TNF-α, iNOS Augmentation Due to Macrophages and Neutrophils Activity in Samples from Patients in Intensive Care Unit with COVID-19 Infection

Author(s):  
Zivar Zangeneh ◽  
Alireza Andalib ◽  
Gholamreza Khamisipour ◽  
Hamid Saadabadimotlagh ◽  
Sareh Zangeneh ◽  
...  

Background and Aims: Cells and secreted molecules by the innate immune system are the essential factors in the pathogenesis and determining the severity of inflammation in COVID-19 patients. Severe inflammation results from increased activity of neutrophils, macrophages, and other cells with their products. Inflammatory cytokines such as tumor necrosis factor-a (TNF-a)  increases the severity and pathogenesis of the disease caused by the virus. Phagocytes are armed with inducible nitric oxide synthase (iNOS), that upon stimulation by proinflammatory cytokines augment an immune response against pathogens. Materials and Methods: Two groups of patients were included with COVID-19 infection from the intensive care unit (ICU, n=52) and (non-ICU-care, n=54). Blood samples were collected to measure cells and serum parameters, including lymphocytes, neutrophils, platelet counts, accompanied with C-reactive protein, lactate dehydrogenase, TNF-a and iNOS levels. Results: In the ICU group, increased white blood cells (p=0.048), decreased lymphocytes (p=0.0007), increased neutrophils (p=0.001), decreased platelets, increase serum levels for lactate dehydrogenase (p =0.0001), c-reactive protein (p=0.003), TNF-a (p=0.018), and iNOS (p=0.008) were statistically obtained. Positive correlations were calculated between TNF-a and iNOS (r=0.65, p=0.0002) and with c-reactive protein (r=0.52, p=0.003) and with lactate dehydrogenase (r=0.68, p=0.0001). Conclusion: Inflammation due to macrophages and neutrophils activity in COVID-19 patients and increased mediators correlate with disease progression. It seems that control of the cell activity and their inflammatory cytokines would be considered for therapeutic goals. Changing the polarization of inflammatory macrophages to anti-inflammatory macrophages with therapeutic applications could prevent the severity of the provocative course of the disease.

2021 ◽  

Objectives: The COVID-19 disease can manifest itself with acute respiratory distress syndrome, renal failure, and septic shock in critically ill patients. There are opinions that there is a correlation between high IL-6 levels and disease severity. In our intensive care unit, we evaluated the changes in the laboratory data and radiological involvement severity of our patients who underwent tocilizumab treatment and examined the appropriate laboratory parameter in the treatment follow-up and its effect on survival. Methods: In the critical patient follow-up of COVID-19, 17 of the 23 patients treated with tocilizumab had a mortal course (Group 1) and the remaining 6 (Group 2) were. The C-reactive protein, lactate dehydrogenase, IL-6, D-dimer, procalcitonin, albumin, and ferritin values, which were routinely screened in our clinic on the day of tocilizumab treatment and the 5th day after, were recorded. Both the change between the two groups and the change between days 1 and 5 were analyzed. Results: A total of 23 patients (55.35 ± 13.31 years) were included in the study. The computed tomography severity score assessed at the intensive care unit admission was statistically significantly higher in Group 2. The procalcitonin and lactate dehydrogenase values measured on day 5 after tocilizumab were significantly lower in Group 2. On the 5th day after treatment, the levels of C-reactive protein, ferritin, chest X-rays, IL-6 and D-dimer statistically significantly changed compared to the first day of the treatment. In correlation with the decrease in PCT as of the 5th day after tocilizumab administration, an increasing tendency was observed in 28-day survival. Conclusion: This study demonstrated that tocilizumab treatment may positively contribute to the treatment by decreasing cytokine levels. PCT and LDH follow-up before and after treatment in critically ill patients who are receiving tocilizumab treatment can give an idea about survival.


