Cannabidiol for Oral Health: A New Promising Therapeutical Tool in Dentistry.

The medical use of cannabis has a very long history. Although many substances called cannabinoids are present in cannabis, Δ9tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD) and cannabinol (CBN) are the three main cannabinoids that are most present and described. CBD itself is not responsible for the psychotropic effects of cannabis, since it does not produce the typical behavioral effects associated with the consumption of this drug. CBD has recently gained growing attention in modern society and seems to be increasingly explored in dentistry. Several subjective findings suggest some therapeutic effects of CBD that are strongly supported by research evidence. However, there is a plethora of data regarding CBD's mechanism of action and therapeutic potential, which are in many cases contradictory. We will first provide an overview of the scientific evidence on the molecular mechanism of CBD's action. Furthermore, we will map the recent developments regarding the possible oral benefits of CBD. In summary, we will highlight CBD's promising biological features for its application in dentistry, despite exiting patents that suggest the current compositions for oral care as the main interest of the industry.

Effectiveness of SARS-CoV-2 Vaccines for Short- and Long-Term Immunity: A General Overview for the Pandemic Contrast.

BACKGROUND: The recent COVID-19 pandemic produced a significant increase in cases and an emergency state was induced worldwide. The current knowledge about the COVID-19 disease concerning diagnoses, patient tracking, the treatment protocol, and vaccines provides a consistent contribution for the primary prevention of the viral infection and decreasing the severity of the SARS-CoV-2 disease. The aim of the present investigation was to produce a general overview about the current findings for the COVID-19 disease, SARS-CoV-2 interaction mechanisms with the host, therapies and vaccines' immunization findings. METHODS: A literature overview was produced in order to evaluate the state-of-art in SARS-CoV-2 diagnoses, prognoses, therapies, and prevention. RESULTS: Concerning to the interaction mechanisms with the host, the virus binds to target with its Spike proteins on its surface and uses it as an anchor. The Spike protein targets the ACE2 cell receptor and enters into the cells by using a special enzyme (TMPRSS2). Once the virion is quietly accommodated, it releases its RNA. Proteins and RNA are used in the Golgi apparatus to produce more viruses that are released. Concerning the therapies, different protocols have been developed in observance of the disease severity and comorbidity with a consistent reduction in the mortality rate. Currently, different vaccines are currently in phase IV but a remarkable difference in efficiency has been detected concerning the more recent SARS-CoV-2 variants. CONCLUSIONS: Among the many questions in this pandemic state, the one that recurs most is knowing why some people become more seriously ill than others who instead contract the infection as if it was a trivial flu. More studies are necessary to investigate the efficiency of the treatment protocols and vaccines for the more recent detected SARS-CoV-2 variant.

Cannabinoids Drugs and Oral Health-From Recreational Side-Effects to Medicinal Purposes: A Systematic Review.

BACKGROUND: marijuana, the common name for cannabis sativa preparations, is one of the most consumed drug all over the world, both at therapeutical and recreational levels. With the legalization of medical uses of cannabis in many countries, and even its recreational use in most of these, the prevalence of marijuana use has markedly risen over the last decade. At the same time, there is also a higher prevalence in the health concerns related to cannabis use and abuse. Thus, it is mandatory for oral healthcare operators to know and deal with the consequences and effects of cannabis use on oral cavity health. This review will briefly summarize the components of cannabis and the endocannabinoid system, as well as the cellular and molecular mechanisms of biological cannabis action in human cells and biologic activities on tissues. We will also look into oropharyngeal tissue expression of cannabinoid receptors, together with a putative association of cannabis to several oral diseases. Therefore, this review will elaborate the basic biology and physiology of cannabinoids in human oral tissues with the aim of providing a better comprehension of the effects of its use and abuse on oral health, in order to include cannabinoid usage into dental patient health records as well as good medicinal practice. METHODS: the paper selection was performed by PubMed/Medline and EMBASE electronic databases, and reported according to the PRISMA guidelines. The scientific products were included for qualitative analysis. RESULTS: the paper search screened a total of 276 papers. After the initial screening and the eligibility assessment, a total of 32 articles were considered for the qualitative analysis. CONCLUSIONS: today, cannabis consumption has been correlated to a higher risk of gingival and periodontal disease, oral infection and cancer of the oral cavity, while the physico-chemical activity has not been completely clarified. Further investigations are necessary to evaluate a therapeutic efficacy of this class of drugs for the promising treatment of several different diseases of the salivary glands and oral diseases.

