Fungal pneumonia in COVID-19 patients: Risk factors and early prediction

Objective To determine the risk factors for developing secondary fungal pneumonia in moderate to severe coronavirus disease 2019 (COVID-19) cases. Using predictors of fungal infection helps to guide the diagnosis and treatment in these cases and save their lives. Patients and methods A total of 257 patients with moderate to severe COVID-19 pneumonia were examined in this retrospective study at Al Qassimi Hospital of EHS. An assessment of clinical, laboratory, and radiologic findings was performed upon admission. The data were collected and analyzed. Results Overall, 32% of critically ill COVID cases had fungal infection;47% of them were candida, whereas aspergillosis and yeast were positive in 26.5% each. At the time of hospitalization, computed tomography chest findings had a strong correlation with fungal culture results in COVID-19 cases. Fungal infection in COVID-19 cases correlated strongly with metabolic acidosis, high erythrocyte sedimentation rate, high blood sugar, need for mechanical ventilation at admission, vasopressor use, renal replacement, long duration of steroid treatment, long stay in ICU, and long duration on mechanical ventilation. The longer the duration of PCR positivity, the higher the incidence of positive sputum fungal culture result. Conclusion COVID-19-infected patients with other risk factors for fungal infections should always be considered to have fungal infections if pathogenic organisms are isolated from respiratory secretions or other microbiological or immunological markers appear positive. Computed tomography chest finding in COVID-19 cases is an important predictor for fungal infection.Copyright © 2023 The Egyptian Journal of Chest Diseases and Tuberculosis.

Tracheostomy outcomes in COVID-19 and non-COVID-19 critical patients

Introduction: Tracheostomy is a common surgical procedure in the setting of acute respiratory failure. And improves outcomes for critically patients requiring prolonged mechanical ventilation. Initially avoided due to it's high risk to biosafety, tracheostomy soon became a routine procedure in the critical support of critical ill patients affected by COVID-19. The aim of this review was to compare tracheostomy done in COVID-19 and non-COVID-19 pneumonias in an UCI. Method(s): This retrospective, observational study included 78 patients (23 female, 55 male;age range: 23-90 years, mean age: 66) with severe pneumonia who were admitted to the intensive care unit (ICU) of Hospital Beatriz Angelo (Portugal) between 01/03/2012 until 31/12/2021, to whom a tracheostomy was performed. Patients underwent orotracheal intubation with invasive mechanical ventilation, followed by percutaneous or open surgical tracheotomy. Indications, timing of the procedure, and time needed to complete weaning and decannulation, as well as complications, were reported and compared between patients with COVID-19 (N = 38) and non-COVID-19 (N = 40) pneumonias. Result(s): In both groups, weaning from difficult ventilation was the most common indication for the procedure, followed by prolonged mechanical ventilation in the COVID-19 group (42%) and protection of the airway/secretions management in the non-COVID-19 group (22.5%). Timing of the procedure was 14.6 and 16.4 days after mechanical ventilation in the COVID-19 and non-COVID group, respectively. The non-COVID-19 group reported more days to decannulation (39.3 vs 15.1 days) as well as more days to wean off from mechanical ventilation (20.3 vs 14.1 days) and more major complications (12.5% vs 2%). Hospital discharge rate was similar in both groups (COVID-19 with 42.1% and 42.5% to non-COVID-19). Conclusion(s): Although the differences between both groups are multifactorial, it's useful for self-evaluation observations, as well as sharing practices and outcomes for further analysis.

Role of mouthwash in prevention of Covid-19: A review

The corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARSCoV-2), first detected in Wuhan, Hubei province of China, has emerged rapidly as a health crisis that has challenged health systems and health professionals all over the world. Transmission occurs primarily through droplet spread or contact routes. Due to these characteristics dental staff and dental practitioners are considered to be at the highest risk of acquiring SARS-CoV-2 infection because of their prolonged face to face exposure to patients and exposure to respiratory secretions and aerosols produced during procedures like ultrasonic scaling and cavity/access preparation using a high-speed air rotor with water jet cooling systems. Antiseptic mouthwashes have been widely used as a standard measure before routine dental treatment, especially preoperatively. They have an essential role in reducing the number of microorganisms in the oral cavity. Hence, present review of literature provides details on role of mouthwash in prevention of Covid-19 transmission.Copyright © 2020 Ubiquity Press. All rights reserved.

Assessing the Effectiveness of a Standardized and Concise End-of-Life (EOL) Care Toolkit for Medical Residents in a Teaching Hospital: A Mixed Methods Exploratory Study (Sch409)

Outcomes: 1. Assess baseline knowledge, attitudes, and practices on EOL non-pain symptom management among internal medicine residents in a teaching hospital using a cross-sectional survey. 2. Develop a standardized inpatient EOL non-pain symptom management educational toolkit for internal medicine residents. Introduction: With palliative care gaining traction as a vital specialty to help patients living with serious illnesses comes the need for further training of healthcare professionals. Frontline providers such as medical residents can benefit from end-of-life (EOL) care training in symptom management. Method(s): There are three phases (over a period of 4 years) to this study: (1) administration of a needs assessment survey of baseline knowledge, attitudes, and practices on EOL non-pain symptom management;(2) development and implementation of a standardized inpatient EOL symptom management toolkit;and (3) a comparison of pre-and postassessment after the educational intervention. Result(s): The baseline survey had 66 participants. There were six non-pain symptoms that were elicited as important for further education and training. These were anorexia, nausea/vomiting, dyspnea, oral secretions, myoclonus, and delirium. Competency-based comfort and confidence levels were assessed using a Likert scale (1-5), with the highest number as the most comfortable. The residents were noted to be more comfortable with EOL communication compared to symptom management. Furthermore, residents who had had previous EOL care experiences with patients were more comfortable in symptom management. The educational intervention implemented at a later time revealed that there was an improvement in posttest scores for EOL symptom management. Discussion(s): This study highlights the needs and gaps in EOL symptom management training for medical residents. The implementation of a standardized inpatient EOL symptom management toolkit might serve as a potential intervention to address the needs and narrow gaps in medical training. This can serve as a possible template for other institutions to integrate an EOL care curriculum in medical residency. Limitations of the study include a small sample size, implementation during the COVID-19 pandemic, variable participant response rate, and interrupted timelines. The next steps include ongoing training for all residents, long-term follow-up postintervention, and institutional buy-in.Copyright © 2023

