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2.
Neuropharmacology ; 201: 108841, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1466809

ABSTRACT

A strong association between perinatal viral infections and neurodevelopmental disorders has been established. Both the direct contact of the virus with the developing brain and the strong maternal immune response originated by viral infections can impair proper neurodevelopment. Coronavirus disease 2019 (COVID-19), caused by the highly-infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently responsible for a large global outbreak and is a major public health issue. While initial studies focused on the viral impact on the respiratory system, increasing evidence suggest that SARS-CoV-2 infects other organs and tissues including the mature brain. While studies continue to determine the neuropathology associated to COVID-19, the consequences of SARS-CoV-2 infection to the developing brain remain largely unexplored. The present review discusses evidence suggesting that SARS-CoV-2 infection may have persistent effects on the course of pregnancy and on brain development. Studies have shown that several proinflammatory mediators which are increased in the SARS-CoV-2-associated cytokine storm, are also modified in other viral infections known to increase the risk of neurodevelopmental disorders. In this sense, further studies should assess the genuine effects of SARS-CoV-2 infection during pregnancy and delivery along with an extended follow-up of the offspring, including neurocognitive, neuroimaging, and electrophysiological examination. It also remains to be determined whether and by which mechanisms SARS-CoV-2 intrauterine and early life infection could lead to an increased risk of developing neuropsychiatric disorders, such as autism (ASD) and schizophrenia (SZ), in the offspring.


Subject(s)
Autism Spectrum Disorder/epidemiology , COVID-19/epidemiology , Cytokine Release Syndrome/epidemiology , Neurodevelopmental Disorders/epidemiology , Pregnancy Complications, Infectious/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Schizophrenia/epidemiology , Autism Spectrum Disorder/immunology , Brain/embryology , Brain/immunology , COVID-19/immunology , Cytokine Release Syndrome/immunology , Female , Humans , Infectious Disease Transmission, Vertical , Neurodevelopmental Disorders/immunology , Pregnancy , Pregnancy Complications, Infectious/immunology , Prenatal Exposure Delayed Effects/immunology , Risk Factors , SARS-CoV-2 , Schizophrenia/immunology
3.
Scand J Immunol ; 94(5): e13102, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1434833

ABSTRACT

During COVID-19 infection, reduced function of natural killer (NK) cells can lead to both compromised viral clearance and dysregulation of the immune response. Such dysregulation leads to overproduction of cytokines, a raised neutrophil/lymphocyte ratio and monocytosis. This in turn increases IL-6 expression, which promotes scar and thrombus formation. Excess IL-6 also leads to a further reduction in NK function through downregulation of perforin expression, therefore forming a pathogenic auto-inflammatory feedback loop. The perforin/granzyme system of cytotoxicity is the main mechanism through which NK cells and cytotoxic T lymphocytes eliminate virally infected host cells, as well as being central to their role in regulating immune responses to microbial infection. Here, we present epidemiological evidence suggesting an association between perforin expression and resistance to COVID-19. In addition, we outline the manner in which a pathogenic auto-inflammatory feedback loop could operate and the relationship of this loop to genes associated with severe COVID-19. Such an auto-inflammatory loop may be amenable to synergistic multimodal therapy.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Killer Cells, Natural/immunology , Lymphohistiocytosis, Hemophagocytic/immunology , Neutrophils/immunology , Perforin/metabolism , SARS-CoV-2/physiology , Animals , Autoimmunity/genetics , COVID-19/epidemiology , Cytokine Release Syndrome/epidemiology , Disease Resistance , Humans , Interleukin-6/metabolism , Lymphohistiocytosis, Hemophagocytic/epidemiology , Perforin/genetics
4.
Adv Biol Regul ; 81: 100818, 2021 08.
Article in English | MEDLINE | ID: covidwho-1313202

