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1.
Revista Cubana de Medicina Militar ; 50(4), 2021.
Article in Spanish | Scopus | ID: covidwho-1801644

ABSTRACT

Introduction: Infection with SARS-CoV-2 induces a prothrombotic state in patients, by the combination of hyperinflammatory response and hypoxia. In Cuba, the drug called Jusvinza, based on an immunomodulatory peptide, is used for the treatment of patients with COVID-19, who present signs and symptoms of hyperinflammation. Objectives: To describe the clinical course and behavior of various biomarkers associated with the inflammation and coagulation, in a group of critically ill patients with COVID-19 treated with Jusvinza, compared to a group of patients who did not receive treatment with this peptide. Methods: 40 critically ill patients with COVID-19 were included. The patients were divided into 2 groups: 20 patients were treated with Jusvinza and 20 were not treated with this peptide (control group). Demographic characteristics, comorbidities, vital signs, respiratory parameters and inflammation and coagulation biomarkers were obtained from the medical records of each patient. Results: Treatment with Jusvinza induced a clinical improvement in the patients, associated with the decrease of several inflammation and coagulation biomarkers. Patients treated with Jusvinza had a significantly higher survival than patients not treated with this peptide. Conclusions: Jusvinza is able to control hyperinflammation and hypercoagulation in critical ill patients with COVID-19. © 2021, Editorial Ciencias Medicas. All rights reserved.

2.
Journal of Gastroenterology and Hepatology Research ; 10(6):3604-3607, 2022.
Article in English | EMBASE | ID: covidwho-1791621

ABSTRACT

The global corona virus disease (COVID-19) pandemic has caused the unforeseen crisis to the modern society. In this brief review, we discussed the putative role of butyrate derived from intestinal fermentation in attenuating the COVID-19 severity, and suggested the use of multifarious butyrate by targeting cytokine storm and gut microbiota dysbiosis for the suppression of hyper-inflammatory immune response of COVID-19 infection.

3.
Cureus ; 14(2): e22614, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1776620

ABSTRACT

Hyperinflammation is a key component of severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. It is imperative to distinguish severe COVID-19 from hyperinflammatory syndromes such as multisystem inflammatory syndrome (MIS) and hemophagocytic lymphohistiocytosis. There is a subset of post-COVID-19 patients who present with some symptoms characteristic of MIS in adults (MIS-A) yet do not meet all the criteria for a diagnosis. We describe the unique case of a patient with this kind of presentation who clinically improved following tocilizumab and corticosteroid usage.

4.
Open Access Macedonian Journal of Medical Sciences ; 10:220-227, 2022.
Article in English | EMBASE | ID: covidwho-1771282

ABSTRACT

BACKGROUND: Cytokine storm in COVID-19 patients has contributed to many morbidities and mortalities in patients. Studies have found that toll-like receptors (TLRs) and some Fc receptors play essential roles in the hyperactivation of the immune system. Up to date, researchers are still in progress to discover effective and safe drugs to alleviate the hyperinflammatory state in COVID-19. The previous studies had shown that Carthamus tinctorius and its bioactive compounds might have anti-inflammatory activities in animal models. AIM: We aimed to investigate the possible interactions of several flavonoids from C. tinctorius with several immune system components using a biocomputational approach. METHODS: Molecular docking was done using the AutoDock program based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) COVID-19 pathway. The most suitable receptors found were studied to study the interactions with several flavonoids from C. tinctorius. RESULTS: TLR4, TLR8, and FcγRIIa were found to bind with SARS CoV2 inflammatory pathway and further selected as macromolecules for potential interactions study with 22 flavonoids from C. tinctorius. Of the 22 flavonoids studied, daphnoretin showed the best binding affinity with TLR4 and Rutin was shown to attach best with FcγRIIa. Unlike its excellent binding to TLR4, daphnoretin showed weak binding to TLR8. CONCLUSION: Daphnoretin showed an excellent affinity with TLR4 and might be a good candidate as an inhibitor in hyperinflammatory reactions in COVID-19 DTLR8.

