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Clinical spectrum of COVID-19 patients and decreased serum level of miR-146a as a sign of inflammation.

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There is increasing evidence that inflammation is an important determinant in COVID-19 pathogenesis. Several studies describe cytokines and microRNAs as important regulators of immune and inflammatory responses in other diseases, regarding them as valuable biomarkers. Identify a potential relationship between cytokines (interleukin [IL]-6, IL-8) and microRNAs (miR-146a-5p, miR-155-5p) and clinical characteristics of COVID-19 patients, focusing on disease severity and mortality risk. Serum expression levels of miR-146a, miR-155, IL-6, IL-8, C-reactive protein, ferritin, and neutrophil-to-lymphocyte ratio, of 25 mild, 73 moderate, and 39 severe COVID-19 patients from Quito-Ecuador, were determined to correlate outcomes with clinical parameters. In all groups, overweight and obesity were the most prevalent comorbidities (75.91%). Serum levels of IL-6 were significantly elevated in patients with moderate and severe COVID-19 (analysis of variance [ANOVA] p ≤ 0.000). miR-146a was significantly decreased in moderate and severe COVID-19 patients when compared with mild cases (ANOVA p = 0.002). ROC curve analysis showed that selected cut-off values for miR-146a > 3.999 ΔCt for mild vs moderate condition (sensitivity 83.56%, specificity 48%) and miR-146a > 3.999 ΔCt for mild vs severe condition (sensitivity 84.62%, specificity 40%), and IL-6 ≥ 72.25 pg/mL (sensitivity 78.95%, specificity 60.61%) when combined with clinical pretest probability, can be used to predict aggravation and death in COVID-19 patients. Odds ratios (ORs) of miR-146a (OR = 4.322) and IL-6 (OR = 3.198) indicate an increased risk of worsening and death, respectively, when cut-off points were taken into consideration. This study shows that elevated inflammatory IL-6 and decreased serum levels of anti-inflammatory miR-146a-5p can be discriminatory markers of COVID-19 severity and mortality.

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  • Research Article
  • 10.18231/j.pjms.2023.052
Biochemical and Clinical profile of COVID-19 patients and its association with severity of the disease: A study at tertiary care centre
  • Jul 28, 2023
  • Panacea Journal of Medical Sciences
  • Anita Rani* + 3 more

Background: The Novel Corona Virus pandemic caused significant morbidity and mortality worldwide. The biochemical parameters in affected individuals can differentiate between moderate and severe COVID-19 infection. Early identification will facilitate appropriate care and reduce the mortality.Objective : In the present study, we are exploring the possibility of association of the data of biochemical investigations done at the time of admission with COVID-19 severity in patients, as timely modulation in medical management could reduce the mortality and shorten hospital stay.Materials and Methods : A cross sectional study including 452RT-PCR positive, moderate to severe cases of COVID-19 patients admitted to a tertiary care centre, New Delhi were enrolled in the study, in the months of June to October 2020.Biochemical profile of moderate and severe COVID 19 patients was evaluated on admission and correlated with severity of the disease.

  • Research Article
  • 10.12114/j.issn.1007-9572.2021.00.548
Prognostic Indicators for Severity in COVID-19 Patients:a Meta-analysis
  • Jan 1, 2021
  • Chinese General Practice
  • J Wang + 3 more