The Role of SARS-CoV-2 Spike Protein in Long-term Damage of Tissues and Organs, the Underestimated Role of Retrotransposons and Stem Cells, a Working Hypothesis.

Coronavirus disease-2019 (COVID-19) is a respiratory disease in which Spike protein from SARS-CoV-2 plays a key role in transferring virus genomic code into target cells. Spike protein, which is found on the surface of the SARS-CoV-2 virus, latches onto angiotensin-converting enzyme 2 receptors (ACE2r) on target cells. The RNA genome of coronaviruses, with an average length of 29 kb, is the longest among all RNA viruses and comprises six to ten open reading frames (ORFs) responsible for encoding replicase and structural proteins for the virus. Each component of the viral genome is inserted into a helical nucleocapsid surrounded by a lipid bilayer. The Spike protein is responsible for damage to several organs and tissues, even leading to severe impairments and long-term disabilities. Spike protein could also be the cause of the long-term post-infectious conditions known as Long COVID-19, characterized by a group of unresponsive idiopathic severe neuro- and cardiovascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Guillaume-Barret's like-disease. In this paper, we suggest a pervasive mechanism whereby the Spike proteins either from SARS-CoV-2 mRNA or mRNA vaccines, tend to enter the mature cells, and progenitor, multipotent, and pluripotent stem cells (SCs), altering the genome integrity. This will eventually lead to the production of newly affected clones and mature cells. The hypothesis presented in this paper proposes that the mRNA integration into DNA occurs through several components of the evolutionarily genetic mechanism such as retrotransposons and retrotransposition, LINE-1 or L1 (long interspersed element-1), and ORF-1 and 2 responsible for the generation of retrogenes. Once the integration phase is concluded, somatic cells, progenitor cells, and SCs employ different silencing mechanisms. DNA methylation, followed by histone modification, begins to generate unlimited lines of affected cells and clones that form affected tissues characterized by abnormal patterns that become targets of systemic immune cells, generating uncontrolled inflammatory conditions, as observed in both Long COVID-19 syndrome and the mRNA vaccine.

Sixty-Month Follow Up of Clinical MRONJ Cases Treated with CGF and Piezosurgery.

AIMS: Medication-related osteonecrosis of the jaw (MRONJ) is a drug-related adverse reaction characterized by bone destruction and necrosis in the jaw. This case series aims to evaluate the treatment approaches and outcomes in MRONJ patients. MATERIALS AND METHODS: The retrospective study was conducted at the Dental Unit of the University of Bari, Italy. Patients with MRONJ were treated and followed up for 60 months. The treatment approach involved piezosurgery and concentrated growth factor (CGF). Six clinical cases from this group are described in detail. RESULTS: None of the patients showed recurrence of necrotic MRONJ lesions during the follow-up period. The surgical interventions, including bone resections and the application of CGF, resulted in successful mucosal healing and the prevention of disease progression. CONCLUSIONS: This study highlights the complexity of managing MRONJ and the importance of a multidisciplinary approach. Conservative treatment options and minimally invasive surgery have shown efficacy in controlling symptoms and improving patients' quality of life. However, the optimal treatment approach remains a challenge, and further studies are needed to evaluate alternative therapies and resective surgery. A comprehensive preoperative evaluation and collaboration among dental, endocrinology, and oncology specialists are crucial for personalized and multidisciplinary management. Ongoing research efforts are necessary to explore new therapeutic modalities and improve our understanding of MRONJ management, providing better support to patients dealing with this complex condition.