5.
Genetics in Medicine ; 24(3):S242, 2022.
Article in English | EMBASE | ID: covidwho-1768096

ABSTRACT

Introduction: The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has resulted in an ongoing vicious pandemic. COVID-19 has a wide range of clinical outcomes ranging from no clinical symptoms to severe respiratory disease and death. Disease severity has been linked to old age and other co-morbidities. In children and infants, the infection has typically a milder and often asymptomatic course. However, Multisystem Inflammatory Syndrome in Children (MIS-C) has been recognized as a pediatric complication of severe acute respiratory syndrome coronavirus-2 infections. It is a state of hyperinflammation that typically presents 4-6 weeks after SARS-CoV-2 acute infection with high fever, organ dysfunction, and raised inflammatory markers leading to multiorgan failure and shock. Family clusters of MIS-C have been reported suggesting heritable traits predisposing to severe infection. The underlying cause of phenotypic heterogeneity, susceptibility, and disease severity among affected individuals is still unclear. It has been thought that both viral and host genetic variations could be probable factors influencing the disease severity and susceptibility. To this end, we have studied the clinical and genetic characteristics of children with MIS-C in Kuwait. Utilizing 28 large kindreds with familial MIS-C clustering, we report, here, the preliminary results obtained from three families. Methods: Children aged ≤ 12 years who met the World Health Organization (WHO) MIS-C diagnostic criteria were identified from the national Pediatric COVID-19 Registry in Kuwait (PCR-Q8). Detailed demographic and clinical phenotype data were obtained from medical charts. All subjects and their families were invited for blood molecular genetic testing. Genetic analysis using genome sequencing at 30x depth has been performed on the affected individuals and their parents. In this , we present preliminary results from three families. Results: Sixty-seven children with MIS-C were identified in the period between April 2020 and October 2021. So far, molecular genetic testing was performed on 28 subjects and their biological parents. Genetic analysis (genome sequencing) of 3 families was completed. All of the three children were previously healthy, non-obese, with no known co-morbidities, and no family history of MIS-C. They all had evidence of recent SARS-CoV-2 infection (positive RT-PCR result and positive IgG antibody detection). One child aged 9 years developed myocarditis as a complication of MIS-C. He presented with hypotension, hemodynamic instability, and required inotropic support. All three kids have fully recovered after receiving respiratory support in the Pediatric Intensive Care Unit (PICU). Consanguinity was observed in two families. Probands harbored various homozygous variants in the BTNL8, IL17RA, and IRS4 genes will be presented and discussed. Conclusion: This is the first study to review the demographic, clinical, epidemiological, and genetic characteristics of children with MIS-C in Kuwait. Although familial clustering of severe COVID-19 infection has not been observed in our cohort, our data shows that utilizing a family-based study allows for significant enrichment for homozygous genetic variants that may impact our understanding of MIS-C.

6.
Open Forum Infectious Diseases ; 8(SUPPL 1):S325, 2021.
Article in English | EMBASE | ID: covidwho-1746547

ABSTRACT

Background. Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare, life-threatening, hyperinflammatory condition presumed to follow SARS-CoV-2 infection. Whether MIS-C can also follow SARS-CoV-2 vaccination is not clear, making MIS-C an adverse event of special interest following immunization. Monitoring for post-vaccine MIS-C is complicated by the clinical overlap of MIS-C with numerous other inflammatory conditions including Kawasaki Disease, toxic shock syndrome, and viral myocarditis. A case definition for MIS-C was recently created with the Brighton Collaboration (BC). We aimed to determine the performance of the BC MIS-C case definition among a large, single-center MIS-C cohort. Methods. Retrospective review was performed for the first 100 MIS-C cases at our institution (May 2020-February 2021). All cases met the Centers for Disease Control and Prevention (CDC) case definition. Data on age, presentation, laboratory results and cardiac studies were collected and used to determine cases that fulfilled the BC case definition for MIS-C (see figure). Case Definition: Definite Case Results. Of 100 children (age < 21 years) diagnosed with MIS-C using the CDC case definition, 93 patients also fulfilled the BC definition. All 100 patients had elevated laboratory markers of inflammation and positive SARS-CoV-2 antibodies. However, 1 patient was excluded for significant respiratory symptoms (pulmonary hemorrhage), 5 were excluded due to only 1 clinical feature, and an additional patient was excluded for having none of the measures of disease activity. Among the 93 patients fulfilling the revised case definition, 88 (95%) met criteria for a definite case. Five of the 93 patients (5%) were considered probable cases, 1 reported only 1 day of fever and 4 had only 1 measure of disease activity. Conclusion. The original case definitions for MIS-C were created rapidly following the first emerging reports of this hyperinflammatory state. Knowledge of the varied clinical presentations of this disorder has grown substantially. Modification of the case definition to include features truly representative of MIS-C will allow for more precise diagnosis in the face of conditions which mimic MIS-C, and for accurate and reliable monitoring for adverse events following immunization.

