Lung cavitation as a rare complication of severe COVID-19: report of 3 cases

Introduction: Lung cavitation is a rare radiological finding of COVID- 19 pneumonia associated with unfavorable outcome. Its pathogenesis is unclear and it is characterized by diffuse alveolar damage, intra-alveolar hemorrhage and necrosis of parenchymal cells. Method(s): We retrospectively reviewed the radiological findings of COVID-19 patients admitted to our ICU during the pandemic in order to identify the development of lung cavitary lesions. Result(s): From 11/2020 until 10/2022 1000 patients were admitted to our COVID-19 ICU (92% on invasive mechanical ventilation). According to our data there were three cases of lung cavity formation. The first case was a 78 years male with history of hypertension. Chest CT (Day26) showed a 11.6 cm cavity in the right middle lobe (Fig. 1). The second case was a 52 year old female with history of diabetes mellitus, obesity, hypertension and rheumatoid arthritis. Follow up chest CT (D29) revealed progressive development of multiple bilateral cavitary lesions. The third case was a 61 year old male with no medical history, who developed (D17) multiple cavitary lesions in both lower lobes, concomitant with left-sided pulmonary embolism. The presence of other well defined etiologies of cavitary lesions such as mycobacterial and fungal infections as well as neoplasmatic or autoimmune diseases had been widely excluded. However, since pulmonary cavitation is a late complication of severe COVID disease, we cannot overlook the fact that all patients suffered from superinfections by XDR Acinetobacter baumanii and/or Klebsiella pneumonia, as most of our patients with prolonged length of stay. Moreover, two of the three patients developed pneumothorax. All patients finally died. Conclusion(s): Although bacterial co-infection does not allow absolute association between cavitary formation and coronavirus disease, it seems that destructive triggers, such as bacteria or mechanical ventilation, may aggravate COVID underlying lung lesions leading to cavitation.

IDWeek 2022

IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). For the first time since the COVID-19 public health emergency began, IDWeek 2022 returned to in-person attendance. It was held in Washington, D.C., and the meeting comprised 5 days of live sessions and on-demand content that included posters and oral presentations.Copyright © 2023 Clarivate.

Occupational Health Hazard Identification and Risk Assessment with Introduction of Biomass in Coal Based Captive Power Plant

Introduction: Occupational Health should aim at the Promotion and Maintenance of the highest degree of physical, mental, and social well-being of all the employees. A pilot project was taken up due to acute shortages of coal during the COVID Pandemic, on industrial level, mixing of biomass with coal at a ratio of 20:80 respectively was considered as a good raw material. With introduction of biomass, workers were exposed to different organic substances either directly through dermal route or respirable dust with risk of becoming victims to Occupational diseases. Objective(s): The objective of the study is to identify and mitigate occupational health hazard of various nature prevailing at workplace after introduction of new raw materials;to safeguard the workforce from discomfort and occupational illness and to provide healthy working environment at RIL-Hazira. Method(s): Walk through survey was initiated by team of industrial hygienist and medical officer along with the process engineer. Subsequent workplace evaluation was done according to ACGIH screening criteria for respirable dust & VOC monitoring. To measure airborne respirable contaminants, we have considered housekeeping staff, operator, field executive, Boiler operation engineer which were found more likely to be at the risk of airborne contaminant exposure. To identify the concentration of contaminants, personal air sampler (SKC Make) was used for collection of respirable dust samples for different job category of workers. NIOSH 600 method was used for exposure assessment and samples were collected by using PVC filter used at the flow rate of 2.5 lpm. The composition of biomass pellets was received from biomass team & chemical analysis of biomass was done at our laboratory. Occupational Diseases known to be caused by organic agricultural compounds used as fuel were taken into account such as Bagasossis, farmer's lung & other hypersensitivity pneumonias, non-tubercular mycobacterial infections, infections caused by various fungi & bacteria. Prevention & Control measures were taken during the project such as modification of process, local exhaust ventilation, worker education on different diseases, personal hygiene, use of PPE, good housekeeping. Result(s): Through effective Risk assessment, Hazard Identification and measures taken to mitigate Occupational health hazards, no occupational health disease was reported after implementation of the change in process in a total of 55 identified workers. Moving forward these workers will be periodically monitored. The amount of total respirable dust was reduced by approx. 10- 25% at different location of the plant after control measures taken. This project also brought huge monetary benefits to the plant. Leading forward as the pilot project for introduction of biomass was a great success it has been planned to be scaled up to 40% mixture of biomass.

