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.