Is there an increased incidence of bacteraemia among COVID-19 patients requiring critical care admission who have received IL-6 inhibitors?

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.

Immunosuppression and Covid-19: Risk factor or treatment?

Introduction: During the Covid-19 pandemic, 540,895 people were identified as immunosuppressed and believed to be at increased risk of severe disease.1 As the pandemic evolved, biologic immunosuppression became a treatment of severe Covid-19.2 The true impact of immunosuppression on disease severity remains unclear. Objective(s): 1. Identify the incidence of immunosuppressed patients admitted to the ICU. 2. Analyse the mortality of those who are immunocompetent and immunosuppressed. 3. Examine the differences in mortality and level of care required between sub groups of patients on immunosuppression;those on biologics, non-biologics, and a combination of both. Method(s): A retrospective search of all Covid-19 positive admissions from March 2020 to November 2021 across two adult ICUs at Chelsea & Westminster NHS Trust was performed, using the EPR system. We identified those on immunosuppressive drugs, the level of care they required, and 28 day mortality. We categorised different types of immunosuppression, vaccination status, if applicable and co-morbidities. The exclusion criteria were primarily those with false positive swabs or incomplete data. Result(s): Baseline characteristics were median age (56 vs 56), and APCHE II score (20.08 in the immunosuppressed group vs 14.0 in immunocompetent). Thirteen immunosuppressed patients were identified. Reasons for drug immunosuppression in this group included solid organ transplant (6/13), and autoimmune conditions (7/13). Two patients were on biologic drugs alone, 8 were on non-biologics, and 3 were on a combination. Four of this group had received at least 2 doses of a Covid-19 vaccine. Mortality was 61.54% (8/13) in the immunosuppressed group vs 36.65% (199/543) in the immunocompetent group. Conclusion(s): Despite similar demographics, patients on immunosuppression had a significantly higher mortality than the immunocompetent group. Interestingly, those on targeted biological immunosuppression had the lowest incidence of requiring level 3 care, and no deaths. It is a possibility that biologics dampen the hyper-inflammation seen in severe Covid-19 pneumonitis, raising the question of a possible protective benefit from severe disease. This reflects the findings of the REMAP-CAP investigators,3 who showed that the IL-6 inhibiting biologics Tocilizumab and Sarilumab are efficacious against the most severe disease following admission to ICU with Covid-19 pneumonitis. The single centre and retrospective observational design, combined with small numbers on immunosuppression, despite a large inclusion criterion, mean it is not possible to make statistical conclusions. Confounding factors include the effects of vaccination, shielding and the change in SARS-CoV-2 variant prevalent during different times during the pandemic.

Efficacy and safety of interleukin-6 receptor antagonists in adult patients admitted to intensive care unit with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

The purpose of the systematic review was to evaluate the efficacy and safety of interleukin-6 receptor (IL-6) antagonists (tocilizumab, sarilumab) in adult patients with severe or critical COVID-19. A systematic review of the literature was conducted in Medline, Cochrane and Embase databases, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov from the inception dates to10 January 2023. Randomized clinical trials comparing IL-6 receptor antagonists (tocilizumab, sarilumab) with a placebo or usual care treatment for adult patients with severe or critical COVID-19 were identified. Two independent reviewers performed the assessment and selection of eligible studies, assessed study quality and extracted data. Relative risk (RR), mean difference (MD), and 95% confidence interval (CI) with random-effects models was performed in meta-analysis. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the quality of the evidence. The search retrieved a total of 11 RCTs involving 5028 participants were eligible for meta-analysis. Our findings suggest that as the new drug used in adult patients with severe or critical COVID-19, IL-6 antagonists (tocilizumab, sarilumab) may reduce the length of ICU stay and hospital stay. However, they did not significantly increase the risks of serious adverse events and did not reduce all-cause mortality (28-day, 14-day, and 7-day).

