Postpartum Pulmonary Cryptococcosis Combined With Pulmonary Embolism:A Case Report

Postpartum Pulmonary Cryptococcosis Combined With Pulmonary Embolism:A Case Report | 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 Case Report Postpartum Pulmonary Cryptococcosis Combined With Pulmonary Embolism:A Case Report Yapei CUI, Peng ZOU, Wangwang LIAO, Ziming HUANG, Hanxiao MA, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6399218/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Oct, 2025 Read the published version in BMC Pulmonary Medicine → Version 1 posted 13 You are reading this latest preprint version Abstract Pulmonary cryptococcosis is an opportunistic infection of the lungs caused by cryptococcus, usually in immunosuppressed patients. Pulmonary embolism is a type of venous thromboembolism. Pregnancy and postpartum are risk factors for pulmonary embolism. However, the cases of postpartum pulmonary cryptococcosis combined with pulmonary embolism have not been reported. This case report describes a 39-year-old female who was diagnosed with HIV-negative pulmonary cryptococcosis with pulmonary embolism 42 days postpartum and experienced improvement in her condition after active antifungal and anticoagulant therapy. Because pregnancy is associated with physiological immunosuppression and hypercoagulability, the possibility of pulmonary cryptococcosis combined with pulmonary embolism should be considered in postpartum women with chest pain and newly discovered lung shadow. Pulmonary cryptococcosis Pulmonary embolism Postpartum Case report Figures Figure 1 Figure 2 Background Cryptococcosis is a global fungal disease caused by cryptococcal infection, usually involving the central nervous system and lungs, mainly through respiratory inhalation of cryptococcal spores [ 1 ]. Pulmonary cryptococcosis usually occurs in immunosuppressed patients, and its clinical manifestations are not specific, ranging from asymptomatic to severe ARDS. Pregnancy-related immune changes may lead to the occurrence of pulmonary cryptococcosis.Venous thromboembolism during pregnancy, including deep vein thrombosis(DVT) and pulmonary embolism(PE),is a major factor in maternal death[ 2 ]. The maternal mortality rate associated with pulmonary embolism in the United States increased from 0.93 in 2003 to 1.96 in 2020[ 3 ], and the risk of pulmonary embolism is significantly increased from the beginning of pregnancy to 60 days after hospitalization during delivery[ 4 ]. PE is characterized by dyspnea, pleurisy chest pain, tachycardia, and hemoptysis, but it can also present as non-specific symptoms [ 5 ]. Pregnancy and the postpartum period are one of the risk factors for pulmonary vascular embolism, which is related to hormonal, cardiovascular, anatomical and behavioral changes during pregnancy [ 6 ]. Pregnant and postpartum women are prone to pulmonary cryptococcosis and pulmonary thromboembolism due to immunosuppression andcoagulable state of blood, but there is no related case report.This case report describes a 39-year-old woman who was diagnosed with HIV-negative pulmonary cryptococcosis combined with pulmonary embol after hospital admission at 42 days postpartum, and who improved with active antifungal and anticoagulant therapy, in order to provide a reference for the diagnosis treatment of chest pain and pulmonary shadows in clinical practice, especially in postpartum women. Case introduction A 39-year-old woman presented to our respiratory department with shadow in her lower left lung for 3 weeks. Three weeks ago, the patient was diagnosed as community-acquired pneumonia due to left lower chest and back pain in a foreign hospital, and the symptoms improved after anti-infection with levofloxacin. However, reexamination of chest CT indicated that the left lower lung shadow was not absorbed. The patient had no symptoms such as chest pain, cough, and fever on admission. The patient delivered a baby vaginally one month ago, and had a history of chronic hepatitis B, taking tenofovir disoproxil fumar tablets 0.3g qd. The patient denied any history of contact with animals, dust, or long-distance travel. Laboratory test: Cryptococcus capsular polysaccharide antigen positive, titer 1:80; D-dimer: 0.47 ug/mL (Reference value: 0 ~ 0.5ug/mL); Protein S: 59.9% (reference value: 60 ~ 130%); Lupus anticoagulant screening test 1:30.2 seconds (reference value: 31–44 seconds); Antithrombin III, protein C and other inherited risk factors for venous thrombosis, as well as antiphospholipid syndrome antibodies, homocysteine and other acquired risk factors for venous thrombosis, sputum culture and so on all normal.CTPA shows pulmonary artery embolism in the left lower lobe, left pneumonia and a small amount of pleural effusion (Fig. 1).Echocardiography: Mild mitral regurgitation. There were no abnormalities in blood vessel color ultrasound of both lower limbs, brain MR Plain scan and enhancement. It was suggested that the patient undergo further tracheoscopy to take alveolar lavage fluid and send it for etiological testing, but the patient refused due to his own reasons. At this point, the diagnosis of pulmonary cryptococcosis combined with pulmonary embolism was clear, and the patient was discharged after 5 days of treatment with enoxaparin injection combined with fluconazole sodium chloride injection without special discomfort. After discharge, rivaroxaban and fluconazole tablets were taken orally, and the patient was asked to stop breastfeeding. Reexamination of CTPA 4 months after taking medicine showed that the pulmonary embolism disappeared and the infection of the left lower lobe of the lung more absorbed than before (Fig. 2 ). At present, oral fluconazole treatment was continued, and no special discomfort was reported during follow-up. Discussion The clinical manifestations of pulmonary cryptococcosis are diverse, ranging from asymptomatic infection to pulmonary nodules and even respiratory failure [ 7 ]. The chest