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1.
Front Immunol ; 11: 586073, 2020.
Article in English | MEDLINE | ID: covidwho-1021888

ABSTRACT

Since the December 2019 outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, the infection has spread locally and globally resulting in a pandemic. As the numbers of confirmed diagnoses and deaths continue to rise, COVID-19 has become the focus of international public health. COVID-19 is highly contagious, and there is no effective treatment yet. New treatment strategies are urgently needed to improve the treatment success rate of severe and critically ill patients. Increasing evidence has shown that a cytokine storm plays an important role in the progression of COVID-19. The artificial-liver blood-purification system (ALS) is expected to improve the outcome of the cytokine storm. In the present study, the levels of cytokines were detected in 12 COVID-19 patients pre- and post-ALS with promising results. The present study shows promising evidence that ALS can block the cytokine storm, rapidly remove the inflammatory mediators, and hopefully, suppress the progression of the disease, thereby providing a new strategy for the clinical treatment of COVID-19.


Subject(s)
/therapy , Cytokine Release Syndrome/therapy , Cytokines/blood , Hemoperfusion , Liver/metabolism , Plasma Exchange , Adult , Aged , Aged, 80 and over , Cytokine Release Syndrome/etiology , Female , Humans , Male , Middle Aged
2.
Cir Cir ; 88(5): 654-663, 2020.
Article in English | MEDLINE | ID: covidwho-1011871

ABSTRACT

The disease caused by a new coronavirus, which started in 2019, was named COVID-19 and declared a pandemic on March 11, 2020 by the World Health Organization. Although it is true that the first reports emphasized the respiratory manifestations of this disease as an initial clinical presentation, little by little cases with different initial manifestations began to appear, involving other systems. In cases where central nervous system involvement was identified, the most frequent findings were dizziness, headache, and alteration of alertness. Regarding the cardiovascular system, elevation of cardiac biomarkers and myocarditis are one of the most frequent findings. The main gastrointestinal symptoms described so far are: anorexia, nausea, vomiting, diarrhea, abdominal pain and/or discomfort. Venous thromboembolism is a frequent complication and a public health problem. Skin manifestations remain a field of investigation. Maculopapular rashes, reticular livedo, acral gangrene, among others, have been identified. Health personnel must be updated on new clinical findings and the forms of presentation of this partially known disease, which will make it possible to make more accurate and timely diagnoses, thus impacting the prognosis of these patients.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Pandemics , Pneumonia, Viral/complications , Cardiovascular Diseases/etiology , Central Nervous System Diseases/etiology , Cytokine Release Syndrome/etiology , Gastrointestinal Diseases/etiology , Humans , Kidney Diseases/etiology , Skin Diseases/etiology
3.
Eur Cytokine Netw ; 31(3): 81-93, 2020 Sep 01.
Article in English | MEDLINE | ID: covidwho-999892

ABSTRACT

Coronavirus disease (COVID-19) reached pandemic proportions at the beginning of 2020 and continues to be a worldwide concern. End organ damage and acute respiratory distress syndrome are the leading causes of death in severely or critically ill patients. The elevated cytokine levels in severe patients in comparison with mildly affected patients suggest that cytokine release syndrome (CRS) occurs in the severe form of the disease. In this paper, the significant role of pro-inflammatory cytokines, including IL-1, IL-6, and TNF-alpha, and their mechanism of action in the CRS cascade is explained. Potential therapeutic approaches involving anti-IL-6 and anti-TNF-alpha antibodies to fight COVID-19 and reduce mortality rate in severe cases are also discussed.


Subject(s)
Antibodies/therapeutic use , Cytokine Release Syndrome , Interleukin-6/antagonists & inhibitors , Pandemics , Tumor Necrosis Factor-alpha/antagonists & inhibitors , /blood , /drug therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/mortality , Humans , Interleukin-6/blood , Tumor Necrosis Factor-alpha/blood
4.
Front Endocrinol (Lausanne) ; 11: 569241, 2020.
Article in English | MEDLINE | ID: covidwho-995769

