Reactivation of Tuberculosis and COVID-19 in Pediatric Patients

Objective Mycobacterium tuberculosis is an immobile aerobic bacillus that causes tuberculosis (TB) disease. We aimed to evaluate the association between coronavirus disease 2019 (COVID-19), COVID-19-related drugs, TB reactivation, and TB incidence during the pandemic. Methods Eight patients who were diagnosed as having TB in Meram Medical Faculty, Necmettin Erbakan University between March 1, 2020, and December 31, 2021, at the beginning of the pandemic, were enrolled in this study. The presence of COVID-19 infection was confirmed using COVID-19 antibody tests and the patients' COVID-19 history. We evaluated the demographic data, laboratory findings, imaging tests, and pathology results of all patients. Results We checked all our patients with TB using COVID-19 antibodies (immunoglobulin [Ig]G + IgM) or polymerase chain reaction. Seven of the eight patients were female (87.5%). The median age was 16 years. Family screening of all patients was negative, and they had bacillus Calmette-Guerin vaccine scars. Two patients had chronic diseases. One was diagnosed as having primary ciliary dyskinesia in our department (patient no. 8) and the second was under follow-up by the rheumatology department with a diagnosis of juvenile idiopathic rheumatoid arthritis. Conclusion There has been an increase in the incidence of TB in children, especially in adolescents, during the pandemic period. This may be due to the pathogenic structure of the COVID-19 virus with an unknown mechanism. In addition, lifestyle changes and changes in health care policies during the pandemic may have caused this. Further research should be performed on this topic.Copyright © 2023 Authors. All rights reserved.

Emerging Tuberculosis Among Patients with Previous COVID-19

COVID-19 patients have a higher incidence of opportunistic infections, but there is little information on tuberculosis (TB). In this study, it was aimed to determine any possible contribution of COVID-19 in TB emergence among patients diagnosed with TB during the pandemic. A retrospective screening of the regional TB laboratory's records identified TB patients diagnosed in the Malatya region between April 1, 2020, and December 31, 2021. Medical data of TB patients with a prior COVID-19 were evaluated. During the study period, 171 TB patients were diagnosed in the region, with 26 also infected with SARS-CoV-2. Patients' histories revealed that 10 (38.5%) of these 26 patients developed TB symptoms in a median 68.5 days after COVID-19. Four patients had one-week to two-month corticosteroid treatment due to severe COVID-19, and one had a hematological malignancy history. However, the remaining five patients had no significant predisposing factor for TB relapse. Four out of 10 patients were free of any finding for active TB before COVID-19. Severe COVID-19 may have some obvious implications for TB reactivation, but there was no conclusive evidence of such an effect in mild to moderate COVID-19. Nonetheless, inquiring about COVID-19 histories from TB patients in large-scale studies may provide high-quality evidence about the interactions between the two pathogens.