imaging manifestations include patchy or ground glass shadows and solid shadows, often distributed along the bronchus with halo signs, voids and pleural effusions [ 8 ]. Cryptococcosis is most commonly seen in HIV infection and solid organ transplant recipients, but other immunosuppressed individuals and immunocompetent populations can develop the disease[ 1 ]. During pregnancy, the body shows a shift from Th1 to Th2 immunity due to hormonal changes, Th2 cells stimulate B lymphocytes to increase antibody production, inhibit cytotoxic T lymphocyte response, and reduce the robustness of cell-mediated immunity. The decline in the number and function of CD4, CD8, and natural killer cells may affect the antifungal response and delay the clearance of pathogenic microorganisms [ 9 ].The onset of postpartum cryptococcosis without HIV infection is usually between one week and six months postpartum (median: two months)[ 10 ].In this case, the patient initially had left thorax and back pain, which disappeared after anti-empirical infection, but the left lower lung flaky shadow still existed, and the pain was considered to be caused by pleurisy. Asymptomatic postpartum pulmonary cryptococcosis has also been reported in the past[ 10 ], so it is considered that the pulmonary cryptococcosis is asymptomatic infection. Although positive etiological smears and cultures of sterile site specimens and histopathological findings of cryptococcal bacteria are important criteria for the diagnosis of cryptococcal disease, these tests have limitations that involve invasive procedures and may lead to delayed diagnosis. Cryptococcal antigen (CrAg) is a low-cost, immediate detection test whose positive results have been identified as one of the diagnostic criteria by the European Guidelines for the diagnosis of cryptococcal meningoencephalitis[ 11 ].The expert consensus on cryptococcal pneumonia in China points out that positive serum cryptococcal antigen detection, combined with medical history and imaging manifestations can clinically diagnose cryptococcal pneumonia[ 12 ]. The overall sensitivity and specificity of CrAg for the diagnosis of cryptococcal infection were 97.6% and 98.1%[ 13 ], and false positives were only present when the titer was 1:2 to 1:5[ 14 , 15 ]. Therefore, although the case was not confirmed by histopathology and fungal culture, the diagnosis could be made based on the patient's medical history, chest CT findings of lung shadow, high cryptococcus capsular antigen titer, and imaging reexamination after antifungal treatment. Pregnant and postpartum women have a six-fold higher risk of VTE compared to non-pregnant women, and the incidence peaks in the first six weeks after delivery [ 16 ]. The increased risk of pulmonary embolism in pregnant and postpartum women is mainly associated with the Virchow triad. Changes in sex hormone levels during pregnancy lead to an increase in coagulation factors (factors I, II, VII, VIII, IX, and X) and a decrease in antithrombotic factors (such as protein C and protein S), leaving pregnant women in a hypercoagulable state[ 17 ]. Hemodynamic changes are related to iliac vein compression, while endothelial injury is due to injury during childbirth[ 18 ]. This case presented with mild decrease of protein S, and other thrombophilia tests were negative, which was considered to be due to the decrease of protein S caused by the body in order to adapt to the possible bleeding risk during delivery[ 19 ]. Infection is the most common cause of hospitalization for VTE [ 20 ]. Research on the immune status of PE patients has found that Th1 activity is reduced and Th2 activity is enhanced in PE patients [21] . Combined with above text, it can be speculated that the occurrence of pulmonary embolism may be related to cryptococcal infection.D-dimer is elevated during acute thrombosis, due to physiological changes in female D-dimer during pregnancy and false negative in some PE patients. American College of Obstetricians and Gynecologists guidelines do not recommend D-dimer as part of VTE evaluation during pregnancy or childbirth [22] . Therefore, although the D-dimer in this patient was within the normal range, the possibility of pulmonary embolism should still be considered due to the existence of risk factors. Computed tomographic pulmonary angiograph (CTPA) is the gold standard for the diagnosis of pulmonary embolism. In this case, CTPA of the patient suggested pulmonary embolism in the posterior basal segment of the left lower lobe, and patchy shadows in left lower lobe, combined with positive Cryptococcus neoformans capsular antigen, and was finally diagnosed with cryptococcus combined with pulmonary embolism. Pulmonary infarction is a condition in which pulmonary blood vessel obstruction leads to ischemia and alveolar hemorrhage. If the latter cannot be absorbed, it will eventually lead to lung tissue necrosis [ 23 ], and fibrous scars will be formed in the infarct area, lasting for weeks or even months [ 24 ]. The clinical manifestations of patients with pulmonary infarction are not specific, but pleurisy chest pain often occurs [ 24 ], which may be related to the pleural inflammation, irritation and necrosis caused by alveolar hemorrhage. At present, the diagnosis of pulmonary infarction is still mainly based on imaging, which is usually wedge-shaped in the subpleura, and its imaging manifestations include consolidation, pulmonary edema, pleural effusion and ground glass changes [ 25 ]. In our case, the shadow in the patient's lung was considered to be caused by cryptococcal infection and pulmonary embolism leading to infar.It was speculated that the patient's chest pain might be related to secondary infection caused by ischemia, bleeding and edema caused by infarct lesions, so her chest pain was improved by empirical anti-infection prior to admission. The treatment of pulmonary cryptococcosis varies according to the severity of the disease. This case was treated with