ABSTRACT

The clinical hallmarks of infections caused by critical respiratory viruses consist of pneumonia, which can progress to acute lung injury (ALI), and systemic manifestations including hypercoagulopathy, vascular dysfunction, and endotheliitis. The disease outcome largely depends on the immune response produced by the host. The bio-molecular mechanisms underlying certain dire consequences of the infection partly arise from an aberrant production of inflammatory molecules, an event denoted as "cytokine storm". Therefore, in addition to antiviral therapies, molecules able to prevent the injury caused by cytokine excess are under investigation. In this perspective, taking advantage of melanocortin peptides and their receptors, components of an endogenous modulatory system that exerts marked anti-inflammatory and immunomodulatory influences, could be an effective therapeutic strategy to control disease evolution. Exploiting the melanocortin system using natural or synthetic ligands can form a realistic basis to counteract certain deleterious effects of respiratory virus infections. The central and peripheral protective actions exerted following melanocortin receptor activation could allow dampening the harmful events that trigger the cytokine storm and endothelial dysfunction while sustaining the beneficial signals required to elicit repair mechanisms. The long standing evidence for melanocortin safety encourages this approach.


Subject(s)
/drug therapy , Receptors, Melanocortin/agonists , Respiratory Tract Infections/drug therapy , Acute Lung Injury/drug therapy , Animals , Anti-Inflammatory Agents/therapeutic use , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokines/metabolism , Humans , Melanocyte-Stimulating Hormones/metabolism , Respiratory Tract Infections/etiology , Respiratory Tract Infections/metabolism
6.
Front Immunol ; 11: 570993, 2020.
Article in English | MEDLINE | ID: covidwho-983708

ABSTRACT

Corona virus disease 2019 (COVID-19) has caused a global outbreak and severely posed threat to people's health and social stability. Mounting evidence suggests that immunopathological changes, including diminished lymphocytes and elevated cytokines, are important drivers of disease progression and death in coronavirus infections. Cytokine storm not only limits further spread of virus in the body but also induces secondary tissue damage through the secretion of large amounts of active mediators and inflammatory factors. It has been determined that cytokine storm is a major cause of deaths in COVID-19; therefore, in order to reverse the deterioration of severe and critically ill patients from this disease, the cytokine storm has become a key therapeutic target. Although specific mechanisms of the occurrences of cytokine storms in COVID-19 have not been fully illuminated, hyper-activated innate immune responses, and dysregulation of ACE2 (angiotensin converting enzyme 2) expression and its downstream pathways might provide possibilities. Tailored immunoregulatory therapies have been applied to counteract cytokine storms, such as inhibition of cytokines, corticosteroids, blood purification therapy, and mesenchymal stem cell therapy. This review will summarize advances in the research of cytokine storms induced by COVID-19, as well as potential intervention strategies to control cytokine storms.


Subject(s)
Cytokine Release Syndrome , Disease Outbreaks , Immunotherapy , /immunology , /immunology , /epidemiology , /therapy , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Humans , Immunity, Innate/immunology
7.
Clin Rheumatol ; 39(7): 2077-2084, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-980874

ABSTRACT

The novel coronavirus (Sars-CoV-2) pandemic has spread rapidly, from December to the end of March, to 185 countries, and there have been over 3,000,000 cases identified and over 200,000 deaths. For a proportion of hospitalized patients, death can occur within a few days, mainly for adult respiratory distress syndrome or multi-organ dysfunction syndrome. In these patients, clinical signs and symptoms, as well as laboratory abnormalities, suggest a cytokine storm syndrome in response to the viral infection. No current targeted treatment is yet available for COVID-19, an unknown disease up to 2 months ago, which challenges doctors and researchers to find new drugs or reallocate other treatments for these patients. Since the beginning of the COVID-19 outbreak, a growing body of information on diagnostic and therapeutic strategies has emerged, mainly based on preliminary experience on retrospective studies or small case series. Antivirals, antimalarials, corticosteroids, biotechnological and small molecules, convalescent plasma and anticoagulants are among the drugs proposed for the treatment or in tested for COVID-19. Given the complexity of this new condition, a multidisciplinary management seems to be the best approach. Sharing and integrating knowledge between specialists, to evaluate the correct timing and setting of every treatment, could greatly benefit our patients. We reviewed the literature, combining it with our experiences and our specialist knowledge, to propose a management algorithm, correlating the clinical features with laboratory and imaging findings to establish the right timing for each treatment.Key Points• Critically ill COVID-19 patients show signs of cytokine storm syndrome.• No current targeted therapy is available, but a lot of drugs are in tested.• A multidisciplinary approach is crucial to manage COVID-19.• Choosing the correct timing of treatment is of pivotal importance to avoid the most severe complications.


