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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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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.
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Patients with cardiovascular disease represent a particularly vulnerable population in a pandemic of the coronavirus infection COVID-19. They are more at risk of infection, a severe course of the disease, as well as a higher mortality rate compared to a healthy population. Currently, there are no randomized clinical trials to determine the most effective approaches to treatment in this category of patients. The presented clinical example demonstrates the possibilities of using various groups of drugs recommended for the treatment of COVID-19, and the high efficiency of treatment with an interleukin-6 receptor inhibitor (IL-6) in a patient with severe new coronavirus infection and the presence of concomitant cardiovascular pathology. © 2020, Media Sphera Publishing Group. All rights reserved.
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Introduction: Relevant clinical studies indicate a significantly poorer outcome in patients with advanced renal failure during Covid 19 probably due to significantly slower clearance of proinflammatory cytokines produced during infection but also in the presence of significantly higher cardiovascular comorbidity in these patients. Method(s): We present the characteristics of patients with chronic renal failure (CRF) who were treated for Covid 19 bronchopneumonia at the Temporary Covid 19 hospital "Stark Arena" Belgrade,during 2020/2021. In this period we have treated about 5200 patients with Covid 19 bronchopneumonia under limited conditions. Result(s): We analyzed a records of 466 patients with a history of CRF: 261 male (56.01%) and 67 female 67(43.99%), mean age 75 +/- 11.14 years (40-88 years), 297 of them (63.73%) suffered from high blood pressure, 154 patients (33,05%) suffered from diabetes mellitus and 114 patients (24,46%) had both diseases.The mean value of sO2 at admission was 92+/-4,45%, CRP 87+/-99.7mg/l, Interleukin-6 61+/-33.4 pg/ml, hemoglobin (Hgb)126+/-14.22g/l, urea 12+/-7,53 mmol /l, creatinine 137.43+/-121.22micromol/l, glomerul filtration rate (GFR) 47.44ml/min/1.73m2. Patients were treated according to the current protocol where 305 out of than (65,45%) also received an interleukin-6 receptor blocker (Tocilizumab 8-16 mg/kg). A total of 452 patients (96.99%) after successful treatment of bronchopneumonia were discharged for home treatment with average creatinine values of 116+/-31.32micromol/l and GFR 56.13ml/min/1.73m2,while 14 patients (3,01%) due to the worsening of their general condition, were transferred to a higher - level health institution, from where they were further discharged without necessity for chronic dialysis treatment. There were no lethal outcomes. Parameters on admission: [Formula presented] Parameters at discharge: [Formula presented] Conclusion(s): Advanced renal failure is a significant risk factor for adverse clinical outcome during Covid 19. In our group majority of patients were with moderate CRF who had a successful end-therapeutic outcome, but a significant percentage of them required the use of Tocilizumab (without adverse effects). The verified improvement of GFR at discharge is most likely a consequence of the remediation of factors (inflammation, dehydration, nephrotoxicity of drugs etc.) which led to worsening of preexistent CRF. Regardless of the existing degree, all patients with renal failure require serious monitoring during Covid 19. No conflict of interestCopyright © 2023
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The COVID-19 mortality is associated with an increase in interleukin-6 (IL-6) levels. Levilimab is an anti-IL-6 receptor antibody with proven clinical efficacy in patients with severe COVID-19. The aim of the study was to assess the association of COVID-19 severity and levilimab effectiveness with IL-6 levels and to explore the potential for using levilimab in other conditions accompanied by cytokine release syndrome. Material(s) and Method(s): the subgroup analysis was based on the data of COVID patients with known baseline IL-6 levels from the CORONA clinical study. Subgroups were formed according to baseline IL-6 levels: <=5 pg/mL (normal) and >5 pg/mL (elevated). The subgroup analysis included descriptive statistics of the patients and time courses of their clinical and laboratory findings (at screening, on the day of investigational product administration, and further until day 14). In order to compare the percentages of patients who had required rescue therapy, the authors used Fisher's exact test. Result(s): the subgroup analysis included 91 patients (47 from the levilimab group and 44 from the placebo group). At baseline, the authors observed elevated levels of IL-6 in 31/47 (66%) subjects in the levilimab group and 29/44 (48.4%) subjects in the placebo group. The subjects with elevated IL-6 demonstrated more pronounced clinical signs of pneumonia and abnormalities in inflammatory markers. Elevated baseline IL-6 levels were associated with the need for rescue therapy (OR=3.714;95% CI: 1.317-9.747;p=0.0183);this association was stronger in the placebo group (OR=8.889;95% CI: 2.098-33.31;p=0.0036). Also, the placebo group showed long-term abnormalities in the clinical and laboratory findings. Conclusion(s): IL-6 is one of the key elements in the pathogenesis of cytokine release syndrome related to COVID-19 and other conditions. Elevated IL-6 levels are associated with the severity of COVID-19. Inhibition of IL-6 receptors by levilimab leads to clinical improvement in patients with severe COVID-19, suggesting the effectiveness of levilimab in pathogenesis-oriented therapy for cytokine release syndrome of other aetiologies.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.