Impact of COVID 19 on bacterial respiratory isolates (2018-2021) from a UK tertiary cardio-thoracic ICU

Aim: To study the impact of COVID-19 admissions during 1st and 2nd surges on bacteriology of ICU respiratory isolates. Method(s): Retrospective time trend analysis of bacterial respiratory isolates from a single centre, tertiary cardiothoracic ICU (CT-ICU) from patients admitted from Jan 2018- June 2021. We compared pre-COVID-19 (January 2018- March 2020) and COVID-19 periods (April 2020- June 2021) and surge periods (surge 1: March 2020- June 2020, surge 2: January- March 2021) to similar time frames in previous years. Chi-square test used to compare proportions. Result(s): 4974 respiratory isolates (Sputum-4230, BAL-563, ET secretions-181) included. During surge 2, culture positivity and gram-negative rates tripled from baseline (20% to 75%;p<0.05). Comparing the pre- pandemic to pandemic period, rates of Klebsiella sp, Acinetobacter sp and Stenotrophomonas sp increased from 12% to 21.3%, 2.4% to 6.2% and 10.5% to 14.3% respectively, while Pseudomonas sp dropped from 30.7% to 23.1% (all p<0.05). MDR Pseudomonas increased significantly from 38.9% to 47.9% (p<0.05), with a non-significant increase in MRSA (5.2% to 9.3%;p=0.34) and MDR enterobacterales (22.6% to 23%;p=0.48). Conclusion(s): This is the first report from a UK CTICU showing a marked epidemiological shift in the bacteriology of respiratory isolates in terms of organism profile, increase in culture positivity and MDR Pseudomonas rates during the pandemic. Analyzing trends on longevity of the findings will help guide changes to infection control and antibiotic policies. This emphasizes the importance of unit specific ecology in choosing appropriate timely antimicrobial therapy and therefore improving patient outcome.

Case study: Manual respiratory physiotherapy manoeuvres facilitating fibroscopy in an intubated and sedated ICU patient

Introduction: The interest of respiratory physiotherapy maneuvers during a difficult fibroscopy in the intubated patient, sedated in a context of Covid-19 has not been reported so far. Case presentation: A 50-years-old patient with a severe form of Covid-19, requiring an endotracheal intubation, complicated by a ventilator-associated pneumonia and a complete atelectasis of the left lung. Because of adherent and purulent mucus, chest physiotherapy techniques and fiberoptic bronchoscopy conducted separately showed low effectiveness to remove the atelectasis. Chest physiotherapy manual techniques used during fiberoptic bronchoscopy allowed extracting easier the mucus;they helped to remove the atelectasis and to improve the hematosis as well as the prognosis for survival of the patient. Conclusion(s): Manual maneuvers of respiratory physiotherapy during the fibroscopy procedure could improve the efficiency of aspiration of very adherent secretions. Level of Evidence: 5.Copyright © 2022 Elsevier Masson SAS

Effect of the COVID-19 Pandemic on Bronchoscopy Indication and Bronchial Microbiology

Background: Lockdowns and mask wearing have impacted infectious disease patterns during the COVID-19 pandemic. We investigated changes in the use of bronchoscopy and the results of routine microbiology in bronchial lavage. Method(s): We included bronchoscopies from 2017-2021 at the LMU University Department of Pulmonology. In this we present an initial cohort comparing bronchoscopies in 2017-2018 to the initial phase of the COVID-19 pandemic in 2020. Comparisons used chi-squared and Fischer's exact tests in SPSS. Result(s): We analysed 480 bronchoscopies from before and 85 during the COVID-19 pandemic. Mean age: 62.6 y (+/-14.1) before vs. 55.2 y (+/-16.3) during the pandemic (p<0.001). Indication for bronchoscopy: secretions/atelectasis (n=122), suspected tumor (n=89) and intervention/therapy (n=80) before;suspected tumor (n=30), respiratory deterioration after lung transplant (n=19) and infection (n=7) during the pandemic. Staphylococcus aureus and Pseudomonas aeruginosa were common in both groups. Frequencies of EBV (p<0.001), CMV (p=0.003) and HHV6 (p<0.001) differed significantly. Conclusion(s): There were clinically relevant differences in the use of bronchoscopy before vs. during the COVID-19 pandemic: pandemic patients were younger and interventions such as bronchial stenting and recanalisation less common. Bacterial results were similar but the frequency of common viruses differed. The effect of lockdowns, mask wearing and social distancing on bronchial microbiology in patients with lung cancer or chronic lung disease will be investigated in further detail in this cohort. Clinical relevant differences may support continued mask wearing in some high-risk situations post-pandemic.

