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1.
J Leukoc Biol ; 111(2): 497-508, 2022 02.
Article in English | MEDLINE | ID: covidwho-1669515

ABSTRACT

Coronaviruses (CoVs) are RNA viruses that cause human respiratory infections. Zoonotic transmission of the SARS-CoV-2 virus caused the recent COVID-19 pandemic, which led to over 2 million deaths worldwide. Elevated inflammatory responses and cytotoxicity in the lungs are associated with COVID-19 severity in SARS-CoV-2-infected individuals. Bats, which host pathogenic CoVs, operate dampened inflammatory responses and show tolerance to these viruses with mild clinical symptoms. Delineating the mechanisms governing these host-specific inflammatory responses is essential to understand host-virus interactions determining the outcome of pathogenic CoV infections. Here, we describe the essential role of inflammasome activation in determining COVID-19 severity in humans and innate immune tolerance in bats that host several pathogenic CoVs. We further discuss mechanisms leading to inflammasome activation in human SARS-CoV-2 infection and how bats are molecularly adapted to suppress these inflammasome responses. We also report an analysis of functionally important residues of inflammasome components that provide new clues of bat strategies to suppress inflammasome signaling and innate immune responses. As spillover of bat viruses may cause the emergence of new human disease outbreaks, the inflammasome regulation in bats and humans likely provides specific strategies to combat the pathogenic CoV infections.


Subject(s)
COVID-19/pathology , Immune Tolerance , Immunity, Innate , Inflammasomes/immunology , SARS-CoV-2/immunology , Animals , COVID-19/immunology , COVID-19/virology , Chiroptera , Humans , Inflammasomes/metabolism , Phylogeny
2.
Am J Trop Med Hyg ; 104(5): 1611-1612, 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1273618

ABSTRACT

COVID-19 can trigger a systemic inflammatory response that in some cases leads to severe lung involvement, multisystem dysfunction, and death. Dexamethasone therapy, because of its potent anti-inflammatory effects, has been proposed for the management of hospitalized patients with severe COVID-19. The subject of this article is to discuss potential strategies to tackle Strongyloides hyperinfection in hospitalized patients with COVID-19 receiving dexamethasone therapy in low- and middle-income countries. In this context, dexamethasone treatment has been found to be generally safe. However, its use in people coinfected with undetected Strongyloides stercoralis increases the risk for Strongyloides hyperinfection/dissemination a potentially fatal complication. Infection caused by S. stercoralis may remain asymptomatic or with mild symptoms in humans for several years. Early detection and specific treatment prevent a fatal evolution of this complication, but the challenge is to screen before corticosteroid therapy. In some cases, presumptive treatment may be justified. Ivermectin is the gold standard for treatment.


Subject(s)
COVID-19/drug therapy , Dexamethasone/adverse effects , SARS-CoV-2 , Strongyloides stercoralis , Strongyloidiasis/etiology , Animals , Developing Countries , Strongyloidiasis/drug therapy
3.
Cardiovasc Res ; 117(10): 2148-2160, 2021 08 29.
Article in English | MEDLINE | ID: covidwho-1266112

ABSTRACT

The pandemic of coronavirus disease (COVID)-19 is a global threat, causing high mortality, especially in the elderly. The main symptoms and the primary cause of death are related to interstitial pneumonia. Viral entry also into myocardial cells mainly via the angiotensin converting enzyme type 2 (ACE2) receptor and excessive production of pro-inflammatory cytokines, however, also make the heart susceptible to injury. In addition to the immediate damage caused by the acute inflammatory response, the heart may also suffer from long-term consequences of COVID-19, potentially causing a post-pandemic increase in cardiac complications. Although the main cause of cardiac damage in COVID-19 remains coagulopathy with micro- (and to a lesser extent macro-) vascular occlusion, open questions remain about other possible modalities of cardiac dysfunction, such as direct infection of myocardial cells, effects of cytokines storm, and mechanisms related to enhanced coagulopathy. In this opinion paper, we focus on these lesser appreciated possibilities and propose experimental approaches that could provide a more comprehensive understanding of the cellular and molecular bases of cardiac injury in COVID-19 patients. We first discuss approaches to characterize cardiac damage caused by possible direct viral infection of cardiac cells, followed by formulating hypotheses on how to reproduce and investigate the hyperinflammatory and pro-thrombotic conditions observed in the heart of COVID-19 patients using experimental in vitro systems. Finally, we elaborate on strategies to discover novel pathology biomarkers using omics platforms.


