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1.
Front Immunol ; 12: 652252, 2021.
Article in English | MEDLINE | ID: covidwho-1463468

ABSTRACT

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host's immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host's innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.


Subject(s)
COVID-19/immunology , Cardiovascular System/virology , Coronavirus Infections/immunology , Coronavirus/physiology , Immunotherapy/methods , Lung/virology , Receptors, Pattern Recognition/metabolism , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/immunology , Animals , Cardiovascular System/pathology , Humans , Immunity, Innate , Lung/pathology
2.
Front Immunol ; 12: 715464, 2021.
Article in English | MEDLINE | ID: covidwho-1430698

ABSTRACT

The mutants resulted from the ongoing SARS-CoV-2 epidemic have showed resistance to antibody neutralization and vaccine-induced immune response. The present study isolated and identified two novel SARS-CoV-2 neutralizing antibodies (nAbs) from convalescent COVID-19 patients. These two nAbs (XG81 and XG83) were then systemically compared with nine nAbs that were reconstructed by using published data, and revealed that, even though these two nAbs shared targeting epitopes on spike protein, they were different from any of the nine nAbs. Compared with XG81, XG83 exhibited a higher RBD binding affinity and neutralization potency against wild-typed pseudovirus, variant pseudoviruses with mutated spike proteins, such as D614G, E484Q, and A475V, as well as the authentic SARS-CoV-2 virus. To explore potential broadly neutralizing antibodies, heavy and light chains from all 18 nAbs (16 published nAbs, XG81 and XG83) were cross-recombined, and some of the functional antibodies were screened and studied for RBD binding affinity, and neutralizing activity against pseudovirus and the authentic SARS-CoV-2 virus. The results demonstrated that several recombined antibodies had a more potent neutralization activity against variant pseudoviruses compared with the originally paired Abs. Taken together, the novel neutralizing antibodies identified in this study are a likely valuable addition to candidate antibody drugs for the development of clinical therapeutic agents against SARS-CoV-2 to minimize mutational escape.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/immunology , Broadly Neutralizing Antibodies/therapeutic use , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/genetics , Antibodies, Viral/therapeutic use , Antibody Affinity/immunology , B-Lymphocytes/immunology , Broadly Neutralizing Antibodies/genetics , COVID-19/immunology , COVID-19/therapy , Cell Line , Epitopes/immunology , Humans , Immunotherapy/methods , Neutralization Tests , SARS-CoV-2/drug effects
3.
Mol Med ; 27(1): 112, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1413278

ABSTRACT

The ongoing global COVID-19 pandemic has thrown into sharp relief the gap between modern biology's ability to investigate and respond to a novel pathogen and modern medicine's ability to marshal effective front-line interventions to limit its immediate health impact. While we have witnessed the rapid development of innovative vaccines against SARS-CoV-2 using novel molecular platforms, these have yet to alter the pandemic's long-term trajectory in all but a handful of high-income countries. Health workers at the clinical front lines have little more in their clinical armamentarium than was available a century ago-chiefly oxygen and steroids-and yet advances in modern immunology and immunotherapeutics suggest an underuse of extant and effective, if unorthodox, therapies, which we now call "Extreme Immunotherapies for Pandemics (EIPs)."


Subject(s)
Pandemics/prevention & control , COVID-19/immunology , COVID-19 Vaccines/immunology , Humans , Immunotherapy/methods , SARS-CoV-2/immunology
4.
Int J Med Sci ; 18(15): 3389-3394, 2021.
Article in English | MEDLINE | ID: covidwho-1409697

ABSTRACT

Current standard vaccine testing protocols take approximately 10-24 months of testing before a vaccine can be declared successful. Sometimes by the time a successful vaccine is out for public use, the outbreak may already be over. With no vaccine or antiviral drug available to treat the infected, we are left with the age-old methods of isolation, quarantine, and rest, to arrest such a viral outbreak. Convalescent blood therapy and covalent plasma therapy have often proved effective in reducing mortality, however, the role of innate and adaptive immune cells in these therapies have been overlooked. Antigen presenting cells (APCs), CD4+ T memory cells, CD8+ T memory cells, and memory B-Cells all play a vital role in sustainable defense and subsequent recovery. This report incorporates all these aspects by suggesting a novel treatment therapy called selective convalescent leukapheresis and transfusion (SCLT) and also highlights its potential in vaccination. The anticipated advantages of the proposed technique outweigh the cost, time, and efficiency of other available transfusion and vaccination processes. It is envisioned that in the future this new approach could serve as a rapid emergency response to subdue a pathogen outbreak and to stop it from becoming an epidemic, or pandemic.


