Oesophageal and oral ulcer tuberculous associated with human T-cell lymphotropic virus type 1 (HTLV-1) and SARS-CoV-2 infection

Oesophageal involvement due to tuberculosis (TB) and coinfection with HTLV-1 is rare and can be complicated by the presence of other infections that affect the mucosa of the upper respiratory tract, such as COVID-19. We present the case of a 27-year-old male patient, with 3 months of illness, weight loss, dysphagia, and ulcers in the oral cavity. Tomography showed oesophageal perforation and after oesophageal ulcer biopsy, TB was diagnosed, in addition to infection by HTLV-1 and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). The patient responded satisfactorily to antituberculous treatment and corticosteroids. Considering the association between rare extrapulmonary tuberculosis and other immunosuppressive pathologies, it is crucial to identify these pathologies in such patients.

Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus 2 infection: a systematic review.

INTRODUCTION: We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity. METHODS: We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded. RESULTS: 169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum. CONCLUSION: Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.

Case report: Unusual patient with dermatomyositis associated with SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a major challenge for clinicians. SARS-CoV-2 infection results in coronavirus disease 2019 (COVID-19), and it is best known for its respiratory symptoms. It can also result in several extrapulmonary manifestations such as neurological complications potentially experienced during the course of COVID-19. The association of dermatomyositis (DM) with COVID-19 pathogenesis has not been well-studied. This study aimed to present a previously healthy 37-year-old man, a soldier by profession, with symptoms of DM on the 4th day from the onset of COVID-19. The patient presented DM symptoms with both skin and muscle manifestations. The patient suffered from cough, fever, and fatigue to begin with, and reverse-transcription polymerase chain reaction (RT-PCR) reported positive for SARS-CoV-2 infection. The laboratory findings showed, intra alia, elevated muscle enzymes CK 8253 U/l (N: <145 U/l), a positive test for myositis-specific autoantibodies (anti-Mi-2), electrodiagnostic tests exhibited features of myopathy, with the presence of muscle and skin symptoms. The patient improved with corticosteroids and immunosuppressive agent therapy. In summary, the association between COVID-19 and the development of multi-system autoimmune disorders such as DM remains unclear. Nevertheless, viral infections such as SARS-CoV-2 may likely serve as a trigger.

Tuberculosis and Hiv Infection - So Many Questions Pending

Since the early days of HIV infection, back in the eighties, TB - particularly extrapulmonary TB emerged as one of the opportunistic infections affecting these patients, specifically as a reactivation of latent TB infections. A diagnosis of TB in the context of HIV infection was then considered as an 'AIDS defining condition' according to classification systems used at that time. It has been recognized for a long time that there are many interactions between HIV and Mycobacterium tuberculosis, which lead to further immune deterioration and to worsening of both conditions due to complex biological and mechanistic interactions between these two agents. Many methods and techniques have been proposed in order to improve diagnosis of TB in HIV-infected subjects, knowing that TB is the most frequent opportunistic infection;and, if not treated in a timely fashion, it may easily take the lives of affected patients. It is not easy to have a diagnosis of TB in HIV-infected subjects, because of the difficulties for obtaining adequate sputum samples, or because of lack of adequate facilities for making a timely diagnosis, particularly in the so-called developing world. On the other hand, extrapulmonary TB is most frequently found in HIV-infected individuals compared to non-infected subjects, and its diagnosis poses significant difficulties, since so many times invasive procedures must be performed in order to obtain an adequate tissue sample and then be able to identify the pathological characteristics of tuberculous disease. In the first days of HIV infection when no antiretroviral therapy was available, a diagnosis of TB was made on clinical grounds, considering a history of contact or some characteristics of the disease, and those of us who are old (or experienced) enough offered antituberculosis therapy for these subjects, obtaining an adequate response many times, but in all cases, the natural history of HIV infection took place, and ultimately these patients died because of the occurrence of another opportunistic infection (or malignancy). With the advent of antiretroviral therapy in the late nineties, another problem occurred. The possibility of drug-drug interactions, taking into account hepatic metabolism of rifampin and the alterations of antiretroviral drug blood - or tissue - concentrations. On top of this, the occurrence of IRIS became another problem, and strategies and protocols have been designed in order to establish the adequate timing of antituberculosis therapy and sometime later antiretroviral therapy. A last point to be considered is the COVID-19 pandemic. The question to be asked is what the influence of the pandemic has been for affecting TB and HIV diagnosis and therapy strategies and programs, particularly in the developing world, knowing that health systems in these countries have many limitations, and that - scant - resources had to be dedicated for the fight against the pandemic.Copyright © 2023

