A Double Pathogen Strike: A Case Report of COVID-19 and Talaromycosis Co-infection in a Patient with Post-Tuberculosis Lung Disease

A Double Pathogen Strike: A Case Report of COVID-19 and Talaromycosis Co-infection in a Patient with Post-Tuberculosis Lung Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Double Pathogen Strike: A Case Report of COVID-19 and Talaromycosis Co-infection in a Patient with Post-Tuberculosis Lung Disease Yuhai Dang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7796566/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract An 80 year-old woman in rural Guangxi with past pulmonary tuberculosis presented for pneumonia. A month earlier, she consumed raw rodent meat, a known risk factor for Talaromyces marneffei. Post-TB structural damage with new bilateral tree-in-bud opacities on HRCT. T was confirmed after negative AFB smears, metagenomic NGS of BAL fluid. SARS-CoV-2 (35,269 reads) and marneffei (224,752 reads), despite a normal CD4 + count and negative HIV. Nirmatrelvir-ritonavir and antifungal therapy showed improvement. This scenario reveals how helpful mNGS can be for co-infections in hosts whose immune systems are competent and who have a structural lung condition—if the usual diagnostic techniques are failing. Talaromyces marneffei(TB) SARS-CoV-2(COVID-19) Coinfection Metagenomic Next-Generation Sequencing (mNGS) Post-Tuberculosis Lung Disease (PTLD) Figures Figure 1 Background The fungus Talaromyces marneffei which is endemic to Southeast Asia can usually cause disseminated infection in patients with HIV infection. Nonetheless, it is now being increasingly recognized in immunocompetent individuals with pre-existing structural lung disease such as post-tuberculosis lung disease (PTLD) which can compromise local pulmonary defense mechanisms. The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has been a new variable. The viral-induced lung injury can create a milieu for secondary fungal infections. It is difficult to diagnose these co-infections because their radiographic findings are similar and regular microbiological techniques are often not sensitive enough. This report presents a compelling instance of such diagnostic complexity, where a patient with PTLD developed concurrent COVID-19 and talaromycosis. The case underscores the critical importance of considering dual pathogens in structurally compromised lungs, even in the absence of systemic immunodeficiency. Furthermore, it highlights the indispensable role of advanced diagnostic tools like metagenomic next-generation sequencing (mNGS) in overcoming the limitations of conventional tests. Ultimately, this case provides valuable insights for optimizing the management of complex pneumonias in similar high-risk patient populations. Clinical Presentation An 80-year-old woman from rural Guangxi, China, presented with a one-month history of cough and fever, consistent with community-acquired pneumonia. Her medical history was significant for pulmonary tuberculosis treated 10 years prior, which had resulted in residual left-lung destruction and bronchiectasis. Crucially, one month before admission, she had ingested raw rodent meat, adhering to a local cultural practice—a well-documented risk factor for Talaromyces marneffei infection. Laboratory Test Results Summary​​ Key laboratory results on admission are summarized below. Notable abnormalities are marked. Variable Reference Range On Presentation ​​Hematology​​ Hemoglobin 110–160 g/L 98 g/L ↓ White-cell count 4.0–10.0 × 10⁹/L 5.44 × 10⁹/L Monocytes 3–10% 12.9% ↑ Eosinophils 0.5-5% 6.6% ↑ Platelet count 100–300 × 10⁹/L 464 × 10⁹/L ↑ ​ ​Blood Chemistry​​ Albumin 3.3-5.0 g/dL 2.4 g/dL ↓ Erythrocyte sedimentation rate (ESR) 0–20 mm/hr > 130 mm/hr ↑ C-reactive protein (CRP) 0.0–8.0 mg/L 40.1 mg/L ↑ ​ ​Blood Gas Analysis​​ pH 7.35–7.45 7.39 PaO₂ 80–100 mmHg 66.0 mmHg ↓ PaCO₂ 35.0–45.0 mmHg 53.0 mmHg ↑ Actual bicarbonate 21–25 mmol/L 32.1 mmol/L ↑ ​​Immunology​​ Helper T cells (CD4+) 400–1610 /µL 344 /µL ↓ Radiological Findings High-resolution computed tomography (HRCT) of the chest was pivotal. It confirmed known sequelae of prior tuberculosis, including a markedly shrunken left lung with an estimated 60% volume loss, associated mediastinal shift, and widespread bronchiectasis in both lungs(Fig. 1 . A ). Critically, new findings indicative of an active infectious process were present : diffuse, bilateral "tree-in-bud" opacities, suggestive of endobronchial spread, and developing honeycombing in the left upper lobe. The presence of these new opacities superimposed on chronic architectural distortion posed a significant diagnostic challenge. Calcified mediastinal lymph nodes were consistent with remote TB. Differential Diagnosis for New Pulmonary