Scedosporium boydii disseminated infection complicating severe SARS-CoV2 infection in an immunocompetent patient: a case report

doi:10.21203/rs.3.rs-4345419/v1

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Case Report

Scedosporium boydii disseminated infection complicating severe SARS-CoV2 infection in an immunocompetent patient: a case report

https://doi.org/10.21203/rs.3.rs-4345419/v1

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Background: Disseminated disease by species in the Scedosporium genus are rare in immunocompetent patients, and have not been reported in the context of severe SARS Cov-2 infection.

Case presentation: A retired, 41-year-old police officer with a history of obesity and arterial hypertension presented to emergency department with acute respiratory hypoxemic failure due to severe SARS-Cov2 pneumonia. He used to practice home aquarium care, biking, river swimming, and fishing. He reported no recent travel to the sea, lakes, or caves. He required prolonged mechanical ventilation, and had several documented episodes of ventilator-associated pneumonia due to Pseudomonas aeruginosa and Klebsiella pneumoniae, which later evolved to necrotizing pneumonia, multiple lung abscesses, bronchopleural fistula, empyema and subpleural abscess. Despite sedation withdrawal he remained unconscious; a brain MRI revealed multiple brain abscesses. Scedosporium boydii was isolated from both lung and brain abscess cultures. In addition to percutaneous drainage of lung abscesses, he was treated with combined therapy with voriconazole and liposomal amphotericin B, considering a possible synergic effect. Drainage of the multiple brain abscesses was not feasible; thus, radiological progression was documented, leading to the patient´s demise despite five weeks of treatment.

Conclusion: Invasive fungal infections (IFIs) by molds are an emerging condition in patients with COVID-19. Cases of aspergillosis, candidiasis and mucormycosis were increasingly reported during the COVID-19 pandemic. This is the first report of a fatal disseminated infection due to Scedosporium boydii preceded by a severe SARS Cov-2 infection.

Invasive fungal infection

Scedosporiosis

lung abscess

brain abscess

SARS-CoV infection

Scedosporium apiospermum complex, formerly Pseudallescheria, is a globally distributed pathogen that can represent up to 25% of non-Aspergillus molds in transplanted patients.(1) It is characterized by ovoidal or ellipsoidal conidia that grow in cottony colonies with greyish or brown coloration. These filamentous fungi reside in soil and contaminated water and can be colonizers of altered lung parenchyma, as in cystic fibrosis. In tissue they produce septate hyphae branching in a 60-70° angle and can be distinguished by their characteristic choremia or ascocarp.(2)

Immunocompromised patients, such as patients with a history of hematopoietic stem cell transplant, solid organ transplants, neutropenia, and/or graft-versus-host disease, are more susceptible to invasive disease. Infection in immunocompetent individuals is unusual and is usually associated with histories of near drowning.(3)

The lung is the main organ involved, followed by articular, paranasal sinus, ocular, and central nervous system (CNS) involvement; CNS involvement is predominantly associated with infection by S. boydii.(4) Thus, pulmonary foci are usually the starting point for disseminated infection. Conidial germination and hyphal angioinvasion can lead to necrosis of lung tissue (necrotizing pneumonia), or, fungal colonization of previously devitalized lung tissue, or a lung abscess, may be the starting point for infection.(4,5) Once the infection is established, deep fungal seeding, intravascular conidiation and hematogenous dissemination ensue, leading to an IFI. Disseminated forms of the disease and CNS involvement are reported in 22 and 24% of patients, respectively. Immunosuppression, disseminated disease and CNS involvement are factors associated with mortality.(6)

Invasive fungal infections (IFIs) by molds in general are an emerging condition in critically ill patients, with associated mortality rates that can be up to 70%.(7)The most common etiologic agents are Aspergillus or Mucorales spp.; however, infections by less common molds such as Fusarium and Scedosporium spp., have been reported. Patients who develop these infections usually have underlying malignancy, malnutrition, chronic kidney disease or previous use of antifungals and antibiotics, which lead to fungal breakthrough infections.(1) Cases of aspergillosis, candidiasis and mucormycosis have been increasing exponentially during the COVID-19 pandemic, such that an association between SARS-Cov2 and IFIs has been formally established.(8)

We describe a case of IFI by Scedosporium boydii complicating severe SARS-CoV2 pneumonia in an immunocompetent man presenting with multiple lung and brain abscesses. He received combined therapy with voriconazole and liposomal amphotericin B considering a possible synergistic effect, in addition to percutaneous drainage of lung abscesses.

A retired, 41-year-old police officer with a history of obesity and arterial hypertension presented to our hospital with acute respiratory hypoxemic failure due to severe SARS-Cov2 pneumonia in April 2021. Among his hobbies, we highlight long time home aquarium maintenance, biking, swimming in a nearby river, and fishing. He reported no recent travel to the sea, lakes, or caves. During his long stay in the intensive care unit, he had multiple complications including several episodes of ventilator-associated pneumonia due to Pseudomonas aeruginosa and Klebsiella pneumoniae which later evolved to necrotizing pneumonia with multiple right lower lobe abscesses and a bronchopleural fistula, leading to empyema as well as left subpleural abscess (Figure 1A). Videothoracoscopic assisted surgical resection of the lower right pulmonary lobe and percutaneous abscess drainage were successfully performed. Despite the withdrawal of sedation, his neurological response was not adequate, leading to a brain CT scan, and later, an MRI, which documented multiple brain abscesses (Figure 1B). Samples for aerobic, mycobacterial, and fungal cultures were taken from both the left pulmonary and brain abscesses. Scedosporium boydii was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and PCR from the pulmonary abscess, the brain abscess, and from broncho-alveolar lavage fluid. It was also identified by fungal culture from the pulmonary abscess and from broncho-alveolar lavage fluid (Figure 2). In addition to percutaneous drainage of the lung abscesses, the patient received combined therapy with voriconazole and liposomal amphotericin B hoping for a possible synergistic effect; however, drainage of the multiple brain abscesses was not feasible. Disease progression was documented on brain MRI. The patient expired after 5 weeks of treatment.