Subject(s)
Antiviral Agents , Clinical Laboratory Techniques/methods , Coronavirus Infections , Cytokine Release Syndrome , Pandemics , Patient Care Team/organization & administration , Pneumonia, Viral , Algorithms , Antiviral Agents/immunology , Antiviral Agents/pharmacology , Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Critical Pathways , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Humans , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy
8.
Mol Med Rep ; 22(6): 4485-4491, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-979150

ABSTRACT

In December 2019, an emergence of pneumonia was detected in patients infected with a novel coronavirus (CoV) in Wuhan (Hubei, China). The International Committee on Taxonomy of Viruses named the virus severe acute respiratory syndrome­CoV­2 and the disease CoV disease­19 (COVID­19). Patients with COVID­19 present with symptoms associated with respiratory system dysfunction and hematological changes, including lymphopenia, thrombocytopenia and coagulation disorders. However, to the best of our knowledge, the pathogenesis of COVID­19 remains unclear. Therefore, understanding the mechanisms underlying the hematological changes that manifest during COVID­19 may aid in the development of treatments and may improve patient prognosis.


Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Pneumonia, Viral/blood , Antibodies, Viral/immunology , Antigen-Antibody Complex/immunology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Betacoronavirus/immunology , Cellular Microenvironment , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/prevention & control , Cytokines/blood , Diagnostic Tests, Routine , Endothelium, Vascular/pathology , Hematologic Tests , Hematopoiesis/drug effects , Hematopoietic Stem Cells/pathology , Humans , Hypoalbuminemia/etiology , Liver/physiopathology , Lung/physiopathology , Lymphopenia/etiology , Lymphopenia/physiopathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/therapy , Reperfusion Injury/etiology , Thrombocytopenia/etiology , Thrombocytopenia/physiopathology , Thrombophilia/etiology
9.
Isr Med Assoc J ; 22(8): 505-513, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-972915

ABSTRACT

BACKGROUND: In this review we described the values of commonly available HScore laboratory markers in patients with coronavirus-19 (COVID-19)-pneumonia associated cytokine storm syndrome (CPN-CSS) and compared results with those of other forms cytokine storm syndrome (O-CSS) to determine a pattern for CPN-CSS. Twelve CPN-CSS studies and six O-CSS studies were included. CPN-CSS typically obtained a single HScore value (e.g., aspartate transaminase > 30 U/L) while failing all other HScore criteria. A typical pattern for CPN-CSS was revealed when compared to O-CSS: lymphopenia vs. pancytopenia and increased vs. decreased fibrinogen. Findings, other than HScore commonly found in CPN-CSS studies, showed elevated lactate dehydrogenase, D-dimer, and C-reactive protein. Although CPN-CSS studies describe severely ill patients, the HScore markers are typically less toxic that O-CSS.


Subject(s)
/blood , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Pneumonia/blood , Pneumonia/virology , Aspartate Aminotransferases/blood , C-Reactive Protein/metabolism , Ferritins/blood , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Humans , L-Lactate Dehydrogenase/blood , Lymphohistiocytosis, Hemophagocytic/blood , Lymphohistiocytosis, Hemophagocytic/complications , Lymphopenia/virology , Pancytopenia/etiology , Patient Acuity
10.
Neurosci Lett ; 742: 135531, 2021 01 18.
Article in English | MEDLINE | ID: covidwho-966786

ABSTRACT

Multiple neuro-ophthalmological manifestations have been described in association with COVID-19. These symptoms and signs may be the result of a range of pathophysiological mechanisms throughout the course from acute illness to recovery phase. Optic nerve dysfunction, eye movement abnormalities and visual field defects have been described.