Background The COVID-19 has become a global pandemic declared by the WHO, and the severity of which affects the prognosis of patients. Objective To explore the prognostic indicators for severity and their predictive values in COVID-19 patients, providing a reference for clinical prediction of patients'outcome and prognosis. Methods Eight databases (The Cochrane Library, Embase, PubMed, Web of Science, SinoMed, CNKI, Wanfang Data Knowledge Service Platform, VIP)were searched from inception to 2020-09-03 for randomized controlled trials(RCTs)about severe versus non-severe COVID-19 patients or deceased versus survived COVID-19 patients with prognostic indicators〔including procalcitonin (PCT), C-reactive protein (CRP), lymphocyte count (LYM), interleukin-6 (IL-6), D-dimer〕studied. The modified Jaded Scale was used to assess the methodological quality. Stata 12.0 was used for meta-analysis. Results Fifteen RCTs were included, involving 1 476 cases, all were assessed with high methodological quality(modified Jadad Scale score ranging from 4 to 5 points). Meta-analysis found that severe COVID-19 patients had higher mean values of PCT〔SMD=-2.28, 95%CI (-3.60, -0.98), P<0.001〕, CRP〔SMD=-2.23, 95%CI (-3.38, -1.07), P<0.001〕, IL-6〔SMD=-2.97, 95%CI (-4.94, -1.00), P<0.001〕, and D-dimer〔SMD=-1.22, 95%CI (-2.66, 0.21), P=0.008〕than non-severe COVID-19 patients. Severe COVID-19 patients had lower mean LYM〔SMD=1.41, 95%CI (0.34, 2.48), P<0.001〕. The deceased COVID-19 patients had higher mean values of PCT〔SMD=-4.11, 95%CI (-9.98, 1.76), P=0.007〕, CRP〔SMD=-2.73, 95%CI (-4.21, -1.25), P<0.001〕, IL-6〔SMD=-3.79, 95%CI (-4.90, -2.67), P<0.001〕, and D-dimer〔SMD=-0.68, 95%CI (-1.46, 0.09), P=0.009〕 than the survived.The deceased COVID-19 patients had lower mean LYM 〔SMD=2.08, 95%CI (0.93, 3.22), P<0.001〕. Conclusion Increased PCT, CRP, IL-6 and D-dimer and decreased LYM were found in severe or deceased COVID-19 patients, indicating that the former three may be positively correlated with severity, while the latter may be negatively correlated with severity. These five indicators may be used as prognostic indicators for severity, too high PCT, CRP, IL-6 and D-dimer, and too low LYM may suggest a poor prognosis. Copyright © 2021 by the Chinese General Practice.

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  • 10.1111/cpr.12927
Impaired lung regeneration after SARS-CoV-2 infection.
  • Oct 20, 2020
  • Cell Proliferation
  • Hongxia Shao + 8 more

Impaired lung regeneration after SARS-CoV-2 infection.

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  • Cite Count Icon 4
  • 10.7759/cureus.44528
Continuous Remote Monitoring in Moderate and Severe COVID-19 Patients.
  • Sep 1, 2023
  • Cureus
  • Avinash H Rajanna + 6 more

Background COVID-19 steadily built up the pressure on healthcare systems worldwide, creating the need for novel methods to alleviate the burden. Continuous remote monitoring of vital parameters reduces morbidity and mortality in hospitals by providing real-time disease data that can be analyzed through web portals. It enables healthcare workers to identify which patients require prompt administration of healthcare. Patients remain under the purview of their doctors and can be notified early if there are any deteriorations in the parameters being monitored. Aims To evaluate the use of remote monitoring in moderate and severe COVID-19 patients and to correlate the Dozee Early Warning Score (DEWS) with severity and outcome in moderate and severe COVID-19 patients. Materials and methods We conducted a prospective study on adult (>18 years old) moderate and severe COVID-19 patients during the second wave of COVID-19. The vitals of the subjects were continuously monitored using Dozee, a contactless remote patient monitoring system enabled with DEWS that reflects the overall patient condition based on respiratory rate (RR), heart rate (HR), and oxygen saturation (SpO2). We assessed the correlation of DEWS with patients' clinical outcomes: deteriorated or recovered. Results Thirty-nine COVID-19 patients were recruited for the study, of whom 29 were discharged after recovery and 10 deteriorated and died. Respiratory rate trend, respiratory rate DEWS, SpO2 DEWS, and total DEWS showed a significant reduction in recovered patients, while the same parameters showed a significant increase followed by consistently high scores in patients who deteriorated and died due to the disease. Total DEWS was proportional to the risk of mortality in a patient. Conclusion We concluded that continuous vitals monitoring and the resulting DEWS in moderate and severe COVID-19 patients were indicators of their improvement or deterioration. DEWS uses continuous remote monitoring of routinely collected vitals (HR, RR, and SpO2) to serve as a predictor of patient outcome.

