Correlations of interleukin levels with the severity of SARS-CoV-2 coronavirus infection.

A new coronavirus infection caused by the SARS-CoV-2 virus is characterized by a systemic hyperinflammatory response with a pronounced increase in the content of pro-inflammatory cytokines. Materials and methods. The study was conducted on the basis of the Samara Regional Children's Infectious Diseases Hospital from 2021 to 2022. 40 patients with moderate (n = 20, group I) and severe forms (n = 20, group II) COVID-19 were studied, the comparison group consisted of patients with viral pneumonia of another etiology (n = 35, group III). Results. The infectious agent SARS-CoV-2 induces high levels of cytokines IL-6 (p < 0.005), IL-8 (p < 0.05) and a slight increase in TNF-alpha (p < 0.05). IL-8 was significantly associated with disease duration (p < 0.01). We assume that the value of this interleukin will increase in the post-COVID period. Conclusions. Changes in IL-6 and IL-8 levels in patients with COVID-19, along with clinical features, are important biomarkers for predicting the severity and duration of the disease.Copyright © Children Infections.All rights reserved

Association of SARS-COV-2 viral RNAemia, IL- 6 gene polymorphism, serum IL-6 and peripheral blood lymphocytes and monocytes with disease severity in COVID-19 patients

Coronavirus disease 2019 (COVID-19) is a fatal pandemic viral disease caused by the severe acute respiratory syndrome corona virus type-2 (SARS-CoV-2). The aim of this study is to observe the associations of IL-6, SARS-COV-2 viral load (RNAemia), IL- 6 gene polymorphism and lymphocytes and monocytes in peripheral blood with disease severity in COVID-19 patients. This study was carried out from March 2021 to January 2022. RT-PCR positive 84 COVID-19 patients and 28 healthy subjects were enrolled. Blood was collected to detect SARS-COV-2 viral RNA (RNAemia) by rRT-PCR, serum IL-6 level by chemiluminescence method, SNPs of IL-6 by SSP-PCR, immunophenotyping of lymphocytes and monocyte by flow cytometry. Serum IL-6 level (pg/ml) was considerably high among critical patients (102.02 +/- 149.7) compared to severe (67.20 +/- 129.5) and moderate patients (47.04 +/- 106.5) and healthy controls (3.5 +/- 1.8). Serum SARS-CoV-2 nucleic acid positive cases detected mostly in critical patients (39.28%) and was correlated with extremely high IL-6 level and high mortality (R =.912, P < 0.001). Correlation between IL-6 and monocyte was statistically significant with disease severity (severe group, p < 0.001, and 0.867*** and critical group p < 0.001 and 0.887***). In healthy controls, moderate, severe and critically ill COVID-19 patients, IL-6 174G/C (rs 1800795) GG genotype was 82.14%, 89.20%, 67.85% and 53.57% respectively. CC and GC genotype had strong association with severity of COVID-19 when compared with GG genotype. Significant statistical difference found in genotypes between critical and moderate groups (p < 0.001, OR-10.316, CI-3.22-23.86), where CC genotype was associated with COVID-19 severity and mortality. The absolute count of T cell, B cell, NK cell, CD4+ T cells and CD8+ T cells were significantly decreased in critical group compared to healthy, moderate and severe group (P < 0.001). Exhaustion marker CD94/NKG2A was increased on NK cells and CD8+ cytotoxic T cell among critical and severe group. Absolute count of monocyte was significantly increased in critical group (P < 0.001). Serum IL-6, IL-6 174 G/C gene and SARS-CoV-2 RNAaemia can be used in clinical practice for risk assessment;T cell subsets and monocyte as biomarkers for monitoring COVID-19 severity. Monoclonal antibody targeting IL-6 receptor and NKG2A for therapeutics may prevent disease progression and decrease morbidity and mortality.Copyright © 2023 Elsevier Inc.

COVID-19: is fibrosis the killer?

COVID-19 is a respiratory disease. A recent report in Lancet examined, retrospectively, 137 patients with COVD-19. Patients that died had elevated IL-6 levels and acute respiratory distress syndrome. These data have obvious implications for how to control mortality in COVID-19.

