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The aim of the research. To study clinical and laboratory features of the new coronavirus infection (COVID-19) in order to develop a model that would allow, taking the publicly available research methods into account, to carry out early diagnosis of severe community-acquired pneumonia against the background of the new coronavirus infection. Material and methods. A total of 82 COVID-19 patients who complied with inclusion and exclusion criteria were enrolled. Depending on the clinical severity, three study groups were formed: group 1 included 13 patients with uncomplicated COVID-19, group 2 consisted of 39 patients with non-severe forms of pneumonia that developed against COVID-19 and group 3 was comprised of 30 patients with COVID-19 complicated by severe pneumonia. The groups were comparable in age and gender. All patients underwent general clinical examination, laboratory tests, including general and biochemical blood analysis, as well as chest computed tomography. Results. The clinical picture in COVID-19 patients differed depending on the disease severity. Coughing and shortness of breath were more often observed in patients with severe pneumonia;sore throat, on the contrary, was more often noted in patients with uncomplicated COVID-19. On admission to the inpatient facility, patients with severe pneumonia had higher body temperature and respiratory rate, with simultaneous decrease in blood oxygen saturation. One half of the patients with severe pneumonia had hypertensive disease in medical history, and one third had ischaemic heart disease. As a rule, uncomplicated COVID-19 patients did not have ischaemic heart disease. It was found through laboratory analysis of blood that groups of patients significantly differed in the levels of neutrophils, lymphocytes, monocytes, basophils and eosinophils. Conclusion. The use of such clinical and laboratory data as acute respiratory failure, fever, the levels of neutrophils, monocytes, lymphocytes, eosinophils and basophils makes it possible to identify patients with more severe pneumonia against the background of COVID-19 even before chest computed tomography. Key words:.Copyright © 2022, Krasnoyarsk State Medical University. All rights reserved.
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Objective: The hyperinflammatory response, caused by severe acute respiratory syndrome-2 (SARS-CoV-2), is the most common cause of death in patients with coronavirus disease 2019 (COVID-19). The etiopathogenesis of this illness is not fully understood. Macrophages appear to play a key part in COVID-19's pathogenic effects. Therefore, this study aims to examine serum inflammatory cytokines associated with the activation state of macrophages in COVID-19 patients and attempt to find accurate predictive markers for disease severity and mortality risk in hospital. Methods: 180 patients with COVID-19 and 90 healthy controls (HCs) participated in this study. Patients were divided into three different subgroups, mild (n=81), severe (n=60), and critical groups (n=39). Serum samples were collected and IL (Interleukin)-10, IL-23, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), IL-17, monocyte chemoattractant protein-1 (MCP-1) and chemokine ligand 3 (CCL3) were determined by ELISA. In parallel, myeloperoxidase (MPO) and C-reactive protein (CRP) were measured using colorimetric and electrochemiluminescence methods, respectively. Data were collected, and their associations with disease progression and mortality were assessed using regression models and receiver operating characteristic (ROC) curves. Results: Compared to HCs, a significant increase in IL-23, IL-10, TNF-α, IFN-γ and MCP-1, were observed in COVID-19 patients. Serum levels of IL-23, IL-10, and TNF-α were significantly higher in COVID-19 patients with critical cases compared to mild and severe cases, and correlated positively with CRP level. However, non-significant changes were found in serum MPO and CCL3 among the studied groups. Moreover, significant positive association has been observed among increased IL-10, IL-23 and TNF-α in serum of COVID-19 patients. Furthermore, a binary logistic regression model was applied to predict death's independent factors. Results showed that IL-10 alone or in combination with IL23 and TNF-α are strongly linked with non-survivors in COVID-19 patients. Finally, ROC curve results uncovered that IL-10, IL-23 and TNF-α were excellent predictors for prognosing COVID-19. Conclusion: The elevations of IL-10, IL-23, and TNF-α levels were seen in severe and critical cases of COVID-19 patients and their elevations were linked to the in-hospital mortality of the disease. A prediction model shows that the determination of these cytokines upon admission is important and should be done on COVID-19 patients as a way of evaluating the prognosis of the disease. COVID-19 Patients with high IL-10, IL-23, and TNF-α on admission are more likely to experience a severe form of the disease; therefore, those patients should be cautionary monitored and treated.