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Objective: to confirm the efficacy and safety of levilimab in patients with rheumatoid arthritis (RA) switched from other interleukin 6 receptor in-hibitors (iIL6R) for non-medical reasons. Patients and methods. A retrospective analysis of data from the register of patients with RA who during the COVID-19 pandemic were switched from foreign iIL6Rs to the Russian drug levilimab. Treatment regimens with levilimab in combination with synthetic disease-modifying antirheumatic drugs (sDMARDs) and/or glucocorticoids (GCs) were used, as well as a monotherapy regimen in case of DMARDs intolerance. Results and discussion. In 150 patients with RA, a successful non-medical switch to levilimab was demonstrated with the preservation and inten-sification of the clinical effect achieved on previous therapy with iIL6R. After switching to levilimab, the DAS28-CRP index decreased by an av-erage of 0.098 at 3 months and by 0.25 at 6 months (p=0.214 for both time points). There was a decrease in the proportion of patients with elevated levels of CRP, as well as with high RA activity. In a number of patients who showed high efficacy of levilimab, it became possible to reduce the dose or number of DMARDs, as well as cease GCs intake. Good tolerability and a favorable safety profile of levilimab were noted, including in relation to the new coronavirus infection that developed during therapy. Conclusion. Therapy with Russian iIL6R levilimab is effective and safe, including in patients switched from other drugs for non-medical reasons, as well as in relation to the novel coronavirus infection that developed during therapy. © 2022, Ima-Press Publishing House. All rights reserved.
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BACKGROUND: Tocilizumab is an interleukin-6 receptor antagonist hypothesized to blunt the uncontrolled immune response, cytokine release syndrome, in severe COVID-19 and prevent attributable morbidity and mortality. Objective: The objective of this study was to assess the impact of tocilizumab on clinical outcomes in COVID-19-associated cytokine release syndrome. METHODS: Single-center, retrospective cohort study assessing sixty-nine adult patients receiving tocilizumab for suspected COVID-19 cytokine release syndrome. The primary outcome was change in WHO clinical status scale on day seven post-dose analyzed using the Wilcoxon signed rank test. Secondary outcomes assessed impact of timing of administration on clinical outcome. Safety analyses included development of neutropenia, thrombocytopenia, transaminitis, and sepsis within 7 days post-dose. Statistical analyses were conducted using Microsoft Excel. RESULTS: No aggregate clinical change was found between day 0 and day 7. Eleven patients improved, twenty-seven worsened, and thirty-one showed no change. Clinical outcomes were weakly correlated with time from symptom onset (rs = 0.21; p = 0.08) or hospital admission (rs = -0.08; p = 0.49) to dose. In-hospital mortality was 63%. Sepsis was diagnosed in 21 patients, five of which were post-dose. Transaminitis, neutropenia, and thrombocytopenia occurred in seven, one, and six patients, respectively. CONCLUSION: Tocilizumab did not appear to influence clinical outcomes in our study population, irrespective of timing of administration. Adverse events were not considered drug-related.
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Background: Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19. Methods: In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76). Findings: Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81-94] in arm A vs 85% [74-93], HR 1.07 [0.8-1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77-96] vs 79% [63-91], HR 1.55 [0.9-2.6]; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7]; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths. Interpretation: The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results. Funding: This study was supported by INMI "Lazzaro Spallanzani" Ricerca Corrente Linea 1 on emerging and reemerging infections, funded by Italian Ministry of Health.