Golden berry leaf extract containing withanolides suppresses TNF-α and IL-17 induced IL-6 expression in HeLa Cells.

Inflammation, characterized by the overexpression of IL-6 in various tissues, has been reported as a symptom of coronavirus disease 2019 (COVID-19). In this study, we established an experimental system for overexpression of IL-6 in HeLa cells stimulated by TNF-α and IL-17, along with identification of anti-inflammatory materials and components from local agricultural, forestry, and fishery resources. We constructed a library of extracts from natural sources, of which 111 samples were evaluated for their anti-inflammatory activities. The MeOH extract of Golden Berry (Physalis peruviana L) leaf was found to exhibit strong anti-inflammatory properties (IC50 = 4.97 µg/mL). Preparative chromatography identified two active constituents, 4ß-hydroxywithanolide E (4ß-HWE) (IC50 = 183 nM) and withanolide E (WE) (IC50 = 65.1 nM). Withanolides are known anti-inflammatory ingredients of Withania somnifera, an Ayurvedic herbal medicine. P. peruviana leaves containing 4ß-HWE and WE should be considered as useful natural resources for anti-inflammatory products.

The Diagnostic Value of Inflammatory Markers (CRP, IL6, CRP/IL6, CRP/L, LCR) for Assessing the Severity of COVID-19 Symptoms Based on the MEWS and Predicting the Risk of Mortality.

Introduction: Various diagnostic tools are used to assess the severity of COVID-19 symptoms and the risk of mortality, including laboratory tests and scoring indices such as the Modified Early Warning Score (MEWS). The diagnostic value of inflammatory markers for assessing patients with different severity of COVID-19 symptoms according to the MEWS was evaluated in this study. Materials and Methods: The concentrations of CRP (C-reactive protein) (immunoassay) and IL6 (interleukin 6) (electrochemiluminescence assay) were determined, and CRP/IL6, CRP/L, and LCR ratios were calculated in blood serum samples collected from 374 COVID-19 patients. Results: We demonstrated that CRP, IL6, CRP/IL6, CRP/L, LCR inflammatory markers increase significantly with disease progression assessed based on the MEWS in COVID-19 patients and may be used to differentiating patients with severe and non-severe COVID-19 and to assess the mortality. Conclusion: The diagnostic value of inflammatory markers for assessing the risk of mortality and differentiating between patients with mild and severe COVID-19 was confirmed.

Pro- and Anti-Inflammatory Prostaglandins and Cytokines in Humans: A Mini Review.

Inflammation has been described for two millennia, but cellular aspects and the paradigm involving different mediators have been identified in the recent century. Two main groups of molecules, the prostaglandins (PG) and the cytokines, have been discovered and play a major role in inflammatory processes. The activation of prostaglandins PGE2, PGD2 and PGI2 results in prominent symptoms during cardiovascular and rheumatoid diseases. The balance between pro- and anti-inflammatory compounds is nowadays a challenge for more targeted therapeutic approaches. The first cytokine was described more than a century ago and is now a part of different families of cytokines (38 interleukins), including the IL-1 and IL-6 families and TNF and TGFß families. Cytokines can perform a dual role, being growth promotors or inhibitors and having pro- and anti-inflammatory properties. The complex interactions between cytokines, vascular cells and immune cells are responsible for dramatic conditions and lead to the concept of cytokine storm observed during sepsis, multi-organ failure and, recently, in some cases of COVID-19 infection. Cytokines such as interferon and hematopoietic growth factor have been used as therapy. Alternatively, the inhibition of cytokine functions has been largely developed using anti-interleukin or anti-TNF monoclonal antibodies in the treatment of sepsis or chronic inflammation.

Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein.