OPTIMIZATION OF MOLECULAR METHODS FOR SARS-CoV-2 QUALITATIVE DETECTION AND GENOTYPING IN RESPIRATORY SPECIMENS FROM PATIENTS WITH LIVER DISEASE

Introduction and Objectives: SARS-CoV-2 active infection diagnosis is currently performed through RT-qPCR. Despite the fact that PCR-based assays can provide results relatively fast, these techniques require capable professionals, specific equipment and adequate infrastructure. In order to facilitate COVID-19 diagnosis in remote areas, an alternative to RT-qPCR would be loop-mediated isothermal (RT-LAMP) amplification. SARS-CoV-2 variant genotyping through high-throughput sequencing (HTS) allows SARS-CoV-2 genomic surveillance, especially for patients with a higher vulnerability. This study aimed to optimize RT-LAMP and HTS methods for SARS-CoV-2 RNA detection and genotyping, respectively, in respiratory samples from patients with liver disease. Material(s) and Method(s): A total of 142 respiratory secretions were obtained from individuals with SARS-CoV-2 RNA detectable by RT-qPCR (N1 Ct <= 30), divided into groups with (n=18) or without (n=124) liver disease. The study also enrolled 55 individuals who had SARS-CoV-2 RNA undetectable at RT-qPCR. For RT-LAMP methodology, primers were used for ORF1 gene amplification. As for HTS genotyping, the steps of cDNA synthesis, complete SARS-CoV-2 genome PCR amplification, preparation of genomic libraries and sequencing in MinION device were performed for 26 swab samples. Result(s): Samples with viral RNA detectable by RT-qPCR had a mean Ct value of 24.3 +/- 3.75. Referring to RT-LAMP, it was observed a sensitivity of 71.1% (101/142). When considering RT-qPCR mean Ct value, RT-LAMP sensitivity was 88.9% (16/18), associated with a mean Ct of 23.3 +/- 3.5 for patients with COVID and hepatitis. A specificity of 100% (55/55) was observed since all negative swabs tested by RT-qPCR were negative at RT-LAMP. Through sequencing by MinION, SARS-CoV-2 lineages gamma (7/26;27%), zeta (1/26;3.9%), delta (6/26;23%) and omicron (12/26;46.1%) were genotyped and detected by RT-LAMP. Conclusion(s): RT-LAMP demonstrated high sensitivity for molecular detection of SARS-CoV-2 RNA for patients with high viral load. Besides, RT-LAMP was capable of detecting all SARS-CoV-2 lineages genotyped by MinION in both groups.Copyright © 2023

It Takes Two to Make a Thing Go Wrong

Seventy-three-year-old diabetic male was a high-risk transfer from Alaska for respiratory decompensation in the setting of progressive bulbar and proximal weakness. He was diagnosed with COVID-19 two months prior and viral mononucleosis 1 month prior to presentation. While the patient had a fall 3 months prior to presentation, and decreased mobility at home, there was abrupt onset of progressive upper/lower extremity weakness, dysphagia, and difficulties managing secretions 2 weeks prior to presentation. Initial exam was notable for MRC 3-4/5 proximal upper/lower extremity weakness, areflexia, and negative inspiratory force of 224 to 230 cm H20. A subtle periorbital heliotrope rash was documented. Lumbar puncture demonstrated albumino-cytologic dissociation (protein 142 mg/dL, 6 WBCs) and CK remained elevated (1930 U/L) despite intravenous hydration. Outside electrodiagnostic testing demonstrated a sensorimotor axonal neuropathy with questionable myopathic features on needle electromyography. Given concern for an inflammatory neuropathy and concomitant inflammatory myopathy, intravenous immunoglobulin 2G/kg and IV methylprednisolone 1G/day over 5 days was started. He was transferred for further diagnostic workup and supportive care 6 days after presentation and required intubation within 24 hours of admission. Exam showed progressive proximal and distal weakness of the extremities and general areflexia/hyporeflexia. Repeat electromyography confirmed a severe sensorimotor axonal polyneuropathy without acquired demyelinating features and normal repetitive nerve stimulation. While the patient could no longer activate muscles voluntarily, proximal muscles had increased spontaneous activity with predominant myotonia. Neuroaxis imaging was notable only for enhancement of the lumbar nerve roots. Combined vastus lateralis muscle biopsy and serologic testing confirmed a second pathologic process contributing to the patient's weakness. This case highlights the cooccurrence of 2 distinct neuropathological entities, with potential relation to a prior viral infection, and the importance of ancillary testing to guide treatment for acute causes of neuromuscular respiratory failure.

An unusual presentation of malignant Invasive Mucinous Adenocarcinoma of Lung mimicking Pulmonary Renal syndrome

Background: A 54-year- old male presented to our centre with a chronic non-productive cough and breathlessness. Recent history of COVID treated and resolved few months back. He had a history of brain surgery performed five years back but details not known. Physical examination revealed no oedema and bilateral coarse creps with bronchiolar breathing. Laboratory findings indicated neutrophilic leucocytosis, elevated inflammatory markers, with elevated troponin I and D dimers. Urine analysis suggested microscopic haematuria with sediments. While 24 hour quantification revealed sub nephrotic proteinuria. As auto immune workup and vasculitis profile was negative and patient has not improved in spite of standard of therapy hence we went ahead with CT-Chest indicating ground-glass opacities in bilateral lung parenchyma and prominent interlobular/intralobular septal thickening. Then Bronchoscopy done which revealed the blood-stained secretions in the main stem bronchi and diffuse alveolar haemorrhage in bilateral bronchial segments indicating an inflammatory study, while tuberculosis diagnostic panel and infective bio fire panel in BAL was negative. Meanwhile, his repeat BAL culture suggested Carbapenem resistant Acinetobacter baumannii complex infection. As the patient did not respond to the standard of care for vasculitis. Probability considered was a small vessel vasculitis (namely Granulomatous polyangiitis) was considered due to lung manifestation involving upper respiratory tract with epistaxis, neutrophilic leucocytosis, elevated acute reactive protein, and renal manifestation including microscopic haematuria and proteinuria. However he responded poorly to conventional standard of treatment including pulse steroids and IVIG. Hence after MDT discussion we proceeded with lung biopsy which showed linear cores of lung tissue infiltrated by a malignant neoplasm and acinar pattern suggesting Invasive mucinous adenocarcinoma. Hence we went ahead with the biopsy diagnosis for the treatment plan. As he was to be started on chemotherapy, but he suddenly collapsed and went into hypotension, bradycardia, and cardiac arrest. In spite of high supports and post 4 cycles of CPR, was unable to revive and sadly succumbed to his illness. Discussion(s): In this rare case, the original diagnosis pointed to the pulmonary-renal syndrome, an autoimmune disease characterized by diffuse pulmonary haemorrhage and glomerulonephritis. However, negative autoimmune antibodies and vasculitis profile along with lung biopsy results indicated an unusual case of malignant lung adenocarcinoma presented with pulmonary renal syndrome. Conclusion(s): In cases suggesting pulmonary-renal syndromes, if autoimmune work up is negative and response is suboptimal relook the diagnosis.

