Cryptococcal Meningoencephalitis in an HIV-Negative Host Infected with COVID-19

Introduction: Cryptococcosis, a fungal infection caused by the yeast Cryptococcus neoformans, is a frequently encountered infection in immunocompromised hosts, including those with HIV infection, long-term corticosteroid use, solid organ transplants, and hematologic malignancies. Common presentations include meningoencephalitis and pneumonia. Cryptococcal meningoencephalitis does rarely occur in patients with no apparent underlying disease or risk factors with an associated poor prognosis. Case: A 52-year-old male with a history of uncontrolled diabetes and alcohol dependence presented to our hospital secondary to a fall and confusion. His initial physical examination revealed tachycardia and disorientation. Laboratory studies at the time demonstrated mild hyponatremia, ketonemia, mildly elevated transaminases, and hyperglycemia. Additionally, a COVID-19 PCR was positive. Radiographs obtained in the ED were unremarkable, but computed tomographic angiogram of the chest revealed ground-glass opacities in the left upper lobe. Thereafter, the patient was begun on Azithromycin and Ceftriaxone for treatment of possible community-acquired pneumonia. Due to his continued altered mentation and increasing lethargy, computed tomography of the head was obtained, which revealed new areas of low attenuation in multiple periventricular and subcortical white matter areas, suggestive of infectious or inflammatory encephalitis. Thereafter, a lumbar puncture was performed and cerebrospinal fluid (CSF) studies and microbiology were obtained. These studies revealed evidence of infection with Cryptococcus neoformans/gatti, hyperproteinorachia of 392, hypoglycorrhachia of 38, and mononuclear pleocytosis of 97. Prior to speciation of the patient's cultures, he was placed on empiric antibiotics and antiviral coverage for infectious meningoencephalitis. After discovery of the patient's infectious agent, his treatment regimen was narrowed to Amphotericin B and Flucytosine. Additionally, workup for HIV was initiated, with findings of decreased CD4 count in the absence of positive HIV serologies. As the patient's treatment for COVID-19 and Cryptococcosis progressed, his CD4 count later spontaneously corrected. Discussion: This case is significant because it demonstrates a case of Cryptococcal meningoencephalitis in a patient with transient lymphocytopenia and active COVID-19 infection. In the literature, it has been demonstrated that there is a significant correlation between COVID-19 infection and low CD4 and CD8 counts. Therefore, in this particular case, it is possible that infection with COVID-19 in combination with increased infection risk from inadequately managed diabetes and daily alcohol use predisposed the patient to transient lymphopenia, leading to Cryptococcosis. Ultimately, it is imperative that physicians be aware of any etiology that may predispose patients to infections with uncommon microbes, particularly in the absence of typical predisposing factors.