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1.
Sci Rep ; 12(1): 20236, 2022 Nov 24.
Article in English | MEDLINE | ID: covidwho-2133578

ABSTRACT

Severe COVID-19 infection results in significant immune dysregulation resulting from excessive recruitment and activation of neutrophils. The aim of this study was to confirm feasibility, initial safety and detect signal of efficacy of a non-propriety device delivered using an intermittent extra-corporeal system (LMOD) allowing leucocytes modulation in the setting of Severe COVID-19 infection. Twelve patients were recruited. Inclusion criteria were > 18 years age, confirmed COVID-19, acute respiratory distress syndrome requiring mechanical support and hypotension requiring vasopressor support. Primary end point was vasopressor requirements (expressed as epinephrine dose equivalents) and principle secondary endpoints related to safety, ability to deliver the therapy and markers of inflammation assessed over five days after treatment initiation. LMOD treatment appeared safe, defined by hemodynamic stability and no evidence of white cell number depletion from blood. We demonstrated a significant decrease in vasopressor doses (-37%, p = 0.02) in patients receiving LMOD therapy (despite these patients having to tolerate an additional extracorporeal intermittent therapy). Vasopressor requirements unchanged/increasing in control group (+ 10%, p = 0.48). Although much about the use of this therapy in the setting of severe COVID-19 infection remains to be defined (e.g. optimal dose and duration), this preliminary study supports the further evaluation of this novel extracorporeal approach.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Humans , Critical Illness , Extracorporeal Membrane Oxygenation/methods , COVID-19/drug therapy , Immunomodulation , Vasoconstrictor Agents/therapeutic use
3.
Front Immunol ; 13: 923286, 2022.
Article in English | MEDLINE | ID: covidwho-2029962

ABSTRACT

Objectives: A major challenge for COVID-19 therapy is dysregulated immune response associated with the disease. Umbilical cord mesenchymal stromal cells (UC-MSCs) may be a promising candidate for COVID-19 treatment owing to their immunomodulatory and anti-inflammatory functions. Therefore, this study aimed to evaluate the effectiveness of UC-MSCs inpatients with COVID-19. Method: Medline, Embase, PubMed, Cochrane Library, and Web of Science databases were searched to collect clinical trials concerning UC-MSCs for the treatment of COVID-19. After literature screening, quality assessment, and data extraction, a systematic review and meta-analysis of the included study were performed. Results: This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022304061. After screening, 10 studies involving 293 patients with COVID-19 were eventually included. Our meta-analysis results showed that UC-MSCs can reduce mortality (relative risk [RR] =0.60, 95% confidence interval [CI]: [0.38, 0.95], P=0.03) in COVID-19 patients. No significant correlation was observed between adverse events and UC-MSC treatment (RR=0.85, 95% CI: [0.65, 1.10], P=0.22; RR=1.00, 95%CI: [0.64, 1.58], P=1.00). In addition, treatment with UC-MSCs was found to suppress inflammation and improve pulmonary symptoms. Conclusions: UC-MSCs hold promise as a safe and effective treatment for COVID-19. Systematic Review Registartion: PROSPERO, identifier CRD42022304061.


Subject(s)
COVID-19 , Mesenchymal Stem Cells , COVID-19/drug therapy , COVID-19/therapy , Humans , Immunomodulation , Umbilical Cord
4.
Front Immunol ; 13: 943333, 2022.
Article in English | MEDLINE | ID: covidwho-2022722

ABSTRACT

Mesenchymal stromal cell (MSC) therapy has seen increased attention as a possible option to treat a number of inflammatory conditions including COVID-19 acute respiratory distress syndrome (ARDS). As rates of obesity and metabolic disease continue to rise worldwide, increasing proportions of patients treated with MSC therapy will be living with obesity. The obese environment poses critical challenges for immunomodulatory therapies that should be accounted for during development and testing of MSCs. In this review, we look to cancer immunotherapy as a model for the challenges MSCs may face in obese environments. We then outline current evidence that obesity alters MSC immunomodulatory function, drastically modifies the host immune system, and therefore reshapes interactions between MSCs and immune cells. Finally, we argue that obese environments may alter essential features of allogeneic MSCs and offer potential strategies for licensing of MSCs to enhance their efficacy in the obese microenvironment. Our aim is to combine insights from basic research in MSC biology and clinical trials to inform new strategies to ensure MSC therapy is effective for a broad range of patients.