fluconazole orally after discharge with mild clinical symptoms. In the treatment of pulmonary thromboembolism, anticoagulation, thrombolysis and interventional therapy can be selected according to the risk stratification. Common oral anticoagulation drugs include warfarin and rivaroxaban. More than 80% of warfarin is metabolized by CYP2C9, while fluconazole is a moderate inhibitor of CYP2C9, and the combination of the two causes an increased risk of bleeding [26] . However, rivaroxaban is quickly absorbed after oral administration, and there is less interaction between drugs, so there is no need to measure INR. Therefore, we gave patients long-term oral rivaroxaban combined with fluconazole treatment after discharge. Considering that fluconazole and rivaroxaban can be secreted by breast milk, we recommend that patients avoid breastfeeding. There are still the following deficiencies in this case: First, the gradual transformation of maternal immune system from Th2 to Th1 after delivery may induce immune reconstitution of inflammatory syndrome [27] . The patient did not provide previous chest imaging data, so it cannot be ruled out that the patient had a pulmonary cryptococcal infection before pregnancy and may have worsened during pregnancy. Secondly, the known genus of Cryptococcus includes 37 species, among which Cryptococcus neoformans and Cryptococcus gattii are the main pathogenic types causing human infection [28] . As the patient refused to perform invasive operations, the pathogen and pathology of the lesion tissue were not detected in this case, and it could not be determined which cryptococcal infection the patient had. Conclusion We report a case of postpartum pulmonary cryptococcosis combined with pulmonary embolism, suggesting that postpartum chest pain and newly discovered shadows should be considered for pulmonary embolism combined with pulmonary cryptococcosis in pregnant women due to their hypercoagulable state of blood and changes in immune, and that the fluconazole combined with rivaroxaban regimen is safe and effective in patients with pulmonary cryptococcosis combined with pulmonary embolism. Abbreviations DVT deep vein thrombosis PE pulmonary embolism Declarations Acknowledgments The authors wish to express their sincere gratitude to Ms. Chen for granting explicit authorization for manuscript preparation, and to Ms. Xingchen Zhou for providing professional guidance on linguistic adaptation of this document. Authors’ contributions Z. Q., P. Z. designed the study. Y. C., W. L. collected data. Z. Q., P. Z.,Y. C. analyzed data and wrote the case report. P. Z., Y. C., W. L., Z. H., H. M., H. G. contributed to the discussion of results and to the review of the manuscript. All authors read and approved the final manuscript. Funding No external funding was obtained from institutional, corporate, or philanthropic sources to support this research. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Z. Q. will make the data available to readers. Ethics approval and consent to participate The Ethics Committee of Foshan Hospital of Traditional Chinese Medicine approved the study. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare that they have no competing interests. Author details 1.The Eighth Clinical Medical School of Guangzhou University of Chinese Medicine, Foshan 528000, Guangdong Province, China. 2.Foshan Hospital of Traditional Chinese Medicine, Foshan 528000,Guangdong Province,China. 3.CLIFFORD HOSPITAL,Guangzhou 511400, Guangdong Province,China. References Chang CC, Harrison TS, Bicanic TA, et al. Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM. Lancet Infect Dis. 2024;24(8):e495-e512,http://dx.doi.org/10.1016/s1473-3099(23)00731-4. Kalaitzopoulos DR, Panagopoulos A, Samant S, et al. Management of venous thromboembolism in pregnancy. Thromb Res. 2022;211:106-13,http://dx.doi.org/10.1016/j.thromres.2022.02.002. Farmakis IT, Barco S, Hobohm L, et al. Maternal mortality related to pulmonary embolism in the United States, 2003-2020. Am J Obstet Gynecol MFM. 2023;5(1):100754,http://dx.doi.org/10.1016/j.ajogmf.2022.100754. Kola O, Huang Y, D'Alton ME, Wright JD, Friedman AM. Trends in Antepartum, Delivery, and Postpartum Venous Thromboembolism. Obstet Gynecol. 2025,http://dx.doi.org/10.1097/aog.0000000000005818. Wrenn JO, Kabrhel C. Emergency department diagnosis and management of acute pulmonary embolism. Br J Haematol. 2024;205(5):1714-6,http://dx.doi.org/10.1111/bjh.19725. Samuelson Bannow B, Federspiel JJ, Abel DE, Mauney L, Rosovsky RP, Bates SM. Multidisciplinary care of the pregnant patient with or at risk for venous thromboembolism: a recommended toolkit from the Foundation for Women and Girls with Blood Disorders Thrombosis Subcommittee. J Thromb Haemost. 2023;21(6):1432-40,http://dx.doi.org/10.1016/j.jtha.2023.03.015. Jani A, Reigler AN, Leal SM, Jr., McCarty TP. Updates in Cryptococcosis. Infect Dis Clin North Am. 2024,http://dx.doi.org/10.1016/j.idc.2024.11.011. Dai C, Bai D, Lin C, et al. The relationship between lung CT features and serum cryptococcal antigen titers in localized pulmonary cryptococcosis patients. BMC Pulm Med. 2024;24(1):441,http://dx.doi.org/10.1186/s12890-024-03259-4. Kourtis AP, Read JS, Jamieson DJ. Pregnancy and infection. N Engl J Med. 2014;370(23):2211-8,http://dx.doi.org/10.1056/NEJMra1213566. Yokoyama T, Kadowaki M, Yoshida M, Suzuki K, Komori M, Iwanaga T. Disseminated Cryptococcosis with Marked Eosinophilia in a Postpartum Woman. Intern Med. 2018;57(1):135-9,http://dx.doi.org/10.2169/internalmedicine.9247-17. De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46(12):1813-21,http://dx.doi.org/10.1086/588660. Association RSoZM. 