Subject(s)
COVID-19/virology , Heart Diseases/virology , Heart/virology , Myocytes, Cardiac/virology , SARS-CoV-2/pathogenicity , Animals , Biomarkers/metabolism , Blood Coagulation , COVID-19/complications , Fibrosis , Heart/physiopathology , Heart Diseases/metabolism , Heart Diseases/pathology , Heart Diseases/physiopathology , Host-Pathogen Interactions , Humans , Inflammation Mediators/metabolism , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Ventricular Remodeling
4.
J Infect Dev Ctries ; 15(5): 630-638, 2021 05 31.
Article in English | MEDLINE | ID: covidwho-1262629

ABSTRACT

INTRODUCTION: Viral infections have been described as triggers for Kawasaki Disease (KD), a medium vessel vasculitis that affects young children. Akin to the H1N1 pandemic in 2009, there is a similar rise in the incidence of KD in children affected with Coronavirus disease 2019 (COVID-19). Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has been reported to induce an exaggerated systemic inflammatory response resulting in multi-organ involvement, particularly initiated with pulmonary parenchymal damage. This review article will discuss KD-like manifestations in COVID-19 patients in the pediatric cohort. METHODOLOGY: Search terms "Kawasaki" "COVID-19" "SARS-COV-2" "PIM-TS" and "MIS-C" were used to look for relevant articles in PubMed and Google Scholar published in the last 5 years. RESULTS: There is some evidence to suggest that SARS-CoV-2 stimulates dysfunctional and hyperactive immune reactions mimicking KD in young patients. CONCLUSIONS: Therapeutic options, both investigational and repurposed, include intravenous immunoglobulins, steroids and anticoagulation. More studies are required to evaluate the effectiveness of these treatment options.


Subject(s)
COVID-19/complications , Mucocutaneous Lymph Node Syndrome , Child , Humans , Immunoglobulins, Intravenous/therapeutic use , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/physiopathology , Mucocutaneous Lymph Node Syndrome/virology , SARS-CoV-2
5.
Scand J Clin Lab Invest ; 81(4): 255-263, 2021 07.
Article in English | MEDLINE | ID: covidwho-1242057

ABSTRACT

Coronaviruses belonging to the Coronaviridae family are single-stranded RNA viruses. The entry of SARS-CoV-2 is accomplished via ACE-2 receptors. SARS-CoV-2 infection coactivates both innate and adaptive immune responses. Although SARS-CoV-2 stimulates antibody production with a typical pattern of IgM/IgG, cellular immunity is also impaired. In severe cases, low CD4 + and CD8 + T cell counts are associated with impaired immune functions, and high neutrophil/lymphocyte ratios accompanying low lymphocyte subsets have been demonstrated. Recently, high IFN -α/γ ratios with impaired T cell responses, and increased IL-1, IL-6, TNF-α, MCP-1, IP-10, IL-4, IL-10 have been reported in COVID-19 infection. Increased proinflammatory cytokines and chemokines in patients with severe COVID-19 may cause the suppression of CD4 + and CD8 + T cells and regulatory T cells, causing excessive inflammatory responses and fatal cytokine storm with tissue and organ damage. Consequently, novel therapeutics to be developed against host immune system, including blockade of cytokines (IL-6, IL-1, IFN) themselves, their receptors or signaling pathways- JAK inhibitors- could be effective as potential therapeutics.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/immunology , COVID-19/physiopathology , Adrenal Cortex Hormones/therapeutic use , Animals , Antiviral Agents/therapeutic use , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/virology , Cytokines/antagonists & inhibitors , Cytokines/metabolism , Glucocorticoids/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Immunotherapy/methods , Macrophages/immunology , Macrophages/pathology , Macrophages/virology
6.
World J Gastroenterol ; 27(19): 2341-2352, 2021 May 21.
Article in English | MEDLINE | ID: covidwho-1239023