Subject(s)
COVID-19 , Mesenchymal Stem Cells , COVID-19/therapy , Cells, Cultured , Humans , Immunomodulation , Mesenchymal Stem Cells/metabolism , Obesity/metabolism , Obesity/therapy
5.
Int J Mol Sci ; 23(17)2022 Sep 02.
Article in English | MEDLINE | ID: covidwho-2010107

ABSTRACT

Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity of self-renewal, homing, and low immunogenicity. These distinct biological characteristics have already shown immense potential in regenerative medicine. MSCs also possess immunomodulatory properties that can maintain immune homeostasis when the immune response is over-activated or under-activated. The secretome of MSCs consists of cytokines, chemokines, signaling molecules, and growth factors, which effectively contribute to the regulation of immune and inflammatory responses. The immunomodulatory effects of MSCs can also be achieved through direct cell contact with microenvironmental factors and immune cells. Furthermore, preconditioned and engineered MSCs can specifically improve the immunomodulation effects in diverse clinical applications. These multifunctional properties of MSCs enable them to be used as a prospective therapeutic strategy to treat immune disorders, including autoimmune diseases and incurable inflammatory diseases. Here we review the recent exploration of immunomodulatory mechanisms of MSCs and briefly discuss the promotion of the genetically engineered MSCs. Additionally, we review the potential clinical applications of MSC-mediated immunomodulation in four types of immune diseases, including systemic lupus erythematosus, Crohn's disease, graft-versus-host disease, and COVID-19.


Subject(s)
COVID-19 , Immune System Diseases , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/therapy , Cytokines/metabolism , Humans , Immune System Diseases/metabolism , Immunity , Immunomodulation , Mesenchymal Stem Cells/metabolism
6.
Int J Mol Sci ; 23(15)2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1957348

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health challenge worldwide. Owing to the emergence of novel viral variants, the risks of reinfections and vaccine breakthrough infections has increased considerably despite a mass of vaccination. The formation of cytokine storm, which subsequently leads to acute respiratory distress syndrome, is the major cause of mortality in patients with COVID-19. Based on results of preclinical animal models and clinical trials of acute lung injury and acute respiratory distress syndrome, the immunomodulatory, tissue repair, and antiviral properties of MSCs highlight their potential to treat COVID-19. This review article summarizes the potential mechanisms and outcomes of MSC therapy in COVID-19, along with the pathogenesis of the SARS-CoV-2 infection. The properties of MSCs and lessons from preclinical animal models of acute lung injury are mentioned ahead. Important issues related to the use of MSCs in COVID-19 are discussed finally.


Subject(s)
Acute Lung Injury , COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Acute Lung Injury/etiology , Acute Lung Injury/therapy , Animals , COVID-19/therapy , Immunomodulation , Mesenchymal Stem Cell Transplantation/methods , Models, Animal , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , SARS-CoV-2
7.
Cells ; 11(14)2022 07 12.
Article in English | MEDLINE | ID: covidwho-1938702

