Fatal SARS-CoV-2 and<i>Mycobacterium tuberculosis</i>coinfection in an infant: insights from Botswana

Mulale, Unami; Kashamba, Thanolo; Strysko, Jonathan; Kyokunda, Lynnette Tumwine

doi:10.1136/bcr-2020-239701

Cited by 12 publications

(17 citation statements)

References 16 publications

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“…Our case with known sickle-cell disease and pulmonary fibrin thrombi recalls 4 reported infant cases of COVID-19 with pulmonary microthrombi. However, our 4 infants did not have acute lung injury (diffuse alveolar damage) as described in iatrogenically immunocompromised 5- and 10-month-old infants after liver transplantation ( 5 ), in a 3-month-old with disseminated tuberculosis ( 7 ), and in a 7-month-old with multiple congenital anomalies ( 8 ). Note that only 1 of those reported infants had a neuropathologic examination (needle biopsy) showing microglia and neuronal ischemia ( 8 ).…”

Section: Discussionmentioning

confidence: 67%

“…Published reports of autopsy pathology of children dying with SARS-CoV-2 infection are limited, and consist of single reports or small series, a subset of which had clinically diagnosed MIS-C (summarized in Table 1 ). Among those reports, general autopsy findings comprised isolated eosinophilic (hypersensitivity-type) myocarditis in a teenager ( 4 ); diffuse alveolar damage and microvascular thrombi in postmortem lung biopsies of 2 infants previously treated with liver transplantation ( 5 ), and in infants and school-age children with pre-existing conditions such as adrenal carcinoma, trisomy 18 with congenital heart disease, neonatal cholestasis, sickle-cell trait, disseminated tuberculosis, and out-of-range body-mass index (BMI) ( 7 , 8 ). Other systemic findings included myocarditis and fibrin thrombi in renal glomeruli ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

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Neuropathology of Pediatric SARS-CoV-2 Infection in the Forensic Setting: Novel Application of Ex Vivo Imaging in Analysis of Brain Microvasculature

et al. 2022

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Two years into the COVID-19 pandemic, there are few published accounts of postmortem SARS-CoV-2 pathology in children. We report 8 such cases (4 infants aged 7–36 weeks, 4 children aged 5–15 years). Four underwent ex vivo magnetic resonance neuroimaging, to assist in identification of subtle lesions related to vascular compromise. All infants were found unresponsive (3 in unsafe sleeping conditions); all but 1 had recent rhinitis and/or influenza-like illness (ILI) in the family; 1 had history of sickle cell disease. Ex vivo neuroimaging in 1 case revealed white matter (WM) signal hyperintensity and diffuse exaggeration of perivascular spaces, corresponding microscopically to WM mineralization. Neurohistology in the remaining 3 infants variably encompassed WM gliosis and mineralization; brainstem gliosis; perivascular vacuolization; perivascular lymphocytes and brainstem microglia. One had ectopic hippocampal neurons (with pathogenic variant in DEPDC5). Among the children, 3 had underlying conditions (e.g., obesity, metabolic disease, autism) and all presented with ILI. Three had laboratory testing suggesting multisystem inflammatory syndrome (MIS-C). Two were hospitalized for critical care including mechanical ventilation and extracorporeal membrane oxygenation (ECMO); one (co-infected with adenovirus) developed right carotid stroke ipsilateral to the ECMO cannula and the other required surgery for an ingested foreign body. Autopsy findings included: acute lung injury in 3 (1 with microthrombi); and one each with diabetic ketoacidosis and cardiac hypertrophy; coronary and cerebral arteritis and aortitis, resembling Kawasaki disease; and neuronal storage and enlarged fatty liver. All 4 children had subtle meningoencephalitis, focally involving the brainstem. On ex vivo neuroimaging, 1 had focal pontine susceptibility with corresponding perivascular inflammation/expanded perivascular spaces on histopathology. Results suggest SARS-CoV-2 in infants may present as sudden unexpected infant death, while in older children, signs and symptoms point to severe disease. Underlying conditions may predispose to fatal outcomes. As in adults, the neuropathologic changes may be subtle, with vascular changes such as perivascular vacuolization and gliosis alongside sparse perivascular lymphocytes. Detection of subtle vascular pathology is enhanced by ex vivo neuroimaging. Additional analysis of the peripheral/autonomic nervous system and investigation of co-infection in children with COVID-19 is necessary to understand risk for cardiovascular collapse/sudden death.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Neuropathology of Pediatric SARS-CoV-2 Infection in the Forensic Setting: Novel Application of Ex Vivo Imaging in Analysis of Brain Microvasculature

et al. 2022

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“…The overlap of clinical and radiological picture complicates this scenario further [ 7 , 17 ]. Current pediatric evidence for this association is limited to case reports [ 18 , 19 ]. Since appropriate matched studies are lacking, we attempted to bridge this gap.…”

Section: Discussionmentioning

confidence: 99%

Effect of Concomitant Tuberculosis Infection on COVID-19 Disease in Children: A Matched, Retrospective Cohort Study