TB DURING THE SEROCONVERSION PHASE

SESSION TITLE: TB and TB-Involved Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Patients who are HIV positive have a high risk of co-infection with tuberculosis (TB). Screening tests for HIV identify antibodies that are present during the seroconversion, or window phase. Here we present a case of reactivation TB during the seroconversion phase of HIV with an initially negative QuantiFERON test. CASE PRESENTATION: A previously healthy 24-year-old female presented with a productive cough. She was found to have leukopenia and apical consolidation on chest CT and was treated for community-acquired pneumonia with mild improvement of symptoms. Her QuantiFERON, COVID-19, and HIV antibody screen were negative;however, her reflex HIV antigen was positive. She re-presented a month later with a worsening cough, drenching night sweats, weight loss, vomiting, and dysphonia. Her chest CT noted a right apical cavitary lesion and bilateral upper lobe micronodules with endobronchial spreading. Her QuantiFERON and HIV antibody were now both positive. She was started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy and on raltegravir and emtricitabine/tenofovir. DISCUSSION: Above we describe a case of reactivation TB during the seroconversion phase of HIV with a negative QuantiFERON. Primary TB presents in the middle lobes without signs of structural damage whereas secondary TB typically involves the apices and presents with cavitation. Secondary TB is typically due to reactivation or reinfection in immunosuppressed patients. Although we believe this case is due to reactivation due to radiographic findings, her initial QuantiFERON was negative. However, studies have shown that QuantiFERON may have uncertain results in latent TB infections in patients with underlying HIV (1). Reliable testing for latent TB in HIV-positive individuals is necessary as HIV increases the risk of developing active TB and TB increases the risk of transitioning from HIV to AIDS (2). CONCLUSIONS: TB is one of the top 10 causes of death worldwide and HIV is a common coinfection. To the best of our knowledge, this is the first published report of reactivation TB during the seroconversion phase of HIV with an initially negative QuantiFERON. Overall, more research must be done to identify the risk of infections during the seroconversion phase and physicians must be able to identify radiographic findings concerning for TB in patients with underlying HIV. Reference #1: Elisa Petruccioli, Teresa Chiacchio, Elisa Petruccioli, et al. Effect of HIV-infection on QuantiFERON-plus accuracy in patients with active tuberculosis and latent infection, Journal of Infection, 2020;80(5): 536-546. https://doi.org/10.1016/j.jinf.2020.02.009. Reference #2: Bruchfeld, Judith et al. "Tuberculosis and HIV Coinfection.” Cold Spring Harbor perspectives in medicine vol. 5,7 a017871. 26 Feb. 2015, doi:10.1101/cshperspect.a017871 Reference #3: Johnson JL, Okwera A, Hom DL, et al. Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults. AIDS. 2001;15(16):2137-2147. doi:10.1097/00002030-200111090-00009 World Health Organization. Tuberculosis [Internet]. 2021 [cited 2022 Mar. 15];Available from: https://www.who.int/news-room/fact-sheets/detail/tuberculosis DISCLOSURES: No relevant relationships by Loor Alshawa No relevant relationships by Angela Binkowski No relevant relationships by Sara Qutubuddin

