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BackgroundThe presence of antiphospholipid antibodies (aPL) has been observed in patients with COVID-19 (1,2), suggesting that they may be associated with deep vein thrombosis, pulmonary embolism, or stroke in severe cases (3). Antiphospholipid syndrome (APS) is a systemic autoimmune disorder and the most common form of acquired thrombophilia globally. At least one clinical criterion, vascular thrombosis (arterial, venous or microthrombosis) or pregnancy morbidity and at least one laboratory criterion- positive aPL two times at least 12 weeks apart: lupus anticoagulant (LA), anticardiolipin (aCL), anti-β2-glycoprotein 1 (anti-β2GPI) antibody, have to be met for international APS classification criteria(4). Several reports also associate anti-phosphatidylserine/prothrombin antibodies (aPS/PT) with APS.ObjectivesTo combine clinical data on arterial/venous thrombosis and pregnancy complications before and during hospitalisation with aPL laboratory findings at 4 time points (hospital admission, worsening of COVID-19, hospital discharge, and follow-up) in patients with the most severe forms of COVID-19 infection.MethodsPatients with COVID-19 pneumonia were consequetively enrolled, as they were admitted to the General hospital Pancevo. Exclusion criteria were previous diagnosis of inflammatory rheumatic disease and diagnosis of APS. Clinical data were obtained from the medical records. Laboratory results, including LA, aCL, anti-β2GPI, and aPS/PT antibodies were taken at hospital admission, worsening (defined as cytokine storm, connection of the patient to the respirator, use of the anti-IL-6 drug- Tocilizumab), at hospital discharge and at 3-months follow-up and sent to University Medical Centre Ljubljana, Slovenia for analysis. Statistics was performed by using SPSS 21.Results111 patients with COVID-19 pneumonia were recruited;7 patients died during hospitalisation (none were aPL-positive on admission and at the time of worsening), 3 due to pulmonary artery embolism. All patients were treated according to a predefined protocol which included antibiotics, corticosteroids, anticoagulation therapy and specific comorbidity drugs;patients with hypoxia were supported with oxygen. During hospitalisation, pulmonary artery thrombosis occurred in 5 patients, one was aPL-positive at all time points (was diagnosed with APS), others were negative. In addition, 9/101 patients had a history of thrombosis (5 arterial thrombosis (coronary and cerebral arteries), none of whom was aPL-positive on admission and at follow-up, and 4 venous thrombosis, one of which was aPL-positive at all time points and received an APS diagnosis). Among 9/101 patients with a history of thrombosis, 55.6% were transiently positive at the time of discharge, compared to patients without prior thrombosis, in whom 26.1% were transiently positive at the hospital release (p=0.074). Two patients had a history of pregnancy complications (both had miscarriage after 10th week of gestation), but did not have aPL positivity at any time point.ConclusionAlthough aPL was expected to be associated with vascular disease in the most severe forms of COVID-19, all patients that have died in our cohort were aPL negative. At hospital discharge, 56% of patients with a history of arterial or venous thrombosis had positive aPL that became negative at the 3-months follow-up (were transienlty positive), which should be considered when prescribing therapy after hospitalisation.References[1]Trahtemberg U, Rottapel R, Dos Santos CC, et al. Anticardiolipin and other antiphospholipid antibodies in critically ill COVID-19 positive and negative patients. Annals of the Rheumatic Diseases 2021;80:1236-1240.[2]Stelzer M, Henes J, Saur S. The Role of Antiphospholipid Antibodies in COVID-19. Curr Rheumatol Rep. 2021;23(9):72-4.[3]Xie Y, Wang X, Yang P, Zhang S. COVID-19 complicated by acute pulmonary embolism. Radiology: Cardiothoracic Imaging 2020: 2: e200067.[4]Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, et al. J.Thromb.Haemost. 2006;4: 295-306.Acknowledgements:NIL.Disclosure of nterestsNone Declared.