Sarilumab use in severe Coronavirus Disease 2019 pneumonia

Background Interleukin-6 (IL-6) signal blockers have an important role in the management of Coronavirus Disease 2019 (COVID-19) and prevent progression of inflammation. Many studies have evaluated the efficacy of Sarilumab in severe COVID-19 pneumonia. Aim Evaluation of sarilumab efficacy in severe COVID-19 pneumonia. Patients and methods In all, 40 patients with severe acute respiratory syndrome coronavirus 2 severe pneumonia received intravenous sarilumab 400 mg. Results Patients were admitted to the ICU with a mean duration of 18.17 +/- 8.75 days. Eighteen (45%) patients on high-flow oxygen with nonrebreather masks and 22 (55%) patients on mechanical ventilation received sarilumab. IL-6 level is with a mean of 62.50 +/- 23.01 before sarilumab and a mean of 31.35 +/- 33.30 after sarilumab. Thirteen (32.5%) patients improved and 27 (67.5%) patients died. No sarilumab serious adverse effects were detected in this study. Patient oxygen saturation on discharge mean was 95.75+/-.97%. Concerning serum IL-6 levels among the recruited patients, there was statistically significant difference between the mean baseline level compared with the follow-up levels, 62.50 +/- 23.01 and 31.35 +/- 33.30 ng/ml, respectively, with a P value of 0.001. Conclusion Sarilumab improves IL-6 level in COVID-19 patients with severe pneumonia with no serious adverse effects. Mortality rate increased in severe COVID-19 cases, so early use of sarilumab in moderate cases may decrease disease progression and decrease mortality rate.Copyright © 2023 The Egyptian Journal of Chest Diseases and Tuberculosis.

Role of IP-10 to Predict Clinical Progression and Response to IL-6 Blockade With Sarilumab in Early COVID-19 Pneumonia. A Subanalysis of the SARICOR Clinical Trial.

Background: The Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR) showed that patients with coronavirus disease 2019 (COVID-19) pneumonia and increased levels of interleukin (IL)-6 might benefit from blockade of the IL-6 pathway. However, the benefit from this intervention might not be uniform. In this subanalysis, we sought to determine if other immunoactivation markers, besides IL-6, could identify which subgroup of patients benefit most from this intervention. Methods: The SARICOR trial was a phase II, open-label, multicenter, controlled trial (July 2020-March 2021) in which patients were randomized to receive usual care (UC; control group), UC plus a single dose of sarilumab 200 mg (sarilumab-200 group), or UC plus a single dose of sarilumab 400 mg (sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, monocyte chemoattractant protein-1, interferon-inducible protein [IP]-10) were included in this secondary analysis. Progression to acute respiratory distress syndrome (ARDS) according to cytokine levels and treatment received was evaluated. Results: One hundred one (88%) of 115 patients enrolled in the SARICOR trial had serum samples (control group: n = 33; sarilumab-200: n = 33; sarilumab-400: n = 35). Among all evaluated biomarkers, IP-10 showed the strongest association with treatment outcome. Patients with IP-10 ≥2500 pg/mL treated with sarilumab-400 had a lower probability of progression (13%) compared with the control group (58%; hazard ratio, 0.19; 95% CI, 0.04-0.90; P = .04). Conversely, patients with IP-10 <2500 pg/mL did not show these differences. Conclusions: IP-10 may predict progression to ARDS in patients with COVID-19 pneumonia and IL-6 levels >40 pg/mL. Importantly, IP-10 value <2500 pg/mL might discriminate those individuals who might not benefit from sarilumab therapy among those with high IL-6 levels.