COVID-19: Clinical Spectrum—It's Multiorgan Syndrome

COVID-19 outbreak caused by SARS-CoV-2 has emerged as a global challenge for the entire health care system worldwide. It has affected the developed as well as developing countries markedly. What began as pneumonia-like illness later evolved into a multiorgan disease leading to severe morbidity and even death. The clinical data and global literature explicitly suggest that in addition to respiratory symptoms, the COVID-19 patients may present with hematological, cardiovascular, renal, gastrointestinal, neurological, ocular, and skin manifestations. The underlying mechanism for multisystem involvement is the expression of angiotensin-converting enzyme 2 (ACE2) receptors at multiple extrapulmonary tissues. Injury to various organs may be attributed to cytokine storms or to disturbances of coagulation and vascular endothelium. The aim of this review is to emphasize the impact of SARS CoV-2 infection on not only the lungs but other organ systems too. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

Epidemiology and factors associated with Extra-pulmonary tuberculosis in a Low-prevalence area.

Background: Tuberculosis is a global public health problem. Extra-pulmonary tuberculosis accounts for an increasing proportion of cases worldwide, although information about epidemiological, clinical, or microbiological factors is lacking. Methods: We conducted a retrospective observational study of tuberculosis cases diagnosed between 2016 and 2021, classified into Pulmonary and Extra-pulmonary tuberculosis. Univariable and multivariable logistic regression models were used to investigate risk factors of Extra-pulmonary tuberculosis. Results: 20.9% of overall cases were classified as Extra-pulmonary tuberculosis, with a rising trend from 22.6% in 2016 to 27.9% in 2021. Lymphatic tuberculosis accounted for 50.6% of cases, followed by pleural tuberculosis (24.1%). 55.4% of cases belonged to foreign-born patients. Microbiological culture tested positive in 92.8% of Extra-pulmonary cases. Logistic regression analysis showed that women were more predisposed to develop Extra-pulmonary tuberculosis (aOR 2.46, 95% CI 1.45-4.20) as well as elderly patients (aged ≥ 65 years) (aOR 2.47, 95% CI 1.19-5.13) and persons with previous history of tuberculosis (4.99, 95% CI 1.40-17.82). Conclusions: Extra-pulmonary Tuberculosis have increased within our study period. A profound decline occurred in 2021 tuberculosis cases, probably due to COVID-19. Women, elderly population, and persons with previous history of tuberculosis are at higher risk of developing Extra-pulmonary tuberculosis in our setting.

Clinical cases of extrapulmonary manifestations in patients with coronavirus disease (COVID-19)