The Anti-Viral Activity of Stem Cells: A Rational Explanation for their Use in Clinical Application.

It is well established the importance of stem cells (SCs) in tissue growth, regeneration and repair, given their ability to self-renew and differentiate into mature cells. Stem cells are present in all individuals and are potentially active to the end of life. However, less is known about their unique function within the immune system as immune regulators and their important task in viral protection. Antiviral resistance is a common mechanism in all cells though stem cells utilize an antiviral RNA interference (RNAi) mechanism, while adult cells react by using the interferondependent repression pathway via interferon-associated protein-based response to induce an antiviral response. Therefore, the idea behind this review is to highlight the mechanisms of viral evasion of host defense, which would then allow us to highlight the rationale use of autologous stem cells and their biochemical and immunological ability to reset the subverted immune responses. Recently, scientists have highlighted their use in the field of immune-therapy, establishing the possibilities of using them outside the conventional protocol with the advancement in manipulating these cells in such a way that specific body activity can be restored. This paper describes the remarkable SCs profile and discusses some ideas regarding their promising use in vivo.

New Translational Trends in Personalized Medicine: Autologous Peripheral Blood Stem Cells and Plasma for COVID-19 Patient.

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), still remains a severe threat. At the time of writing this paper, the second infectious wave has caused more than 280,000 deaths all over the world. Italy was one of the first countries involved, with more than 200,000 people reported as infected and 30,000 deaths. There are no specific treatments for COVID-19 and the vaccine still remains somehow inconclusive. The world health community is trying to define and share therapeutic protocols in early and advanced clinical stages. However, numbers remain critical with a serious disease rate of 14%, ending with sepsis, acute respiratory distress syndrome (ARDS), multiple organ failure (MOF) and vascular and thromboembolic findings. The mortality rate was estimated within 2-3%, and more than double that for individuals over 65 years old; almost one patient in three dies in the Intensive Care Unit (ICU). Efforts for effective solutions are underway with multiple lines of investigations, and health authorities have reported success treating infected patients with donated plasma from survivors of the illness, the proposed benefit being protective antibodies formed by the survivors. Plasma transfusion, blood and stem cells, either autologous or allograft transplantation, are not novel therapies, and in this short paper, we propose therapeutic autologous plasma and peripheral blood stem cells as a possible treatment for fulminant COVID-19 infection.

The Sub-Molecular and Atomic Theory of Cancer Beginning: The Role of Mitochondria.

Life as we know it is made of strict interaction of atom, metabolism, and genetics, made around the chemistry of the most common elements of the universe: hydrogen, oxygen, nitrogen, sulfur, phosphorus, and carbon. The interaction of atomic, metabolic, and genetic cycles results in the organization and de-organization of chemical information of what we consider living entities, including cancer cells. In order to approach the problem of the origin of cancer, it is therefore reasonable to start from the assumption that the atomic structure, metabolism, and genetics of cancer cells share a common frame with prokaryotic mitochondria, embedded in conditions favorable for the onset of both. Despite years of research, cancer in its general acceptation remains enigmatic. Despite the increasing efforts to investigate the complexity of tumorigenesis, complementing the research on genetic and biochemical changes, researchers face insurmountable limitations due to the huge presence of variabilities in cancer and metastatic behavior. The atomic level of all biological activities it seems confirmed the electron behavior, especially within the mitochondria. The electron spin may be considered a key factor in basic biological processes defining the structure, reactivity, spectroscopic, and magnetic properties of a molecule. The use of magnetic fields (MF) has allowed a better understanding of the grade of influence on different biological systems, clarifying the multiple effects on electron behavior and consequently on cellular changes. Scientific advances focused on the mechanics of the cytoskeleton and the cellular microenvironment through mechanical properties of the cell nucleus and its connection to the cytoskeleton play a major role in cancer metastasis and progression. Here, we present a hypothesis regarding the changes that take place at the atomic and metabolic levels within the human mitochondria and the modifications that probably drive it in becoming cancer cell. We propose how atomic and metabolic changes in structure and composition could be considered the unintelligible reason of many cancers' invulnerability, as it can modulate nuclear mechanics and promote metastatic processes. Improved insights into this interplay between this sub-molecular organized dynamic structure, nuclear mechanics, and metastatic progression may have powerful implications in cancer diagnostics and therapy disclosing innovation in targets of cancer cell invasion.