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COVID-19 , Humans , Interleukin-10 , Tumor Necrosis Factor-alpha , Hospital Mortality , SARS-CoV-2 , Cytokines , Interferon-gamma , Interleukin-23ABSTRACT
Objectives: Aim of this study was to evaluate hepcidin levels and its correlation with inflammatory markers, vitamin D levels as well as its effects on intensive care unit (ICU) mortality in critically ill coronavirus disease-2019 (COVID-19) patients. Materials and Methods: Adult patients those were admitted to pandemic ICU between March 1st, 2021 and May 17th 2021 were prospectively included to the study. Hepcidin levels and inflammatory markers on day 1, 2, 3 and 7, admission vitamin D levels, length of ICU stay and ICU mortality were recorded and analysed. Results: Median age of patients was 60.5 (52.50-71.25) and 20 (66.7%) of them was male. It was observed that hepcidin levels and lymphocyte counts were increased significantly from day 1 to day 7 (p=0.01 and p<0.01, respectively). In contrast, C-reactive protein (CRP) and procalsitonin levels were decreased from day 1 to day 7 (p=0.01 and p<0.01, respectively). In the analysis admission hepcidin levels and inflammatory markers [IL-6 (p=0.61), CRP (p=0.82) and ferritin (p=0.27)], vitamin D (p=0.13) and iron level (p=0.90) was not correlated. There was no correlation between hepcidin levels and ICU mortality (p=0.95). Conclusion: In this study, hepcidin levels were above normal limits in critically ill COVID-19 patients. However, our findings do not support the use of hepcidin, IL6, serum ferritin, and vitamin D levels in predicting COVID-19 mortality.
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Introduction. The novel coronavirus infection caused by the SARS-CoV-2 remains the main problem, which is being studied by all the efforts of the global scientific community. Large clinical recourse has been accumulated that allows to conduct more effective treatment of patients, but there are still unresolved issues on the pathogenesis for development and course of the disease. Materials and methods. The study included 163 patients admitted to the infectious diseases hospital diagnosed with "Novel coronavirus infection caused by the SARS-CoV-2". Upon admission, all patient serum samples were quantified for IL- 6 level that allowed to stratify patients into three groups: A - 55 patients with IL-6 below 5.0 pg/ml. The mean age in the group was 57.3 +/- 14.9 years, body mass index (BMI) was 28.2 +/- 5.6 kg/m(2);C - 52 patients whose serum IL-6 level was in the range of 5-49 pg/ml. The average age in the group was 60.8 +/- 11.8 years, BMI 29.6 +/- 5.5 kg/m(2);C - 56 patients in whom the level of IL-6 in the blood serum ranged within 50-300 pg/ml. The average age in the group was 62.5 +/- 15.6 years, BMI - 28.8 +/- 5.6 kg/m(2). Patients at admission were analysed for serum level of IL-6, IL-8, and C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH) were also determined on day 3 and 7. Results. The minimum production of IL-6 within the range of 0.1-5 pg/ml, corresponds to the minimum changes in IL-8, CRP, and ferritin as well as LDH that was within the range of physiological values. Moderate cytokinemia, IL-6 is within the range of 5-49 pg/ml was associated with elevated ferritin and LDH not tending to decline by the end of treatment. Significant cytokinemia, the level of IL-6 within the range of 50-300 pg/ml was associated with hyperferritinemia and increased LDH. The course of COVID-19 in such patients is characterized by increased ferritin by day 3 of treatment, consistently high level of LDH, without a significant trend towards a decline in the studied markers by the end of treatment. Conclusion. The risk of developing macrophage activation syndrome is not observed of the serum IL- 6 level was below 5 pg/ml, whereas ferritin and LDH were within the range of physiological values, with no/degree I ARF. Moderate macrophage activation syndrome is characterized by increased serum IL-6 level within the range 5-49 pg/ml, a moderate increase in LDH and ferritin, as well as signs of ARF I-II degree. Severe signs are diagnosed in case of serum IL-6 level exceeded 50 pg/ml, along with significant increase in LDH and ferritin, as well as signs of II-III degree ARF.
