Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late December 2019, causing a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19). This disease can cause a plethora of clinical manifestations, ranging from mild to severe respiratory conditions which can also escalate to acute respiratory distress syndrome (ARDS) or multi-organ failure. COVID-19 is also associated with immune dysregulation which can increase the risk of co-infections, such as those caused by Candida species. The Candida genus embraces a highly heterogeneous group of eukaryotic unicellular fungi. These organisms are usually commensal, colonizer of the mucosal surfaces, respiratory, genitourinary and gastrointestinal tracts in humans. However, in specific individuals, such as immuno-suppressed patients or those under surgery, they can turn into opportunistic pathogens, causing either superficial infections or systemic threatening conditions. Based on these considerations, for my thesis project, I conducted a retrospective study in which I genomically analyzed a number of Candida isolates collected at San Matteo Hospital in Pavia (Italy), before and during the first wave of the COVID-19 outbreak, starting from 2015. I (i) deeply characterized these Candida genomes for the presence of virulence genes and resistance to antifungal agents; (ii) inferred the evolutionary relationships between samples to identify the presence of outbreaks and lastly (iii) studied the co-presence of COVID-19 among the isolates. From these analyses, I identified a various number of different Candida species, among which Candida albicans and Candida parapsilosis appeared to be the most abundant groups. All C. albicans infections are caused by susceptible strains which are not evolutionary correlated but rather vertical acquired. Instead, within C. parapsilosis species, phylogenetic analysis based on coreSNPs defined the presence of two well separated, highly correlated clusters, one of which highly resistant to antifungals and responsible for an extended outbreak also covering the first COVID-19 wave.
Il coronavirus della sindrome respiratoria acuta grave 2 (SARS-CoV-2) è emerso alla fine di dicembre 2019, causando una pandemia di malattia respiratoria acuta, denominata "malattia da coronavirus 2019" (COVID-19). Questa malattia può causare una pletora di manifestazioni cliniche, che vanno da condizioni respiratorie da lievi a gravi che possono anche degenerare in sindrome da distress respiratorio acuto (ARDS) o insufficienza multiorgano. Il COVID-19 è anche associato a una disregolazione immunitaria che può aumentare il rischio di co-infezioni, come quelle causate dalle specie di patogeni fungini del genere Candida. Il genere Candida abbraccia un gruppo altamente eterogeneo di funghi unicellulari eucariotici. Questi organismi sono generalmente commensali, colonizzatori delle superfici mucose, del tratto respiratorio, genitourinario e gastrointestinale nell’uomo. Tuttavia, in individui specifici, come i pazienti immunosoppressi o quelli sottoposti a intervento chirurgico, possono trasformarsi in patogeni opportunisti, causando infezioni o condizioni sistemiche potenzialmente letali. Sulla base di queste considerazioni, per il mio progetto di tesi, ho condotto uno studio retrospettivo in cui ho analizzato i genomi di 111 isolati di Candida raccolti presso l’Ospedale San Matteo di Pavia (Italia), prima e durante la prima ondata dell’epidemia di COVID-19, iniziando dal 2015. Ho quindi (i) caratterizzato questi genomi di Candida determinando la presenza di geni di virulenza e resistenza agli agenti antimicotici; (ii) dedotto le relazioni evolutive tra i campioni per identificare la presenza di focolai e infine (iii) studiato la compresenza di COVID-19 nei pazienti. Da queste analisi, ho identificato in totale sei specie diverse di Candida, tra le quali Candida albicans e Candida parapsilosis risultano essere le più abbondanti. Tutte le infezioni da C. albicans sono causate da ceppi suscettibili che non sono correlati evolutivamente ma acquisiti verticalmente. Invece, all’interno delle specie di C. parapsilosis, l’analisi filogenetica basata su coreSNPs ha definito la presenza di due cluster filogenetici ben separati e altamente correlati, uno dei quali è altamente resistente agli antimicotici e responsabile per un focolaio esteso che ha causato tutti i casi di candidemia riportati durante la prima ondata di COVID-19.
Genomic epidemiology of Candida spp. isolated from patients before and during the first COVID-19 wave in the San Matteo Hospital in Pavia
KILIC, DINCER
2021/2022
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late December 2019, causing a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19). This disease can cause a plethora of clinical manifestations, ranging from mild to severe respiratory conditions which can also escalate to acute respiratory distress syndrome (ARDS) or multi-organ failure. COVID-19 is also associated with immune dysregulation which can increase the risk of co-infections, such as those caused by Candida species. The Candida genus embraces a highly heterogeneous group of eukaryotic unicellular fungi. These organisms are usually commensal, colonizer of the mucosal surfaces, respiratory, genitourinary and gastrointestinal tracts in humans. However, in specific individuals, such as immuno-suppressed patients or those under surgery, they can turn into opportunistic pathogens, causing either superficial infections or systemic threatening conditions. Based on these considerations, for my thesis project, I conducted a retrospective study in which I genomically analyzed a number of Candida isolates collected at San Matteo Hospital in Pavia (Italy), before and during the first wave of the COVID-19 outbreak, starting from 2015. I (i) deeply characterized these Candida genomes for the presence of virulence genes and resistance to antifungal agents; (ii) inferred the evolutionary relationships between samples to identify the presence of outbreaks and lastly (iii) studied the co-presence of COVID-19 among the isolates. From these analyses, I identified a various number of different Candida species, among which Candida albicans and Candida parapsilosis appeared to be the most abundant groups. All C. albicans infections are caused by susceptible strains which are not evolutionary correlated but rather vertical acquired. Instead, within C. parapsilosis species, phylogenetic analysis based on coreSNPs defined the presence of two well separated, highly correlated clusters, one of which highly resistant to antifungals and responsible for an extended outbreak also covering the first COVID-19 wave.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
Per maggiori informazioni e per verifiche sull'eventuale disponibilità del file scrivere a: unitesi@unipv.it.
https://hdl.handle.net/20.500.14239/14748