Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial.

BACKGROUND: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. METHODS: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. DISCUSSION: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.

Predictive models-assisted diagnosis of AIDS-associated Pneumocystis jirovecii pneumonia in the emergency room, based on clinical, laboratory, and radiological data.

We assessed predictive models (PMs) for diagnosing Pneumocystis jirovecii pneumonia (PCP) in AIDS patients seen in the emergency room (ER), aiming to guide empirical treatment decisions. Data from suspected PCP cases among AIDS patients were gathered prospectively at a reference hospital's ER, with diagnoses later confirmed through sputum PCR analysis. We compared clinical, laboratory, and radiological data between PCP and non-PCP groups, using the Boruta algorithm to confirm significant differences. We evaluated ten PMs tailored for various ERs resource levels to diagnose PCP. Four scenarios were created, two based on X-ray findings (diffuse interstitial infiltrate) and two on CT scans ("ground-glass"), incorporating mandatory variables: lactate dehydrogenase, O2sat, C-reactive protein, respiratory rate (> 24 bpm), and dry cough. We also assessed HIV viral load and CD4 cell count. Among the 86 patients in the study, each model considered either 6 or 8 parameters, depending on the scenario. Many models performed well, with accuracy, precision, recall, and AUC scores > 0.8. Notably, nearest neighbor and naïve Bayes excelled (scores > 0.9) in specific scenarios. Surprisingly, HIV viral load and CD4 cell count did not improve model performance. In conclusion, ER-based PMs using readily available data can significantly aid PCP treatment decisions in AIDS patients.

Disseminated mycobacterium genavense infection with central nervous system involvement in an HIV patient: a case report and literature review.

BACKGROUND: Immunodeficient patients, particularly HIV patients, are at risk of opportunistic infections. Nontuberculous mycobacteria can cause severe complications in immunodeficient patients. CASE PRESENTATION: We describe a 57-year-old HIV patient, primarily presented with coughs and constitutional symptoms, with a unique Mycobacterium genavense abdominal, pulmonary, and central nervous system infection, accompanied by intracranial masses. CONCLUSION: The diagnosis of NTM, including M. genavense, must always be considered by clinicians in immunodeficient patients, especially those with HIV, who have a compromised immune system.

HIV-associated disseminated cryptococcosis-An unusual clinical and diagnostic picture with successful cure by single dose liposomal amphotericin B treatment.

BACKGROUND: Cryptococcosis is an invasive, opportunistic fungal infection seen especially in human immunodeficiency virus (HIV) infected patients. Cryptococcal meningitis (CM) is the second leading cause of mortality in HIV patients. We report a case of disseminated cryptococcosis presenting with altered mental status in a newly diagnosed HIV infection. METHODS AND RESULTS: A 50-year-old with a short history of altered mental sensorium and a history of low-grade fever and weight loss for few months presented at a tertiary care hospital in North India. He was detected positive for HIV-1. Cryptococcal antigen (CRAG) was positive in Cerebrospinal fluid (CSF), and negative in serum. The fungal culture in CSF was sterile while the fungal blood culture grew Cryptococcus neoformans. The patient was treated with single high-dose Liposomal Amphotericin B (LAmB) therapy followed by Fluconazole and Flucytosine for the next two weeks followed by fluconazole daily for consolidation and maintenance therapy. Antiretroviral therapy (ART) was started 4 weeks after induction therapy. After 6 months, the patient is doing fine. CONCLUSION: Single dose LAmB along with the backbone of fluconazole and flucytosine appears promising in disseminated cryptococcal infection in HIV-infected individuals.