Hospitalization rates for fungal infections increased significantly during the pandemic; these infections were primarily COVID-19–associated invasive candidiasis and aspergillosis with increased ICU admissions and in-hospital death rates.(9) Cases of rhino-orbital mucormycosis and rhino-orbital cerebral mucormycosis associated to COVID-19 were also reported from from India and Pakistan, and outbreaks of invasive infections due to Candida albicans and Candida auris emerged from different countries. (10,11)

Scedosporium spp infectionsare unusual in immunocompetent individuals, and are usually associated with histories of near drowning. (3) The incidence of IFIs in critically-ill COVID-19 patients has been calculated to be 10.7% (3.4% for invasive candida infections and 7.9% for aspergillus), although an incidence of up to 11% for COVID-19-associated invasive mold infection (CAIMI) has been reported for this patient population (12-13). It is worthy to note that although CAIMI has been reported predominantly in immunocompetent patients, up to 94% of these patients receive treatment with corticosteroids and up to 19% anti IL-6 receptor antibodies. (13) The incidence of IFIs due to Scedosporium spp. in patients COVID-19 has only been mentioned in a case series, representing one of 16 patients with CAIMI, for an overall incidence of 0.7%.(12)

To our knowledge, only seven cases of CAIMI due to Scedosporium spp. have been reported in COVID-19 patients: none of these infections were disseminated (3 rhinosinal, 2 pulmonary and 2 lymphocutaeous infections), 5 of 7 (72%) presented in patients with diabetes, and only 1 of 7 (14%) had a reported fatal outcome; 4 of the 7 (57%) infections were due to Scedosporium apiospermum. (12–18,28) We report the first case of a disseminated infection due to Scedosporium boydii in a critically-ill immunocompetent patient with COVID-19.

Why IFIs and particularly CAIMIs are reported with greater frequency in apparently immunocompetent, COVID-19 patients is not completely understood, but is likely related to SARS Cov-2 associated immune dysregulation. The hosts´ antiviral response promotes inflammatory adaptations which create favorable conditions for a fungal infection to occur, leading to ciliary dysfunction and lung injury. The virus´ cytopathic effect favors the expression of cellular integrins which facilitate the adherence and invasion of the fungus. Defective monocyte activation, lymphopenia, defective lymphocyte function, decreased IFN-B activity, depletion in the natural killer (NK) cell count and defects on the innate immunity, in addition to the use of immunomodulatory drugs for the treatment of COVID -19 infection, decrease the immune response against the fungus and enhance their capacity to produce tissular injuries and infection. (17,19)

The mortality rate for invasive fungal infections associated to COVID-19 is wide, ranging from 2% in a systematic review of post-mortem cases to 31.2% in observational studies, and 60% in a case series of patients with Candida auris bloodstream infections.(20) Additionally, mortality is increased in COVID-19 patients IFIs (53% with versus 31%).(20,21) Reported overall mortality for Scedosporium pulmonary infections in immunocompetent patients is 12.5% (22) Of the seven previously reported cases of Scedosporium spp infections associated to COVID-19, only one previous fatal outcome is reported in addition to our case, for a total of 2 of 8 cases (25%). However, all these prior cases represented localized infections, and two of these presented 5 and 9 months after the index COVID-19 infection.(15,16)).

The treatment of pulmonary and disseminated infections by Scedosporium spp. may be complex given a well-known resistance to flucytosine, amphotericin B, fluconazole and itraconazole, and decreased sensitivity to isavuconazole and echinocandins (mainly caspofungin and anidulafungin); (4) currently, voriconazole is the treatment of choice.(10) A correlation between the voriconazole MIC and clinical outcomes has been reported in murine models; an MIC less than 2 was associated to clinical response in 92.3% of cases, compared to only 33.3% when the MIC was greater than 4 mg / L .(23) In a series of 107 patients treated with voriconazole, a clinical response was documented in 57% of patients (31% complete and 26% partial).(24) This low response rate has led to research exploring voriconazole combination therapies with liposomal amphotericin B, echinocandins and terbinafine; (25,26) however, the evidence so far is only anecdotal. Thus, surgical control of the focus of infection remains essential given the limitations in pharmacological management. Retrospective studies have shown a trend towards a survival benefit associated to surgical control of the infection. (22,27) Our patient was treated with combination therapy with voriconazole and liposomal amphotericin B hoping for a possible synergistic effect; despite achieving percutaneous drainage of the lung abscesses, drainage of the multiple brain abscesses was not feasible, leading to a fatal outcome.

Among COVID-19-associated invasive fungal infections in immunocompetent patients, localized infections due to non-boydii Scedosporium spp have been reported, mainly with non-fatal outcomes (86%). We report the first case of a disseminated infection in a previously immunocompetent patient due to Scedosporium boydii with a fatal outcome.

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Competing interests

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Author’s contributions

Acknowledgements

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No competing interests reported.

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Scedosporium boydii disseminated infection complicating severe SARS-CoV2 infection in an immunocompetent patient: a case report

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