Subject(s)
/complications , Cytokine Release Syndrome/etiology , Nervous System Diseases/etiology , Vision Disorders/etiology , /diagnosis , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/metabolism , Humans , Nervous System Diseases/diagnosis , Nervous System Diseases/metabolism , Vision Disorders/diagnosis , Vision Disorders/metabolism
11.
Mediators Inflamm ; 2020: 8829674, 2020.
Article in English | MEDLINE | ID: covidwho-961174

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a virus-induced respiratory disease that may progress to acute respiratory distress syndrome (ARDS) and is triggered by immunopathological mechanisms that cause excessive inflammation and leukocyte dysfunction. Neutrophils play a critical function in the clearance of bacteria with specific mechanisms to combat viruses. The aim of this review is to highlight the current advances in the pathways of neutrophilic inflammation against viral infection over the past ten years, focusing on the production of neutrophil extracellular traps (NETs) and its impact on severe lung diseases, such as COVID-19. We focused on studies regarding hyperinflammation, cytokine storms, neutrophil function, and viral infections. We discuss how the neutrophil's role could influence COVID-19 symptoms in the interaction between hyperinflammation (overproduction of NETs and cytokines) and the clearance function of neutrophils to eliminate the viral infection. We also propose a more in-depth investigation into the neutrophil response mechanism targeting NETosis in the different phases of COVID-19.


Subject(s)
/immunology , Inflammation/immunology , Neutrophils/immunology , /complications , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Extracellular Traps/immunology , Extracellular Traps/virology , Host Microbial Interactions/immunology , Humans , Immunity, Innate , Inflammation/etiology , Inflammation/virology , Inflammation Mediators/immunology , Lung/immunology , Lung/virology , Models, Immunological , Neutrophils/virology , Pandemics , /immunology , /immunology , /pathogenicity
12.
J Med Virol ; 92(9): 1533-1541, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-950346

ABSTRACT

Since December 2019, novel coronavirus infected pneumonia emerged in Wuhan city and rapidly spread throughout China. In severe novel coronavirus pneumonia cases, the number of platelets, their dynamic changes during the treatment, platelet-to-lymphocyte ratio (PLR) were a concern. We sought to describe the platelet feature of these cases. Single-center case series of the 30 hospitalized patients with confirmed coronavirus disease (COVID)-19 in Huizhou municipal central hospital from January 2020 to February 2020 were retrospectively analyzed. Demographic, clinical, blood routine results, other laboratory results, and treatment data were collected and analyzed. Outcomes of severe patients and nonsevere patients were compared. Univariate analysis showed that: age, platelet peaks, and PLR at peak platelet were the influencing factors in severe patients, multivariate analysis showed that the PLR value at peak platelet during treatment was an independent influencing factor in severe patients. The average hospitalization day of patients with platelet peaks during treatment was longer than those without platelet peaks (P < .05). The average age of patients with platelet peaks during treatment was older than those without platelet peaks (P < .05). The patients with significantly elevated platelets during treatment had longer average hospitalization days. And the higher PLR of patients during treatment had longer average hospitalization days. Single-center case series of the 30 hospitalized patients with confirmed COVID-19 in Huizhou Municipal Central Hospital, presumed that the number of platelets and their dynamic changes during the treatment may have a suggestion on the severity and prognosis of the disease. The patient with markedly elevated platelets and longer average hospitalization days may be related to the cytokine storm. The PLR of patients means the degree of cytokine storm, which might provide a new indicator in the monitoring in patients with COVID-19.


Subject(s)
/blood , Lymphocyte Count , Platelet Count , Adult , Aged , Biomarkers , /virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/mortality , Female , Humans , Leukocyte Count , Male , Middle Aged , Prognosis , Severity of Illness Index , Tomography, X-Ray Computed
13.
Biomed Pharmacother ; 133: 111064, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-947124

ABSTRACT

COVID-19 is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early reported symptoms include fever, cough, and respiratory symptoms. There were few reports of digestive symptoms. However, with COVID-19 spreading worldwide, symptoms such as vomiting, diarrhoea, and abdominal pain have gained increasing attention. Research has found that angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, is strongly expressed in the gastrointestinal tract and liver. Whether theoretically or clinically, many studies have suggested a close connection between COVID-19 and the digestive system. In this review, we summarize the digestive symptoms reported in existing research, discuss the impact of SARS-CoV-2 on the gastrointestinal tract and liver, and determine the possible mechanisms and aetiology, such as cytokine storm. In-depth exploration of the relationship between COVID-19 and the digestive system is urgently needed.