  • Research Article
  • 10.1164/ajrccm.2025.211.abstracts.a5664
Clinical Characteristics of COVID-19 Patients Who Received Ventilator Management During the Omicron Variant Period in a Tertiary Hospital in Japan
  • May 1, 2025
  • American Journal of Respiratory and Critical Care Medicine
  • M Seki

RATIONALE: Severe COVID-19 patients who received ventilator management were not very rare even when the omicron variant became dominant, but the clinical characteristics of these patients are still unclear. METHODS: The clinical characteristics of severe COVID-19 patients requiring ventilator management were retrospectively investigated from January 2023 to December 2023. RESULTS: Severe COVID-19 patients who received ventilator management accounted for 11 of 275 (4.2%) patients during the omicron variant period. Their mean age was 70.7 (51-85) years, and males were predominant. Ten of eleven (91.7%) patients were managed in the emergency department and had underlying diseases, including chronic lung/heart/kidney diseases and neurological diseases. However, only 4 of 11 (36.4%) had a clear history of vaccination. The patients showed a positive SARS-CoV-2 antigen titer of 3305.7 (12.9-20912). All 11 patients were treated with remdesivir and dexamethasone, and 5 (45.5%) also received sotrovimab. Pathogenic bacteria were isolated from 7 of 11 (63.6%) patients, and all 11 patients were treated with antibiotics. Only 3 of 11 (27.3%) patients were managed using extracorporeal membrane oxygenation (ECMO), but 9 of 11(81.8%) patients survived. CONCLUSION: These data suggest that severe COVID-19 patients who required ventilator management were less-vaccinated, elderly patients with underlying disease. These patients were treated successfully using antiviral agents, steroids, neutralizing antibodies, and antibiotics, with a few also treated using ECMO in the omicron era.

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  • Cite Count Icon 1
  • 10.1371/journal.pone.0324987
Phagocytic activity of blood monocytes and neutrophils in moderate COVID-19 patients and impact of immune therapy with bacterial lysates.
  • Jun 5, 2025
  • PloS one
  • Mikhail Kostinov + 18 more

Monocytes, macrophages and dendritic cells are involved in phagocytic reactions, which potentially play an important role in the pathogenesis of COVID-19. Imbalance of these cells in peripheral blood has proven to affect not only innate but also adaptive immunity. It is possible that a search for strategies to restore monocyte activity could be a major step in achieving immune control over COVID-19. The aim of this study was to investigate the relationship between phagocytic activity of peripheral-blood monocytes and neutrophils, and COVID-19 severity, to assess the effects of a bacteria-based immunostimulating agent on phagocytosis parameters in in-hospital COVID-19 patients. The study included 105 adult patients with moderate COVID-19, who had been hospitalized in 2020-2021 and treated in accordance with the recommendations of the Ministry of Health of the Russian Federation. All patients were divided into two groups: in Group 1 patients received standard treatment and Immunovac VP4 therapeutic vaccine, a bacteria-based immunostimulating agent as add-on therapy from Day 1 of hospitalization; in Group 2 patients did not receive any add-on treatment. The study parameters included C-reactive protein (CRP), aspartate aminotransferase (AST), SpO2, lung involvement on chest computer tomography (CT) scan, and phagocytic activity of peripheral-blood leukocytes based on the absorption activity (AA) of monocytes and neutrophilic granulocytes against S. аureus). The parameters were assessed at 1, 14 and 30 days. Based on a cluster analysis of the clinical findings and the results of diagnostic tests obtained on admission, the patients were divided into 2 clusters: cluster 1 including patients with a more severe disease (n = 34) and cluster 2 including patients with a less severe disease (n = 71). Cluster 1 patients had higher levels of CRP (20.1 vs. 2.2 mg/mL, p < 0.001), AST (32.9 vs. 26.2 U/L, p = 0.003), lower SpO2 (94% vs. 96%, p < 0,001) and more extensive lung involvement on chest CT scan (35% vs. 12%, p < 0,001). There was a statistically significant direct correlation between blood monocyte AA and SpO2 (p = 0.04), an inverse correlation between monocyte AA and CRP (p = 0.003) and the extent of lung involvement on CT scan (p = 0.05). In less severe COVID-19 patients (cluster 2), no statistically significant correlation was observed. In more severe COVID-19 patients (cluster 1), there was a rise in monocyte AA on day 30 of hospitalization both in the control group (from 86.6 to 92.2, p = 0.03) and the main group, who received Immunovac VP4 add-on therapy (from 87.3 to 98.3, p = 0.05). However, the patients who received the immunostimulating agent, had higher monocyte PI than the controls, without the immunostimulant (p = 0.05). Patients from cluster 1 who were given Immunovac VP4 had higher SpO2 levels (98% vs. 97%, p = 0.01) than those who had received only the standard treatment. Blood monocyte AA correlates with COVID-19 severity: patients with less severe disease have higher AA and those with more severe illness have lower AA. The standard treatment, combined with Immunovac VP4 enhances phagocytic activity of peripheral-blood monocytes, which is associated with a more marked increase in SpO2, especially in more severe patients.