Infiltrates in this Context Infectious Etiologies Non-Infectious Etiologies SARS-CoV-2 Pneumonia Acute exacerbation of bronchiectasis Talaromycosis Diffuse alveolar damage Bacterial superinfection Drug-induced lung injury Reactivation Tuberculosis Nontuberculous Mycobacterial (NTM) Infection Pathological and Microbiological Diagnosis Sputum and bronchoalveolar lavage (BAL) fluid samples were obtained. Both were negative on acid-fast bacilli (AFB) smear. The definitive diagnosis was achieved through metagenomic next-generation sequencing (mNGS) of the BAL fluid, which revealed an overwhelming number of sequence reads for Talaromyces marneffei (224,752 reads) alongside a significant number for SARS-CoV-2 (35,269 reads). A concurrent nasopharyngeal swab was positive for SARS-CoV-2 with a low cycle threshold (Ct) value of 17, confirming active COVID-19 with a high viral load. Immunological workup showed a CD4 + count within the normal range (344 cells/µL) and a negative HIV test. The final diagnosis was a co-infection with COVID-19 and talaromycosis in an immunocompetent host with underlying structural lung disease. Management and Follow-up The patient was treated with a dual approach: nirmatrelvir–ritonavir for COVID-19 and a combination of intravenous amphotericin B followed by voriconazole for talaromycosis. This targeted therapy led to significant clinical improvement. A follow-up SARS-CoV-2 test two weeks later was negative, and a repeat chest CT showed a marked reduction in the tree-in-bud nodules and consolidation. The patient remained well at a 6-month follow-up, with no evidence of relapse(Fig. 1 . B ). Discussion This case depicts a diagnostic difficulty of co-infection with SARS-CoV-2 and Talaromyces marneffei in an immunocompetent host with multilobar post-tuberculous structural lung disease(PTLD). characterized by bronchiectasis and architectural distortion, is increasingly recognized as a major risk factor for chronic respiratory impairment and recurrent infections, creating a vulnerable pulmonary microenvironment [ 1 ] . The COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to cause global morbidity [ 2 ] . Hence, a high-throughput and accurate test for this novel virus is vital for diagnosis and management [ 3 ] . This case demonstrates the important diagnostic and management issues related to complex pneumonias in this vulnerable group. Testing of bronchoalveolar lavage fluid (BAL) using mNGS finally confirmed the diagnosis. The substantial sequence reads for T.marneffei.The relatively high isolate count of T. marneffei (224,752), along with SARS-CoV-2 (35,269), suggests a pulmonary fungal activity rather than colonization, something that is broadly difficult to assert. This is consistent with data on the usefulness of mNGS in identifying rare or unexpected pathogens in complicated clinical situations [ 4 ] . Moreover, this role has been substantiated by the diagnosis of other unusual infections [ 5 ] . Although demanding in resources, mNGS can be definitive when standard diagnostics fail. The epidemiological clue of the patient eating raw rodents was crucial as it is a known risk factor for a talaromycosis in endemic regions. Disseminated talaromycosis, which is commonly documented in patients with HIV [ 6 ] , is being increasingly recognized among immunocompetent patients with risk factors [ 7 ] . The prior PTLD was probably the main predisposing factor for local immune impairment in these “vulnerable” lungs that could have allowed invasive fungal disease to develop, even in the absence of systemic immunodeficiency [ 1 , 8 ] . The concurrent infection with SARS-CoV-2, a pathogen associated with significant inflammatory response in the lungs and hindrance of local defenses [ 9 10 ] , could have contributed to a prevailing pathophysiological environment that worsened the clinical presentation. Continuing research is being conducted to find out innovative therapeutic approaches for COVID-19 [ 11 ] . However, the standard antiviral regimens are the mainstay of treatment. The success of our patient emphasises the importance of a targeted dual-therapy approach. She underwent a current regular COVID-19 treatment with nirmatrelvir–ritonavir for COVID-19 [ 9 ] , and antifungal treatment with intravenous amphotericin B followed by oral voriconazole for talaromycosis infection [ 12 ] . The on-target strategy for treating these infections is verytherapeutic for the management of complex coinfections [ 9 , 12 ] and led to substantial clinical and radiological improvement. This shows the need of customizing antimicrobial strategies for the specific pathogens found. Limitations This report has limitations. The single case retrospective nature of this study limits its