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a wide spectrum of symptom severity, which is manifested at different phases of infection and demands different levels of care. Viral load, host innate-immune response to SARS-CoV-2, and comorbidities have a direct impact on the clinical outcomes of COVID-19 patients and determine the diverse disease trajectories. The initial SARS-CoV-2 penetrance and replication in the host causes death of infected cells, determining the viral response. SARS-CoV-2 replication in the host triggers the activation of host antiviral immune mechanisms, determining the inflammatory response. While a healthy immune response is essential to eliminate infected cells and prevent spread of the virus, a dysfunctional immune response can result in a cytokine storm and hyperinflammation, contributing to disease progression. Current therapies for COVID-19 target the virus and/or the host immune system and may be complicated in their efficacy by comorbidities. Here we review the evidence for use of two classes of anti-inflammatory drugs, glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of COVID-19. We consider the clinical evidence regarding the timing and efficacy of their use, their potential limitations, current recommendations and the prospect of future studies by these and related therapies.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19/drug therapy , Glucocorticoids/therapeutic use , SARS-CoV-2/physiology , Virus Replication/drug effects , COVID-19/epidemiology , COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/immunology , Humans , Viral Load/drug effects , Viral Load/immunology , Virus Replication/immunology
5.
Indian J Pharmacol ; 53(3): 226-228, 2021.
Article in English | MEDLINE | ID: covidwho-1282691

ABSTRACT

Although many potent drugs have been used for cytokine storm, mortality is high for patients with coronavirus disease-2019 (COVID-19), which is followed up in the intensive care unit. Interferons (IFNs) are the major cytokines of the antiviral defense system released from many cell types. However, IFN-γ plays a key role in both primary and secondary cytokine storms. If the cytokine storm is not treated urgently, it will be fatal; therefore, it should be treated immediately. Anakinra, an interleukin-1 (IL-1) antagonist, tocilizumab, an IL-6 antagonist, and Janus kinase (JAK) inhibitors are successfully used in cytokine storm caused by COVID-19. However, sometimes, despite these treatments, the patient's clinical course does not improve. Emapalumab (Eb) is the human immunoglobulin G1 monoclonal antibody and is a potent and noncompetitive antagonist of IFN-γ. Eb can be life saving for cytokine storm caused by COVID-19, which is resistant to anakinra, tocilizumab, and JAK inhibitors.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Neutralizing/pharmacology , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , COVID-19/epidemiology , COVID-19/immunology , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/immunology , Disease Progression , Drug Resistance, Viral , Humans , Interferon-gamma/antagonists & inhibitors , Interferon-gamma/immunology , Interleukin 1 Receptor Antagonist Protein/pharmacology , Interleukins/antagonists & inhibitors , Interleukins/immunology , Janus Kinase Inhibitors/pharmacology , Recurrence
6.
Naunyn Schmiedebergs Arch Pharmacol ; 394(3): 561-567, 2021 03.
Article in English | MEDLINE | ID: covidwho-1235720

ABSTRACT

Coronavirus disease 2019 (COVID-19) has been characterized by lymphopenia as well as a proinflammatory cytokine storm, which are responsible for the poor prognosis and multiorgan defects. The transcription factor nuclear factor-κB (NF-κB) modulates the functions of the immune cells and alters the gene expression profile of different cytokines in response to various pathogenic stimuli, while many proinflammatory factors have been known to induce NF-κB signalling cascade. Besides, NF-κB has been known to potentiate the production of reactive oxygen species (ROS) leading to apoptosis in various tissues in many diseases and viral infections. Though the reports on the involvement of the NF-κB signalling pathway in COVID-19 are limited, the therapeutic benefits of NF-κB inhibitors including dexamethasone, a synthetic form of glucocorticoid, have increasingly been realized. Considering the fact, the abnormal activation of the NF-κB resulting from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection might be associated with the pathogenic profile of immune cells, cytokine storm and multiorgan defects. Thus, the pharmacological inactivation of the NF-κB signalling pathway can strongly represent a potential therapeutic target to treat the symptomatology of COVID-19. This article signifies pharmacological blockade of the phosphorylation of inhibitor of nuclear factor kappa B kinase subunit beta (IKKß), a key downstream effector of NF-κB signalling, for a therapeutic consideration to attenuate COVID-19.


Subject(s)
COVID-19/drug therapy , Drug Delivery Systems/trends , I-kappa B Kinase/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Signal Transduction/physiology , Animals , COVID-19/epidemiology , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/metabolism , Heterocyclic Compounds, 3-Ring/administration & dosage , Humans , I-kappa B Kinase/metabolism , Lymphopenia/drug therapy , Lymphopenia/epidemiology , Lymphopenia/metabolism , NF-kappa B/metabolism , Nitriles/administration & dosage , Pyridines/administration & dosage , Signal Transduction/drug effects , Sulfones/administration & dosage
7.
Front Immunol ; 12: 589095, 2021.
Article in English | MEDLINE | ID: covidwho-1231334

