After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People’s Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.

Vibrio harveyi, which now includes Vibrio carchariae as a junior synonym, is a serious pathogen of marine fish and invertebrates, particularly penaeid shrimp. In fish, the diseases include vasculitis, gastro-enteritis and eye lesions. With shrimp, the pathogen is associated with luminous vibriosis and Bolitas negricans. Yet, the pathogenicity mechanisms are imprecisely understood, with likely mechanisms involving the ability to attach and form biofilms, quorum sensing, various extracellular products including proteases and haemolysins, lipopolysaccharide, and interaction with bacteriophage and bacteriocin-like substances

Many Vibrio species are pathogenic to humans, and/or marine vertebrates and invertebrates. The pathogenic species produce various virulence factors including enterotoxin, haemolysin, cytotoxin, protease, lipase, phospholipase, siderophore, adhesive factor and/or haemagglutinins. Haemolysin, which is an exotoxin that lyses erythrocyte membranes with the liberation of haemoglobin, is arguably the most widely distributed toxin among pathogenic vibrios and exerts various roles in the infection process. Haemolysins act on erythrocytes membranes thus lysing the cells which leads to the freeing up of the iron-binding proteins namely haemoglobin, transferrin and lactoferrin. This iron can then be picked up by various siderophores, and is subsequently taken up through receptors in the cell membrane. In many cases, the pore-forming activity of haemolysin is not restricted to erythrocytes, but extends to a wide range of other cell types including mast cells, neutrophils, and polymorphonuclear cells, and enhances virulence by causing tissue damage. There are four representative haemolysin families in Vibrio spp., including the TDH (thermostable direct haemolysin) family, the HlyA (E1 Tor haemolysin) family, the TLH (thermolabile haemolysin) family and the d-VPH (thermostable haemolysin) family. Some haemolysins, for example, TDH of Vibrio parahaemolyticus and HlyA of Vibrio cholerae have been studied extensively, and are closely associated with virulence. However, the role of some haemolysins, e.g. TLH and d-VPH are unclear, and await the outcome of further research.

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bGram-negative bacteria use N-acyl homoserine lactones (AHLs) as quorum sensing (QS) signaling molecules for interspecies communication, and AHL-dependent QS is related with virulence factor production in many bacterial pathogens. Quorum quenching, the enzymatic degradation of the signaling molecule, would attenuate virulence rather than kill the pathogens, and thereby reduce the potential for evolution of drug resistance. In a previous study, we showed that Muricauda olearia Th120, belonging to the class Flavobacteriia, has strong AHL degradative activity. In this study, an AHL lactonase (designated MomL), which could degrade both short-and long-chain AHLs with or without a substitution of oxo-group at the C-3 position, was identified from Th120. Liquid chromatography-mass spectrometry analysis demonstrated that MomL functions as an AHL lactonase catalyzing AHL degradation through lactone hydrolysis. MomL is an AHL lactonase belonging to the metallo-␤-lactamase superfamily that harbors an N-terminal signal peptide. The overall catalytic efficiency of MomL for C 6 -HSL is ϳ2.9 ؋ 10 5 s ؊1 M ؊1 . Metal analysis and site-directed mutagenesis showed that, compared to AiiA, MomL has a different metal-binding capability and requires the histidine and aspartic acid residues for activity, while it shares the "HXHXDH" motif with other AHL lactonases belonging to the metallo-␤-lactamase superfamily. This suggests that MomL is a representative of a novel type of secretory AHL lactonase. Furthermore, MomL significantly attenuated the virulence of Pseudomonas aeruginosa in a Caenorhabditis elegans infection model, which suggests that MomL has the potential to be used as a therapeutic agent. N-Acyl homoserine lactones (AHLs) are quorum-sensing (QS) signaling molecules that are used by many Gram-negative bacteria to communicate within species, to regulate gene expression and to synchronize social behaviors, such as biofilm formation, bioluminescence, and secretion of virulence factors (1, 2). An AHL molecule typically consists of a homoserine lactone and an acyl chain with an even number of carbons, with an occasional modification (hydroxy or olefinic double bond) at the C-3 position (1). It has been well established that AHL-dependent QS regulates virulence factor production in many bacterial pathogens, such as Pseudomonas aeruginosa, Erwinia carotovora, Vibrio spp., and Burkholderia spp. (1). Interference with QS has been recognized as a promising antivirulence therapy. Disturbing the QS systems in these pathogens would attenuate virulence rather than kill the bacteria and thereby weaken the selective pressure imposed on the pathogens and reduce the potential for evolution of drug resistance (3). QS inhibitors (QSIs; small molecules) and quorum-quenching (QQ) enzymes can both be used to interfere with QS. QSIs generally act to inactivate autoinducer synthases or receptors through competitive binding, whereas QQ enzymes switch off signal transmission through degradation of the signaling molecules. It has been demonstrated th...