7.
Journal of the Hong Kong College of Cardiology ; 28(2):105, 2020.
Article in English | EMBASE | ID: covidwho-1743807

ABSTRACT

Objectives: To have a comprehensive review on effects of novel coronavirus on heart. Methods: review article. Results: The novel coronavirus may affect cardiac tissue via three main mechanisms: 1-direct myocardial injury and myocarditis caused by the virus, 2-hyper-inflammation and immunopathology, and 3-respiratory failure, acute respiratory distress syndrome, and effects of hypoxemia on cardiac tissue. In a large number of patients, all three mechanisms are involved. Hypercoagulability is a mechanism for coronary artery stenosis and acute coronary syndrome or myocardial infarction. Also, blood pressure abnormalities, either hypertension or hypotension are frequent in severely ill patients. A high proportion of critically ill patients develop arrhythmias. Arrhythmias may arise due to hypoxemia, metabolic derangements, systemic inflammation, or myocarditis. In a postmortem study, real-time polymerase chain reaction analyses on heart tissue detected the viral genome in nearly one third of patients. Interleukin-6, serum ferritin, brain natriuretic peptide, and high sensitivity cardiac troponin are among the various biomarkers elevated during the course of the disease. It has been shown that as the disease severity increases and in the 3rd stage of the disease-host response-inflammatory and cardiac markers show elevations. Cardiac involvement ad elevated cardiac biomarkers are prominent features in COVID-19 and associated with a worse prognosis and increased mortality. In a survey in Wuhan, 40% of deaths were attributed to myocardial damage or heart failure, alone or in combination with respiratory failure. In autopsies, mononuclear infiltrates of macrophages and CD4+ T cells have been shown in areas of cardiac necrosis. It has been proposed that acute cardiac involvement is a stronger risk factor for increased mortality than age, diabetes mellitus, chronic pulmonary disease, or even history of cardiovascular disease. Since the virus is new-emerging, we do not know much about its long term consequences. So, its effects on heart in the convalescent and chronic phases are not well-known. Delayed myocarditis, cardiac arrest, hyperlipidemia and pulmonary fibrosis are possible long term consequences of the disease. Conclusion: We have to be aware of cardiac consequences of COVID-19 to manage the disease optimally.

8.
Biomolecules ; 12(3)2022 03 13.
Article in English | MEDLINE | ID: covidwho-1742313

ABSTRACT

Severe COVID-19 disease leads to hypoxemia, inflammation and lymphopenia. Viral infection induces cellular stress and causes the activation of the innate immune response. The ubiquitin-proteasome system (UPS) is highly implicated in viral immune response regulation. The main function of the proteasome is protein degradation in its active form, which recognises and binds to ubiquitylated proteins. Some proteasome subunits have been reported to be upregulated under hypoxic and hyperinflammatory conditions. Here, we conducted a prospective cohort study of COVID-19 patients (n = 44) and age-and sex-matched controls (n = 20). In this study, we suggested that hypoxia could induce the overexpression of certain genes encoding for subunits from the α and ß core of the 20S proteasome and from regulatory particles (19S and 11S) in COVID-19 patients. Furthermore, the gene expression of proteasome subunits was associated with lymphocyte count reduction and positively correlated with inflammatory molecular and clinical markers. Given the importance of the proteasome in maintaining cellular homeostasis, including the regulation of the apoptotic and pyroptotic pathways, these results provide a potential link between COVID-19 complications and proteasome gene expression.