ABSTRACT

Gastrointestinal (GI) symptoms, such as diarrhea, abdominal pain, vomiting, and anorexia, are frequently observed in patients with coronavirus disease 2019 (COVID-19). However, the pathophysiological mechanisms connecting these GI symptoms to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remain elusive. Previous studies indicate that the entry of SARS-CoV-2 into intestinal cells leads to downregulation of angiotensin converting enzyme 2 (ACE2) receptors resulting in impaired barrier function. While intestinal ACE2 functions as a chaperone for the amino acid transporter B0AT1, the B0AT1/ACE2 complex within the intestinal epithelium acts as a regulator of gut microbiota composition and function. Alternations to the B0AT1/ACE2 complex lead to microbial dysbiosis through increased local and systemic immune responses. Previous studies have also suggested that altered serotonin metabolism may be the underlying cause of GI disorders involving diarrhea. The findings of elevated plasma serotonin levels and high fecal calprotectin in COVID-19 patients with diarrhea indicate that the viral infection evokes a systemic inflammatory response that specifically involves the GI. Interestingly, the elevated proinflammatory cytokines correlate with elevated serotonin and fecal calprotectin levels further supporting the evidence of GI inflammation, a hallmark of functional GI disorders. Moreover, the finding that rectal swabs of COVID-19 patients remain positive for SARS-CoV-2 even after the nasopharynx clears the virus, suggests that viral replication and shedding from the GI tract may be more robust than that of the respiratory tract, further indicating fecal-oral transmission as another important route of viral spread. This review summarized the evidence for pathophysiological mechanisms (impaired barrier function, gut inflammation, altered serotonin metabolism and gut microbiota dysbiosis) underlying the GI symptoms in patients with COVID-19.


Subject(s)
COVID-19 , Gastrointestinal Diseases , Dysbiosis , Gastrointestinal Tract , Humans , SARS-CoV-2
7.
Neurol Sci ; 42(8): 3079-3081, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1237505

ABSTRACT

BACKGROUND: Headache is a frequent symptom of the novel coronavirus 19 disease (COVID-19). To date, there are limited information on how COVID-19 affects migraine and its treatment. CASE DESCRIPTION: A 47-year-old patient, suffering from chronic migraine and medication-overuse headache, in September 2020 started erenumab at 70 mg once monthly. Two months later, monthly migraine days decreased from 20 to 5. On the third month, the patient developed mild COVID-19 symptoms, experiencing extreme fatigue, hyposmia, and attention deficit, resulting positive for SARS-Cov-2 RNA. A significant increase in migraine attacks frequency was reported. Brain MRI and EEG were normal. Erenumab was increased to 140 mg/month, and attacks decreased to 3 monthly migraine days and remained stable. All the headaches experienced by our patient during the infection fulfilled the criteria of the migraine attacks, without tensive-like features. CONCLUSION: We report the first case showing the effects of SARS-CoV-2 infection in a patient with chronic migraine and medication-overuse headache treated with erenumab. Our case description suggests that inflammatory processes induced by SARS-CoV-2 infection may increase the frequency of migraine attacks, probably through an activation of the trigeminovascular system. Whether treatment with CGRP receptor antagonist may influence COVID is still debated. Additional studies regarding anti-CGRP monoclonal antibodies in COVID-19 patients are warranted.


Subject(s)
COVID-19 , Migraine Disorders , Antibodies, Monoclonal, Humanized , Calcitonin Gene-Related Peptide Receptor Antagonists , Humans , Middle Aged , Migraine Disorders/drug therapy , RNA, Viral , SARS-CoV-2
8.
Front Immunol ; 12: 593595, 2021.
Article in English | MEDLINE | ID: covidwho-1229174

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1ß, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.