Current Advances in Novel SARS-CoV-2 Disease (COVID-19) Treatment and Intervention Strategies

Background: During the eleven months of the novel SARS-CoV-2 disease (COVID-19) outbreak in China and its global spread, there is a remarkable understanding of its epidemiology, pathobiol-ogy, and clinical management strategies. While countering a heavy toll on health and the economy, world's regional authorities are enforcing safety guidelines and providing patient care. Currently, there is no globally approved treatment or intervention for COVID-19. Method(s): A structured online literature search for peer-reviewed articles was conducted on PubMed, Europe PMC, Google, WHO, CDC, FDA, and ClinicalTrials portals, using phrases such as COVID-19 treatment and intervention, COVID-19 drugs and COVID-19 vaccines. Result(s): Analysis of the retrieved data showed that as a part of 'Solidarity Clinical Trials', hundreds of treatment and intervention strategies, including antiviral drugs, cytokine antagonists, convalescent plasma therapy, and vaccine candidates, have been registered worldwide. While remdesivir, the anti-Ebola virus drug, has been approved as an 'emergency use' drug in the USA, favipiravir, the anti-flu drug, has been recently approved in Russia. Tocilizumab and sarilumab, the cytokine (IL-6) antagonists, have entered Phase-II/III clinical trials in hospitalized COVID-19 patients. Among the leading vaccine candidates, Phase-III clinical trial results of Moderna, Pfizer and Oxford vaccines seem to be game changers for COVID19. Conclusion(s): The world health authorities have strongly and quickly responded to the COVID-19 pan-demic. Nonetheless, world bodies must unite in combating this health crisis by developing cost-effective drugs and vaccines and making them accessible to resource-poor countries.Copyright © 2021 Bentham Science Publishers.

Pathogenesis, Clinical Manifestation, Diagnosis, Pathological Findings, Treatment Options, Preventive Measures, and Risk Factors of COVID-19

Background: COVID-19 is an infectious disease caused by SARS-CoV-2. The disease has hit hard around the globe and is now a pandemic. As of April 01, 2020, a total of 875,560 cases have been reported and the figures are increasing day by day. Currently, there is no treatment or vaccine available for curing COVID-19 and pharmaceutical companies are racing toward the common goal of achieving the cure. Method(s): Scientific databases, including Science direct, Pub med, Elsevier, Scopus, and Nature, were explored. Data has also been accessed from case reports, newspaper reports, internet data, World Health Organisation (WHO) reports, and Centre of Disease Control (CDCs) reports. The US National Library of Medicine, Clinicaltrials.gov, were accessed to get information about the ongoing clinical trials. The literature survey started in the first week of February 2020 and was completed in the first week of April 2020. Additional literature survey was done in the second week of June 2020. Result(s): The epicentre of COVID-19 is Wuhan City, Hubei Province, China. Coronavirus belongs to Order Nidovirale and is subdivided into four groups alpha, beta, gamma, and delta. Coronavirus 229E, NL63, HKU1, MERS-CoV and SARS-CoV are known to infect humans. It is an enveloped, non-segmented positive-sense RNA virus of size 30-32 kb with several structural and accessory proteins. The pathogenesis of COVID-19 involves attachment of Spike (S) protein of SARS-CoV-2 to the angio-tensin-converting enzyme 2(ACE2) receptor present on the host cell membrane. Clinical manifestation of COVID-19 include fever, cough, complicated dyspnoea, pneumonia, etc. Real-time-PCR is a sensi-tive test for the detection of SARS-CoV. Remdesivir, Bevacizumab, Darunavir and cobicistat, lopinavir-ritonavir, Oseltamavir, hydroxychloroquine, Sarilumab, mRNA-1273, Ad5-nCoV are some of the drugs under the clinical phase of the trial. People with A-positive blood group, with comorbidities like diabe-tes, hypertension, chronic pulmonary obstructive disease, substance abuse disorders, immunocom-promised individuals, health care workers, and older adults are at high risk of getting infected with SARS-CoV-2 Conclusion(s): This article gives insight into the occurrence of COVID-19, classification and structure of SARS-CoV-2, pathogenesis, pathological findings, clinical manifestation, diagnosis, potential treatment options and prevention, and people at risk of COVID-19.Copyright © 2021 Bentham Science Publishers.