Subject(s)
COVID-19 , Lymphopenia , COVID-19/genetics , Humans , Hypoxia , Inflammation/genetics , Lymphopenia/genetics , Prospective Studies , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/metabolism
9.
J Allergy Clin Immunol ; 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1739828

ABSTRACT

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening sequela of SARS-COV-2 infection characterized by hyperinflammation and multi-organ dysfunction. Though hyperinflammation is a prominent manifestation of MIS-C, there is limited understanding of how the inflammatory state of MIS-C differs from well characterized hyperinflammatory syndromes such as hemophagocytic lymphohistiocytosis (HLH). OBJECTIVES: To compare the qualitative and quantitative inflammatory profile differences between MIS-C, COVID-19 and HLH patients. METHODS: Clinical data abstraction from patient charts, T cell immunophenotyping and multiplex cytokine and chemokine profiling were performed for MIS-C, COVID-19 and HLH patients. RESULTS: We found that both MIS-C and HLH showed robust T cell activation, markers of senescence, and exhaustion along with elevated Th1 and pro-inflammatory cytokines such as IFN-γ, CXCL9, and CXCL10. In comparison, the amplitude of T cell activation and the levels of cytokines/chemokines were higher in HLH when compared to MIS-C. Distinguishing inflammatory features of MIS-C included elevation in Th2 inflammatory cytokines such as IL-4 and IL-13 and cytokine mediators of angiogenesis, vascular injury, and tissue repair such as VEGF-A and PDGF. Immune activation and hypercytokinemia in MIS-C resolved at follow-up. In addition, when these immune parameters were correlated with clinical parameters, CD8+ T cell activation correlated with cardiac dysfunction parameters such as BNP and troponin and inversely correlated with platelet count. CONCLUSION: Overall, this study characterizes unique and overlapping immunological features that help to define the hyperinflammation associated with MIS-C versus HLH.

10.
Biology (Basel) ; 11(3)2022 Mar 04.
Article in English | MEDLINE | ID: covidwho-1731933

ABSTRACT

The coronavirus disease 2019 (COVID-19) global pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains uncontrolled, with the spread of emerging variants. According to accumulating evidence, diabetes is one of the leading risk factors for a severe COVID-19 clinical course, depending on the glycemic state before admission and during COVID-19 hospitalization. Multiple factors are thought to be responsible, including an altered immune response, coexisting comorbidity, and disruption of the renin-angiotensin system through the virus-host interaction. However, the precise underlying mechanisms remain under investigation. Alternatively, the focus is currently on the diabetogenic and ketosis-prone potential of SARS-CoV-2 itself, even for probable triggers of stress and steroid-induced hyperglycemia in COVID-19. In this article, we present a comprehensive review of the recent literature on the clinical and experimental findings associated with diabetes and COVID-19, and we discuss their bidirectional relationship, i.e., the risk for an adverse prognosis and the deleterious effects on glycometabolism. Accurate assessments of the incidence of new-onset diabetes induced by COVID-19 and its pathogenicity are still unknown, especially in the context of the circulation of SARS-CoV-2 variants, such as Omicron (B.1.1.529), which is a major challenge for the future.