generalizability. While the diagnostic efficacy of mNGS is unquestionable, it may not be practical in all resource-poor areas with these infections [ 4 , 5 ] . In addition, we do not have longitudinal data to assess these outcomes. Future studies should validate these findings in relative larger cohorts and determine the cost-effectiveness of mNGS for diagnostic use [ 5 ] . Conclusion In conclusion, this case of a challenging SARS-CoV-2 and T. Marnieffei co infection highlights that structural lung disease, such as post tuberculous lung damage (PTLD), is an important risk factor for severe complex infection, even in immunocompetent persons [ 1 , 8 ] . A comprehensive account of exposures is essential for diagnosis. The final diagnosis obtained by mNGS underscores the important role of mNGS to demonstrate the presence of two pathogens after routine tests fail. The result supports the essential need for a broad diagnostic approach combined with directed antimicrobial therapy [ 8 , 9 , 12 ] . Further studies are needed to verify this comprehensive management strategy for complex pneumonias in patients with underlying lung disease. Declarations Consent to Publish declaration The patient has provided written informed consent for the publication of this case report and any accompanying images. Ethics Approval and Consent to Participate This case report was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval for the publication of this case was granted by the Institutional Review Board / Ethics Committee of Guangxi Zhuang Autonomous Region Jiangbin Hospital. Written informed consent was obtained from the patient for both participation in the clinical study and publication of the case details and accompanying images. Authors' contributions Yuhai Dang is the sole author and corresponding author of this work. Acknowledgements The authors would like to thank Guangxi Zhuang Autonomous Region Jiangbin Hospital for its support and cooperation in conducting this study. Competing interests we confirm that we have no potential or perceived conflicts of interest Availability of data and material Study datasets are available from the corresponding author upon reasonable request. Funding This research received no financial support. References Meghji J, Auld SC, Bisson GP, et al. Post-tuberculosis lung disease: towards prevention, diagnosis, and care. Lancet Respir Med. 2025;13(5):460–72. Washington-Brown L, Cirilo R. Coronavirus Disease – 2019-nCoV (COVID-19). J Natl Black Nurses Assoc. 2020;31(1):19–25. Haque N, Bari MS, Ahmed S, et al. Detection of 2019-Novel Coronavirus (2019-nCoV) by rRT-PCR at Mymensingh Medical College, Mymensingh, Bangladesh. Mymensingh Med J. 2020;29(3):589–95. Wilson MR, O'Donovan BD, Gelfand JM, et al. Chronic Meningitis Investigated via Metagenomic Next-Generation Sequencing. JAMA Neurol. 2018;75(8):947–55. Chen H, Fan C, Gao H et al. Leishmaniasis Diagnosis via Metagenomic Next-Generation Sequencing. Front Cell Infect Microbiol 10:528884. Chang CY, Wahid AA, Ong ELC. Disseminated talaromycosis in an HIV-infected patient. Rev Soc Bras Med Trop. 54:e0896–2020. Harika P, Asthana B, Vashisht R, et al. Disseminated talaromycosis: Truly uncommon or uncommonly recognized? Med J Armed Forces India. 2024;80(Suppl 1):S247–51. Li X, Hu W, Wan Q, et al. Non-HIV talaromycosis: Radiological and clinical analysis. Med (Baltim). 2020;99(10):e19185. Khamees A, Bani-Issa J, Zoubi MSA et al. SARS-CoV-2 and Coronavirus Disease Mitigation: Treatment Options, Vaccinations and Variants. Pathogens. 2022;11(2). Wang M, Liao Z. SARS-CoV-2 and COVID-19: How much do we know? Acta Virol. 2020;64(3):288–96. Bagherani N, Smoller BR, Hypothesis. Designation of Liposomal Scavenger System for Fight against 2019-nCoV. Infect Disord Drug Targets. 2022;22(1):e150621194093. Lu Y, Shi Q, Yu J. Drug-related talaromycosis: A case report. Int J Immunopathol Pharmacol 34:2058738420934611. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7796566","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":526233679,"identity":"cf76332e-9701-4177-b68f-2a8b1a6f824d","order_by":0,"name":"Yuhai 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1","display":"","copyAsset":false,"role":"figure","size":482536,"visible":true,"origin":"","legend":"\u003cp\u003eChest computed tomography images captured at (A) admission, (B) 6 month post-discharge\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7796566/v1/73eae630b9f132707b59067c.png"},{"id":95224284,"identity":"3cf5fe05-9d44-49ec-bee7-55d5e476b121","added_by":"auto","created_at":"2025-11-05 16:23:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1143968,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7796566/v1/b6faa186-e255-4bbf-9638-827f31ab4352.