Glucocorticoids as a risk factor for infection and adverse outcomes in non-HIV and non-transplant patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM), an opportunistic fungal infection affecting immunocompromised hosts, leads to high mortality. The role of previous exposure to glucocorticoids as a risk factor and as an outcome modulator has been observed, but systematic studies are lacking. OBJECTIVE: The primary aim of this study is to evaluate the impact of glucocorticoid use on the clinical outcomes, specifically mortality, of non-HIV and non-transplant (NHNT) patients diagnosed with CM. METHODS: We queried a global research network to identify adult NHNT patients with CM based on ICD codes or recorded specific Cryptococcus CSF lab results with or without glucocorticoid exposure the year before diagnosis. We performed a propensity score-matched analysis to reduce the risk of confounding and analysed outcomes by glucocorticoid exposure. We used a Cox proportional hazards model for survival analysis. RESULTS: We identified 764 patients with a history of glucocorticoid exposure and 1267 patients without who developed CM within 1 year. After propensity score matching of covariates, we obtained 627 patients in each cohort. The mortality risk in 1 year was greater in patients exposed to prior glucocorticoids (OR: 1.3, CI: 1.2-2.0, p = 0.002). We found an excess of 45 deaths among CM patients with previous glucocorticoid use (7.4% increased absolute risk of dying within 1 year of diagnosis) compared to CM controls without glucocorticoid exposure. Hospitalisation, intensive care unit admission, emergency department visits, stroke and cognitive dysfunction also showed significant, unfavourable outcomes in patients with glucocorticoid-exposed CM compared to glucocorticoid-unexposed CM patients. CONCLUSIONS: Previous glucocorticoid administration in NHNT patients seems to associate with 1-year mortality after CM adjusted for possible confounders related to demographics, comorbidities and additional immunosuppressive medications. Serial CrAg screening might be appropriate for higher-risk patients on glucocorticoids after further cost-benefit analyses.

Cytomegalovirus infection among people living with HIV in Sweden: Case profiles, treatment strategies and patient outcomes at Karolinska University Hospital 2010-2020.

OBJECTIVES: In countries with access to early antiretroviral treatment (ART), opportunistic infections caused by cytomegalovirus (CMV) in people living with HIV (PLWH) are becoming increasingly rare. As potential complications are severe, it is critical to remain aware of this important diagnosis. However, clinical characteristics and prognosis of CMV infection in PLWH in the era of modern ART have not been well described. METHODS: Here, we compiled the clinical presentation, management and outcome of CMV infection in PLWH treated at the infectious diseases clinic of Karolinska University Hospital during 2010-2020. RESULTS: We identified 51 cases of active CMV infection, based on detection of CMV-DNA, mainly diagnosed in patients with CD4 T-cell count <200 cells/µL (86%). Median time from HIV diagnosis to detection of CMV infection was 16 days. In 20 cases (39%), CMV infection was symptomatic with retinitis identified as a manifestation in 70% of cases. Symptomatic CMV infection was treated for 73 (20-313) days upon diagnosis, mostly using valganciclovir. One-year mortality was 22% and was associated with longer time to ART initiation from HIV diagnosis and with comorbidities, but not with CMV-DNA levels or CD4 count. Immune reconstitution was not significantly compromised in patients with symptomatic CMV, although CD4/8 ratio tended to be lower in patients with systemic CMV infection. CONCLUSIONS: Retinitis remains the most common manifestation of symptomatic CMV infection in PLWH. Recognizing CMV infection is important, especially in the management of 'late presenters'. Adequate duration of antiviral therapy and appropriate follow-up must be ensured to avoid complications.

Opportunistic Infections among newly diagnosed HIV patients in the largest tertiary facility in Ghana.