Subject(s)
/complications , Gastrointestinal Diseases/etiology , Liver Diseases/etiology , Pandemics , /pathogenicity , /metabolism , Anorexia/etiology , Antiviral Agents/adverse effects , Bile Ducts/metabolism , Bile Ducts/virology , /immunology , Chemical and Drug Induced Liver Injury/etiology , Comorbidity , Cytokine Release Syndrome/etiology , Cytopathogenic Effect, Viral , Gastrointestinal Diseases/epidemiology , Gastrointestinal Microbiome , Gastrointestinal Tract/metabolism , Gastrointestinal Tract/pathology , Gastrointestinal Tract/virology , Humans , Immunosuppressive Agents/adverse effects , Liver/metabolism , Liver/pathology , Liver/virology , Liver Diseases/epidemiology , Liver Transplantation , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/virology , Postoperative Complications , Receptors, Virus/metabolism
14.
Mol Med Rep ; 22(6): 4485-4491, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-918906

ABSTRACT

In December 2019, an emergence of pneumonia was detected in patients infected with a novel coronavirus (CoV) in Wuhan (Hubei, China). The International Committee on Taxonomy of Viruses named the virus severe acute respiratory syndrome­CoV­2 and the disease CoV disease­19 (COVID­19). Patients with COVID­19 present with symptoms associated with respiratory system dysfunction and hematological changes, including lymphopenia, thrombocytopenia and coagulation disorders. However, to the best of our knowledge, the pathogenesis of COVID­19 remains unclear. Therefore, understanding the mechanisms underlying the hematological changes that manifest during COVID­19 may aid in the development of treatments and may improve patient prognosis.


Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Pneumonia, Viral/blood , Antibodies, Viral/immunology , Antigen-Antibody Complex/immunology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Betacoronavirus/immunology , Cellular Microenvironment , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/prevention & control , Cytokines/blood , Diagnostic Tests, Routine , Endothelium, Vascular/pathology , Hematologic Tests , Hematopoiesis/drug effects , Hematopoietic Stem Cells/pathology , Humans , Hypoalbuminemia/etiology , Liver/physiopathology , Lung/physiopathology , Lymphopenia/etiology , Lymphopenia/physiopathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/therapy , Reperfusion Injury/etiology , Thrombocytopenia/etiology , Thrombocytopenia/physiopathology , Thrombophilia/etiology
15.
Respir Med ; 175: 106188, 2020 12.
Article in English | MEDLINE | ID: covidwho-912592

ABSTRACT

OBJECTIVES: Cytokine release syndrome (CRS) is a potentially severe complication of COVID-19 most commonly resulting in respiratory failure. This ten-patient study was designed to determine the efficacy of therapeutic plasma exchange (TPE) in improving oxygenation and in reducing the cytokine load in a critically ill subset of patients. METHODS: Five single volume plasma exchanges over eight days within a 14-day study period. In mechanically ventilated patients, oxygenation was measured via the PaO2/FiO2 (P/F) ratio and the oxygenation index (OI) daily for 14 days. Supplemental oxygen requirements were tracked daily for non-ventilated patients. RESULTS: Non-ventilated patients were liberated from supplemental oxygen after TPE. The response was rapid with an 87% average reduction in oxygenation requirements following and average time to return to room air of 5.25 days. All mechanically ventilated patients demonstrated improvement in oxygenation with a 78% average improvement in the P/F ratio and a 43% improvement in OI. C-reactive protein (CRP) and serum levels of IL-6, IL-8, IL-10, TNFα, IFNγ and GM-CSF, were measured daily with immediate post TPE levels drawn on days 1, 2, 4, 6 and 8. All patients demonstrated significant reductions in CRP, IL-6, IL-10 and TNFα. CONCLUSIONS: In the majority of patients with Penn class 3 and 4 CRS complicating COVID-19, TPE demonstrated a prompt improvement in oxygenation and reduction in cytokine load without compromising patient safety. As this pilot study was envisioned to be hypothesis generating, expanded trials using TPE alone and in conjunction with novel pharmacologic agents are warranted. REGISTRATION: ClinicalTrials.gov NCT04374149.