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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
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BackgroundImpaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown, due to unstudied kinetics of the immune response after booster vaccinations.ObjectivesThis study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster.MethodsIn 29 IA patients and 16 healthy controls (HC) humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2.ResultsIA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p=0.026 and p=0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. However, none of the immunomodulatory drugs affected the kinetics of both humoral and cellular responses (measured as the difference between response rates at T1 and T2).ConclusionOur study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Objectives: Varicella is common infectious disease mainly in childhood, usually is a mild, self-limited illness and complications are usually rare. The incubation period for this disease is generally 14- 16 days but may vary from 7 to 21 days. Varicella in the adults with comorbidities or immunosuppressed children may be severe and prolonged with complications. Method(s): A case report of a 6-year-old girl hospitalized for new-onset manifestations of disseminated vesicular exanthema, the manifestations of which occurred mainly on the chest, back, capillitium, oral cavity, and genital area. The child was suffering from abdominal, knee and lumbosacral pain at that time. The patient's history revealed that 10 days prior to the cutaneous manifestations, she had influenza with bronchopneumonia requiring oxygen therapy, steroids and antibiotics. Result(s): The condition progressed within 48 h, complicated by the development of multi-organ failure, coagulopathy with the development of disseminated intravascular coagulopathy over the course of antiviral, antibiotic and antifungal therapy. Laboratory parameters included high elevation of C-reactive protein, il-6, leukocytosis, neutrophilia and highly elevated liver enzymes. Varicella infection was confirmed by detection of herpes zoster virus - polymerase chain reaction (PCR) from vesicles. The patient received intravenous immunoglobulin therapy at a dose of 2 g/L and fresh frozen plasma, thrombocyte concentrate. The girl was intubated with analogization. Laboratory parameters subsequently revealed high anti CoV-2 positivity, high CoV-2 IgG positivity and negative CoV-2 IgM. The patient's condition did not preclude the course of multisystem inflammatory syndrome in children (MIS-C) corticosteroids were added to the treatment at a dose of 1 mg/kg weight. Patient's condition stabilized after 1 month. Discussion(s): Our case report presents an example of fulminant complicated life-threatening course of varicella. Even in common respiratory infections, we must think about the risk and consequences of coinfections and post-infectious complications such as in our case especially influenza and COVID-19.
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Severe pneumonia is a condition with a high risk of death and mandatory hospitalization in the intensive care unit. The incidence of severe pneumonia has increased dramatically during the pandemic of new coronavirus infection. Timely diagnosis and early initiation of adequate treatment of severe pneumonia are crucial for improving survival of critically ill patients. The aim of this review was to analyze published scientific research on molecular markers that allow to objectively assess the severity of pneumonia and to determine treatment tactics based on the predicted outcome upon admission to the hospital. A systematic search was conducted in the electronic databases PubMed, Medline, Web of Science for the period 2019 - 2022. Conclusion. The review focuses on the prognostic role of a number of markers of immune response, vascular transformation, as well as angiotensin II and angiotensin converting enzyme-2. Further prospective studies of potential predictors of severe pneumonia will enable using marker molecules in a comprehensive clinical and laboratory diagnosis for early prediction of the hospitalized patient's condition and expected outcome.Copyright © Volchkova E.V. et al., 2023.
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This study aims to study the clinical-laboratory peculiarities of the coronavirus disease (COVID-19) course in patients with type 2 diabetes mellitus (DM). There were examined 60 patients with the coronavirus disease COVID-19. Patients were divided into two groups: group I - 30 patients with the coronavirus disease (COVID-19) with concomitant type 2 diabetes mellitus;group II - 30 patients with coronavirus disease (COVID-19) without diabetes mellitus;control group - 20 people. There were studied peculiarities of clinical-laboratory changes in patients with coronavirus disease with type 2 diabetes mellitus. General clinical laboratory tests, determination of biochemical parameters, coagulogram, ferritin, CRP, procalcitonin, D-dimer and endothelin-1 were performed. Blood saturation was measured. Out of the instrumental methods, an ultrasound examination of the lungs and RTG of thoracic organs was performed. Patients were admitted on the 5.46+/-0.87 day of the disease. The length of the hospital stay for patients of group I was 19.9+/-1.66 bed days and 14.7+/-0.91 bed days for the patients of group II. A severe course of the disease was observed in 83.3% of patients of group I and 33.3% of group II;a moderate severity course was observed in 16.7% of patients with concomitant DM and 66.7% of patients without concomitant DM. Respiratory failure (RF) of 1 degree was observed in 30% of patients of group 1, RF of the 2 degree - in 16.7% of patients, and RF of the 3 degree - in 10% of patients. In patients without DM, RF of 1 degree - was in 30% of patients, and RF of the 2 degree - was in 13.3% of patients. The laboratory diagnostic methods determined that the levels of leukocytes, D-dimer, endothelin-1, IL-6, procalcitonin, and ferritin were higher in patients with concomitant type 2 DM. In patients with type 2 DM, the course of the coronavirus disease is more severe and longer, with the development of pneumonia and respiratory failure. It is accompanied by leukocytosis, lymphopenia, increased ESR, prothrombin index, IL-6, CRP level, procalcitonin and endothelin-1. Copyright © 2023 The Authors.
