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1.
Stem Cell Res Ther ; 13(1): 126, 2022 03 25.
Article in English | MEDLINE | ID: covidwho-1759776

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has become in the spotlight regarding the serious early and late complications, including acute respiratory distress syndrome (ARDS), systemic inflammation, multi-organ failure and death. Although many preventive and therapeutic approaches have been suggested for ameliorating complications of COVID-19, emerging new resistant viral variants has called the efficacy of current therapeutic approaches into question. Besides, recent reports on the late and chronic complications of COVID-19, including organ fibrosis, emphasize a need for a multi-aspect therapeutic method that could control various COVID-19 consequences. Human amniotic epithelial cells (hAECs), a group of placenta-derived amniotic membrane resident stem cells, possess considerable therapeutic features that bring them up as a proposed therapeutic option for COVID-19. These cells display immunomodulatory effects in different organs that could reduce the adverse consequences of immune system hyper-reaction against SARS-CoV-2. Besides, hAECs would participate in alveolar fluid clearance, renin-angiotensin-aldosterone system regulation, and regeneration of damaged organs. hAECs could also prevent thrombotic events, which is a serious complication of COVID-19. This review focuses on the proposed early and late therapeutic mechanisms of hAECs and their exosomes to the injured organs. It also discusses the possible application of preconditioned and genetically modified hAECs as well as their promising role as a drug delivery system in COVID-19. Moreover, the recent advances in the pre-clinical and clinical application of hAECs and their exosomes as an optimistic therapeutic hope in COVID-19 have been reviewed.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Epithelial Cells , Female , Humans , Inflammation/therapy , Placenta , Pregnancy , Respiratory Distress Syndrome/therapy , SARS-CoV-2
2.
Sci Rep ; 12(1): 4801, 2022 03 21.
Article in English | MEDLINE | ID: covidwho-1751764

ABSTRACT

Ubiquitous microthromboses in the pulmonary vasculature play a crucial role in the pathogenesis of COVID-19 associated acute respiratory distress syndrome (ARDS). Excess of Willebrand factor (vWf) with intravascular multimer formation was identified as a key driver of this finding. Plasma exchange (PLEX) might be a therapeutic option to restore the disbalance between vWf and ADAMTS13. We report the effects of PLEX on vWf, ADAMTS13, inflammatory cytokines and parameters of ventilation. We investigated 25 patients, who were on mechanical ventilation for COVID-19 pneumonia with ARDS at two German university hospitals. All patients received PLEX as an ultima ratio measure for refractory ARDS. VWf antigen (vWf:Ag), ADAMTS13 activity, a cytokine panel mirroring the inflammatory situation and clinical parameters were assessed before and after three to six PLEX therapies with fresh frozen plasma. Before the PLEX sequence there was an excessive release of vWf:Ag (425.4 ± 167.5%) and mildly reduced ADAMTS13 activity (49.7 ± 23.3%). After the PLEX series, there was a significant increase of ADAMTS13 activity to 62.4 ± 17.7% (p = 0.029) and a significant decrease of vWf:Ag to 336.1 ± 138.2% (p = 0.041) resulting in a 63% improvement of the ADAMT13/vWf:Ag ratio from 14.5 ± 10.0 to 23.7 ± 14.6, p = 0.024. Comparison of parameters before and after individual PLEX sessions (n = 35) revealed a mean reduction of vWf from 387.8 ± 165.1 to 213.2 ± 62.3% (p = 0.001) and an increase of ADAMTS13 activity from 60.4 ± 20.1 to 70.5 ± 14.0% (p = 0.001). Parallelly, monocyte chemotactic protein-1 and interleukin-18 decreased significantly (p = 0.034 each). Along the PLEX sequence lactate dehydrogenase (p = 0.001), C-reactive protein (p = 0.001), and positive end expiratory pressure (p = 0.01) significantly decreased accompanied by an improvement of Horovitz index (p = 0.001). PLEX restores the disbalance between ADAMTS13 and vWf:Ag, a driver of immunothrombosis. Moreover, it reduces the inflammatory state and is associated with a benefit of ventilation parameters. These findings render a further rationale to regard PLEX as a therapeutic option in severe COVID-19.