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The COVID-19 pandemic caused by SARS-CoV-2 spread across many countries between 2020 and 2022. The similarities in clinical presentation with other endemic diseases pose a challenge to physicians in effectively diagnosing and treating the infection. Approximately 129 nations have a risk of dengue infection, and more than 100 of those are endemic to dengue. During the COVID-19 pandemic, the number of dengue cases decreased in many countries owing to the isolation measures followed. However, the common clinical presentation between them has led to misdiagnosis. Both COVID-19 and dengue fever cause a surge in pro-inflammatory cytokines and chemokines, thus sharing a common pathophysiology. False positive serological test results also posed difficulty differentiating between COVID-19 and dengue fever. This review aims to compare the clinical features, pathophysiology, and immune response between dengue and COVID-19, to benefit public health management during the pandemic.
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Introduction: the daily increase in cases and deaths, the economic losses in the millions suffered by affected nations and the consequent strain on the human resources involved in reversing this situation have made the COVID-19 pandemic an unprecedented international challenge. Background: to describe the orchestrated immune response following SARS-CoV-2 infection. Methods: an up-to-date bibliometric study was conducted on the type of articles stated in the objective, using a total of 30 bibliographies. Documentary review and analysis-synthesis methods were used to prepare the final report. Resources available on the Infomed network were used to select the information, specifically: PubMed and SciELO, through the databases: Medline, Search Premier and Scopus. Development: the core elements in the immunopathology of COVID-19 involve innate immunity, with the sustained increase of pro-inflammatory interleukins associated with failures in the interferon system, which can trigger a potentially fatal cytokine storm. In terms of elements linked to adaptive immunity, there is evidence of marked lymphopenia which, depending on the degree, may indicate the severity of the disease. Conclusions: understanding the orchestrated immune response following SARS-CoV-2 infection and its temporal sequence allows us to choose timely and effective therapies, specifically when selecting anti-inflammatory drugs and the time of their application, as it is difficult to determine when they will be clearly beneficial, that they do not impair the response and that it is not too late, given the irreversibility of the process.
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With a global burden of 844 million, chronic kidney disease (CKD) is now considered a public health priority. Cardiovascular risk is pervasive in this population, and low-grade systemic inflammation is an established driver of adverse cardiovascular outcomes in these patients. Accelerated cellular senescence, gut microbiota-dependent immune activation, posttranslational lipoprotein modifications, neuroimmune interactions, osmotic and nonosmotic sodium accumulation, acute kidney injury, and precipitation of crystals in the kidney and the vascular system all concur in determining the unique severity of inflammation in CKD. Cohort studies documented a strong link between various biomarkers of inflammation and the risk of progression to kidney failure and cardiovascular events in patients with CKD. Interventions targeting diverse steps of the innate immune response may reduce the risk of cardiovascular and kidney disease. Among these, inhibition of IL-1ß (interleukin-1 beta) signaling by canakinumab reduced the risk for cardiovascular events in patients with coronary heart disease, and this protection was equally strong in patients with and without CKD. Several old (colchicine) and new drugs targeting the innate immune system, like the IL-6 (interleukin 6) antagonist ziltivekimab, are being tested in large randomized clinical trials to thoroughly test the hypothesis that mitigating inflammation may translate into better cardiovascular and kidney outcomes in patients with CKD.
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Cardiovascular Diseases , Renal Insufficiency, Chronic , Humans , Immunity, Innate , Inflammation , Cohort Studies , Cardiovascular Diseases/epidemiologyABSTRACT
INTRODUCTION: With a growing knowledge of Inborn errors immunity (IEI), immunological profiling and genetic predisposition to IEI phenocopies have been developed in recent years. AREAS COVERED: Here we summarized the correlation between various pathogen invasions, autoantibody profiles, and corresponding clinical features in the context of patients with IEI phenocopies. It has been extensively evident that patients with anti-cytokine autoantibodies underly impaired anti-pathogen immune responses and lead to broad unregulated inflammation and tissue damage. Several hypotheses of anti-cytokine autoantibodies production are summarized here, including a defective negative selection of autoreactive T cells, abnormal germinal center formation, molecular mimicry, HLA class II allele region, lack of auto-reactive lymphocyte apoptosis, and other possible hypotheses. EXPERT OPINION: Phenocopies of IEI associated with anti-cytokine autoantibodies are increasingly recognized as one of the causes of acquired immunodeficiency and susceptibility to certain pathogen infections, especially facing the current challenge of the COVID-19 pandemic. By investigating clinical, genetic, and pathogenesis autoantibodies profiles associated with various pathogens' susceptibilities, we could better understand the IEI phenocopies with anti-cytokine autoantibodies, especially for those that underlie life-threatening SARS-CoV-2.