Evaluation of PCR Negativity in Respiratory Specimens of COVID-19 Patients After Hydroxychloroquine and/or Favipiravir Treatment

Objective: We evaluated PCR negativity in oropharyngeal and nasopharyngeal secretions of COVID-19 patients at the end of hydroxychloroquine and/or favipiravir treatments. Method(s): Study inclusion criteria were being hospitalized, being older than 18 years, PCR positivity in oropharyngeal and nasopharyngeal secretions and being tested for SARS CoV-2-RNA PCR after treatment. Initially hydroxychloroquine treatment (group 1) was administered to the patients according to COVID-19 guide of Health Ministry. Favipiravir (group 2) alone or in combination with hydroxychloroquine (group 3) was administered to patients who were unre-sponsive to hydroxychloroquine or had severe pneumonia or were admitted to intensive care unit. Control respiratory specimens were taken no earlier than 24 hours, after the end of therapy. Repeated tests with 24-48-hour intervals were performed in patients with still positive PCR test results. The detection of SARS CoV-2-RNA was made by real-time PCR. Result(s): The study group included 492 patients who received treatment. Mean duration of symptoms was similar among three groups. PCR negativity rate was 52.8% in the specimens taken 24 hours after the end of treatment. PCR negativity rates was 27.9% (200/492) in 48 hours after the end of treatment, %13.8 (123/492) in 72nd hour and %3.8 (80/492) in 96th hour. The ratios of PCR negativity for all specimen days were similar in three groups. There was no statistically significant difference between the groups for time to PCR negativity from the date of positivity and after the end of treatment. We determined that early or late treatment did not make a difference in terms PCR negativity time. Conclusion(s): No difference was found in terms of the ratios of PCR negativity or time for negativity in oropharyngeal and/or nasopharyngeal specimens taken after the end of treatment in COVID-19 patients receiving hydroxychloro-quine and/or favipiravir treatment. Copyright © 2022, DOC Design and Informatics Co. Ltd.. All rights reserved.

Medication Use Evaluation of Ketamine for Sedation and Analgesia in Mechanically Ventilated Patients

INTRODUCTION: Ketamine, an NMDA receptor antagonist and mu/kappa opioid agonist, may be used for its anesthetic and analgesic properties as an alternative for sedation and analgesia in mechanically ventilated patients. Currently, there is limited literature evaluating the utilization of ketamine in critically ill patients. This study compared the efficacy and safety of ketamine as an adjunctive agent for sedation and analgesia compared to a non-ketamine cohort. METHOD(S): This was a multi-center, retrospective analysis of patients receiving ketamine as an adjunctive agent for sedation and analgesia compared to standard of care. Mechanically ventilated adult patients who received at least two continuous infusion sedative or analgesic agents from May 2020 to May 2021 were included. Patients receiving ketamine infusion as an adjunctive agent for at least six hours were included in the comparator group. The primary outcome evaluated was 28-day ventilator-free days. Secondary outcomes included impact on sedation and analgesic requirements, incidence of tachyarrhythmias, and increased secretions. RESULT(S): A total of 107 patients met criteria for inclusion, of which 54 received ketamine and 53 received nonketamine-based sedation. A COVID-19 diagnosis was present in 40 patients (74%) in the ketamine group and 14 (26%) in the non-ketamine group (p< 0.001). Ketamine was used less often in patients with history of head trauma (3 [5%] vs. 11 [21%];p=0.02), cirrhosis (0 [0%] vs. 7 [13%];p=0.006), and elevated intracranial pressure (0 [0%] vs. 5 [9%];p=0.03). Patients receiving ketamine had significantly fewer 28-day ventilator-free days (median 0 [0, 11] vs. 8 [0, 11] days;p=0.047). Patients receiving ketamine utilized greater median daily fentanyl doses (112 [65, 146] mcg/ kg vs. 30 [15, 59] mcg/kg;p< 0.001) and midazolam doses (70 [0, 171] mg vs. 0 [0, 59] mg;p< 0.001), but used no difference in propofol doses (19296 [0, 40387] mcg/kg vs. 24761 [12702, 41682] mcg/kg;p=0.1). There was no difference found in other outcomes evaluated. CONCLUSION(S): Addition of ketamine for sedation was chosen in select patient populations such as patients with COVID-19. Patients receiving ketamine had fewer 28-day ventilator-free days, potentially indicative of their presenting problem.