Subject(s)
COVID-19 , Plasma Exchange , von Willebrand Factor , ADAMTS13 Protein/metabolism , COVID-19/therapy , Critical Illness/therapy , Humans , Inflammation/therapy , von Willebrand Factor/metabolism
3.
PLoS Pathog ; 18(1): e1010171, 2022 01.
Article in English | MEDLINE | ID: covidwho-1622378

ABSTRACT

The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Lung/virology , SARS-CoV-2/physiology , Virus Internalization , Adult , Animals , Antiviral Agents/pharmacology , COVID-19/immunology , COVID-19/pathology , Cells, Cultured , Chlorocebus aethiops , Drug Evaluation, Preclinical , Drugs, Investigational/pharmacology , Drugs, Investigational/therapeutic use , HEK293 Cells , Host-Pathogen Interactions/drug effects , Humans , Inflammation/pathology , Inflammation/therapy , Inflammation/virology , Lung/pathology , SARS-CoV-2/drug effects , Vero Cells , Virus Internalization/drug effects
4.
J Neuroinflammation ; 18(1): 123, 2021 May 31.
Article in English | MEDLINE | ID: covidwho-1571835

ABSTRACT

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is a member of the NLR family of inherent immune cell sensors. The NLRP3 inflammasome can detect tissue damage and pathogen invasion through innate immune cell sensor components commonly known as pattern recognition receptors (PRRs). PRRs promote activation of nuclear factor kappa B (NF-κB) pathways and the mitogen-activated protein kinase (MAPK) pathway, thus increasing the transcription of genes encoding proteins related to the NLRP3 inflammasome. The NLRP3 inflammasome is a complex with multiple components, including an NAIP, CIITA, HET-E, and TP1 (NACHT) domain; apoptosis-associated speck-like protein containing a CARD (ASC); and a leucine-rich repeat (LRR) domain. After ischemic stroke, the NLRP3 inflammasome can produce numerous proinflammatory cytokines, mediating nerve cell dysfunction and brain edema and ultimately leading to nerve cell death once activated. Ischemic stroke is a disease with high rates of mortality and disability worldwide and is being observed in increasingly younger populations. To date, there are no clearly effective therapeutic strategies for the clinical treatment of ischemic stroke. Understanding the NLRP3 inflammasome may provide novel ideas and approaches because targeting of upstream and downstream molecules in the NLRP3 pathway shows promise for ischemic stroke therapy. In this manuscript, we summarize the existing evidence regarding the composition and activation of the NLRP3 inflammasome, the molecules involved in inflammatory pathways, and corresponding drugs or molecules that exert effects after cerebral ischemia. This evidence may provide possible targets or new strategies for ischemic stroke therapy.


Subject(s)
Inflammasomes/drug effects , Inflammasomes/metabolism , Inflammation/metabolism , Inflammation/therapy , Ischemic Stroke/metabolism , Ischemic Stroke/therapy , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Animals , Brain/metabolism , Brain/pathology , COVID-19/complications , Humans
5.
Stem Cells Transl Med ; 10(12): 1588-1601, 2021 12.
Article in English | MEDLINE | ID: covidwho-1549284

ABSTRACT

Mesenchymal stem cells (MSCs) have natural immunoregulatory functions that have been explored for medicinal use as a cell therapy with limited success. A phase Ib study was conducted to evaluate the safety and immunoregulatory mechanism of action of MSCs using a novel ex vivo product (SBI-101) to preserve cell activity in patients with severe acute kidney injury. Pharmacological data demonstrated MSC-secreted factor activity that was associated with anti-inflammatory signatures in the molecular and cellular profiling of patient blood. Systems biology analysis captured multicompartment effects consistent with immune reprogramming and kidney tissue repair. Although the study was not powered for clinical efficacy, these results are supportive of the therapeutic hypothesis, namely, that treatment with SBI-101 elicits an immunotherapeutic response that triggers an accelerated phenotypic switch from tissue injury to tissue repair. Ex vivo administration of MSCs, with increased power of testing, is a potential new biological delivery paradigm that assures sustained MSC activity and immunomodulation.