Introduction: Many people with long COVID symptoms suffer from debilitating neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). Although symptoms of Neuro-PASC are widely documented, it is still unclear whether PASC symptoms impact virus-specific immune responses. Therefore, we examined T cell and antibody responses to SARS-CoV-2 Nucleocapsid protein to identify activation signatures distinguishing Neuro-PASC patients from healthy COVID convalescents. Results: We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated CD4+ T cell responses and diminished CD8+ memory T cell activation toward the C-terminal region of SARS-CoV-2 Nucleocapsid protein when examined both functionally and using TCR sequencing. CD8+ T cell production of IL-6 correlated with increased plasma IL-6 levels as well as heightened severity of neurologic symptoms, including pain. Elevated plasma immunoregulatory and reduced pro-inflammatory and antiviral response signatures were evident in Neuro-PASC patients compared with COVID convalescent controls without lasting symptoms, correlating with worse neurocognitive dysfunction. Discussion: We conclude that these data provide new insight into the impact of virus-specific cellular immunity on the pathogenesis of long COVID and pave the way for the rational design of predictive biomarkers and therapeutic interventions.

Inflammatory Response in COVID-19 Depending on the Severity of the Disease and the Vaccination Status.

The aim of this study was to analyze the serum concentration of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, and procalcitonin in COVID-19 patients with different forms of the disease. We performed a prospective cohort study on 137 COVID-19 consecutive patients, divided into four groups according to the severity of the disease as follows: 30 patients in the mild form group, 49 in the moderate form group, 28 in the severe form group, and 30 in the critical form group. The tested parameters were correlated with COVID-19 severity. Significant differences were registered between the form of COVID-19 depending on the vaccination status, between LDH concentrations depending on the virus variant, and in IL-6, CRP, and ferritin concentrations and vaccination status depending on the gender. ROC analysis revealed that D-dimer best predicted COVID-19 severe forms and LDH predicted the virus variant. Our findings confirmed the interdependence relationships observed between inflammation markers in relation to the clinical severity of COVID-19, with all the tested biomarkers increasing in severe and critical COVID-19. IL-6, CRP, ferritin, LDH, and D-dimer were increased in all COVID-19 forms. These inflammatory markers were lower in Omicron-infected patients. The unvaccinated patients developed more severe forms compared to the vaccinated ones, and a higher proportion of them needed hospitalization. D-dimer could predict a severe form of COVID-19, while LDH could predict the virus variant.

Association of Polymorphisms of IL-6 Pathway Genes (IL6, IL6R and IL6ST) with COVID-19 Severity in an Amazonian Population.

Interleukin-6 has been recognized as a major role player in COVID-19 severity, being an important regulator of the cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of the IL-6 pathway, namely IL6, IL6R, and IL6ST, may provide valuable prognostic/predictive markers for COVID-19. The present cross-sectional study genotyped three SNPs (rs1800795, rs2228145, and rs7730934) at IL6. IL6R and IL6ST genes, respectively, in 227 COVID-19 patients (132 hospitalized and 95 non-hospitalized). Genotype frequencies were compared between these groups. As a control group, published data on gene and genotype frequencies were gathered from published studies before the pandemic started. Our major results point to an association of the IL6 C allele with COVID-19 severity. Moreover, IL-6 plasmatic levels were higher among IL6 CC genotype carriers. Additionally, the frequency of symptoms was higher at IL6 CC and IL6R CC genotypes. In conclusion, the data suggest an important role of IL6 C allele and IL6R CC genotype on COVID-19 severity, in agreement with indirect evidence from the literature about the association of these genotypes with mortality rates, pneumonia, and heightening of protein plasmatic levels pro-inflammatory driven effects.

What do we know about IL-6 in COVID-19 so far?