11.
Turk J Med Sci ; 51(SI-1): 3301-3311, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1726157

ABSTRACT

The COVID-19 pandemic has created a major alteration in the medical literature including the sepsis discussion. From the outset of the pandemic, various reports have indicated that although there are some unique features pertinent to COVID-19, many of its acute manifestations are similar to sepsis caused by other pathogens. As a consequence, the old definitions now require consideration of this new etiologic agent, namely SARS-CoV-2. Although the pathogenesis of COVID-19 has not been fully explained, the data obtained so far in hospitalized patients has revealed that serum cytokine and chemokine levels are high in severe COVID-19 patients, similar to those found with sepsis. COVID-19 may involve multiple organ systems. In addition to the lungs, the virus has been isolated from blood, urine, faeces, liver, and gallbladder. Results from autopsy series in COVID-19 patients have demonstrated a wide range of findings, including vascular involvement, congestion, consolidation, and hemorrhage as well as diffuse alveolar damage in lung tissue consistent with acute respiratory distress syndrome (ARDS). The presence of viral cytopathic-like changes, infiltration of inflammatory cells (mononuclear cells and macrophages), and viral particles in histopathological samples are considered a consequence of both direct viral infection and immune hyperactivation. Thromboembolism and hyper-coagulopathy are other components in the pathogenesis of severe COVID-19. Although the pathogenesis of hypercoagulability is not fully understood, it has been pointed out that all three components of Virchow's triad (endothelial injury, stasis, and hypercoagulable state) play a major role in contributing to clot formation in severe COVID-19 infection. In severe COVID-19 cases, laboratory parameters such as hematological findings, coagulation tests, liver function tests, D-dimer, ferritin, and acute phase reactants such as CRP show marked alterations, which are suggestive of a cytokine storm. Another key element of COVID-19 pathogenesis in severe cases is its similarity or association with hemophagocytic lymphohistiocytosis (HLH). SARS-CoV-2 induced cytokine storm has significant clinical and laboratory findings overlapping with HLH. Viral sepsis has some similarities but also some differences when compared to bacterial sepsis. In bacterial sepsis, systemic inflammation affecting multiple organs is more dominant than in COVID-19 sepsis. While bacterial sepsis causes an early and sudden onset clinical deterioration, viral diseases may exhibit a relatively late onset and chronic course. Consideration of severe COVID-19 disease as a sepsis syndrome has relevance and may assist in terms of determining treatments that will modulate the immune response, limit intrinsic damage to tissue and organs, and potentially improve outcome.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome , Inflammation , Lymphohistiocytosis, Hemophagocytic , Sepsis/complications , Chemokines/blood , Cytokines/blood , Humans , Lymphohistiocytosis, Hemophagocytic/immunology , Pandemics , SARS-CoV-2 , Sepsis/blood
12.
Infection ; 2022 Feb 26.
Article in English | MEDLINE | ID: covidwho-1712372

ABSTRACT

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has led to the approval of novel vaccines with different mechanisms of action. Until now, more than 4.7 billion persons have been vaccinated around the world, and adverse effects not observed in pre-authorization trials are being reported at low frequency. METHODS: We report a case of severe hemophagocytic lymphohistiocytosis (HLH) after SARS-CoV-2 immunization and performed a literature search for all reported cases of COVID-19 vaccine-associated HLH. RESULTS: A 24-year-old female developed HLH after immunization with the mRNA COVID-19 vaccine Comirnaty. Diagnosis was made according to HLH-2004 criteria; the HScore was 259 (> 99% HLH probability) with maximum ferritin of 138.244 µg/L. The patient was initially treated with intravenous immunoglobulins (IVIGs) and dexamethasone without response. The addition of the human interleukin 1 receptor antagonist Anakinra resulted in full recovery within 6 weeks after vaccination. A literature search revealed 15 additional cases of HLH after SARS-CoV-2 vaccination, the majority after immunization with Comirnaty (n = 7) or the viral vector vaccine Vaxzevria (n = 6). Treatment modalities included corticosteroids (n = 13), Anakinra (n = 5), IVIGs (n = 5), and etoposide (n = 2). Eight patients underwent combination treatment. Three of 16 patients died. CONCLUSION: COVID-19 vaccines may occasionally trigger HLH, and Anakinra may be an efficacious treatment option for this condition.