The aim of the work - to provide variants of extrapulmonary manifestations of coronavirus disease (COVID-19) based on the analysis of the relevant course of the disease in adults.Results. The paper presents two clinical cases of coronavirus disease (COVID-19) with the manifestation of extrapulmonary symptoms, which required some individualization of therapy.The first clinical observation showed that in a 56-year-old patient with moderate COVID-19, the development of oxygen dependence on the 8th day of the disease was combined with the manifestation of extrapulmonary symptoms in the form of cutaneous manifestations. Individualization of glucocorticosteroid therapy and endothelioprotective therapy has been shown to be effective in regressing both oxygen dependence and cutaneous vasculitis.The second clinical observation showed that in a 35-year-old patient, moderate COVID-19 without oxygen dependence was accompanied by the development of extrapulmonary manifestations, namely short-lasting diarrheal syndrome, which manifested in the onset of the disease and of the development of orchiepididymitis on the 9th day of illness, which required the appointment of anti-inflammatory therapy.Conclusions. The abovementioned clinical observations of COVID-19 cases show relatively rare cases of SARS-CoV-2-associated extrapulmonary manifestations in patients with moderate disease, but their development necessitated individualization of treatment.

Influence of COVID-19 pandemic on the main epidemiological data of TB in Azerbaijan

During the COVID-19 pandemic, especially in 2020, the strict quarantine regime limited access to medical facilities for people at high risk of infection, including people with tuberculosis (TB). This has led to a decrease in TB detection and treatment in many countries, including Azerbaijan, and has made it difficult to monitor patients undergoing treatment. The aim: assessment of the main epidemiological indicators for tuberculosis in Azerbaijan for 2020. Material(s) and Method(s): the main statistical data of TB morbidity and mortality in Azerbaijan for the 2020 year analyzed and compared with previous years' data. Result(s): The total TB morbidity decreased from 39.4 to 25.3 per 100000 of the population in the interim 2016-2020. The percentage of the men patients every year was 2 times higher than the percentage of women. The number of primary TB patients at the same period of time changed from 3793 to 2558 (bacteriologically confirmed cases 1660 and 1331 respectively), including reduced incidence of extrapulmonary tuberculosis from 833 to 604. The TB incidence in children and adolescents is also decreased from 12.8 to 8.1 per 100000 of the population in the interim 2016-2020. It should be noted that the sharp decline in indicators occurred in 2020, that is, during the COVID-19 pandemic. However, the mortality did not significantly change - 4.6 per 100000 of the population in 2016 and 4.3 in 2020. Conclusion(s): The COVID-19 pandemic has led to a false improvement in TB incidence rates with a stable TB mortality rate, which indicates the seriousness of the problem of detection and monitoring of the disease.

[IMPACT ON TUBERCULOSIS DIAGNOSTIC DURING COVID-19 PANDEMIC IN A TERTIARY CARE HOSPITAL]. / IMPACTO DE LA PANDEMIA COVID-19 EN EL DIAGNOSTICO DE TUBERCULOSIS EN UN HOSPITAL DE TERCER NIVEL.

INTRODUCTION: The aim of this study is to review how did the first three COVID-19 waves affected the diagnostic of tuberculosis and to describe the extra-pulmonary Mycobacterium tuberculosis complex (TB) diagnosis. MATERIALS AND METHODS: A retrospective observational study was done during the first three waves of pandemic to ascertain the impact on TB samples and to recover the extra-pulmonary TB cases we included the first two years of COVID-19. All relevant data was recovered from hospital and Clinical Microbiology records. RESULTS: Prepandemic period showed an average of 44 samples per week for TB study; during the first three waves this number dropped to 23.1 per week. A reduction of 67.7% of pulmonary TB diagnosis was observed and an increase of 33.3% diagnosis of extra-pulmonary TB was noted when comparing pre-pandemic and pandemic period. DISCUSSION: The number of declared cases and samples for TB diagnosis dropped during the first three COVID-19 waves due to the overstretched Public Health System which could lead to a delay in diagnosis, treatment and to the spread of TB disease in the general population. Surveillance programs should be reinforced to avoid this.

Berbamine suppresses intestinal SARS-CoV-2 infection via a BNIP3-dependent autophagy blockade.

