The emergence of multiple lower respiratory tract infection clusters in China during 2019 resulted in the identification of the SARS-CoV-2 ((+) ssRNA virus, Family: Coronaviridae) virus as a pathogen of COVID-19 disease and, within a few months, the development of those clusters into a global pandemic[1]. In turn, the spread of SARS-CoV-2 has led to an increase in hospital admissions that required high levels of oxygen therapy, multi-day hospitalization, the use of individual protection measures, and the inclusion of corticosteroids, antiviral treatments, and in most cases, broad-spectrum antimicrobials for inpatients and outpatients too[2].

Secondary bacterial infections have been observed in several respiratory tract infections, from opportunistic pathogens of the upper respiratory microbiota to pathogens such as Clostridioides difficile (C. difficile), especially in hospital conditions[3]. C. difficile is an anaerobic Gram-positive sporogenic bacteria that can result in a variety of clinical manifestations, from asymptomatic colonization to mild acute diarrheal syndrome or severe life-threatening colitis[4]. Based on the origin of symptom onset, CDI is usually divided into two distinct categories. Healthcare-associated CDI (HA-CDI))is defined as CDI associated with healthcare facilities and further subdivided by whether the onset of symptoms occurs beyond 48 hours of arrival at the hospital (hospital-onset CDI, HO-CDI) or up to one month from the previous discharge (community-onset, healthcare-associated CDI, CO-HA-CDI). Community-associated CDI (CA-CDI) is defined by the onset of symptoms <48 hours after admission to the hospital, at least three months after the last visit to a health facility[5], [6].

In the last twenty years, there has been an increase in CDI occurrence, especially in elderly patients with a more severe clinical presentation and often resistant to standard treatment, mainly due to the spread of hypervirulent strains and the widespread use of antibiotics. According to the ECDC prevalence survey for nosocomial infections and antimicrobial stewardship for 2011-2012, C. difficile was the 8th most common nosocomial pathogen [7]. In the USA in 2017, there were 223900 new cases of CDI, with almost two-thirds involving hospital-onset cases and 12800 deaths [8]. Moreover, in 2016, twenty European countries reported 7711 new cases of CDI, 74.6% of which were HA-CDI and 25.4% CA-CDI or of unknown origin, with a 7.9% rate of recurrence and 16.7% of complicated infection[9]. In Greece, the incidence of CDI is 4.6/10,000 hospital patient days, with a point prevalence of 0.86% and 15.7% among patients with reported healthcare-associated diarrhea. Cases are more often reported in Oncology (37.5%), General Surgery (18.2%), and Internal Medicine wards (14.3%) [10].

The COVID-19 pandemic has brought several changes in the implementation of individual infection prevention measures and the control of healthcare-associated infections. The increased use of personal protective equipment and personal hygiene probably limited the transmission of infections. In contrast, the over-administration of broad-spectrum antibiotics, such as macrolides and respiratory quinolones, or the overuse of alcohol-based disinfectants, probably affected the development and occurrence of C. difficile in hospitals and the community [11]. In addition, the clinical presentation of COVID-19 includes symptoms such as acute diarrhoea, which probably prevented in some cases the further investigation of CDI for inpatients or, in other cases, led to the possible over-sampling for C. difficile, leading to ambiguous results[11]. Based on the international literature that is constantly updated and enriched, CDI in the context of hospitalization due to COVID-19 has inevitably started to concern the medical community. Recent studies have investigated CDI occurrence in the context of the COVID-19 pandemic, with varying results[12], [13], [14]. Therefore, there is a significant debate with regard to the effect of the COVID-19 pandemic on CDI prevalence.

This study focuses on documenting the epidemiological and disease-related differences between patients hospitalized in an Internal Medicine and a COVID-19 ward, as well as reporting CDI prevalence and mortality during the COVID-19 pandemic. The primary aim was to study the prevalence, mortality, epidemiological, and infection characteristics of patients with CDI during the COVID-19 pandemic. The secondary outcomes included differences between COVID-19 patients and patients from the internal medicine ward in terms of epidemiological and disease characteristics, morbidity, and mortality.