Cytokine Storm and Immunomodulation in COVID-19: A Review

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has taken over the world, and more than 38 lakh deaths had been reported till now due to this infectious disease. It has been declared a global pandemic by the world health organization. SARS-CoV-2 causes coronavirus disease of 2019 (COVID-19), and the major problem called "Cytokine storm" is reported, which may lead to death among the COVID-19 patients. This study aimed to review the Cytokine storm and its mechanism along with few immunomodulatory therapies for SARSCoV-2 infection suppression effectively. Method(s): The recently published works of literature were selected and reviewed based on the subject of this study. The databases, including Pubmed, ScienceDirect, Scopus, and Google Scholar, were searched extensively. Result(s): The review of the literature showed that an uncontrolled immune response causes excess inflammation. Evidence from recent trials has demonstrated that cytokine storms can be an important factor in the COVID-19 severity, leading to multiple organ failure and death. Conclusion(s): This study reviewed immunomodulatory therapies and strategies for SARS-CoV-2 infected patients to suppress the immune response. Ultimately, the cytokine storm can prove to be a boon and reduce the significant death tolls to SARS-CoV-2 infection.Copyright © 2022 Bentham Science Publishers.

COVID-19 Infection: A Review of Summarized Clinical Trials Study for the Treatment

Background: Coronavirus Disease 2019 (COVID-19) is a widely infectious and pathogenic viral infection. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was reported in Wu-han, China, and spread throughout the world. Coronavirus is indeed an enveloped RNA virus of the ge-nus Betacoronavirus, which is transmitted to birds, humans as well as other mammals. The fastest human to human transition has been generally established. On July 19, 2020, the WHO has reported total confirmed cases: 1,40, 43,176, total confirmed new cases: 1,66,735, total deaths: 5,97,583, and total new deaths: 4,496 globally. Material(s) and Method(s): In this review, the Clinical trial database is analyzed and systematically summarized drugs which are in the recruiting phase and the completion phase of the clinical trial. Result(s): Total 383 clinical trials are listed, involving more than 350 medicines such as Deferoxamine, Favipiravir, DAS181, Tocilizumab Injection, Sarilumab, Placebo, Sildenafil citrate tablets, Sargramo-stim, Lopinavir/ritonavir, Remdesivir, Bevacizumab, Tetrandrine, Fingolimod, Methylprednisolone, Plaquenil, Tocilizumab, Hydroxychloroquine, Abidol hydrochloride, Bevacizumab Injection, Methyl-prednisolone, Amoxicillin-clavulanate, Moxifloxacin, Sarilumab, Darunavir, Cobicistat, etc. Conclusion(s): There is no commercially authorized antiviral treatment or vaccine suitable for use against COVID-19. However, clinical trials represent an effective approach because they facilitate the development of new types of pharmaceutical drugs.Copyright © 2021 Bentham Science Publishers.

Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study).

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.

Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials (RCT) established the mortality reduction by tocilizumab (Actemra), baricitinib (Olumiant), and sarilumab (Kevzara) in hospitalized COVID-19 patients. However, uncertainty remains about which treatment performs best in patients receiving corticosteroids. OBJECTIVES: To estimate probabilities of noninferiority between baricitinib and sarilumab compared to tocilizumab in patients treated with corticosteroids. DATA SOURCES: PubMed, Embase, Cochrane Library, and MedRxiv. STUDY ELIGIBILITY CRITERIA: Eligible RCTs assigning hospitalized adults with COVID-19 treated with corticosteroids to tocilizumab or baricitinib or sarilumab versus standard of care or placebo (control). METHODS: Reviewers independently abstracted published data and assessed study quality with the Risk of Bias 2 tool. Unpublished data, if required, were requested from authors of included studies. The outcome of interest was all-cause mortality at 28 days. PARTICIPANTS: Twenty-seven RCTs with 13 549 patients were included. Overall, the risk of bias was low. Bayesian pairwise meta-analyses were used to aggregate results of each treatment versus control. The average odds ratio for mortality was 0.78 (95% credible interval [CrI]: 0.65, 0.94) for tocilizumab; 0.78 (95% CrI: 0.56, 1.03) for baricitinib; and 0.91 (95% CrI: 0.60, 1.40) for sarilumab. The certainty of evidence (GRADE) ranged from moderate to low. Bayesian meta-regressions with multiple priors were used to estimate probabilities of noninferiority (margin of 13% greater effect by tocilizumab). Compared to tocilizumab, there were ≤94% and 90% probabilities of noninferiority with baricitinib and sarilumab, respectively. RESULTS: All but two studies included data with only indirect evidence for the comparison of interest. CONCLUSIONS: Among hospitalized COVID-19 treated with corticosteroids, there are high probabilities that both baricitinib and sarilumab are associated with similar mortality reductions in comparison to tocilizumab.