Subject(s)
COVID-19/therapy , Immunotherapy/methods , Antigen-Presenting Cells/cytology , Antiviral Agents/therapeutic use , Blood Transfusion , CD4-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/cytology , COVID-19 Vaccines , Cytokines/metabolism , Humans , Immunization, Passive/methods , Immunologic Factors , Leukapheresis , Pandemics , SARS-CoV-2
6.
Adv Drug Deliv Rev ; 176: 113900, 2021 09.
Article in English | MEDLINE | ID: covidwho-1384817

ABSTRACT

The recent approval of messenger RNA (mRNA)-based vaccines to combat the SARS-CoV-2 pandemic highlights the potential of both conventional mRNA and self-amplifying mRNA (saRNA) as a flexible immunotherapy platform to treat infectious diseases. Besides the antigen it encodes, mRNA itself has an immune-stimulating activity that can contribute to vaccine efficacy. This self-adjuvant effect, however, will interfere with mRNA translation and may influence the desired therapeutic outcome. To further exploit its potential as a versatile therapeutic platform, it will be crucial to control mRNA's innate immune-stimulating properties. In this regard, we describe the mechanisms behind the innate immune recognition of mRNA and provide an extensive overview of strategies to control its innate immune-stimulating activity. These strategies range from modifications to the mRNA backbone itself, optimization of production and purification processes to the combination with innate immune inhibitors. Furthermore, we discuss the delicate balance of the self-adjuvant effect in mRNA vaccination strategies, which can be both beneficial and detrimental to the therapeutic outcome.


Subject(s)
Gene Amplification/immunology , Immunity, Innate/immunology , Immunotherapy/methods , RNA, Messenger/immunology , Vaccines, Synthetic/immunology , Animals , COVID-19/genetics , COVID-19/immunology , COVID-19/prevention & control , Gene Amplification/drug effects , Humans , Immunity, Innate/drug effects , Immunotherapy/trends , RNA, Messenger/administration & dosage , RNA, Messenger/genetics , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics
8.
Endocr Metab Immune Disord Drug Targets ; 21(8): 1392-1405, 2021.
Article in English | MEDLINE | ID: covidwho-1389051

ABSTRACT

The complications of the SARS-CoV-2 infection and its COVID-19 disease on mothers and their offspring are less known. This review aimed to determine the transmission, severity, and complications of SARS- CoV-2 infection during pregnancy. This review showed the influence of COVID-19 disease on neonatal neurogenesis. Owing medicines that were reported for the treatment of COVID-19 disease, this review suggested some control strategies like treatments (medicinal plants, antiviral therapy, cellular therapy, and immunotherapy), nutrition uptake, prevention, and recommendations. This overview showed that severe infection of SARS-CoV-2 during the early stage of pregnancy might increase the risk of stress, panic, and anxiety. This disorder can disturb the maternal immune system, and thus causing a neurodevelopmental disturbance. This hypothesis may be depending on the severity and intensity of the SARS-CoV-2 infection during pregnancy. However, vertical transmission of SARS-CoV-2 from dams to their fetuses is absent until now. During this global pandemic disease, maintaining safety during pregnancy, vaginal delivery, and breastfeeding may play a vital role in a healthy life for the offspring. Thus, international, and national organizations should be continuing for perinatal management, particularly during the next pandemic or disaster time.