Versatile Use of Mycobacterium indicus pranii (MIP) Vaccine

Mycobacterium indicus pranii (MIP) earlier known as Mw is a soil-borne, non-pathogenic, saprophytic and rapidly growing strain of mycobacteria. MIP is approved as a vaccine/ immunomodulator for various indications including mycobacterium infections like leprosy in humans. Its administration has resulted in satisfactory clinical improvement, accelerated bacillary clearance, and increased immune responses to Mycobacterium leprae antigens, thereby shortening the full recovery time of the patients. It also shares its antigens with M.tuberculosis. In the last decade, RCTs have been done establishing immunotherapeutic properties of MIP in the treatment of leprosy, tuberculosis, warts and experimently in leishmaniasis. Through its immune inducing and cytotoxic property, it has also proved beneficial for human use especially in treating lung cancer. The beneficial role of it is also being explored in breast, cervical, oral, liver, and bladder cancers. Various studies on MIP have shown that it has immune-modulating properties in humans. The curiosity of the human mind has led to it being tried in Covid treatment trials. The results have shown that administering MIP has lowered inflammatory markers in Covid 19 patients, promising us for it to be a potential treatment option. More RCTs with a larger sample size should be done to establish this. Cytokine storm seen in bacterial sepsis is also decreased with MIP administration. Considering the encouraging results in hastening recovery in various diseases it appears that MIP is perhaps not being exploited to its fullest potential. © 2023, Hind Kusht Nivaran Sangh (Indian Leprosy Association). All rights reserved.

Granulomatous Interstitial Nephropathy : When the Kidney Spills the Bean

Introduction: Sarcoidosis is a rare granulomatosis. The absence of well-defined criteria for definition and the existence of differential diagnosis makes the positive diagnosis difficult. Method(s): We report a case of sarcoidosis that illustrates the difficulty of this diagnosis in the presence of atypical clinical manifestations and a strong suspicion of tuberculosis. Ultimately, renal histology allowed the positive diagnosis and the response to corticosteroids confirmed it retrospectively. Result(s): Our patient was a 66 years-old female with a history of hypertension who presented with a sensory and motor polyneuropathy a couple of months after a mild COVID-19 pneumonia, hospitalized for exploration of a worsening renal function due to a tubulointerstitial neuropathy (creatinine upon admission at 250 micromol/l, eGFR = 16 ml/min/1,73m2 -MDRD). Kidney biopsy revealed an interstitial infiltrate of monocytes and fibrosis alongside non-necrotic and giant-cell epithelioid interstitial granulomas. Extra-renal signs consisted of the above-mentioned neuropathy, bilateral mediastinal adenopathies with no signs of a pulmonary disease at the bodyscan, a hepatomegaly, splenomegaly, a pleural and pericardial effusion of low abundance, and a peritoneal thickening. Bronchoscopy and bronchoalveolar washing found no evidence for malignancies and screening for mycobacterial infections by polymerase chain reaction was negative. No granulomas were found at the hepatic biopsy. Digestive tract endoscopy and biopsies showed no abnormalities. During hospitalization, the patient presented an episode of acute polyradiculonevritis confirmed by cerebral-spine fluid study and nerve conduction study results. Our patient received intraveinous immunoglobulins (IgIV) with a favorable outcome but relapsed one month later, showing signs of respiratory failure. Upon the second relapse of the chronic polyradiculonevritis and based on the absence of bacteriological and histological evidence for a mycobacterial infection and the results or the renal biopsy, the patient received high-dose corticosteroids alongside a second course of IgIV. The neuropathy regressed totally within a month with a decrease of creatinine level to 140 micromol/l (eGFR = 35ml/min/1,73m2) alongside the polyserositis and organomegaly. The final diagnosis was that of a sarcoidosis with pulmonary and renal involvement. Although the neuropathy could be considered a manifestation of sarcoidosis, its origin was intricated as post-viral original could not be formally excluded. Conclusion(s): The etiological diagnosis for granulomatous interstitial nephropathies can be challenging due to similar clinical presentations and the need to start specific treatments especially in the presence of life-threatening situations and the absence of clear criteria defining sarcoidosis further enhances the level of difficulty. No conflict of interestCopyright © 2023