Subject(s)
COVID-19 , Cytokines , Humans , Pandemics , SARS-CoV-2 , AutoantibodiesABSTRACT
The COVID-19 pandemic had a profound impact on global health, economies, and social systems. The crucial factor that determines the success of COVID-19 treatments is preventing the need for mechanical ventilation and intensive care admission. In the context of COVID-19, several treatments have been found to play a role in the disease's progression and severity. Interleukins (ILs) have been identified as key mediators of the cytokine storm that can occur in severe cases of COVID-19, leading to respiratory failure and other complications. For instance, IL-1 antagonist (anakinra) and IL-6 antagonist (tocilizumab) are supposed to be promising treatments as well as cortisones for COVID-19. This prospective study aims to evaluate the effectiveness of anakinra or tocilizumab in addition to cortisone in preventing the progression of mild to moderate COVID-19 cases to severe intensive care admission. Biochemical and hematological parameters, such as D-dimer, ferritin, LDH, CRP, and white blood cells (WBCs), were measured after treatment with either anakinra or tocilizumab in addition to cortisone or cortisone alone. The study also recorded the number of deaths and patients admitted to intensive care. The results indicate that anakinra significantly improved outcomes and decreased the number of intensive care admissions compared to tocilizumab or cortisone alone. Therefore, anakinra may play a vital role in controlling the progression of COVID-19, and its use in mild to moderate cases may prevent the worsening of the disease to severe stages.
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INTRODUCTION: The management of hospitalized COVID-19 patients depends largely on controlling the intensified inflammatory response known as the cytokine storm. Candidate inflammatory cytokines can serve as new biomarkers for the management of hospitalized COVID-19 patients. METHODS: Patients (80) were recruited into three groups: room air (RA), oxygen (OX) and mechanical ventilator (MV). Blood analysis was performed for RBC, WBC, Hb, Platelets, serum albumin and creatinine, INR, PTT, and hematocrit. ELISA was used to quantify a panel of inflammatory mediators including GM-SCF, IFN-α, IFNγ, IL-1ß, IL-1R, IL-2, IL-2Ra, IL-6, IL-8, IL-10, IL-12p70, IL-13, MCP-1, MIP-1a, and TNF-α. Correlations between laboratory results and the levels of circulating inflammation mediators were investigated. RESULTS: Patients on MV had low RBC, Hb, albumin, and HCT and high WBC count, PTT, and INR when compared to RA and OX groups. A statistical positive correlation was found between WBC and the levels of IL-6 and MCP-1. RBCs correlated negatively with IL-6 and IL-10 and positively with IL-8. Higher TNF-α correlated with lower platelet counts while higher levels of IL-1Rα and IL-10 were associated with lower Hb levels. Increases in IFN-γ and TNF-α were indicative of compromised kidney functions as creatinine levels increased significantly. Most significant correlations were found between IL-6 and lab results, showing positive correlation with WBC and INR, and negative correlation with RBC, albumin, and HCT. CONCLUSIONS: Having the most significant correlations, IL-6 high levels in mechanically ventilated patients were shown to affect laboratory results, and, therefore, is suggested as a severity biomarker of COVID-19.
Subject(s)
COVID-19 , Interleukin-10 , Humans , Albumins , Biomarkers , Creatinine , Cytokine Release Syndrome , Cytokines , Inflammation Mediators , Interleukin-6 , Interleukin-8 , Tumor Necrosis Factor-alphaABSTRACT
PURPOSE: Tocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19 with 8 mg/kg (max 800 mg) being the standard dose. Our study sought to assess whether a low dose (400 mg) shows similar benefit compared to a high dose for COVID patients concurrently on the same median dose of steroids. MATERIALS/METHODS: A retrospective, multihospital observational study of COVID-19 patients who received tocilizumab in conjunction with steroids between March 2020 and August 2021 was conducted. RESULTS: A total of 407 patients were analyzed with low dose group being significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis, both groups receiving a median dexamethasone equivalent dose of 10 mg showed no difference in 28-day mortality (p = 0.613). The high dose group had a higher rate of fungal and viral infections. CONCLUSION: Compared to low dose tocilizumab, the high dose did not provide additional efficacy and mortality benefit but resulted in higher fungal and viral infections. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients.