Pharmacological treatment of COVID-19: an opinion paper.

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.

A comparison of the effectiveness of different doses of tocilizumab and sarilumab in the treatment of severe COVID-19: a natural experiment due to drug shortages.

OBJECTIVES: Interleukin (IL)-6 inhibitors are administered to treat patients hospitalized with COVID-19. In 2021, due to shortages, different dosing regimens of tocilizumab, and a switch to sarilumab, were consecutively implemented. Using real-world data, we compare the effectiveness of these IL-6 inhibitors. METHODS: Hospitalized patients with COVID-19, treated with IL-6 inhibitors, were included in this natural experiment study. Sixty-day survival, hospital- and intensive care unit (ICU) length of stay, and progression to ICU or death were compared between 8 mg/kg tocilizumab, fixed-dose tocilizumab, low-dose tocilizumab, and fixed-dose sarilumab treatment groups. RESULTS: A total of 5485 patients from 49 hospitals were included. After correction for confounding, increased hazard ratios (HRs) for 60-day mortality were observed for fixed-dose tocilizumab (HR 1.20, 95% confidence interval [CI] 1.04-1.39), low-dose tocilizumab (HR 1.12, 95% CI 0.97-1.31), and sarilumab (HR 1.24, 95% CI 1.08-1.42), all relative to 8 mg/kg. The 8 mg/kg dosing regimen had lower odds of progression to ICU or death. Both hospital- and ICU length of stay were shorter for low-dose tocilizumab than for the 8 mg/kg group. CONCLUSION: We found differences in the probability of 60-day survival and the incidence of the combined outcome of mortality or ICU admission, mostly favoring 8 mg/kg tocilizumab. Because of potential time-associated residual confounding, further clinical studies are warranted.

Drug-induced liver injury following the use of tocilizumab or sarilumab in patients with coronavirus disease 2019.

BACKGROUNDS: Interleukin-6 (IL-6) blockers including tocilizumab and sarilumab were approved by the U.S. Food and Drug Administration (FDA) in June 2021 for the treatment of patients with moderate to severe COVID-19. The use of sarilumab or tocilizumab in COVID-19 patients has been related to a reduction in mortality compared to standard care. Recent evidence has emerged concerning drug-induced liver injury (DILI) after sarilumab or tocilizumab applications in COVID-19 patients. AIMS: The study aimed to estimate DILI associated with sarilumab or tocilizumab in treating moderate to severe patients infected with SARS-Cov-2. METHODS: We conducted a retrospective pharmacovigilance study by data mining of the FDA's adverse event reporting systems (FAERS) database from the first quarter of 2004 to the fourth quarter of 2021 in confirmed COVID-19 patients. We analyzed DILI cases associated with tocilizumab or sarilumab in treating COVID-19 patients from the FAERS during this period. Disproportionality analysis and Bayesian analysis of COVID-19 patients were utilized for case analysis, and we also next compared the onset time and fatality rates of DILI following tocilizumab or sarilumab. RESULTS: A total of 275 cases of TCZ or SAR-related DILI reports were extracted. A total of 192 AEs cases were related to tocilizumab (TCZ), and 83 were related to sarilumab (SAR). In patients treated with TCZ, most were < 75 years old (51.57%), with more male than female (46.35% vs. 13.02%). The correlation between IL-6 receptor antagonists and DILI was stronger in SAR (ROR = 12.94; 95%CI 9.6-17.44) than in TCZ (ROR = 1.33; 95%CI 1.14-1.55). The onset time of DILI was different between TCZ and SAR, and a significant difference was observed in TCZ than SAR (P < 0.0001). A significant difference was observed in the mortality rate of TCZ and SAR (P = 0.0009). DILI associated with COVID-19 patients treated with TCZ appeared to have earlier onset-time (1(0-46) day) VS. SAR (3.5(0-27) day). CONCLUSION: This study shows strict monitor ought to be paid for TCZ or SAR when used for COVID-19 patients with poor liver function.