Interleukin 6 (IL-6) is a cytokine with dual functions of pro-inflammation and anti-inflammation. It is mainly produced by mononuclear macrophages, Th2 cells, vascular endothelial cells and fibroblasts. IL-6 binds to glycoprotein 130 and one of these two receptors, membrane-bound IL-6R or soluble IL-6R, forming hexamer (IL-6/IL-6R/gp130), which then activates different signaling pathways (classical pathway, trans-signaling pathway) to exert dual immune-modulatory effects of anti-inflammation or pro-inflammation. Abnormal levels of IL-6 can cause multiple pathological reactions, including cytokine storm. Related clinical studies have found that IL-6 levels in severe COVID-19 patients were much higher than in healthy population. A large number of studies have shown that IL-6 can trigger a downstream cytokine storm in patients with COVID-19, resulting in lung damages, aggravating clinical symptoms and developing excessive inflammation and acute respiratory distress syndrome (ARDS). Monoclonal antibodies against IL-6 or IL-6R, such as tocilizumab, sarilumab, siltuximab and olokizumab may serve as therapeutic options for COVID-19 infection.

A Web-Based Method for the Identification of IL6-Based Immunotoxicity in Vaccine Candidates.

Interleukin 6 (IL6) is a major pro-inflammatory cytokine that plays a pivotal role in both innate and adaptive immune responses. In the past, a number of studies reported that high level of IL6 promotes the proliferation of cancer, autoimmune disorders, and cytokine storm in COVID-19 patients. Thus, it is extremely important to identify and remove the antigenic regions from a therapeutic protein or vaccine candidate that may induce IL6-associated immunotoxicity. In order to overcome this challenge, our group has developed a computational tool, IL6pred, for discovering IL6-inducing peptides in a vaccine candidate. The aim of this chapter is to describe the potential applications and methodology of IL6pred. It sheds light on the prediction, designing, and scanning modules of IL6pred webserver and standalone package ( https://webs.iiitd.edu.in/raghava/il6pred/ ).

SARS-CoV-2 Infection in Venezuelan Pediatric Patients-A Single Center Prospective Observational Study.

Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analyzed by flow cytometry, and IFNγ, IL-6, and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month to 18 years. The majority, 52.8%, had mild disease, and 30.6% of the patients were diagnosed with MIS-C. The main symptoms reported were fever, cough, and diarrhea. A correlation was found between IL-10 and IL-6 concentrations and age group, lymphocyte subpopulations and nutritional status and steroid use, and IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.

IL-10/IL-6 ratio from nasal & oral swab samples, acts as an inflammatory indicator for COVID-19 patients infected with the delta variant.

Background: Hyper-inflammatory immune response of SARS-CoV-2 is often characterized by the release of multiple pro-inflammatory cytokines with an impact on the expression of numerous other interleukins (ILs). However, from oral and nasal swab samples the specific quantitative association of the different IL-markers with the disease progression and its relationship with the status of vaccination remains unclear. Materials and methods: Patients' combined oral and nasal swab samples were collected from both non-vaccinated and double-vaccinated individuals with high (Ct value < 25) and low (Ct value > 30) viral loads, along with uninfected donors. None of the patients were critically ill, or needed ICU support. The expression of different cytokines (IL6, IL10, IL1B, IFNG) and mucin (MUC5AC, MUC1) markers were assessed between different groups by qRT-PCR. The important cytokine markers differentiating between vaccinated and non-vaccinated patients were identified by PCA. Conclusion: IL6 expression was higher in non-vaccinated COVID-19 patients infected with delta-variant irrespective of their viral-load compared to uninfected individuals. However, in double-vaccinated patients, only in high viral-load patients (Ct value < 25), IL6 expression increased. In high viral-load patients, irrespective to their vaccination status, IL10 expression was lower compared to the uninfected control group. Surprisingly, IL10 expression was lower in double-vaccinated patients with Ct value > 30. IL1B, and IFNG expression remained unaltered in uninfected and infected individuals. However, MUC5AC expression was lower in non-vaccinated patients with Ct value < 25 compared to control group. Our study unveiled that IL10/IL6 ratio can be used as a biomarker for COVID-19 patients upon proper establishment of it in a clinical setting.