Subject(s)
COVID-19 , Respiratory Insufficiency , Humans , SARS-CoV-2 , Retrospective Studies , Treatment Outcome , COVID-19 Drug Treatment , Respiratory Insufficiency/drug therapyABSTRACT
The neuroimmune system is a specialized immune system in the brain crucial for both responding to illness and injury as well as regulating normal neural function and behavior. As such, it is perhaps not surprising that activation of the neuroimmune system results in significant impairments in synaptic plasticity and learning and memory mechanisms. In fact, neuroimmune dysregulation has been implicated in memory- and cognitive-related disorders including Alzheimer's disease, Post-Traumatic Stress disorder, and most recently long-COVID, a series of long-lasting cognitive impairments caused by the virus SARS-CoV-2. There are known sex differences in the neuroimmune response to various pathogens, and because the neuroimmune system is at the convergence of pathological and normal function, the immune cells and signaling mechanisms involved are well-poised to modulate memory processes differently in males and females which may contribute to sex differences in the prevalence or severity of memory-related disorders. Here, we aimed to investigate the interaction of neuroimmune and memory processes in both males and females using central administration of a viral mimic, polyinosinic:polycytidylic acid (poly I:C), in C57BL/6N mice. Poly I:C is synthetic, double-stranded RNA that stimulates several cell types involved in mounting an immune response in the brain including astrocytes, microglia, and neurons, making it an excellent tool for studying broad-based neuroinflammation. Poly I:C treatment induced significant inflammation in the hippocampus of both sexes. Males had a greater magnitude of response than females for cytokines IL-1alpha, IL-1beta, IL-6, IL-10, IFNalpha, TNFalpha, CCL2, and CXCL10. Additionally, while both males and females showed increased expression of the anti-viral Type I interferon beta, only males showed increased anti-viral Type I interferon alpha, highlighting a potentially important sex difference in the anti-viral response to poly I:C. We used a T-maze task and a contextual fear-based memory task to determine the effects of neuroinflammation on learning and memory mechanisms. Pre-training poly I:C did not impair learning in the T-maze task. In contrast, pre-training poly I:C disrupted learning of contextual fear conditioning in both males and females, and analysis of cFos levels revealed significant sex differences in hippocampal activation during context fear conditioning training with poly I:C on board. Together, these findings suggest that a similar behavioral deficit induced by poly I:C in males and females involve sex-specific molecular and signaling mechanisms of learning and memory. To further investigate this, we targeted Type I interferon signaling because of the sex difference in Type I interferon induction we found previously and the capacity for Type I interferons to modulate synaptic plasticity mechanisms. We found that inhibiting Type I interferon receptors prior to treatment with poly I:C attenuated the poly I:C-induced learning deficits in males, and we did not find the same effect in females. This suggests that Type I interferons play a more important role in modulating learning in males compared with females, and Type I interferon signaling is a potential target for understanding sex differences in biological mechanisms of memory impairment induced by neuroimmune activation. (PsycInfo Database Record (c) 2023 APA, all rights reserved)
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Objectives: Fetuin-A, a glycoprotein with several functions, is also a negative acute phase reactant. The purpose of this study was to investigate levels of serum fetuin-A in coronavirus disease 2019 (COVID-19) patients, its association with disease severity, and whether it has superiority over C-reactive protein (CRP). Methods: The research comprised 56 individuals with COVID-19(+) and 30 healthy controls. The COVID-19(+) patient population was split into three subgroups: mild, moderate, and severe. All participants' serum concentrations of fetuin- A, tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6) were measured using ELISA commercial test kits. In addition, CRP and other biochemical values from biochemistry laboratory data were gathered, and the CRP/fetuin-A ratio was calculated. Results: The fetuin-A concentration of the COVID-19(+) patient group was shown to be statistically lower than that of the healthy control group. TNF-a and IL-6 levels were found to be significantly different in both groups. While fetuin-A had a higher area under the curve (AUC) value than CRP (0.875 and 0.800, respectively), CRP/fetuin-A had the strongest AUC (0.933). Conclusion: Low serum fetuin-A concentrations in COVID-19 patients suggest that fetuin-A is a negative acute phase reactant for severe acute respiratory syndrome coronavirus 2. Furthermore, fetuin-A alone and CRP/fetuin-A value are both contenders for being more remarkable markers than CRP.