Pulmonary Hemorrhage Due to Granulomatosis with Polyangiitis in a Pediatric Patient

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a rare rheumatologic disease in pediatric patients but with a similar presentation and organ involvement as an adult patient. We present a case of a patient with pulmonary hemorrhage due to GPA who was managed without extracorporeal life support. DESCRIPTION: A 14 year-old female with no medical history presented with migratory polyarthritis, sore throat, chest tightness, fatigue, and positive rheumatoid factor. Found to be hypoxic on presentation. Her respiratory failure progressed, requiring intubation and inhaled nitric oxide, with minimal improvement. A chest CT showed nonspecific bilateral multifocal, patchy airspace opacification. Her C-ANCA and proteinase 3 antibody were positive, making GPA the most likely diagnosis for which she was started on methylprednisolone and rituximab. Her hypoxemia continued to worsen despite maximal mechanical ventilator support and neuromuscular blockade infusion. She had bloody secretions from her endotracheal tube, concerning for pulmonary hemorrhage, despite high positive end-expiratory pressure. A chest radiograph at that time was consistent with worsening bilateral infiltrates. Echocardiogram showed normal biventricular function, pulmonary hypertension, and a 1.8 cm by 1.5 cm thrombus at the cavoatrial junction. A multidisciplinary team determined that the location of the clot precluded placement of ECMO cannulas without risking clot mobilization. Plasmapheresis was emergently initiated followed by further rituximab and cyclophosphamide. Her respiratory status stabilized after being placed in the prone position. She was ultimately discharged home after a prolonged period of intubation and hospitalization, on a steroid taper, oral anticoagulation for her cavoatrial thrombus, and maintenance rituximab therapy. DISCUSSION: This case highlights a rare case of GPA with multiorgan involvement in a pediatric patient resulting in refractory hypoxemia treated with aggressive rheumatologic therapy and proning. There is limited evidence for the efficacy of plasmapheresis in patients with GPA, although this patient may have benefited from it since she was not safe for extracorporeal life support. Furthermore, as highlighted through the COVID-19 pandemic, proning proved crucial in managing her severe hypoxemia.

Antiviral Drugs for the Treatment of Covid-19 Patients: Applications of Drug Monitoring

In the last years, several studies on new and/or repurposing antiviral drugs were initiated to fight Coronavirus disease 2019 (COVID-19) pandemic. Three antivirals have so far been authorised in Italy for the treatment of COVID-19 in adults who do not need supplemental oxygen and who are at high risk of progressing to severe COVID-19. Specifically, the drugs currently authorized are Remdesivir (intravenous route) and the orally administered Molnupiravir and Nirmatrelvir-Ritonavir (Paxlovid). Remdesivir is a prodrug of the nucleotide analogue (GS-441524) which inhibits the SARS-CoV-2 RNA-dependent RNA polymerase. Remdesivir has been shown to improve the COVID-19 outcome in different settings. Molnupiravir is a prodrug that after entering in the cells changes into an active form of triphosphate, ready to be incorporated into viral genome causing many errors in SARS-CoV-2 RNA. In a clinical trial, Molnupiravir compared to placebo showed a 30% reduction of COVID-19-related hospitalizations. Paxlovid is a combination of Nirmatrelvir and Ritonavir. Nirmatrelvir acts by inhibiting protease enzyme, essential step to transform some viral proteins into their final functional form. The relative risk reduction of hospitalization or all-cause death at day 28 for Paxlovid compared to placebo was 88%. To guarantee safe and effectiveness of the pharmacological therapies, the evaluation of patient's pharmacokinetics (PK) profile is mandatory. Therefore, the monitoring of drug concentration of antivirals against SARS-CoV2 could be pivotal to optimise drug regimens, increase efficacy and avoid drug-related toxicity and to evaluate intra-individual variability and drug-drug interactions. Actually, few data on antiviral drugs concentrations in COVID-19 subjects are published. Among them, the most interesting are the following: i) Remdesivir and its main metabolite showed high PK interpatient variability due to both age and renal function in COVID-19 inpatients. The PK variability may have a potential effect in determining the efficacy of Remdesivir administration in patients affected by COVID-19. ii) Molnupiravir metabolite penetration into upper airways and mucosal secretions was demostred. These data could support the use of molnupiravir in a prophylaxis for SARS-CoV-2 infection iii) Nirmatrelvir displays a short half-life, which could result in suboptimal drug exposure and difficulties in achieving efficacy. Therefore, there is the need to use ritonavir (CYP3A4 Inhibitor) to slow down the metabolism and to increase the plasma concentrations of Nirmetrelvir. Drug-drug interactions are expected when drugs metabolized by CYP3A4 are co-administered with Paxlovid. Further research on antiviral drugs concentrations in COVID-19 patients could help to define therapeutic strategies more efficient and appropriate to treat SARSCoV-2 infection.

Mechanisms by which cystic fibrosis transmembrane conductance regulator may influence SARS-CoV-2 infection