Subject(s)
Acute Kidney Injury , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Acute Kidney Injury/therapy , Humans , Immunomodulation , Immunotherapy , Inflammation/therapy
6.
Stem Cells Transl Med ; 10(11): 1482-1490, 2021 11.
Article in English | MEDLINE | ID: covidwho-1490914

ABSTRACT

As our life expectancy increases, specific medical conditions appear, and new challenges are met in terms of global health. Frailty has become a medical and scientific concept to define pathologies where inflammation, depressed immune system, cellular senescence, and molecular aging converge. But more importantly, frailty is the ultimate cause of death that limits our life span and deteriorates health in an increasing proportion of the world population. The difficulty of tackling this problem is the combination of factors that influence frailty appearance, such as stem cells exhaustion, inflammation, loss of regeneration capability, and impaired immunomodulation. To date, multiple research fields have found mechanisms participating in this health condition, but to make progress, science will need to investigate frailty with an interdisciplinary approach. This article summarizes the current efforts to understand frailty from their processes mediated by inflammation, aging, and stem cells to provide a new perspective that unifies the efforts in producing advanced therapies against medical conditions in the context of frailty. We believe this approach against frailty is particularly relevant to COVID-19, since people in a state of frailty die more frequently due to the hyperinflammatory process associated with this infection.


Subject(s)
COVID-19 , Frailty , Inflammation/complications , Mesenchymal Stem Cell Transplantation , Aging/physiology , COVID-19/complications , COVID-19/therapy , Frailty/etiology , Frailty/therapy , Humans , Immunomodulation/physiology , Inflammation/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/trends , Mesenchymal Stem Cells/physiology , Regeneration/physiology , SARS-CoV-2 , Signal Transduction/physiology
7.
Front Immunol ; 12: 738697, 2021.
Article in English | MEDLINE | ID: covidwho-1477824

ABSTRACT

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19.


Subject(s)
COVID-19/therapy , Cell- and Tissue-Based Therapy/methods , Cytokine Release Syndrome/therapy , Mesenchymal Stem Cell Transplantation/methods , Cytokine Release Syndrome/pathology , Humans , Inflammation/therapy , Mesenchymal Stem Cells/immunology , SARS-CoV-2 , Sepsis/therapy
9.
Oxid Med Cell Longev ; 2021: 8671713, 2021.
Article in English | MEDLINE | ID: covidwho-1378091

ABSTRACT

The outbreak of the COVID-19 pandemic represents an ongoing healthcare emergency responsible for more than 3.4 million deaths worldwide. COVID-19 is the disease caused by SARS-CoV-2, a virus that targets not only the lungs but also the cardiovascular system. COVID-19 can manifest with a wide range of clinical manifestations, from mild symptoms to severe forms of the disease, characterized by respiratory failure due to severe alveolar damage. Several studies investigated the underlying mechanisms of the severe lung damage associated with SARS-CoV-2 infection and revealed that the respiratory failure associated with COVID-19 is the consequence not only of acute respiratory distress syndrome but also of macro- and microvascular involvement. New observations show that COVID-19 is an endothelial disease, and the consequent endotheliopathy is responsible for inflammation, cytokine storm, oxidative stress, and coagulopathy. In this review, we show the central role of endothelial dysfunction, inflammation, and oxidative stress in the COVID-19 pathogenesis and present the therapeutic targets deriving from this endotheliopathy.


Subject(s)
COVID-19/complications , Cytokine Release Syndrome/pathology , Endothelium, Vascular/pathology , Inflammation/pathology , Oxidative Stress , SARS-CoV-2/isolation & purification , Vascular Diseases/pathology , COVID-19/virology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/therapy , Endothelium, Vascular/virology , Humans , Inflammation/etiology , Inflammation/therapy , Vascular Diseases/etiology , Vascular Diseases/therapy
10.
Clin Immunol ; 231: 108842, 2021 10.
Article in English | MEDLINE | ID: covidwho-1372923

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 causes coronavirus disease 2019, a pandemic which was originated from Wuhan city of China. The pandemic has affected millions of people worldwide. The pathogenesis of SARS-CoV-2 is characterized by a cytokine storm in the blood (cytokinemia) and tissues, especially the lungs. One of the major repercussions of this inflammatory process is the endothelial injury-causing intestinal bleeding, coagulopathy, and thromboembolism which result in various sudden and unexpected post-COVID complications including kidney failure, myocardial infarction, or multiorgan failure. In this review, we have summarized the immune responses, biochemical changes, and inflammatory responses in the human body after infection with the SARS-CoV-2 virus. The increased amount of inflammatory cytokines, chemokines, and involvement of complement proteins in inflammatory reaction increase the risk of occurrence of disease.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Immunomodulation , Immunotherapy , SARS-CoV-2 , COVID-19/pathology , Humans , Inflammation/pathology , Inflammation/therapy
11.
Ann Palliat Med ; 10(7): 7468-7478, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1344618