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Double Pathogen Strike: A Case Report of COVID-19 and Talaromycosis Co-infection in a Patient with Post-Tuberculosis Lung Disease","fulltext":[{"header":"Background","content":"\u003cp\u003eThe fungus Talaromyces marneffei which is endemic to Southeast Asia can usually cause disseminated infection in patients with HIV infection. Nonetheless, it is now being increasingly recognized in immunocompetent individuals with pre-existing structural lung disease such as post-tuberculosis lung disease (PTLD) which can compromise local pulmonary defense mechanisms. The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has been a new variable. The viral-induced lung injury can create a milieu for secondary fungal infections. It is difficult to diagnose these co-infections because their radiographic findings are similar and regular microbiological techniques are often not sensitive enough.\u003c/p\u003e\u003cp\u003eThis report presents a compelling instance of such diagnostic complexity, where a patient with PTLD developed concurrent COVID-19 and talaromycosis. The case underscores the critical importance of considering dual pathogens in structurally compromised lungs, even in the absence of systemic immunodeficiency. Furthermore, it highlights the indispensable role of advanced diagnostic tools like metagenomic next-generation sequencing (mNGS) in overcoming the limitations of conventional tests. Ultimately, this case provides valuable insights for optimizing the management of complex pneumonias in similar high-risk patient populations.\u003c/p\u003e"},{"header":"Clinical Presentation","content":"\u003cp\u003eAn 80-year-old woman from rural Guangxi, China, presented with a one-month history of cough and fever, consistent with community-acquired pneumonia. Her medical history was significant for pulmonary tuberculosis treated 10 years prior, which had resulted in residual left-lung destruction and bronchiectasis. \u003cb\u003eCrucially, one month before admission, she had ingested raw rodent meat, adhering to a local cultural practice\u0026mdash;a well-documented risk factor for Talaromyces marneffei infection.\u003c/b\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eLaboratory Test Results Summary​​\u003c/h2\u003e\u003cp\u003eKey laboratory results on admission are summarized below. Notable abnormalities are marked.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eReference Range\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOn Presentation\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003e​​Hematology​​\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e110\u0026ndash;160 g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e98 g/L \u0026darr;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite-cell count\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.0\u0026ndash;10.0 \u0026times; 10⁹/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.44 \u0026times; 10⁹/L\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonocytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u0026ndash;10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.9% \u0026uarr;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEosinophils\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5-5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.6% \u0026uarr;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelet count\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e100\u0026ndash;300 \u0026times; 10⁹/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e464 \u0026times; 10⁹/L \u0026uarr;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e​\u003cb\u003e​Blood Chemistry​​\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.3-5.0 g/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.4 g/dL \u0026darr;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eErythrocyte sedimentation rate (ESR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u0026ndash;20 mm/hr\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;130 mm/hr \u0026uarr;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC-reactive protein (CRP)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0\u0026ndash;8.0 mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40.1 mg/L \u0026uarr;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e​\u003cb\u003e​Blood Gas Analysis​​\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.35\u0026ndash;7.