Subject(s)
COVID-19 , Cytokines , Influenza A Virus, H1N1 Subtype , Influenza, Human , Matrix Metalloproteinase 1 , Matrix Metalloproteinase 3 , Receptors, Immunologic , Adult , Aged , COVID-19/blood , COVID-19/epidemiology , COVID-19/immunology , Cytokines/blood , Cytokines/immunology , Female , Humans , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H1N1 Subtype/metabolism , Influenza, Human/blood , Influenza, Human/epidemiology , Influenza, Human/immunology , Male , Matrix Metalloproteinase 1/blood , Matrix Metalloproteinase 1/immunology , Matrix Metalloproteinase 3/blood , Matrix Metalloproteinase 3/immunology , Middle Aged , Prospective Studies , Receptors, Immunologic/blood , Receptors, Immunologic/immunology , Th1 Cells/immunology , Th2 Cells/immunology
9.
Sci Transl Med ; 13(596)2021 06 02.
Article in English | MEDLINE | ID: covidwho-1225692

ABSTRACT

Patients diagnosed with coronavirus disease 2019 (COVID-19) become critically ill primarily around the time of activation of the adaptive immune response. Here, we provide evidence that antibodies play a role in the worsening of disease at the time of seroconversion. We show that early-phase severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific immunoglobulin G (IgG) in serum of critically ill COVID-19 patients induces excessive inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for patients with severe COVID-19. First, inflammation is driven by high titers of anti-spike IgG, a hallmark of severe disease. Second, we found that anti-spike IgG from patients with severe COVID-19 is intrinsically more proinflammatory because of different glycosylation, particularly low fucosylation, of the antibody Fc tail. Low fucosylation of anti-spike IgG was normalized in a few weeks after initial infection with SARS-CoV-2, indicating that the increased antibody-dependent inflammation mainly occurs at the time of seroconversion. We identified Fcγ receptor (FcγR) IIa and FcγRIII as the two primary IgG receptors that are responsible for the induction of key COVID-19-associated cytokines such as interleukin-6 and tumor necrosis factor. In addition, we show that anti-spike IgG-activated human macrophages can subsequently break pulmonary endothelial barrier integrity and induce microvascular thrombosis in vitro. Last, we demonstrate that the inflammatory response induced by anti-spike IgG can be specifically counteracted by fostamatinib, an FDA- and EMA-approved therapeutic small-molecule inhibitor of Syk kinase.


Subject(s)
Antibodies, Viral/chemistry , COVID-19/immunology , Immunoglobulin G/chemistry , Macrophages, Alveolar/immunology , Glycosylation , Humans , Inflammation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
10.
MEDICC Rev ; 23(2): 42, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1224445

ABSTRACT

INTRODUCTION: Advanced age and chronic disease comorbidities are indicators of poor prognosis in COVID-19 clinical progression. Fatal outcomes in patients with these characteristics are due to a dysfunctional immune response. Understanding COVID-19's immunopathogenesis helps in designing strategies to prevent and mitigate complications during treatment. OBJECTIVE: Describe the main immunopathogenic alterations of COVID-19 in patients of advanced age or with chronic non-communicable diseases. DATA ACQUISITION: We carried out a bibliographic search of primary references in PubMed, Elsevier, Science Direct and SciELO. A total of 270 articles met our initial search criteria. Duplicate articles or those unrelated to at least one chronic comorbidity, senescence or inflammation and those that studied only patient clinical characteristics, laboratory tests or treatments were excluded. Finally, our selection included 124 articles for analysis: 10 meta-analyses, 24 original research articles, 67 review articles, 9 editorials, 9 comments, 3 books and 2 websites. DEVELOPMENT: Hypertension and diabetes mellitus are the most common comorbidities in COVID-19 patients. Risk of developing severe manifestations of the disease, including death, is increased in senescent and obese patients and those with cardiovascular disease, cancer or chronic obstructive pulmonary disease. Low-grade chronic inflammation is characteristic of all these conditions, reflected in a pro-inflammatory state, endothelial dysfunction, and changes to innate immunity; mainly of the monocyte-macrophage system with changes in polarization, inflammation, cytotoxicity and altered antigenic presentation. In the case of SARS-CoV-2 infection, mechanisms involved in acute inflammation overlap with the patient's pro-inflammatory state, causing immune system dysfunction. SARS-CoV-2 infection amplifies already-existing alterations, causing failures in the immune system's control mechanisms. The resulting cytokine storm causes an uncontrolled systemic inflammatory response marked by high serum levels of inflammatory biomarkers and a pro-inflammatory cytokine profile with decompensation of underlying diseases. In asthma, chronic eosinophilic inflammation protects against infection by producing a reduced interferon-mediated response and a reduced number of ACE2 receptors. CONCLUSIONS: Low-grade chronic inflammation present in advanced age and chronic diseases-but not in bronchial asthma-produces a pro-inflammatory state that triggers a dysregulated immune response, favoring development of severe forms of COVID-19 and increasing lethality.