Tsukamurella and mycobacterium tuberculosis pneumonia co-infection

Case Report: Tsukamurella species are aerobic, partially acid fast saprophytes commonly isolated from soil and water. They are opportunistic pathogens known to infect multiple organs and can contribute to significant pathologies such as bacteremia, peritonitis, and respiratory tract infections. Moreover, Tsukamurella shares certain characteristic properties to Mycobacterium tuberculosis and Actinomyces species, including the acid fast stain, which can contribute to misdiagnosis of patients. A 68 year old female patient presented to the ED for shortness of breath, fatigue, and weight loss for 6 months. The patient's past medical history includes pulmonary fibrosis, type 2 diabetes, coronary artery disease with stent, hyperlipidemia, hypertension, and M. tuberculosis infection when she was 3 years old in Finland. On admission, labs revealed thrombocytosis (reactive 555 000/microL), leukocytosis (14 450/microL), and microcytic anemia (9.4 microg/dl). Moreover, C reactive protein was elevated and procalcitonin was normal (0.06 microg/l);a COVID-19 PCR was negative. An X-ray revealed severe patchy and interstitial infiltrates throughout both lungs with parenchymal scarring and pleural thickening in the periphery of the left mid-lung zone with multifocal pneumonia. Blood and sputum cultures were performed under the impression of pneumonia, and treatment with azithromycin and ceftriaxone was started. A M. tuberculosis infection was suspected due to a positive AFS. Further chest CT suggested multifocal pneumonia within the left lung in addition to apparent cavitary lesions versus bulla, a chronic interstitial lung disease with traction bronchiectasis, calcified right lower lung nodule, and calcified hilar lymph nodes suggesting a history of granulomatosis diseases. A bronchoscopy with Bronchoalveolar lavage was performed. The initial sputum specimen direct smear showed acid-fast stain positive with Actinomyces growth, and Penicillin G was added to the treatment. Samples were sent to the state department lab, and biopsy revealed granulomatous inflammation negative for malignant cells. One month later, the patient's sputum culture showed Tsukamurella for High-performance liquid chromatography (HPLC). Moreover, a rifampicin sensible M. tuberculosis complex by NAA was also positive six weeks later. The patient was started on a complete TB regimen and continued in the outpatient pulmonology clinic with the addition of levofloxacin for three months and rifampicin substituted for rifabutin. As demonstrated in the case above, a Tsukamurella infection can present similarly to a Mycobacterium infection. Patients may be misdiagnosed or potentially be co-infected. Our patient was further tested and appropriately treated for Tsukamurella after further extensive diagnostic screenings. Due to a high rate of missed cases, it is important to keep Tsukamurella infection on the differential diagnosis as the patient presentation may initially appear to be a Mycobacterium or other pulmonary infection. Copyright © 2023 Southern Society for Clinical Investigation.

GATA2 deficiency presenting as fever and rash

Case Report: Our patient is an 8-year-old Caucasian female with a history of choanal atresia, first degree heart block, recurrent urinary tract infections, and recent COVID-19 infection, who initially presented with an episode of syncope and vomiting. By history, she had two weeks of daily fever and an intermittent nonspecific rash. She was diagnosed with a UTI 5 days prior to presentation but had not defervesced despite treatment. Shewas initially found to be in shock with tachycardia and poor perfusion and was treated with fluid resuscitation, antipyretics, and empiric antibiotics. Labs were significant for leukopenia, elevated inflammatory markers, lactic acidosis, coagulopathy, and mildly elevated troponin. Chest x-ray showed abnormal but non-specific widespread infiltrates. She was initially treated with IVIG and pulse steroids for a working diagnosis of MIS-C, however she did not improve and a more extensive infectious, oncologic, and rheumatologic work-up was performed. Her workup revealed a disseminated Mycobacterium abscessus infection. Bone marrow biopsy revealed myelodysplasia with monosomy 7. Her buccal swab testing revealed a heterozygous germline mutation in the GATA2 gene, a variant that is predicted to cause loss of normal protein function. She is presently on multidrug regimen for her mycobacterial infection. Her myelodysplasia evolved into an acute leukemia, and she is undergoing chemotherapy for that at this time. Discussion(s): GATA2 deficiency, first identified in 2011, is a rare immune disorder resulting in a wide variety of clinical presentations. It is caused by a germline mutation of the GATA2 gene that disrupts blood cell differentiation, resulting in decreased or absent monocytes, B cells, NK cells, and dendritic cells1. This case presented multiple challenges due to the broad range of differential diagnoses. This patient was ultimately diagnosed with myelodysplastic syndrome associated with monosomy 7 and GATA2 deficiency, confirmed by FISH testing. Due to the presentation and lab derangements this patient had, there was a delay in targeted treatment while managing her cytopenias and presumed pulmonary infection. GATA2 deficiency carries a high risk of progression from myelodysplastic syndrome to acute myelogenous leukemia. The best long-term treatment for GATA2 deficiency is hematopoietic stem cell transplant, which is the ultimate goal for our patient. Copyright © 2023 Southern Society for Clinical Investigation.

Infective Endocarditis Pulmonary Septic Emboli Due to Mrsa in a Patient with Chronic End Stage Kidney Disease on Maintenance Hemodialysis a Case Report and Few Learning Points