Background: People with cystic fibrosis (PwCF) have chronic, pronounced respiratory damage and have been considered among those at highest risk for serious harm from SARS-CoV-2. Numerous clinical studies have reported that individuals with CF in North America and Europe, although highly susceptible to COVID-19, do not have mortality levels that exceed those of the general population. Method(s): To understand features that might influence lethality of COVID- 19 in PwCF, we tested potential relationships between CFTR and viral pathogenesis. As one approach to evaluate impact of CF transmembrane conductance regulator (CFTR) on COVID-19 severity, independent sets of blood samples fromvirally infected individualswere genotyped. Bloodwas obtained from 424 U.S. patients hospitalized with severe COVID-19 and a much larger European cohort of 7147 healthy individuals and 2587 individuals with severe COVID-19. Deoxyribonucleic acid in both studies was probed for the F508del variant. In other experiments, we investigated the possibility that lack of CFTR might alter viral binding and propagation. We used human bronchial epithelial cell (HBEC) monolayers from individuals without functional CFTR for this purpose. Finally, we examined effects of CF airway secretions and features such as viscosity, pH, and protease/anti-protease imbalance during SARS-CoV-2 infection. Result(s): We found no evidence of a relationship between deficient CFTR function (based on carrier status for the severe F508del defect) and clinical outcomes from COVID-19. In addition, viral propagation studies using airway epithelial monolayers (a model that reproduces many aspects of in vivo tissue biology) were not influenced by homozygous absence of CFTR. We show that levels of angiotensin converting enzyme-2 receptor messenger ribonucleic acid (mRNA) appear normal in CF primary epithelium, whereas transmembrane serine protease 2 mRNA is variable but lower ( p < 0.001) in a manner that correlates with viral infectivity (R2 = 0.76). Dependence of viral proliferation on features of CF mucosal fluid-including pH (viral replication optimum at pH 7-7.5), viscosity (diminished propagation in highly viscous apical media), and protease/ anti-protease imbalancewere identified as likely contributors to efficiency of SARS-CoV-2 replication and pathogenesis. Conclusion(s): These findings using patient data, CF and non-CF primary airway epithelia, and CF airway secretions fail to demonstrate a causal relationship between loss of CFTR and susceptibility to severe COVID-19. Notwithstanding the caveat that addition of virus in small buffer volumes disrupts airway surface liquid depth and composition, our findings also argue against a role for CFTR during acute infection of airway cells in vitro. On the other hand, chronic disruption of periciliary liquid, diminished pH, altered protease/anti-protease homeostasis, and increased fluid viscosity (sequelae that occur in CF lungs) were implicated as contributors to impaired SARS-CoV-2 propagation. Such studies provide a basis for future work to test relationships between CFTR and severity of COVID-19. Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Organ Transplantation from Donors with Active SARS-CoV-2 Infection: The Italian Experience

Purpose: In the present study we want to report safety and outcome of organ transplantation from donors with active SARS-CoV-2 infection in Italy. Method(s): In November 2020 the Italian CNT allowed the use of hearts and livers from asymptomatic donors with incidentally discovered active SARS-CoV-2 infection. Organ could be offered to candidates with asymptomatic or resolved COVID-19 or with a full COVID-19 vaccination (3 doses with documented seroconversion) and to Kidney transplant candidates with resolved COVID-19 or with a full course of anti-COVID-19 vaccination. After transplantation all recipients underwent SARS-CoV-2 RNA detection on respiratory secretions on a weekly basis for up to 4 weeks after transplantation. Result(s): From November 21, 2020 to January 23, 2022 we have performed 44 solid organ transplants (33 livers, including 3 split, 5 hearts and 6 kidneys), in 34 males, and 10 females, mean age 49.5 years, range 0-70), from 32 donors (18 males, mean age 47.9, range 14-82) with active SARS-CoV-2 infection and cause of death unrelated to COVID-19. None of the recipients developed a donor derived SARS-CoV-2 infection. Conclusion(s): We believe that the use of non-lung organs from donors with active SARS-CoV-2 infection in selected and consented recipients may contribute to safely increase the donors pool.

"Tranq dope" in infancy: A 19- day-old with life-threatening poisoning due to fentanyl/xylazine

Background: More and more, young children are victims of the ongoing epidemic of opioid use disorder. Xylazine, an alpha-2 adrenergic agonist with notorious use as a veterinary tranquilizer, is an increasingly encountered component of the illicit opioid supply in the US, but has been rarely documented in biological samples obtained from children. We report a 19-day-old infant with classic manifestations of central nervous system and respiratory depression associated with fentanyl and xylazine poisoning. Case report: A 19-day-old boy was taken to the emergency department (ED) by his parents for episodes of straining, breathholding, and his eyes rolling backwards. The formula-fed boy was born of an uncomplicated full-term spontaneous vaginal delivery and had previously been thriving. During ED triage assessment he had a period of apnea, then bradypnea, with pulse-oximetric oxygen saturation drop to 55%. He was supported with stimulation and supplemental oxygen via nonrebreather mask but remained lethargic, with temperature 96F, heart rate 166/min, and brisk capillary refill. Point of care blood dextrose testing was 88mg/dL. Analysis of respiratory secretions for common viruses by polymerase chain reaction was negative for respiratory syncytial virus, influenza, or SARS-CoV-2. Computed tomography imaging of the brain was unremarkable. A urine drug immunoassay (Vitros 4600 Chemistry , Ortho- Clinical Diagnostics) resulted positive for fentanyl (cutoff 1 ng/ mL), but negative for amphetamine, barbiturate, benzodiazepine, cannabinoids, cocaine, heroin, morphine, buprenorphine, methadone, or oxycodone. Liquid chromatography tandem mass spectroscopy analysis of the urine confirmed the presence of fentanyl (25 ng/mL) and norfentanyl (245 ng/mL). Gas chromatography with mass spectrometry also detected the presence of xylazine (qualitative result based on spectra matching). Over the ensuing hours the boy recovered fully and the family was connected with child protection services;an exposure route was not identified. Discussion(s): This 19-day-old infant suffered fentanyl/xylazine poisoning. The infant's age and urine fentanyl concentrations exclude pre-natal exposure as an explanation for the drug test findings, and the baby was bottle-fed excluding drug transmission through breast milk. Xylazine has been known to be in this hospital's regional heroin supply since the early 2000s, and in 2019 xylazine was implicated in more than 31% of opioid-associated deaths at the city's medical examiner's office. In 2022, many fentanyl samples tested by regional law enforcement find more xylazine than fentanyl. Until recently, xylazine was an uncommon finding in our testing of pediatric opioid poisoning victims. Similar to fentanyl, xylazine may cause pupillary miosis and CNS depression;unfortunately it may be resistant to reversal with naloxone. Conclusion(s): This case is remarkable for the young age of this infant ill from post-natal fentanyl poisoning and for the detection of xylazine in his urine. Healthcare providers may not immediately consider opioid poisoning in the differential diagnosis of infants with altered mental status, and proper toxicological testing is important for appropriate child protection support. Detection of xylazine is a marker for a non-medical, or "street," source of fentanyl.