13.
Journal of Investigative Medicine ; 70(2):589, 2022.
Article in English | EMBASE | ID: covidwho-1707355

ABSTRACT

Case Report Multi-system inflammatory syndrome in children (MIS-C) is a recently described clinical syndrome in children that continues to progress in its manifestations. The syndrome is associated with the novel coronavirus disease 2019 (COVID-19), and can affect any organ system in the body, leading to a wide variety of symptoms. This syndrome is often misdiagnosed in its initial presentation, and many families require multiple evaluations before finally being diagnosed and admitted for the appropriate treatment. Symptoms are caused by overwhelming inflammation and often involve the gastrointestinal, integumentary, cardiac, and hematologic systems. A high index of suspicion at the time of initial presentation should be maintained to obtain an accurate diagnosis of MIS-C. Patient Case We report the case of a previously healthy 11-year-old male who presents with acute cervical lymphadenitis that did not respond to appropriate outpatient antibiotic therapy. He has a history of testing positive for SARS-CoV-2 via PCR, associated with mild cough and rhinorrhea, about three weeks prior to the onset of current symptoms. Upon initial presentation physical exam and laboratory results were not consistent with MIS-C, however inflammatory markers were slightly elevated which was consistent with a diagnosis of cervical lymphadenitis. Over the course of the next several days, the patient developed gastrointestinal symptoms including abdominal pain, vomiting and diarrhea. He also developed non-purulent conjunctivitis, and a generalized erythematous rash, associated with significant leukocytosis, transaminitis, and elevated coagulation markers. His electrocardiogram (EKG), and echocardiogram (ECHO) remained within normal limits despite elevated pro-BNP levels, and he later developed significant hypotension, hypoxemia, and bilateral pleural effusions requiring a short course of diuretics. The patient remained febrile despite receiving a normal saline bolus, treatment with intravenous immune globulin (IVIG), and intravenous steroids. He had ongoing symptoms, and the erythematous rash reappeared. His steroid dose was increased, and the patient had a good response in both labs, and clinical status. Leukocytosis has continued, but there is significant improvement in all other inflammatory markers, and the patient is on course to be discharged home safely. Conclusion Many patients are unfortunately misdiagnosed after multiple evaluations before the final diagnosis of MIS-C is made. Multi-system inflammatory syndrome in children (MISC) may mimic other conditions such as gastroenteritis, acute appendicitis, Kawasaki Disease, sepsis, or even lymphadenitis. Clinicians should be alert to subtle signs of inflammation, such as lymphadenitis, that may progress to more classic symptoms of MIS-C such as persistent fever, abdominal pain, and a rash.

14.
Kidney International Reports ; 7(2):S407-S408, 2022.
Article in English | EMBASE | ID: covidwho-1706951

ABSTRACT

Introduction: Mankind has been ravaged by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since 2019. To date, we are still battling with coronavirus disease 2019 (COVID19). Although children seem to experience milder symptoms with acute COVID19 illness, some are burdened by multisystem inflammatory syndrome in children (MIS-C) that classically observes a temporal relationship with COVID19. Methods: Clinical data retrieved from medical records and hospital electronic database with permission. Results: We report herein a 7-year-old incident dialysis patient with an atypical presentation of MIS-C. He had previously experienced recurrent peritoneal dialysis-related peritonitis, which resulted in the removal of his tenckhoff catheter and was subsequently on chronic hemodialysis. He developed COVID-19 pneumonia after adults in the family caught the infection. The child experienced an uneventful recovery with nasal oxygen supplementation and a course of steroids. However, he developed gross abdominal distension approximately three weeks post COVID-19 which was not associated with fever or abdominal tenderness. A bedside ultrasound of the lungs suggested a normohydrated state with no signs of increased extravascular lung water. Simple ascites was demonstrated on ultrasound of the abdomen with a serum-ascites albumin gradient (SAAG) of less than 1.1g/dL and an ascitic protein of 48g/L. The sample had a normal fluid cytology and was negative for bacterial, fungal and mycobacterial cultures. Interestingly, our patient had remarkably high inflammatory markers ie C-Reactive Protein (CRP) 111 mg/L, Procalcitonin 7.47 ng/mL, D-Dimer >7.65 mcg/mL and Ferritin 1650 mcg/L despite the absence of fever. The liver enzymes and complete blood counts were unremarkable apart from transient reactive thrombocytosis. His echocardiogram showed minimal pericardial effusion and the absence of coronary arteries dilatation. In the light of his complex clinical presentation, temporal relation with recent COVID-19 and unexplained signs of hyperinflammation, he was treated with Intravenous Immunoglobulin 2g/kg. Following that, we observed steady improvement of the inflammatory markers and resolution of the reactive ascites. At the time of writing, six weeks lapsed and he remained well on chronic hemodialysis. Conclusions: In conclusion, the exorbitantly high inflammatory markers and gross ascites otherwise unexplained by another disease proess could reflect an immune dysregulation post COVID-19 or an atypical presentation of MIS-C. Much is yet to be known of this very complex disease in children. No conflict of interest