Analysis of Gene Single Nucleotide Polymorphisms in COVID-19 Disease Highlighting the Susceptibility and the Severity towards the Infection.

Many factors may influence the risk of being infected by SARS-CoV-2, the coronavirus responsible for coronavirus disease 2019 (COVID-19). Exposure to the virus cannot explain the variety of an individual's responses to the virus and the high differences of effect that the virus may cause to some. While a person's preexisting condition and their immune defenses have been confirmed to play a major role in the disease progression, there is still much to learn about hosts' genetic makeup towards COVID-19 susceptibility and risk. The host genetic makeup may have direct influence on the grade of predisposition and outcomes of COVID-19. In this study, we aimed to investigate the presence of relevant genetic single nucleotide polymorphisms (SNPs), the peripheral blood level of IL6, vitamin D and arterial blood gas (ABG) markers (pH, oxygen-SpO2 and carbon dioxide-SpCO2) on two groups, COVID-19 (n = 41, study), and the healthy (n = 43, control). We analyzed cytokine and interleukin genes in charge of both pro-inflammatory and immune-modulating responses and those genes that are considered involved in the COVID-19 progression and complications. Thus, we selected major genes, such as IL1ß, IL1RN (IL-1 ß and α receptor) IL6, IL6R (IL-6 receptor), IL10, IFNγ (interferon gamma), TNFα (tumor necrosis factor alpha), ACE2 (angiotensin converting enzyme), SERPINA3 (Alpha-1-Antiproteinase, Antitrypsin member of Serpin 3 family), VDR (vitamin D receptor Tak1, Bsm1 and Fok1), and CRP (c-reactive protein). Though more research is needed, these findings may give a better representation of virus pleiotropic activity and its relation to the immune system.

An Alternative "Trojan Horse" Hypothesis for COVID-19: Immune Deficiency of IL-10 and SARS-CoV-2 Biology.

The coronavirus disease 2019 (COVID-19) pandemic has been a challenge for emergency care units worldwide due to the large numbers of patients, the scarcity of information, the medical resources, and the uncertainty regarding the disease's etiology and pathogenesis. The transmission of the virus and a probable post-pandemic of SARS-CoV-2 will depend on how deep this disease, the duration of immunity and the degree of cross immunity between SARS-CoV-2 and other pathogens either bacteria or fungi can be understood. Most mortalities have been related to an atypical pneumonia consisted of a sudden worsening of general condition of the admitted positive COVID-19 patients. The severe thromboembolism, often characterized by violent pulmonary and systemic complications, have been described with a blend of inflammatory-infectious patterns that rapidly shifted into a typical systemic inflammatory response syndrome (SIRS) or into an acute respiratory distress syndrome (ARDS) that eventually concluded into a multi-organ failure (MOF) and death. The fatality rate reported in our Covid-19 structure, SG Moscati Hospital of Taranto province in Italy, was higher in elderly male people with preexisting chronic pulmonary disease (COPD), patients with cancer and preexisting cardio-vascular diseases (CVD). We assumed a different theoretical position to clarify the higher mortality seen among those patients that was not as obvious as it appeared, we thus offered different pathophysiological picture that could help to recent solutions in therapy and prevention.

Characteristics of Hepatitis B Virus Genotype and Sub-Genotype in Hepatocellular Cancer Patients in Vietnam.