Subject(s)
COVID-19/therapy , COVID-19/transmission , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/therapy , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/immunology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Female , Humans , Immunotherapy/methods , Pregnancy , SARS-CoV-2/drug effects , SARS-CoV-2/immunology
10.
Nat Commun ; 12(1): 1087, 2021 02 17.
Article in English | MEDLINE | ID: covidwho-1333934

ABSTRACT

The introduction of immune checkpoint inhibitors has demonstrated significant improvements in survival for subsets of cancer patients. However, they carry significant and sometimes life-threatening toxicities. Prompt prediction and monitoring of immune toxicities have the potential to maximise the benefits of immune checkpoint therapy. Herein, we develop a digital nanopillar SERS platform that achieves real-time single cytokine counting and enables dynamic tracking of immune toxicities in cancer patients receiving immune checkpoint inhibitor treatment - broader applications are anticipated in other disease indications. By analysing four prospective cytokine biomarkers that initiate inflammatory responses, the digital nanopillar SERS assay achieves both highly specific and highly sensitive cytokine detection down to attomolar level. Significantly, we report the capability of the assay to longitudinally monitor 10 melanoma patients during immune inhibitor blockade treatment. Here, we show that elevated cytokine concentrations predict for higher risk of developing severe immune toxicities in our pilot cohort of patients.


Subject(s)
Immunotherapy/methods , Melanoma/therapy , Monitoring, Immunologic/methods , Spectrum Analysis, Raman/methods , Chemokine CX3CL1/immunology , Chemokine CX3CL1/metabolism , Cohort Studies , Cytokines/immunology , Cytokines/metabolism , Granulocyte Colony-Stimulating Factor/immunology , Granulocyte Colony-Stimulating Factor/metabolism , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/immunology , Immune Checkpoint Inhibitors/therapeutic use , Ipilimumab/adverse effects , Ipilimumab/immunology , Ipilimumab/therapeutic use , Melanoma/immunology , Melanoma/metabolism , Microscopy, Confocal/methods , Pilot Projects , Reproducibility of Results
11.
Biomed Pharmacother ; 142: 111957, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1330662

ABSTRACT

The outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, in December 2019, and its global dissemination became the coronavirus disease 2019 (COVID-19) pandemic declared by the World Health Organization (WHO) on 11 March 2020. In patients undergoing immunotherapy, the effect and path of viral infection remain uncertain. In addition, viral-infected mice and humans show T-cell exhaustion, which is identified after infection with SARS-CoV-2. Notably, they regain their T-cell competence and effectively prevent viral infection when treated with anti-PD-1 antibodies. Four clinical trials are officially open to evaluate anti-PD-1 antibody administration's effectiveness for cancer and non-cancer individuals influenced by COVID-19 based on these findings. The findings may demonstrate the hypothesis that a winning strategy to combat SARS-CoV-2 infection could be the restoration of exhausted T-cells. In this review, we outline the potential protective function of the anti-PD-1 blockade against SARS-CoV-2 infection with the aim to develop SARS-CoV-2 therapy.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antiviral Agents/immunology , COVID-19/drug therapy , COVID-19/immunology , Humans , Immune Checkpoint Inhibitors/immunology , Immune Checkpoint Inhibitors/pharmacology , Immunotherapy/methods , Mice , Protective Agents/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , T-Lymphocytes/immunology
12.
Med Sci Monit ; 27: e934077, 2021 Jul 26.
Article in English | MEDLINE | ID: covidwho-1326004

ABSTRACT

Current treatments for patients with Alzheimer's disease aim to improve behavioral, cognitive, and non-cognitive symptoms. There have been no new drug approvals for preventing or treating Alzheimer's disease for more than two decades. Drug development in Alzheimer's disease aims to identify disease-modifying therapies that will delay or slow the clinical course of this disease. More than 50% of the current Alzheimer's disease drug pipeline now involves immunotherapies or oral small molecule agents. The most promising disease-modifying drug targets are amyloid ß and tau protein. In June 2021, aducanumab, a humanized recombinant monoclonal antibody to amyloid ß, was the first potential disease-modifying therapy approved by the US Food and Drug Administration (FDA) to treat Alzheimer's disease and mild cognitive impairment. Accelerated approval of aducanumab was based on the results of only one of two phase 3 clinical trials. Several clinical trials of targeted disease-modifying immunotherapies to the tau protein and amyloid ß that commenced before the current COVID-19 pandemic have been delayed. This Editorial aims to provide an update on past, present, and future disease-modifying therapies in Alzheimer's disease, including targeted therapies for amyloid ß and tau protein.