SARS-CoV-2, the causative virus of COVID-19, continues to threaten global public health. COVID-19 is a multi-organ disease, causing not only respiratory distress, but also extrapulmonary manifestations, including gastrointestinal symptoms with SARS-CoV-2 RNA shedding in stool long after respiratory clearance. Despite global vaccination and existing antiviral treatments, variants of concern are still emerging and circulating. Of note, new Omicron BA.5 sublineages both increasingly evade neutralizing antibodies and demonstrate an increased preference for entry via the endocytic entry route. Alternative to direct-acting antivirals, host-directed therapies interfere with host mechanisms hijacked by viruses, and enhance cell-mediated resistance with a reduced likelihood of drug resistance development. Here, we demonstrate that the autophagy-blocking therapeutic berbamine dihydrochloride robustly prevents SARS-CoV-2 acquisition by human intestinal epithelial cells via an autophagy-mediated BNIP3 mechanism. Strikingly, berbamine dihydrochloride exhibited pan-antiviral activity against Omicron subvariants BA.2 and BA.5 at nanomolar potency, providing a proof of concept for the potential for targeting autophagy machinery to thwart infection of current circulating SARS-CoV-2 subvariants. Furthermore, we show that autophagy-blocking therapies limited virus-induced damage to intestinal barrier function, affirming the therapeutic relevance of autophagy manipulation to avert the intestinal permeability associated with acute COVID-19 and post-COVID-19 syndrome. Our findings underscore that SARS-CoV-2 exploits host autophagy machinery for intestinal dissemination and indicate that repurposed autophagy-based antivirals represent a pertinent therapeutic option to boost protection and ameliorate disease pathogenesis against current and future SARS-CoV-2 variants of concern.

Non-pulmonary involvement in COVID-19: A systemic disease rather than a pure respiratory infection.

During the early phase of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), diagnosis was difficult due to the diversity in symptoms and imaging findings and the variability of disease presentation. Pulmonary manifestations are reportedly the main clinical presentations of COVID-19 patients. Scientists are working hard on a myriad of clinical, epidemiological, and biological aspects to better understand SARS-CoV-2 infection, aiming to mitigate the ongoing disaster. Many reports have documented the involvement of various body systems and organs apart from the respiratory tract including the gastrointestinal, liver, immune system, renal, and neurological systems. Such involvement will result in diverse presentations related to effects on these systems. Other presentations such as coagulation defects and cutaneous manifestation may also occur. Patients with specific comorbidities including obesity, diabetes, and hypertension have increased morbidity and mortality risks with COVID-19.

Extrapulmonary manifestations of coronavirus disease (COVID-19) current status (a literature review)

The aim of the study is to analyze the literature data on modern views concerning extrapulmonary manifestations of coronavirus disease (COVID-19).Based on the analysis of current publications, the article analyzes the clinical manifestations of coronavirus disease (COVID-19) as a multisystem disorder with two main types of clinical manifestations, namely pulmonary and extrapulmonary. Determining pathogenetic mechanisms of extrapulmonary symptoms are, on the one hand, the tropism of SARS-CoV-2 to ACE2 receptors, expressed not only by alveolar epithelial type II cells, but also by cells of the heart, nervous system, vascular endothelium, small and large intestine, basal layer cells of the epidermis, cells of endocrine organs, etc., and on the other hand, immune-dependent mechanisms, in particular the development of "cytokine storm".It is shown that the spectrum of extrapulmonary manifestations of COVID-19 is very wide, and clinical manifestations are characterized by significant polymorphism. Extrapulmonary symptoms of COVID-19 were analyzed considering the organs of the gastrointestinal tract, nervous, cardiovascular and endocrine systems, skin and others. Attention is drawn to a certain association between definite extrapulmonary manifestations and the severity of COVID-19 course.Thus, particular extrapulmonary manifestations are associated with a milder course of COVID-19 (anosmia, dysgeusia, etc.), others, vice versa, occur in severe disease (damage to liver, kidney, heart, pancreas). In addition, some extrapulmonary manifestations, especially of the nervous system, may remain in patients even after an acute period of the disease. Some extrapulmonary manifestations, which are currently described in a small number of patients, are also reviewed.Conclusions. COVID-19 is characterized by a wide range and high frequency of extrapulmonary manifestations, which is ex-plained by both the direct action of SARS-CoV-2 and immune-dependent mechanisms. Some extrapulmonary manifestations are associated with a milder course of COVID-19, others, on the contrary, occur in severe disease.