Subject(s)
COVID-19/immunology , Inflammation/immunology , Pneumonia, Viral/immunology , Age Factors , COVID-19/pathology , Chronic Disease , Comorbidity , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Humans , Inflammation/pathology , Pneumonia, Viral/pathology , Risk Factors , SARS-CoV-2
11.
Pathogens ; 10(5)2021 May 07.
Article in English | MEDLINE | ID: covidwho-1224096

ABSTRACT

The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection's outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.

12.
Nat Immunol ; 22(7): 829-838, 2021 07.
Article in English | MEDLINE | ID: covidwho-1220263

ABSTRACT

The innate immune response is critical for recognizing and controlling infections through the release of cytokines and chemokines. However, severe pathology during some infections, including SARS-CoV-2, is driven by hyperactive cytokine release, or a cytokine storm. The innate sensors that activate production of proinflammatory cytokines and chemokines during COVID-19 remain poorly characterized. In the present study, we show that both TLR2 and MYD88 expression were associated with COVID-19 disease severity. Mechanistically, TLR2 and Myd88 were required for ß-coronavirus-induced inflammatory responses, and TLR2-dependent signaling induced the production of proinflammatory cytokines during coronavirus infection independent of viral entry. TLR2 sensed the SARS-CoV-2 envelope protein as its ligand. In addition, blocking TLR2 signaling in vivo provided protection against the pathogenesis of SARS-CoV-2 infection. Overall, our study provides a critical understanding of the molecular mechanism of ß-coronavirus sensing and inflammatory cytokine production, which opens new avenues for therapeutic strategies to counteract the ongoing COVID-19 pandemic.


Subject(s)
COVID-19/immunology , Coronavirus Envelope Proteins/metabolism , Cytokine Release Syndrome/immunology , SARS-CoV-2/immunology , Toll-Like Receptor 2/metabolism , Animals , COVID-19/complications , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Chlorocebus aethiops , Cytokine Release Syndrome/diagnosis , Cytokines/metabolism , Disease Models, Animal , Female , Gene Expression Profiling , Humans , Immunity, Innate/drug effects , Leukocytes, Mononuclear , Macrophages , Male , Mice , Mice, Knockout , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Primary Cell Culture , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Severity of Illness Index , Signal Transduction/drug effects , Signal Transduction/genetics , Signal Transduction/immunology , Toll-Like Receptor 2/antagonists & inhibitors , Toll-Like Receptor 2/genetics , Vero Cells
13.
ACS Appl Mater Interfaces ; 13(18): 20995-21006, 2021 May 12.
Article in English | MEDLINE | ID: covidwho-1209173