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing major threat to global health and has posed significant challenges for the treatment of severely ill COVID-19 patients. Several studies have reported that cytokine storms are an important cause of disease deterioration and death in COVID-19 patients. Consequently, it is important to understand the specific pathophysiological processes underlying how cytokine storms promote the deterioration of COVID-19. Here, we outline the pathophysiological processes through which cytokine storms contribute to the deterioration of SARS-CoV-2 infection and describe the interaction between SARS-CoV-2 and the immune system, as well as the pathophysiology of immune response dysfunction that leads to acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS), and coagulation impairment. Treatments based on inhibiting cytokine storm-induced deterioration and occurrence are also described.


Subject(s)
COVID-19 , Cytokine Release Syndrome , Pandemics , SARS-CoV-2/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/pathology , COVID-19/physiopathology , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/physiopathology , Humans
8.
Nutrients ; 13(4)2021 Apr 14.
Article in English | MEDLINE | ID: covidwho-1187013

ABSTRACT

The novel severe acute respiratory syndrome coronavirus (COVID-19) has hit older adults harder due to a combination of age-related immunological and metabolic alterations. The aim of this review was to analyze the COVID-19 literature with respect to nutritional status and nutrition management in older adults. No studies only on people aged 65+ years were found, and documentation on those 80+ was rare. Age was found to be strongly associated with worse outcomes, and with poor nutritional status. Prevalence of malnutrition was high among severely and critically ill patients. The studies found a need for nutrition screening and management, and for nutrition support as part of follow-up after a hospital stay. Most tested screening tools showed high sensitivity in identifying nutritional risk, but none were recognized as best for screening older adults with COVID-19. For diagnosing malnutrition, the Global Leadership Initiative on Malnutrition (GLIM) criteria are recommended but were not used in the studies found. Documentation of olfactory and gustatory dysfunction in relation to nutritional status is missing in older adults. Other COVID-19-associated factors with a possible impact on nutritional status are poor appetite and gastrointestinal symptoms. Vitamin D is the nutrient that has attracted the most interest. However, evidence for supplementation of COVID-19 patients is still limited and inconclusive.


Subject(s)
Aging , COVID-19/epidemiology , Nutrition Assessment , Nutrition Therapy/methods , Nutritional Status , Age Factors , Aged , Aged, 80 and over , Agnosia/epidemiology , COVID-19/therapy , Cytokine Release Syndrome/epidemiology , Female , Gastrointestinal Diseases/epidemiology , Hospitalization , Humans , Male , Malnutrition/epidemiology , Middle Aged , Olfaction Disorders/epidemiology , Prevalence , Risk Factors , SARS-CoV-2 , Sarcopenia/epidemiology , Vitamin D/therapeutic use
9.
J Clin Neurosci ; 88: 108-112, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1174389

ABSTRACT

The novel human coronavirus disease (COVID-19) has been associated with vascular and thrombotic complications, some of which may result from endothelial dysfunction, including the posterior reversible encephalopathy syndrome (PRES). We report a case series of 8 patients with COVID-19 and PRES diagnosed at two academic medical centers between March and July of 2020. The clinical, laboratory and radiographic data, treatment, and short-term outcomes were retrospectively analyzed. The mean age was 57.9 ± 12 years, and 50% were women. Four patients had previous vascular comorbidities. All the patients suffered from severe pneumonia, requiring intensive care unit admission. Five patients were not hypertensive at presentation (all SBP < 127 mmHg). Neurologic symptoms included seizures in 7 patients; impaired consciousness in 5 patients; focal neurological signs in 3 patients; and visual disturbances in 1 patient. All patients underwent brain magnetic resonance imaging which indicated asymmetric T2 prolongation or diffusion changes (50%), extensive fronto-parieto-occipital involvement (25%), vascular irregularities (12.5%) and intracranial hemorrhage (25%). Four patients were treated with tocilizumab. Three patients were discharged without neurologic disability, 2 patients had persistent focal neurologic deficits and 2 expired. One patient's prognosis remains guarded. Together, these data support the relationship between PRES and endothelial dysfunction associated with severe COVID-19. In patients with severe COVID-19, PRES can be triggered by uncontrolled hypertension, or occur independently in the setting of systemic illness and certain medications. Like other infectious processes, critically ill patients with COVID-19 may be at greater risk of PRES because of impaired vasoreactivity or the use of novel agents like Tocilizumab.