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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.
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Objectives: We sought to evaluate 2-year outcome of V-V ECMO support for COVID-19 related severe respiratory failure in our center. Method(s): Retrospective analysis of 41 consecutive patients (73% male, mean age 51.6+/-14.2 years, mean BMI 35.1+/-12.5 kg/m2) with critical hypoxemic and/or hypercapnic refractory respiratory failure (mean P/F ratio 67.9+/-14.3 mmHg, mean pCO2 77.6.0+/-185.7 mmHg, Murray Score 3.71+/-0.4) on V-V ECMO support from October 2020 to January 2022 Results: With mean support duration of 234.4+/-63.2 hours, 29 patients (70.7%) were successfully weaned off. Finally, 19 of them (46.3%) were discharged home with good neurological outcome (CPC 1,2). During followup, 30-day, 6-, 12-, and 24 -month survival rate was 61.3%, 46.2%, 41.9%, and 41,9% respectively. In survivor group shorter symptoms onset to respiratory failure time (4+/-4.7 vs. 7+/-6.7 days, p=0.04), higher P/F ration (86+/-41.5 vs. 65+/-37.5 mmHg, p=0.04) and norepinephrine support (0.03+/-0.06 vs. 0.09+/-0.12 ug/kg/min, p=0.04), and lower IL-6 level (12.3+/-7.5 vs. 25.9+/-8.8 ng/l, p=0.03) p=0.01) were analysed before cannulation. Mean in-ICU stay and in-hospital stay in survivors;groups reached 32.5+/-27.7 days and 42.6+/-35.8 days, respectively. All long-term survivors (17 patients) complained about slight functional health limitation only with normal 6MWT (542.6+/- 89.2 min), near to normal spirometry parameters (FEV/VC 87+/-7.4%, DLCO 63.1+/-13.7%, KCO 82.,1+/-19.4%) and minimal neurological disability (CPC 1-2) Conclusion(s): 2-year outcome of V-V ECMO support in COVID-19 severe respiratory failure is acceptable even in the scope of low-volume ECMO centre. Reported functional status of long-term survivors was good despite the complicated and prolonged in-hospital stay. (Table Presented).
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Introduction: Spontaneous pneumothorax is a rare complication of coronavirus disease 2019 (COVID-19), primarily reported in adults. Pediatric cases with bilateral pneumothorax are much less reported. Case Presentation: We presented the case of a five-year-old previously healthy boy who developed persistent fever, abdominal pain, generalized maculopapular rash, and dyspnea before admission. His chest computed tomography (CT) showed a viral involvement pattern of pneumonia suggestive of COVID-19. Subsequently, he was confirmed with multisystem inflammatory syndrome in children (MIS-C). While he responded well to the therapies, on the fifth day of admission, he developed respiratory distress again. A chest roentgenogram showed bilateral spontaneous pneumothorax. Bilateral chest tubes were inserted, and his condition improved sig-nificantly after five days of admission to the intensive care unit. Two weeks later, he was discharged in good condition. Conclusion(s): Children with MIS-C associated with COVID-19 may develop primary spontaneous pneumothorax. Owing to the clinical picture overlapping with MIS-C associated with COVID-19, the timely diagnosis of pneumothorax may be challenging in such patients.Copyright © 2022, Author(s).
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Background: Serum interleukin 6 (IL-6) levels have been studied in the diagnostic evaluation of patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19). Methods: We studied the utility of treatment with tocilizumab in COVID-19 patients (n=19) with a negative nasopharyngeal swab real time reverse transcriptase polymerase chain reaction (RT-PCR) test for SARS-CoV-2 who had suggestive computed tomography (CT) findings, namely, COVID-19 Reporting and Data System (CO-RADS) 4,5. Results: Receiver operator characteristic (ROC) curve analysis showed that serum IL 6 at a cut-off of >56.9 pg/L was a predictor of mortality in nasopharyngeal swab RT-PCR negative patients with suggestive CT findings. Tocilizumab had no significant effect on the mortality. Conclusions: In nasopharyngeal swab RT-PCR negative patients with suggestive chest CT findings, elevated serum IL-6 levels > 56.9 pg/L predicted mortality. However, treatment with tocilizumab had no effect on mortality.