Monoclonal antibodies to the interleukin-6 receptor in the treatment of COVID-19 in patients with chronic kidney disease

Interleukin-6 (IL-6) plays a key role in the pathogenesis of COVID-19, which determines the indications for the therapeutic use of its antagonists. However, data on their effectiveness and optimal timing of appointment are contradictory. The question of the possibility of their use in patients with impaired kidney function has not been studied. The aim of the study is to evaluate the efficacy and safety of the use of monoclonal antibodies to IL-6 receptors in COVID-19 in patients with chronic kidney disease (CKD) of stages 2-5 (predialysis) who do not need renal replacement therapy. Material and methods. A clinical retrospective uncontrolled single-center study included 45 patients (60% of men) with CKD stages 2-5 aged 22-95 years (median - 58 years) hospitalized with predominantly severe uncritical COVID-19 infection. Treatment of COVID-19 was carried out in accordance with the Interim guidelines for the prevention and treatment of new coronavirus infection of the Ministry of Health of Russian Federation. Results. The majority of patients (n=36;73.3%) had CKD stage 3b-5, CKD stage 2 was in 7 (15.5%) and stage 3a - in 5 (11.1%) patients. The median serum creatinine level (Cr) was 164 [131;292] mumol/l, glomerular filtration rate (GFR) was 30 [13;49] ml/min/1.73 m2, CRP 67.5 [37.2;106.75] mg/l. The introduction of monoclonal antibody to IL-6 receptors led to a decrease in the activity of the infectious process (CRP 1.55 [0.33;4.15] mg/l, p<0.001), regression of pneumonia, which did not require mechanical ventilation and hospitalization in the intensive care unit. According to the decision of the medical commission, patients were injected with monoclonal antibodies to IL-6 receptors: tocilizumab (n=36;80%), levilimab (n=2;4.4%), combined therapy with two drugs (n=7;15.5%). Therapy with IL-6 antagonists did not have a negative effect on kidney function. The levels of Cr decreased on average from 224.3+/-145.2 mmol/l at admission to 160+/-92.55 mmol/l at discharge (p<0.001), GFR increased from 32.6+/-20.9 ml/min/1.73 m2 at admission to 53+/-31.7 ml/min/1.73 m2 at discharge (p<0.001). In the majority of patients (n=36, 80%) GFR has risen, and only in 9 (20%) cases it remained approximately at the same low level. No serious adverse events have been reported with the use of IL-6 antagonists, as well as concomitant infectious complications. No deaths have been reported. The median length of stay in bed was 14 [10;19] days. Conclusion. The results of the study allow us to state that in patients with CKD, monoclonal antibodies to IL-6 receptors have a good safety profile and can be successfully used in moderate and severe forms of COVID-19, regardless of the state of kidney function.Copyright © 2022 by the authors.

Evaluation of the Genes and Molecular Pathways Involved in Skin Lesions in Patients with COVID-19: Systems Biology and Bioinformatics Analysis Approach

Background: Coronavirus disease 2019 (COVID-19) was first identified in 2019 in Wuhan, China. Initially, although the number of COVID-19-infected individuals was very low, the infected cases increased as the virus spread worldwide. Skin manifestation is one of the symptoms observed in COVID-19 patients. Objectives: This study investigated the critical genes and molecular pathways involved in skin manifestations in COVID-19 patients through a biological system approach. Methods: In this study, the microarray dataset was downloaded from the Gene Expression Omnibus (GEO) database and analyzed for identifying differentially expressed genes (DEGs). The enrichment analysis of DEGs was evaluated using the DAVID database. Afterward, protein-protein interaction (PPI) networks were constructed via the STRING database and visualized using Cytoscape software. The hub genes were recognized using the cytoHubba. The interaction of the microRNA (miRNA)-hub genes, transcription factor (TF)-hub genes, and drug-hub genes was also evaluated in this study. Results: After analysis, some genes with the highest degree of connectivity, which were involved in the pathogenesis of HELLP syndrome were identified, and they were known as hub genes. These genes are as follows: IFN-gamma CXCL1, CCL2, CCL3, TLR2, IL-1B, CXCL6, IL-6, CCL4, and CXCL2. has-mir-34a-5p, has-mir-20a-5p, and has-mir-27a-3p as miRNA, as well as RELA as TF had the most interaction with the hub genes. Conclusion: Finally, IL-6 and CXCL10 that were compared to the other hub genes had the highest interaction with other genes;therefore, their role in Shamgir's pathogenesis is significant. Targeting the cited genes would be a strategy to prevent symptom manifestation and better patient management.