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Objective: The aim of this study was to explore the polarization of peripheral blood macrophages and peripheral blood mononuclear lymphocyte (PBMC) thioredoxin-interacting protein (TXNIP)/nuc1eotide-binding oligo-merization domain-like receptor protein 3 (NLRP3) mRNA changes in patients with hepatitis B virus acute-on-chronic liver failure (HBV- ACLF). Methods 57 patients with HBV-ACLF and 43 patients with chronic hepatitis B (CHB) were enrolled in our hospital between June 2019 and June 2020, and the percentages of peripheral blood M1 and M2 macrophages were detected by flow cytometry. The PBMC TXNIP, NLRP3 and cysteine protease-l (caspase- 1) mRNA were assayed by real-time fluorescence quantification RT-PCR. Serum interleukin-6 (1L) -6, IL-10 and tumor necrosis factor-a (TNF-a) were detected by ELISA. Results: The percentage of M1 macrophages and M1/M2 cell ratio in patients with HBV-ACLF were (3.5..0.4) % and (1.2..0.2), significantly higher than [(2.1..0.2) % and (0.6..0.1), P < 0.05], while the percentage of M2 macrophages was (2.5..0.3) %, significantly lower than [(4.1..0.4) %, P < 0.05] in patients with CHB;serum IL-6 and TNF-a in patients with HBV- ACLF were (37.9..4.2) ng/L and (2.3..0.2) pg/mL, significantly higher than [(28.8..3.6) ng/L and (1.2..0.1) pg/mL, respectivley, P < 0.05], while serum IL-10 level was (1.410.2) pg/mL, significantly lower than [(2.9..0.3) pg/mL, P < 0.05] in patients with CHB;the PBMCs NLRP3, TXNIP and caspase-1 mRNA in patients with HBV-ACLF were (0.5..0.1), (0.7..0.1) and (1.2..0.1), all significantly lower than [(08..02), (1.0..01) and (1.6..0.2), respectively, P< 0.05] in patients with CHB;the percentage of PBMC M1 macrophages in 15 dead patients was (4.1..0.4) %, significantly higher than [(3.3..0.3) %, P < 0.05], while the percentage of M2 macrophages, PBMCS NLRP3 and TXNIP mRNA were (1.9..0.2) %, (0.2..0.1) and (0.4..0.1), significantly lower than [(2.7..0.3) %, (0.6..0.1) and (0.8..0.1), respectively, 3P < 0.05] in 42 survivals. Conclusion The peripheral blood macrophages are polarized in the pro-inflammatory direction and the down-regulation of TXNIP and NLRP3 mRNA might be related to immunosuppression in patients With HBV-ACLF.
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Coronavirus disease 2019 (COVID-19), an extremely infectious illness caused by a novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that has spread over the worldwide, has become one of the most difficult public health problems of our time. Age and gender are two major characteristics that influence the risks and outcomes of numerous diseases. Our study will investigate and compare the difference in hematological, biochemical, and serological biomarkers between sexes in order to evaluate severity and pathogenicity. Clinical records were taken from 150 SARS-CoV-2 positive patients were included in this study;the infection was confirmed by real time reverse transcriptase polymerase chain reaction. Blood samples subjected to measure changes in hematological parameters and serum subjected to measure biochemical test including ferritin, creatinine, CRP, D-dimer, and liver function enzyme either for ELISA test to measure serological biomarkers including IgM, IgG, TNF-α, IFN-γ, IL-6, and IL-10. 90 (60%) of whom were male and 60 (40%) of whom were female. Our study found a significant increase in CRP, IgM, IL-6, IL-10, TNF-α, IFN-γ, AST, ALP, and TBIL levels in males compared to females, and the age group most susceptible to SARS-CoV-2 infection was 41-60 years. Based on these findings, we concluded that males and those of older age had a high prevalence of severity and progression than females.