BACKGROUND: Small percentage of catheter-related bloodstream infection may present atypically with persistent low-grade fever without chills and rigor and in some of these cases blood culture can be negative. These may lead to diagnostic confusion and delay in detection of the common entity of catheter-related blood stream infections. AIM OF THE STUDY: Case discussion with learning points METHODS: We report a case with multiple pictorial images and discuss differential diagnosis with few learning points. RESULT(S): 42-year-old male patient, a known case of end-stage chronic kidney disease on maintenance hemodialysis through a tunneled catheter, presented with a history of intermittent, low-to-moderate fever for 3 weeks. The fever associated with generalized weakness, night sweats but was not associated with chill and rigor. His past medical history included endstage chronic kidney disease due to chronic glomerulonephritis and was on maintenance hemodialysis thrice weekly for last 6 months through tunneled catheter in right IJV. On physical examination, the patient had tachycardia, normotension with a blood pressure of 120/70.mmHg, normal saturation at room air with respiratory rate of 20 /minute. On auscultation, there was reduced breath sounds on left side and normal heart sounds. The catheter site showed no heat, erythema, swelling, tenderness. Chest radiograph revealed left hydropneumothorax with multiple focal pulmonary nodular opacities. CECT chest showed left loculated hydropneumothorax with multiple cavitary nodules with reverse halo sign (Figures 1 and 2). Lab investigations showed significant leukocytosis with neurophilia, random serum glucose of 250.mg/dL, and D-dimer of 3624.ng/mL. Blood cultures from hemodialysis catheter and contralateral peripheral vein were negative for pathogenic bacteria, mycobacteria, and fungal etiology. Urine analysis was sterile and did not have pus cells. On day 4 of admission, patient had left axillary pain. On clinical examination, there was focal tenderness on examination in the left axilla. On ultrasonography, there was a small collection which was aspirated under ultrasound guidance and showed gram-positive bacteria on microscopy. Trans esophageal echocardiography revealed multiple tiny vegetations on right side of interatrial septum on tricuspid valve (Figure 3). Subsequent culture results showed methicillin resistant staphylococcus sensitive to clindamyin, vancomycin, linezolid, ciprofloxacin (Figure 4 and 5). The patient was started on vancomycin and ceftazidine on empirical basis for microscopic findings, and after subsequent culture revealed methicillin-resistant Staphylococcus aureus, he was treated with vancomycin. Permanent catheter was removed. Hemodialysis was continued through temporary right IJV catheter. Blood cultures were cleared from MRSA on hospital day ten. She got discharged home on intravenous Vancomycin for 6-8 weeks and was reported doing well on follow-up. CONCLUSION(S): The learning points are- 1. MRSA infection is common in chronic kidney disease patient on hemodialysis. 2. Clinical presentation of metastatic MRSA infection with infective endocarditis may be indolent with cardiovascular and respiratory stability with absence of fever spikes, chill, and rigor. 3. Common infective causes of cavitary nodules in lung are typical and atypical mycobacterial infection, fungal infection, and pyogenic septic emboli. 4. Uncommon infective causes of reverse halo sign on CT chest need to be remembered and include bacterial pneumonia, septic embolism, mycobacterial infection, invasive aspergillosis, in addition to common infective etiology of reverse halo sign like mucormycosis infection and COVID19 infection.

Improving mycobacterial sputum culture collection in adult patients during the highly effective modulator therapy era

Background: Taking annual mycobacterial sputum cultures (MSCx) is a best practice standard for surveillance of nontuberculous mycobacterium (NTM) infection. MSCx collection among sputum-producing people with CF (PwCF) is essential for early identification and management of NTM. Initiation of highly effective modulator therapy (HEMT), elexacaftor/ tezacaftor/ivacaftor in 2019, resulted in a reduction in sputum production in PwCF. The concurrent emergence of the COVID-19 pandemic led to a shift from in-person to virtual clinic visits. These two events led to a dramatic decline in the rate of MSCx collection at our center-from 52.7% (2019) to 26.5% (2020) based on our CF Patient Registry report. We used a multidisciplinary approach to evaluate and implement continuous quality improvement (CQI) measures with the aim of increasing MSCx collection from 52.7% to 65% in 12 months. Eligibility was defined as producing 1 mL or more of sputum and no MSCx within the past 12 months. Method(s): The Minnesota CF Center care team consists of multidisciplinary specialties and approximately 450 PwCF. The CQI team generated the aim and developed a process map highlighting key stakeholders and barriers to MSCx collection. The team used a plan-do-study-act (PDSA) model to optimize key steps involved in MSCx collection. The first PDSA model included microbiology lab leadership identifying optimal (5-10 mL) and acceptable (>=1 mL) sputum volumes to avoid rejected specimens. Next, providers approved a new protocol to prioritize first sputum collection for MSCx and subsequent collection for CF bacterial cultures in eligible PwCF. Development of a certified medical assistant flowchart guided determination of eligibility for MSCx collection (Figure 1). Certified medical assistant then used a paper tool to document eligibility, specimen type, and lab orders placed for PwCF in clinic during the 4-week PDSA cycle. The paper tool was adapted using electronic health record (EHR) capabilities to generate date of last MSCx and allow electronic documentation of specimen collection type and orders placed. Result(s):With the use of HEMT, the percentage of sputum-producing PwCF declined from 74% to 40%. Use of process mapping and paper tool identified barriers to collecting MSCx in our clinic. Workflows were established through recurrent PDSA cycles to identify actionable interventions (education of lab personnel, paper tool, EHR documentation), which has led to collection of 53% of eligible samples-up from 26.5% in 2020 and on Figure 1 : Certified medical assistant (CMA) flowchart for mycobacterial sputum culture (MSCx) collection to determine patient eligibility and order placement(Figure Presented) track for 65% MSCx collection for the year. The paper tool revealed that the greatest barrier to obtaining MSCx was lab cancellation. By November, the team will complete another PDSA cycle after further lab education with the aim of decreasing the number of MSCx that the lab erroneously rejects. Conclusion(s): Despite the reduction in sputum production after use of HEMT, approximately 40% of PwCF still produce sufficient sputum for MSCx monitoring. Applying effective CQI tools including process mapping, PDSA cycles, pareto charts, and run charts to implement an improved, standardized workflow can increase the rate of MSCx, which will aid in detection and management of NTM infections and inform the epidemiology of NTM in the era of HEMT Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