COVID-19 and stroke: A review.

COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating. We have reviewed current studies, case series, and case reports with a focus on COVID-19 patients complicated with stroke, and presented the current understanding of stroke in this patient population. As evidenced by increased D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Collectively, it predisposes patients to cerebrovascular events. Additionally, due to the unprecedented strain on the healthcare system, stroke care has been inevitably compromised. The underlying mechanism between COVID-19 and stroke warrants further study, so does the development of an effective therapeutic or preventive intervention.

Serum calprotectin can indicate current and future severity of COVID-19.

BACKGROUND: Predictive and prognostic biomarkers to guide 2019 novel coronavirus disease (COVID-19) are critically evolving. Dysregulated immune responses are the pivotal cause of severity mainly mediated by neutrophil activation. Thus, we evaluated the association of calprotectin, neutrophil secretory protein, and other mediators of inflammation with the severity and outcomes of COVID-19. METHODS: This two-center prospective study focused on PCR-proven COVID-19 patients (n = 76) with different clinical presentations and SARS-CoV-2 negative control subjects (n = 24). Serum calprotectin (SC) was compared with IL-6 and other laboratory parameters. RESULTS: Median levels of SC were significantly higher in COVID-19 patients in comparison to the control group (3760 vs. 2100 ng/ml, p < 0.0001). Elevated SC was significantly respective of disease severity (3760 ng/ml in mild up to 5700 ng/ml in severe cases, p < 0.0001). Moreover, the significant positive and negative correlations of SC with disease severity and oxygenation status indicated disease progression and respiratory worsening, respectively. It was found that SC was high in severe patients during hospitalization and significantly declined to normal after recovery. The logistic analysis identified the independent predictive power of SC for respiratory status or clinical severity. Indeed, SC behaved as a better discriminator for both outcomes, as it exhibited the largest area under the curve (receiver operating curve analysis), with the highest specificity and sensitivity when the predictive value of inflammatory biomarkers was compared. CONCLUSION: Calprotectin can be used as a reliable prognostic tool to predict the poor clinical outcomes of COVID-19 patients.

Early Use of Ibuprofen in Moderate Cases of COVID-19 Might be a Promising Agent to Attenuate the Severity of Disease: A Randomized Controlled Trial

Introduction: Critically ill COVID-19 patients undergoing cytokine storm are believed to have a worse prognosis and increased fatality rate. Ibuprofen is a non-steroidal anti-inflammatory drug (NSAIDs) that might prove beneficial for the early management of COVID-19 due to its immunomodulatory effects. This study aimed to assess the efficacy and safety of the early use of ibuprofen to attenuate the severity of the course of COVID-19 and improve outcomes in patients diagnosed with a moderate case of COVID-19 disease. Method(s): This randomized, double-blinded prospective study was conducted from January, 2022 to May, 2022, which included a total sample size of 180 patients with moderate cases of COVID-19. The number of patients transferred to intensive care was used as a primary outcome with a proposed large effect size (0.8), alfa =0.05, and power=0.80, so 90 cases were included in each group. Secondary outcomes were inflammatory markers: C-Reactive Protein (CRP), serum ferritin, and interleukin-6 (IL-6), duration of hospital stay, and need for ICU admission. Result(s): One hundred eighty patients with moderate case of COVID-19 disease were divided in a 1: 1 ratio to receive ibuprofen (IG) or paracetamol (CG). The average age of the included patients was almost 41 years. Statistically significant differences were reported between both groups in terms of improvement in cough symptoms and lymphopenia in IG compared to CG (p= 0.034 and p= 0.044, respectively). Regarding secondary outcomes, statistically, significant differences were reported between the study's groups in terms of the mean number of patients transferred to the ICU in IG compared to the CG (p =0.0.047) and duration of hospitalization (p =0.013), with no significant differences (p > 0.9999) in the occurrence of side effects. Concerning the follow-up of the cytokine storm marker, there was a statistically significant reduction in serum cytokine marker compared to the baseline value (P < 0.05) in the same group. No statistically significant differences were observed when comparing both groups together in terms of serum ferritin level (p =0.570), serum IL-6 level (p =0.580), and CRP level (p =0.401). Conclusion(s): It can be concluded that early use of ibuprofen as adjuvant therapy in COVID-19 management is effective and safe to attenuate the severity of diseases and improve outcomes. Trial Registration: Project manager for the Pan African Clinical Trial Registry PACTR202202880140319. Registered 9th February, 2022-Retrospectively registered, (https://pactr.samrc.ac.za/).Copyright © 2023 Sobhy et al.