Mathur

Saxena

Pallavi

et al. 2022

Journal of Tropical Pediatrics

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Background Coronavirus disease 2019 (COVID-19) has had devastating effects on the health of millions globally. Patients with tuberculosis (TB) are a vulnerable population. There is paucity of data to assess association between the 2 diseases in Pediatric population. Objective To elucidate the effect of concomitant TB on clinical course of pediatric COVID-19 disease. Methods Retrospective matched cohort study was conducted at dedicated tertiary COVID-19 hospital in India. All consecutive patients aged <18 y admitted with COVID-19 were line listed. Patients with current or recently diagnosed TB were included. Consecutive age and sex matched COVID-19 patients with no history of TB were included as controls. Medical records were retrieved, clinical data entered in pre-determined proforma. Results During study period, 327 pediatric COVID-19 patients were admitted. Study group included 17 patients with TB. These patients, tended to be referred from other hospitals, be sicker, had lower SpO2 at arrival and higher severity of COVID-19 as compared to controls (All P < 0.05). They required more mechanical ventilation, had longer length of stay and worse outcome. Conclusion COVID-19 may secondarily affect and modify the course of TB in children. Given the high case fatality rate in this association and potentially treatable nature of TB, attention of the policy makers is drawn to this. Name of IEC committee Maulana Azad Medical College and Associated Hospital Institutional Ethics Committee. IEC no: F.1/IEC/MAMC/(80/8/2020/No274). Dated 9 November 2020. Trial registration CTRI/2021/02/031197 [Registered on: 10 February 2021].

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“…Despite empirical treatment for TB, the patient rapidly deteriorated and died: diagnosis of TB was confirmed post mortem [ 63 ]. An additional fatal case of coinfection has been reported in a 3-month-old infant in Botswana who presented with fever and respiratory distress in the setting of failure to thrive [ 64 ]. The patient’s rapid clinical decline could not be explained by TB alone, and presence of diffuse microthrombi on autopsy together suggested a likely synergistic pathophysiologic effect of co-infection.…”

Section: Effect Of Covid On Active Tbmentioning

confidence: 99%

TB and COVID-19: An Exploration of the Characteristics and Resulting Complications of Co-infection

Luke¹,

Swafford²,

Shirazi³

et al. 2022

Front. Biosci. (Schol Ed)

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Tuberculosis (TB) and Coronavirus Disease-19 (COVID-19) infection are two respiratory diseases that are of particular concern epidemiologically. Tuberculosis is one of the oldest diseases recorded in the history of mankind dating back thousands of years. It is estimated that approximately one quarter of the world’s population is infected with latent Mycobacterium tuberculosis (LTBI). This contrasts with COVID-19, which emerged in late 2019. Data continues to accumulate and become available on this pathogen, but the long-term side effect of fibrotic damage in COVID-19 patients evokes parallels between this novel coronavirus and its ancient bacterial affiliate. This similarity as well as several others may incite inquiries on whether coinfection of individuals with latent TB and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lead to excessive fibrosis in the lungs and thus the emergence of an active TB infection. While it is well understood how TB leads to structural and immunological lung complications including granuloma formation, fibrosis, and T cell exhaustion, less is known about the disease course when coinfection with SARS-CoV-2 is present. Past and present research demonstrate that IL-10, TNF- α , IFN class I-III, TGF- β , IL-35, and Regulatory T cells (T-regs) are all important contributors of the characteristics of host response to mycobacterium tuberculosis. It has also been noted with current research that IL-10, TNF- α , IFN class I, II, and III, TGF- β , ACE-2, and T-regs are also important contributors to the host response to the SARS-CoV-2 virus in different ways than they are to the TB pathogen. Both pathogens may lead to an unbalanced inflammatory immune response, and together a shared dysregulation of immune response suggests an increased risk of severity and progression of both diseases. We have reviewed 72 different manuscripts between the years 1992 and 2021. The manuscripts pertaining to the SARS-COV-2 virus specifically are from the years 2020 and 2021. Our literature review aims to explore the biomolecular effects of these contributors to pathogenicity of both diseases along with current publications on TB/COVID-19 coinfection, focusing on the pathogenicity of SARS-CoV-2 infection with both latent and active TB, as well as the challenges in treating TB during the COVID-19 pandemic. The compiled material will then aid the latticework foundation of knowledge for future research leading to a hopeful improved system of therapeutic strategies for coinfection.

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Fatal SARS-CoV-2 andMycobacterium tuberculosiscoinfection in an infant: insights from Botswana

Cited by 12 publications

References 16 publications

Neuropathology of Pediatric SARS-CoV-2 Infection in the Forensic Setting: Novel Application of Ex Vivo Imaging in Analysis of Brain Microvasculature

Neuropathology of Pediatric SARS-CoV-2 Infection in the Forensic Setting: Novel Application of Ex Vivo Imaging in Analysis of Brain Microvasculature

Effect of Concomitant Tuberculosis Infection on COVID-19 Disease in Children: A Matched, Retrospective Cohort Study

TB and COVID-19: An Exploration of the Characteristics and Resulting Complications of Co-infection

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