  • Research Article
  • 10.7454/jpdi.v9i4.1019
Association between Early Antibiotic Administration and In-Hospital Mortality in Moderate and Severe COVID-19 Patients
  • Dec 31, 2022
  • Jurnal Penyakit Dalam Indonesia
  • Laporan Penelitian + 12 more

Introduction. Patients with moderate and severe COVID-19 generally receive antibiotic therapy with consideration of the possibility of co-infection or secondary bacterial infection which clinically is difficult to distinguish from COVID-19 symptoms. Overuse of antibiotics can lead to an increased risk of bacterial resistance to antibiotics which is associated with poor outcomes in COVID-19 patients. This study aimed to assess the effect of early antibiotic administration on mortality in moderate and severe COVID-19 patients. Methods. An observational study with a retrospective cohort design was conducted at Dr. Cipto Mangunkusumo Hospital. Data were obtained from medical records of patients admitted from March to September 2020. Patients who received early antibiotics were defined as patients who received antibiotics hospital, 108 subjects were included in this study, 74 (68.5%) with moderate degrees and 34 (31.5%) with severe degrees. Early antibiotics were administered to 79 (73.1%) subjects with a median start time of one day. The results of the bivariate analysis did not find a significant effect of early antibiotic administration on mortality in moderate or severe COVID-19 patients (p=0.42). Subgroup analysis based on the degree of disease also found no significant results. Conclusion. There is no relationship between early antibiotic administration and mortality of moderate and severe COVID-19 patients.

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  • Cite Count Icon 1
  • 10.2147/idr.s418788
A Retrospective Data Audit of Outcome of Moderate and Severe Covid-19 Patients Who Had Received MP and Dex: A Single Center Study
  • Dec 9, 2024
  • Infection and Drug Resistance
  • Yupeng Li + 16 more

PurposeTo evaluate the necessity of the application of glucocorticoid (GC) in moderate COVID-19 patients, and which is the optimal choice between methylprednisolone (MP) and dexamethasone (DEX) in the clinical use of GC in different types of COVID-19 patients.Patients and MethodsThe study included patients with COVID-19 in Shanxi, China, from December 18, 2022, to March 1, 2023. The main clinical outcomes were 30-day mortality, disease exacerbations, and hospitalization days. Secondary outcomes included the demand for non-invasive ventilator-assisted ventilation (NIPPV)/invasive mechanical ventilation (IMV), the need for GC regimen escalation in follow-up treatment, duration of GC treatment, and complications including hyperglycemia and fungal infection.ResultsIn moderate patients (N = 351), the rate of exacerbation and the need for GC regimen escalation in follow-up treatment was highest in the no-use GC group (P = 0.025, P = 0.01), the rate of fungal infections was highest in the DEX group (P = 0.038), and MP 40 mg/day or DEX 5 mg/day reduced exacerbations with consistent effects. In severe patients (N = 371), the two GC regimens do not affect their 30-day mortality and exacerbation rate, but the number of hospital days was significantly lower in the MP group compared with the DEX group (P < 0.001).ConclusionGC use is beneficial in mitigating exacerbations in moderate patients and in patients with moderate COVID-19. In severe patients, MP reduces the number of hospitalization days compared with DEX and may be a superior choice.