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Background: Several pro- and anti-inflammatory cytokines involved in COVID-19 and it is reasonable to speculate that their removal from blood might limit organ damage. Hemoperfusion with CytoSorb is a technique developed to adsorb molecules in the middle molecular weight range (up to 55 kDa). Studies in vitro and in vivo have shown that HP is highly effective in clearing blood from a number of cytokines. Method(s): We report a case series of 9 consecutive COVID-patients admitted to our COVID Intensive Care Unit (ICU). Five of them were treated with HP using CytoSorb (T), due to the heavy emergency overload it was impossible to deliver blood purification in the other 4 patients (C), who were also considered as potential candidates by the attending medical team. All patients had pneumonia and respiratory failure requiring continuous positive airway pressure. Different antibacterial prophylaxes, antiviral, and anti-inflammatory therapies including steroids were delivered. Result(s): Our results show a better clinical course of T compared to control patients (C), in fact all T except 1 survived, and only 2 of them were intubated, while all C required intubation and died. CRP decreased in both groups, but to a greater extent after HP. Lymphocytopenia worsened in control patient but not in treated patient after HP. Procalcitonin increased in 2 of the not treated patients. In all survived patients (n = 4) HP reduced pro-inflammatory cytokines, as IL-6, TNF-alpha, and IL-8. Notably, a striking effect was observed on IL-6 levels that at the end of the second session were decreased by a 40% than before the first treatment. Serum levels of IL-8 and TNF-alpha were lowered within normal range. In all patients the treatment was safe and there were no complications. Conclusion(s): Our study suggests a potential efficacy of HP in an early phase of viral infection not only for improving survival in the treated patients but also by the remodeling treatment-associated cytokine levels.
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Background: Tocilizumab, an interleukin-6 (IL-6) antagonist, is being evaluated for the management of covid-19 pneumonia. The objective of this study was to assess the effectiveness of Tocilizumab in severe covid-19 pneumonia. Method(s): This was a retrospective, observational, single centre study performed in 121 patients diagnosed with severe covid-19 pneumonia. 83 patients received standard of care treatment whereas 38 patients received tocilizumab along with standard of care. Tocilizumab was administered intravenously at 8mg/kg (upto a maximum of 800mg). The second dose of Tocilizumab was given 12 to 24 hours apart. The primary outcome measure was ICU related and hospital related mortality. The secondary outcome measures were change in clinical status of patients measured by WHO (World Health Organisation) 7 category ordinary scale, changes in interleukin-6 (IL-6) levels, secondary infections and duration of ICU stay. Result(s): Tocilizumab was administered between 3-27 days after the patient reported symptoms ( a median of 10.9 days ) and between the 1st to 3rd day of ICU admission (median of 2.1 days) . In Tocilizumab group, 16(42.1%) of 38 patients died in ICU whereas in standard of care group, 27(32.53%) of 83 patients died. The difference in clinical status assessed using WHO (World Health Organisation) 7 category ordinary scale at 28 days between Tocilizumab group and standard of care group was not statistically significant (odds ratio 1.35, 95% confidence interval 0.61 to 2.97, p = 0.44). Conclusion(s): Tocilizumab plus standard care was not superior to standard care alone in reducing mortality and improving clinical outcomes at day 28.Copyright © RJPT All right reserved.
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Background: COVID-19 infection can cause an exaggerated immune response. This immune response is associated with an increase in proinflammatory cytokines, especially interleukin-6 (IL-6). High IL-6 levels are found in the acute stage of COVID-19, and IL-6 can induce an excessive humoral inflammatory response. This study aimed to provide an overview of IL-6 levels in coronavirus disease 2019 (COVID-19) patients at Dr. M. Djamil General Hospital, Padang, Indonesia. Methods: Descriptive observational study of 102 research subjects. Observations on sociodemographic, clinical, and laboratory data were carried out in this study. Univariate analysis was carried out using SPSS version 25. Results: Patients with symptom onset <7 days had higher IL-6 levels than those with an onset of more than 7 days. Patients with critical degrees have the highest IL-6 levels compared to moderate and severe degrees. Patients with more than 1 comorbid had higher IL-6 levels than patients who had no comorbid or only had 1 comorbid. Patients with <21 days of treatment had higher IL-6 levels than patients with more than 21 days of treatment. Conclusion: COVID-19 patients at Dr. M. Djamil General Hospital, Padang, Indonesia, with an onset of less than 7 days, a critical degree, and more than 1 comorbidity have higher IL-6 levels.
