Detection of anti-Histoplasma capsulatum antibodies and seroconversion patterns in critically ill patients with COVID-19

TOSCANINI MA; BARBERIS F; VIDELA GARRIDO A; POSSE GB; CAPECE P; NUSBLAT AD; CUESTAS ML

Congreso; 19TH INFOCUS.; 2021

Objectives: Patients with severe COVID-19 are at increased risk for invasive fungal infections, which increase morbidity and mortality. Among them, invasive pulmonary aspergillosis or candidiasis are commonly reported and are associated with severe illness and death. However, clinicians should also consider the possibility of acquisition or reactivation of 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, a retrospective study for the eventual detection of histoplasmosis from serum samples of 38 patients from Buenos Aires (an endemic area for H. capsulatum) who required mechanical ventilation due to severe COVID-19 pneumonia was performed.Methods: Sera from a cohort of 38 patients that were initially sampled to study the presence of Aspergillus (serum galactomannan testing) and that were kept at -80 °C for further studies were retrospectively studied for anti-H. capsulatum antibodies detection and seroconversion analysis by ELISA. All these patients were admitted to the intensive care unit (ICU) of Hospital Posadas with acute respiratory distress syndrome (ARDS) due to severe COVID-19 pneumonia. Since patients with severe COVID-19 might have an impaired ability to mount a humoral immune response, either related to the immune dysfunction caused by SARS-CoV-2 or to the immunosuppressants used at ICU orticosteroids), the detection of specific fungal antibodies by immunodifusion might be limited, as it occurs with HIV/AIDS patients with disseminated histoplasmosis. Thus, histoplasmosis serodiagnosis in severe COVID-19 patients can be improved through the use of a paired serum diagnostic algorithm. Thus, an in-house ELISA using a commercially available standardized histoplasmin as reagent was used for detecting anti-H. capsulatum antibodies.Results: Antibodies against the H and M glycoproteins of a commercially available standardized histoplasmin were detected by ELISA in the sera of 8/38 patients (21.05%). 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 two weeks were evaluated. Of them, 5 patients (62.5%) with negative H. capsulatum specific IgG antibodies at baseline became seropositive two weeks later; 2 patients (25%) had positive H. capsulatum-specific IgG antibodies at both time-points, and 1 (12.5%) had positive H. capsulatum specific IgG antibody levels at baseline and become negative two weeks later, thus suggesting that all these patients had a concomitant histoplasmosis.Noteworthy, all patients that rendered positive anti-H. capsulatum antibodies were non-HIV/AIDS patients that received broad-spectrum antibiotics, corticosteroids (8 mg/day), and required mechanical ventilation due to moderate-severe ARDS. All patients except one were male with a median age of 62.4 years (range 23-69) and have ≥ 1 underlying comorbidities such as hypertension, diabetes and obesity. Two of them were ex-smokers.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.