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  • Cite Count Icon 5
  • 10.3390/jpm13010034
Relation between Cytokine Levels and Pulmonary Dysfunction in COVID-19 Patients: A Case-Control Study.
  • Dec 23, 2022
  • Journal of Personalized Medicine
  • Salma A El Kazafy + 7 more

Aim: The study aimed to assess the relationships between serum cytokine levels and pulmonary dysfunctions in individuals with COVID-19. These correlations may help to suggest strategies for prevention and therapies of coronavirus disease. Patients and methods: Fifty healthy participants and one hundred COVID-19 patients participated in this study. COVID-19 participants were subdivided into moderate and severe groups based on the severity of their symptoms. In both patients and healthy controls, white blood cells (WBCs) and lymphocytes counts and serum C-reactive protein (CRP), interleukin (IL)-1, IL-4, IL-6, IL-18, and IL-35 levels were estimated. All the patients were examined by chest computed tomography (CT) and the COVID-19 Reporting and Data System (CO-RADS) score was assessed. Results: All COVID-19 patients had increased WBCs count and CRP, IL-1β, IL-4, IL-6, IL-18, and IL-35 serum levels than healthy controls. Whereas WBCs, CRP, and cytokines like IL-6 showed significantly higher levels in the severe group as compared to moderate patients, IL-4, IL-35, and IL-18 showed comparable levels in both disease groups. Lymphocytes count in all patient groups exhibited a significant decrease as compared to the heathy controls and it was significantly lower in severe COVID-19 than moderate. Furthermore, CO-RADS score was positively connected with WBCs count as well as CRP and cytokine (IL-35, IL-18, IL-6, IL-4 and IL-1β) levels in both groups. CO-RADS score, also demonstrated a positive correlation with lymphocytes count in the moderate COVID-19 patients, whereas it demonstrated a negative correlation in the severe patients. The receiver operator characteristic (ROC) curve analysis indicated that IL-1β, IL-4, IL-18, and IL-35 were fair (acceptable) predictors for COVID-19 in moderate cases. Whereas IL-6 was good predictor of COVID-19 in severe cases (AUC > 0.800), IL-18 and IL-35 were fair. Conclusion: Severe COVID-19 patients, compared to individuals with moderate illness and healthy controls, had lower lymphocyte counts and increased CRP with greater WBCs counts. In contrast to moderate COVID-19 patients, severe COVID-19 patients had higher levels of IL-6, but IL-4, IL-18, and IL-35 between both illness categories were at close levels. IL-6 level was the most potent predictor of COVID-19 progress and severity. CO-RADS 5 was the most frequent category in both moderate and severe cases. Patients with a typical CO-RADS involvement had a higher CRP and cytokine (IL-1β, IL-6, IL-4, IL-18, and IL-35) levels and WBCs count with a lower lymphocyte number than the others. Cytokine and CRP levels as well as WBCs and lymphocyte counts were considered surrogate markers of severe lung affection and pneumonia in COVID 19 patients.