Subject(s)
Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , tau Proteins/metabolism , Antibodies, Monoclonal, Humanized/therapeutic use , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/immunology , Humans , Immunotherapy/methods , Immunotherapy/trends , Tauopathies/drug therapy
13.
Front Immunol ; 12: 673699, 2021.
Article in English | MEDLINE | ID: covidwho-1325526

ABSTRACT

Conventional vaccinations and immunotherapies have encountered major roadblocks in preventing infectious diseases like HIV, influenza, and malaria. These challenges are due to the high genomic variation and immunomodulatory mechanisms inherent to these diseases. Passive transfer of broadly neutralizing antibodies may offer partial protection, but these treatments require repeated dosing. Some recombinant viral vectors, such as those based on lentiviruses and adeno-associated viruses (AAVs), can confer long-term transgene expression in the host after a single dose. Particularly, recombinant (r)AAVs have emerged as favorable vectors, given their high in vivo transduction efficiency, proven clinical efficacy, and low immunogenicity profiles. Hence, rAAVs are being explored to deliver recombinant antibodies to confer immunity against infections or to diminish the severity of disease. When used as a vaccination vector for the delivery of antigens, rAAVs enable de novo synthesis of foreign proteins with the conformation and topology that resemble those of natural pathogens. However, technical hurdles like pre-existing immunity to the rAAV capsid and production of anti-drug antibodies can reduce the efficacy of rAAV-vectored immunotherapies. This review summarizes rAAV-based prophylactic and therapeutic strategies developed against infectious diseases that are currently being tested in pre-clinical and clinical studies. Technical challenges and potential solutions will also be discussed.


Subject(s)
Communicable Diseases/therapy , Dependovirus , Genetic Vectors , Immunotherapy/methods , Humans , Vaccines
14.
J Exp Clin Cancer Res ; 40(1): 240, 2021 Jul 23.
Article in English | MEDLINE | ID: covidwho-1322942

ABSTRACT

BACKGROUND: The yearly Think Tank Meeting of the Italian Network for Tumor Biotherapy (NIBIT) Foundation, brings together in Siena, Tuscany (Italy), experts in immuno-oncology to review the learnings from current immunotherapy treatments, and to propose new pre-clinical and clinical investigations in selected research areas. MAIN: While immunotherapies in non-small cell lung cancer and melanoma led to practice changing therapies, the same therapies had only modest benefit for patients with other malignancies, such as mesothelioma and glioblastoma. One way to improve on current immunotherapies is to alter the sequence of each combination agent. Matching the immunotherapy to the host's immune response may thus improve the activity of the current treatments. A second approach is to combine current immunotherapies with novel agents targeting complementary mechanisms. Identifying the appropriate novel agents may require different approaches than the traditional laboratory-based discovery work. For example, artificial intelligence-based research may help focusing the search for innovative and most promising combination partners. CONCLUSION: Novel immunotherapies are needed in cancer patients with resistance to or relapse after current immunotherapeutic drugs. Such new treatments may include targeted agents or monoclonal antibodies to overcome the immune-suppressive tumor microenvironment. The mode of combining the novel treatments, including vaccines, needs to be matched to the patient's immune status for achieving the maximum benefit. In this scenario, specific attention should be also paid nowadays to the immune intersection between COVID-19 and cancer.


Subject(s)
Neoplasms/immunology , Neoplasms/therapy , Antibodies, Monoclonal/immunology , COVID-19/immunology , Humans , Immunity/immunology , Immunotherapy/methods , Italy , Medical Oncology/methods
15.
J Immunother Cancer ; 9(7)2021 07.
Article in English | MEDLINE | ID: covidwho-1317020

ABSTRACT

The clinical and immunologic implications of the SARS-CoV-2 pandemic for patients with cancer receiving systemic anticancer therapy have introduced a multitude of clinical challenges and academic controversies. This review summarizes the current evidence, discussion points, and recommendations regarding the use of immune checkpoint inhibitors (ICIs) in patients with cancer during the SARS-CoV-2 pandemic, with a focus on patients with melanoma and renal cell carcinoma (RCC). More specifically, we summarize the theoretical concepts and available objective data regarding the relationships between ICIs and the antiviral immune response, along with recommended clinical approaches to the management of melanoma and RCC patient cohorts receiving ICIs throughout the course of the COVID-19 pandemic. Additional insights regarding the use of ICIs in the setting of current and upcoming COVID-19 vaccines and broader implications toward future pandemics are also discussed.


