This post is in support of the CDC’s Fungal Disease Awareness Week — September 20-24, 2021.

The impact of fungal diseases on human health has often been neglected, but increased association of fungal infections with severe illness and death during the COVID-19 pandemic has brought fungal diseases into the spotlight.

According to the CDC, the most common fungal co-infections in patients with COVID-19 include aspergillosis or invasive candidiasis including healthcare-associated infection from Candida auris.  Other reported diseases are mucormycosis, coccidioidomycosis and cryptococcosis. Aspergillosis is commonly caused by Aspergillus fumigatus, mucormycosis by Rhizopus species, coccidioidomycosis by Coccidioides immitis and C. posadasii and cryptococcosis by Cryptococcus neoformans.

This post explores several NCBI resources that have relevant information about the fungal pathogens implicated in these COVID-19 related illnesses.

Assembled genomes

Correctly identified and annotated genome assemblies are available for the fungal taxa implicated as co-infections in COVID-19 patients are summarized in table below.  These and  many other fungi are also available as curated RefSeq genome assemblies.

Literature

Publications about Covid-19 and fungal infection are available  in PubMed and in the curated resource LitCovid  set, which identifies articles related to COVID-19.  The following search in LitCovid produces a relevant set of over 500 literature citations.

“Fungi OR yeast OR Aspergillus OR Coccidioides OR Candida auris OR Rhizopus OR Mucor ”

The same search in PubMed restricted to the Abstract/Title field combined with COVID-19 produces a slightly smaller set of relevant citations.

Fungal rRNA ITS and 28S reference sequences

The causal agents of fungal infections need to be accurately identified to ensure timely and appropriate treatment. For example, Candida auris  that causes outbreaks in healthcare settings may be difficult to treat effectively because of multi-drug resistance. Correct identification  is important for appropriate management. However, according to the CDC,  C. auris can be misidentified by traditional phenotypic methods for yeast identification.  Molecular methods based on sequencing the D1-D2 region of the 28s rRNA gene or the internal transcribed region (ITS) flanking the 5.8S rRNA gene are necessary to accurately identify C. auris. The ITS and 28s rRNA gene sequences (ITS: NR_154998.1 and 28S: NG_055302.1) from the specimen (type material) originally used to describe the species are present in NCBI’s curated RefSeq Targeted Loci (RTL) databases. As expected, the forward (V2424F (CAURF)) and reverse (V2426 (CAURR)) primers, developed by Leach et al., (2018) and used in the CDC’s real-time PCR protocol, perfectly match in the 5.8S gene and in the ITS2 region, in a highly specific region for the C. auris sequence (NR_154998.1).

Note: The genus Candida is polyphyletic — arising from multiple ancestral sources. Therefore Candida auris is displayed as [Candida] auris at NCBI Taxonomy. This is to indicate that C. auris is not related to Candida yeasts in the narrow sense such as Candida albicans , but  is instead a member of the Clavispora/Candida phylogenetic clade. This information is very important when making treatment and management decisions.

NCBI Pathogen detection

Whole genome sequencing is another molecular tool used to detect and monitor disease-causing fungi,  and can provide information on how the pathogen evolves during an infection and identifying phylogenetic clades during an outbreak. Fungal disease outbreaks are rare, but more than 1 in 3 patients with invasive C. auris infection — for example, an infection that affects the blood, heart, or brain — die. It is therefore important to identify and monitor this fungus closely. To help with traceback and outbreak investigations, C. auris has been included in NCBI’s Pathogen Detection resource . The Pathogen Detection Isolates Browser clusters related isolates based on genome similarity and facilitates tracing outbreaks back to a source. The interactive tree display of a SNP (single nucleotide polymorphism) cluster is annotated with geographic and isolation source information related to each isolate.

NCBI provides essential resources for research on and identification of fungal pathogens and monitoring outbreaks of fungal disease. Please write to us at [email protected] with any questions, comments or suggestions about these resources.

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