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The COVID-19 mortality is associated with an increase in interleukin-6 (IL-6) levels. Levilimab is an anti–IL-6 receptor antibody with proven clinical efficacy in patients with severe COVID-19. The aim of the study was to assess the association of COVID-19 severity and levilimab effectiveness with IL-6 levels and to explore the potential for using levilimab in other conditions accompanied by cytokine release syndrome. Materials and methods: the subgroup analysis was based on the data of COVID patients with known baseline IL-6 levels from the CORONA clinical study. Subgroups were formed according to baseline IL-6 levels: ≤5 pg/mL (normal) and >5 pg/mL (elevated). The subgroup analysis included descriptive statistics of the patients and time courses of their clinical and laboratory findings (at screening, on the day of investigational product administration, and further until day 14). In order to compare the percentages of patients who had required rescue therapy, the authors used Fisher's exact test. Results: the subgroup analysis included 91 patients (47 from the levilimab group and 44 from the placebo group). At baseline, the authors observed elevated levels of IL-6 in 31/47 (66%) subjects in the levilimab group and 29/44 (48.4%) subjects in the placebo group. The subjects with elevated IL-6 demonstrated more pronounced clinical signs of pneumonia and abnormalities in inflammatory markers. Elevated baseline IL-6 levels were associated with the need for rescue therapy (OR=3.714;95% CI: 1.317–9.747;p=0.0183);this association was stronger in the placebo group (OR=8.889;95% CI: 2.098–33.31;p=0.0036). Also, the placebo group showed long-term abnormalities in the clinical and laboratory findings. Conclusions: IL-6 is one of the key elements in the pathogenesis of cytokine release syndrome related to COVID-19 and other conditions. Elevated IL-6 levels are associated with the severity of COVID-19. Inhibition of IL-6 receptors by levilimab leads to clinical improvement in patients with severe COVID-19, suggesting the effectiveness of levilimab in pathogenesis-oriented therapy for cytokine release syndrome of other aetiologies.
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Despite the measures taken and the molecular advances for the development of new agents for the control of SARS-CoV-2 infection, there is still insufficient development of an effective treatment. The objective of the review was to de-scribe the clinical studies and reported articles on drugs used as possible therapeutic agents for COVID-19 and the main conclusions on their reuse. A non-systematic review through PubMed, ScienceDirect, and clinical trials at ClinicalTrials. gov on original articles and case report in English and Span-ish that will report information on COVID-19 treatment and its main conclusions. Articles that were not relevant or that did not mention updated information to that reported in other articles were excluded. A total of 99 bibliographic references were included. COVID-19 appears as a multisystemic disease with variable clinical symptoms. Since no specific treatment is yet known, multiple drugs have been proposed that attack the different pathways of SARS-CoV-2. For severe disease in patients who require hospitalization and oxygen support, the use of remdesivir, dexamethasone, or tocilizumab is recommended if there are patient conditions that apply to use them. The use of ivermectin, colchicine, lopinavir/ritonavir, hydroxy-chloroquine, and chloroquine have not reported benefits that surpass adverse effects.
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We aimed to assess the factors associated with mortality in patients treated with tocilizumab for a SARS-CoV-2 pneumonia due to the delta or omicron variants of concern (VOC) and detect an effect of tocilizumab on mortality. We conducted a prospective cohort study in a tertiary hospital from 1 August 2021 to 31 March 2022 including patients with severe COVID-19, treated with tocilizumab. Factors associated with mortality were assessed in a Cox model; then, the 60-day mortality rates of COVID-19 patients treated with standard of care (SoC) +/- tocilizumab were compared after 1:1 propensity score matching. The mortality rate was 22% (N = 26/118) and was similar between delta and omicron cases (p = 0.6). The factors independently associated with mortality were age (HR 1.06; 95% CI (1.02-1.11), p = 0.002), Charlson index (HR 1.33; 95% CI (1.11-1.6), p = 0.002), WHO-CPS (HR 2.56; 95% CI (1.07-6.22) p = 0.03), and tocilizumab infusion within the first 48 h following hospital admission (HR 0.37, 95% CI (0.14-0.97), p = 0.04). No significant differences in mortality between the tocilizumab plus SoC and SoC alone groups (p = 0.5) were highlighted. However, the patients treated with tocilizumab within the 48 h following hospital admission had better survival (p = 0.04). In conclusion, our results suggested a protective effect on mortality of the early administration of tocilizumab in patients with severe COVID-19 regardless of the VOC involved.