ROCK AND ROLL AND LASER IN BETWEEN: BRONCHOSCOPIC LITHOTRIPSY

SESSION TITLE: Case Reports of Procedure Treatments Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Broncholiths are calcifications in the tracheobronchial tree that are most commonly associated with indolent infections. Disease manifestations range from asymptomatic stones in the airway to major complications such as massive hemoptysis or post-obstructive pneumonias. Depending on severity of the disease, patient management can range from conservative strategies to surgical interventions. We report successful reduction of a large obstructive broncholith in the right middle lobe via Holmium-yttrium aluminum garnet (Ho:YAG) laser lithotripsy. CASE PRESENTATION: Patient is a 55 year old male who presented with on going purulent cough, fever and pleuritic chest pain for 3 months. He had associated weight loss (>10 lbs in 3 months), malaise, increased fatigue, and scant hemoptysis. Initial chest x-ray was evident of right middle lobe consolidation. Respiratory infection panel, COVID PCR, AFB cultures and fungal cultures were negative. Subsequent CT of his chest showed right middle lobe opacities with areas of obstruction with a broncholith. Subsequently, patient underwent rigid bronchoscopy to allow for left sided airway protection via direct tamponade if patient develops massive hemoptysis. A bronchoscopic inspection was performed through the rigid scope that confirmed the broncholith. Obliteration of broncholith was then performed via Ho:YAG. After multiple laser treatments, we noted improvement in the size of the broncholith. Patient admitted to significant improvement in chest pain, hemoptysis and cough since the procedure. DISCUSSION: Broncholithiasis refers to calcified material eroding the tracheobronchial tree and causing inflammation and obstruction. Etiology of broncholiths include calcified peribronchiolar lymph nodes that erode into the airway lumen. Lymph node calcifications in the thorax are associated with lymphadenitis from fungal or mycobacterial infections. Management depends on the size of broncholiths. For larger stones, flexible bronchoscopy is often used to confirm diagnosis. When forceps extraction is not feasible, stone fragmentation with Ho:YAG is generally utilized, but they carry the risk of massive hemoptysis or bronchial injury. Surgical interventions, such as lobectomy or pneumonectomy, are reserved for patients with recurrent pneumonias, bronchiectasis, bronchial stenosis or broncho-esophageal or aorto-tracheal fistulas. In our case, we demonstrate successful reduction of a non-mobile broncholith by protecting the airway using rigid bronchoscopy by interventional pulmonology and subsequently avoiding surgical intervention in a patient with repeated post-obstructive pneumonia. CONCLUSIONS: Management of broncholiths should be individualized for symptomatic patients. A comprehensive assessment with appropriate imaging and involvement of interventional pulmonology can result in successful reduction of the stone and minimizing complications. Reference #1: Dakkak, M., Siddiqi, F., & Cury, J. D. (2015). Broncholithiasis presenting as bronchiectasis and recurrent pneumonias. Case Reports, 2015, bcr2014209035. Reference #2: Krishnan, S., Kniese, C. M., Mankins, M., Heitkamp, D. E., Sheski, F. D., & Kesler, K. A. (2018).Management of broncholithiasis. Journal of thoracic disease, 10(Suppl 28), S3419. Reference #3: Olson, E. J., Utz, J. P., & Prakash, U. B. (1999). Therapeutic bronchoscopy in broncholithiasis. American journal of respiratory and critical care medicine, 160(3), 766-770 DISCLOSURES: No relevant relationships by Jalal Damani No relevant relationships by Joseph Gatuz No relevant relationships by Fereshteh (Angel) Yazdi