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Pregnancy-Related Thromboembolism-Current Challenges at the Emergency Department. J Pers Med. 2024;14(9),http://dx.doi.org/10.3390/jpm14090926. Makowska A, Treumann T, Venturini S, Christ M. Pulmonary Embolism in Pregnancy: A Review for Clinical Practitioners. J Clin Med. 2024;13(10),http://dx.doi.org/10.3390/jcm13102863. Blondon M, Skeith L. Preventing Postpartum Venous Thromboembolism in 2022: A Narrative Review. Front Cardiovasc Med. 2022;9:886416,http://dx.doi.org/10.3389/fcvm.2022.886416. Georgescu T. The role of maternal hormones in regulating autonomic functions during pregnancy. J Neuroendocrinol. 2023;35(12):e13348,http://dx.doi.org/10.1111/jne.13348. Rogers MA, Levine DA, Blumberg N, Flanders SA, Chopra V, Langa KM. Triggers of hospitalization for venous thromboembolism. Circulation. 2012;125(17):2092-9,http://dx.doi.org/10.1161/circulationaha.111.084467. Duan Q, Lv W, Wang L, et al. mRNA expression of interleukins and Th1/Th2 imbalance in patients with pulmonary embolism. Mol Med Rep. 2013;7(1):332-6,http://dx.doi.org/10.3892/mmr.2012.1142. ACOG Practice Bulletin No. 196: Thromboembolism in Pregnancy. Obstet Gynecol. 2018;132(1):e1-e17,http://dx.doi.org/10.1097/aog.0000000000002706. Kaptein FHJ, Kroft LJM, van Dam LF, et al. Impact of pulmonary infarction in pulmonary embolism on presentation and outcomes. Thromb Res. 2023;226:51-5,http://dx.doi.org/10.1016/j.thromres.2023.04.005. Gagno G, Padoan L, D'Errico S, et al. Pulmonary Embolism Presenting with Pulmonary Infarction: Update and Practical Review of Literature Data. J Clin Med. 2022;11(16),http://dx.doi.org/10.3390/jcm11164916. Lio KU, O'Corragain O, Bashir R, et al. Clinical outcomes and factors associated with pulmonary infarction following acute pulmonary embolism: a retrospective observational study at a US academic centre. BMJ Open. 2022;12(12):e067579,http://dx.doi.org/10.1136/bmjopen-2022-067579. Geng K, Shen C, Wang X, et al. A physiologically-based pharmacokinetic/pharmacodynamic modeling approach for drug-drug-gene interaction evaluation of S-warfarin with fluconazole. CPT Pharmacometrics Syst Pharmacol. 2024;13(5):853-69,http://dx.doi.org/10.1002/psp4.13123. Singh N, Perfect JR. Immune reconstitution syndrome and exacerbation of infections after pregnancy. Clin Infect Dis. 2007;45(9):1192-9,http://dx.doi.org/10.1086/522182. Yang C, Huang Y, Zhou Y, et al. Cryptococcus escapes host immunity: What do we know? Front Cell Infect Microbiol. 2022;12:1041036,http://dx.doi.org/10.3389/fcimb.2022.1041036. 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-6399218","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":454789778,"identity":"7344c197-62a8-496b-b548-8e6750c833e8","order_by":0,"name":"Yapei CUI","email":"","orcid":"","institution":"The Eighth Clinical Medical School of Guangzhou University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yapei","middleName":"","lastName":"CUI","suffix":""},{"id":454789779,"identity":"a57595fc-5c4a-420d-9e29-119b9932f057","order_by":1,"name":"Peng ZOU","email":"","orcid":"","institution":"The Eighth Clinical Medical School of Guangzhou University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"ZOU","suffix":""},{"id":454789780,"identity":"582b5328-e039-4340-b94f-74faf8c37a45","order_by":2,"name":"Wangwang LIAO","email":"","orcid":"","institution":"The Eighth Clinical Medical School of Guangzhou University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Wangwang","middleName":"","lastName":"LIAO","suffix":""},{"id":454789781,"identity":"1a8790ec-e300-4035-9cbf-d9690f8e96fd","order_by":3,"name":"Ziming HUANG","email":"","orcid":"","institution":"CLIFFORD HOSPITAL","correspondingAuthor":false,"prefix":"","firstName":"Ziming","middleName":"","lastName":"HUANG","suffix":""},{"id":454789782,"identity":"c4dbcef9-5c89-4a49-9678-4bd44746a73d","order_by":4,"name":"Hanxiao MA","email":"","orcid":"","institution":"CLIFFORD HOSPITAL","correspondingAuthor":false,"prefix":"","firstName":"Hanxiao","middleName":"","lastName":"MA","suffix":""},{"id":454789783,"identity":"3c63c956-61dd-4a8b-a646-1277aec1e9a9","order_by":5,"name":"Huilin GAN","email":"","orcid":"","institution":"The Eighth Clinical Medical School of Guangzhou University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Huilin","middleName":"","lastName":"GAN","suffix":""},{"id":454789784,"identity":"d846d436-44fc-48df-a731-cb9cb20f1828","order_by":6,"name":"Zhenhong QI","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYDACZgY2IHkAxDr44IOBjR0pWtiSDWcUpCUTYw9MC4+ZNM+HQ4wNhNTzHWd/9uDjjjty5vzLEqRtDA4wM7AfProBnxbJwwzphjPPPDO2nPH4gHGOwR0+Bp60tBv4tBgcZjgmzdt2OHHDjWMJyTkGz5gZJHjMCGhhbJP+C9ZyxuCwBZDbQFgLM5s0I0jL+R7DZgZitEgeZmOT7G07bGxwgy2ZsccgLZmNkF/4zh9/JvGz7bCcwfnDx3/8+GNjx89++BheLeAYAQOJBAjNhlc5ihb+A7gVjYJRMApGwcgGAInUUk49CeMUAAAAAElFTkSuQmCC","orcid":"","institution":"The Eighth Clinical Medical School of Guangzhou University of Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Zhenhong","middleName":"","lastName":"QI","suffix":""}],"badges":[],"createdAt":"2025-04-08 04:53:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6399218/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6399218/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12890-025-03902-8","type":"published","date":"2025-10-01T15:58:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82623782,"identity":"42f60fe9-1bf2-4ee3-a9aa-8600007b1874","added_by":"auto","created_at":"2025-05-13 12:45:04","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":70350,"visible":true,"origin":"","legend":"\u003cp\u003eA and B are pre-treatment pulmonary artery CTA images, showing posterior basal pulmonary embolism in the left lower lung, posterior basal inflammation outside the left lower lobe, and a small amount of pleural effusion on the left side; C is enlarged image of posterior basal pulmonary embolism in the left lower lung.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6399218/v1/9a5d8bff3d3be43bb28a72a2.jpg"},{"id":82623783,"identity":"84591e68-8fa6-41f0-9f71-84c0e27f632e","added_by":"auto","created_at":"2025-05-13 12:45:04","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":69853,"visible":true,"origin":"","legend":"\u003cp\u003eD and E are the images after treatment, showing that pulmonary artery was not blocked by CT angiography, and the infection of the posterior basal segment outside the left lower lobe of the lung was more absorbed than that in the front. F is the enlarged images of the posterior basal segment of the left lower lung.