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The Advisory Board chaired by the chief specialist in infectious diseases of the Ministry of Health of Russian Federation, Professor V.P. Chulanov was held on June 18, 2022 in Saint Petersburg. Aim. The main purpose of the Board was following discussion: the analysis of the real-world data of levilimab as an anticipatory therapy for COVID-19 in hospitalized patients; the review of the experience and perspectives of levilimab as an anticipatory anti-inflammatory option for outpatient patients who meet defined clinical and laboratory criteria. Results. The analyzed data on clinical efficacy and safety formed the basis of recommendations proposed by experts for the use of levilimab in the inpatient and outpatient medical care for COVID-19.
Subject(s)
COVID-19 Drug Treatment , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Anti-Inflammatory Agents , Receptors, Interleukin-6ABSTRACT
Tocilizumab (Actemra®), as the first human interleukin-6 receptor (IL-6R) antagonist, has been used in treating moderate to severe active rheumatoid arthritis (RA) patients who were undertreatment with one or more disease-modifying anti-rheumatic drugs (DMARDs) and did not improve significantly. Tocilizumab also has been administrated and confirmed in several inflammatory-based diseases. Recently, tocilizumab has been prescribed to treat patients with advanced coronavirus disease (COVID-19) and is used as one of the effective drugs in reducing the increased inflammation in these patients. On the other hand, cancer treatment has been considered by researchers one of the most important challenges to human health. Regarding inflammatory-associated malignancies, it has been shown that inflammatory mediators such as interleukin-1 beta (IL-1ß), IL-6, and tumour necrosis factor-alpha (TNF-α) may play a role in tumorigenesis, thus targeting these cytokines as evidence suggested can be useful in the treatment of these types of cancers. This review summarized the role of the IL-6/IL-6R axis in inflammation-based cancers and discussed the effectiveness and challenges of treating cancer with tocilizumab.
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How to cite this article: Garg SK. Anti-cytokine Therapy in Hospitalized Patients with COVID-19: The Jury is Out. Indian J Crit Care Med 2022;26(10):1069-1071.
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SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Biological disease modifying anti-rheumatic drugs (bDMARDs) are commonly used to treat interstitial lung disease (ILD) in patients with connective tissue disease (CTD). These patients often develop concurrent COVID-19 disease and existing data is scarce to guide treatment. We describe a case with a rare anti-Pl-7 Anti-Synthetase Syndrome (ASS) receiving Rituximab treatment for ILD who developed acute respiratory distress syndrome (ARDS) secondary to COVID-19 disease. CASE PRESENTATION: A 58-year-old female presented with worsening shortness of breath, loss of taste and smell, cough and headaches for 1 week. She had pre-existing severe chronic ILD secondary to ASS on Rituximab therapy. She tested positive on SARS-CoV-2 PCR testing, CT chest showed bilateral lung honeycombing, reticulations, traction bronchiectasis along with ground glass opacities consistent with active inflammatory interstitial process superimposed on ILD. She was diagnosed with COVID-19 pneumonia. She was initially started on high-dose Dexamethasone, Remdesivir and supplemental oxygen via high flow nasal cannula and supportive care for ARDS, however level of care was escalated due to worsening respiratory distress. Rituximab was discontinued due to active COVID-19 infection, the decision was made to start Baricitinib at 4 mg daily. She received treatment for 14 days, that led to a significant improvement in her respiratory status. DISCUSSION: ASS is a rare autoimmune condition involving multiple organs, with ILD being the major cause of morbidity. bDMARDS, especially Rituximab, have shown promising results in management of severe and refractory ILD in ASS. However, the role of bDMARDs as protective or risk factor for developing severe COVID-19 disease in these patients is unclear. ARDS in COVID-19 disease involves a vigorous inflammatory response and cytokine production leading to diffuse alveolar damage. Literature supports that use of corticosteroids, IL-1 