Subject(s)
/complications , Cytokine Release Syndrome/therapy , Plasma Exchange/methods , /genetics , Adult , /metabolism , Critical Illness/therapy , Cytokine Release Syndrome/classification , Cytokine Release Syndrome/etiology , Female , Humans , Male , Middle Aged , Oxygen Inhalation Therapy/methods , Pilot Projects , Prospective Studies , Respiration, Artificial/methods , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/therapy , Severity of Illness Index
16.
Exp Gerontol ; 142: 111147, 2020 12.
Article in English | MEDLINE | ID: covidwho-912193

ABSTRACT

SARS-CoV-2 causes a severe pneumonia (COVID-19) that affects essentially elderly people. In COVID-19, macrophage infiltration into the lung causes a rapid and intense cytokine storm leading finally to a multi-organ failure and death. Comorbidities such as metabolic syndrome, obesity, type 2 diabetes, lung and cardiovascular diseases, all of them age-associated diseases, increase the severity and lethality of COVID-19. Mitochondrial dysfunction is one of the hallmarks of aging and COVID-19 risk factors. Dysfunctional mitochondria is associated with defective immunological response to viral infections and chronic inflammation. This review discuss how mitochondrial dysfunction is associated with defective immune response in aging and different age-related diseases, and with many of the comorbidities associated with poor prognosis in the progression of COVID-19. We suggest here that chronic inflammation caused by mitochondrial dysfunction is responsible of the explosive release of inflammatory cytokines causing severe pneumonia, multi-organ failure and finally death in COVID-19 patients. Preventive treatments based on therapies improving mitochondrial turnover, dynamics and activity would be essential to protect against COVID-19 severity.


Subject(s)
Aging/immunology , Mitochondria/physiology , Animals , /mortality , Cytokine Release Syndrome/etiology , Humans , Inflammation/immunology , Inflammation/physiopathology , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology
17.
Transplant Proc ; 52(9): 2688-2692, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-899633

ABSTRACT

BACKGROUND: Cytokine release storm (CRS) is a potentially fatal, hyperinflammatory condition common to both coronavirus disease 2019 (COVID-19) and reactive hemophagocytic lymphohistiocytosis (rHLH). We present our experience with the use of a diagnostic score, developed for rHLH, in a kidney transplant recipient hospitalized with COVID-19. METHODS: We applied the H-Score to risk-stratify our patient to help predict his hospital course. This study was exempt from requiring specific Institutional Review Board approval, but met all the criteria required by our institution for this type of study and report including consent from the patient. RESULTS: The calculated H-Score for our patient fell below the diagnostic cut-off value for rHLH. Because rHLH is characterized by CRS, we expected him to have a milder hospital course with COVID-19. Correlating with his below cut-off H-score, the patient had a more benign than expected hospital course. CONCLUSIONS: Because this is only a single case, we plan to retrospectively review a series of patients to validate our initial experience-that a low H-Score may correlate with a milder hospital course in kidney transplant patients with COVID-19.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/therapy , Immunocompromised Host , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Severity of Illness Index , Betacoronavirus , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/etiology , Humans , Kidney Transplantation , Male , Middle Aged , Pandemics , Prognosis , Retrospective Studies
18.
Biomaterials ; 267: 120389, 2021 01.
Article in English | MEDLINE | ID: covidwho-898508

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.


Subject(s)
/complications , Cytokine Release Syndrome/drug therapy , DNA/blood , Deoxyribonuclease I/therapeutic use , Drug Carriers/administration & dosage , Nanoparticles/administration & dosage , Neutrophils/drug effects , Sepsis/drug therapy , Animals , /immunology , Cytokine Release Syndrome/etiology , Deoxyribonuclease I/administration & dosage , Dexamethasone/therapeutic use , Disease Models, Animal , Drug Evaluation, Preclinical , Extracellular Traps/drug effects , Humans , Indoles , Male , Mice , Mice, Inbred C57BL , Multiple Organ Failure/blood , Multiple Organ Failure/etiology , Multiple Organ Failure/prevention & control , NF-kappa B/blood , Neutrophils/enzymology , Peroxidase/blood , Polyethylene Glycols , Polyglactin 910 , Polymers , Sepsis/etiology , Sepsis/immunology
19.
Sci Rep ; 10(1): 18277, 2020 10 26.
Article in English | MEDLINE | ID: covidwho-892043