ABSTRACT

COVID-19 has been diffusely pandemic around the world, characterized by massive morbidity and mortality. One of the remarkable threats associated with mortality may be the uncontrolled inflammatory processes, which were induced by SARS-CoV-2 in infected patients. As there are no specific drugs, exploiting safe and effective treatment strategies is an instant requirement to dwindle viral damage and relieve extreme inflammation simultaneously. Here, highly biocompatible glycyrrhizic acid (GA) nanoparticles (GANPs) were synthesized based on GA. In vitro investigations revealed that GANPs inhibit the proliferation of the murine coronavirus MHV-A59 and reduce proinflammatory cytokine production caused by MHV-A59 or the N protein of SARS-CoV-2. In an MHV-A59-induced surrogate mouse model of COVID-19, GANPs specifically target areas with severe inflammation, such as the lungs, which appeared to improve the accumulation of GANPs and enhance the effectiveness of the treatment. Further, GANPs also exert antiviral and anti-inflammatory effects, relieving organ damage and conferring a significant survival advantage to infected mice. Such a novel therapeutic agent can be readily manufactured into feasible treatment for COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Glycyrrhizic Acid/therapeutic use , Inflammation/drug therapy , Nanoparticles/therapeutic use , Virus Diseases/drug therapy , Animals , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Antioxidants/therapeutic use , Antiviral Agents/chemistry , COVID-19/drug therapy , Coronavirus Nucleocapsid Proteins/pharmacology , Cytokines/metabolism , Female , Glycyrrhizic Acid/chemistry , Humans , Liver/pathology , Lung/pathology , Mice , Mice, Inbred BALB C , Murine hepatitis virus/drug effects , Nanoparticles/chemistry , Phosphoproteins/pharmacology , RAW 264.7 Cells , SARS-CoV-2/chemistry , THP-1 Cells , Viral Load/drug effects , Virus Diseases/pathology , Virus Replication/drug effects
14.
J Infect Public Health ; 14(7): 863-875, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1202178

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health problem. The SARS-CoV-2 triggers hyper-activation of inflammatory and immune responses resulting in cytokine storm and increased inflammatory responses on several organs like lungs, kidneys, intestine, and placenta. Although SARS-CoV-2 affects individuals of all age groups and physiological statuses, immune-compromised individuals such as pregnant women are considered as a highly vulnerable group. This review aims to raise the concerns of high risk of infection, morbidity and mortality of COVID-19 in pregnant women and provides critical reviews of pathophysiology and pathobiology of how SARS-CoV-2 infection potentially increases the severity and fatality during pregnancy. This article also provides a discussion of current evidence on vertical transmission of SARS-CoV-2 during pregnancy and breastfeeding. Lastly, guidelines on management, treatment, preventive, and mitigation strategies of SARS-CoV-2 infection during pregnancy and pregnancy-related conditions such as delivery and breastfeeding are discussed.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Infectious Disease Transmission, Vertical , Pandemics , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/prevention & control , SARS-CoV-2
15.
World J Gastroenterol ; 27(14): 1406-1418, 2021 Apr 14.
Article in English | MEDLINE | ID: covidwho-1197563

ABSTRACT

Gastrointestinal (GI) symptoms have been described in a conspicuous percentage of coronavirus disease 2019 (COVID-19) patients. This clinical evidence is supported by the detection of viral RNA in stool, which also supports the hypothesis of a possible fecal-oral transmission route. The involvement of GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is corroborated by the theoretical assumption that angiotensin converting enzyme 2, which is a SARS-CoV-2 target receptor, is present along the GI tract. Studies have pointed out that gut dysbiosis may occur in COVID-19 patients, with a possible correlation with disease severity and with complications such as multisystem inflammatory syndrome in children. However, the question to be addressed is whether dysbiosis is a consequence or a contributing cause of SARS-CoV-2 infection. In such a scenario, pharmacological therapies aimed at decreasing GI permeability may be beneficial for COVID-19 patients. Considering the possibility of a fecal-oral transmission route, water and environmental sanitation play a crucial role for COVID-19 containment, especially in developing countries.


Subject(s)
COVID-19 , Gastrointestinal Diseases , Child , Dysbiosis , Gastrointestinal Tract , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
16.
J Neurol ; 268(11): 3980-3987, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1196579