Untreated chronic hepatitis B virus (HBV) infection can lead to chronic liver disease and may progress to cirrhosis or hepatocellular carcinoma (HCC). HBV infection has been prevalent in Vietnam, but there is little information available on the genotypes, sub-genotypes, and mutations of HBV in patients with HBV-related HCC confirmed by histopathological diagnosis. We studied the molecular characteristics of HBV and its genetic variants in Vietnamese HCC patients after liver tumor resection. We conducted a descriptive cross-sectional study on 107 HBV-related HCC hospitalized patients from October 2018 to April 2019. The specimens collected included EDTA anticoagulant blood and liver tissues. Extracted HBV DNA was subjected to whole genome sequencing by the Sanger method. We discovered 62 individuals (57.9%) with genotype B and 45 patients (42.1%) with genotype C, with only sub-genotypes B4 and C1. Among the mutations, the double mutation, A1762T-G1764A, had the most significant frequency (73/107 samples; 68.2%) and was higher in genotype C than in genotype B (p < 0.001). The most common genotypes found in HCC patients in this investigation were B and C, with sub-genotypes B4 and C1 for each. The prevalence of genotype B4 was greater in HBV-infected Vietnamese HCC patients.

Antispike Immunoglobulin-G (IgG) Titer Response of SARS-CoV-2 mRNA-Vaccine (BNT162b2): A Monitoring Study on Healthcare Workers.

The secretion of IgG SARS-CoV-2 antispike antibodies after vaccination with BNT162b2 and the protection represent the response of the human organism to the viral vector symptomatic infections. The aim of the present investigation was to evaluate the immune reaction in health workers of the Polyclinic of Bari to identify the relationship of antispike titers with blood type, sex, age, and comorbidities. This prospective observational study (RENAISSANCE) had as its primary endpoint the assessment of serologic response to BNT162b2 at three blood titers: the first at 60 days after the second dose (3 February 2021); the second titer at 75 days after the first titer; and the third titer at 130 days after the second titer. Out of 230 enrolled staff members, all responded excellently to the mRna Pfizer (BNT162b) vaccine. Only one patient, 40 days after the second dose (3 February 2021), was positive on the swab control performed on 15 March 2021, although completely asymptomatic, and was negative on the subsequent molecular swab performed on 30 March 2021. All the patients responded to the mRNA Pfizer (BNT162b) vaccine with an antispike IgG level above 500 BAU/mL at the first antispike protein essay (60 days after the second dose on 3 April 2021); at the second titer (75 days after the first titer on 20 June 2021), 4 (1.7% of 230 enrolled) patients showed an antispike IgG level under 500 BAU/mL; at the third titer (130 days after the second titer on 30 June 2021, which means 9 months after the second dose), 37 (16.1% of 230 enrolled) patients showed an antispike IgG level under 500 BAU/mL. The data analysis demonstrated that patients belonging to blood group 0, regardless of their rhesus factor, showed the strongest level of antibodies compared to the other groups. No dependency was found between low antibodies level and sex or age. Molecular swab controls were performed every 15th of the month continuously. However, the enrolled patients' activity was at high risk because they carried out medical activities such as dental and surgical as well with droplets of water vaporized by the effect of turbines, piezosurgery. The vaccination campaign among health workers of the Policlinico of the University of Bari "Aldo Moro" led to an excellent serological response and the complete absence of COVID-19 incident cases, so the antibody response was excellent. The COVID-19 vaccine booster shot should be administered after 9 months and not without prompt antispike titer detection to assess if any sign of waning immunity is present in that specific patient.

Human Chondrocytes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Seeded on a Dermal-Derived Collagen Matrix Sheet: Our Preliminary Results for a Ready to Go Biotechnological Cartilage Graft in Clinical Practice.