Atrio-Ventricular Block by Legionella Disease.

Although Legionnaires' disease mainly affects the lungs, it can also present with other systemic involvement, including rare cardiac manifestations. Recognised presentations are endocarditis, myocarditis, pericarditis, and pericardial effusion. A 72-year-old British man presented with a six-day history of dry cough and a four-day history of fever during the peak of the COVID-19 pandemic. His electrocardiogram showed Mobitz type II atrio-ventricular block. Although all the cultures were negative, the chest X-ray demonstrated COVID-19 infection-like features. With high clinical suspicions and chest X-ray features, the polymerase chain reaction of the COVID tests was repeated three times and all were negative. He had a positive urinary Legionella antigen, and his bradycardia and heart block improved after treatment with amoxicillin/clavulanic acid, and clarithromycin. As the electrocardiogram showed Mobitz type II, a permanent pacemaker was implanted. The follow-up pacemaker check showed that he still required active pacing.

Impact on tuberculosis diagnostic during COVID-19 pandemic in a tertiary care hospital.

INTRODUCTION: The aim of this study is to review how did the first three COVID-19 waves affected the diagnostic of tuberculosis and to describe the extra-pulmonary Mycobacterium tuberculosis complex (TB) diagnosis. MATERIALS AND METHODS: A retrospective observational study was done during the first three waves of pandemic to ascertain the impact on TB samples and to recover the extra-pulmonary TB cases we included the first two years of COVID-19. All relevant data was recovered from hospital and Clinical Microbiology records. RESULTS: Prepandemic period showed an average of 44 samples per week for TB study; during the first three waves this number dropped to 23.1 per week. A reduction of 67.7% of pulmonary TB diagnosis was observed and an increase of 33.3% diagnosis of extra-pulmonary TB was noted when comparing pre-pandemic and pandemic period. DISCUSSION: The number of declared cases and samples for TB diagnosis dropped during the first three COVID-19 waves due to the overstretched Public Health System which could lead to a delay in diagnosis, treatment and to the spread of TB disease in the general population. Surveillance programs should be reinforced to avoid this.

Diagnostic dilemma in a patient with nasopharyngeal tuberculosis: A case report and literature review.

Tuberculosis remains a major cause of morbidity and mortality globally, with a global total of about 10 million people falling ill with it in 2020. Until the coronavirus (COVID-19) pandemic, tuberculosis was the leading cause of death from a single infectious agent. Nasopharyngeal tuberculosis is a rare type of extrapulmonary tuberculosis that may be either primary or secondary to pulmonary tuberculosis. Nasopharyngeal tuberculosis may be mistaken for nasopharyngeal carcinoma as both conditions may present with a nasopharyngeal mass and cervical lymph node enlargement. We present a case of nasopharyngeal tuberculosis secondary to pulmonary tuberculosis who presented without any nasal or respiratory symptoms. The patient presented with a cervical lymph node enlargement and a nasopharyngeal mass was detected on nasal endoscopy. Fine needle cytology from the cervical node and the initial biopsy report from the nasopharyngeal mass were not confirmatory, causing a diagnostic dilemma. A repeat biopsy from the nasopharyngeal mass with the demonstration of caseating granuloma and acid-fast bacilli in the specimen pointed to the diagnosis of nasopharyngeal tuberculosis. The patient responded well to the standard 6-month anti-tubercular regimen. Nasopharyngeal tuberculosis may mimic nasopharyngeal carcinoma and a repeat biopsy may be necessary to confirm the diagnosis.

A Comparative Study of Severe and Critical Influenza B in Children in the 2021-2022 Winter Season.