Background: Opportunistic infections (OIs) among newly diagnosed HIV patients are a marker for inadequateness of HIV awareness and testing. Despite global efforts at creating awareness for early detection, late HIV diagnosis and its associated OIs still exist. This study sought to determine the prevalence and patterns of OIs and associated factors among newly diagnosed HIV patients in Ghana. Methods: A retrospective study using data extraction was conducted among 423 newly diagnosed HIV patients aged ≥18 years at the Korle-Bu Teaching Hospital from July 1st 2018 to December 2019. Multivariate logistic regression was adopted to assess factors associated to OIs. Analysis was performed using SPSS version 16, and p-value < 0.05 was deemed significant. Results: The mean age of patients with a new HIV diagnosis was 40.15 ± 11.47 years. Male versus female sex differential was 30.3% and 69.7%, respectively. The prevalence of OIs among newly diagnosed HIV patients was 33.1% (95% CI = 34.6-44.1). About 70% (120/166) of patients with OIs were classified into WHO clinical stage III and IV. The most common OIs were candidiasis (oro-pharyhngeal-esophageal) (36.9%), and cerebral toxoplasmosis (19.9%). The odds of an OI at the time of HIV diagnosis among females was 51% lower than in males (aOR = 0.49, 95% CI = 0.28-0.86). Being employed increased the odds of OIs by 2.5 compared to the unemployed (aOR = 2.5; 95% CI = 1.11-5.61). Participants classified as World Health Organization (WHO) HIV clinical stage III and IV were 15.88 (95% CI = 9.41-26.79) times more likely to experience OIs. Conclusion: One in three patients newly diagnosed with HIV presented with an opportunistic infection, with men more likely to experience such infections. Significant attention should be given to improving case-finding strategies, especially among men.

Clinical characteristics, diagnosis, treatment and outcomes of patients living with HIV and co-infected with tuberculosis and histoplasmosis: a 5-y retrospective case series.

BACKGROUND: In Latin America, tuberculosis (TB) and histoplasmosis are two of the most frequent opportunistic infections affecting people living with human immunodeficiency virus (HIV). However, there are limited data on the clinical characteristics and outcomes of patients with concurrent TB and histoplasmosis infections. METHODS: This was a retrospective observational study to describe the clinical, epidemiological and laboratory characteristics and outcomes of 21 patients living with HIV (PLHIV) who were diagnosed with concurrent histoplasmosis and TB between 2017 and 2021 in Guatemala City, Guatemala. RESULTS: Most patients were male and were newly diagnosed with HIV. All patients had advanced HIV disease (AHD). They presented with a median CD4 count of 20 cells/µl. The most common symptoms reported by the patients were fever, weight loss, cough and diarrhoea. Twelve patients died within 6 months of baseline evaluation, for a mortality rate of 57.1%. CONCLUSIONS: PLHIV with concurrent TB and histoplasmosis infections are characterised by AHD, predominantly presenting with disseminated forms of these infections and with unspecific symptoms and signs. This evidence calls for early HIV and opportunistic infection screening and insights into the challenges and opportunities for the efficient diagnostic and therapeutic management of patients with AHD with concurrent histoplasmosis and TB infections.

HIV and skin infections.

HIV infection alters the skin microbiome and predisposes to a wide range of cutaneous infections, from atypical presentations of common skin infections to severe disseminated infections involving the skin that are AIDS-defining illnesses. Bacterial infection of the skin, most commonly caused by Staphylococcus aureus, occurs frequently and can result in bacteremia. Nontuberculous mycobacterial infections that are usually localized to the skin may disseminate, and guidance on the treatment of these infections is limited. Herpes simplex can be severe, and less common presentations such as herpetic sycosis and herpes vegetans have been reported. Severe herpes zoster, including disseminated infection, requires intravenous antiviral treatment. Viral warts can be particularly difficult to treat, and in atypical or treatment-resistant cases a biopsy should be considered. Superficial candidosis occurs very commonly in people living with HIV, and antifungal resistance is an increasing problem in non-albicans Candida species. Systemic infections carry a poor prognosis. In tropical settings the endemic mycoses including histoplasmosis are a problem for people living with HIV, and opportunistic infections can affect those with advanced HIV in all parts of the world. Most cutaneous infections can develop or worsen as a result of immune reconstitution in the weeks to months after starting antiretroviral therapy. Direct microscopic examination of clinical material can facilitate rapid diagnosis and treatment initiation, although culture is important to provide microbiological confirmation and guide treatment.

Recurrent Cryptococcal Meningitis in a Late Presenter of HIV: A Rare Case Report and Review of Literature.