BACKGROUND: The articular cartilage is unique in that it contains only a single type of cell and shows poor ability for spontaneous healing. Cartilage tissue engineering which uses mesenchymal stem cells (MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs) is considered an attractive treatment for cartilage lesions and osteoarthritis. The establishment of cartilage regenerative medicine is an important clinical issue, but the search for cell sources able to restore cartilage integrity proves to be challenging. The aim of this study was to create cartilage grafts from the combination of AT-MSCs and collagen substrates. METHODS: Mesenchymal stem cells were obtained from human donors' adipose tissue, and collagen scaffold, obtained from human skin and cleaned from blood vessels, adipose tissues, and debris, which only preserve dermis and epidermis, were seeded and cultured on collagen substrates and differentiated to chondrocytes. The obtained chondrocyte extracellular matrix of cartilage was then evaluated for the expression of chondrocyte-/cartilage-specific markers, the Cartilage Oligomeric Matrix Protein (COMP), collagen X, alpha-1 polypeptide (COL10A1), and the Collagen II, Human Tagged ORF Clone (COL2A1) by using the reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Our findings have shown that the dermal collagen may exert important effects on the quality of in vitro expanded chondrocytes, leading in this way that the influence of collagen skin matrix helps to produce highly active and functional chondrocytes for long-term cartilage tissue regeneration. CONCLUSION: This research opens up the possibility of generating cartilage grafts with the precise purpose of improving the existing limitation in current clinical procedures.

Rebalancing the Oral Microbiota as an Efficient Tool in Endocrine, Metabolic and Immune Disorders.

The current treatment and prevention procedures of oral disorders follow a very targeted approach considering mouth and its structures as a system that is completely independent, than the rest of the body. The main therapeutic approach is to keep the levels of oral bacteria and hygiene in an acceptable range compatible with oral-mouth health, completely separated from systemic microbial homeostasis (eubiosis vs dysbiosis). This can negatively impact the diagnosis of a more complex systemic disease and its progression. Dysbiosis occurs as a consequence of imbalance in oral and gut microbiota which leads to cardiovascular diseases, diabetes mellitus, rheumatoid arthritis, and Alzheimer's disease, as reported in current literature. Likewise, there is a need to highlight and develop a novel philosophical approach in the treatments for oral diseases that will necessarily involve nonconventional approaches.

The Effectiveness of Osseodensification Drilling Protocol for Implant Site Osteotomy: A Systematic Review of the Literature and Meta-Analysis.

Many different osteotomy procedures has been proposed in the literature for dental implant site preparation. The osseodensification is a drilling technique that has been proposed to improve the local bone quality and implant stability in poor density alveolar ridges. This technique determines an expansion of the implant site by increasing the density of the adjacent bone. The aim of the present investigation was to evaluate the effectiveness of the osseodensification technique for implant site preparation through a literature review and meta-analysis. The database electronic research was performed on PubMed (Medline) database for the screening of the scientific papers. A total of 16 articles have been identified suitable for the review and qualitative analysis-11 clinical studies (eight on animals, three on human subjects), four literature reviews, and one case report. The meta-analysis was performed to compare the bone-to-implant contact % (BIC), bone area fraction occupied % (BAFO), and insertion torque of clockwise and counter-clockwise osseodensification procedure in animal studies. The included articles reported a significant increase in the insertion torque of the implants positioned through the osseodensification protocol compared to the conventional drilling technique. Advantages of this new technique are important above all when the patient has a strong missing and/or low quantity of bone tissue. The data collected until the drafting of this paper detect an improvement when the osseodensification has been adopted if compared to the conventional technique. A significant difference in BIC and insertion torque between the clockwise and counter-clockwise osseodensification procedure was reported, with no difference in BAFO measurements between the two approaches. The effectiveness of the present study demonstrated that the osseodensification drilling protocol is a useful technique to obtain increased implant insertion torque and bone to implant contact (BIC) in vivo. Further randomized clinical studies are required to confirm these pieces of evidence in human studies.