Subject(s)
COVID-19/complications , Posterior Leukoencephalopathy Syndrome/etiology , Adult , Aged , Brain/diagnostic imaging , Comorbidity , Consciousness Disorders/etiology , Critical Care/statistics & numerical data , Critical Illness , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/etiology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nervous System Diseases/epidemiology , Nervous System Diseases/etiology , Pneumonia/etiology , Pneumonia/therapy , Retrospective Studies , Seizures/etiology , Vision Disorders/etiology
10.
Ann Clin Transl Neurol ; 8(4): 968-979, 2021 04.
Article in English | MEDLINE | ID: covidwho-1155205

ABSTRACT

OBJECTIVE: Many neurological manifestations are associated with COVID-19, including a distinct form of encephalopathy related to cytokine storm, the acute systemic inflammatory syndrome present in a subgroup of COVID-19 patients. Cytokine storm is also associated with immune effector cell-associated neurotoxicity syndrome (ICANS), a complication of chimeric antigen receptor T-cell (CAR-T) therapy, a highly effective treatment for refractory hematological malignancies. We investigated whether COVID-19-related encephalopathy, ICANS, and other encephalopathies associated with cytokine storm, share clinical and investigative findings. METHODS: Narrative literature review. RESULTS: Comparisons between COVID-19-related encephalopathy and ICANS revealed several overlapping features. Clinically, these included dysexecutive syndrome, language disturbances, akinetic mutism and delirium. EEG showed a prevalence of frontal abnormalities. Brain MRI was often unrevealing. CSF elevated cytokine levels have been reported. A direct correlation between cytokine storm intensity and severity of neurological manifestations has been shown for both conditions. Clinical recovery occurred spontaneously or following immunotherapies in most of the patients. Similar clinical and investigative features were also reported in other encephalopathies associated with cytokine storm, such as hemophagocytic lymphohistiocytosis, sepsis, and febrile infection-associated encephalopathies. INTERPRETATION: COVID-19-related encephalopathy and ICANS are characterized by a predominant electro-clinical frontal lobe dysfunction and share several features with other encephalopathies associated with cytokine storm, which may represent the common denominator of a clinical spectrum of neurological disorders. Therefore, we propose a unifying definition of cytokine storm-associated encephalopathy (CySE), and its diagnostic criteria.


Subject(s)
Brain Diseases/physiopathology , Brain/physiopathology , COVID-19/physiopathology , Cytokine Release Syndrome/physiopathology , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen , Brain Diseases/epidemiology , Brain Diseases/therapy , COVID-19/epidemiology , COVID-19/therapy , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/therapy , Humans , Immunotherapy, Adoptive/trends
11.
Vascul Pharmacol ; 138: 106857, 2021 06.
Article in English | MEDLINE | ID: covidwho-1144980

ABSTRACT

COVID-19 is a pandemic illness caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2). It has been estimated that 80% of subject infected are asymptomatic or have mild to moderate symptoms. Differently, in severe cases of COVID-19, cytokine storm, acute respiratory distress syndrome (ARDS), severe systemic inflammatory response and cardiovascular diseases were observed Even if all molecular mechanisms leading to cardiovascular dysfunction in COVID-19 patients remain to be clarified, the evaluation of biomarkers of cardiac injury, stress and inflammation proved to be an excellent tool to identify the COVID-19 patients with worse outcome. However, the number of biomarkers used to manage COVID-19 patients is expected to increase with the increasing knowledge of the pathophysiology of the disease. It is our view that soluble suppressor of tumorigenicity 2 (sST2) can be used as biomarker in COVID-19. sST2 is routinely used as prognostic biomarker in patients with HF. Moreover, high circulating levels of sST2 have also been found in subjects with ARDS, pulmonary fibrosis and sepsis. Keeping in mind these considerations, in this review the possible mechanisms through which the SARS-CoV2 infection could damage the cardiovascular system were summarized and the possible role of sST2 in COVID-19 patients with CVD was discussed.