POST-COVID-19 CHANGES MASKED A MALIGNANCY: INVASIVE MUCINOUS ADENOCARCINOMA

SESSION TITLE: Challenges in Lung Tumors SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Patients can have a variety of post Coronovirus induced disease (COVID) associated interstitial lung diseases (ILD) ranging from cystic lung disease to fibrinous organizing pneumonia. However, very little is known about malignancies that have been overshadowed by post COVID associated pulmonary changes. We present one such case of insidious invasive mucinous adenocarcinoma of the lung that was masked by post COVID related changes. CASE PRESENTATION: A 70 year old female with COPD, systolic heart failure and significant tobacco use disorder presented with progressively worsening hypoxemic respiratory failure. She has had 4 hospitalizations in past year all for acute on chronic hypoxemic respiratory failure following COVID. She has been on Supplemental Oxygen 3L/min since her infection with SARS-COV2. Patient was found to have worsening bibasilar ground glass opacities (GGO) on CT of chest over the past 1 year since having COVID. She was treated with several rounds of steroids without any relief. Patient had a PET scan that showed a very avid left upper lobe consolidation. Given these worsening abnormalities and symptoms, she underwent bronchoscopy with transbronchial biopsy guided by the positive PET scan and fluoroscopy. However, during bronchoscopy she had copious secretions which were therapeutically cleared helping relieve some of patient's hypoxemia. All her cultures and Fungitell assay on bronchoalveolar lavage were negative. However, post biopsy pathology came back positive for Invasive Mucinous Adenocarcinoma. Patient was treated with chemo and radiation therapy with good response against her malignancy and significant relief in her hypoxemia. DISCUSSION: COVID associated pneumonia is well known to cause chronic hypoxemic respiratory failure. Post COVID related pulmonary changes range from organizing pneumonia to fungal pneumonia. However, patients should start to recover with time as inflammatory changes resolve on CT scan with adequate steroids or anti-fungals. If patients continue to deteriorate then a prompt work-up that rules out other infections and even malignancies is warranted as seen in our patient. This case brings forth an important consideration for aggressively pursuing an adequate work-up in the face of worsening GGO on the CT and patient's continual deterioration due to her hypoxemic respiratory failure. Our patient was able to be adequately diagnosed with malignancy and was then started on chemotherapy that allowed for adequate control of her hypoxemic respiratory failure and helped improve her quality of life. CONCLUSIONS: Post COVID related pulmonary changes can be from a variety of ILD and infections. However, clinician should be vigilant in considering malignancy as a possible etiology of post COVID related changes and initiate an adequate work-up to help evaluate for cancer that can be masked amongst post COVID related ILD. Reference #1: Beck KS, Sung YE, Lee KY, Han DH. Invasive mucinous adenocarcinoma of the lung: Serial CT findings, clinical features, and treatment and survival outcomes. Thorac Cancer. 2020 Dec;11(12):3463-3472. doi: 10.1111/1759-7714.13674. Epub 2020 Oct 5. Reference #2: Matsui T, Sakakura N, Koyama S, Nakanishi K, Sasaki E, Kato S, Hosoda W, Murakami Y, Kuroda H, Yatabe Y. Comparison of Surgical Outcomes Between Invasive Mucinous and Non-Mucinous Lung Adenocarcinoma. Ann Thorac Surg. 2020 Nov 24:S0003-4975(20)32001-4. doi: 10.1016/j.athoracsur.2020.09.042. Epub ahead of print. Reference #3: Lee MA, Kang J, Lee HY, Kim W, Shon I, Hwang NY, Kim HK, Choi YS, Kim J, Zo JI, Shim YM. Spread through air spaces (STAS) in invasive mucinous adenocarcinoma of the lung: Incidence, prognostic impact, and prediction based on clinicoradiologic factors. Thorac Cancer. 2020 Nov;11(11):3145-3154. doi: 10.1111/1759-7714.13632. Epub 2020 Sep 25. DISCLOSURES: No relevant relationships by Danya Ahmed No relevant relationships by David Chambers No rele ant relationships by Jalal Damani No relevant relationships by Deon Ford No relevant relationships by Rachaita Lakra

A TALE OF A DRUG THAT KILLED A BUG BUT CAUSED PNEUMONIA: A CASE REPORT OF DAPTOMYCIN-INDUCED ACUTE EOSINOPHILIC PNEUMONIA