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6399218/v1/b2245d49e02d3158da0d7b5e.jpg"},{"id":92884479,"identity":"3f938d78-675d-4a39-948a-496e91a2df60","added_by":"auto","created_at":"2025-10-06 16:13:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":527506,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6399218/v1/3028c0f6-76e8-4889-a20a-8585d54ed399.pdf"},{"id":82623789,"identity":"0357421d-2646-4974-88cb-6abd57279ad4","added_by":"auto","created_at":"2025-05-13 12:45:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":108563,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklistEnglish2013.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6399218/v1/b5560859a45d3033ec472515.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Postpartum Pulmonary Cryptococcosis Combined With Pulmonary Embolism:A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eCryptococcosis is a global fungal disease caused by cryptococcal infection, usually involving the central nervous system and lungs, mainly through respiratory inhalation of cryptococcal spores [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Pulmonary cryptococcosis usually occurs in immunosuppressed patients, and its clinical manifestations are not specific, ranging from asymptomatic to severe ARDS. Pregnancy-related immune changes may lead to the occurrence of pulmonary cryptococcosis.Venous thromboembolism during pregnancy, including deep vein thrombosis(DVT) and pulmonary embolism(PE),is a major factor in maternal death[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The maternal mortality rate associated with pulmonary embolism in the United States increased from 0.93 in 2003 to 1.96 in 2020[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], and the risk of pulmonary embolism is significantly increased from the beginning of pregnancy to 60 days after hospitalization during delivery[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. PE is characterized by dyspnea, pleurisy chest pain, tachycardia, and hemoptysis, but it can also present as non-specific symptoms [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Pregnancy and the postpartum period are one of the risk factors for pulmonary vascular embolism, which is related to hormonal, cardiovascular, anatomical and behavioral changes during pregnancy [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePregnant and postpartum women are prone to pulmonary cryptococcosis and pulmonary thromboembolism due to immunosuppression andcoagulable state of blood, but there is no related case report.This case report describes a 39-year-old woman who was diagnosed with HIV-negative pulmonary cryptococcosis combined with pulmonary embol after hospital admission at 42 days postpartum, and who improved with active antifungal and anticoagulant therapy, in order to provide a reference for the diagnosis treatment of chest pain and pulmonary shadows in clinical practice, especially in postpartum women.\u003c/p\u003e"},{"header":"Case introduction","content":"\u003cp\u003eA 39-year-old woman presented to our respiratory department with shadow in her lower left lung for 3 weeks. Three weeks ago, the patient was diagnosed as community-acquired pneumonia due to left lower chest and back pain in a foreign hospital, and the symptoms improved after anti-infection with levofloxacin. However, reexamination of chest CT indicated that the left lower lung shadow was not absorbed. The patient had no symptoms such as chest pain, cough, and fever on admission. The patient delivered a baby vaginally one month ago, and had a history of chronic hepatitis B, taking tenofovir disoproxil fumar tablets 0.3g qd. The patient denied any history of contact with animals, dust, or long-distance travel. Laboratory test: Cryptococcus capsular polysaccharide antigen positive, titer 1:80; D-dimer: 0.47 ug/mL (Reference value: 0\u0026thinsp;~\u0026thinsp;0.5ug/mL); Protein S: 59.9% (reference value: 60\u0026thinsp;~\u0026thinsp;130%); Lupus anticoagulant screening test 1:30.2 seconds (reference value: 31\u0026ndash;44 seconds); Antithrombin III, protein C and other inherited risk factors for venous thrombosis, as well as antiphospholipid syndrome antibodies, homocysteine and other acquired risk factors for venous thrombosis, sputum culture and so on all normal.CTPA shows pulmonary artery embolism in the left lower lobe, left pneumonia and a small amount of pleural effusion (Fig.\u0026nbsp;1).Echocardiography: Mild mitral regurgitation. There were no abnormalities in blood vessel color ultrasound of both lower limbs, brain MR Plain scan and enhancement. It was suggested that the patient undergo further tracheoscopy to take alveolar lavage fluid and send it for etiological testing, but the patient refused due to his own reasons. At this point, the diagnosis of pulmonary cryptococcosis combined with pulmonary embolism was clear, and the patient was discharged after 5 days of treatment with enoxaparin injection combined with fluconazole sodium chloride injection without special discomfort. After discharge, rivaroxaban and fluconazole tablets were taken orally, and the patient was asked to stop breastfeeding. Reexamination of CTPA 4 months after taking medicine showed that the pulmonary embolism disappeared and the infection of the left lower lobe of the lung more absorbed than before (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e). At present, oral fluconazole treatment was continued, and no special discomfort was reported during follow-up.