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  • Conference Article
  • Cite Count Icon 2
  • 10.11594/nstp.2022.2816
Bacterial Sputum Culture Results with Moderate and Severity Covid-19 Patients in Pinere Room Arifin Achmad Hospital, Riau Province
  • Dec 2, 2022
  • Dewi Wijaya + 2 more

SARS CoV-2 is a new type of coronavirus and infects respiratory tract. Covid-19 may occur secondary bacterial infection, notably in severe degrees. Secondary bacterial infections are generally associated with viral respiratory infections concurrently after the primary infection. Sputum examination is essential to diagnose the etiology of the disease. So far, there has not been much research on secondary bacterial infections in Covid-19 patients. This research is a descriptive retrospective study. The study was conducted on moderate and severe Covid-19 patients treated in the PINERE Room by looking at the results of bacterial sputum cultures in confirmed Covid-19 patients from the Clinical Pathology Laboratory of Arifin Achmad Hospital, Riau Province starting from August 2020 to July 2021. This study is for the results of bacterial sputum culture with secondary infection in moderate and severe Covid-19 patients. The purpose of this research to analyze the relationship between sputum culture results and severity and outcome in Covid-19 patients. Of the 204 samples of bacterial sputum culture, the results obtained were normal flora 42.16%, Klebsiella pneumonia 22.55%, no growth of bacteria 10.78%, Acinetobacter baumannii 6.37%, Staphylococcus aureus 5.39%, Pseudomonas aureginosa 3, 43%, Staphylococcus maltophilia, Escheria colli, Enterobacter clocae 2.45% each. Based on the morphology of Gram-negative bacteria, 41.1% more than Gram-positive 6.37%.

  • Research Article
  • 10.31590/ejosat.1266055
Assessment of WBCs, CRP, LDH and other Biomarkers of Moderate and Severe COVID-19 Patients in Iraq
  • Mar 22, 2023
  • European Journal of Science and Technology
  • Mustafa Salman + 1 more

Background:&#x0D; Though most Iraqi patients who are infected by COVID-19 only suffering from mild symptoms, but in some cases a patient’s condition deteriorates, leading to a negative outcome. This study aims to assess the clinical laboratory features of moderate and severe COVID-19 patients&#x0D; Methods: &#x0D; One hundred diagnosed as moderate and severe COVID-19 patients as well as fifty healthy participants were involved in our current study. Assessment was made for WBCs, Monocytes, Lymphocyte, and Platelets. In addition, serum levels of lactate dehydrogenase (LDH) and C-reactive protein (CRP). &#x0D; Results: &#x0D; A hundred patients aged 33 to 70 years with COVID-19 had severe and moderate cases. Present in DAR AL-SALAM for COVID-19 isolation in Baghdad, Iraq. COVID-19 patients showed increased serum levels LDH and CRP as well as WBCs count and others when compared to healthy individuals. The severe group showed a statistically significant increase in WBCs account, neutrophil activity and LDH levels, compared with moderate group. While the moderate COVID-19 groups displayed a significant rise in lymphocytes activity, CRP, and Platelet. Conclusion: &#x0D; The current investigation found that WBC count, lymphocyte count, LDH activity, and CRP level were effective indicators for determining the severity of COVID-19, making them good assessment indicators.

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  • Cite Count Icon 1
  • 10.1158/1538-7445.am2022-5274
Abstract 5274: Mechanisms of action (MOA) for proxalutamide, an androgen receptor (AR) antagonist, for the treatment of mild, moderate and severe COVID-19 patients
  • Jun 15, 2022
  • Cancer Research
  • Liandong Ma + 11 more