WHEN NOTHING HELPS: A RARE CASE OF COVID-19 EMPYEMA IN A YOUNG HEALTHY MALE

SESSION TITLE: Problems in the Pleura Case Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Severe COVID 19 has now been known to cause devastating damage to the lungs. The manifestations include severe pneumonia, acute respiratory distress syndrome, spontaneous pneumothorax, etc. As we were learning about the pathogenesis of the infection, we were also learning rapidly about the therapeutics targeted against it. A report a case of severe COVID 19 ARDS in a non-vaccinated young male, who later developed empyema during his hospital course. CASE PRESENTATION: A 29-year-old male with no past medical history presented to the emergency department complaining of chest pain and shortness of breath. He was not vaccinated against COVID-19. He was discharged from the hospital on 2 liters of supplemental oxygen two days ago after undergoing treatment for COVID-19 pneumonia with dexamethasone and remdesivir. Physical examination revealed bilateral diminished lung sounds on auscultation. His blood pressure was 112/75 mm Hg, heart rate (HR) 120 per minute, respiratory rate 25 per minute, the temperature of 38.5 Celsius and he was saturating 91% on 15 L of oxygen via a non-rebreather mask. Initial CT scan revealed bilateral ground-glass opacities (figure 1.). Due to high oxygen requirements and CRP of 10.5 MG/DL, the patient was started on Sarilumab. Given his escalating oxygen requirements and worsening respiratory distress, he was intubated and transferred to the intensive care unit. Despite intermittent prone positioning, he became progressively hypoxemic and eventually required Veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO). One week later he developed intermittent fever spikes up to 39.5 C with HR of 120 per minute and leukocytosis of 40.8 K/µL. Bedside point of care ultrasound revealed new bilateral complex pleural effusions. Chest CT-scan showed moderate bilateral pleural effusions with new cystic changes and worsening consolidations (figure 2). Pleural fluid analysis showed lactate dehydrogenase of 2798, pH of 7.11, and cell count of 100 with 98% neutrophils. Despite aggressive therapy with chest tube placements and broad-spectrum antibiotics his condition continued to worsen over the next month with the development of hydropneumothoraxes and traction bronchiectasis (figure 3). Given the clinical deterioration despite aggressive care, his family decided to pursue a comfort-oriented treatment approach and he eventually passed away. DISCUSSION: COVID-19 related pleural effusion is a reported complication of COVID-19 pneumonia in up to 2-11% of the cases [1]. Most cases are associated with comorbid conditions, such as heart failure, superimposed bacterial infections, and pulmonary embolism [2]. CONCLUSIONS: Our case indicates that bacterial empyema may complicate COVID-19 pneumonia later in the disease course even in young immune-competent patients, it is unclear if empyema is directly related to the disease process itself r the therapeutic used to treat the COVID 19 infection. Reference #1: Chong WH, Saha BK, Conuel E, Chopra A. The incidence of pleural effusion in COVID-19 pneumonia: State-of-the-art review. Heart Lung. 2021;50(4):481-490. doi:10.1016/j.hrtlng.2021.02.015 Reference #2: Zhang L, Kong X, Li X, et al. CT imaging features of 34 patients infected with COVID-19. Clin Imaging. 2020;68:226-231. doi:10.1016/j.clinimag.2020.05.016 DISCLOSURES: No relevant relationships by Rimsha Ali No relevant relationships by Konstantin Golubykh No relevant relationships by Iuliia Kovalenko No relevant relationships by Maidah Malik No relevant relationships by Taaha Mirza No relevant relationships by Navitha Ramesh