\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eThe clinical manifestations of pulmonary cryptococcosis are diverse, ranging from asymptomatic infection to pulmonary nodules and even respiratory failure [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The chest imaging manifestations include patchy or ground glass shadows and solid shadows, often distributed along the bronchus with halo signs, voids and pleural effusions [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Cryptococcosis is most commonly seen in HIV infection and solid organ transplant recipients, but other immunosuppressed individuals and immunocompetent populations can develop the disease[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. During pregnancy, the body shows a shift from Th1 to Th2 immunity due to hormonal changes, Th2 cells stimulate B lymphocytes to increase antibody production, inhibit cytotoxic T lymphocyte response, and reduce the robustness of cell-mediated immunity. The decline in the number and function of CD4, CD8, and natural killer cells may affect the antifungal response and delay the clearance of pathogenic microorganisms [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].The onset of postpartum cryptococcosis without HIV infection is usually between one week and six months postpartum (median: two months)[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].In this case, the patient initially had left thorax and back pain, which disappeared after anti-empirical infection, but the left lower lung flaky shadow still existed, and the pain was considered to be caused by pleurisy. Asymptomatic postpartum pulmonary cryptococcosis has also been reported in the past[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], so it is considered that the pulmonary cryptococcosis is asymptomatic infection.\u003c/p\u003e \u003cp\u003eAlthough positive etiological smears and cultures of sterile site specimens and histopathological findings of cryptococcal bacteria are important criteria for the diagnosis of cryptococcal disease, these tests have limitations that involve invasive procedures and may lead to delayed diagnosis. Cryptococcal antigen (CrAg) is a low-cost, immediate detection test whose positive results have been identified as one of the diagnostic criteria by the European Guidelines for the diagnosis of cryptococcal meningoencephalitis[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].The expert consensus on cryptococcal pneumonia in China points out that positive serum cryptococcal antigen detection, combined with medical history and imaging manifestations can clinically diagnose cryptococcal pneumonia[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The overall sensitivity and specificity of CrAg for the diagnosis of cryptococcal infection were 97.6% and 98.1%[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and false positives were only present when the titer was 1:2 to 1:5[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Therefore, although the case was not confirmed by histopathology and fungal culture, the diagnosis could be made based on the patient's medical history, chest CT findings of lung shadow, high cryptococcus capsular antigen titer, and imaging reexamination after antifungal treatment.\u003c/p\u003e \u003cp\u003ePregnant and postpartum women have a six-fold higher risk of VTE compared to non-pregnant women, and the incidence peaks in the first six weeks after delivery [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The increased risk of pulmonary embolism in pregnant and postpartum women is mainly associated with the Virchow triad. Changes in sex hormone levels during pregnancy lead to an increase in coagulation factors (factors I, II, VII, VIII, IX, and X) and a decrease in antithrombotic factors (such as protein C and protein S), leaving pregnant women in a hypercoagulable state[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Hemodynamic changes are related to iliac vein compression, while endothelial injury is due to injury during childbirth[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis case presented with mild decrease of protein S, and other thrombophilia tests were negative, which was considered to be due to the decrease of protein S caused by the body in order to adapt to the possible bleeding risk during delivery[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Infection is the most common cause of hospitalization for VTE [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Research on the immune status of PE patients has found that Th1 activity is reduced and Th2 activity is enhanced in PE patients\u003csup\u003e[21]\u003c/sup\u003e. Combined with above text, it can be speculated that the occurrence of pulmonary embolism may be related to cryptococcal infection.D-dimer is elevated during acute thrombosis, due to physiological changes in female D-dimer during pregnancy and false negative in some PE patients. American College of Obstetricians and Gynecologists guidelines do not recommend D-dimer as part of VTE evaluation during pregnancy or childbirth \u003csup\u003e[22]\u003c/sup\u003e. Therefore, although the D-dimer in this patient was within the normal range, the possibility of pulmonary embolism should still be considered due to the existence of risk factors. Computed tomographic pulmonary angiograph (CTPA) is the gold standard for the diagnosis of pulmonary embolism. In this case, CTPA of the patient suggested pulmonary embolism in the posterior basal segment of the left lower lobe, and patchy shadows in left lower lobe, combined with positive Cryptococcus neoformans capsular antigen, and was finally diagnosed with cryptococcus combined with pulmonary embolism.