ABSTRACT

Considering the similarities with other pandemics due to respiratory virus infections and subsequent development of neurological disorders (e.g. encephalitis lethargica after the 1918 influenza), there is growing concern about a possible new wave of neurological complications following the worldwide spread of SARS-CoV-2. However, data on COVID-19-related encephalitis and movement disorders are still limited. Herein, we describe the clinical and neuroimaging (FDG-PET/CT, MRI and DaT-SPECT) findings of two patients with COVID-19-related encephalopathy who developed prominent parkinsonism. None of the patients had previous history of parkinsonian signs/symptoms, and none had prodromal features of Parkinson's disease (hyposmia or RBD). Both developed a rapidly progressive form of atypical parkinsonism along with distinctive features suggestive of encephalitis. A possible immune-mediated etiology was suggested in Patient 2 by the presence of CSF-restricted oligoclonal bands, but none of the patients responded favorably to immunotherapy. Interestingly, FDG-PET/CT findings were similar in both cases and reminiscent of those observed in post-encephalitic parkinsonism, with cortical hypo-metabolism associated with hyper-metabolism in the brainstem, mesial temporal lobes, and basal ganglia. Patient's FDG-PET/CT findings were validated by performing a Statistical Parametric Mapping analysis and comparing the results with a cohort of healthy controls (n = 48). Cerebrum cortical thickness map was obtained in Patient 1 from MRI examinations to evaluate the structural correlates of the metabolic alterations detected with FDG-PET/CT. Hypermetabolic areas correlated with brain regions showing increased cortical thickness, suggesting their involvement during the inflammatory process. Overall, these observations suggest that SARS-CoV-2 infection may trigger an encephalitis with prominent parkinsonism and distinctive brain metabolic alterations.


Subject(s)
COVID-19 , Encephalitis , Parkinsonian Disorders , Fluorodeoxyglucose F18 , Humans , Parkinsonian Disorders/diagnostic imaging , Parkinsonian Disorders/etiology , Positron Emission Tomography Computed Tomography , SARS-CoV-2
17.
Acta Neurobiol Exp (Wars) ; 81(1): 69-79, 2021.
Article in English | MEDLINE | ID: covidwho-1190720

ABSTRACT

The recent pandemic of the coronavirus infectious disease 2019 (COVID-19) has affected around 192 countries, and projections have shown that around 40% to 70% of world population could be infected in the next months. COVID-19 is caused by the virus SARS- CoV-2, it enters the cells through the ACE2 receptor (angiotensin converting enzyme 2). It is well known that SARS-CoV-2 could develop mild, moderate, and severe respiratory symptoms that could lead to death. The virus receptor is expressed in different organs such as the lungs, kidney, intestine, and brain, among others. In the lung could cause pneumonia and severe acute respiratory syndrome (SARS). The brain can be directly affected by cellular damage due to viral invasion, which can lead to an inflammatory response, by the decrease in the enzymatic activity of ACE2 that regulates neuroprotective, neuro-immunomodulatory and neutralizing functions of oxidative stress. Another severe damage is hypoxemia in patients that do not receive adequate respiratory support. The neurological symptoms that the patient presents, will depend on factors that condition the expression of ACE2 in the brain such as age and sex, as well as the mechanism of neuronal invasion, the immune response and the general state of the patient. Clinical and histopathological studies have described neurological alterations in human patients with COVID-19. These conditions could have a possible contribution to the morbidity and mortality caused by this disease and may even represent the onset of neurodegenerative activity in recovered patients.The recent pandemic of the coronavirus infectious disease 2019 (COVID-19) has affected around 192 countries, and projections have shown that around 40% to 70% of world population could be infected in the next months. COVID-19 is caused by the virus SARS- CoV-2, it enters the cells through the ACE2 receptor (angiotensin converting enzyme 2). It is well known that SARS-CoV-2 could develop mild, moderate, and severe respiratory symptoms that could lead to death. The virus receptor is expressed in different organs such as the lungs, kidney, intestine, and brain, among others. In the lung could cause pneumonia and severe acute respiratory syndrome (SARS). The brain can be directly affected by cellular damage due to viral invasion, which can lead to an inflammatory response, by the decrease in the enzymatic activity of ACE2 that regulates neuroprotective, neuro-immunomodulatory and neutralizing functions of oxidative stress. Another severe damage is hypoxemia in patients that do not receive adequate respiratory support. The neurological symptoms that the patient presents, will depend on factors that condition the expression of ACE2 in the brain such as age and sex, as well as the mechanism of neuronal invasion, the immune response and the general state of the patient. Clinical and histopathological studies have described neurological alterations in human patients with COVID-19. These conditions could have a possible contribution to the morbidity and mortality caused by this disease and may even represent the onset of neurodegenerative activity in recovered patients.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Brain/virology , COVID-19/epidemiology , Communicable Diseases/virology , SARS-CoV-2/pathogenicity , COVID-19/virology , Humans , Neurons/virology
18.
EClinicalMedicine ; 34: 100831, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1184949