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePaO₂\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e80\u0026ndash;100 mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66.0 mmHg \u0026darr;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePaCO₂\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35.0\u0026ndash;45.0 mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53.0 mmHg \u0026uarr;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eActual bicarbonate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21\u0026ndash;25 mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32.1 mmol/L \u0026uarr;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e​​Immunology​​\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHelper T cells (CD4+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e400\u0026ndash;1610 /\u0026micro;L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e344 /\u0026micro;L \u0026darr;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eRadiological Findings\u003c/b\u003eHigh-resolution computed tomography (HRCT) of the chest was pivotal. It confirmed known sequelae of prior tuberculosis, including a markedly shrunken left lung with an estimated 60% volume loss, associated mediastinal shift, and widespread bronchiectasis in both lungs(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003cb\u003eA\u003c/b\u003e). \u003cb\u003eCritically, new findings indicative of an active infectious process were present\u003c/b\u003e: diffuse, bilateral \"tree-in-bud\" opacities, suggestive of endobronchial spread, and developing honeycombing in the left upper lobe. The presence of these new opacities superimposed on chronic architectural distortion posed a significant diagnostic challenge. Calcified mediastinal lymph nodes were consistent with remote TB.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDifferential Diagnosis for New Pulmonary Infiltrates in this Context\u003c/h3\u003e\n\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfectious Etiologies\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNon-Infectious Etiologies\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSARS-CoV-2 Pneumonia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcute exacerbation of bronchiectasis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTalaromycosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDiffuse alveolar damage\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBacterial superinfection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDrug-induced lung injury\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReactivation Tuberculosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNontuberculous Mycobacterial (NTM) Infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003ePathological and Microbiological Diagnosis\u003c/b\u003eSputum and bronchoalveolar lavage (BAL) fluid samples were obtained. Both were negative on acid-fast bacilli (AFB) smear. The definitive diagnosis was achieved through metagenomic next-generation sequencing (mNGS) of the BAL fluid, which revealed an overwhelming number of sequence reads for \u003cb\u003eTalaromyces marneffei\u003c/b\u003e (224,752 reads) alongside a significant number for \u003cb\u003eSARS-CoV-2\u003c/b\u003e (35,269 reads). A concurrent nasopharyngeal swab was positive for SARS-CoV-2 with a low cycle threshold (Ct) value of 17, confirming active COVID-19 with a high viral load. Immunological workup showed a CD4\u0026thinsp;+\u0026thinsp;count within the normal range (344 cells/\u0026micro;L) and a negative HIV test. The final diagnosis was a \u003cb\u003eco-infection\u003c/b\u003e with COVID-19 and talaromycosis in an immunocompetent host with underlying structural lung disease.\u003c/p\u003e\u003cp\u003e\u003cb\u003eManagement and Follow-up\u003c/b\u003eThe patient was treated with a dual approach: nirmatrelvir\u0026ndash;ritonavir for COVID-19 and a combination of intravenous amphotericin B followed by voriconazole for talaromycosis. This targeted therapy led to significant clinical improvement. A follow-up SARS-CoV-2 test two weeks later was negative, and a repeat chest CT showed a marked reduction in the tree-in-bud nodules and consolidation. The patient remained well at a 6-month follow-up, with no evidence of relapse(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003cb\u003eB\u003c/b\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case depicts a diagnostic difficulty of co-infection with SARS-CoV-2 and Talaromyces marneffei in an immunocompetent host with multilobar post-tuberculous structural lung disease(PTLD). characterized by bronchiectasis and architectural distortion, is increasingly recognized as a major risk factor for chronic respiratory impairment and recurrent infections, creating a vulnerable pulmonary microenvironment\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to cause global morbidity \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Hence, a high-throughput and accurate test for this novel virus is vital for diagnosis and management \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. This case demonstrates the important diagnostic and management issues related to complex pneumonias in this vulnerable group.