INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/ L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.

A high fosfomycin resistance rate was observed in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) in our previous study, but little is known about its mechanisms. In this study, we explored the prevalence of plasmidmediated fosfomycin resistance determinants among fosfomycin-resistant KPC-KP strains from a Chinese university hospital and determined the complete sequence of a novel fosA3-carrying plasmid isolated from an epidemic K. pneumoniae sequence type (ST) 11 strain. A total of 97 KPC-KP strains were studied, of which 57 (58.8%) were resistant to fosfomycin, including 44 (45.4%) harboring fosA3 and 1 harboring fosA. All fosA3-positive strains belonged to the dominant ST11-pulse type (PT) A clone according to multilocus sequence typing and pulsed-field gel electrophoresis, suggesting clonal dissemination. The fosA-positive isolate belonged to ST11-PTE. The fosA3-carrying plasmid pKP1034 is 136,848 bp in length and is not self-transmissible. It is a multireplicon plasmid belonging to IncR-F33:A؊: B؊. Besides fosA3, a variety of other resistance determinants, including bla KPC-2 , rmtB, bla CTX-M-65 , and bla SHV-12 , are identified in pKP1034, which would allow for coselection of fosA3 by most ␤-lactams and/or aminoglycosides and facilitate its dissemination despite limited use of fosfomycin in China. Detailed comparisons with related plasmids revealed that pKP1034 is highly mosaic and might have evolved from alarming recombination of the bla KPC-2 -carrying plasmid pKPC-LK30 from Taiwan and the epidemic fosA3-carrying plasmid pHN7A8 from mainland China. Increasing prevalence of Klebsiella pneumoniae carbapenemaseproducing K. pneumoniae (KPC-KP) has presented an alarming clinical threat. Fosfomycin seems to retain in vitro activity against many carbapenem-resistant Enterobacteriaceae and has been recently reintroduced into the fight against these superbugs, including KPC-KP strains (1-4). A previous study showed that only 43.4% of KPC-KP strains retained susceptibility to fosfomycin in a Chinese university hospital (5). Recently, Jiang et al. reported a comparable fosfomycin susceptibility rate (39.2%) in KPC-KP collected from 12 hospitals in China, and fosfomycin resistance could be attributed to the plasmid-mediated fosA3 gene in 94 (55.6% of fosfomycin-resistant KPC-KP) strains (6).FosA3 inactivates fosfomycin by glutathione S-transferase activity and was characterized first in CTX-M-producing Escherichia coli in Japan (7). Thereafter, it has been detected in foodproducing animals, pets, patients, and healthy individuals in Asian countries (8-11). In most cases, the fosA3 gene is associated with bla CTX-M genes and sometimes with rmtB as well, and it resides on IS26-composite transposons, facilitating its dissemination. More recently, fosA3 has been characterized in two atypical bla KPC -carrying plasmids (6, 12). Here we explored the prevalence of plasmid-mediated fosfomycin resistance determinants among KPC-KP strains from a Chinese university hospital and determined the comple...