Subject(s)
COVID-19/epidemiology , COVID-19/metabolism , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/metabolism , Interleukin-1 Receptor-Like 1 Protein/metabolism , Animals , Biomarkers/metabolism , COVID-19/diagnosis , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/metabolism , Cytokine Release Syndrome/diagnosis , Humans , Prognosis
12.
Prostaglandins Other Lipid Mediat ; 154: 106539, 2021 06.
Article in English | MEDLINE | ID: covidwho-1083625

ABSTRACT

The World Health Organization has described the 2019 Coronavirus disease caused by an influenza-like virus called SARS-CoV-2 as a pandemic. Millions of people worldwide are already infected by this virus, and severe infection causes hyper inflammation, thus disrupting lung function, exacerbating breath difficulties, and death. Various inflammatory mediators bio-synthesized through the arachidonic acid pathway play roles in developing cytokine storms, injuring virus-infected cells. Since pro-inflammatory eicosanoids, including prostaglandins, and leukotrienes, are key brokers for physiological processes such as inflammation, fever, allergy, and pain but, their function in COVID-19 is not well defined. This study addresses eicosanoid's crucial role through the arachidonic pathway in inflammatory cascading and recommends using bioactive lipids, NSAIDs, steroids, cell phospholipase A2 (cPLA2) inhibitors, and specialized pro-resolving mediators (SPMs) to treat COVID-19 disease. The role of soluble epoxide hydrolase inhibitors (SEHIs) in promoting the activity of epoxyeicosatrienoic acids (EETs) and 17-hydroxide-docosahexaenoic acid (17-HDHA) is also discussed. Additional research that assesses the eicosanoid profile in COVID-19 patients or preclinical models generates novel insights into coronavirus-host interaction and inflammation regulation.


Subject(s)
Arachidonic Acids/metabolism , COVID-19 , Inflammation Mediators/metabolism , Pandemics , SARS-CoV-2/metabolism , COVID-19/epidemiology , COVID-19/metabolism , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/metabolism , Humans
13.
Front Immunol ; 11: 603389, 2020.
Article in English | MEDLINE | ID: covidwho-1069720

ABSTRACT

The catastrophic outbreak of coronavirus disease 2019 (COVID-19) is currently a public emergency. Adult-onset Still's disease (AOSD) is an autoinflammatory disease characterized by life-threatening complications. Systemic hyperinflammation and cytokine storm play a critical role in the pathogenesis of both COVID-19 and AOSD. We aimed to compare the similarities and differences focusing on ferritin and cytokine levels between severe COVID-19 and active AOSD. A literature search was performed using the databases PubMed, EMBASE, and Web of Science to collect the levels of cytokine including IL-1ß, IL-6, IL-18, TNF-α, IL-10, and ferritin in severe COVID-19 patients. After extracting available data of indicators of interest, we acquired these statistics with a single-arm meta-analysis. Furthermore, a comparison was conducted between 52 patients with active AOSD in our center and severe COVID-19 patients from databases. The levels of IL-6 and IL-10 were higher in severe COVID-19 compared with those in active AOSD. There were no significant differences on the cytokine of IL-1ß and TNF-α. Fold changes of IL-18 were defined as the mean expression level ratio of severe COVID-19 to healthy controls in the COVID-19 study and active AOSD to healthy controls in our study, individually. Although the fold change of IL-18 in patients with AOSD was significantly higher than patients with severe COVID-19 (fold change: 594.00 vs 2.17), there was no statistical comparability. In addition, the level of ferritin was higher in active AOSD in comparison with severe COVID-19. Our findings suggest that severe COVID-19 and active AOSD have differences in cytokine panel and ferritin level, indicating the pathogenic role of ferritin in overwhelming inflammation. And it paves the way to make efficacy therapeutic strategy targeting the hyperinflammatory process in COVID-19 according to AOSD management, especially in severe COVID-19.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Inflammation/immunology , Still's Disease, Adult-Onset/immunology , Adult , Aged , COVID-19/epidemiology , Cytokine Release Syndrome/epidemiology , Cytokines/blood , Female , Ferritins/blood , Humans , Male , Middle Aged , Still's Disease, Adult-Onset/epidemiology
14.
Int Urol Nephrol ; 53(10): 2117-2125, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1064574