BACKGROUND The highly active antiretroviral treatment (HAART) and the primary prophylaxis in newly diagnosed people living with HIV (PLHIV) have reduced the incidence of opportunistic infections such as cryptococcal meningitis (CM). Relapse of CM is associated with increased morbidity and mortality. The aim of the present case presentation is to report the clinical progress relapse of CM in a man who was a late presenter PLHIV, 1 year after ART initiation with increased CD4 cell count, undetectable viral load, and excellent compliance after disruption of secondary antifungal prophylaxis. CASE REPORT One year after initial diagnosis of HIV and CM, the patient had no neurological or other symptoms, and viral suppression and increased CD4 cell count were achieved. After the completion of 12 months of secondary prophylaxis with fluconazole, an episode of partial seizure with secondary generalization occurred, followed by a short-term memory loss. Magnetic resonance imaging (MRI) indicated a focal lesion in right frontal-parietal brain region. Lumbar puncture was conducted and Cryptococcus neoformans non-resistant to fluconazole was isolated. He received antiepileptic treatment, induction antifungal treatment with liposomal amphotericin and fluconazole, consolidation treatment with fluconazole, and secondary prophylaxis with fluconazole, as in the first episode of CM. One year after the relapse, antiepileptic treatment and secondary prophylaxis with fluconazole continues and no new episode has been reported. The diagnosis of immune reconstitution inflammatory syndrome (IRIS)-related relapse of CM cannot be excluded. CONCLUSIONS Further studies are needed for the evaluation of parameters such as duration of secondary prophylaxis and treatment options for induction and consolidation therapy to reduce the relapse rate of CM.

The 'pulmonary diseases spectrum' in HIV infected children.

Despite advances in diagnostic, therapeutic and preventive strategies for HIV, pulmonary diseases continue to be the major cause of morbidity and mortality in infants and children infected with HIV. With effective programs to prevent perinatal HIV-1 transmission to early diagnosis in infants, we have seen a substantial decline in paediatric HIV incidence. Early initiation of Highly Active Anti-Retroviral Therapy (HAART) in all HIV infected children coupled with consistent use of Pneumocystis prophylaxis in all HIV exposed/infected children under 5 years of age has considerably reduced associated infections overall and respiratory infections in particular. In developing countries already burdened with poverty, malnutrition, suboptimal immunization coverage and limited access to health care and treatment, acute and chronic HIV-associated respiratory disease remain a major cause for concern. Prevention of severe respiratory infections in advanced HIV disease among children consists mostly of rapid and optimal HAART initiation & continuation, preventing severe TB disease with BCG and TB preventive treatment, preventing Pneumocystis jirovecii pneumonia with cotrimoxazole prophylaxis and administering age-appropriate vaccinations and catch-up vaccines as per National Immunization schedule.

Coexistence of Cryptococcal Fungemia and Pneumocystis jirovecii Pneumonia in an HIV-Infected Patient: A Case Report.

INTRODUCTION: Opportunistic infections caused by bacteria and fungi are common in human immunodeficiency virus (HIV)-infected patients. Cryptococcus neoformans and Pneumocystis jirovecii are the most common opportunistic infections in immunosuppressed individuals, but their coexistence is rare. To our knowledge, this is the first case presented in Turkey involving the coexistence of C.neoformans fungemia and P.jirovecii pneumonia. CASE PRESENTATION: A 26-year-old male patient presented with a cachectic appearance, cough, sputum, weakness, shortness of breath, and a weight loss of 15 kg in the last three months. It was learned that the patient was diagnosed with HIV three years ago, did not go to follow-ups, and did not use the treatments. CD4 cell count was 7/mm3 (3.4%), CD8 cell count was 100 (54%) mm3, and HIV viral load was 5670 copies/mL. In thorax computed tomography (CT), increases in opacity in diffuse ground glass density in both lungs and fibroatelectasis in lower lobes were observed. With the prediagnosis of P. jiroveci pneumonia, the HIV-infected patient was given trimethoprim-- sulfamethoxazole 15 mg/kg/day intravenously (i.v.). On the 4th day of the patient's hospitalization, mutiplex PCR-based rapid syndromic Biofire (Film Array) blood culture identification 2 (BCID2) test (Biomerieux, France) was applied for rapid identification from blood culture. C. neoformans was detected in the blood culture panel. The treatment that the patient was taking with the diagnosis of C. neoformans fungemia was started at a dose of liposomal amphotericin B 5 mg/kg/- day + fluconazole 800 mg/day. CONCLUSION: While the incidence of opportunistic infections has decreased with antiretroviral therapy (ART), it remains a problem in patients who are unaware of being infected with HIV or who fail ART or refuse treatment. High fungal burden, advanced age, low CD4+ cell count, and being underweight are risk factors for mortality in HIV-positive patients. Our case was a cachectic patient with a CD4 count of 7 cells/mm3. Despite the early and effective treatment, the course was fatal.

