Hospital-acquired infections (HAIs) are a global public health concern. As the COVID-19 pandemic continues, its contribution to mortality and antimicrobial resistance (AMR) grows, particularly in intensive care units (ICUs). A two-year retrospective study from April 2019–April 2021 was conducted in an adult ICU at the Hospital for Infectious and Tropical Diseases, Belgrade, Serbia to assess causative agents of HAIs and AMR rates, with the COVID-19 pandemic ensuing halfway through the study. Resistance rates >80% were observed for the majority of tested antimicrobials. In COVID-19 patients, Acinetobacter spp. was the dominant cause of HAIs and more frequently isolated than in non-COVID-19 patients. (67 vs. 18, p = 0.001). Also, resistance was higher for imipenem (56.8% vs. 24.5%, p < 0.001), meropenem (61.1% vs. 24.3%, p < 0.001) and ciprofloxacin (59.5% vs. 36.9%, p = 0.04). AMR rates were aggregated with findings from our previous study to identify resistance trends and establish empiric treatment recommendations. The increased presence of Acinetobacter spp. and a positive trend in Klebsiella spp. resistance to fluoroquinolones (R² = 0.980, p = 0.01) and carbapenems (R² = 0.963, p = 0.02) could have contributed to alarming resistance rates across bloodstream infections (BSIs), pneumonia (PN), and urinary tract infections (UTIs). Exceptions were vancomycin (16.0%) and linezolid (2.6%) in BSIs; tigecycline (14.3%) and colistin (0%) in PNs; and colistin (12.0%) and linezolid (0%) in UTIs. COVID-19 has changed the landscape of HAIs in our ICUs. Approval of new drugs and rigorous surveillance is urgently needed.

Chronic pulmonary aspergillosis (CPA) is a chronic progressive lung disease associated with a poor prognosis and a 5-year mortality rate of approximately 40–50%. The disease is characterized by slowly progressive destruction of the lung parenchyma, in the form of multiple cavities, nodules, infiltrates or fibrosis. CPA can be challenging to diagnose due to its non-specific symptoms and similarities with other respiratory conditions combined with the poor awareness of the medical community about the disease. This can result in delayed treatment even for years and worsening of the patient’s condition. Serological tests certainly play a significant role in diagnosing CPA but cannot be interpreted without radiological confirmation of CPA. Although many data are published on this hot topic, there is yet no single definitive test for diagnosing CPA, and a multidisciplinary approach which involves a combination of clinical picture, radiological findings, microbiological results and exclusion of other mimicking diseases, is essential for the accurate diagnosis of CPA.

Understanding the sequelae of COVID-19 is of utmost importance. Neuroinflammation and disturbed redox homeostasis are suggested as prevailing underlying mechanisms in neurological sequelae propagation in long-COVID. We aimed to investigate whether variations in antioxidant genetic profile might be associated with neurological sequelae in long-COVID. Neurological examination and antioxidant genetic profile (SOD2, GPXs and GSTs) determination, as well as, genotype analysis of Nrf2 and ACE2, were conducted on 167 COVID-19 patients. Polymorphisms were determined by the appropriate PCR methods. Only polymorphisms in GSTP1AB and GSTO1 were independently associated with long-COVID manifestations. Indeed, individuals carrying GSTP1 Val or GSTO1 Asp allele exhibited lower odds of long-COVID myalgia development, both independently and in combination. Furthermore, the combined presence of GSTP1 Ile and GSTO1 Ala alleles exhibited cumulative risk regarding long-COVID myalgia in carriers of the combined GPX1 LeuLeu/GPX3 CC genotype. Moreover, individuals carrying combined GSTM1-null/GPX1LeuLeu genotype were more prone to developing long-COVID “brain fog”, while this probability further enlarged if the Nrf2 A allele was also present. The fact that certain genetic variants of antioxidant enzymes, independently or in combination, affect the probability of long-COVID manifestations, further emphasizes the involvement of genetic susceptibility when SARS-CoV-2 infection is initiated in the host cells, and also months after.