ABSTRACT

BACKGROUND: The prognostic factors for COVID-19 in patients with chronic kidney disease (CKD) are uncertain. We conducted a study to compare clinical and prognostic features between hospitalized COVID-19 patients with and without CKD. METHODS: Fifty-six patients with stage 3-5 CKD and propensity score-matched fifty-six patients without CKD were included in the study. Patients were followed-up at least fifteen days or until death after COVID-19 diagnosis. The endpoints were death from all causes, development of acute kidney injury (AKI) or cytokine release syndrome or respiratory failure, or admission to the intensive care unit (ICU). RESULTS: All patients were reviewed retrospectively over a median follow-up of 44 days (IQR, 36-52) after diagnosis of COVID-19. Patients with CKD had higher intensive care unit admission and mortality rates than the patients without CKD, but these results did not reach statistical significance (16 vs. 19; p = 0.54 and 11 vs. 16, p = 0.269, respectively). The frequency of AKI development was significantly higher in predialysis patients with CKD compared to the other group (8 vs. 5; p < 0.001), but there was no significant difference between the groups in terms of cytokine release syndrome (13 vs. 8; p = 0.226), follow-up in the ICU (19 vs. 16; p = 0.541), and respiratory failure (25 vs. 22, p = 0.566). Multivariate logistic regression analysis revealed that respiratory failure and AKI were independent risk factors for mortality. CONCLUSION: The mortality rates of COVID-19 patients with CKD had higher than COVID-19 patients without CKD. Also, AKI and respiratory failure were independently related to mortality.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Renal Insufficiency, Chronic/complications , Acute Kidney Injury/epidemiology , Adult , Aged , COVID-19/therapy , Critical Care , Cytokine Release Syndrome/epidemiology , Female , Hospital Mortality , Hospitalization , Humans , Male , Middle Aged , Propensity Score , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/therapy , Respiratory Insufficiency/epidemiology , Retrospective Studies , Risk Factors , Survival Rate
15.
Clin Microbiol Rev ; 34(1)2020 10 14.
Article in English | MEDLINE | ID: covidwho-1029783

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, introduced the third highly pathogenic coronavirus into humans in the 21st century. Scientific advance after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic and Middle East respiratory syndrome coronavirus (MERS-CoV) emergence enabled clinicians to understand the epidemiology and pathophysiology of SARS-CoV-2. In this review, we summarize and discuss the epidemiology, clinical features, and virology of and host immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2 and the pathogenesis of coronavirus-induced acute respiratory distress syndrome (ARDS). We especially highlight that highly pathogenic coronaviruses might cause infection-associated hemophagocytic lymphohistiocytosis, which is involved in the immunopathogenesis of human coronavirus-induced ARDS, and also discuss the potential implication of hemophagocytic lymphohistiocytosis therapeutics for combating severe coronavirus infection.


Subject(s)
Coronavirus Infections/epidemiology , Cytokine Release Syndrome/epidemiology , Lymphohistiocytosis, Hemophagocytic/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Betacoronavirus/genetics , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/physiopathology , Host-Pathogen Interactions , Humans , Infectious Disease Incubation Period , Lung/immunology , Lung/physiopathology , Lung/virology , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/mortality , Lymphohistiocytosis, Hemophagocytic/physiopathology , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Phylogeny , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , SARS Virus/genetics , SARS Virus/immunology , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/physiopathology , Severity of Illness Index , Survival Analysis
16.
Biomed Pharmacother ; 135: 111233, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1009323

ABSTRACT

Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, has led to the ongoing global pandemic. Although most patients experience no or only mild symptoms, some patients can develop severe illness, such as progressive pneumonia, acute respiratory distress syndrome, secondary hemophagocytic lymphohistiocytosis and multiple organ failure caused by cytokine release syndrome. A majority of COVID-19 patients also develop gastrointestinal symptoms. These can present special challenges to the management of patients with inflammatory bowel disease (IBD) due to potential interactions between the immune response related to SARS-CoV-2 infection and dysregulated immunity associated with IBD. In this context, the pathogenesis of COVID-19 is reviewed in order to address these questions regarding immune interactions between COVID-19 and IBD.


Subject(s)
COVID-19/epidemiology , COVID-19/physiopathology , Immunity/physiology , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/physiopathology , Angiotensin-Converting Enzyme 2/drug effects , Angiotensin-Converting Enzyme 2/immunology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/physiopathology , Humans , Immunity/drug effects , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/immunology
17.
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)
COVID-19 , Cytokine Release Syndrome , Disease Outbreaks , Immunotherapy , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/immunology , COVID-19/complications , COVID-19/epidemiology , COVID-19/immunology , COVID-19/therapy , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Humans , Immunity, Innate/immunology
18.
Molecules ; 25(24)2020 Dec 12.
Article in English | MEDLINE | ID: covidwho-972696