and IL-6 receptor blockers and Janus Kinase (JAK) inhibitors for severe COVID-19 pneumonia is associated with decreased morbidity. Baricitinib is a JAK1 and JAK2 with anti-cytokine and anti-viral properties and has been associated with reduction in morbidity and mortality in patients with COVID-19 as demonstrated in our case. Generally, use of bDMARDs does not contribute to worse outcomes in COVID-19 disease in patients receiving these agents for rheumatological conditions. However, use of Rituximab and high dose glucocorticoids have been associated with worse outcomes, while Baricitinib may have a protective effect. Therefore, holding Rituximab in those with active COVID-19 infection is recommended. CONCLUSIONS: Management of COVID-19 in patients with CTD is a challenge due to the novel nature of the disease and scarcity of available data. The association of use of bDMARDs in rheumatological disease with outcomes in SARS-CoV-2 infection is yet to be elucidated. Reference #1: Barbosa AN, Silvinato A, Bacha H, Floriano I, Tanni S, Bernardo W. Use of disease-modifying drugs (tocilizumab, tofacitinib, and baricitinib-a biological or synthetic target specific) in patients hospitalized with COVID-19. Rev Assoc Med Bras (1992). 2022;68(1):3-8. Reference #2: Santos CS, Férnandez XC, Moriano Morales C, Álvarez ED, Álvarez Castro C, López Robles A, Pérez Sandoval T. Biological agents for rheumatic diseases in the outbreak of COVID-19: friend or foe? RMD Open. 2021 Jan;7(1):e001439. doi: 10.1136/rmdopen-2020-001439. PMID: 33455920;PMCID: PMC7813407. Reference #3: Galarza-Delgado DÁ, Serna-Peña G, Compeán-Villegas JE, Cardenas-de la Garza JA, Pineda-Sic RA, Colunga-Pedraza IJ, Vega-Morales D, Pérez-Barbosa L, Skinner-Taylor CM, Flores-Alvarado DE. Characteristics and evolution of 38 patients with rheumatic diseases and COVID-19 under DMARD therapy. Clin Rheumatol. 2021 Mar;40(3):1197-1199. doi: 10.1007/s10067-020-05510-9. Epub 2020 Nov 24. PMID: 33231774;PM
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SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: COVID-19 patients requiring admission to an ICU have a higher risk of invasive pulmonary aspergillosis (IPA) with a reported incidence of 19.6%-33.3%. CASE PRESENTATION: A 63-year-old male presented with progressively worsening dyspnea for one week. He has a past medical history of atrial fibrillation, hypertension, and obesity. He was tested positive for COVID about two weeks prior. He did receive a single dose of Moderna vaccine. Initial chest x-ray(CXR) showed diffuse ground-glass opacities. He was initiated on Remdesivir and decadron, and later received a dose of tocilizumab. He was intubated on hospital day 3 for worsened hypoxemia. Repeat CXR suggested some improvement but a new left lower lobe airspace haziness. He also had new-onset leukocytosis with elevated procalcitonin level. He was started on cefepime for concern of superimposed hospital-acquired pneumonia. A second dose of tocilizumab was administered. No clinical improvement was seen, and additional workups were obtained. Serial CXRs revealed increasing diffuse airspace opacities concerning for ARDS. Tracheal aspirate culture grew coagulase-negative staphylococcus and Aspergillosis Fumigatus. Cefepime was changed to vancomycin, and voriconazole and caspofungin were added. Unfortunately, the patient's respiratory status worsened with increasing ventilation requirement. He also developed septic shock and acute renal failure requiring CVVH. He became even more hypotensive after CVVH initiation, and multiple vasopressors were required to maintain his hemodynamics. Unfortunately, he continued to deteriorate and he also developed profound respiratory acidosis. He died shortly afterwards after family decided to withdraw care. DISCUSSION: In this case, in addition to superimposed bacterial pneumonia, pulmonary aspergillosis likely also contributed to his clinical deterioration. The mechanism by which fungal infections develop in COVID-19 infection is not well-understood. Severe COVID-related immune dysregulation, ARDS, and high-dose steroids use are potential culprits for the increased risk of IPA. Tocilizumab, an IL-6 receptor monoclonal antibody used in patients with severe COVID-19 infection, may also predispose the patient to IPA according to post-marketing data. The mortality rate from current case reports is as high as 