Evidence of anti-Hcp100 antibodies in COVID-19 critically ill patients with detectable anti-histoplasmin antibodies in a highly endemic area for histoplasmosis.

Patients with severe COVID-19 are at increased risk for invasive fungal infections, which are underestimated. Histoplasmosis reactivation in endemic areas should not be overlooked in this population. In a previous study, seroconversion to anti-histoplasmin antibodies by ELISA was detected in 6/39 (15.4%) patients with severe COVID-19. In this work, samples were further investigated to detect seroconversion to antibodies against the Histoplasma capsulatum 100-kDa antigen (Hcp100) by ELISA. Seroconversion to anti-Hcp100 antibodies was detected in 7/39 patients, of whom 6 also seroconverted anti-histoplasmin antibodies. These results reinforce previous findings that show histoplasmosis as an underdiagnosed fungal entity complicating COVID-19.

This study verifies that patients with severe COVID-19 at intensive care units are at risk for histoplasmosis reactivation in endemic areas. Accurate diagnosis of this deadly fungal disease among critically ill patients with COVID-19 living in endemic areas for histoplasmosis is needed.

Detection of anti-Histoplasma capsulatum antibodies and seroconversion patterns in critically ill patients with COVID-19: An underdiagnosed fungal entity complicating COVID-19?

The patients with severe COVID-19 are at increased risk for invasive fungal infections, such as invasive pulmonary aspergillosis and candidiasis, which increase morbidity and mortality. However, clinicians should also consider the possibility of reactivating latent Histoplasma capsulatum in patients with severe COVID-19 living within areas of endemicity who have worsening respiratory function or sepsis, even if they do not have classical risk factors for histoplasmosis (e.g., HIV/AIDS). Bearing in mind this scenario, serum samples of 39 non-HIV/AIDS patients from Buenos Aires hospitalized due to severe COVID-19 pneumonia were analyzed for anti-H. capsulatum-specific IgG antibodies by an in-house ELISA. Antibodies against H. capsulatum were detected in the sera of 8/39 patients (20.51%). To exclude the possibility that these antibodies arose from past exposure of these patients to the fungus, paired serum samples obtained after an interval of at least 10 days were evaluated. Of them, five patients (62.5%) with negative anti-H. capsulatum antibodies at baseline became seropositive 7-10 days later. Three patients (37.5%) had positive anti-H. capsulatum antibodies at baseline, but at time point 2, one of them became seronegative and the other one diminished the antibody titers (4000 vs. 16000 at baseline). The remaining patients displayed higher antibody titers at time point 2 (4000 vs. 1000 at baseline) and died immediately thereafter. In conclusion, awareness of the possibility of fungal co-infections is essential to reduce delays in diagnosis and treatment in order to help prevent severe illness and death from these infections. LAY SUMMARY: This study verifies that patients with severe COVID-19 at ICU are at risk for histoplasmosis reactivation in endemic areas. Accurate diagnosis of this deadly fungal disease among critically ill patients with COVID-19 living in endemic areas for histoplasmosis is needed.

Disseminated histoplasmosis in an immunocompetent patient with COVID-19 pneumonia.

Disseminated histoplasmosis is usually associated with immunosuppressive conditions like AIDS. People with respiratory distress syndrome secondary to SARS-CoV-2 pneumonia are vulnerable to bacterial infections. Additionally, coinfection with fungal pathogens should be considered as a differential diagnosis even in immunocompetent patients who remain on mechanical ventilation secondary to COVID-19. The case presents a 61-year-old immunocompetent man, admitted to the medical ward due to COVID-19 pneumonia. Despite appropriate therapy, the patient required transfer to the intensive care unit for invasive mechanical ventilation. He remained critically ill with worsening respiratory failure. Two weeks later, coinfection by disseminated histoplasmosis was detected. After immediate treatment with amphotericin B and itraconazole, the patient tolerated weaning from mechanical ventilation until extubation. Awareness of this possible fungal coinfection in immunocompetent patients is essential to reduce delays in diagnosis and treatment, and prevent severe illness and death.

COVID-19 associated with disseminated histoplasmosis in a kidney transplant patient.

