Pulmonary cryptococcosis after recovery from COVID-19 in an immunocompetent patient: A rare case report

Abstract

Rationale: Cryptococcus neoformans (C neoformans) infection typically occurs in immunocompromised patients infected with human immunodeficiency virus (HIV), or those taking immunosuppressive drugs, corticosteroids, or chemotherapy. Recently, there have been an increasing number of reports of cryptococcosis as opportunistic infections in COVID-19 patients, all of which have been related to immunocompromising conditions, underlying medical diseases, immune suppression drugs, or corticosteroids. Here, we report the first case of pulmonary cryptococcosis in an immunocompetent patient with a history of COVID-19 who had no history of underlying diseases or immune modulation drugs.Patient concerns: A previously healthy 46-year-old man presented with tiny lung nodules. He had quit smoking 6 years prior. He had no significant medical history except for COVID-19 3 months prior, and had not received corticosteroids or cytokine blockers when he had COVID-19. He had been coughing since he recovered from COVID-19.Diagnosis: Bronchoalveolar lavage cultures showed the growth of C neoformans. A CT-guided percutaneous needle biopsy of the lung lesion was performed. Histopathology of the biopsy specimen showed granulomas with encapsulated yeast. There was no growth of C neoformans in the CSF or blood. He was diagnosed with pulmonary cryptococcosis.Intervention: Antifungal drug (fluconazole) was administered for 6 months in the outside clinic.Outcomes: The lung lesions disappeared after 6 months medication.Lessons: This case may illustrate the risk of pulmonary cryptococcosis after SARS-CoV-2 infection in an immunocompetent patient. Opportunistic infections can occur even after recovery from COVID-19 for several reasons. First, SARS-CoV-2 infection causes immune dysregulation including lymphocytopenia. Second, T lymphocytes play a principal role against Cryptococcus. Third, these changes in the immune system due to COVID-19 may last for several weeks. Thus, we suggest careful consideration of lung lesions in patients with a history of COVID-19.

COVID-19 Associated with Cryptococcosis: A New Challenge during the Pandemic

“…We had the similar findings that half (n = 8) of them were elderly and had underlying diseases, particularly for diabetes mellitus (n = 7). However, some patients did not have underlying diseases [ 17 , 23 ].…”

“…Similarly, Regalla et al reported that in addition to two patients who had cryptococcosis diagnosed postmortem, the median time duration between COVID-19 diagnosis and Cryptococcus infection was 13 days (interquartile range [IQR], 5–49) in 11 patients [ 16 ]. Choi reported rare unusual presentation in an immunocompetent patient who developed culture-confirmed pulmonary cryptococcosis three months after COVID-19 [ 17 ]. Pulmonary and cerebral cryptococcosis were the most common form of COVID-19-associated cryptococcal infections, followed by disseminated and cutaneous infections [ 16 , 18 ].…”

“…Based on our analysis of 18 cases with detail data, disseminated infection, defined by either a positive blood culture or the involvement of cryptococcosis at least two different sites, was the most common type of cryptococcosis, followed by pulmonary and meningoencephalitis ( Table 1 ). For patients with pulmonary cryptococcosis, the clinical manifestations include fever, cough, shortness of breath, hypotension, respiratory insufficiency, and hypoxia [ 16 , 17 , 28 ]. For patients with cryptococcal meningoencephalitis, patients may present with fever, headache, fatigue, vomiting, presyncope, unsteady gait, frequent falls, aphasia, agitation, somnolence, obtundation, impaired memory, delayed verbal responses, inattention, and confusion [ 16 , 23 , 27 , 31 , 34 ].…”

“…Among patients with COVID-19-associated cryptococcosis, C. neoformans was the most common reported causative pathogen in the culture-confirmed cases [ 17 , 20 , 21 , 22 , 23 , 25 , 26 , 27 , 32 ], and one case of endophthalmitis was caused by Cryptococcus laurentii [ 19 ]. Additionally, co- or secondary infections with other microorganisms have been reported in patients with COVID-19-associated cryptococcosis, and the reported pathogens included methicillin-resistant Staphylococcus aureus (MRSA) [ 26 ], Leclercia adecarboxylata [ 22 ], multidrug-resistant Enterobacter cloacae [ 21 ], Alcaligenes spp.…”

“…However, the COVID-19-associated fungal infections caused by Candida , Aspergillus , and Mucor ales cannot be neglected [ 5 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. Recently, several cases of COVID-19 with Cryptococcus co- or secondary infection as opportunistic infections have been reported [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ], However, many issues about the epidemiology, pathogenesis, clinical and microbiological manifestations, and treatment of COVID-19-associated cryptococcosis remained unclear due to limited studies. Therefore, we did a literature search using the keywords—“cryptococcus,” “opportunistic infection,” “COVID-19,” and “SARS-CoV-2,” and conducted this review to provide updated and comprehensive information about this rare COVID-19-associated cryptococcosis.…”