\u003c/p\u003e \u003cp\u003ePulmonary infarction is a condition in which pulmonary blood vessel obstruction leads to ischemia and alveolar hemorrhage. If the latter cannot be absorbed, it will eventually lead to lung tissue necrosis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], and fibrous scars will be formed in the infarct area, lasting for weeks or even months [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The clinical manifestations of patients with pulmonary infarction are not specific, but pleurisy chest pain often occurs [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], which may be related to the pleural inflammation, irritation and necrosis caused by alveolar hemorrhage. At present, the diagnosis of pulmonary infarction is still mainly based on imaging, which is usually wedge-shaped in the subpleura, and its imaging manifestations include consolidation, pulmonary edema, pleural effusion and ground glass changes [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In our case, the shadow in the patient's lung was considered to be caused by cryptococcal infection and pulmonary embolism leading to infar.It was speculated that the patient's chest pain might be related to secondary infection caused by ischemia, bleeding and edema caused by infarct lesions, so her chest pain was improved by empirical anti-infection prior to admission.\u003c/p\u003e \u003cp\u003eThe treatment of pulmonary cryptococcosis varies according to the severity of the disease. This case was treated with fluconazole orally after discharge with mild clinical symptoms. In the treatment of pulmonary thromboembolism, anticoagulation, thrombolysis and interventional therapy can be selected according to the risk stratification. Common oral anticoagulation drugs include warfarin and rivaroxaban. More than 80% of warfarin is metabolized by CYP2C9, while fluconazole is a moderate inhibitor of CYP2C9, and the combination of the two causes an increased risk of bleeding \u003csup\u003e[26]\u003c/sup\u003e. However, rivaroxaban is quickly absorbed after oral administration, and there is less interaction between drugs, so there is no need to measure INR. Therefore, we gave patients long-term oral rivaroxaban combined with fluconazole treatment after discharge. Considering that fluconazole and rivaroxaban can be secreted by breast milk, we recommend that patients avoid breastfeeding.\u003c/p\u003e \u003cp\u003eThere are still the following deficiencies in this case: First, the gradual transformation of maternal immune system from Th2 to Th1 after delivery may induce immune reconstitution of inflammatory syndrome \u003csup\u003e[27]\u003c/sup\u003e. The patient did not provide previous chest imaging data, so it cannot be ruled out that the patient had a pulmonary cryptococcal infection before pregnancy and may have worsened during pregnancy. Secondly, the known genus of Cryptococcus includes 37 species, among which Cryptococcus neoformans and Cryptococcus gattii are the main pathogenic types causing human infection \u003csup\u003e[28]\u003c/sup\u003e. As the patient refused to perform invasive operations, the pathogen and pathology of the lesion tissue were not detected in this case, and it could not be determined which cryptococcal infection the patient had.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe report a case of postpartum pulmonary cryptococcosis combined with pulmonary embolism, suggesting that postpartum chest pain and newly discovered shadows should be considered for pulmonary embolism combined with pulmonary cryptococcosis in pregnant women due to their hypercoagulable state of blood and changes in immune, and that the fluconazole combined with rivaroxaban regimen is safe and effective in patients with pulmonary cryptococcosis combined with pulmonary embolism.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDVT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edeep vein thrombosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epulmonary embolism\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors wish to express their sincere gratitude to Ms. Chen for granting explicit authorization for manuscript preparation, and to Ms. Xingchen Zhou for providing professional guidance on linguistic adaptation of this document.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZ. Q., P. Z. designed the study. Y. C., W. L. collected data. Z. Q., P. Z.,Y. C. analyzed data and wrote the case report. P. Z., Y. C., W. L., Z. H., H. M., H. G. contributed to the discussion of results and to the review of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo external funding was obtained from institutional, corporate, or philanthropic sources to support this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Z. Q. will make the data available to readers.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Ethics Committee of Foshan Hospital of Traditional Chinese Medicine approved the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.The Eighth Clinical Medical School of Guangzhou University of Chinese Medicine, Foshan 528000, Guangdong Province, China.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.Foshan Hospital of Traditional Chinese Medicine, Foshan 528000,Guangdong Province,China.\u003c/p\u003e\n\u003cp\u003e3.CLIFFORD HOSPITAL,Guangzhou 511400, Guangdong Province,China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChang CC, Harrison TS, Bicanic TA, et al. Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM. Lancet Infect Dis. 2024;24(8):e495-e512,http://dx.doi.org/10.1016/s1473-3099(23)00731-4.\u003c/li\u003e\n\u003cli\u003eKalaitzopoulos DR, Panagopoulos A, Samant S, et al. Management of venous thromboembolism in pregnancy. Thromb Res. 2022;211:106-13,http://dx.doi.org/10.1016/j.thromres.2022.02.002.\u003c/li\u003e\n\u003cli\u003eFarmakis IT, Barco S, Hobohm L, et al. Maternal mortality related to pulmonary embolism in the United States, 2003-2020. Am J Obstet Gynecol MFM. 2023;5(1):100754,http://dx.doi.org/10.1016/j.ajogmf.2022.100754.\u003c/li\u003e\n\u003cli\u003eKola O, Huang Y, D\u0026apos;Alton ME, Wright JD, Friedman AM. Trends in Antepartum, Delivery, and Postpartum Venous Thromboembolism. Obstet Gynecol. 2025,http://dx.doi.org/10.1097/aog.0000000000005818.\u003c/li\u003e\n\u003cli\u003eWrenn JO, Kabrhel C. Emergency department diagnosis and management of acute pulmonary embolism. 