ABSTRACT

BACKGROUND: Previous studies have reported that C reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in Coronavirus disease 2019 (COVID-19) patients are significantly increased, and their progressive increases are clinical warning indicators of severe and critical severity. The purpose of this meta-analysis is to evaluate the efficacy of Tai Chi on CRP, TNF-alpha and IL-6, and provide a basis for complementary treatment of COVID-19. METHODS: Five English databases (PubMed, Web of Science, Physiotherapy Evidence Database, Cochrane Library and Embase) and four Chinese electronic databases (CNKI, Wanfang, China Science and Technology Journal Database and SinoMed) were searched from inception to April 1st, 2020. Combination MeSH and free text terms were used to make up search strategy. Interventions in RCTs were Tai Chi with or without comparison (usual care, health education, drug therapy, psychosocial therapy). Revman version 5.3 was used to analyze the extracted data. Continuous outcomes were described by SMD, and the I2 test was used to assess heterogeneity. Revised Physiotherapy Evidence Database scale was used to assess methodological quality. RESULTS: Nine RCTs involving 571 participants met the inclusion criteria, and the sample size ranged from 19 to 100 per study. Tai Chi can significantly reduce TNF-alpha (Tai Chi intervention: SMD =-0.92, 95% CI: -1.32 to -0.53; Tai Chi plus drug treatment intervention: SMD =-0.63, 95% CI: -1.15 to -0.11), moreover, it could reduce the amount of IL-6 (Tai Chi intervention: SMD =-0.62, 95% CI: -1.00 to -0.23; Tai Chi plus drug treatment intervention: SMD =-2.17, 95% CI: -3.69 to -0.64) and CRP (Tai Chi plus drug treatment intervention: SMD =-1.98, 95% CI: -2.47 to -1.50) while with a high exercise amount. A low exercise amount of Tai Chi showed poor efficacy on CRP (Tai Chi intervention: SMD =-0.18, 95% CI: -0.61 to 0.25; Tai Chi plus drug treatment intervention: SMD =-0.15, 95% CI: -0.47 to 0.16) and IL-6 (Tai Chi intervention: SMD =0.15, 95% CI: -0.24 to 0.55). DISCUSSION: The strength of evidence might be limited due to relatively low methodological quality, heterogeneity and indirectness. The overall results elucidate that Tai Chi could significantly reduce TNF-alpha while it did not show the same effects in IL-6 and CRP. After subgroup analysis, Tai Chi with a high exercise amount can reduce IL-6 and CRP. Tai Chi with a high exercise amount could be suggested as a complementary intervention for people with COVID-19. TRIAL REGISTRATION: PROSPERO CRD42020177655.


Subject(s)
COVID-19 , Tai Ji , C-Reactive Protein , Humans , Inflammation/therapy , Interleukin-6 , SARS-CoV-2 , Tumor Necrosis Factor-alpha
12.
Metabolism ; 123: 154845, 2021 10.
Article in English | MEDLINE | ID: covidwho-1340768

ABSTRACT

PURPOSE: Individuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications. METHODS: We prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia. RESULTS: Among 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p = 0.001), fasting blood glucose (HR 4.32, p < 0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p = 0.010) or fasting blood glucose ≥7 mmol/L (HR 3.07, p = 0.015). CONCLUSIONS: Thromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Hyperglycemia/epidemiology , Thromboembolism/etiology , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/diagnosis , COVID-19/therapy , Diabetes Complications/diagnosis , Diabetes Complications/epidemiology , Diabetes Complications/therapy , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Diabetes Mellitus/therapy , Female , Follow-Up Studies , Hospitalization/statistics & numerical data , Humans , Hyperglycemia/diagnosis , Hyperglycemia/etiology , Hyperglycemia/therapy , Inflammation/complications , Inflammation/diagnosis , Inflammation/epidemiology , Inflammation/therapy , Italy/epidemiology , Male , Middle Aged , Mortality , Prognosis , Risk Factors , Stress, Psychological/complications , Stress, Psychological/diagnosis , Stress, Psychological/epidemiology , Thromboembolism/diagnosis , Thromboembolism/epidemiology , Treatment Outcome
13.
Life Sci Alliance ; 4(9)2021 09.
Article in English | MEDLINE | ID: covidwho-1332524