We report a case of disseminated histoplasmosis and COVID-19 infection in a renal transplant recipient in Argentina. The patient exhibited respiratory symptoms, and a chest computed tomography scan (CT) showed multiple bilateral centrilobular opacities with a tree-in-bud pattern in both lobes. The patient was initially treated as having bacterial community-acquired pneumonia, and then tuberculosis. A month later, histoplasmosis was diagnosed, and Histoplasma capsulatum LAmB clade was isolated from sputum, skin and oral lesions. The patient was hospitalized and treatment was started with intravenous liposomal amphotericin B. During the course of the antifungal therapy the respiratory symptoms worsened, a new chest CT showed a unilateral lesion with a ground glass appearance and SARS-CoV-2 was detected in a new nasopharyngeal sample. In addition, plasma therapy was administered, and the immunosuppressive regimen was adjusted (everolimus was interrupted, mycophenolate mofetil reduced, and meprednisone increased). Finally, the patient's progress was favorable and was discharged after five days on oral itraconazole treatment for histoplasmosis.

Case Report: Incidental Finding of COVID-19 Infection after Positron Emission Tomography/CT Imaging in a Patient with a Diagnosis of Histoplasmosis and Recurring Fever.

This is a case report of a 37-year-old woman evaluated with 18F-fludeoxyglucose (18F-FDG) positron emission computed tomography/CT with recurrent fever after treatment with itraconazole for 6 weeks for histoplasmosis. The examination demonstrated a decrease in the dimensions of the pulmonary opacities previously identified in the left lower lobe and attributed to histoplasmosis. In addition to these pulmonary opacities, increased FDG uptake was also observed in lymph nodes present in the cervical region, mediastinum, left lung hilum, and hepatic hilum. Notably, other pulmonary opacities with ground-glass pattern that were not present in the previous computed tomography were detected in the right lower lobe, with mild 18F-FDG uptake. Nasal swab performed shortly after the examination was positive for COVID-19. In this case, the 18F-FDG positron emission computed tomography/CT study demonstrated findings consistent with active COVID-19 infection coexisting with inflammatory changes associated with histoplasmosis infection.

Pulmonary histoplasmosis diagnosed in a Japanese woman after traveling to central and South America: A case report.

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum, and Japan is considered a non-endemic area for histoplasmosis. Most patients diagnosed with histoplasmosis in the past usually have exposure to caves and bat guano with travel history to endemic areas. Therefore, travel history and risk activities should be comprehensively assessed when suspecting histoplasmosis because this important information may be overlooked. Although few, possibilities of indigenous cases have also been suggested. Moreover, it is assumed that the number of travelers and endemic mycoses has decreased with the recent coronavirus disease 2019 epidemic. However, clinicians should carefully consider the differential diagnosis of histoplasmosis for travelers traveling to endemic areas. In this case report, we describe an immunocompetent Japanese woman who developed histoplasmosis due to a history of travel to an endemic country. Our case report suggests that clinicians should not exclude histoplasmosis from the differential diagnosis even in the absence of risk features such as activities or immunodeficiencies during travel.

COVID-19-Associated Histoplasmosis in an AIDS Patient.

Most reports associating fungal infections with COVID-19 have been cases of invasive aspergillosis. Here, we report a case of severe histoplasmosis and COVID-19 infections in an HIV patient in Rio Grande, Southern Brazil. Histoplasmosis must be included as a diagnostic possibility in opportunistic fungal co-infections in COVID-19 patients with AIDS, mainly in endemic areas.

COVID-19 associated histoplasmosis in an AIDS patient (preprint)

Most reports associating fungal infections with Covid-19 have been cases of invasive aspergillosis. Here we report a case of severe histoplasmosis and Covid-19 infections in an HIV patient in Rio Grande, Southern Brazil. Histoplasmosis must be included on the list of opportunist fungal co-infections in Covid-19 patients with AIDS, mainly in endemic areas.

COVID-19 associated with AIDS-related disseminated histoplasmosis: a case report.

Limited information is available concerning the coexistence of COVID-19 and opportunistic infections in people living with HIV. The possible association of COVID-19 with AIDS-related respiratory diseases should be considered, particularly in patients with advance immunosuppression. We report the case of a male patient with AIDS-related disseminated histoplasmosis associated with COVID-19.