Pulmonary Histoplasmosis in People Living with Human Immunodeficiency Virus in French Guiana: Clinical Epidemiology, Medical Imaging and Prognostic.

BACKGROUND: Histoplasmosis is mainly described as a disseminated disease in people living with HIV (PLHIV). Compared to historical descriptions in immunocompetent individuals, knowledge is lacking on the detailed clinical and radiological findings and outcomes of pulmonary histoplasmosis (PH). Overlooked or misdiagnosed with other AIDS-defining condition, prognostic of PLHIV may be at risk because of inappropriate care. METHODS: A retrospective multicentric study was conducted in PLHIV from French Guiana between January 1988 and October 2019. Proven PH were documented through mycological direct examination, culture, or histology. Patients with concomitant respiratory infections were excluded. RESULTS: Among 65 patients, sex ratio M:F was 2.4 with a median age of 39 years [IQR 25-75%: 34-44]. Median CD4 count was 24 cells/mm3 [11-71], with histoplasmosis as the AIDS-defining condition in 88% and concomitant AIDS-defining conditions in 29%. Clinical findings were fever (89%), cough (58%), dyspnea (35%), expectoration (14%), and hemoptysis (5%). Sixty-one X-rays and 24 CT-scans were performed. On X-rays, an interstitial lung disease was mainly found (77%). On CT-scans, a nodular pattern was predominant (83%): mostly miliary disease (63%), but also excavated nodules (35%). Consolidations were present in 46%, associated with miliary disease in 21%. Thoracic lymphadenopathies were found in 58%, mainly hilar and symmetric (33%). Despite antifungal treatment, case-fatality rate at one month was 22%. CONCLUSION: When faced with an interstitial lung disease on X-rays or a miliary pattern on CT-scans in advanced PLHIV, physicians in endemic areas, apart from tuberculosis or pneumocystosis, should include histoplasmosis as part of their differential diagnoses.

Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Talaromyces marneffei and Cytomegalovirus Infections in an HIV-Infected Patient.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening syndrome led by a highly stimulated but invalid immune response, and Talaromyces marneffei (T. marneffei) is an opportunistic infection with high mortality commonly among acquired immunodeficiency syndrome (AIDS) patients. METHODS: Here is a rare case, in which secondary HLH is caused by dual infections of T. marneffei and cytomega-lovirus (CMV). A 15 year old man with a 20-day history of fatigue and intermittent fever (maximum 41.0℃) was admitted to the department of infectious diseases. Marked hepatosplenomegaly and pulmonary infection were detected by computed tomography. Examination of peripheral blood and bone marrow (BM) smears provided clues pointing toward T. marneffei infection, and indicated prominent hemophagocytosis. RESULTS: Cytomegalovirus (CMV) and T. marneffei infections were confirmed by CMV quantitative nucleic acid testing and culture of blood and bone marrow, respectively. A diagnosis of acquired HLH caused by dual infections of T. marneffei and CMV was established because 5 of the 8 HLH diagnostic criteria were met. CONCLUSIONS: The case highlights the contribution of the morphological examination on peripheral blood and bone marrow smears in the diagnosis, which sometimes are the only locations that HLH and T. marneffei can be diagnosed.

Clinical metagenomics-assisted diagnosis of relapsed HIV-associated cryptococcal meningitis.