ABSTRACT

The use of high-dose of intravenous immunoglobulins (IVIGs) as immunomodulators for the treatment of COVID-19-affected individuals has shown promising results. IVIG reduced inflammation in these patients, who progressively restored respiratory function. However, little is known about how they may modulate immune responses in COVID-19 individuals. Here, we have analyzed the levels of 41 inflammatory biomarkers in plasma samples obtained at day 0 (pretreatment initiation), 3, 7, and 14 from five hospitalized COVID-19 patients treated with a 5-d course of 400 mg/kg/d of IVIG. The plasmatic levels of several cytokines (Tumor Necrosis Factor, IL-10, IL-5, and IL-7), chemokines (macrophage inflammatory protein-1α), growth/tissue repairing factors (hepatic growth factor), complement activation (C5a), and intestinal damage such as Fatty acid-binding protein 2 and LPS-binding protein showed a progressive decreasing trend during the next 2 wk after treatment initiation. This trend was not observed in IVIG-untreated COVID-19 patients. Thus, the administration of high-dose IVIG to hospitalized COVID-19 patients may improve their clinical evolution by modulating their hyperinflammatory and immunosuppressive status.


Subject(s)
COVID-19/therapy , Immunoglobulins, Intravenous/therapeutic use , Administration, Intravenous , Adult , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Chemokines/blood , Cytokines/blood , Female , Humans , Immunity/immunology , Immunoglobulins/immunology , Immunoglobulins/therapeutic use , Immunoglobulins, Intravenous/immunology , Inflammation/blood , Inflammation/therapy , Inflammation/virology , Male , Middle Aged , SARS-CoV-2/isolation & purification
14.
Br J Haematol ; 194(3): 518-529, 2021 08.
Article in English | MEDLINE | ID: covidwho-1266318

ABSTRACT

The COVID-19 pandemic has been the most significant health crisis in recent global history. Early studies from Wuhan highlighted COVID-19-associated coagulopathy and a significant association with mortality was soon recognised. As research continues across the world, more evidence is emerging of the cross-talk between the innate immune system, coagulation activation and inflammation. Immunothrombosis has been demonstrated to play a key role in the pathophysiology of severe COVID-19, with extracellular histones and neutrophil extracellular traps detected in the plasma and cardiopulmonary tissues of critically ill patients. Targeting the components of immunothrombosis is becoming an important factor in the treatment of patients with COVID-19 infection. Recent studies report outcomes of intermediate and therapeutic anticoagulation in hospitalised patients with varying severities of COVID-19 disease, including optimal dosing and associated bleeding risks. Immunomodulatory therapies, including corticosteroids and IL-6 receptor antagonists, have been demonstrated to significantly reduce mortality in COVID-19 patients. As the pandemic continues, more studies are required to understand the driving factors and upstream mechanisms for coagulopathy and immunothrombosis in COVID-19, and thus potentially develop more targeted therapies for SARS-CoV-2 infection, both in the acute phase and in those who develop longer-term symptom burden.


Subject(s)
COVID-19/complications , Thrombosis/etiology , Animals , Blood Coagulation , COVID-19/blood , COVID-19/immunology , COVID-19/therapy , Disease Management , Humans , Immunogenic Cell Death , Inflammation/blood , Inflammation/etiology , Inflammation/immunology , Inflammation/therapy , SARS-CoV-2/immunology , Thrombosis/blood , Thrombosis/immunology , Thrombosis/therapy
15.
Int Immunopharmacol ; 96: 107761, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1253056

ABSTRACT

Since the discovery of lymphocytes with immunosuppressive activity, increasing interest has arisen in their possible influence on the immune response induced by vaccines. Regulatory T cells (Tregs) are essential for maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory diseases. However, they also limit beneficial immune responses by suppressing anti-infectious and anti-tumor immunity. Mounting evidence suggests that Tregs are involved, at least in part, in the low effectiveness of immunization against various diseases where it has been difficult to obtain protective vaccines. Interestingly, increased activity of Tregs is associated with aging, suggesting a key role for these cells in the lower vaccine effectiveness observed in older people. In this review, we analyze the impact of Tregs on vaccination, with a focus on older adults. Finally, we address an overview of current strategies for Tregs modulation with potential application to improve the effectiveness of future vaccines targeting older populations.