64.7%. Diagnosis and treatment in such a scenario remain a challenge. Sputum culture, serum Beta-galactomannan, Beta-D glucan, and aspergillosis PCR have low sensitivity. Tissue biopsy and CT scan in critically ill patients are often not feasible. Voriconazole is usually considered the first-line treatment in IPA. CYP3A4-mediated drug interactions between azoles and antiviral agents require further investigation. CONCLUSIONS: Clinicians should be aware that severe COVID-19 patients are at higher risk of IPA. The prognosis is poor. Early detection and treatment in clinically deteriorated patients are warranted. Reference #1: Borman, A.M., Palmer, M.D., Fraser, M., Patterson, Z., Mann, C., Oliver, D., Linton, C.J., Gough, M., Brown, P., Dzietczyk, A. and Hedley, M., 2020. COVID-19-associated invasive aspergillosis: data from the UK National Mycology Reference Laboratory. Journal of clinical microbiology, 59(1), pp.e02136-20. Reference #2: Lai CC, Yu WL. COVID-19 associated with pulmonary aspergillosis: A literature review. J Microbiol Immunol Infect. 2021;54(1):46-53. doi:10.1016/j.jmii.2020.09.004 Reference #3: Thompson Iii GR, Cornely OA, Pappas PG, et al. Invasive Aspergillosis as an Under-recognized Superinfection in COVID-19. Open Forum Infect Dis. 2020;7(7):ofaa242. Published 2020 Jun 19. doi:10.1093/ofid/ofaa242 DISCLOSURES: No relevant relationships by Jason Chang No relevant relationships by Jason Chang No relevant relationships by kaiqing Lin No relevant relationships by Guangchen Zou
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SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Since the start of Covid-19 pandemic, several respiratory microorganisms have been identified that cause coinfection with Sars-Cov-2. Bacteria like Staphylococcus aureus and viruses like influenza are some of the identified pathogens. Rarely, fungal infections from Aspergillus are also being reported. CASE PRESENTATION: 59-year-old male with past medical history of hypertension and hyperlipidemia was admitted for shortness of breath and was found to be positive for Covid-19. He received Remdesivir, dexamethasone & tocilizumab. He required non-invasive ventilation via continuous positive airway pressure but continued to remain hypoxemic with elevated procalcitonin, he was treated with cefepime for bacterial pneumonia. Patient required emergent intubation and eventually underwent tracheostomy. He developed methicillin-resistant Staphylococcus aureus pneumonia for which he received vancomycin. He was eventually discharged to long term acute care facility. Patient was readmitted after 2 months due to worsening respiratory status. Computed Tomography Angiography of chest was negative for pulmonary embolism but showed pleural effusion. He underwent thoracentesis which showed exudative effusion with negative cultures. Echocardiogram showed right heart failure. Patient's symptoms were believed to be due to Covid-19 fibrosis. He required home oxygen and also received pulmonary rehabilitation. One year after the initial Covid-19 infection, he developed pulmonary hypertension and was referred for lung transplant consultation. However, he developed severe hemoptysis requiring intubation and vasopressors. Galactomannan was positive, Karius digital culture revealed Aspergillus Niger for which he received voriconazole. He was not deemed a suitable candidate for lobectomy. Patient developed arrhythmia and had prolonged QT interval so voriconazole was switched to Isavuconazole. He continued to have hemoptysis and his condition did not improve so family requested to transition care and patient passed away. DISCUSSION: Several studies have proven co-infection of Aspergillus with Covid-19. This case highlights Aspergillus infection approximately 1 year after initial Covid-19 infection. Sars-Cov-2 causes damage to airway lining which can result in Aspergillus invading tissues. IL-6 is increased in severe Covid-19 infection. Tocilizumab is an anti-IL-6 receptor antibody that has been approved for treatment of Covid-19 pneumonia. However, IL-6 provides immunity against Aspergillus so use of tocilizumab decreases protection against Aspergillosis which is usually the reason for co-infection. However, in this case patient developed fungal infection later during Covid-19 fibrosis stage. CONCLUSIONS: Recognizing fungal etiology early on is important in Covid-19 patients as mortality is high and appropriate intervention can reduce morbidity and mortality. Some patient may eventually require lung resection. Reference #1: Kakamad FH, Mahmood SO, Rahim HM, Abdulla BA, Abdullah HO, Othman S, Mohammed SH, Kakamad SH, Mustafa SM, Salih AM. Post covid-19 invasive pulmonary Aspergillosis: a case report. International journal of surgery case reports. 