ABSTRACT

Severe COVID-19 associated respiratory failure, poses the one challenge of our days. Assessment and treatment of COVID-19 associated hyperinflammation may be key to improve outcomes. It was speculated that in subgroups of patients secondary hemophagocytic lymphohistiocytosis (sHLH) or cytokine release syndrome (CRS) with features of macrophage activation syndrome might drive severe disease trajectories. If confirmed, profound immunosuppressive therapy would be a rationale treatment approach. Over a median observation period of 11 (IQR: 8; 16) days, 19 consecutive confirmed severe COVID-19-patients admitted to our intensive-care-unit were tested for presence of sHLH by two independent experts. HScores and 2004-HLH diagnostic criteria were assessed. Patients were grouped according to short-term clinical courses: discharge from ICU versus ongoing ARDS or death at time of analysis. The median HScore at admission was 157 (IQR: 98;180), without the key clinical triad of HLH, i.e. progressive cytopenia, persistent fever and organomegaly. Independent expert chart review revealed the absence of sHLH in all cases. No patient reached more than 3/6 of modified HLH 2004 criteria. Nevertheless, patients presented hyperinflammation with peripheral neutrophilic signatures (neutrophil/lymphocyte-ratio > 3.5). The latter best paralleled their short-term clinical courses, with declining relative neutrophil numbers prior to extubation (4.4, [IQR: 2.5;6.3]; n = 8) versus those with unfavourable courses (7.6, [IQR: 5.2;31], n = 9). Our study rules out virus induced sHLH as the leading cause of most severe-COVID-19 trajectories. Instead, an associated innate neutrophilic hyperinflammatory response or virus-associated-CRS appears dominant in patients with an unfavourable clinical course. Therapeutic implications are discussed.


Subject(s)
Coronavirus Infections/pathology , Cytokine Release Syndrome/etiology , Lymphohistiocytosis, Hemophagocytic/pathology , Pneumonia, Viral/pathology , Aged , Betacoronavirus/isolation & purification , Cohort Studies , Coronavirus Infections/complications , Coronavirus Infections/virology , Critical Illness , Cytokine Release Syndrome/diagnosis , Female , Ferritins/analysis , Humans , Intensive Care Units , Interleukin-6/metabolism , Lymphocytes/cytology , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis , Male , Middle Aged , Neutrophils/cytology , Pandemics , Pilot Projects , Pneumonia, Viral/complications , Pneumonia, Viral/virology
20.
Cardiorenal Med ; 10(6): 462-469, 2020.
Article in English | MEDLINE | ID: covidwho-889976

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a pandemic that has affected >188 countries, involved >24 million people, and caused >840,000 deaths. COVID-19, in its severe form, presents as acute respiratory distress syndrome (ARDS), shock, and multiorgan failure. Thrombotic microangiopathy of the lungs and kidneys has been observed in these patients. Elevated D-dimer levels have been observed in people with serious COVID-19 illness, and this could be helpful in guiding treatment with anticoagulation in these patients. OBJECTIVE: To analyze the role of anticoagulation as a treatment modality for COVID-19. METHODS: We present the unique case of a COVID-19 patient who developed sepsis, ARDS, acute kidney injury, and deep-vein thrombosis (DVT), who was deteriorating clinically. She was treated with anticoagulation. RESULTS: There was rapid recovery after treatment with systemic anticoagulation. CONCLUSIONS: Systemic anticoagulation could prove to be essential in the treatment of CO-VID-19. Further studies are required to assess its role in improving long-term morbidity and mortality in these patients.


Subject(s)
/complications , Thromboembolism/etiology , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Anticoagulants/therapeutic use , /virology , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/etiology , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Middle Aged , /etiology , Sepsis/diagnosis , Sepsis/etiology , Thromboembolism/diagnosis , Thromboembolism/prevention & control , Thrombotic Microangiopathies/complications , Thrombotic Microangiopathies/prevention & control , Treatment Outcome , Venous Thrombosis/diagnosis , Venous Thrombosis/etiology
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