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BACKGROUND: According to the results of the ESSE-RF study, the frequency of obesity in the population reached 29.7%. Obesity is one of the main risk factors for the development of cardiovascular diseases. Features of the course of COVID-19 in patients with obesity is a very urgent problem. AIM: The aim of the study was a comparative investigation of clinical and laboratory-instrumental parameters in AH patients with or without obesity who had COVID-19 associated pneumonia, to identify the role of obesity as a potential predictor of post-COVID cardiovascular complications 3 months after discharge from the hospital. MATERIALS AND METHODS: Materials and methods. The study included 174 patients with COVID-19-associated pneumonia. Group 1 included 78 patients with AH without obesity, group 2 - 96 patients with AH and obesity. All patients were tested with a blood sample at the time of admission and 3 months after discharge from the hospital. We assessed parameters of general blood test, biochemistry, hemostasis, inflammation biomarkers - concentration of C-reactive protein (CRP), highly sensitive CRP (hs-CRP), homocysteine, IL-6, etc. All patients initially underwent computed tomography of the chest. In both groups, 24-hour blood pressure monitoring was performed using BPLaB device, according to the standard protocol;echocardiography using an expert class ultrasound diagnostic system Vivid S70. The study is registered with the Clinical Trials.gov database Identifier: NCT04501822. RESULT(S): Results. The biomarker that significantly distinguished the both groups of patients, as well as subgroups according to the degree of obesity was the concentration of maxCRP and hs-CRP, which was significantly higher in group 2. In addition, the registered maximum values of MPO, NT-proBNP, IL-1,6, TNA-alpha and NRL parameters in group 2 of patients with 2-3 degrees of obesity, may indicate the highest probability of developing delayed adverse cardiovascular complications in this group of patients. Mean systolic blood pressure, variability of systolic and diastolic blood pressure, and heart rate at night were significantly higher in AH patients with obesity. Numerous correlations of obesity with laboratory and instrumental parameters have been registered, which may indicate an increased likelihood of delayed unwanted cardiovascular complications in this particular group of patients. Multiple regression showed that obesity is an independent predictor of an increase in LDH, hs-CRP and right atrium. CONCLUSION(S): Dynamic control of the studied parameters in patients with AH and OB registered an increased concentration of CRP at the initial stage and 3 months after treatment, with a general trend towards a decrease in the increased initial structural parameters of ECHO CG. The logistic regression method showed that the presence of OB in patients with AH is an independent factor causing increased levels of immune inflammation (CRP), a marker of tissue destruction (LDH), and load on the right atrium.Copyright © Endocrinology Research Centre, 2022.
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Is there an increased incidence of bacteraemia among COVID-19 patients requiring critical care admission who have received IL-6 inhibitors? Introduction: Interleukin-6 (IL-6) inhibitors have been shown to reduce mortality in hospitalised COVID-19 patients. There is, however, concern that induced immunosuppression may increase the risk of secondary nosocomial infection. Objective(s): Our primary aim was to determine if there was increased incidence of bacteraemia in COVID-19 patients requiring critical care admission who had received IL-6 inhibitors compared to those who had not. Method(s): A retrospective review of all COVID-19 admissions to two critical care units in Liverpool from 4th March 2020 to 31st October 2021. Patients were divided into those who received an IL-6 inhibitor (sarilumab or tociluzimab) and those who did not. Hospital antimicrobial policy was to administer a five day prophylactic course of co-amoxiclav and clarithromycin for patients with severe COVID-19 during the study period. Blood culture results from 14 days before admission to critical care and 90 days after admission were included. The blood culture results comprised cultures taken in both critical care and on the wards. Data were linked and analysed using Stata V15.1 (StataCorp, Stata Statistical Software: Release 15, College Station, Texas, USA). Result(s): 894 patients were included in the study. 134 patients had at least one positive blood culture result. The most commonly identified pathogens were Coliforms (23/134, 17.2%), Enterobacter (22/134, 16.4%) and Escherichia coli (16/134, 11.9%). Of patients administered an IL-6 antagonist, 16.8% (114/565) developed a positive blood culture compared to 11.6% (20/172) who did not, p=0.096. We did not observe an increased frequency of antimicrobial resistant culture in the IL-6 administered group 22.8% (26/114) vs. 20.0% (4/20) in this cohort, p=0.781. Data have not been adjusted for demographic and clinical factors in this preliminary analysis. Conclusion(s): We observed a trend toward increased frequency of blood culture positivity in patients administered an IL-6 antagonist within this COVID-19 positive cohort but this was not statistically significant. Further analysis is required to adjust for relevant demographic and clinical factors.