TB REACTIVATION FOLLOWING COVID-19 INFECTION

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: The COVID-19 pandemic has been full of obstacles for the medical field. Considerable advancements have been made, yet we continue to discover new associations with this novel virus. In this case, we discuss a patient who was hospitalized for COVID-19 on 7/18/2020 in the intensive care unit. He developed a persistent cough with hemoptysis several months after discharge and was found to have active tuberculosis. The COVID-19 pandemic has continued to raise concerns regarding the repercussions of this infection, and as this case shows, includes reactivation of latent tuberculosis infections (LTBI) in affected patients. CASE PRESENTATION: A 59-year-old Latino male never-smoker with a history of diabetes (A1c 8.4%) presented 07/18/2020 for complaints of shortness of breath and cough. At that time, he tested positive for COVID-19. He was escalated to the ICU and required intubation. During his hospitalization, he received remdesivir for 5 days and dexamethasone 6 mg daily for 10 days with taper prior to his discharge. He was able to be extubated and oxygen requirement decreased to 2 liters nasal cannula. Patient was subsequently discharged on 09/14/2020. He began developing a persistent cough with noted hemoptysis in 02/2021 and was referred to pulmonology at that time. High resolution CT scan of the chest was ordered and revealed thick-walled cavitary lesions of various sizes throughout both lungs although with an upper lobe predominance and tree-in-bud nodularity as well as tracheomegaly. AFB and QuantiFERON Gold assay were positive. Patient reported he had done multiple mission trips to endemic areas before COVID pandemic but had not been during the pandemic. Patient underwent quarantine and treatment for active tuberculosis. DISCUSSION: Tuberculosis reactivation results from previous latent bacteria that becomes active either from inducible factors or spontaneously. Risk factors for reactivation include HIV/AIDS, steroid use, diabetes, kidney disease, and smoking. [1] The primary basis of these risk factors is the immunosuppression conferred to the patient. COVID-19 has the potential to cause a disruption of the immune system which could predispose a patient to reactivation of LTBI. Studies have shown that defects or interference of the IFN-γ pathway can cause susceptibility to intracellular infections, including tuberculosis.[2] There may be an acquired disruption in this pathway caused by COVID-19, although more research is required. CONCLUSIONS: The COVID-19 pandemic has raised concerns for increased risk of reactivation of latent infection as well. In this case, the patient had multiple risk factors, but certainly a diagnosis of COVID-19 could weaken the immune system allowing for the reactivation of LTBI. This association will require more research to solidify. It is important, as seen in the case discussed above, to continue to be vigilant in diagnosis and treatment of our patients. Reference #1: Riley L. UpToDate. UpToDate – Evidence-based Clinical Decision Support ;Wolters Kluwer. Published September 15, 2021. Accessed February 2, 2022. https://www.uptodate.com/contents/tuberculosis-natural-history-microbiology-and-pathogenesis?search=tuberculosis&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4 Reference #2: Kampmann B, Hemingway C, Stephens A, et al. Acquired predisposition to mycobacterial disease due to autoantibodies to IFN-gamma. J Clin Invest 115: 2480-2488, 2005. DISCLOSURES: No relevant relationships by Steven Colby No relevant relationships by Radhika Shah

MANAGEMENT OF RELAPSED / REFRACTORY (R/R) B-CELL NON HODGKIN LYMPHOMA (B-NHL) WITH ANTI-CD20XCD3 BISPECIFIC ANTIBODY GLOFITAMAB. A SINGLE CENTER EXPERIENCE

Background: Prognosis of r/r B-NHL is detrimental. Potentially curative therapeutic approaches, such as autologous stem cell transplantation and innovative CAR-T cell therapy, require maximum disease control to achieve optimal results. Glofitamab is a new bispecific antibody, with a unique 2:1 molecular configuration resulting in superior potency compared with other CD20xCD3 bispecific antibodies with a 1:1 format. Aims: Based on these encouraging results, we included 5 heavily pretreated patients in the early access program of Glofitamab, available in our country. Methods: We collected the data of 5 consecutive patients with r/r B-NHL, who were treated with Glofitamab in our department during the last 15 months. Results: Three men and 2 women, median age of 57 years (38-62), were resistant to 4 (n = 3) and 5 (n = 2) previous lines of treatment. The underlying lymphoma was Richter's transformation of CLL after allogeneic transplantation (alloHSCT), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), r/r diffuse large B-cell lymphoma (DLBCL) after CAR-T therapy and gray zone lymphoma (GZL) transformed to DLBCL. The median number of Glofitamab cycles administered was 3 (2-7). All 5 patients responded early to treatment, which became apparent immediately after the first dose of 2.5 mg. The patient with Richter's syndrome achieved metabolic remission after the 4th cycle and underwent second alloHSCT after the 7th cycle. Unfortunately, he passed away 8 months after alloHSCT due to disseminated atypical mycobacterial infection, remaining however disease free. The patient with tFL also achieved metabolic remission, but the drug was discontinued after the 7th cycle due to COVID-19 infection. He died two months after Glofitamab interruption due to disease progression and CMV encephalitis. The patient with PMBCL, responded partially after Glofitamab and had mediastinal radiotherapy as bridging therapy to CAR-T therapy. As the latter was delayed due to CMV reactivation and CMV enteritis, our patient deceased due to progressive disease. The patient with DLBCL after CAR-T therapy had initial clinical response after two Glofitamab cycles. Due to severe COVID-19, we decided to hold Glofitamab. COVID-19 and disease progression led to his death, a few weeks after COVID-19 diagnosis. Finally, the patient with transformed GZL had Glofitamab administered as bridging therapy prior to CAR-T treatment. After 3 cycles, while she was prepared to proceed to CAR-T therapy, she was diagnosed with invasive aspergillosis. She is currently been treated with antifungal agents, whereas disease is still active. Cytokine release syndrome (CRS) occurred in 3 out of 5 patients. In all cases it was grade 1-2 and manifested at the first administration of the drug, after 4, 32 and 10 hours respectively, from infusion initiation. CRS was managed with antipyretics and steroids, whereas none patient required Intensive Care Unit support. Only one patient required tocilizumab. No Immune effector cell-Associated Neurotoxicity Syndrome (ICANS) was observed. Summary/Conclusion: Glofitamab is effective in treating patients with r/r aggressive B-cell NHL. Efficacy makes it an appropriate bridging tool to autologous, alloHSCT or CAR-T therapy. Nevertheless, relapse remains a challenge for r/r disease. Adverse events, such as CRS, were generally manageable. Given the fact that it was administered to heavily pretreated patients, caution to opportunistic pathogens should be paid. Indeed, toxicity profile may be proven to be more favorable if the agent is being administered earlier in therapeutic algorithms.