Subject(s)
Autoimmune Diseases/therapy , Chronic Disease/therapy , Inflammation/therapy , T-Lymphocytes, Regulatory/physiology , Vaccines/immunology , Age Factors , Aged , Aged, 80 and over , Animals , Autoimmune Diseases/immunology , Humans , Immunologic Factors/pharmacology , Immunomodulation/physiology , Immunosuppressive Agents/pharmacology , Inflammation/immunology , Membrane Proteins/metabolism , Middle Aged , Vaccination
16.
Biochimie ; 187: 94-109, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1252495

ABSTRACT

Despite the development of a number of vaccines for COVID-19, there remains a need for prevention and treatment of the virus SARS-CoV-2 and the ensuing disease COVID-19. This report discusses the key elements of SARS-CoV-2 and COVID-19 that can be readily treated: viral entry, the immune system and inflammation, and the cytokine storm. It is shown that the essential nutrients zinc, ω-3 polyunsaturated fatty acids (PUFAs), vitamin D and magnesium provide the ideal combination for prevention and treatment of COVID-19: prevention of SARS-CoV-2 entry to host cells, prevention of proliferation of SARS-CoV-2, inhibition of excessive inflammation, improved control of the regulation of the immune system, inhibition of the cytokine storm, and reduction in the effects of acute respiratory distress syndrome (ARDS) and associated non-communicable diseases. It is emphasized that the non-communicable diseases associated with COVID-19 are inherently more prevalent in the elderly than the young, and that the maintenance of sufficiency of zinc, ω-3 PUFAs, vitamin D and magnesium is essential for the elderly to prevent the occurrence of non-communicable diseases such as diabetes, cardiovascular diseases, lung diseases and cancer. Annual checking of levels of these essential nutrients is recommended for those over 65 years of age, together with appropriate adjustments in their intake, with these services and supplies being at government cost. The cost:benefit ratio would be huge as the cost of the nutrients and the testing of their levels would be very small compared with the cost savings of specialists and hospitalization.


Subject(s)
COVID-19/prevention & control , Fatty Acids, Omega-3/therapeutic use , Magnesium/therapeutic use , Noncommunicable Diseases/prevention & control , Vitamin D/therapeutic use , Zinc/therapeutic use , Aged , COVID-19/therapy , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/therapy , Cytokine Release Syndrome/therapy , Diabetes Mellitus/prevention & control , Diabetes Mellitus/therapy , Humans , Inflammation/therapy , Lung Diseases/prevention & control , Lung Diseases/therapy , Neoplasms/prevention & control , Neoplasms/therapy , Noncommunicable Diseases/therapy , Nutritional Status , SARS-CoV-2 , Vitamins/therapeutic use
17.
Inflamm Res ; 70(6): 731-742, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1222757

ABSTRACT

OBJECTIVE: To investigate whether a simplified inflammation-based risk scoring system comprising three readily available biomarkers (albumin, C-reactive protein, and leukocytes) may predict major adverse outcomes in patients with COVID-19. METHODS: Upon admission to the emergency room, the inflammation-based risk scoring system was applied and patients were classified as having mild, moderate, or severe inflammation. In-hospital occurrence of thrombosis, need for mechanical ventilation, and death were recorded. RESULTS: One-hundred patients (55 ± 13 years; 71% men) were included and classified as having mild (29%), moderate (12%), or severe (59%) inflammation. The need for mechanical ventilation differed among patients in each group (16%, 50%, and 71%, respectively; P < 0.0001), yielding a 4.1-fold increased risk of requiring mechanical ventilation in patients with moderate inflammation and 5.4 for those with severe inflammation. On the contrary, there were no differences for the occurrence of thrombosis (10%, 8%, and 22%, respectively; P = 0.142) or death (21%, 42%, and 39%, respectively; P = 0.106). In the multivariate analysis, only severe inflammation (hazard ratio [HR] = 4.1), D-dimer > 574 ng/mL (HR = 3.0), and troponin I ≥ 6.7 ng/mL (HR = 2.4) at hospital admission were independent predictors of the need for mechanical ventilation. CONCLUSION: The inflammation-based risk scoring system predicts the need for mechanical ventilation in patients with severe COVID-19.