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Neutrophilic granulocytes (NG) are the main drivers of pathological inflammation in COVID-19. Objective. To specify the mechanisms of immunopathogenesis of COVID-19 based on a comparative immunological study of the number and phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets with an assessment of their effector functions against changing profile of NG-associated cytokines IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma. Patients and methods. In patients with moderate-to-severe and severe COVID-19, we determined IL-1beta, TNFalpha, IL-6, IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma (ELISA), the phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets, NF-kappaB-NG (CYTOMICS FC500), phagocytically active NG (%), neutrophil extracellular traps (NETs), NG in apoptosis, and the activity of NADPH oxidase. Results. In COVID-19 against the background of IFNalpha and IFNgamma production blockade and high levels of NG-associated IL-8, IL-18, IL-17A, VEGF-A, a reduction in the number of mature and functionally active CD16brightSD62LbrightCD11bbrightCD63-NG subsets was revealed, as well as an increase in the number of CD16dimSD62LdimSD11bbrightCD63-NG subsets with an immunosuppressive phenotype and CD16brightSD62LbrightSD11bbrightCD63bright-NG subsets with high cytotoxic activity and ability to form NETs, a decrease in the percentage of phagocytically active NG and an increase in the activity of NADPH oxidase, NETs, and NG in apoptosis. Conclusion. IFNalpha deficiency provokes a hyperergic response of NG-associated cytokines, which leads to the formation of uncontrolled immune inflammation involving NG subsets with an immunosuppressive and cytotoxic phenotype, exacerbating the course of COVID-19. The use of recombinant IFNalpha-2b with antioxidants (Viferon) in the early stages of the disease can help to restore immune homeostasis, normalize the level of NG-associated cytokines, reduce NERTs, and achieve good clinical efficacy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
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Objective. To evaluate some parameters of the psychosomatic state, cytokine levels (IL-6, IL-8, IL-17A), and free radical status (levels of nitrates and nitrites, antioxidant plasma activity) in convalescent patients after severe COVID-19. Patients and methods. We examined 64 patients who had severe COVID-19 and underwent either a 30-35-day course of inpatient rehabilitation after their discharge from a hospital for infectious diseases or a 60-65-day course of outpatient rehabilitation at the Ambulatory Center of Nalchik, Clinical Hospital No 1. Results. We surveyed patients after severe COVID-19 and found that they required a long rehabilitation. Many of them reported asthenic syndrome, psycho-emotional disorders, and other complaints upon discharge from the hospital. Serum levels of proinflammatory cytokines remained high in patients after severe COVID-19 even 30-35 days following their discharge (p < 0.05). Serum levels of IL-6, IL-8, nitrites, and nitrates remained elevated on days 60-65 following discharge (p < 0.05), despite comprehensive therapy in a rehabilitation department. Plasma antioxidant activity was reduced, whereas IL-17A level normalized by this time. Conclusion. Our findings suggest that currently used rehabilitation measures for COVID-19 are insufficient. Adequate rehabilitation of convalescent COVID-19 patients requires proper monitoring of their immune system condition, as well as new effective methods for immune correction and restoration of their psychoemotional status after the acute phase of the disease.Copyright © 2022, Dynasty Publishing House. All rights reserved.