ADULT-ONSET STILL'S DISEASE AND MACROPHAGE ACTIVATION SYNDROME FOLLOWING COVID-19 PNEUMONIA

CASE: A 41-year-old woman with recent COVID-19 pneumonia presented to the hospital with several months of fever, polyarthralgia, and weight loss. She reported waxing and waning shoulder, elbow, wrist, hip, knee, and ankle pain without identifiable triggers. She had no pertinent medical or family history. Vital signs were only notable for fever of 40C which recurred daily. Exam revealed tenderness to palpation of multiple joints;her skin had no rash, purpura, or nodules. Hepatosplenomegaly and axillary lymphadenopathy were noted. Infectious workup was negative for bacterial, viral, fungal, mycobacterial, parasitic, and protozoal infections. Initial studies demonstrated hemoglobin 8.2 mg/dL, lymphopenia, and aspartate transaminase 58 U/L. Flow cytometry, excisional lymph node biopsy, and bone marrow biopsy were negative for lymphoproliferative disease. Rheumatologic workup revealed elevated ferritin, triglycerides, Interleukin-6, soluble Interleukin-2 receptor (sIL-2R), and “C-X-C Motif Chemokine Ligand 9” (CXCL9);extensive rheumatologic serologies were otherwise negative. Her clinical picture was consistent with Macrophage Activation Syndrome (MAS). She also met diagnostic criteria for Adult-Onset Still's Disease (AOSD) given arthralgia, fever, lymphadenopathy, splenomegaly, abnormal liver function test (LFT), and otherwise negative workup. Her presentation suggested COVID-19 triggered AOSD which triggered MAS. We administered intravenous immune globulin (IVIG) and high-dose steroids. She clinically improved and was discharged with oral steroids. She returned to the hospital two months later for fever, arthralgia, and faint, evanescent rash with elevated erythrocyte sedimentation rate, C-reactive protein, ferritin, lactate dehydrogenase, and LFT consistent with an AOSD flare. She received intravenous steroids and Anakinra. Symptoms resolved, and she was discharged with plans to continue Anakinra and oral steroids. At followup, she had resolution of all symptoms. IMPACT/DISCUSSION: COVID-19 has many chronic complications, including triggering of underlying rheumatic disease. This sequence of events suggests that COVID-19 Pneumonia triggered an underlying diagnosis of AOSD. AOSD should be considered in the differential diagnosis of patients with quotidian fever and arthralgia following COVID-19 infection. AOSD is a diagnosis of exclusion and requires ruling out infectious, malignant, and rheumatic etiologies. AOSD may trigger MAS, a dysregulated immune response to underlying inflammation, and should be considered in patients with suspected infection refractory to treatment who have fever, splenomegaly, cytopenias, and elevated ferritin, triglycerides, sIL-2R, and CXCL9. CONCLUSION: COVID-19 has many chronic complications. AOSD may manifest after COVID-19 infection and should be considered in the differential diagnosis of patients with persistent fever and arthralgia. MAS should be suspected in patients with systemic inflammation refractory to treatment. AOSD may cause MAS.