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N Engl J Med. 2014;370(23):2211-8,http://dx.doi.org/10.1056/NEJMra1213566.\u003c/li\u003e\n\u003cli\u003eYokoyama T, Kadowaki M, Yoshida M, Suzuki K, Komori M, Iwanaga T. Disseminated Cryptococcosis with Marked Eosinophilia in a Postpartum Woman. Intern Med. 2018;57(1):135-9,http://dx.doi.org/10.2169/internalmedicine.9247-17.\u003c/li\u003e\n\u003cli\u003eDe Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46(12):1813-21,http://dx.doi.org/10.1086/588660.\u003c/li\u003e\n\u003cli\u003eAssociation RSoZM. Expert consensus on diagnosis and treatment of pulmonary cryptococcosis. Chin J Clin Infect Dis. 2017;10(5):321-6\u003c/li\u003e\n\u003cli\u003eHuang HR, Fan LC, Rajbanshi B, Xu JF. 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Circulation. 2012;125(17):2092-9,http://dx.doi.org/10.1161/circulationaha.111.084467.\u003c/li\u003e\n\u003cli\u003eDuan Q, Lv W, Wang L, et al. mRNA expression of interleukins and Th1/Th2 imbalance in patients with pulmonary embolism. Mol Med Rep. 2013;7(1):332-6,http://dx.doi.org/10.3892/mmr.2012.1142.\u003c/li\u003e\n\u003cli\u003eACOG Practice Bulletin No. 196: Thromboembolism in Pregnancy. Obstet Gynecol. 2018;132(1):e1-e17,http://dx.doi.org/10.1097/aog.0000000000002706.\u003c/li\u003e\n\u003cli\u003eKaptein FHJ, Kroft LJM, van Dam LF, et al. Impact of pulmonary infarction in pulmonary embolism on presentation and outcomes. Thromb Res. 2023;226:51-5,http://dx.doi.org/10.1016/j.thromres.2023.04.005.\u003c/li\u003e\n\u003cli\u003eGagno G, Padoan L, D\u0026apos;Errico S, et al. Pulmonary Embolism Presenting with Pulmonary Infarction: Update and Practical Review of Literature Data. J Clin Med. 2022;11(16),http://dx.doi.org/10.3390/jcm11164916.\u003c/li\u003e\n\u003cli\u003eLio KU, O\u0026apos;Corragain O, Bashir R, et al. Clinical outcomes and factors associated with pulmonary infarction following acute pulmonary embolism: a retrospective observational study at a US academic centre. BMJ Open. 2022;12(12):e067579,http://dx.doi.org/10.1136/bmjopen-2022-067579.\u003c/li\u003e\n\u003cli\u003eGeng K, Shen C, Wang X, et al. A physiologically-based pharmacokinetic/pharmacodynamic modeling approach for drug-drug-gene interaction evaluation of S-warfarin with fluconazole. CPT Pharmacometrics Syst Pharmacol. 2024;13(5):853-69,http://dx.doi.org/10.1002/psp4.13123.\u003c/li\u003e\n\u003cli\u003eSingh N, Perfect JR. Immune reconstitution syndrome and exacerbation of infections after pregnancy. Clin Infect Dis. 2007;45(9):1192-9,http://dx.doi.org/10.1086/522182.\u003c/li\u003e\n\u003cli\u003eYang C, Huang Y, Zhou Y, et al. Cryptococcus escapes host immunity: What do we know? Front Cell Infect Microbiol. 2022;12:1041036,http://dx.doi.org/10.3389/fcimb.2022.1041036.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pulmonary cryptococcosis, Pulmonary embolism, Postpartum, Case report","lastPublishedDoi":"10.21203/rs.3.rs-6399218/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6399218/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePulmonary cryptococcosis is an opportunistic infection of the lungs caused by cryptococcus, usually in immunosuppressed patients. Pulmonary embolism is a type of venous thromboembolism. Pregnancy and postpartum are risk factors for pulmonary embolism. However, the cases of postpartum pulmonary cryptococcosis combined with pulmonary embolism have not been reported. This case report describes a 39-year-old female who was diagnosed with HIV-negative pulmonary cryptococcosis with pulmonary embolism 42 days postpartum and experienced improvement in her condition after active antifungal and anticoagulant therapy. Because pregnancy is associated with physiological immunosuppression and hypercoagulability, the possibility of pulmonary cryptococcosis combined with pulmonary embolism should be considered in postpartum women with chest pain and newly discovered lung shadow.\u003c/p\u003e","manuscriptTitle":"Postpartum Pulmonary Cryptococcosis Combined With Pulmonary Embolism:A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 12:44:59","doi":"10.21203/rs.3.rs-6399218/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-20T08:17:07+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-18T10:30:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-15T23:35:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"221295302346237964933244766669206358459","date":"2025-06-10T23:54:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"175462244729984496987265521079021072434","date":"2025-06-10T08:01:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-11T02:00:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"325134096757674086002452806910116963338","date":"2025-05-09T22:42:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"339134762893532394753467789412598823988","date":"2025-05-08T12:42:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-08T12:31:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-30T12:09:55+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-30T11:56:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-29T17:36:55+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2025-04-29T17:35:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0ce6fa12-0853-4c52-b5df-2e372310d8e3","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T16:10:10+00:00","versionOfRecord":{"articleIdentity":"rs-6399218","link":"https://doi.org/10.1186/s12890-025-03902-8","journal":{"identity":"bmc-pulmonary-medicine","isVorOnly":false,"title":"BMC Pulmonary Medicine"},"publishedOn":"2025-10-01 15:58:00","publishedOnDateReadable":"October 1st, 2025"},"versionCreatedAt":"2025-05-13 12:44:59","video":"","vorDoi":"10.1186/s12890-025-03902-8","vorDoiUrl":"https://doi.org/10.1186/s12890-025-03902-8","workflowStages":[]},"version":"v1","identity":"rs-6399218","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6399218","identity":"rs-6399218","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}