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Objective To investigate the clinical features of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection and abnormal liver function in Guangdong Province, China. Methods The patients with SARS-CoV-2 Delta variant infection who belonged to the same chain of transmission in Guangdong Province (Guangzhou and Foshan) and were admitted to Guangzhou Eighth People's Hospital, Guangzhou Medical University from May 21 to June 18, 2021 were enrolled in this study, and the judgment criteria for liver function were alanine aminotransferase (male/female) > 50/40 U/L, aspartate aminotransferase > 40 U/L, total bilirubin > 26 mumol/L, gamma-glutamyl transpeptidase > 60 U/L, and alkaline phosphatase (ALK) > 125 U/L. Abnormality in any one item of the above criteria was defined as abnormal liver function, and such patients were included in analysis (the patients, aged < 18 years, who had a mild or moderate increase in ALP alone were not included in analysis). Clinical data were compared between the patients with normal liver function and those with abnormal liver function, and the etiology and prognosis of abnormal liver function were analyzed. The Mann-Whitney U test was used for comparison of continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups. Results Among the 166 patients with SARS-CoV-2 Delta variant infection, 32 (19.3%) had abnormal liver function with mild-to-moderate increases in liver function parameters, and compared with the normal liver function group, the abnormal liver function group had a significantly higher proportion of critical patients (chi2=38.689, P < 0.001) and significantly higher age and inflammatory cytokines [C-reactive protein type, serum amyloid A, and interleukin-6 (IL-6)](all P < 0.05). Among the 32 patients with abnormal liver function, 13 patients had abnormal liver function on admission (defined as primary group), while 19 patients had normal liver function on admission but were found to have abnormal liver function by reexamination after treatment (defined as secondary group). For the primary group, the evidence of abnormal liver function was not found for 3 patients (3/13, 23.1%), and the possibility of toxic liver injury directly associated with SARS-CoV-2 infection was considered. Among the 19 patients in the secondary group, 9 (47.4%) had mild/common type and 10 (52.6%) had critical type, and all critical patients had the evidence of liver injury indirectly caused by the significant increases in C-reactive protein type, serum amyloid A, and IL-6 and hypoxemia;the evidence of abnormal liver function was not found for only 1 patient (1/19, 5.3%), and the possibility of toxic liver injury directly associated with SARS-CoV-2 infection was considered. All 32 patients with abnormal liver function had [JP2]significant reductions in liver function parameters after treatment including liver protection. Conclusion As for the patients with SARS-CoV-2 Delta variant infection who belong to the same chain of transmission in Guangdong Province, the critical patients show a significantly higher proportion of patients with abnormal liver function than the patients with other clinical types, and other factors except SARS-CoV-2 infection and indirect injury caused by SARS-CoV-2 infection are the main cause of liver injury.Copyright © 2022 Editorial Board of Jilin University. All rights reserved.
ABSTRACT
Background: Only recently studies have been able to demonstrate the safety and efficacy of purification therapies in inflammatory diseases. Here we present the management of a young (21y) male patient in severe cardiogenic shock due to COVID-19 perymyocarditis admitted to the ICU at Bolzano Central Hospital. November 30th 2020 the patient developed high fever (>40 C) and diarrhea. After unsuccessfully being treated orally with a macrolide he was admitted to a peripheral hospital the 4th of December. The day after he deteriorated, required transfer to the ICU, endotracheal intubation and pharmacological cardiovascular support (Norepinephrine, Levosimendan). Antimicrobial treatment was started with piperacillin/tazobactam, linezolid and metronidazole. Despite multiple radiological and microbiological diagnostic attempts the origin of this severe septic shock remained unclear. December 6th the patient was transferred to Bolzano Central Hospital for VA-ECMO evaluation. Method(s): The transesophageal echocardiography revealed 15-20% of EF, lactate (5,2 mmol/l), cardiac enzymes (TropT 1400 mcg/l) and inflammatory parameters (PCT 35 ng/ml, IL-6 685 pg/ml) were elevated. We performed cardiac monitoring via Swan-Ganz catheter. The cardiac index was 1,6 l/min/m2. The peak dosage for Norepinephrine reached 7,5mg/h (1,47 mcg/kg/min). At Bolzano ICU we facilitate the pharmacological therapy with milrinone, vasopressin and low dose epinephrine. Furthermore, we impost continuous hemodiafiltration with CytoSorb filter. Result(s): Only hours after the start of filtration therapy the patient improved and we were able to gradually reduce catecholamine therapy, lactate values decreased. A VA-ECMO implantation was no more necessary. December 10th, we saw a stable patient without ventilatory or cardiovascular support, at echocardiography we revealed a normal EF. Conclusion(s): Clinically we saw a young patient in severe septic/cardiogenic shock due to perimyocarditis. Yet diagnostic attempts (CT-scan, multiple blood/urinary/liquor cultures) remained negative. Despite multiple negative PCR tests for SARS-CoV2 infection we performed specific immunoglobulin analysis and received a positive result for IgM. We therefore conclude on a COVID-19 associated perymyocarditis. Furthermore, this case illustrates the potential benefit of cytokine filtration and elimination in COVID-19 patients with altered IL6 levels.