15.
International Journal of Academic Medicine and Pharmacy ; 4(1):60-64, 2022.
Article in English | EMBASE | ID: covidwho-1702733

ABSTRACT

A novel coronavirus disease 2019 (COVID-19) outbreak has started in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The relationship between altered iron homeostasis and hyperinflammation may be hallmarks of COVID-19 disease. We aimed to compare some iron (ferritin and iron), inflammation (C-reactive protein [CRP], hemoglobin, lactate dehydrogenase [LDH], neutrophil) and coagulation (prothrombin time [PT], activated partial thromboplastin time [APTT], D-dimer, platelet) marker results of critical COVID-19 patients with healthy controls results. In this single center retrospective study, 50 critical patients diagnosed with COVID-19 were included, demographic, clinical characteristics, severity of disease and laboratory test results were elicited from electronic medical records and compared to 50 healthy people. A statistically significant increase in CRP, LDH, neutrophil, PT, APTT, D-dimer ferritin levels was observed in critical COVID-19 patients compared with healthy people while a statistically significant decrease was observed in hemoglobin and iron levels. In addition, no statistically significant change in platelet levels was observed. Ferroptosis may be a significant cause of multiple organ failure in critical COVID-19 patients. Ferroptosis inhibitors might have potential to combat ferroptosis in COVID-19. Therefore, larger studies are needed to ferroptosis in COVID-19 in vivo and in vitro.

16.
Purinergic Signal ; 18(1): 13-59, 2022 03.
Article in English | MEDLINE | ID: covidwho-1694363

ABSTRACT

Hyperinflammation plays an important role in severe and critical COVID-19. Using inconsistent criteria, many researchers define hyperinflammation as a form of very severe inflammation with cytokine storm. Therefore, COVID-19 patients are treated with anti-inflammatory drugs. These drugs appear to be less efficacious than expected and are sometimes accompanied by serious adverse effects. SARS-CoV-2 promotes cellular ATP release. Increased levels of extracellular ATP activate the purinergic receptors of the immune cells initiating the physiologic pro-inflammatory immune response. Persisting viral infection drives the ATP release even further leading to the activation of the P2X7 purinergic receptors (P2X7Rs) and a severe yet physiologic inflammation. Disease progression promotes prolonged vigorous activation of the P2X7R causing cell death and uncontrolled ATP release leading to cytokine storm and desensitisation of all other purinergic receptors of the immune cells. This results in immune paralysis with co-infections or secondary infections. We refer to this pathologic condition as hyperinflammation. The readily available and affordable P2X7R antagonist lidocaine can abrogate hyperinflammation and restore the normal immune function. The issue is that the half-maximal effective concentration for P2X7R inhibition of lidocaine is much higher than the maximal tolerable plasma concentration where adverse effects start to develop. To overcome this, we selectively inhibit the P2X7Rs of the immune cells of the lymphatic system inducing clonal expansion of Tregs in local lymph nodes. Subsequently, these Tregs migrate throughout the body exerting anti-inflammatory activities suppressing systemic and (distant) local hyperinflammation. We illustrate this with six critically ill COVID-19 patients treated with lidocaine.


Subject(s)
Adenosine Triphosphate/metabolism , COVID-19/immunology , Cytokine Release Syndrome/etiology , Inflammation/etiology , Lidocaine/therapeutic use , Purinergic P2X Receptor Antagonists/therapeutic use , Receptors, Purinergic/physiology , Anti-Inflammatory Agents/therapeutic use , Critical Care , Cytokine Release Syndrome/drug therapy , Humans , Inflammation/drug therapy , Infusions, Subcutaneous , Lidocaine/administration & dosage , Lidocaine/pharmacology , Lymph Nodes/immunology , Lymphatic System/immunology , Male , Maximum Tolerated Dose , Middle Aged , Models, Immunological , Purinergic P2X Receptor Antagonists/administration & dosage , Purinergic P2X Receptor Antagonists/pharmacology , Receptors, Purinergic/drug effects , Receptors, Purinergic P1/drug effects , Receptors, Purinergic P1/physiology , Receptors, Purinergic P2X7/physiology , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/etiology , Signal Transduction , T-Lymphocytes, Regulatory/immunology
17.
Front Nutr ; 8: 821824, 2021.
Article in English | MEDLINE | ID: covidwho-1686518