Pulmonary cavity- An aftermath of the recent apocalypse

Background: Post COVID-19 complications have been a matter of concern because of various presentations with unknown mechanisms underlying the condition. While the common complications ranged from fatigue, dyspnoea to thromboembolic events and pulmonary fibrosis, lung cavitation was an uncommon finding on CT thorax. Case Study: Four patients, with diabetes mellitus and documented COVID-19 infection developed cavitatory lesions in lung during the course of their recovery from the viral illness. With the rise in number of sino-orbital mucormycosis cases during the second wave, a possibility of pulmonary mucormycosis could not be ruled out. One patient had a bacterial infection known to cause cavitation, while fungal infection was documented in one case, and the rest yielded no results, probably owing to the antibiotic cover provided. All were referred to a thoracic surgeon for further management of lung cavitations. Discussion: Cavitatory lung lesions are usually related to fungal, mycobacterial, autoimmune or neoplastic etiologies, uncommonly caused by viral pneumonias, but have been observed in COVID-19 patients. The velocity of development of cavitatory lesions can be atypical to mycobacterial infections, and hence regarded as a complication of COVID-19 pneumonia. Conclusion: The development of lung cavitations in COVID- 19 infected individuals, warrants vigilant monitoring through regular follow ups, especially the immuno-compromised, for early recognition and definitive treatment of the disease. Further studies are needed to determine the causative factors. It also warrants the clinicians to be aware of the evolving CT findings in COVID-19 and appropriate follow-up of convalescent patients to ensure complete recovery.

Non-tuberculous mycobacteria in Australians with cystic fibrosis: A national survey

Introduction/Aim: We are seeing the rapid emergence of a significant new threat to CF survival;chronic nontuberculous mycobacterial (NTM) infection. This study aims to understand the aetiology and epidemiology of NTM in Australians with CF. Methods: Nationally, nine adult and nine paediatric CF services prospectively collected respiratory samples from people with CF (pwCF) for acid fast bacilli (AFB) culture at regular clinic appointments (Baseline, 6 months, 1 year, then annual to 4 years);associated clinical data, geographic and social data was also collected. Sites commenced recruitment between December 2016 and August 2018. Retrospective clinical and culture data were also collected to offset the shift to a telehealth model of care during the global coronavirus pandemic. Results: 15.1% of 1322 study participants cultured NTM (NTM+) from at least one AFB culture during the study, 5.1% of study participants were M. abscessus (MABS) positive. Adolescents and young adults (11-25 years) had the highest rates of NTM infection (19%, p = 0.0004). MABS was more commonly isolated in participants <25 years (6.7%) compared to participants 25 years and older (2.5%, p < 0.001). Of NTM+ study participants, 49% were incident cases. The species of NTM recovered from participants varied depending on the Australian state of residence, with South Australia, Western Australia and Tasmania having greater diversity of isolated species. Conclusion: In Australia, during this sampling period pwCF <25 years of age were more likely to be infected with MABS than older pwCF. We hypothesize that this may be due to increasing attempts at eradication of Pa in early life and/or increased exposure from environmental sources at a vulnerable age.

Pulmonary Non-tuberculous Mycobacterium Infection (PNTMI) and COVID-19: Characterization of the National COVID Collaborative Cohort (N3C)

Background. Establishing whether a low-prevalence clinical condition is a risk factor for COVID-19 infection, or serious adverse outcomes, is difficult due to a limited number of patients, and lack of access to patient's data by researchers. The National COVID Collaborative Cohort (N3C), a centralized national data resource to study COVID-19, provides access to structured clinical data derived from electronic health records. As of June 2021, N3C contains data on 6,193,738 patients (2,090,138 with COVID-19, 33.7%) from 55 participating sites (Figure 1). We describe the characteristics of patients with PNTMI based on COVID-19 infection status. Methods. COVID-19 is defined by positive lab result (PCR, antigen, or antibody) or COVID-19 coding diagnosis, as defined by N3C. PNTMI phenotype was built with N3C Data Enclave concept set tool, and ATLAS (https://atlas.ohdsi.org/). We limited analysis to adults (18 years-old or older). We used de-identified data sets stripped of protected health information (PHI). We used N3C Data Enclave analytical tools for exploratory data analysis, and descriptive statistics. Results. We identified five hundred and eighty six individuals from 19 sites fulfilling the PNTMI phenotype (9.46 cases per 100,000 people). After our age limit, 555 individuals were included for analysis (Figure 2). 340 were females (61.3%), 447 of white race (80.5%), and 30 were Hispanic (5.4%). Additional descriptive statistics and statistical significance testing are provided (Table 1). The most common concept were "Non-tuberculous mycobacterial pneumonia", and "Pulmonary Mycobacterium avium complex infection". Four sites accounted for more than 50% of identified patients (Figure 2). We identified 24 individuals with COVID-19 (4.32%), and 44 deaths in this cohort (7.9%). Deaths were unrelated to COVID-19 event. Conclusion. In N3C, the PNTMI cohort has a lower proportion of COVID-19 infection than the general population, and it was not a cause of mortality. Further analysis to study impact of comorbidities, and differences in race and geographical location are warranted. N3C is a powerful research platform to study the impact of COVID-19 in special populations with low prevalence, and it can be used to study other populations of interest.