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped, positive sense, single stranded RNA (+ssRNA) virus, belonging to the genus Betacoronavirus and family Coronaviridae. It is primarily transmitted from infected persons to healthy ones through inhalation of virus-laden respiratory droplets. After an average incubation period of 2-14 days, the majority of infected individuals remain asymptomatic and/or mildly symptomatic, whereas the remaining individuals manifest a myriad of clinical symptoms, including fever, sore throat, dry cough, fatigue, chest pain, and breathlessness. SARS-CoV-2 exploits the angiotensin converting enzyme 2 (ACE-2) receptor for cellular invasion, and lungs are amongst the most adversely affected organs in the body. Thereupon, immune responses are elicited, which may devolve into a cytokine storm characterized by enhanced secretion of multitude of inflammatory cytokines/chemokines and growth factors, such as interleukin (IL)-2, IL-6, IL-7, IL-8, IL-9, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (GCSF), basic fibroblast growth factor 2 (bFGF2), monocyte chemotactic protein-1 (MCP1), interferon-inducible protein 10 (IP10), macrophage inflammatory protein 1A (MIP1A), platelet-derived growth factor subunit B (PDGFB), and vascular endothelial factor (VEGF)-A. The systemic persistence of inflammatory molecules causes widespread histological injury, leading to functional deterioration of the infected organ(s). Although multiple treatment modalities with varying effectiveness are being employed, nevertheless, there is no curative COVID-19 therapy available to date. In this regard, one plausible supportive therapeutic modality may involve administration of mesenchymal stem cells (MSCs) and/or MSC-derived bioactive factors-based secretome to critically ill COVID-19 patients with the intention of accomplishing better clinical outcome owing to their empirically established beneficial effects. MSCs are well established adult stem cells (ASCs) with respect to their immunomodulatory, anti-inflammatory, anti-oxidative, anti-apoptotic, pro-angiogenic, and pro-regenerative properties. The immunomodulatory capabilities of MSCs are not constitutive but rather are highly dependent on a holistic niche. Following intravenous infusion, MSCs are known to undergo considerable histological trapping in the lungs and, therefore, become well positioned to directly engage with lung infiltrating immune cells, and thereby mitigate excessive inflammation and reverse/regenerate damaged alveolar epithelial cells and associated tissue post SARS-CoV-2 infection. Considering the myriad of abovementioned biologically beneficial properties and emerging translational insights, MSCs may be used as potential supportive therapy to counteract cytokine storms and reduce disease severity, thereby facilitating speedy recovery and health restoration.


Subject(s)
COVID-19 , Mesenchymal Stem Cells , Adult , COVID-19/therapy , Cytokine Release Syndrome , Humans , Immunity , Immunomodulation , Mesenchymal Stem Cells/metabolism , SARS-CoV-2
8.
BMC Complement Med Ther ; 22(1): 191, 2022 Jul 18.
Article in English | MEDLINE | ID: covidwho-1938309

ABSTRACT

BACKGROUND: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has a significant mortality rate of 3-5%. The principal causes of multiorgan failure and death are cytokine release syndrome and immune dysfunction. Stress, anxiety, and depression has been aggravated by the pandemic and its resultant restrictions in day-to-day life which may contribute to immune dysregulation. Thus, immunity strengthening and the prevention of cytokine release syndrome are important for preventing and minimizing mortality in COVID-19 patients. However, despite a few specific remedies that now exist for the SARS-CoV-2virus, the principal modes of prevention include vaccination, masking, and holistic healing methods, such as yoga. Currently, extensive research is being conducted to better understand the neuroendocrinoimmunological mechanisms by which yoga alleviates stress and inflammation. This review article explores the anti-inflammatory and immune-modulating potentials of yoga, along with its role in reducing risk for immune dysfunction and impaired mental health. METHODS: We conducted this narrative review from published literature in MEDLINE, EMBASE, COCHRANE databases. Screening was performed for titles and abstracts by two independent review authors; potentially eligible citations were retrieved for full-text review. References of included articles and articles of major non-indexed peer reviewed journals were searched for relevance by two independent review authors. A third review author checked the excluded records. All disagreements were resolved through discussion amongst review authors or through adjudication by a fourth review author. Abstracts, editorials, conference proceedings and clinical trial registrations were excluded. OBSERVATIONS: Yoga is a nonpharmacological, cost-effective, and safe intervention associated with several health benefits. Originating in ancient India, this vast discipline consists of postures (asanas), breathing techniques (pranayama), meditation (dhyana/dharana), and relaxation. Studies have demonstrated yoga's ability to bolster innate immunity and to inhibit cytokine release syndrome. As an intervention, yoga has been shown to improve mental health, as it alleviates anxiety, depression, and stress and enhances mindfulness, self-control, and self-regulation. Yoga has been correlated with numerous cardioprotective effects, which also may play a role in COVID-19 by preventing lung and cardiac injury. CONCLUSION AND RELEVANCE: This review paves the path for further research on yoga as a potential intervention for enhancing innate immunity and mental health and thus its role in prevention and adjunctive treatment in COVID-19.