Introduction: Influenza B viruses are less common than influenza A viruses in most seasons and cause relatively milder forms of infection that are less studied. We witnessed a dominance of influenza B in Shijiazhuang, China, in the 2021-2022 winter season. In this study, we comparatively investigated the severe and critical influenza B in pediatric patients. Methods: Children who were hospitalized from December 2021 to January 2022 and diagnosed with influenza B were included in this study. Those who tested positive for COVID-19 were excluded. Demographic data, clinical features, underlying medical conditions, laboratory testing results, and treatment outcomes were retrieved and analyzed retrospectively. Disease severity was classified as severe or critical according to Chinese expert consensus on diagnosis and treatment of influenza in children. Results: A significantly greater proportion of patients with critical influenza had extra-pulmonary complications and bacterial coinfections. Children with critical influenza B had substantially higher levels of procalcitonin and lactate dehydrogenase, a markedly higher neutrophil percentage and a significantly lower CD4+ lymphocyte percentage. Conclusion: Our findings suggest that, to effectively manage critical influenza B, therapeutic regimens should consist of organ-specific supportive care, antibiotic application if bacterial coinfection is present, and anti-inflammatory and immune-boosting treatments.

TUBERCULOUS TAMPONADE WITH A TWIST: A CASE OF TB AND COVID-19

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: We present a case of tuberculous pericarditis and cardiac tamponade due to suspected sequela of SARS-Coronavirus 19 (COVID-19) infection. It is important for clinicians to include tuberculosis (TB) in the differential diagnoses for patients presenting with presumptive viral pericarditis and tamponade. CASE PRESENTATION: A 52-year-old Hispanic man with chronic kidney disease not on hemodialysis was admitted with shortness of breath, fluid overload, hypoxemia and concern for uremic pericarditis. The patient tested positive for COVID-19 to which the symptoms were initially attributed, and he was treated with steroids, remdesevir, tocilizumab and hemodialysis. The patient incidentally had a positive QuantiFERON gold test obtained before initiating hemodialysis. On day 60 of hospitalization, the clinical exam abruptly deteriorated with stuporous mentation, hypotension, and cool skin. Bedside point of care echocardiography revealed a new large circumferential pericardial effusion with right ventricular diastolic collapse and increased respiratory variation in peak E-wave mitral inflow velocity consistent with tamponade physiology. Emergent pericardiocentesis was performed, and hemodynamic instability resolved immediately after aspiration of 750 milliliters of frank pus. Empiric antibiotics were initially given for pyogenic pericarditis. When the pericardial fluid later tested positive for acid-fast bacilli and adenosine deaminase, anti-TB therapy was started. The hospitalization was further complicated by septic shock and cardiac arrest. Though found to have a re-accumulated pericardial effusion on bedside ultrasound peri-arrest, there was no tamponade physiology (suggestive of at least a partial response to the TB treatment in the setting of overall poor underlying reserve). DISCUSSION: The coexistence of COVID-19 and tuberculous pericarditis with tamponade has been reported to date in one other case to our knowledge. COVID-19 with massive pericardial tamponade is rare and a careful diagnostic approach involving multi-modality imaging with bedside echocardiogram is invaluable in the evaluation and treatment of obstructive shock. In this case, we hypothesize that the COVID-19 infection may have led to re-activation of latent TB despite treatment of COVID-19 with corticosteroids (which are an adjunct tuberculostatic treatment in patients with tuberculous pericarditis). Tuberculous pericarditis with tamponade is a relatively uncommon manifestation of extrapulmonary TB and is a major cause of cardiovascular death and morbidity. Even with aggressive antituberculosis therapy, 30-60% of patients may need surgical pericardiectomy for constrictive pericarditis. CONCLUSIONS: This case highlights the need to consider possibility of concomitant viral and TB pericarditis in the diagnostic differential for tamponade. More histopathologic or post-mortem examinations of COVID-19 pericarditis cases are needed. Reference #1: Asif T, Kassab K, Iskander F, Alyousef T. Acute pericarditis and cardiac tamponade in a patient with COVID19: a therapeutic challenge. Eur J Case Rep Intern Med. 2020 May 6;7(6):001701. Reference #2: Barrett et al. Increase in disseminated TB during the COVID19 pandemic. Int J Tuberc Lung Dis. 2021 Feb 1;25(2):160-166. Reference #3: Wong SW, Ng J. K.X., Chia YW. Tuberculous pericarditis with tamponade diagnosed concomittantly with COVID19: a case report. Eur Heart J Case Rep. 2020 Dec 28;5(1):ytaa491. eCollection 2021 Jan. DISCLOSURES: No relevant relationships by Jaskiran Khosa No relevant relationships by Walter Klein No relevant relationships by Amy Tran No relevant relationships by Michael Ulrich