ABSTRACT

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children is associated with better outcomes than in adults. The inflammatory response to COVID-19 infection in children remains poorly characterised. METHODS: We retrospectively analysed the medical records of 127 laboratory-confirmed COVID-19 patients aged 1 month to 16 years from Wuhan and Jingzhou of Hubei Province. Patients presented between January 25th and March 24th 2020. Information on clinical features, laboratory results, plasma cytokines/chemokines and lymphocyte subsets were analysed. FINDINGS: Children admitted to hospital with COVID-19 were more likely to be male (67.7%) and the median age was 7.3 [IQR 4.9] years. All but one patient with severe disease was aged under 2 and the majority (5/7) had significant co-morbidities. Despite 53% having viral pneumonia on computed tomography (CT) scanning only 2 patients had low lymphocyte counts and no differences were observed in the levels of plasma proinflammatory cytokines, including interleukin (IL)-2, IL-4, IL-6, tumour necrosis factor (TNF)- α , and interferon (IFN)- γ between patients with mild, moderate or severe disease. INTERPRETATIONS: We observed that the immune responses of children to COVID-19 infection is significantly different from that seen in adults. Our evidence suggests that SARS-CoV-2 does not trigger a robust inflammatory response or 'cytokine storm' in children with COVID-19, and this may underlie the generally better outcomes seen in children with this disease.

19.
Postgrad Med J ; 98(1159): 395-402, 2022 May.
Article in English | MEDLINE | ID: covidwho-1183381

ABSTRACT

Rising incidence of thromboembolism secondary to COVID-19 has become a global concern, with several surveys reporting increased mortality rates. Thrombogenic potential of the SARS-CoV-2 virus has been hypothesised to originate from its ability to produce an exaggerated inflammatory response leading to endothelial dysfunction. Anticoagulants have remained the primary modality of treatment of thromboembolism for decades. However, there is no universal consensus regarding the timing, dosage and duration of anticoagulation in COVID-19 as well as need for postdischarge prophylaxis. This article seeks to review the present guidelines and recommendations as well as the ongoing trials on use of anticoagulants in COVID-19, identify discrepancies between all these, and provide a comprehensive strategy regarding usage of these drugs in the current pandemic.


Subject(s)
COVID-19 , Thromboembolism , Venous Thromboembolism , Aftercare , Anticoagulants/therapeutic use , Humans , Patient Discharge , SARS-CoV-2 , Thromboembolism/drug therapy , Thromboembolism/etiology , Thromboembolism/prevention & control , Venous Thromboembolism/etiology
20.
Nitric Oxide ; 111-112: 64-71, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1164254

ABSTRACT

Symptoms of COVID-19 range from asymptomatic/mild symptoms to severe illness and death, consequence of an excessive inflammatory process triggered by SARS-CoV-2 infection. The diffuse inflammation leads to endothelium dysfunction in pulmonary blood vessels, uncoupling eNOS activity, lowering NO production, causing pulmonary physiological alterations and coagulopathy. On the other hand, iNOS activity is increased, which may be advantageous for host defense, once NO plays antiviral effects. However, overproduction of NO may be deleterious, generating a pro-inflammatory effect. In this review, we discussed the role of endogenous NO as a protective or deleterious agent of the respiratory and vascular systems, the most affected in COVID-19 patients, focusing on eNOS and iNOS roles. We also reviewed the currently available NO therapies and pointed out possible alternative treatments targeting NO metabolism, which could help mitigate health crises in the present and future CoV's spillovers.


Subject(s)
COVID-19/metabolism , Nitric Oxide Synthase Type III/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide/metabolism , SARS-CoV-2 , Blood Vessels/metabolism , Gene Expression Regulation, Enzymologic , Humans , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type III/genetics , Respiratory System/metabolism
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