Subject(s)
COVID-19 , Meditation , Yoga , Cytokine Release Syndrome , Humans , Immunomodulation , Mental Health
9.
Med Res Rev ; 42(2): 897-945, 2022 03.
Article in English | MEDLINE | ID: covidwho-1925975

ABSTRACT

Propolis is a complex natural product that possesses antioxidant, anti-inflammatory, immunomodulatory, antibacterial, and antiviral properties mainly attributed to the high content in flavonoids, phenolic acids, and their derivatives. The chemical composition of propolis is multifarious, as it depends on the botanical sources from which honeybees collect resins and exudates. Nevertheless, despite this variability propolis may have a general pharmacological value, and this review systematically compiles, for the first time, the existing preclinical and clinical evidence of propolis activities as an antiviral and immunomodulatory agent, focusing on the possible application in respiratory diseases. In vitro and in vivo assays have demonstrated propolis broad-spectrum effects on viral infectivity and replication, as well as the modulatory actions on cytokine production and immune cell activation as part of both innate and adaptive immune responses. Clinical trials confirmed propolis undeniable potential as an effective therapeutic agent; however, the lack of rigorous randomized clinical trials in the context of respiratory diseases is tangible. Since propolis is available as a dietary supplement, possible use for the prevention of respiratory diseases and their deleterious inflammatory drawbacks on the respiratory tract in humans is considered and discussed. This review opens up new perspectives on the clinical investigation of neglected propolis biological properties which, now more than ever, are particularly relevant with respect to the recent outbreaks of pandemic respiratory infections.


Subject(s)
Propolis , Animals , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Bees , Humans , Immunity , Immunomodulation , Propolis/chemistry , Propolis/pharmacology , Propolis/therapeutic use
10.
Innate Immun ; 28(6): 189-198, 2022 08.
Article in English | MEDLINE | ID: covidwho-1902320

ABSTRACT

At the end of 2019, an outbreak of a severe respiratory disease occurred in Wuhan China, and an increase in cases of unknown pneumonia was alerted. In January 2020, a new coronavirus named SARS-CoV-2 was identified as the cause. The virus spreads primarily through the respiratory tract, and lymphopenia and cytokine storms have been observed in severely ill patients. This suggests the existence of an immune dysregulation as an accompanying event during a serious illness caused by this virus. Natural killer (NK) cells are innate immune responders, critical for virus shedding and immunomodulation. Despite its importance in viral infections, the contribution of NK cells in the fight against SARS-CoV-2 has yet to be deciphered. Different studies in patients with COVID-19 suggest a significant reduction in the number and function of NK cells due to their exhaustion. In this review, we summarize the current understanding of how NK cells respond to SARS-CoV-2 infection.


Subject(s)
COVID-19 , Humans , Immunomodulation , Killer Cells, Natural , SARS-CoV-2
11.
Indian J Pediatr ; 89(12): 1236-1242, 2022 12.
Article in English | MEDLINE | ID: covidwho-1889047

ABSTRACT

OBJECTIVE: To determine the outcomes in children with MIS-C receiving different immunomodulatory treatment. METHODS: In this multicentric, retrospective cohort study, data regarding treatment and outcomes of children meeting the WHO case definition for MIS-C, were collected. The primary composite outcome was the requirement of vasoactive/inotropic support on day 2 or beyond or need of mechanical ventilation on day 2 or beyond after initiation of immunomodulatory treatment or death during hospitalization in the treatment groups. Logistic regression and propensity score matching analyses were used to compare the outcomes in different treatment arms based on the initial immunomodulation, i.e., IVIG alone, IVIG plus steroids, and steroids alone. RESULTS: The data of 368 children (diagnosed between April 2020 and June 2021) meeting the WHO case definition for MIS-C, were analyzed. Of the 368 subjects, 28 received IVIG alone, 82 received steroids alone, 237 received IVIG and steroids, and 21 did not receive any immunomodulation. One hundred fifty-six (42.39%) children had the primary outcome. On logistic regression analysis, the treatment group was not associated with the primary outcome; only the children with shock at diagnosis had higher odds for the occurrence of the outcome [OR (95% CI): 11.4 (5.19-25.0), p < 0.001]. On propensity score matching analysis, the primary outcome was comparable in steroid (n = 45), and IVIG plus steroid (n = 84) groups (p = 0.515). CONCLUSION: While no significant difference was observed in the frequency of occurrence of the primary outcome in different treatment groups, data from adequately powered RCTs are required for definitive recommendations.