A CHALLENGING CASE OF MYCOBACTERIUM TB-INDUCED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

SESSION TITLE: Challenging Cases of Hemophagocytic Lymphohistiocytosis SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive immune activation in response to a variety of insults including malignant, autoimmune and infectious processes. The most common infectious trigger is a viral infection, but other pathogens have also been implicated including Mycobacterium tuberculosis (MTB) CASE PRESENTATION: 62-year-old male from Bangladesh presented due to lethargy, weakness, and anorexia for several weeks. He also reported fevers, diarrhea, and unintentional weight loss. On examination, he appeared acutely ill with diffuse bibasilar crackles on lung exam. Labs showed platelets of 132, ESR 45 mm/hr, CRP 9.6mg/dL, ferritin 1,765ng/mL and transaminitis. A viral panel was positive for Rhinovirus. Computed tomography (CT) of the chest showed diffuse bilateral ground-glass opacities and he was started on antibiotics for pneumonia. On day 3, his respiratory status worsened and he was emergently intubated. He underwent bronchoscopy and bronchoalveolar lavage (BAL) and started on high-dose steroids for possible hypersensitivity pneumonitis. On day 5, he was extubated to nasal cannula, however, his condition worsened despite treatment. Extensive infectious workup, including HIV, Covid and P jirovecii PCR, sputum, and blood cultures, and preliminary AFB smear were negative. Subsequent labs noted rising ferritin levels (4,164 ng/mL), high triglycerides, pancytopenia and transaminitis. Calculated H score was 211 which gave a 93-96% probability of HLH. Initiation of Etoposide was discussed but family deferred. He was later transferred to another facility. On follow-up, IL-2 receptor antibodies were elevated, bone marrow biopsy showed hemophagocytosis and necrotizing granulomas. He was intubated for worsening hypoxemia. Repeat bronchoscopy and BAL analysis showed many acid-fast bacilli. Anti TB treatment (ATT) was deferred due to his critical state. He further declined and eventually expired. DISCUSSION: The exact mechanism for which MTB triggers HLH is unclear, however, it is thought that MTB serves as an obligate intracellular pathogen after phagocytosis by phagocytic cells to induce TH1-mediated cytotoxicity, activating macrophages and NK cells, further releasing a large quantity of cytokines and chemokines. The lack of specific clinical signs, low sensitivity for acid-fast staining, and time-consuming culture make the diagnosis of TB-HLH difficult. However, the use of NAATs has improved the yield of sputum testing. Exceedingly high ferritin levels should serve as a red flag in cases of undetermined diagnosis. Moreso, Cytopenias, elevated LFTs, and coagulation dysfunction are other clues that a diagnosis of HLH should be on the differential. It is believed that early and effective ATT is the key to preventing HLH in TB patients. CONCLUSIONS: It is paramount to both recognize the features of TB as well as HLH as early diagnosis and treatment favor better outcomes. Reference #1: Padhi S, Ravichandran K, Sahoo J, Varghese RG, Basheer A. Hemophagocytic Lymphohistiocytosis: An Unusual Complication in Disseminated Mycobacterium Tuberculosis. Lung India (2015) 32(6):593–601. doi: 10.4103/0970-2113.168100 Reference #2: Dalugama, C., Gawarammana, I.B. Fever with pancytopenia: unusual presentation of extrapulmonary tuberculosis: a case report. J Med Case Reports 12, 58 (2018). https://doi.org/10.1186/s13256-018-1596-0 Reference #3: O M P Jolobe, Timely recognition of hematophagocytosis attributable to coexistence of lymphoma and tuberculosis, QJM: An International Journal of Medicine, Volume 112, Issue 4, April 2019, Page 315, https://doi.org/10.1093/qjmed/hcy198 DISCLOSURES: No relevant relationships by Katherine Acosta No relevant relationships by Chika Winifred Akabusi No relevant relationships by Uma Medapati No relevant relationships by Hector Ojeda-Martinez No relevant relationships by Busala Oke No relevant relationships by Mar o Torres