\u003c/p\u003e\u003cp\u003eTesting of bronchoalveolar lavage fluid (BAL) using mNGS finally confirmed the diagnosis. The substantial sequence reads for T.marneffei.The relatively high isolate count of T. marneffei (224,752), along with SARS-CoV-2 (35,269), suggests a pulmonary fungal activity rather than colonization, something that is broadly difficult to assert. This is consistent with data on the usefulness of mNGS in identifying rare or unexpected pathogens in complicated clinical situations \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Moreover, this role has been substantiated by the diagnosis of other unusual infections\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Although demanding in resources, mNGS can be definitive when standard diagnostics fail.\u003c/p\u003e\u003cp\u003eThe epidemiological clue of the patient eating raw rodents was crucial as it is a known risk factor for a talaromycosis in endemic regions. Disseminated talaromycosis, which is commonly documented in patients with HIV \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e, is being increasingly recognized among immunocompetent patients with risk factors\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. The prior PTLD was probably the main predisposing factor for local immune impairment in these \u0026ldquo;vulnerable\u0026rdquo; lungs that could have allowed invasive fungal disease to develop, even in the absence of systemic immunodeficiency \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. The concurrent infection with SARS-CoV-2, a pathogen associated with significant inflammatory response in the lungs and hindrance of local defenses \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e, could have contributed to a prevailing pathophysiological environment that worsened the clinical presentation. Continuing research is being conducted to find out innovative therapeutic approaches for COVID-19\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. However, the standard antiviral regimens are the mainstay of treatment.\u003c/p\u003e\u003cp\u003eThe success of our patient emphasises the importance of a targeted dual-therapy approach. She underwent a current regular COVID-19 treatment with nirmatrelvir\u0026ndash;ritonavir for COVID-19 \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, and antifungal treatment with intravenous amphotericin B followed by oral voriconazole for talaromycosis infection \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. The on-target strategy for treating these infections is verytherapeutic for the management of complex coinfections \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e and led to substantial clinical and radiological improvement. This shows the need of customizing antimicrobial strategies for the specific pathogens found.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis report has limitations. The single case retrospective nature of this study limits its generalizability. While the diagnostic efficacy of mNGS is unquestionable, it may not be practical in all resource-poor areas with these infections \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. In addition, we do not have longitudinal data to assess these outcomes. Future studies should validate these findings in relative larger cohorts and determine the cost-effectiveness of mNGS for diagnostic use \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this case of a challenging SARS-CoV-2 and T. Marnieffei co infection highlights that structural lung disease, such as post tuberculous lung damage (PTLD), is an important risk factor for severe complex infection, even in immunocompetent persons \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. A comprehensive account of exposures is essential for diagnosis. The final diagnosis obtained by mNGS underscores the important role of mNGS to demonstrate the presence of two pathogens after routine tests fail. The result supports the essential need for a broad diagnostic approach combined with directed antimicrobial therapy \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Further studies are needed to verify this comprehensive management strategy for complex pneumonias in patients with underlying lung disease.