Subject(s)
COVID-19 , Child , Humans , COVID-19/epidemiology , COVID-19/therapy , Immunoglobulins, Intravenous/therapeutic use , Retrospective Studies , Immunomodulation , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/therapy , Steroids/therapeutic use
13.
Molecules ; 27(7)2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1776290

ABSTRACT

Many mushroom species are consumed as food, while significant numbers are also utilised medicinally. Mushrooms are rich in nutrients and bioactive compounds. A growing body of in vitro, in vivo, and human research has revealed their therapeutic potentials, which include such properties as anti-pathogenic, antioxidant, anti-inflammatory, immunomodulatory, gut microbiota enhancement, and angiotensin-converting enzyme 2 specificity. The uses of medicinal mushrooms (MMs) as extracts in nutraceuticals and other functional food and health products are burgeoning. COVID-19 presents an opportunity to consider how, and if, specific MM compounds might be utilised therapeutically to mitigate associated risk factors, reduce disease severity, and support recovery. As vaccines become a mainstay, MMs may have the potential as an adjunct therapy to enhance immunity. In the context of COVID-19, this review explores current research about MMs to identify the key properties claimed to confer health benefits. Considered also are barriers or limitations that may impact general recommendations on MMs as therapy. It is contended that the extraction method used to isolate bioactive compounds must be a primary consideration for efficacious targeting of physiological endpoints. Mushrooms commonly available for culinary use and obtainable as a dietary supplement for medicinal purposes are included in this review. Specific properties related to these mushrooms have been considered due to their potential protective and mediating effects on human exposure to the SARS CoV-2 virus and the ensuing COVID-19 disease processes.


Subject(s)
Agaricales , COVID-19 , COVID-19/drug therapy , Dietary Supplements , Functional Food , Humans , Immunomodulation
14.
J Immunol ; 207(5): 1275-1287, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1771322

ABSTRACT

The airway epithelial cells (AECs) lining the conducting passageways of the lung secrete a variety of immunomodulatory factors. Among these, PGE2 limits lung inflammation and promotes bronchodilation. By contrast, IL-6 drives intense airway inflammation, remodeling, and fibrosis. The signaling that differentiates the production of these opposing mediators is not understood. In this study, we find that the production of PGE2 and IL-6 following stimulation of human AECs by the damage-associated molecular pattern extracellular ATP shares a common requirement for Ca2+ release-activated Ca2+ (CRAC) channels. ATP-mediated synthesis of PGE2 required activation of metabotropic P2Y2 receptors and CRAC channel-mediated cytosolic phospholipase A2 signaling. By contrast, ATP-evoked synthesis of IL-6 occurred via activation of ionotropic P2X receptors and CRAC channel-mediated calcineurin/NFAT signaling. In contrast to ATP, which elicited the production of both PGE2 and IL-6, the uridine nucleotide, UTP, stimulated PGE2 but not IL-6 production. These results reveal that human AECs employ unique receptor-specific signaling mechanisms with CRAC channels as a signaling nexus to regulate release of opposing immunomodulatory mediators. Collectively, our results identify P2Y2 receptors, CRAC channels, and P2X receptors as potential intervention targets for airway diseases.


Subject(s)
Dinoprostone/metabolism , Inflammation/immunology , Interleukin-6/metabolism , Respiratory Mucosa/metabolism , Adenosine Triphosphate/pharmacokinetics , Alarmins/metabolism , Calcium Release Activated Calcium Channels/metabolism , Cells, Cultured , Humans , Immunomodulation , Interleukin-6/genetics , NFATC Transcription Factors/metabolism , Phospholipases A2/metabolism , Receptors, Purinergic P2X/metabolism , Respiratory Mucosa/pathology , Signal Transduction , Uracil Nucleotides/metabolism
16.
Int J Mol Sci ; 23(3)2022 Feb 04.
Article in English | MEDLINE | ID: covidwho-1745038

ABSTRACT

This review article is focused on antihypertensive drugs, namely angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), and their immunomodulatory properties reported in hypertensive patients as well as in experimental settings involving studies on animal models and cell lines. The immune regulatory action of ACEI and ARB is mainly connected with the inhibition of proinflammatory cytokine secretion, diminished expression of adhesion molecules, and normalization of CRP concentration in the blood plasma. The topic has significant importance in future medical practice in the therapy of patients with comorbidities with underlying chronic inflammatory responses. Thus, this additional effect of immune regulatory action of ACEI and ARB may also benefit the treatment of patients with metabolic syndrome, allergies, or autoimmune disorders.