Outcomes of Tuberculosis contact tracing and predictors of success: a 10-year retrospective cohort analysis

Background: The Covid-19 pandemic risks disruption to diagnosis and treatment of Tuberculosis (TB) globally, jeopardising the 2035 eradication target. Between 1990-2010 40.9% of contacts did not complete Tuberculosis (TB) contact screening in Birmingham, UK. Understanding screening outcome success is urgently needed to guide future resource allocation. Aim: To evaluate changes made to TB screening since 2010. To identify predictors of contact screening non-completion, and of screening outcomes. Methods: A retrospective cohort analysis of all index and contact patients in Birmingham between 2011-2020, with separation of Covid-19 data, and stratification of contacts by Pulmonary TB (PTB) or Extra-Pulmonary TB (EPTB) index infection. Univariate and multiple logistic regression models were used to identify predictors of screening completion and clinical outcome. Results: 3,255 index cases and 27,820 contacts were identified. Screening non-completion has improved from 40.9% of contacts to 25% since 2010. Contacts were less likely to complete screening if they were >65 years (P=0.001) had no BCG (P<0.001), were male (P<0.001 PTB, P=0.02 EPTB), had had TB themselves (P<0.001 PTB, P=0.025 EPTB), were a close contact (P<0.001), or were from the Indian subcontinent (PTB only, P=0.019). Contacts were significantly more likely to require treatment for TB if they were born outside the UK (P<0.001), were <65 years (P<0.001 PTB, P=0.01 EPTB), if they were male, close contacts, or of Black ethnicity (all P=0.001, PTB only). Conclusions: Changes to contact screening since 2010 have substantially improved screening completion rates. Significant predictors of screening non-completion exist, which warrant further investigation and targeted screening support.

Microbiological and Clinical Findings of SARS-CoV-2 Infection after 2 Years of Pandemic: From Lung to Gut Microbiota.

Early recognition and prompt management are crucial for improving survival in COVID-19 patients, and after 2 years of the pandemic, many efforts have been made to obtain an early diagnosis. A key factor is the use of fast microbiological techniques, considering also that COVID-19 patients may show no peculiar signs and symptoms that may differentiate COVID-19 from other infective or non-infective diseases. These techniques were developed to promptly identify SARS-CoV-2 infection and to prevent viral spread and transmission. However, recent data about clinical, radiological and laboratory features of COVID-19 at time of hospitalization could help physicians in early suspicion of SARS-CoV-2 infection and distinguishing it from other etiologies. The knowledge of clinical features and microbiological techniques will be crucial in the next years when the endemic circulation of SARS-CoV-2 will be probably associated with clusters of infection. In this review we provide a state of the art about new advances in microbiological and clinical findings of SARS-CoV-2 infection in hospitalized patients with a focus on pulmonary and extrapulmonary characteristics, including the role of gut microbiota.