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More than 2 years into the COVID-19 pandemic with more than 6 million death worldwide, a dysregulated immune response to the pathogen associated with super-activation of pro-inflammatory cytokines, which may cause tissue injury, particularly lung tissue, IL-10 levels can impact on the clinical performance of the patients. this search conducted to detect the effect of Interleukin-10 gene polymorphisms on severity and outcome COVID-19 patients. A case - control study design for 120 COVID-19 patients that divided into sever, critical and moderate/mild patients in addition to 60 healthy subjects as control group to compare IL-10 serum level by ELISA technique and IL-10 gene polymorphism by ARMS-PCR assay. The result illustrated that 120 patients with covid-19 disease m classified as Critical cases 33 (27.5%), sever 42 (35%) and Mild/Moderate were 45 (37.5%). IL-10 increased in the serum of Covid-19 pneumonia patient's to (48.76 ± 12.3) pg / ml in compared with healthy controls (5.47±1.33) pg/ml. genotype results revealed that IL-10 gene distribution was GG homozygous (58.3%) higher in Covid-19 patients in compared to healthy controls (21.7)% and G allele was 124 for patient and 42 for healthy, so GG consider risk factor for coronavirus while AA genotype regard protective factor with frequency reach to 12% in patients and 48.3 % in healthy. The genotype distribution for critical/sever revealed the GG was 74.7% while in M/M was 31.1%. In conclusion: a significant association of GG genotype and allele G was observed with severity of COVID-19 infection.
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Background: The severity of Coronavirus Disease-2019 (COVID-19) cases is associated with hyperinflammation. Patients with critical and severe COVID-19 have been observed to have high amounts of circulating cytokines. Neopterin, a crucial cytokine in the antiviral immune response that is released by macrophages upon stimulation with interferon-gamma, can be utilized to forecast the severity of illness in COVID-19 patients. Methods: The study included 185 patients with COVID-19. The patients with COVID-19 were divided into three groups according to disease severity as critical disease (n=51), severe disease (n=81), and moderate disease (n=53). All basic demographic and clinical data of the patients were recorded and blood samples were collected. Results: Neopterin levels were significantly higher in critical COVID-19 patients compared with severe and moderate COVID-19 patients (p < 0.0001). Further, neopterin showed significantly higher levels in the age group >50 years of patients with COVID-19 than in the age group <50 years. Neopterin levels were correlated with WBCs, Platelet, CRP, D-Dimer, Ferritin, Fibrinogen, IL-6, and Procalcitonin levels positively (ρ= 0.569, 0.474, 0.338, 0.696, 0.605, 0.77, 0.727, and 0.585;p < 0.01 respectively), and correlated with BMI, SpO2, and lymphocyte negatively (ρ= - 0.165;p < 0.05, p= - 0.754, - 0. 548;p < 0.01 respectively). A cutoff value of 23.62 nmol/L for neopterin predicted COVID-19 with a sensitivity of 95.7% and a specificity of 95.5% (AUC: 0.986;p < 0.0001). Conclusion: Neopterin may be a useful prognostic biomarker for assessing the severity of COVID-19.
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PURPOSE: The COVID-19 pandemic caused by the novel Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has put the world in a medical crisis for the past three years; nearly 6.3 million lives have been diminished due to the virus outbreak. This review aims to update the recent findings on COVID-19 infections from an epigenetic scenario and develop future perspectives of epi-drugs to treat the disease. METHODS: Original research articles and review studies related to COVID-19 were searched and analyzed from the Google Scholar/PubMed/Medline databases mainly between 2019 and 2022 to brief the recent work. RESULTS: Numerous in-depth studies of the mechanisms used by SARS-CoV-2 have been going on to minimize the consequences of the viral outburst. Angiotensin-Converting Enzyme 2 receptors and Transmembrane serine protease 2 facilitate viral entry to the host cells. Upon internalization, it uses the host machinery to replicate viral copies and alter the downstream regulation of the normal cells, causing infection-related morbidities and mortalities. In addition, several epigenetic regulations such as DNA methylation, acetylation, histone modifications, microRNA, and other factors (age, sex, etc.) are responsible for the regulations of viral entry, its immune evasion, and cytokine responses also play a major modulatory role in COVID-19 severity, which has been discussed in detail in this review. CONCLUSION: Findings of epigenetic regulation of viral pathogenicity open a new window for epi-drugs as a possible therapeutical approach against COVID-19.