Subject(s)
Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Immunomodulation/drug effects , Animals , Antihypertensive Agents/pharmacology , COVID-19 , Humans
17.
Nat Rev Immunol ; 22(9): 576-588, 2022 09.
Article in English | MEDLINE | ID: covidwho-1744179

ABSTRACT

Blood vessel endothelial cells (ECs) have long been known to modulate inflammation by regulating immune cell trafficking, activation status and function. However, whether the heterogeneous EC populations in various tissues and organs differ in their immunomodulatory capacity has received insufficient attention, certainly with regard to considering them for alternative immunotherapy. Recent single-cell studies have identified specific EC subtypes that express gene signatures indicative of phagocytosis or scavenging, antigen presentation and immune cell recruitment. Here we discuss emerging evidence suggesting a tissue-specific and vessel type-specific immunomodulatory role for distinct subtypes of ECs, here collectively referred to as 'immunomodulatory ECs' (IMECs). We propose that IMECs have more important functions in immunity than previously recognized, and suggest that these might be considered as targets for new immunotherapeutic approaches.


Subject(s)
Endothelial Cells , Immune System , Antigen Presentation , Humans , Immunomodulation , Inflammation
18.
Int J Mol Sci ; 23(5)2022 Feb 24.
Article in English | MEDLINE | ID: covidwho-1736942

ABSTRACT

With the growing problem of the emergence of antibiotic-resistant bacteria, the search for alternative ways to combat bacterial infections is extremely urgent. While analyzing the effect of antimicrobial peptides (AMPs) on immunocompetent cells, their effect on all parts of the immune system, and on humoral and cellular immunity, is revealed. AMPs have direct effects on neutrophils, monocytes, dendritic cells, T-lymphocytes, and mast cells, participating in innate immunity. They act on B-lymphocytes indirectly, enhancing the induction of antigen-specific immunity, which ultimately leads to the activation of adaptive immunity. The adjuvant activity of AMPs in relation to bacterial and viral antigens was the reason for their inclusion in vaccines and made it possible to formulate the concept of a "defensin vaccine" as an innovative basis for constructing vaccines. The immunomodulatory function of AMPs involves their influence on cells in the nearest microenvironment, recruitment and activation of other cells, supporting the response to pathogenic microorganisms and completing the inflammatory process, thus exhibiting a systemic effect. For the successful use of AMPs in medical practice, it is necessary to study their immunomodulatory activity in detail, taking into account their pleiotropy. The degree of maturity of the immune system and microenvironment can contribute to the prevention of complications and increase the effectiveness of therapy, since AMPs can suppress inflammation in some circumstances, but aggravate the response and damage of organism in others. It should also be taken into account that the real functions of one or another AMP depend on the types of total regulatory effects on the target cell, and not only on properties of an individual peptide. A wide spectrum of biological activity, including direct effects on pathogens, inactivation of bacterial toxins and influence on immunocompetent cells, has attracted the attention of researchers, however, the cytostatic activity of AMPs against normal cells, as well as their allergenic properties and low stability to host proteases, are serious limitations for the medical use of AMPs. In this connection, the tasks of searching for compounds that selectively affect the target and development of an appropriate method of application become critically important. The scope of this review is to summarize the current concepts and newest advances in research of the immunomodulatory activity of natural and synthetic AMPs, and to examine the prospects and limitations of their medical use.


