key: cord-0923323-uql08e87
authors: Thyagarajan; Mondy, Kristin E; Rose, Dusten T
title: Cryptococcus neoformans blood stream infection in severe COVID-19 pneumonia
date: 2021-08-31
journal: IDCases
DOI: 10.1016/j.idcr.2021.e01274
sha: c3c36eea1067f5f9614ea347c48f5f7942f86b2b
doc_id: 923323
cord_uid: uql08e87

Severe coronavirus disease (COVID-19) associated pneumonia leads to acute respiratory distress syndrome and emerging data suggest fungal coinfections also contribute to mortality in this patient population. Aspergillus ventilator associated pneumonia is increasingly recognized. We describe a case of likely reactivation of community acquired Cryptococcus neoformans in a patient with severe COVID-19.

Keywords: Coronavirus, COVID-19, Respiratory distress Syndrome-Adult, Pandemic,

Severe coronavirus disease (COVID-19) associated pneumonia leads to acute respiratory distress syndrome and emerging data suggest fungal coinfections also contribute to mortality in this patient population. Aspergillus ventilator associated pneumonia is increasingly recognized.

We describe a case of likely reactivation of community acquired Cryptococcus neoformans in a patient with severe COVID-19.

As the pandemic continues, global deaths due to COVID-19 have surpassed one million (1). Lansbury et al completed a meta-analysis of 3834 COVID-19 patients between January and April 2020 and found 14% of patients in intensive care units (ICU) had bacterial coinfections and 3% had coinfections with other viruses (2) . While invasive aspergillus infections (IAI) have been well described in severe influenza with acute respiratory syndrome, in (SARS-CoV-1) infections, only a handful of fungal coinfections were reported (3, 4) . Since that publication, fungal coinfections, especially Aspergillosis, have been increasingly reported in the setting of COVID-19 and mortality contributing to IAI are emerging in case reports and larger cohorts (5, 6) .

We report the case of a 75-year old, immunocompetent male who died of Cryptococcus neoformans fungemia in the setting of severe COVID-19 associated pneumonia and acute respiratory distress syndrome (ARDS).

A Hispanic male with a history of diabetes mellitus, hypertension, obesity, osteoarthritis presented with a four-day history of fever, difficulty breathing and was diagnosed with COVID-19 by reverse transcription polymerase chain reaction (RT PCR) (Abbott ID NOW SARS CoV RNA). His oxygen saturation was 50% on room air in the emergency department (ED) prompting intubation and intensive care unit (ICU) admission. Social and travel history was unremarkable.

Admission labs were unremarkable including a negative HIV test. His lymphocyte % was 3.0 to 8.1% throughout his hospitalization, with an absolute lymphocyte nadir of 400 on day eight of hospitalization. HgBA1C was 9% and blood and sputum cultures were negative. He was treated with remdesivir for 5 days, convalescent plasma, and dexamethasone 6 mg IV daily for 10 days starting on day two of hospitalization. Due to persistent fevers starting on day 11, increasing oxygen requirements, and bilateral airspace disease on chest x-ray, sputum cultures were obtained and grew methicillin-resistant Staphylococcus aureus (MRSA). MRSA was also documented from sputum on day 17 and 22. He received vancomycin, which was eventually switched to linezolid for possible treatment failure with worsening ARDS. His hospital course was complicated by acute kidney injury and bilateral cerebral infarcts.

In the last week of hospitalization, he was oxygenating adequately on 50% Fi02. He acutely worsened and FIO2 use increased to 90% and did not improve despite proning, neuromuscular agents, and inhaled nitric oxide. Due to persistent fevers and eosinophilia, and concern of drug fever, he received prednisone for eight days, which ended two days before his death. Due to his age, multiple strokes, inability to oxygenate despite using multiple methods, and prolonged ICU stay, he transitioned to comfort measures. On day 26 of hospitalization, J o u r n a l P r e -p r o o f bacterial blood cultures were obtained. The patient expired the following day. Four days later

Studies to date have demonstrated that COVID-19 can invoke a severe inflammatory response resulting in significant damage to lung tissue, allowing fungal species that would otherwise be colonizers in normal hosts to invade lung tissue and disseminate (6) . Previous studies have shown that pulmonary epithelial and alveolar cells, often destroyed in severe COVID-19 pneumonia, are otherwise critical in the initial immune and inflammatory response to Cryptococcus (7) . These patients are also frequently lymphopenic and have been noted to have specific decreases in CD4 + and CD8 + T cell counts, as well as suppressed IFN-γ production by CD4 + T cells (8) . This relative deficiency in cell-mediated immunity would also be a risk factor for invasive Cryptococcal disease.

Although we hypothesize that this patient's infection was a result of direct fungal invasion into damaged lung tissue, we cannot completely rule out the possibility of reactivation of latent/asymptomatic cryptococcal infection or potential nosocomial acquisition (i.e. airborne or central venous catheter acquisition). Cryptococcus can remain latent and asymptomatic for many years following initial airway acquisition (9) . Clinical disease and dissemination later occur when the host immune system is suppressed. However, if this was the predominant pathogenesis then one would expect more reported cases of other reactivated endemic mycoses (e.g., histoplasmosis, coccidioidomycosis), and fewer cases of Aspergillus (which typically does not exist in a latent phase). In review of the literature, there have also been rare reported cases of possible nosocomial spread of Cryptococcus, but only in the setting of case clusters within a single facility (10) . No other recent cases of Cryptococcus in our hospital have been reported, thus nosocomial spread would be highly unlikely. 

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Cluster of Cryptococcus neoformans infections in intensive care unit