Based on the close relationship between dysregulation of redox homeostasis and immune response in SARS-CoV-2 infection, we proposed a possible modifying role of ACE2 and glutathione transferase omega (GSTO) polymorphisms in the individual propensity towards the development of clinical manifestations in COVID-19. The distribution of polymorphisms in ACE2 (rs4646116), GSTO1 (rs4925) and GSTO2 (rs156697) were assessed in 255 COVID-19 patients and 236 matched healthy individuals, emphasizing their individual and haplotype effects on disease development and severity. Polymorphisms were determined by the appropriate qPCR method. The data obtained showed that individuals carrying variant GSTO1*AA and variant GSTO2*GG genotypes exhibit higher odds of COVID-19 development, contrary to ones carrying referent alleles (p = 0.044, p = 0.002, respectively). These findings are confirmed by haplotype analysis. Carriers of H2 haplotype, comprising GSTO1*A and GSTO2*G variant alleles were at 2-fold increased risk of COVID-19 development (p = 0.002). Although ACE2 (rs4646116) polymorphism did not exhibit a statistically significant effect on COVID-19 risk (p = 0.100), the risk of COVID-19 development gradually increased with the presence of each additional risk-associated genotype. Further studies are needed to clarify the specific roles of glutathione transferases omega in innate immune response and vitamin C homeostasis once the SARS-CoV-2 infection is initiated in the host cell.

Antimicrobial resistance (AMR) is a global concern, and antibiotic use has risen throughout the COVID-19 pandemic. Up to 75% of COVID-19 patients are treated with antibiotics despite little evidence for their use. A retrospective study from 6 March 2020 (the start of the pandemic in Serbia) to 31 December 2021 was conducted at the Clinic for Infectious and Tropical Diseases, University Clinical Centre of Serbia. In total, 523 patients with a microbiological diagnosis of COVID-19 were included. Patient data were analysed, including antibiotic use before and after admission. Pre-admission use of antibiotics for COVID-19 treatment was documented in more than half of patients (58.1%), of which a third (34.1%) used more than one antibiotic. Macrolides, cephalosporins, and fluoroquinolones were mainly used, most frequently among patients aged between 31–45 years (75.2%). Prior antibiotic use was associated with a longer duration of illness at admission (8.8 vs. 5.7, p < 0.001), oxygen therapy upon admission (27.6% vs. 16.0%, p = 0.002), and a lower vaccination rate (60.7% vs. 50.7%, p = 0.04). When hospitalised, 72.1% of patients received antibiotics, primarily cephalosporins (71.9%). Significant efforts are needed to reduce antibiotic use in the community and improve prescribing rates by healthcare professionals.

Studies suggest that the incidence of coinfections in patients with the coronavirus disease 2019 (COVID-19) is low, but a large number of patients receive antimicrobials during hospitalisation. This may fuel a rise in antimicrobial resistance (AMR). We conducted a multicentre point-prevalence survey in seven tertiary university hospitals (in medical wards and intensive care units) in Croatia, Italy, Serbia and Slovenia. Of 988 COVID-19 patients, 521 were receiving antibiotics and/or antifungals (52.7%; range across hospitals: 32.9–85.6%) on the day of the study. Differences between hospitals were statistically significant (χ² (6, N = 988) = 192.57, p < 0.001). The majority of patients received antibiotics and/or antifungals within 48 h of admission (323/521, 62%; range across hospitals: 17.4–100%), their most common use was empirical (79.4% of prescriptions), and pneumonia was the main indication for starting the treatment (three-quarters of prescriptions). The majority of antibiotics prescribed (69.9%) belonged to the “Watch” group of the World Health Organization AWaRe classification. The pattern of antimicrobial use differed across hospitals. The data show that early empiric use of broad-spectrum antibiotics is common in COVID-19 patients, and that the pattern of antimicrobial use varies across hospitals. Judicious use of antimicrobials is warranted to prevent an increase in AMR.