Significance of Measuring the Proinflammatory Response Biomarkers in Covid-19 Patients

Objectives: In the management of COVID-19, bio-inflammatory cytokines (IL-6 and others) can be measured as inflammatory markers to detect conditions in response to treatment, risk assessment, monitoring disease progression, prognosis determination and treatment selection. The purpose of this study is to identify changes in inflammation markers of COVID-19 patients and to determine whether it should be used as a prognosis marker. Materials-Methods: Three groups of the patients consisting of 138 patients (12 non-survived, 35 severe and 91 mild/moderate) aged 16 to 86 years who were diagnosed with COVID-19 by real-time polymerase chain reaction were included in the study. Acute phase serum levels such as CRP, D-Dimer, Ferritin, IL-1B and IL-6 were measured and compared in serum samples taken from these patients. It was examined whether these parameters can be a biomarker that can be monitored for the course of the disease. IL-6 and ferritin were measured with CLIA, D-dimer immunassay, CRP with photometry and IL1-B was measured with flow cytometry methods. Result(s): It has been observed that all parameters, except for ferritin (P=0.94), increase significantly during the transition from mild to severe form of the disease. (CRP P:0.005, D-Dimer P<0.0001, IL-1B P:0.03, IL-6 P:0.002). A significant difference was observed in the levels of CRP, IL-6 and D-Dimer in the patient survival. (P=0.003, P=0.03, P:0,0001). According to our results, the use of IL-1B in the prognosis monitoring of patients with severe forms was not found to be significant (P:0.48). ROC curve analysis showed that the area under the ROC curve (AUC) of CRP, D-Dimer and IL-6 was 0.645 (0,559 to 0,725), 0.637 (0,551 to 0,717) and 0.663 (0,577 to 0,741) respectively, and the cutoff values were >3.77 (sensitivity, 72.3%;specificity, 55%), >0.48 (sensitivity 68.1%;specificity, 57.1%) and <14.9 (sensitivity, 65,9%;specificity, 62.6%), respectively. Conclusion(s): Our results confirmed that the dynamic change in IL-6, CRP, D-Dimer can be used as a marker for disease monitoring in patients with severe COVID-19.

Computed Tomography Severity Score in COVID-19: Association with Inflammatory Markers and Patient Outcome

Objective: To associate CT severity score with inflammatory markers and to determine outcomes of COVID-19 patients admitted to CMH Lahore. Study Design: Comparative cross-sectional study. Place and Duration of Study: Combined Military Hospital, Lahore Pakistan, from Mar to Jun 2021. Methodology: Patients of COVID-19 age 18 and above, with a positive RT-PCR, were included in the study Clinical and radiological data of 200 patients was retrieved and analysed from the hospital registry. Results: In the present study, we studied the role of inflammatory markers in predicting the severity of COVID-19. We have compared the levels of LDH, CRP, IL-6 and serum Ferritin between the two groups. LDH (p=0.015), IL-6 (p=0.001) and Ferritin (p=0.001) were significantly different between the two groups, but CRP was not (p=0.811) significant. Conclusion: CT severity score associates well with the COVID-19 clinical severity. Our data suggest that the chest CT scoring system can predict the severity of COVID-19 disease and significantly associates with inflammatory markers.