MACROGLOSSIA IN THE SETTING OF COVID-19

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: Macroglossia is a rare but life-threatening symptom that disrupts a person's ability to talk, swallow, and can also compromise their airway. Although not very well studied, there are several case reports describing a possible association between COVID-19 infection and macroglossia in people with African ancestry. We present an African American man who developed significant macroglossia several days after testing positive for COVID-19. CASE PRESENTATION: A 59 y/o African American male with a history of chronic bronchitis and tobacco use presented with 4 days of dyspnea. Sars-Cov-2 PCR was positive. Chest x-ray revealed bilateral, diffuse lung infiltrates. He had an elevated CRP of 295 and a d-dimer of 265. He became lethargic and hypercapnic requiring intubation which was nontraumatic. He was sedated, paralyzed, and proned. He received steroid therapy, broad spectrum antibiotics and a dose of Sarilumab. About a week later, he developed macroglossia that worsened over the course of days. Side effect profiles of each of his medications did not reveal any increased likelihood of macroglossia. C1Q complement cascade was mildly elevated and C1 esterase inhibitor level was normal. Diagnosis and treatment was necessary at this point as concerns for tongue central necrosis were raised and baseline tongue size would be required for proper evaluation and surgical intervention if necessary. He was given 4 units of FFP for possible angioedema with no improvement. CT Neck W/ contrast revealed edema and protrusion of the tongue without a discrete mass. Workup for acromegaly, sarcoidosis, amyloidosis, and hypothyroidism were negative. A pressure ulcer developed on his tongue due to the endotracheal tube and so he underwent tracheostomy. His tongue was draped in Chlorhexidine soaked gauze as well as Vashe wound solution. As he recovered from COVID-19 pneumonia, his respiratory status improved as well as his macroglossia. His tracheostomy was decannulated and his tongue returned to its baseline size. DISCUSSION: Macroglossia can lead to complications including airway compromise, dysphagia, or speech difficulties. It has been heavily proposed in the literature that COVID-19 infection can lead to postinfectious inflammatory peripheral nerve injury secondary to immune driven mechanisms. It was also previously proposed in literature based on immune-histochemical analysis of a tongue tissue sample taken from a COVID-19 patient that tongue muscle atrophy occurs as well as macrophage infiltration similar to that of nerve injury repair which can eventually lead to macroglossia. CONCLUSIONS: As the effects of COVID-19 are becoming better studied overtime, macroglossia, especially in those with African ancestry, is increasingly coming under the radar. This case report seeks to educate clinicians on this possible sequela and encourage supportive treatment in hopes that the tongue will recover. Reference #1: McCrossan S, Martin S, Hill C. Tongue Reduction for Macroglossia. J Craniofac Surg. 2021;32(5):1856-1859. doi:10.1097/SCS.0000000000007276 Reference #2: Colombo D, Del Nonno F, Nardacci R, Falasca L. May macroglossia in COVID-19 be related not only to angioedema?. J Infect Public Health. 2022;15(1):112-115. doi:10.1016/j.jiph.2021.10.026 Reference #3: Fernandez CE, Franz CK, Ko JH, et al. Imaging Review of Peripheral Nerve Injuries in Patients with COVID-19. Radiology. 2020;298 (3). https://doi.org/10.1148/radiol.2020203116 DISCLOSURES: No relevant relationships by Megan Devine No relevant relationships by Devin Haney No relevant relationships by Es-Haq Hassanin No relevant relationships by Nadim Islam No relevant relationships by Alyssa Weyer