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient has provided written informed consent for the publication of this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval for the publication of this case was granted by the Institutional Review Board / Ethics Committee of Guangxi Zhuang Autonomous Region Jiangbin Hospital. Written informed consent was obtained from the patient for both participation in the clinical study and publication of the case details and accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYuhai Dang is the sole author and corresponding author of this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Guangxi Zhuang Autonomous Region Jiangbin Hospital for its support and cooperation in conducting this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ewe confirm that we have no potential or perceived conflicts of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy datasets are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no financial support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMeghji J, Auld SC, Bisson GP, et al. Post-tuberculosis lung disease: towards prevention, diagnosis, and care. Lancet Respir Med. 2025;13(5):460\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWashington-Brown L, Cirilo R. Coronavirus Disease \u0026ndash;\u0026thinsp;2019-nCoV (COVID-19). J Natl Black Nurses Assoc. 2020;31(1):19\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHaque N, Bari MS, Ahmed S, et al. Detection of 2019-Novel Coronavirus (2019-nCoV) by rRT-PCR at Mymensingh Medical College, Mymensingh, Bangladesh. Mymensingh Med J. 2020;29(3):589\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWilson MR, O'Donovan BD, Gelfand JM, et al. Chronic Meningitis Investigated via Metagenomic Next-Generation Sequencing. JAMA Neurol. 2018;75(8):947\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen H, Fan C, Gao H et al. Leishmaniasis Diagnosis via Metagenomic Next-Generation Sequencing. Front Cell Infect Microbiol 10:528884.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChang CY, Wahid AA, Ong ELC. Disseminated talaromycosis in an HIV-infected patient. Rev Soc Bras Med Trop. 54:e0896\u0026ndash;2020.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHarika P, Asthana B, Vashisht R, et al. Disseminated talaromycosis: Truly uncommon or uncommonly recognized? Med J Armed Forces India. 2024;80(Suppl 1):S247\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi X, Hu W, Wan Q, et al. Non-HIV talaromycosis: Radiological and clinical analysis. Med (Baltim). 2020;99(10):e19185.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKhamees A, Bani-Issa J, Zoubi MSA et al. SARS-CoV-2 and Coronavirus Disease Mitigation: Treatment Options, Vaccinations and Variants. Pathogens. 2022;11(2).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang M, Liao Z. SARS-CoV-2 and COVID-19: How much do we know? Acta Virol. 2020;64(3):288\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBagherani N, Smoller BR, Hypothesis. Designation of Liposomal Scavenger System for Fight against 2019-nCoV. Infect Disord Drug Targets. 2022;22(1):e150621194093.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLu Y, Shi Q, Yu J. Drug-related talaromycosis: A case report. Int J Immunopathol Pharmacol 34:2058738420934611.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Talaromyces marneffei(TB), SARS-CoV-2(COVID-19), Coinfection, Metagenomic Next-Generation Sequencing (mNGS), Post-Tuberculosis Lung Disease (PTLD)","lastPublishedDoi":"10.21203/rs.3.rs-7796566/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7796566/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAn 80 year-old woman in rural Guangxi with past pulmonary tuberculosis presented for pneumonia. A month earlier, she consumed raw rodent meat, a known risk factor for Talaromyces marneffei. Post-TB structural damage with new bilateral tree-in-bud opacities on HRCT. T was confirmed after negative AFB smears, metagenomic NGS of BAL fluid. SARS-CoV-2 (35,269 reads) and marneffei (224,752 reads), despite a normal CD4\u0026thinsp;+\u0026thinsp;count and negative HIV. Nirmatrelvir-ritonavir and antifungal therapy showed improvement. This scenario reveals how helpful mNGS can be for co-infections in hosts whose immune systems are competent and who have a structural lung condition\u0026mdash;if the usual diagnostic techniques are failing.\u003c/p\u003e","manuscriptTitle":"A Double Pathogen Strike: A Case Report of COVID-19 and Talaromycosis Co-infection in a Patient with Post-Tuberculosis Lung Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-12 14:38:43","doi":"10.21203/rs.3.rs-7796566/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"38f9ce61-fd27-4c05-af42-c1ac99e2ef43","owner":[],"postedDate":"October 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-04T12:09:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-12 14:38:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7796566","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7796566","identity":"rs-7796566","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}