Subject(s)
COVID-19/immunology , Carcinoma, Renal Cell/immunology , Immune Checkpoint Inhibitors/immunology , Kidney Neoplasms/immunology , Melanoma/immunology , SARS-CoV-2/immunology , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Carcinoma, Renal Cell/therapy , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Kidney Neoplasms/therapy , Melanoma/therapy , Pandemics/prevention & control , SARS-CoV-2/drug effects
16.
J Immunother Cancer ; 8(2)2020 12.
Article in English | MEDLINE | ID: covidwho-1317007

ABSTRACT

BACKGROUND: Adenoviral vectors emerged as important platforms for cancer immunotherapy. Vaccination with adenoviral vectors is promising in this respect, however, their specific mechanisms of action are not fully understood. Here, we assessed the development and maintenance of vaccine-induced tumor-specific CD8+ T cells elicited upon immunization with adenoviral vectors. METHODS: Adenoviral vaccine vectors encoding the full-length E7 protein from human papilloma virus (HPV) or the immunodominant epitope from E7 were generated, and mice were immunized intravenously with different quantities (107, 108 or 109 infectious units). The magnitude, kinetics and tumor protection capacity of the induced vaccine-specific T cell responses were evaluated. RESULTS: The adenoviral vaccines elicited inflationary E7-specific memory CD8+ T cell responses in a dose-dependent manner. The magnitude of these vaccine-specific CD8+ T cells in the circulation related to the development of E7-specific CD8+ tissue-resident memory T (TRM) cells, which were maintained for months in multiple tissues after vaccination. The vaccine-specific CD8+ T cell responses conferred long-term protection against HPV-induced carcinomas in the skin and liver, and this protection required the induction and accumulation of CD8+ TRM cells. Moreover, the formation of CD8+ TRM cells could be enhanced by temporal targeting CD80/CD86 costimulatory interactions via CTLA-4 blockade early after immunization. CONCLUSIONS: Together, these data show that adenoviral vector-induced CD8+ T cell inflation promotes protective TRM cell populations, and this can be enhanced by targeting CTLA-4.


Subject(s)
Cancer Vaccines/immunology , Immunologic Memory/immunology , Immunotherapy/methods , Neoplasms/drug therapy , Animals , Humans , Mice , Neoplasms/immunology
17.
Med Sci Monit ; 27: e933088, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1314975

ABSTRACT

Synthetic mRNA and the expression of therapeutic proteins have accelerated vaccine development to prevent infection and heralds a new era in targeted immunotherapy in oncology. Therapeutic mRNA vaccines rely on available tumor tissue for gene sequencing analysis to compare the patient's normal cellular DNA sequences and those of the tumor. Carrier-based mRNA vaccines for cancer immunotherapy are now in development that use delivery systems based on peptides, lipids, polymers, and cationic nano-emulsions. There have also been recent developments in dendritic cell-based mRNA vaccines. For patients with available tumor tissue samples, it is possible to develop mRNA vaccines that result in the expression of tumor antigens by antigen-presenting cells (APCs), resulting in innate and adaptive immune responses. Ongoing developments in mRNA immunotherapy include modifications in the route of administration and combined delivery of multiple mRNA vaccines with checkpoint inhibitors. This Editorial aims to present a brief overview of how mRNA immunotherapy may change the therapeutic landscape of personalized medicine for patients with solid malignant tumors.


Subject(s)
Cancer Vaccines/immunology , Neoplasms/immunology , Neoplasms/therapy , RNA, Messenger/immunology , Vaccines, Synthetic/immunology , Humans , Immunotherapy/methods , Medical Oncology/methods , Precision Medicine/methods
18.
Int J Biol Macromol ; 186: 490-500, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1293830

ABSTRACT

Researchers from the world over are working to create prophylactic and therapeutic interventions to combat the COVID-19 global healthcare crisis. The current therapeutic options against the COVID-19 include repurposed drugs aimed at targets other than virus-specific proteins. Antibody-based therapeutics carry a lot of promise, and there are several of these candidates for COVID-19 treatment currently being investigated in the preclinical and clinical research stages around the world. The viral spike protein (S protein) appears to be the main target of antibody development candidates, with the majority being monoclonal antibodies. Several antibody candidates targeting the SARS-CoV-2 S protein include LY-CoV555, REGN-COV2, JS016, TY027, CT-P59, BRII-196, BRII-198 and SCTA01. These neutralizing antibodies will treat COVID-19 and possibly future coronavirus infections. Future studies should focus on effective immune-therapeutics and immunomodulators with the purpose of developing specific, affordable, and cost-effective prophylactic and treatment regimens to fight the COVID-19 globally.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/prevention & control , COVID-19/transmission , Immunotherapy/methods , Pandemics/prevention & control , COVID-19/epidemiology , COVID-19/immunology , Humans
19.
Front Immunol ; 12: 682850, 2021.
Article in English | MEDLINE | ID: covidwho-1285293