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Dopamine (DA) is a key neurotransmitter in the basal ganglia, implicated in the control of movement and motivation. Alteration of DA levels is central in Parkinson's disease (PD), a common neurodegenerative disorder characterized by motor and non-motor manifestations and deposition of alpha-synuclein (α-syn) aggregates. Previous studies have hypothesized a link between PD and viral infections. Indeed, different cases of parkinsonism have been reported following COVID-19. However, whether SARS-CoV-2 may trigger a neurodegenerative process is still a matter of debate. Interestingly, evidence of brain inflammation has been described in postmortem samples of patients infected by SARS-CoV-2, which suggests immune-mediated mechanisms triggering the neurological sequelae. In this review, we discuss the role of proinflammatory molecules such as cytokines, chemokines, and oxygen reactive species in modulating DA homeostasis. Moreover, we review the existing literature on the possible mechanistic interplay between SARS-CoV-2-mediated neuroinflammation and nigrostriatal DAergic impairment, and the cross-talk with aberrant α-syn metabolism.
Subject(s)
COVID-19 , Parkinson Disease , Humans , Dopamine/metabolism , Neuroinflammatory Diseases , SARS-CoV-2/metabolism , Parkinson Disease/metabolism , alpha-Synuclein/metabolismABSTRACT
The clinical presentation, disease course, and outcome of SARS-CoV-2 infection in pediatrics differ from the presentation in adults. In a review by Hoang et al., the prevalence of dermatological manifestations was estimated in 0.25% of a total of 2,445 children with confirmed COVID-19. Similarly, the prevalence of skin manifestations was reported in 3% of 100 children in the Parri's study. A systematic review by Shah et al. analyzed 13 studies with 149 children who met eligibility criteria. The acral erythematous maculopapular lesion was the most common, as well as erythema multiforme, varicella rash, and presentations similar to Kawasaki disease. The duration of the skin lesion was one to two weeks in 43%. Skin biopsy of 18 cases complete superficial and deep perivascular and paracrine lymphocytic infiltrate and lymphocytic vasculitis were reported. RT-PCR was positive in 13.8 % of the cases. The serological markers of herpes simplex virus and parvovirus B19 analyzed were negative, except for Mycoplasma pneumoniae in two of 20 cases. The pathophysiological mechanism of skin lesions secondary to SARS-CoV-2 infection has not yet been explained; likely to be a combination of one or more complex mechanisms, direct skin damages induced by the virus, vasculitis-like reactions either indirect or secondary injuries as a consequence of a systemic inflammatory reaction. Publications from years 2019 to 2021 are reviewed in PubMed as the main search source, using key words.
La presentación clínica, curso de la enfermedad y resultado de la infección por SARS-CoV-2 en pediatría difieren de los observados en adultos. En una revisión de Hoang et al. se estimó que la prevalencia de las manifestaciones dermatológicas fue de 0.25 % de un total de 2445 niños con COVID-19 confirmada. Según Parri, se documentó 3 % en 100 niños. En la revisión sistemática de Shah et al.se analizaron 13 estudios que incluyeron 149 niños que cumplieron con los criterios de elegibilidad. La lesión maculopapular eritematosa acral fue la más común, también el eritema multiforme, el exantema de la varicela y las presentaciones similares a enfermedad de Kawasaki. La duración de las lesiones cutáneas fue de una a dos semanas en 43 %. La biopsia de piel de 18 casos reveló infiltrado linfocítico perivascular, infiltrado paracrino superficial y profundo y vasculitis linfocítica. La RT-PCR fue positiva en 13.8 %. Los marcadores serológicos analizados de virus de herpes simple y parvovirus B19 fueron negativos, y fueron positivos para Mycoplasma pneumoniae en dos de 20 casos. El mecanismo fisiopatológico de las lesiones en piel secundarias a infección por SARS-CoV-2 aún no se ha podido explicar; es probable que se trate de la combinación de uno o más mecanismos complejos, daños cutáneos directos inducidos por el virus, reacciones vasculíticas o lesiones indirectas o secundarias como consecuencia de una reacción inflamatoria sistemática. Se revisaron las publicaciones de 2019 a 2021 en PubMed como fuente principal de búsqueda, para lo cual se utilizaron palabras clave.