ABSTRACT

The use of nutraceutical approaches may regulate the immune system, performing a potential strategy to contain the worst outcomes of COVID-19. We reviewed the current evidence surrounding nutritional/nutraceutical approaches for the therapy in patients with COVID-19. We searched the PubMed database to report randomized controlled trials (RCTs) and observational research that used melatonin, zinc, or vitamin C supplementation as an intervention for COVID-19 treatment. To date, we found only three concluded studies that assessed zinc supplementation and melatonin therapy in patients with COVID-19, but with inconclusive data, relatively small sample size, and early termination of the trial. On the other hand, vitamin C therapy appears to reduce hyperinflammation and improve the oxygen support status of patients with COVID-19. However, a large part of this research involves pilot trials, and there are still conflicting data regarding mortality rate, mechanical ventilation, and duration of symptoms of patients with COVID-19. Melatonin, zinc, and vitamin C supplementation should be investigated further on the nutritional status-immune response, and data from ongoing trials are needed to understand these molecules as a therapy strategy in patients COVID-19.

18.
Front Immunol ; 12: 738532, 2021.
Article in English | MEDLINE | ID: covidwho-1686470

ABSTRACT

Background: The benefits of intravenous immunoglobulin administration are controversial for critically ill COVID-19 patients. Methods: We analyzed retrospectively the effects of immunoglobulin administration for critically ill COVID-19 patients. The primary outcome was 28-day mortality. Inverse probability of treatment weighting (IPTW) with propensity score was used to account for baseline confounders. Cluster analysis was used to perform phenotype analysis. Results: Between January 1 and February 29, 2020, 754 patients with complete data from 19 hospitals were enrolled. Death at 28 days occurred for 408 (54.1%) patients. There were 392 (52.0%) patients who received intravenous immunoglobulin, at 11 (interquartile range (IQR) 8, 16) days after illness onset; 30% of these patients received intravenous immunoglobulin prior to intensive care unit (ICU) admission. By unadjusted analysis, no difference was observed for 28-day mortality between the immunoglobulin and non-immunoglobulin groups. Similar results were found by propensity score matching (n = 506) and by IPTW analysis (n = 731). Also, IPTW analysis did not reveal any significant difference between hyperinflammation and hypoinflammation phenotypes. Conclusion: No significant association was observed for use of intravenous immunoglobulin and decreased mortality of severe COVID-19 patients. Phenotype analysis did not show any survival benefit for patients who received immunoglobulin therapy.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Immunoglobulins, Intravenous/therapeutic use , Aged , China , Critical Care/methods , Critical Illness/therapy , Female , Humans , Immunization, Passive/methods , Immunization, Passive/mortality , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , Treatment Outcome
20.
Bmb Reports ; 55(1):11-19, 2022.
Article in English | Web of Science | ID: covidwho-1667556

ABSTRACT

The coronavirus disease 2019 (COVID-19) is an ongoing global pandemic caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). Patients with severe COVID-19 exhibit hyper-inflammatory responses characterized by excessive activation of myeloid cells, including monocytes, macrophages, and neutrophils, and a plethora of pro-inflammatory cytokines and chemokines. Accumulating evidence also indicates that hyper inflammation is a driving factor for severe progression of the disease, which has prompted the development of anti-inflammatory therapies for the treatment of patients with COVID-19. Corticosteroids, IL-6R inhibitors, and JAK inhibitors have demonstrated promising results in treating patients with severe disease. In addition, diverse forms of exosomes that exert anti-inflammatory functions have been tested experimentally for the treatment of COVID-19. Here, we briefly describe the immunological mechanisms of the hyper-inflammatory responses in patients with severe COVID-19. We also summarize current anti-inflammatory therapies for the treatment of severe COVID-19 and novel exosome-based therapeutics that are in experimental stages.

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