ABSTRACT

SARS-CoV-2 first emerged in China during late 2019 and rapidly spread all over the world. Alterations in the inflammatory cytokines pathway represent a strong signature during SARS-COV-2 infection and correlate with poor prognosis and severity of the illness. The hyper-activation of the immune system results in an acute severe systemic inflammatory response named cytokine release syndrome (CRS). No effective prophylactic or post-exposure treatments are available, although some anti-inflammatory compounds are currently in clinical trials. Studies of plant extracts and natural compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation. The aim of this manuscript is to review the published background on the possible effectiveness of polyphenols to fight SARS-COV-2 infection, contributing to the reduction of inflammation. Here, some of the anti-inflammatory therapies are discussed and although great progress has been made though this year, there is no proven cytokine blocking agents for COVID currently used in clinical practice. In this regard, bioactive phytochemicals such as polyphenols may become promising tools to be used as adjuvants in the treatment of SARS-CoV-2 infection. Such nutrients, with anti-inflammatory and antioxidant properties, associated to classical anti-inflammatory drugs, could help in reducing the inflammation in patients with COVID-19.


Subject(s)
COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Pandemics , Phytochemicals/therapeutic use , Polyphenols/therapeutic use , SARS-CoV-2 , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/epidemiology , China/epidemiology , Cytokine Release Syndrome/epidemiology , Humans , Inflammation/drug therapy , Inflammation/epidemiology , Polyphenols/chemistry
19.
Biochim Biophys Acta Mol Basis Dis ; 1867(2): 166014, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-938765

ABSTRACT

The coronavirus disease 2019 (COVID-19) has been threatening the globe since the end of November 2019. The disease revealed cracks in the health care system as health care providers across the world were left without guidelines on definitive usage of pharmaceutical agents or vaccines. The World Health Organization (WHO) declared COVID-19 as a pandemic on the 11th of March 2020. Individuals with underlying systemic disorders have reported complications, such as cytokine storms, when infected with the virus. As the number of positive cases and the death toll across the globe continue to rise, various researchers have turned to cell based therapy using stem cells to combat COVID-19. The field of stem cells and regenerative medicine has provided a paradigm shift in treating a disease with minimally invasive techniques that provides maximal clinical and functional outcome for patients. With the available evidence of immunomodulatory and immune-privilege actions, mesenchymal stem cells (MSCs) can repair, regenerate and remodulate the native homeostasis of pulmonary parenchyma with improved pulmonary compliance. This article revolves around the usage of novel MSCs therapy for combating COVID-19.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Cytokine Release Syndrome/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/immunology , Pandemics , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/pathology , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Female , Humans , Male , Mesenchymal Stem Cells/pathology
20.
Expert Opin Biol Ther ; 21(5): 615-626, 2021 05.
Article in English | MEDLINE | ID: covidwho-915830

ABSTRACT

Introduction: The coronavirus disease 2019 (COVID-19) pandemic, caused by a newly discovered coronavirus (severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2), continues to spread all around the world. Despite the emergency of COVID-19 worldwide, remdesivir is the only treatment that has been recently approved to treat the diseases, and other effective therapies are still lacking. SARS-CoV-2 may cause severe illness in 20% of patients. Based on available data, there is an association between interleukin-6 (IL-6) and severe COVID-19. Sarilumab is a fully human immunoglobulin G1 monoclonal antibody binding to both membrane-bound and soluble IL-6 receptors with high affinity and has been considered for off-label use in the treatment of COVID-19.Areas covered: The present article reviews recently published literature focusing on the pathophysiology of COVID-19 induced cytokine storm, the potential therapeutic role, and important clinical issues of sarilumab in the treatment of COVID-19 patients.Expert opinion: The off-label treatment administration is unavoidable in the critical situation of the COVID-19 pandemic. Further efforts should be directed to determine mechanisms of SARS-CoV-2 induced immune dysregulation as well as indications of sarilumab in the patients with COVID-19 to minimize concerns regarding its off-label administration.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , SARS-CoV-2/drug effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/metabolism , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/metabolism , Alanine/therapeutic use , Animals , Antibodies, Monoclonal, Humanized/metabolism , Antibodies, Monoclonal, Humanized/pharmacology , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19/metabolism , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/metabolism , Humans , Pandemics , SARS-CoV-2/metabolism
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