TUBERCULOUS PLEURAL EFFUSION MASQUERADING AS DRUG-INDUCED LUPUS

SESSION TITLE: Critical Care Presentations of TB SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: TNFα plays a pivotal role in inflammation and maintenance of immune response against tuberculosis. The use of TNF inhibitors (TNFi) is associated with a significant increase in the incidence of tuberculosis (TB). TNFi may cause drug-induced lupus (ATIL) presenting as constitutional symptoms, rashes, pericardial and pleural effusions with positive autoantibodies. We present a case of pleural TB masquerading as drug-induced lupus. CASE PRESENTATION: A 68y/o woman with a history of ulcerative colitis (on infliximab, mesalamine), hypertension, T2DM, CAD, complained of low-grade fever, rashes, left-sided chest pain, dyspnea, and arthralgias for two weeks. Chest pain- worse with inspiration and cough. She emigrated from India to the USA 40 years ago. Six months before infliximab therapy, Quantiferon gold was negative. Exam: faint hyperpigmentation over shins, minimal swelling of MCPs and ankles, dullness to percussion over the left chest with decreased breath sounds. Labs: CRP 101 mg/dL, Hb 10.8 iron deficient, rheumatoid factor and anti-CCP negative, ANA 1:40, dsDNA 1:640, a reminder of ENA negative, anti-histone negative, C3/C4 normal, UA bland, protein/Cr 0.4 mg/gm, negative blood cultures, SPEP and LDH normal. CXR: opacification of the left lung up to midfield. CT chest: moderate left and small right pleural effusions, enlarged mediastinal lymph nodes. COVID and Quantiferon: negative. Thoracentesis: 850 ml of exudative fluid (2 out of 3 Light's criteria), lymphocytic predominance (76% of 4148 nucleated cells), adenosine deaminase (ADA) 42 U/L, gram stain, culture, acid-fast and MTB PCR negative, cytology negative. Thoracoscopy with biopsy of the parietal pleura: necrotizing granulomatous pleuritis with acid-fast bacilli. Sensitivity: pan-sensitive M. tuberculosis. Sputum: negative for TB. She was discharged on RIPE treatment for reactivation of TB. DISCUSSION: The incidence of infliximab-induced lupus is approximately 0.19% and confirming the diagnosis is challenging. The immunogenicity of infliximab is high, 66% of patients develop positive ANA. Anti-histone antibodies are less commonly associated with ATIL as opposed to classic drug-induced lupus and dsDNA is positive in up to 90% of cases of ATIL. Renal involvement is rare. The diagnostic usefulness of ADA (over 40 U/L) in lymphocytic pleural effusions for the diagnosis of tuberculosis in an immunosuppressed individual is demonstrated here. In countries with low TB burden, such as the USA, the positive predictive value of ADA in pleural fluid declines but the negative predictive value remains high. CONCLUSIONS: Tuberculous pleuritis is not always easily diagnosed since AFB smears and sputum may remain negative. When ADA level in lymphocytic pleural fluid is not low thorough search for TB with thoracoscopy and biopsy is justified. Reference #1: Shovman O, Tamar S, Amital H, Watad A, Shoenfeld Y. Diverse patterns of anti-TNF-α-induced lupus: case series and review of the literature. Clin Rheumatol. 2018 Feb;37(2):563-568. Reference #2: Benucci, M., Gobbi, F. L., Fossi, F., Manfredi, M. & Del Rosso, A. (2005). Drug-Induced Lupus After Treatment With Infliximab in Rheumatoid Arthritis. JCR: Journal of Clinical Rheumatology, 11 (1), 47-49. Reference #3: Valdés L, San José ME, Pose A, Gude F, González-Barcala FJ, Alvarez-Dobaño JM, Sahn SA. Diagnosing tuberculous pleural effusion using clinical data and pleural fluid analysis A study of patients less than 40 years-old in an area with a high incidence of tuberculosis. Respir Med. 2010 Aug;104(8):1211-7. DISCLOSURES: No relevant relationships by Adam Adam No relevant relationships by Moses Bachan No relevant relationships by Chen Chao No relevant relationships by Zinobia Khan No relevant relationships by Milena Vukelic

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

IMMUNOSUPPRESSION SECONDARY TO SEPSIS AND POSTACUTE CARE SYNDROME LEADING TO LATENT TUBERCULOSIS REACTIVATION

CASE: A 59-year-old Mexican-American man with hypertension and type II diabetes (Hemoglobin A1c 11.5) was admitted for sepsis and Acute Respiratory Distress Syndrome secondary to COVID-19 pneumonia. He was ventilator- dependent for 66 days. His clinical course was complicated by acute renal failure requiring hemodialysis, pulmonary embolism, and recurrent ventilator-associated bacterial pneumonia. He was discharged to a long-term acute care center four months after his initial presentation, but was readmitted two weeks later for abdominal pain and fever. CT abdomen revealed diffuse mesenteric nodular stranding and pelvic ascites concerning for peritoneal carcinomatosis. Biopsy of an omental nodule, however, showed necrotizing granulomatous inflammation and no malignant cells. No cultures were sent from the initial biopsy, so repeat sampling was performed and culture was positive for Mycobacterium tuberculosis complex. Treatment for active tuberculosis was initiated with subsequent recovery. IMPACT/DISCUSSION: Initial infection by tuberculosis occurs in the lungs, where alveolar macrophages encounter and phagocytose the bacteria. The macrophages initiate a cytokine response and recruit lymphocytes to form a granuloma, which segregates the infection within the host. The granuloma is then perpetually maintained by an ongoing immune response that is driven by monocytes and CD-4 T cells. Reactivation of tuberculosis occurs when the ongoing immune response is disrupted. Sepsis has profound and complex effects on the immune system, including marked inhibition of lymphocyte proliferation that leads to reduced levels of B cells, CD-4 T cells, and follicular dendritic cells. Signaling pathways are disrupted without these lymphocytes, which then leads to the dysfunction of the remaining leukocytes. Further, critically ill patients often suffer from post-intensive care unit syndrome. This syndrome is marked by persistent inflammation, which prompts an immunosuppressive response that suppresses T-cell function and leads to T-cell apoptosis. Both sepsis and post-intensive care unit syndrome predispose patients to opportunistic infection by attenuation of the usual immune response. In this particular case, the specific loss of T-cell function in both syndromes allowed this patient's latent tuberculosis to reactivate several months after his initial presentation with sepsis from COVID-19 pneumonia. This case highlights the importance of maintaining a high index of suspicion for opportunistic infection after critical illness. CONCLUSION: Sepsis and post-intensive care unit syndrome disrupted this patient's ability to maintain the immune responses that prevent the progression of latent tuberculosis infection. The diagnosis was delayed due to a lack of awareness of the profound immunosuppression that accompanies and follows critical illness. Providers must recognize these syndromes and the impact they have on immunity in order to diagnose and treat opportunistic infections in a timely manner.

