While the presence of airway bacteria is known to be associated with improved immunity against influenza virus, the mechanism by which endogenous microbiota influence antiviral immunity remains unclear. Here we show that specific pathogen-free mice are more sensitive to influenza-mediated death than mice living in a natural environment. Priming with Toll-like receptor 2-ligand+ Staphylococcus aureus, which commonly colonizes the upper respiratory mucosa, significantly attenuates influenza-mediated lung immune injury. Toll-like receptor 2 deficiency or alveolar macrophage depletion abolishes this protection. S. aureus priming recruits peripheral CCR2+CD11b+ monocytes into the alveoli that polarize to M2 alveolar macrophages in an environment created by Toll-like receptor 2 signalling. M2 alveolar macrophages inhibit influenza-mediated lethal inflammation via anti-inflammatory cytokines and inhibitory ligands. Our results suggest a previously undescribed mechanism by which the airway microbiota may protect against influenza-mediated lethal inflammation.

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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.

Severe viral hepatitis with high mortality is the most common cause of liver failure in China. Treatment of severe viral hepatitis by hemoperfusion was initially adopted in the late 1970s and early 1980s. Following 10 years of development in China, a plasma exchange (PE)-centered artificial liver support system (ALSS), principally dependent on PE technology was developed. Based on the condition and symptoms of each patient, PE was given alone, or combined with hemodialysis, hemofiltration, hemodiafiltration, hemoperfusion, or plasma perfusion. In the late 1990s, training courses for ALSS were developed, and ALSS began to be carried out across China. Guidelines for artificial liver therapy were formulated and published by the Artificial Liver and Liver Failure Group of the Chinese Society of Infection. In recent years, new methods have been attempted, including small pore-size plasma separators, a molecular adsorbent-based recirculating system (MARS), and a continuous albumin purification system (CAPS). According to a retrospective analysis published in 2004, ALSS therapy significantly (P < 0.001) improved the survival rate of patients with severe hepatitis compared with patients who received only medicines (43.4%, 157/362 vs. 15.4%, 55/358 in chronic patients and 78.9%, 30/38 vs. 11.9%, 5/42 in acute and subacute patients). Furthermore, ALSS has also proved valuable as a bridge to liver transplantation in the treatment of patients with end-stage severe hepatitis in China. More recently, ALSS has been used in the treatment of drug-induced liver failure, acute fatty liver during pregnancy, and other difficult-to-treat disorders in China.

a b s t r a c tMiddle East respiratory syndrome (MERS) is a viral respiratory disease caused by a de novo coronavirus-MERS-CoV-that is associated with high mortality. However, the mechanism by which MERS-CoV infects humans remains unclear. To date, there is no effective vaccine or antibody for human immunity and treatment, other than the safety and tolerability of the fully human polyclonal Immunoglobulin G (IgG) antibody (SAB-301) as a putative therapeutic agent specific for MERS. Although rapid diagnostic and public health measures are currently being implemented, new cases of MERS-CoV infection are still being reported. Therefore, various effective measures should be taken to prevent the serious impact of similar epidemics in the future. Further investigation of the epidemiology and pathogenesis of the virus, as well as the development of effective therapeutic and prophylactic anti-MERS-CoV infections, is necessary. For this purpose, detailed information on MERS-CoV proteins is needed. In this review, we describe the major structural and nonstructural proteins of MERS-CoV and summarize different potential strategies for limiting the outbreak of MERS-CoV. The combination of computational biology and virology can accelerate the advanced design and development of effective peptide therapeutics against MERS-CoV. In summary, this review provides important information about the progress of the elimination of MERS, from prevention to treatment.

BACKGROUNDDiarrhea is a major infectious cause of childhood morbidity and mortality worldwide. In clinical trials, Lactobacillus rhamnosus GG ATCC 53013 (LGG) has been used to treat diarrhea. However, recent randomized controlled trials (RCTs) found no evidence of a beneficial effect of LGG treatment.AIMTo evaluate the efficacy of LGG in treating acute diarrhea in children.METHODSThe EMBASE, MEDLINE, PubMed, Web of Science databases, and the Cochrane Central Register of Controlled Trials were searched up to April 2019 for meta-analyses and RCTs. The Cochrane Review Manager was used to analyze the relevant data.RESULTSNineteen RCTs met the inclusion criteria and showed that compared with the control group, LGG administration notably reduced the diarrhea duration [mean difference (MD) -24.02 h, 95% confidence interval (CI) (-36.58, -11.45)]. More effective results were detected at a high dose ≥ 1010 CFU per day [MD -22.56 h, 95%CI (-36.41, -8.72)] vs a lower dose. A similar reduction was found in Asian and European patients [MD -24.42 h, 95%CI (-47.01, -1.82); MD -32.02 h, 95%CI (-49.26, -14.79), respectively]. A reduced duration of diarrhea was confirmed in LGG participants with diarrhea for less than 3 d at enrollment [MD -15.83 h, 95%CI (-20.68, -10.98)]. High-dose LGG effectively reduced the duration of rotavirus-induced diarrhea [MD -31.05 h, 95%CI (-50.31, -11.80)] and the stool number per day [MD -1.08, 95%CI (-1.87, -0.28)].CONCLUSIONHigh-dose LGG therapy reduces the duration of diarrhea and the stool number per day. Intervention at the early stage is recommended. Future trials are expected to verify the effectiveness of LGG treatment.

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...

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