SARS-CoV-2 Disease Adjuvant Therapies and Supplements Breakthrough for the Infection Prevention.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a high-risk viral agent involved in the recent pandemic stated worldwide by the World Health Organization. The infection is correlated to a severe systemic and respiratory disease in many cases, which is clinically treated with a multi-drug pharmacological approach. The purpose of this investigation was to evaluate through a literature overview the effect of adjuvant therapies and supplements for the SARS-CoV-2 infection. The research has analyzed the advantage of the EK1C4, by also assessing the studies on the resveratrol, vitamin D, and melatonin as adjuvant supplements for long hauler patients' prognosis. The evaluated substances reported important benefits for the improvement of the immune system and as a potential inhibitor molecules against SARS-CoV-2, highlighting the use of sartans as therapy. The adjuvant supplements seem to create an advantage for the healing of the long hauler patients affected by chronic symptoms of constant chest and heart pain, intestinal disorders, headache, difficulty concentrating, memory loss, and tachycardia.

SARS-CoV-2 Disease through Viral Genomic and Receptor Implications: An Overview of Diagnostic and Immunology Breakthroughs.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which is believed to have originated in China towards the end of November 2019, has now spread across the globe, causing a pandemic in 192 countries. The World Health Organization has called it the SARS-CoV-2 pandemic. Rapid dissemination of the virus occurs mainly through the saliva (Flügge's droplets) and aerosol, together with nasal and lachrymal passages. The literature associated with the recent advancement in terms of rapid diagnostics and SARS-CoV-2 vaccines has thoroughly studied the role of ACE2 receptors and Furin, as well as viral agent access into the host cell and its significant persistence at the level of the oral mucosa, which represents the main access to the virus. The purpose of this review was to underline the processes of SARS-CoV-2 infection mechanisms and novel breakthroughs in diagnostics and vaccines. Different technologies, such as the RT-PCR molecular test and the antigenic test, have been developed to identify subjects affected by the SARS-CoV-2 in order to improve the tracking of infection geographical diffusion. Novel rapid and highly sensitive diagnostic tests has been proposed for the detection of SARS-CoV-2 to improve the screening capability of suspected contagions. The strengthening of the vaccination campaign represents the most effective means to combat the SARS-CoV-2 infection and prevent severe manifestations of the virus-different classes of vaccines have been developed for this purpose. Further attention on the novel SARS-CoV-2 variant is necessary in order to verify the protection efficacy and virulence reduction of the infective agent in the recent vaccine campaign.

The 15-Months Clinical Experience of SARS-CoV-2: A Literature Review of Therapies and Adjuvants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease of 2019 (COVID-19) that emerged in December 2019 in Wuhan, China, and rapidly spread worldwide, with a daily increase in confirmed cases and infection-related deaths. The World Health Organization declared a pandemic on the 11th of March 2020. COVID-19 presents flu-like symptoms that become severe in high-risk medically compromised subjects. The aim of this study was to perform an updated overview of the treatments and adjuvant protocols for COVID-19. METHODS: A systematic literature search of databases was performed (MEDLINE PubMed, Google Scholar, UpToDate, Embase, and Web of Science) using the keywords: "COVID-19", "2019-nCoV", "coronavirus" and "SARS-CoV-2" (date range: 1 January 2019 to 31st October 2020), focused on clinical features and treatments. RESULTS: The main treatments retrieved were antivirals, antimalarials, convalescent plasma, immunomodulators, corticosteroids, anticoagulants, and mesenchymal stem cells. Most of the described treatments may provide benefits to COVID-19 subjects, but no one protocol has definitively proven its efficacy. CONCLUSIONS: While many efforts are being spent worldwide in research aimed at identifying early diagnostic methods and evidence-based effective treatments, mass vaccination is thought to be the best option against this disease in the near future.

Sars-CoV-2 Virus Infection May Interfere CD34+ Hematopoietic Stem Cells and Megakaryocyte-Erythroid Progenitors Differentiation Contributing to Platelet Defection towards Insurgence of Thrombocytopenia and Thrombophilia.