2020 ◽  
Vol 12 (3) ◽  
pp. 17-33
Author(s):  
Rohmantuah Trada Purba ◽  
Mahendratama Purnama Adhi ◽  
Erna Kusumawardhani ◽  
Rapto Hardian ◽  
Andri Lumban Tobing

Latar Belakang: Corona Virus Disease 2019 (COVID-19) adalah penyakit pandemi yang menjadi masalah global yang melanda seluruh dunia. Manifestasi klinis dan tingkat keparahan penyakit COVID-19 sangat bervariasi. Pada pasien COVID-19 derajat kritis yang memerlukan perawatan di intensive care unit (ICU) telah ditemukan adanya proses badai sitokin yang meningkatkan mortalitas dan morbiditas. Interleukin-6 (IL-6) berperan dalam terjadinya badai sitokin.Kasus: Berikut kami laporkan serial kasus 5 pasien COVID-19 terkonfirmasi positif derajat sedang-kritis yang diberikan tocilizumab (TCZ) sebagai suatu IL-6 inhibitor yang memiliki potensi terapi menurunkan mortalitas dan morbiditas pasien COVID-19 derajat berat-kritis.Pembahasan: Dari 5 pasien yang diberikan TCZ, didapatkan hasil 3 pasien bisa pulang dan 2 pasien meninggal. Terdapat potensi pemberian IL-6 inhibitor karena dari patofisiologi penyakit COVID-19 yang berkaitan dengan IL-6 dan badai sitokin. IL-6 inhibitor dapat menurunkan mortalitas dan morbiditas dengan mencegah terjadinya badai sitokin. Hal ini diukur menggunakan evaluasi onset penyakit, kadar biomarker inflamasi dan gangguan koagulasi yang sering diteliti pada pasien COVID-19 seperti c-reactive protein (CRP), lactate dehydrogenase (LDH), D-Dimer dan ferritin.Kesimpulan: Pemberian TCZ memiliki potensi efek terapeutik jika diberikan pada onset penyakit <10 hari. Perlu dilakukan penelitian lebih lanjut untuk menilai efek terapeutik dan timing pemberian yang tepat.


2019 ◽  
Vol 32 (12) ◽  
pp. 737
Author(s):  
Marta Ayres Pereira ◽  
Ana Lídia Rouxinol-Dias ◽  
Tatiana Vieira ◽  
José Artur Paiva

Introduction: The ideal biomarker to assess response and prognostic assessment in the infected critically ill patient is still not available. The aims of our study were to analyze the association between early C-reactive protein kinetics and duration and appropriateness of antibiotic therapy and its usefulness in predicting mortality in infected critically ill patients.Material and Methods: We have carried out an observational retrospective study in a cohort of 60 patients with community-acquired pneumonia, aspiration pneumonia and bacteremia at an intensive care unit. We have collected C-reactive protein consecutive serum levels for eight days as well as duration and appropriateness of initial antibiotic therapy. C-reactive protein kinetic groups were defined based on the levels at days 0, 4 and 7. With a follow-up of one year, we have evaluated mortality at different time-points.Results: We have obtained three different C-reactive protein kinetic groups from the sample: fast response, delayed but fast response and delayed and slow response. We did not find statistically significant associations between C-reactive protein kinetics and early (intensive care unit, hospital and 28-days) or late (six months and one year) mortality and antibiotic therapy duration (p > 0.05). Although there were no statistically significant differences between the appropriateness of antibiotic therapy and the defined groups (p = 0.265), no patient with inappropriate antibiotic therapy presented a fast response pattern.Discussion: Several studies suggest the importance of this protein in infection.Conclusion: Early C-reactive protein kinetics is not associated with response and prognostic assessment in infected critically ill patients. Nevertheless, a fast response pattern tends to exclude initial inappropriate antibiotic therapy.


PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e55964 ◽  
Author(s):  
Zainna C. Meyer ◽  
Jennifer M. J. Schreinemakers ◽  
Paul G. H. Mulder ◽  
Ruud A. L. de Waal ◽  
Antonius A. M. Ermens ◽  
...  

2021 ◽  
Vol 13 (2) ◽  
pp. 114-124
Author(s):  
Andi Taufik Amiruddin ◽  
Haizah Nurdin ◽  
Syafri Kamsul Arif ◽  
Andi Muhammad Takdir Musba ◽  
Andi Salahuddin ◽  
...  

