Nirmatrelvir/ritonavir (Paxlovid™) is an effective and safe antiviral drug that inhibits the main protease (M^pro), 3CL protease, of SARS-CoV-2. A reduction in COVID-19-related hospitalization or death was observed in patients treated with nirmatrelvir/ritonavir within five days of symptom onset. Moreover, good oral availability enables the usage of nirmatrelvir/ritonavir, not only in hospitalized patients, but also among outpatients. Nirmatrelvir (PF-07321332) has been demonstrated to stop the spread of COVID-19 in animal models. Despite frequent mutations in the viral genomes of SARS-CoV-2, nirmatrelvir shows an effective antiviral effect against recent coronavirus mutants. Despite the promising antiviral effect of nirmatrelvir, there are several unresolved concerns. First, the final results of large-scale clinical trials for early therapy of mild cases of COVID-19 are not yet published. Second, the effectiveness of nirmatrelvir against upcoming variants in the coming years requires close monitoring. Considering the promising preliminary results of the EPIC-HR trial, nirmatrelvir/ritonavir in conjunction with vaccines and non-pharmacological interventions, may represent the dawn in the dark of the COVID-19 pandemic.

The incidence of COVID-19-associated candidiasis (CAC) is increasing, resulting in a grave outcome among hospitalized patients with COVID-19. The most alarming condition is the increasing incidence of multi-drug resistant Candida auris infections among patients with COVID-19 worldwide. The therapeutic strategy towards CAC caused by common Candida species, such as Candida albicans, Candida tropicalis, and Candida glabrata, is similar to the pre-pandemic era. For non-critically ill patients or those with a low risk of azole resistance, fluconazole remains the drug of choice for candidemia. For critically ill patients, those with a history of recent azole exposure or with a high risk of fluconazole resistance, echinocandins are recommended as the first-line therapy. Several novel therapeutic agents alone or in combination with traditional antifungal agents for candidiasis are potential options in the future. However, for multidrug-resistant C. auris infection, only echinocandins are effective. Infection prevention and control policies, including strict isolation of the patients carrying C. auris and regular screening of non-affected patients, are suggested to prevent the spread of C. auris among patients with COVID-19. Whole-genome sequencing may be used to understand the epidemiology of healthcare-associated candidiasis and to better control and prevent these infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus of the family Coronaviridae, causes coronavirus disease 2019 (COVID-19), an influenza-like disease that chiefly infects the lungs through respiratory transmission. The spike protein of SARS-CoV-2, a transmembrane protein in its outer portion, targets angiotensin-converting enzyme 2 (ACE2) as the binding receptor for the cell entry. As ACE2 is highly expressed in the gut and pulmonary tissues, SARS-CoV-2 infections frequently result in gastrointestinal inflammation, with presentations ordinarily ranging from intestinal cramps to complications with intestinal perforations. However, the evidence detailing successful therapy for gastrointestinal involvement in COVID-19 patients is currently limited. A significant change in fecal microbiomes, namely dysbiosis, was characterized by the enrichment of opportunistic pathogens and the depletion of beneficial commensals and their crucial association to COVID-19 severity has been evidenced. Oral probiotics had been evidenced to improve gut health in achieving homeostasis by exhibiting their antiviral effects via the gut–lung axis. Although numerous commercial probiotics have been effective against coronavirus, their efficacies in treating COVID-19 patients remain debated. In ClinicalTrials.gov, 19 clinical trials regarding the dietary supplement of probiotics, in terms of Lactobacillus and mixtures of Bifidobacteria and Lactobacillus, for treating COVID-19 cases are ongoing. Accordingly, the preventive or therapeutic role of probiotics for COVID-19 patients can be elucidated in the near future.

Clostridium difficile is the leading cause of nosocomial infectious diarrhea. Hospitalized patients were at risk of C. difficile-associated diarrhea (CDAD). However the risk factors of CDAD in patients with different hospitalization period are not clear. A prospective investigation was conducted in medical wards of a district hospital in southern Taiwan, from January 2011 to January 2013. We arbitrary divided patients into two groups: hospitalized for at most 14 days and 15-30 days, and analyzed their risk factors for CDAD. Overall 451 patients were enrolled. The multivariable analysis of 19 (8.0%) patients developing CDAD within 14 days' hospital stay and 216 patients hospitalized for ≤ 14 days without CDAD showed malignancy (odds ratio [OR] 7.15, 95% confidence interval [CI] 1.82-28.09; P = 0.005), prior cephalosporin (OR 10.8, 95% CI 1.3-93.9; P = 0.03) and proton pump inhibitor (PPI; OR 7.1, 95% CI 2.1-24.7; P = 0.002) therapy were independently related to CDAD (Table 3), but hypertension (OR 0.2, 95% CI 0.1-0.7; P = 0.01) was reversely related to CDAD. However, of 9 (4.2%) patients developing CDAD later (15-30 days' hospital stay) and 207 patients with longer hospitalization (15-30 days) but free of CDAD, malignancy (OR 14.0, 95% CI 1.6-124.9; P = 0.02) and underlying diabetes mellitus (OR 20.5, 95% CI 2.9-144.9; P = 0.002) were independent risk factors of CDAD. Risk factors for CDAD among hospitalized patients varied by the duration of hospital stay. Intervention strategies to prevent CDAD may be different in terms of hospital stay duration.

Bacteria-targeting nanomaterials have been widely used in the diagnosis and treatment of bacterial infectious diseases. These nanomaterials show great potential as antimicrobial agents due to their broad-spectrum antibacterial capacity and relatively low toxicity. Recently, nanomaterials have improved the accurate detection of pathogens, provided therapeutic strategies against nosocomial infections and facilitated the delivery of antigenic protein vaccines that induce humoral and cellular immunity. Biomaterial implants, which have traditionally been hindered by bacterial colonization, benefit from their ability to prevent bacteria from forming biofilms and spreading into adjacent tissues. Wound repair is improving in terms of both the function and prevention of bacterial infection, as we tailor nanomaterials to their needs, select encapsulation methods and materials, incorporate activation systems and add immune-activating adjuvants. Recent years have produced numerous advances in their antibacterial applications, but even further expansion in the diagnosis and treatment of infectious diseases is expected in the future.