Covid-19 in pediatric hematology-oncology and stem cell transplant patients –The spectrum of illness, complications and comparison of first two waves

Introduction: Indian subcontinent witnessed first wave of COVID-19 around March 2020 and second wave in April 2021. The mutant delta variant was ≈2.5 times more transmissible and led to the severe second wave. We compared the impact of two waves on pediatric hematology and oncology patients at our tertiary care centre that was at heart of managing COVID-19. Methods: Children between 0 and 18 years, who were treated for a haematological illness, malignancy or stem cell transplant with confirmed COVID-19 infection or who developed multisystem inflammatory syndrome in children were included. Results: A total of 48 (22-first, 26-second wave) children were evaluated. Despite better understanding of disease and standardised management algorithms, we found a trend towards younger age, increased requirements of oxygen, severe pneumonia and other post-covid complications in admitted patients during the second wave. We observed early RTPCR negativity in second wave. Invasive aspergillosis, disseminated candidiasis, reactivation of tuberculosis, HLH and MISC were the main complications. No child died of COVID-19. Conclusion: The second wave hit pediatric hematology and oncology patients harder than the first wave.COVID-19 infection in these patients may lead to significant morbidity and complications that interfere with treatment of their primary illnesses. They need close monitoring for development of life threatening infections. Early recognition and prompt therapy can optimise outcomes.

Cardiac Temponade post COVID-19 vaccination due to reactivation of tuberculosis

Background: 35yrs female, without comorbidities hospitalised in emergency in icu due to sudden severe breathlessness and chest pain, fever, weakness, cold, throat pain, vomiiting of 4 to 5 days duration. Case Study: H/o 1st dose covid vaccination received 4 to 5 days ago. Latest COVID RT-PCR negative. Patient required o2 support as her Spo2 on admission was 87%.All necessary lab done. 2DECHO done by cardiologist s/o moderate pericardial effusion causing temponade, also dilated RA/ RV, RV dysfunction, septal buging s/o effussion/constrictive pericarditis. Hence emergency pericardiocentesis was done under fluroscopic guidence. 500ml pale yellow fluid aspirated and pigtail was placed. Fluid was sent for testing. It showed on Gene Xpert detection of mycobacterium tuberculosis and no resistance to rifampicin. Pulmonary embolism and other systemic causes of pericardial effusion ruled out. Patient gave history of Miliary tuberculosis and completed treatment 1 month ago with HRCT chest after treatment completed showing normal lung parenchyama. All symptoms started on the day of vaccination in evening. She also had associated bilateral moderate pleural effusion L>>R. Left sided pleural fluid tapping done and sent for examination. Pt was started on 1st line anti-TB drugs along with diuretics, steroids. She responded well to treatment. Subsequent follow up 2DECHO screening and CXR showed resolution of effusion. Pigtail pericardial catheter removed, O2 tapered off and patient discharged home. Called for follow up after 1 week for 2DECHO screening. Pericardial fluid TB liquid culture was sent which showed no growth after 8 weeks. Discussion: Reactivation of tuberculosis doesn't occur in all cases who has received covid-19 vaccination but we noted in 1 of our case. Conclusion: Reactivation of tuberculosis causing life threatning complication post COVID-19 vaccination.