Risk Factors for Fungal Co-Infections in Critically Ill COVID-19 Patients, with a Focus on Immunosuppressants

Abstract

Severe cases of coronavirus disease 2019 (COVID-19) managed in the intensive care unit are prone to complications, including secondary infections with opportunistic fungal pathogens. Systemic fungal co-infections in hospitalized COVID-19 patients may exacerbate COVID-19 disease severity, hamper treatment effectiveness and increase mortality. Here, we reiterate the role of fungal co-infections in exacerbating COVID-19 disease severity as well as highlight emerging trends related to fungal disease burden in COVID-19 patients. Furthermore, we provide perspectives on the risk factors for fungal co-infections in hospitalized COVID-19 patients and highlight the potential role of prolonged immunomodulatory treatments in driving fungal co-infections, including COVID-19-associated pulmonary aspergillosis (CAPA), COVID-19-associated candidiasis (CAC) and mucormycosis. We reiterate the need for early diagnosis of suspected COVID-19-associated systemic mycoses in the hospital setting.

Keywords: COVID-19; COVID-19-associated candidiasis; COVID-19-associated pulmonary aspergillosis; corticosteroid treatment; fungal co-infections; mucormycosis.

Figure 1

Distribution (a) and co-occurrence (b) of fungal species across randomly selected 50 case studies, prospective and retrospective published reports on fungal co-infections in hospitalized COVID-19 patients [5,7,9,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56] (also see Supplementary Table S1). Searches were done on PubMed (Medline) and Google Scholar using query terms such as “Co-infections”, “coinfections”, “fungi” or “Fungal infections” in combination with either “COVID-19” or “SARS-CoV-2”. Most (>50%) of the selected articles included cases from the onset of the COVID-19 pandemic in several countries (December 2019–April 2020). In the co-occurrence network, nodes are colored based on betweenness centrality (species with high co-occurrence), while edges (connecting lines) indicate significant (p < 0.05) co-occurrence between species. The network was constructed using the visNetwork package of R (https://cran.r-project.org/web/packages/visNetwork/index.html, accessed on 21 May 2021) and further annotated in Gephi (https://gephi.org/, accessed on 21 May 2021).