Case Presentation: A 54-year-old female with essential hypertension, hyperlipidemia, hypothyroidism and MGUS presented to Wheeling Hospital complaining of weakness, dyspnea on exertion and right lower extremity pain for two weeks. Patient was treated for a right gastrocnemius DVT, acute SARS-CoV-2 pneumonia and pulmonary emboli in right middle and lower lobe pulmonary artery branches with smaller emboli in the upper lobe. Therapy included Remdesivir, dexamethasone and heparin infusion transitioned to Eliquis on day of discharge.Two weeks later, patient presented to the ED again with complaints of severe headaches, vomiting, gait unsteadiness and transient vision loss. MRI brain revealed multiple scattered embolic infarcts in the anterior and posterior circulation with punctate infarcts in the left cerebellum. Patient became increasingly lethargic on day three and a repeat MRI brain revealed three new areas of ischemic strokes involving the right medial temporal lobe, insula, and superior cerebellar peduncle. Also noted was a mild hydrocephalus and diffuse cerebral edema treated with hypertonic saline and mannitol. An EEG revealed delta slowing consistent with diffuse cerebral dysfunction. A lumbar puncture revealed xanthochromia, elevated protein and decreased glucose. Patient’s CSF culture grew many budding yeast consistent with Cryptococcus Neoformans and started on Amphotericin B. Due to the unavailability of Flucytosine, the patient was transferred to WVU Ruby Hospital for further management.Shortly after transfer, our patient became unresponsive to voice and painful stimuli with fixed and dilated pupils. She was intubated and noted to have a tonsillar herniation from increased intracranial pressure on CT brain. Subsequently, an EVD was placed by neurosurgery for immediate decompression. Albeit aggressive therapy, the patient’s prognosis remained guarded with re-demonstration of tonsillar herniation, diffuse cerebellar edema, and hemorrhage on serial CT imaging. Following extensive discussions with family, the patient was transitioned to comfort measures until her passing a few days later.

Discussion: Although, severely ill patients with SARS-CoV-2 have an increased risk of developing a venous thromboembolism, co-infection with bacteria, fungi, and respiratory viruses is also important when considering risk factors of morbidity and mortality. We present a patient with immunodeficiency from MGUS who developed an acute COVID19 pneumonia treated with steroids, which likely contributed to her fungal meningitis. About 90 percent of cases of cryptococcal meningoencephalitis are seen among patients with AIDS and a CD4 count < 100 cells/microL. The regions of highest prevalence for infection are in sub-Saharan Africa followed by South and Southeast Asia. Our patient's clinical course was further complicated by a delay in her diagnosis and unavailable therapy at her initial facility, both of which resulted in a fatal outcome.

Conclusions: All differentials considered, a timely diagnosis is important to initiate appropriate therapy for an effective response even in rare infections. This clinical case reminds physicians to always suspect and investigate other opportunistic infections when a patient’s symptoms continue to persist despite standard therapy. Given the recurrent variants and subsequent rapid deterioration seen in patients diagnosed with severe SARS-CoV-2 infections, it remains a challenge to adequately treat patients without the risk of developing adverse events.

IMAGE 1: Initial CT Brain without acute infarct or intracranial hemorrhage

IMAGE 2: Repeat CT brain with mild hydrocephalus and diffuse mass effect/cerebral edema with sulcal and partial basal cistern effacement