To date, several cases of thrombosis have been confirmed to be related to Sars-CoV-2 infection. Multiple attempts detected the prolonged occurrence of Sars-CoV-2 viral RNA (long COVID) in whole blood suggesting that virus byproducts may remain within cells and tissues well over the disease has finished. Patients may develop severe thrombocytopenia, acute anemia of inflammation and, systemic thrombosis with the fatal course of disease, which is suggestive of further interferences of Sars-CoV-2 on hematopoietic stem cells (HSCs) within the differentiation process towards erythroid and megakaryocytic cells. Therefore, we speculated whether Sars-CoV-2 propagates in or compartmentalizes with hematopoietic progenitor, erythroid, and megakaryocytic cells as the main cause of thrombotic events in either COVID-19 patients or vaccinated individuals. Results: The Sars-CoV-2 RNA replication, protein translation and infectious particle formation as the spike proteins in hematopoietic cell lines take place via the angiotensin-converting enzyme 2 (ACE2) entry pathway within primary CD34+ HSCs inducing, ex vivo, the formation of defected erythroid and megakaryocytic cells that eventually become targets of humoral and adaptive immune cells. Conclusions: Viral particles from affected CD34+ HSCs or the cellular component of RBC units and eventually platelets, present the greatest risk for sever thrombosis-transmitted Sars-CoV-2 infections.

Immunity Profiling of COVID-19 Infection, Dynamic Variations of Lymphocyte Subsets, a Comparative Analysis on Four Different Groups.

BACKGROUND: A novel coronavirus (SARS-CoV-2)-induced pneumonia (COVID-19) emerged in December 2019 in China, spreading worldwide. The aim of the present investigation was to evaluate the immunological response and the clinical subset of peripheral lymphocyte subset alteration in COVID-19 infection. METHODS: the study was conducted on four different clinical groups (n = 4; total n = 138). Each individual was assigned to different groups based on specific criteria evaluated at the admission such as fever, dyspnea, arterial blood gas analysis (ABG), oral-nasopharyngeal swab/RT-PCR, and thoracic CT-scan. Treatment was performed only after blood samples were collected from each patient (PP and PP) at day 1. The blood samples were analyzed and tested the same day (CBC and Flowcytometry). The positive-positive group (PP n = 45; F = 18/ M = 27; median age = 62.33), comprised individuals affected by COVID-19 who showed fever, dyspnea (ABG = pO2 < 60), confirmed positive by oral-nasopharyngeal swab/RT-PCR and with CT-scan showing ground-glass opacities. The negative-positive (NP; n = 37; F = 11/M = 26; median age = 75.94) or "COVID-like" group comprised individuals with fever and dyspnea (ABG = pO2 < 60), who tested negative to nasopharyngeal swab/RT-PCR, with CT-scans showing ground-glass opacities in the lungs. The negative-affected group (NA; n = 40; F = 14/M = 26; median age = 58.5) included individuals negative to COVID-19 (RT-PCR) but affected by different chronic respiratory diseases (the CT-scans didn't show ground-glass opacities). Finally, the negative-negative group (NN; n = 16; F = 14/M = 2) included healthy patients (NN; n = 16; median age = 42.62). Data and findings were collected and compared. RESULTS: Lymphocytes (%) cells showed a decline in COVID-19 patients. The subsets showed a significant association with the inflammatory status in COVID-19, especially with regard to increased neutrophils, T-killer, T-active, T-suppressor, and T-CD8+CD38+ in individuals belong to the either COVID-19 and Covid-like NP group. CONCLUSIONS: Peripheral lymphocyte subset alteration was associated with the clinical characteristics and progression of COVID-19. The level of sub-set cells T-lymphocytes (either high or low) and B-lymphocytes could be used as an independent predictor for COVID-19 severity and treatment efficacy.