological status to spread or affect the maternal immune system, adopting several evasion strategies. In fact, both DNA and RNA virus might have a deep impact on both innate and acquired immune systems. For this reason, investigating the interaction with these pathogens and the host's immune system during pregnancy is crucial not only for the development of most effective therapies and diagnosis but mostly for prevention. In this review, we will analyze some of the most important DNA and RNA viruses related to gestational infections

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

Vaccines against severe acute respiratory syndrome coronavirus 2 (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 sera of thirty healthy volunteers at 9 months after the second vaccination dose of mRNA-vaccines and 1-month after the booster dose; ii) the levels of IFN-γ (Interferon-γ) production by blood T-cells exposed to SARS-CoV-2 spike antigen (Wuhan, Alpha B.1.1.7, Delta B.1.617.2, 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 leads to early activation of memory CD8+ T subset

Comparison Between Moxifloxacin and Chloramphenicol for the Treatment of Bacterial Eye Infections

Background: Moxifloxacin is a bactericidal methoxyquinolone used for the treatment of conjunctivitis and prophylactic therapy in cataract and refractive surgeries. Chloramphenicol is a bacteriostatic organochlorine introduced into clinical practice in 1948 and used mainly in topical preparations because of its known toxicity. Objectives: The study aimed to evaluate the in vitro antibacterial effect and the ocular cytotoxicity of these broad-spectrum antibiotics. Methods: Antimicrobic activity was tested on 4 bacteria strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis), and determined through calculation of MIC and half inhibitory concentration for each microorganism. Antibacterial activity was determined by microdilution method after 24 hours’ incubation with 2-fold serial dilutions (2.5 mg/mL to 4.883 μg/mL) of moxifloxacin and chloramphenicol. Disk diffusion test were performed according to European Committee on Antimicrobial Susceptibility Testing methodology. Biofilm formation inhibition and biofilm eradication concentration assay were conducted for P aeruginosa and S epidermidis using the microdilution method. Cytotoxicity of antibiotics was evaluated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) colorimetric assay on human corneal cell. Results: Cytotoxicity of antibiotics was evaluated on human epithelial corneal cells after 4 hours treatment by viability assay. Results showed that corneal cell viability was significantly higher after moxifloxacin treatment compared with chloramphenicol (P < 0.01). Moxifloxacin is characterized by a significantly lower MIC and half inhibitory concentration values and a larger inhibition zone for all the strain tested, with high performance in controlling gram-negative growth, compared with chloramphenicol. Moreover, moxifloxacin showed higher activity compared with chloramphenicol in the inhibition of biofilm formation and in the disruption of biofilm, especially against S epidermidis biofilm. Conclusions: The lower corneal cell toxicity and the broader spectrum of antibacterial activity observed with moxifloxacin suggests its use in ophthalmic solution for the treatment of bacterial eye infections

EFFECT OF SARS-CoV-2 ON THE COAGULATION CASCADE IN COVID-19 ASSOCIATED COAGULOPATHIES

Background: Coagulation decompensation is one of the complications most frequently encountered in COVID-19 patients and particularly the onset of thrombi and ischemia are often associated with a poor prognosis. Although the evidence for an association between SARS-CoV2 infection and coagulopathies is known (Levi et al, 2020), to date the mechanism underlying the alteration of the coagulation cascade in some COVID-19 patients remains misunderstood. Recently, protein S (PROS1), an anticoagulant plasma protein involved in the correct homeostasis of the coagulation cascade, has been described as a potential risk factor for complications related to COVID19 (Lemke et al, 2020) and represents a potential target for PLpro SARS-CoV-2 enzyme proteolysis (Ruzika, 2020). Aim: This study aims to identify peculiar expression patterns in COVID19-associated coagulopathies, to identify possible pharmacological targets, focusing on PROS1 protein alteration. Methods: Thrombotic, arteriosclerotic plaques, venous \ arterial, perivascular fat samples and blood samples were collected from COVID-positive and COVID-negative subject, and from COVID-positive subjects with no coagulopathies. SARS-CoV-2 presence will be evaluated by Real time PCR and by IHC and gene expression, and ELISA analysis will be performed to identify specific expression profiles associated with coagulation imbalances, with particular attention to protein S (PROS1). Results and Conclusions: We reported substantial differences in the activation of the coagulative cascade, and particularly a significant decrease of PROS1, in the COVID-19 cohort experiencing coagulative disorders, in association with SARS-CoV-2 positivity by IHC and real time PCR. These data suggested that, possibly, SARS-CoV-2 associated thrombotic/ischemic events might involve PROS-1 cleavage by viral PLpro, leading to the loss of its anticoagulant function. Basing on this evidence, the use of PLpro inhibitors might be suggest as a therapeutical tool for COVID-19 coagulopathies