Latar Belakang: Organisasi Kesehatan Dunia (WHO) mendeklarasikan penyebaran dari coronavirus disease 2019 (COVID-19). Faktor risiko terhadap mortalitas pasien COVID-19 rawat intensive care unit (ICU) belum banyak diteliti.Tujuan: Mengetahui hubungan penanda infeksi, penanda oksigenasi dan faktor risiko lainnya terhadap mortalitas pasien COVID-19 dengan pneumonia.Metode: Penelitian retrospektif dilakukan di ICU Infection Centre RSUP Dr. Wahidin Sudirohusodo, Makassar pada April – Agustus 2020. Sampel penelitian adalah data pasien COVID-19 dengan pneumonia yang dirawat di ICU. Pasien dibagi ke dalam dua kelompok survivor grup (SG) dan non-survivor (NSG). Variabel penelitian berupa penanda infeksi, penanda oksigenasi dan faktor risiko yang didapatkan dari rekam medis pasien. Analisis bivariat dan multivariat dilakukan terhadap semua variabel penelitian.Hasil: Dari 92 pasien didapatkan 46 NSG dan 46 SG. Perbandingan jenis kelamin dan indeks massa tubuh antara kedua kelompok tidak signifikan bermakna secara statistik. Tidak didapatkan perbedaan signifikan secara statistik pada level c-reactive protein (CRP) antara kelompok NSG dengan median 91,1 (IQR 32,3-200,45) dan SG 88,95 (IQR 33,50-177,80), p= 0,899. Faktor risiko usia tua, diabetes mellitus (DM), dan peningkatan rasio neutrofil-limfosit (RNL) berdasarkan klasifikasi cut-off signifikan secara statistik pada mortalitas antar kedua kelompok.  Pada NSG didapatkan median usia 60,5 (IQR 53-67,25) vs SG 56 (IQR 35-61,25), p= 0.02. Komorbid DM SG 8 dari 46 pasien (17,4%) dan NSG 17 dari 46 pasien (37%), p = 0,035. Pemeriksaan kadar RNL berdasarkan klasifikasi cut-off > 3,4 NSG 42 dari 46 pasien (91,3%) dan NS 11 dari 46 (23,9%), p= 0,048.  Analisis multivariat regresi logistik didapatkan rasio P/F merupakan faktor risiko independen. Mortalitas pasien COVID-19 dengan pneumonia (OR 0,99 95% CI 0,988-1,00, p = 0,043).  Kesimpulan: Umur di atas 60 tahun, DM, RNL, dan indeks oksigenasi bermakna secara signifikan terhadap kejadian mortalitas pasien COVID-19 dengan pneumonia, dimana pada indeks oksigenasi yang rendah didapatkan kejadian mortalitas yang tinggi.


2013 ◽  
Vol 34 (8) ◽  
pp. 800-808 ◽  
Author(s):  
Marios Karvouniaris ◽  
Demosthenes Makris ◽  
Efstratios Manoulakas ◽  
Paris Zygoulis ◽  
Konstantinos Mantzarlis ◽  
...  

Objective.To investigate prospectively the clinical course and risk factors for ventilator-associated tracheobronchitis (VAT) and the impact of VAT on intensive care unit (ICU) morbidity and mortality.Design.Prospective cohort study.Setting.University Hospital Larissa, Larissa, GreecePatients.Critical care patients who received mechanical ventilation for more than 48 hours were prospectively studied between 2009 and 2011.Methods.The modified Clinical Pulmonary Infection Score, white blood cell count, and C-reactive protein level were systematically assessed every 2 days for the first 2 weeks of ICU stay. Bronchial secretions were assessed daily. Quantitative cultures of endotracheal secretions were performed on the first ICU day for every patient and every 2 days thereafter for the first 2 weeks or more at the discretion of the attending physicians. Definition of VAT was based on previously published criteria.Results.A total of 236 patients were observed; 42 patients (18%) presented with VAT. Gram-negative pathogens, which were usually multidrug resistant, were responsible for 92.9% of cases. Patients with a neurosurgical admission presented with VAT significantly more often than did other ICU patients (28.5% vs 14.1%; P = .02). The occurrence of VAT was a significant risk factor for increased duration of ICU stay (OR [95% CI], 3.04 [1.35-6.85]; P = .01). Age (OR [95% CI], 1.04 [1.015-1.06]; P = .02), Acute Physiology and Chronic Health Evaluation II score (OR [95% CI], 1.08 [1.015-1.16]; P = .02), and C-reactive protein level at admission (OR [95% CI], 1.05 [1.011.1]; P = .02) were independent factors for ICU mortality.Conclusions.VAT is a nosocomial infection that might be associated with prolonged stay in the ICU, especially in neurocritical patients. VAT was not associated with increased mortality in our study.


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