As of November 2021, there were 21 million confirmed active cases of COVID-19, including 77,016 patients in serious or critical condition (virusncov.com). However, there are no effective oral drugs for the treatment of severe COVID 19 patients. We here discuss the mechanism of action for Proxalutaminde to treat mild, moderate and severe COVID-19 Patients. Cellular entry and infection of SARS-CoV-2 virus are mediated by two key proteins in host cells, angiotensin converting enzyme 2 (ACE2), a host transmembrane protein, providing the binding sites for SARS-CoV-2 on the host cell surface, and transmembrane protease serine 2 protein (TMPRSS2), priming the S protein of SARS-Cov-2 to facilitate the viral entry into the host cells. Both ACE2 and TMPRSS2 proteins are regulated by androgen receptor (AR) signaling. Previously, Proxalutamide has been reported to downregulate the expression of ACE2 and TMPRSS2 in cells derived from prostate, lung cancer and normal lung epithelial cells. In this study, we demonstrate that Proxalutamide inhibited the infection of SARS-COV-2 wild type, alpha and delta variants, with IC50s of 69, 48 and 39 nM, respectively. Moreover, Proxalutamide reduced SARS-COV-2 viral load in outpatients with COVID-19 (82% viral RT-PCR negative rate in active group vs. 31% in placebo group after treatment for 7 days (p-value&amp;lt;0.0001). Severe COVID-19 disease leads to cytokine storm resulting in pulmonary inflammation and extensive damage in lung and other organs. Anti-inflammatory drugs, including Baricitinib and dexamethasone, have shown limited clinical benefit for hospitalized COVID-19 patients. Therefore, more effective drugs are in urgent need for patients suffering from severe COVID-19. Recently, Proxalutamide has been reported to reduce the mortality rate (HR=0.16) and lung injury (by 57%, active drug vs placebo groups) in hospitalized patients with COVID-19 in an IIT phase III study. We presented here the mechanism of action of Proxalutamide for targeting cytokine storm in severe COVID-19 patients. Proxalutamide was demonstrated to activate nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages, which stimulates the antioxidant response element (ARE) for reducing cytokine storm-induced organ damage in COVID-19. In addition, Proxalutamide inhibited TNF alpha and IL-6 expression and blocked INF gamma signaling by downregulating STAT1 expression in immune cells. Importantly, Proxalutamide reduced inflammatory cells in lungs in a Poly (I:C), pseudoviral induced-lung injury animal models. Further, Proxalutamide decreased C-reactive protein, D-Dimer and improved lymphocyte count, biomarkers for COVID-19 progression in clinical studies. Together, these results provide a strong rationale for the treatment of severe COVID-19 patients with Proxalutamide. Citation Format: Liandong Ma, Youzhi Tong, Qianxiang Zhou, Hongha Yan, Xiaodan Hou, Zhiha Ren, Jiangwei Li, Huiyuan Wang, Weidong Qian, Yu Zhang, Andy Goren, Arul Chinnaiyan. Mechanisms of action (MOA) for proxalutamide, an androgen receptor (AR) antagonist, for the treatment of mild, moderate and severe COVID-19 patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5274.

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  • Cite Count Icon 2
  • 10.24293/ijcpml.v30i1.2096
Comparative Analysis of Hematological and Inflammatory Biomarkers in Moderate and Severe COVID-19 Patients
  • Nov 3, 2023
  • INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY
  • Maimun Zulhaidah Arthamin + 5 more

In COVID-19 patients, abnormal blood clotting is common, characterized by elevated D-dimer and fibrinogen levels, reduced platelets, and prolonged clotting times. The second week of infection can trigger a cytokine storm, marked by heightened proinflammatory Interleukin-6 (IL-6) levels, associated with Acute Respiratory Distress Syndrome (ARDS) and organ failure. This study compared hematological biomarkers, D-dimer, and IL-6 in moderate and severe COVID-19 cases. In a cross-sectional study, 81 patients meeting inclusion criteria were examined at a leading private COVID-19 referral hospital in Malang Regency. Data from clinical records and lab results encompassing blood counts, D-dimer, and IL-6 levels were collected. D-dimer was assessed through immunoturbidimetry (STA-Procoag-PPL, Diagnostica Stago S.A.S.), while IL-6 was measured using a chemiluminescent immunoassay (Cobas e411 Elecsys, Roche). Data distribution normality was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Non-normally distributed data were analyzed using the Mann-Whitney U test for numerical data and the Fisher exact test for comorbidity-severity correlation. Moderate COVID-19 cases disproportionately affected females, while severe cases had an even gender distribution. The median age was comparable, but mild cases were typically younger. Hemoglobin, hematocrit, leukocyte, neutrophil, platelet, and procalcitonin levels were normal in both groups, with lowered lymphocyte counts. Severe cases displayed a higher Neutrophil-to-Lymphocyte Ratio (NLR). D-dimer and IL-6 were significantly elevated in extreme cases. This study underscores potential gender and age-related discrepancies in COVID-19 severity, emphasizing the significance of monitoring specific blood parameters for disease progression indicators. Further investigation is vital to unveil underlying mechanisms and clinical implications, aiding the management of COVID-19 patients.