ABSTRACT

Objective: Serology could help to define the real extent of SARS-CoV-2 diffusion, especially in individuals considered at higher risk of COVID-19, such as spondyloarthritis (SpA) patients undergoing immunosuppressant. Our aim was to detect, by serology, previous SARS-CoV-2 contact in SpA, compared to health care workers (HCW), and healthy controls. Methods: Sera from consecutive patients affected by SpA undergoing cytokine-targeted therapy, HCW and healthy controls from 2015 were analysed through chemiluminescent analytical system for the presence of IgG and IgM anti-SARS-CoV-2. Positive patients (IgM or IgG, or both) additionally underwent real-time Polymerase-Chain-Reaction (RT-PCR) to test for active infection. Serology was repeated at 3-months in SpA. Data across 3 groups were compared by Kruskal Wallis/Chi-square, and between 2 groups by Wilcoxon rank test/Chi-Square. P ≤ 0.05 were considered significant. Results: 200 SpA, 95 HCW and 101 controls were recruited. Positive serology was found in 25(12.5%) SpA, 8(8.4%) HCW, 0(0%) controls (p=0.001). SpA patients with positive serology more frequently reported COVID-19-like symptoms than those with negative serology (20% vs. 4%, p=0.009) and 2 had COVID-19 as confirmed by RT-PCR, non severe. No HCW reported symptoms or had positive RT-PCR. In SpA patients, at 3 months, mean IgM titres decreased from 2.76 ± 2.93 to 2.38 ± 2.95 (p=0.001), while IgG titres from 0.89 ± 3.25 to 0.31 ± 0.87 (p=ns). Conclusions: Serology revealed that exposure to SARS-CoV-2 in SpA patients and HCW was higher than expected based on reported symptoms. In SpA, anti-cytokine therapy could act as a protective factor for a severe disease course. However, a seroconversion was not observed at 3-months.


Subject(s)
COVID-19/immunology , Immunosuppressive Agents/therapeutic use , Immunotherapy/methods , SARS-CoV-2/physiology , Spondylitis, Ankylosing/immunology , Adult , Aged , Antibodies, Viral/blood , Biotechnology , COVID-19/drug therapy , Cytokines/immunology , Female , Humans , Male , Middle Aged , Serology , Spondylitis, Ankylosing/drug therapy
20.
Front Immunol ; 12: 667862, 2021.
Article in English | MEDLINE | ID: covidwho-1285290

ABSTRACT

With the pandemic of COVID-19, maintenance of oral health has increasingly become the main challenge of global health. Various common oral diseases, such as periodontitis and oral cancer, are closely associated with immune disorders in the oral mucosa. Regulatory T cells (Treg) are essential for maintaining self-tolerance and immunosuppression. During the process of periodontitis and apical periodontitis, two typical chronic immune-inflammatory diseases, Treg contributes to maintain host immune homeostasis and minimize tissue damage. In contrast, in the development of oral precancerous lesions and oral cancer, Treg is expected to be depleted or down-regulated to enhance the anti-tumor immune response. Therefore, a deeper understanding of the distribution, function, and regulatory mechanisms of Treg cells may provide a prospect for the immunotherapy of oral diseases. In this review, we summarize the distribution and multiple roles of Treg in different oral diseases and discuss the possible mechanisms involved in Treg cell regulation, hope to provide a reference for future Treg-targeted immunotherapy in the treatment of oral diseases.


Subject(s)
COVID-19/immunology , Immunotherapy/methods , Mouth Neoplasms/immunology , Periodontitis/immunology , SARS-CoV-2/physiology , T-Lymphocytes, Regulatory/immunology , Animals , Humans , Immune Tolerance , Self Tolerance
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