Subject(s)
Antimicrobial Cationic Peptides , Allergens/pharmacology , Antimicrobial Cationic Peptides/chemistry , Bacteria , Immunity, Innate , Immunomodulation
19.
Mult Scler Relat Disord ; 62: 103737, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1734832

ABSTRACT

BACKGROUND: Prior studies suggest reduced humoral response to COVID-19 vaccination in immunosuppressed populations. Disease modifying therapies (DMTs) for multiple sclerosis (MS) have variable immunomodulatory effects, and limited data are available for all DMTs. We aimed to determine the impact of DMTs on antibody response to COVID-19 vaccination among MS patients. METHODS: Patients with documented COVID-19 vaccination dates and anti-spike antibody results post-vaccination were identified between March-August 2021. Clinical data were retrospectively abstracted from chart review. Deidentified data were analyzed to evaluate antibody response, and multivariable logistic regression analyses were used to identify clinical and demographic predictors of antibody response. Data analysis was completed with SAS Studio, v3.8. RESULTS: A total of 353 individuals had documented COVID-19 vaccine and antibody test dates (58% Pfizer, 38% Moderna, and 4% Johnson & Johnson). Of these 353 patients, 72% developed antibodies, with a mean antibody test interval of 53 days (median 46) post final vaccine dose. 100% of those on no DMT (n = 34), injectables (n = 20), teriflunomide (n = 10), natalizumab (n = 71), and 97.8% of those on fumarates (n = 46/47) had a positive antibody result. One patient on cladribine (n = 1) had a negative antibody result. Of those on sphingosine-1 phosphate (S1P) modulators, 72.4% (n = 21/29) had a positive antibody result. Of those on anti-CD20 therapies, 37.6% (n = 53/141) had a positive antibody result. Multivariate modeling of the total cohort showed anti-CD20 therapy was significantly associated with lower odds of positive antibody response (OR = 0.024, 95% CI 0.01;0.05, p < 0.0001). Among S1P modulators, increased duration of therapy, and not lymphopenia, may be associated with lower odds of positive antibody response. Multivariate modeling of anti-CD20 therapies showed therapy duration < 1 year (OR 8.14, 95% CI 2.896;22.898 p < .0001) and prior COVID-19 infection (OR = 3.95, 95% CI 1.137;13.726, p = .03) were significantly associated with higher odds of a positive antibody response. In patients with recent B-cell data, mean B-cell count was higher in antibody-positive individuals compared to antibody-negative (32.9 vs. 3.9 cells, p = .0056). CONCLUSION: MS DMTs had variable impact on antibody response with mRNA and viral vector COVID-19 vaccines. All patients on no DMT, interferons, glatiramer acetate, teriflunomide, natalizumab, and nearly all on fumarates had positive antibody responses post-vaccine. S1P modulators and anti-CD20 therapies attenuated antibody response post-vaccine. For patients on anti-CD20 therapies, shorter duration of therapy and prior COVID-19 infection predicted positive antibody response. Further studies are needed to determine clinical significance of antibody testing, development of cellular mediated immunity, and benefits of booster vaccinations.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines , Fumarates , Humans , Immunomodulation , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/chemically induced , Multiple Sclerosis/drug therapy , Natalizumab/therapeutic use , Retrospective Studies
20.
Nutrients ; 12(6)2020 Jun 10.
Article in English | MEDLINE | ID: covidwho-1725886

ABSTRACT

Infection caused by the SARS-CoV-2 coronavirus worldwide has led the World Health Organization to declare a COVID-19 pandemic. Because there is no cure or treatment for this virus, it is emergingly urgent to find effective and validated methods to prevent and treat COVID-19 infection. In this context, alternatives related to nutritional therapy might help to control the infection. This narrative review proposes the importance and role of probiotics and diet as adjunct alternatives among the therapies available for the treatment of this new coronavirus. This review discusses the relationship between intestinal purine metabolism and the use of Lactobacillus gasseri and low-purine diets, particularly in individuals with hyperuricemia, as adjuvant nutritional therapies to improve the immune system and weaken viral replication, assisting in the treatment of COVID-19. These might be promising alternatives, in addition to many others that involve adequate intake of vitamins, minerals and bioactive compounds from food.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/therapy , Diet/methods , Immunomodulation/physiology , Pneumonia, Viral/therapy , Probiotics/therapeutic use , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/microbiology , Humans , Lactobacillus gasseri/immunology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/microbiology , Purines/immunology , Purines/metabolism , SARS-CoV-2 , Virus Replication/immunology
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