2021 May 1;82:105865. Reference #2: Nasrullah A, Javed A, Malik K. Coronavirus Disease-Associated Pulmonary Aspergillosis: A Devastating Complication of COVID-19. Cureus. 2021 Jan 30;13(1). Reference #3: Dimopoulos G, Almyroudi MP, Myrianthefs P, Rello J. COVID-19-associated pulmonary aspergillosis (CAPA). Journal of Intensive Medicine. 2021 Oct 25;1(02):71-80. DISCLOSURES: No relevant relationships by Maria Haider Baig
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SESSION TITLE: Global Pulmonary Cases SESSION TYPE: Global Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: COVID 19 is associated with hyper- inflammation with levels of IL 6 correlating with the severity of COVID 19. IL6 causes increased vascular permeability and endothelial dysfunction and plays a major role in the development of ARDS.[1] Tocilizumab is a monoclonal antibody against the IL6 receptor which is being used for COVID pneumonia. Large randomized controlled trials including REMAP-CAP and RECOVERY reported a mortality benefit of tocilizumab in certain patients [3]. Aspergillus is a mold that causes variety of pulmonary infections depending on host's immune status. In immunocompromised hosts, it causes invasive pulmonary aspergillosis [2]. Symptoms initially are similar to bronchopneumonia: cough with sputum, dyspnea, fever not responsive to antibiotics. With disease progression, patients experience pleuritic chest pain and hemoptysis. CASE PRESENTATION: 69 y/o female came to ER with complaint of dyspnea and cough. PMH significant for Diabetes. She had a recent admission for COVID 3 weeks ago during which she received tocilizumab. This time, her vitals were HR- 96 RR- 24 Temp- 99.6 BP- 124/72, Sat- 88% on 2L NC. Labs WBC 31.1 D dimer- 2.17 ABG PO2- 61. CT pulmonary angiogram was consistent with left mid lung zone cavitary mass with an air-fluid level measuring 5 x 8 cm in transverse and AP dimension. Patient was started on broad-spectrum antibiotics (vancomycin, cefepime, metronidazole). Sputum cultures, Beta glucan assay, AFB and fungal immunodiffusion panel was ordered. Beta D Glucan assay came positive. Fungal immunodiffusion panel was negative. Bronchoscopy was done and AFB, aspergillus antigen and cultures were collected. BAL aspergillus antigen came positive and KOH fungal culture grew Aspergillus Fumigatus. Voriconazole was started. She was discharged on voriconazole for 12 weeks, ceftriaxone and clindamycin for 6 weeks for antibacterial coverage with plan to repeat CT chest in 3 weeks. DISCUSSION: We use tocilizumab for COVID 19 patients requiring invasive or non invasive mechanical ventilation and CRP ≥7.5 and exclude patients with ANC <2000, platelet <50,000 and history of serious bacterial, fungal or viral infection. This patient did not have any exclusion criteria but developed invasive fungal infection 3-4 weeks later. Due to worsening hypoxia and high D dimer, initial consideration was pulmonary embolism for which CT angiogram was done and a cavitary lesion was found. Differentials were bacterial abscess, tuberculosis or fungal infection. BAL played a crucial role in diagnosing aspergillosis. CONCLUSIONS: In patients presenting with worsening respiratory symptoms post tocilizumab administration we must keep a low index of suspicion for superimposed opportunistic infections including aspergillosis. Appropriate workup including CT chest, sputum or bronchoalveolar lavage for cultures (bacterial, fungal), Beta D Glucan and fungal panel is essential for diagnosis. Reference #1: Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia Ivan O Rosas;Norbert Bräu;Michael Waters;et al. New England Journal of Medicine, v384 n16 (20210422): 1503-1516 Reference #2: Pulmonary aspergillosis: a clinical review M. Kousha, R. Tadi, A.O. Soubani European Respiratory Review 2011 20: 156-174;DOI: 10.1183/09059180.00001011 Reference #3: Interleukin-6 Inhibitors. Available at: https://www.covid19treatmentguidelines.nih.gov. DISCLOSURES: No relevant relationships by Shaylika Chauhan No relevant relationships by Vipul Gidwani