To date, the identification of crypotococcal relapse remains clinically challenging as it often has similar manifestation with paradoxical immune reconstitution inflammatory syndrome. This study reports on the use of metagenomics assisted next generation sequencing to aid in diagnosing recurrent cryptococcal meningitis in an person living with HIV experiencing recurring symptoms, despite negative culture results for Cryptococcus neoformans in the cerebrospinal fluid. Although fungal culture was negative, when reads from metagenomic and metatranscriptomic sequencing performed on the Day 308 cerebrospinal fluid sample were mapped onto the genome from the Day 4 isolate, 589 specific reads were identified. NCBI BLAST search also revealed Cryptococcus-specific 18S/25S/28S ribosomal RNA, indicating a relapse of the disease.

Development of a case fatality prognostic score for HIV-associated histoplasmosis.

OBJECTIVES: The burden of histoplasmosis is as great as that of tuberculosis in Latin America and the attributable mortality is even higher. A better assessment of severity could help reduce mortality. METHODS: From the French Guiana HIV-histoplasmosis database, we attempted to identify factors associated with 30-day death after antifungal drug initiation and constructed a prognostic score. We evaluated its discrimination performance using several resampling methods. RESULTS: Of the 415 patients included, 56 (13.5%) died within 30 days of treatment. The fatality-associated factors were performance status ≥3, altered mental status, dyspnea, C-reactive protein ≥75 mg/l, hemoglobin <9 g/dl and/or a platelet <100000/ml, and an interstitial lung pattern on chest X-ray. We constructed a 12-point prognostic score. A threshold ≥5 classified patients as alive or dead at 30 days with a sensitivity of 84%, a specificity of 81%, a positive predicted value of 40%, and a negative predicted value of 97%. The area under the curve of the receiver operating characteristic curves from the different resamples were stable between 0.88 and 0.93. CONCLUSION: The histoplasmosis case fatality score, which is easy and inexpensive to perform, is a good tool for assessing severity and helping in the choice of induction therapy. An external validation remains necessary to generalize these results.

Impact of prior cryptococcal antigen screening on in-hospital mortality in cryptococcal meningitis or fungaemia among HIV-seropositive individuals in South Africa: a cross-sectional observational study.

OBJECTIVES: We investigated whether patients with cryptococcal meningitis (CM) or fungaemia detected through South Africa's laboratory cryptococcal antigen (CrAg) screening programme had better outcomes than those presenting directly to the hospital. METHODS: We compared 14-day in-hospital case-fatality ratios of HIV-seropositive individuals with CD4 counts below 100 cells/µL and laboratory-confirmed CM/fungaemia from 2017-2021, with or without evidence of a positive blood CrAg test within 14 days prior to diagnosis. We evaluated whether the impact of prior CrAg screening on mortality varied according to the study period (pre-COVID-19: before March 2020 vs. COVID-19: after March 2020). RESULTS: Overall, 24.5% (830/3390) of patients had a prior positive CrAg test within 14 days of diagnosis. CrAg-screened patients were less likely to have an altered mental status at baseline than non-CrAg-screened patients (38.1% [296/776] vs. 42.6% [1010/2372], p = 0.03), and had a lower crude 14-day case-fatality ratio (24.7% [205/830] vs. 28.3% [724/2560]; OR, 0.83 [95% CI, 0.69-0.99]; p = 0.045). Previous CrAg screening was associated with a greater reduction in the crude 14-day mortality during the COVID-19 period (OR, 0.64 [0.47-0.87]; p = 0.005) compared with before (OR, 0.95 [0.76-1.19]; p = 0.68). After adjustment, previous CrAg screening within 14 days was associated with increased survival only during the COVID-19 period (adjusted OR, 0.70 [0.51-0.96]; p = 0.03). DISCUSSION: Previous CrAg screening was associated with a survival benefit in patients hospitalized with CM/fungaemia during the COVID-19 period, with fewer patients having an altered mental status at baseline, suggesting that these patients may have been diagnosed with cryptococcosis earlier.