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  • Cite Count Icon 31
  • 10.3389/fimmu.2022.947401
Serum soluble Fas ligand is a severity and mortality prognostic marker for COVID-19 patients
  • Aug 31, 2022
  • Frontiers in Immunology
  • Kiarash Saleki + 7 more

Finding cytokine storm initiator factors associated with uncontrolled inflammatory immune response is necessary in COVID-19 patients. The aim was the identification of Fas/Fas Ligand (FasL) role in lung involvement and mortality of COVID-19 patients. In this case-control study, mild (outpatient), moderate (hospitalized), and severe (ICU) COVID-19 patients and healthy subjects were investigated. RNA isolated from PBMCs for cDNA synthesis and expression of mFas/mFasL mRNA was evaluated by RT-PCR. Serum sFas/sFasL protein by ELISA and severity of lung involvement by CT-scan were evaluated. Also, we docked Fas and FasL via Bioinformatics software (in silico) to predict the best-fit Fas/FasL complex and performed molecular dynamics simulation (MDS) in hyponatremia and fever (COVID-19 patients), and healthy conditions. mFasL expression was increased in moderate and severe COVID-19 patients compared to the control group. Moreover, mFas expression showed an inverse correlation with myalgia symptom in COVID-19 patients. Elevation of sFasL protein in serum was associated with reduced lung injury and mortality. Bioinformatics analysis confirmed that blood profile alterations of COVID-19 patients, such as fever and hyponatremia could affect Fas/FasL complex interactions. Our translational findings showed that decreased sFasL is associated with lung involvement; severity and mortality in COVID-19 patients. We think that sFasL is a mediator of neutrophilia and lymphopenia in COVID-19. However, additional investigation is suggested. This is the first report describing that the serum sFasL protein is a severity and mortality prognostic marker for the clinical management of COVID-19 patients.

  • Research Article
  • Cite Count Icon 2
  • 10.12688/f1000research.125115.1
The role of IL-6, ferritin, and coagulopathy in COVID-19 clinical progression
  • Nov 10, 2022
  • F1000Research
  • Alvin Tagor Harahap + 8 more

Background In COVID-19, the release of pro-inflammatory mediators in the cytokine storm, primarily interleukin-6 (IL-6), has been hypothesized to induce pulmonary intravascular coagulation. However, the relationship between IL-6 and coagulopathy remains unclear in COVID-19 progression. We aimed to investigate the correlation of IL-6 with D-dimer, fibrinogen, prothrombin time (PT), and ferritin. Furthermore, we also analyzed the effect of those parameters on the worsening of COVID-19 patients. Methods A prospective cohort study was conducted in moderate and severe COVID-19 patients from June 2020 to January 2021. A serial evaluation of IL-6, D-dimer, fibrinogen, ferritin, and PT was performed and correlated with the patient's condition at admission and on the 14th day. The outcomes (improvement, worsening, or discharged patients) were recorded during the study. Results Of 374 patients, 73 study subjects (61 severe and 12 moderate COVID-19) were included in this study. A total of 35 out of 61 severe and one out of 12 moderate illness subjects had experienced worsening. Spearman-rank correlation of IL-6 with with ferritin, D-dimer, fibrinogen, and PT was 0.08 (p=0.5), −0.13 (p=0.27), 0.01 (p=0.91), and 0.03 (p=0.77), respectively. In ROC analysis, D-dimer (74,77%) and IL-6 (71,32%) were the highest among other variables (&gt;60%). Conclusions In COVID-19 patients, there was a correlation between elevated IL-6 and D-dimer levels with disease deterioration. There was no correlation between elevated IL-6 levels with ferritin, D-dimer, fibrinogen, and PT levels. Therefore, changes in IL-6 and D-dimer can predict worsening in moderate and severe COVID-19 patients.

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