SESSION TITLE: Critical Diffuse Lung Disease Cases 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Acute eosinophilic pneumonia (AEP) is dramatic in presentation mimicking infectious pneumonia or acute respiratory distress syndrome in previously healthy individuals. Medications are a commonly recognized cause of AEP. Daptomycin, has been strongly linked to AEP. Herein, we present a case of a patient with a septic joint treated with Daptomycin who went on to develop AEP. CASE PRESENTATION: Patient is an 80 year old man with history of hypertension, hypothyroidism, atrial flutter, complete heart block status post pacemaker, who had a hx of a mucinous cyst on his left index finger, requiring hospitalization. Blood cultures were positive for MRSA s/p debridement of the joint. He was discharged on 4 weeks of intravenous daptomycin. Two weeks after being discharged he presented back to the hospital with fevers, fatigue and worsening shortness of breath. His temperature was 103.8 and O2 saturation of 90% on 2L NC. Laboratory findings included WBC count of 8.6 with no eosinophilia on differential, ESR 110, negative blood cultures, sputum cultures with commensal flora, negative urine legionella, PCR for SARS COV-2 was negative. Chest radiograph showed mild interstitial airspace disease in the left mid and lower thorax, along with small bilateral pleural effusions. CT chest showed scattered bilateral consolidations and ground glass opacities and trace bilateral effusions. Daptomycin was switched to Vancomycin. Patients oxygen requirements had increased to 6l NC. Patient underwent airway exam with bronchoscopy and broncheoalveolar lavage in superior segment of the lingula, which showed inflamed bronchial mucosa with copious secretions. Cell count of the BAL showed increased eosinophil count with negative gram stain and culture. Patient was started on methylprednisolone 60 mg four times per day and then tapered. Vancomycin was switched to oral linezolid. Patient's hypoxia improved and was discharged home on 3l NC. At four week follow up, he no longer required oxygen on ambulation and chest radiograph showed complete resolution of infiltrates. DISCUSSION: Over 140 drugs have been recognized as a cause of drug induced eosinophilic pneumonia (DIEP). The diagnosis of DIEP requires febrile illness <5 days, diffuse bilateral infiltrates, hypoxemia and BAL showing 25% eosinophils or eosinophilic pneumonitis on lung biopsy. Additionally, a diagnosis of DIEP requires exposure to a candidate drug in the appropriate time frame, exclusion of infectious causes of eosinophilic pulmonary opacities. It also requires clinical improvement after cessation of medication. Daptomycin has been strongly linked to DIEP. In 2010 US FDA issued a warning about the risk of developing eosinophilic pneumonia during treatment with Daptomycin. CONCLUSIONS: Daptomycin is strongly linked with DIEP. Clinicians should maintain a high index of suspicion for DIEP in patient treated with daptomycin who develop respiratory distress. Reference #1: Uppal, P., LaPlante, K.L., Gaitanis, M.M. et al. Daptomycin-induced eosinophilic pneumonia - a systematic review. Antimicrob Resist Infect Control 5, 55 (2016). https://doi.org/10.1186/s13756-016-0158-8 Reference #2: Cottin V. Eosinophilic Lung Diseases. Clin Chest Med. 2016 Sep;37(3):535-56. doi: 10.1016/j.ccm.2016.04.015. Epub 2016 Jun 25. PMID: 27514599. Reference #3: Rosenberg CE, Khoury P. Approach to Eosinophilia Presenting With Pulmonary Symptoms. Chest. 2021 Feb;159(2):507-516. doi: 10.1016/j.chest.2020.09.247. Epub 2020 Sep 28. PMID: 33002503;PMCID: PMC8039005. DISCLOSURES: No relevant relationships by Kamelia Albujoq No relevant relationships by Rajaninder Sharma

BRONCHIAL TREE ULCERATION: BACTERIAL OR FUNGAL

SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: SARS-CoV-2 pandemic has shown rare and varied presentations of known pathology and infectious processes. We discuss the case of a patient developing bronchial tree ulcerations in the backdrop of SARS-CoV-2 and superimposed infections. CASE PRESENTATION: This was a 59-year-old male with past medical history of B-cell lymphoma, diagnosed with SARS-CoV-2 infection. He was admitted with shortness of breath and increased oxygen requirement. In brief, his hospital course included bilevel positive airway pressure noninvasive ventilation along with steroids, baricitinib and therapeutic anticoagulation. His clinical status worsened to severe acute respiratory distress syndrome and he progressed to mechanical ventilation. While on the ventilator he was treated with paralysis and proning. Due to worsening hypoxia and secretions, he underwent bronchoscopy showing copious thick mucoid white patches and secretions in trachea extending to the right and left mainstem bronchi and extensive mucus plugging. Baricitinib was discontinued and he was placed on empiric micafungin, broad spectrum antibiotics while results were pending. He required repeat bronchoscopy for therapeutic suctioning of recurrent copious thick white secretions with mucus plugging. Cultures resulted as aspergillus fumigatus and micafungin was switched to voriconazole. Two weeks later, in an ongoing prolonged intubated state, he developed cuff leak requiring tube exchange and repeat bronchoscopy, which showed development of multiple bilateral ulcerations with central necrosis and sloughing in the right and left bronchial tree. Repeat lab evaluation of the bronchoscopy samples now resulted in growth of nocardia along with aspergillus species. DISCUSSION: Ulceration of bronchial tree may be seen in malignant lesions, autoimmune conditions, poisoning or toxicology cases. Occurrence of pulmonary ulcerations are rare in infectious cases as sequalae in the SARS-CoV-2 pandemic. Patient's immunocompromised state, with history of B-cell lymphoma, prolonged steroid and JAK inhibitor administration, predisposes to higher propensity of infections. Bronchial tree ulceration also leads to suspicion of viral infections such as herpes, varicella which were found to be negative from bronchial samples. It remains difficult to ascertain if the prolonged aspergillus infection led to progression of white plaques into ulcerations, or the newly diagnosed secondary infection of nocardia caused bronchial tree ulcers. Historically, aspergillus has been associated with blackened ulcerations as opposed to the findings here. Also, patient had been receiving treatment with voriconazole for 2 weeks prior to diagnosis of ulcers, therefore raising suspicion for a rare nocardial etiology as well. CONCLUSIONS: Prolonged intubation in immunocompromised patients may lead to superimposed nocardial and aspergillus infections causing airway ulcerations and increased mortality. Reference #1: Judson MA, Sahn SA. Endobronchial lesions in HIV-infected individuals. Chest. 1994;105(5):1314-1323. doi:10.1378/chest.105.5.1314 Reference #2: Abdel-Rahman N, Izhakian S, Wasser WG, Fruchter O, Kramer MR. Endobronchial Enigma: A Clinically Rare Presentation of Nocardia beijingensis in an Immunocompetent Patient [published correction appears in Case Rep Pulmonol. 2016;2016:1950463]. Case Rep Pulmonol. 2015;2015:970548. doi:10.1155/2015/970548 DISCLOSURES: No relevant relationships by Habiba Hussain No relevant relationships by Matthew Sehring