Subject(s)
COVID-19/therapy , Respiration, Artificial , SARS-CoV-2 , Severity of Illness Index , Adult , Aged , Biomarkers/blood , COVID-19/blood , Female , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization , Humans , Inflammation/blood , Inflammation/therapy , Male , Middle Aged , Proportional Hazards Models , Risk Factors , Troponin I/blood
18.
Am J Physiol Heart Circ Physiol ; 320(6): H2240-H2254, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1180981

ABSTRACT

The outbreak of severe acute respiratory syndrome coronavirus 2 that first emerged in Wuhan in December 2019 has resulted in the devastating pandemic of coronavirus disease 2019, creating an emerging need for knowledge sharing. Meanwhile, myocardial infarction is and will probably remain the foremost cause of death in the Western world throughout the coming decades. Severe deregulation of the immune system can unnecessarily expand the inflammatory response and participate in target and multiple organ failure, in infection but also in critical illness. Indeed, the course and fate of inflammatory cells observed in severe ST-elevation myocardial infarction (neutrophilia, monocytosis, and lymphopenia) almost perfectly mirror those recently reported in severe coronavirus disease 2019. A pleiotropic proinflammatory imbalance hampers adaptive immunity in favor of uncontrolled innate immunity and is associated with poorer structural and clinical outcomes. The goal of the present review is to gain greater insight into the cellular and molecular mechanisms underlying this canonical activation and downregulation of the two arms of the immune response in both entities, to better understand their pathophysiology and to open the door to innovative therapeutic options. Knowledge sharing can pave the way for therapies with the potential to significantly reduce mortality in both infectious and noninfectious scenarios.


Subject(s)
COVID-19/immunology , Immune System/physiopathology , ST Elevation Myocardial Infarction/immunology , COVID-19/complications , Humans , Inflammation/etiology , Inflammation/therapy , Myocardial Infarction/etiology , ST Elevation Myocardial Infarction/complications
20.
Aging (Albany NY) ; 13(7): 9243-9252, 2021 04 03.
Article in English | MEDLINE | ID: covidwho-1168300

ABSTRACT

BACKGROUND: Coronavirus disease (COVID-19) has spread rapidly since 2019. Approximately 15% of the patients will develop severe complications such as multiple organ disease syndrome related to cytokine release syndrome (CRS). Continuous renal replacement therapy (CRRT) can remove inflammatory cytokines through filtration or adsorption. We evaluated the effectiveness of CRRT in COVID-19 patients with CRS. METHODS: This retrospective, multicenter, descriptive study included 83 patients with CRS from three hospitals in Wuhan. RESULTS: In COVID-19 patients with CRS, the fatality rate was even higher in CRRT group (P=0.005). However, inflammatory markers such as C-reactive protein, neutrophil counts, and D-dimer decreased after CRRT (P<0.05). Results of Lasso model showed that tracheotomy (ß -1.31) and convalescent plasma (ß -1.41) were the protective factors. In contrast, CRRT (ß 1.07), respiratory failure (ß 1.61), consolidation on lung CT (ß 0.48), acute kidney injury (AKI) (ß 0.47), and elevated neutrophil count (ß 0.02) were the risk factors for death. CONCLUSIONS: Our results showed that although CRRT significantly reduced the inflammation, it did not decrease the fatality rate of patients with CRS. Therefore, the choice of CRRT indication, dialysis time and dialysis mode should be more careful and accurate in COVID-19 patients with CRS.


Subject(s)
COVID-19/therapy , Continuous Renal Replacement Therapy , Critical Illness/therapy , Cytokine Release Syndrome/therapy , Aged , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , China , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Inflammation/blood , Inflammation/etiology , Inflammation/therapy , Male , Middle Aged , SARS-CoV-2/isolation & purification , Treatment Outcome
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