Accumulating evidence shows that microbial co-infection increases the risk of disease severity in humans. There have been few studies about SARS-CoV-2 co-infection with other pathogens. In this retrospective study, 257 laboratory-confirmed COVID-19 patients in Jiangsu Province were enrolled from January 22 to February 2, 2020. They were reconfirmed by real-time RT-PCR and tested for 39 respiratory pathogens. In total, 24 respiratory pathogens were found among the patients, and 242 (94.2 %) patients were co-infected with one or more pathogens. Bacterial co-infections were dominant in all COVID-19 patients, Streptococcus pneumoniae was the most common, followed by Klebsiella pneumoniae and Haemophilus influenzae. The highest and lowest rates of co-infections were found in patients aged 15-44 and below 15, respectively. Most co-infections occurred within 1-4 days of onset of COVID-19 disease. In addition, the proportion of viral co-infections, fungal co-infections and bacterial-fungal co-infections were the highest severe COVID-19 cases. These results will provide a helpful reference for diagnosis and clinical treatment of COVID-19 patients.

BackgroundMounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) remains unknown. Therefore, we examined the presence of P. gingivalis in esophageal mucosa, and the relationship between P. gingivalis infection and the diagnosis and prognosis of ESCC.MethodsThe presence of P. gingivalis in the esophageal tissues from ESCC patients and normal controls was examined by immunohistochemistry using antibodies targeting whole bacteria and its unique secreted protease, the gingipain Kgp. qRT-PCR was used as a confirmatory approach to detect P. gingivalis 16S rDNA. Clinicopathologic characteristics were collected to analyze the relationship between P. gingivalis infection and development of ESCC.ResultsP. gingivalis was detected immunohistochemically in 61 % of cancerous tissues, 12 % of adjacent tissues and was undetected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis 16S rDNA was also observed. Moreover, statistic correlations showed P. gingivalis infection was positively associated with multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate.ConclusionThese findings demonstrate for the first time that P. gingivalis infects the epithelium of the esophagus of ESCC patients, establish an association between infection with P. gingivalis and the progression of ESCC, and suggest P. gingivalis infection could be a biomarker for this disease. More importantly, these data, if confirmed, indicate that eradication of a common oral pathogen could potentially contribute to a reduction in the overall ESCC burden.Electronic supplementary materialThe online version of this article (doi:10.1186/s13027-016-0049-x) contains supplementary material, which is available to authorized users.

macromolecular complex which allows transcription factors to interact with the class II MHC promoter in a spatially and helically constrained fashion.The major histocompatibility complex (MHC) class II proteins play a central role in the immune response. Extensive analysis has underscored that much of the fluctuation in class II MHC antigen expression can be attributed to changes at the transcriptional level (46,47). In addition to the class II MHC molecules themselves, associative accessory molecules that are necessary for class II antigen MHC function appear to be controlled in a similar fashion. These associative molecules include the MHC class II-associated invariant chain (Ii) and the more recently described DM heterodimer. All class II MHC, Ii, and DM promoters share the unique presence of three DNA elements, called W, X, and Y, which are highly conserved and critical for promoter function (2, 15). The W-X-Y elements are not only important for constitutive gene expression in B cells but also critical for inducible gene expression. In addition to the conservation in sequence, the spacing between the X and Y elements is highly conserved at approximately two helical turns. Increasing the number of helical turns between these two elements preserves function, while disrupting this orientation destroys promoter activation. Our group previously hypothesized that this restrictive spacing may be required to align the X and Y elements on the same side of the DNA helix, thus allowing transcription factors which can bind these elements to directly interact or to participate in the assembly of a larger promoter complex (48,49).The Y box is a CCAAT motif, and it interacts with NF-Y/ CBF (also known as YEBP/CP-1). NF-Y/CBF is composed of A, B, and C subunits (26,27,57), with the conserved core sequences of NF-YC (CBF-C) and NF-YB (CBF-A) forming a histone fold motif similar to the nucleosome subunits H2A and H2B (1). NF-Y/CBF plays a critical role in opening chromatin because mutation of the NF-Y/CBF-binding sites in both the DRA and Ii promoters results in the loss of protein binding across these promoters in intact cells (24,54). NF-Y/CBF can preset chromatin for other transcriptional coactivators, such as the histone acetylase GCN5, p300, and pCAF (10,19,23). The X box is a bipartite sequence. X1 is bound by the trimeric transcription factor, RFX, formed by RFX5, RFXAP, and RFXANK/RFXB (12,28,45). The lack of RFX results in several subclasses of bare lymphocyte syndrome (BLS), a severe immunodeficiency attributed to the lack of class II MHC expression. RFX is required for both the constitutive and gamma interferon (IFN-␥) induction of class II MHC expression (5). The X2 element binds a protein complex, X2BP, which has been recently identified as the CREB protein (29).Despite the extensive demonstration that X and Y boxbinding proteins are important for class II MHC regulation, these proteins are constitutively expressed and cannot explain the cell-, tissue-, developmentally, and cytokine-inducible expression of class ...

Mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene have been recently linked to three chronic autoinflammatory disorders. These observations point to an important role for CIAS1 in regulating inflammatory processes. We report that TNF-α and ligands recognized by multiple Toll-like receptors rapidly induce CIAS1 gene expression in primary human monocytes. Transfection of full-length CIAS1 or either of two shorter, naturally occurring isoforms dramatically inhibited TNF-α-induced activation of NF-κB reporter activity. Furthermore, CIAS1 suppressed TNF-α-induced nuclear translocation of endogenous p65. Transcriptional activity of exogenous NF-κB p65 was also blocked by CIAS1. The nucleotide-binding and leucine-rich repeat regions, but not the pyrin domain of CIAS1, are responsible for this inhibition. These data suggest CIAS1/cryopyrin may act as a key regulator of inflammation, induced to dampen NF-κB-dependent proinflammatory signals.

Dectin-1 signalling in dendritic cells (DCs) has an important role in triggering protective antifungal Th17 responses. However, whether dectin-1 directs DCs to prime antitumour Th9 cells remains unclear. Here, we show that DCs activated by dectin-1 agonists potently promote naive CD4+ T cells to differentiate into Th9 cells. Abrogation of dectin-1 in DCs completely abolishes their Th9-polarizing capability in response to dectin-1 agonist curdlan. Notably, dectin-1 stimulation of DCs upregulates TNFSF15 and OX40L, which are essential for dectin-1-activated DC-induced Th9 cell priming. Mechanistically, dectin-1 activates Syk, Raf1 and NF-κB signalling pathways, resulting in increased p50 and RelB nuclear translocation and TNFSF15 and OX40L expression. Furthermore, immunization of tumour-bearing mice with dectin-1-activated DCs induces potent antitumour response that depends on Th9 cells and IL-9 induced by dectin-1-activated DCs in vivo. Our results identify dectin-1-activated DCs as a powerful inducer of Th9 cells and antitumour immunity and may have important clinical implications.

The class II transactivator (CIITA) is induced by gamma interferon (IFN-␥The class II transactivator (CIITA) is a master regulator of major histocompatibility complex class II (MHC-II), Ii, and DM genes (8,9,10,55,56). CIITA was initially identified by complementation of an HLA-DR Ϫ mutant B-cell line, RJ2.2.5 (55), which was created by mutagenesis followed by negative immunoselection for MHC-II-defective cells (1). CIITA is important for the constitutive expression of MHC-II in B cells and dendritic cells and the cytokine induction of these genes in a variety of other cell types. Gamma interferon (IFN-␥) is a prime example of a cytokine which induces CIITA and subsequently MHC-II expression.

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Since SARS-CoV-2 spreads rapidly around the world, data have been needed on the natural fluctuation of viral load and clinical indicators associated with it. We measured and compared viral loads of SARS-CoV-2 from pharyngeal swab, IgM anti-SARS-CoV-2, CRP and SAA from serum of 114 COVID-19 patients on admission. Positive rates of IgM anti-SARS-CoV-2, CRP and SAA were 80.7%, 36% and 75.4% respectively. Among IgMpositive patients, viral loads showed different trends among cases with different severity, While viral loads of IgM-negative patients tended to increase along with the time after onset. As the worsening of severity, the positive rates of CRP and SAA also showed trends of increase. Different CRP/SAA type showed associations with viral loads in patients in different severity and different time after onset. Combination of the IgM and CRP/SAA with time after onset and severity may give suggestions on the viral load and condition judgment of COVID-19 patients. Dear Editor I'm sending a original article entitled "Association of Viral Load With Serum Biomakers Among COVID-19 Cases", which we would like to submit for publication in VIROLOGY. No part of this article has been published or submitted elsewhere, and no conflict of interest exists in the submission of this manuscript. In this article, we investigated the natural fluctuation of viral load among COVID-19 cases before antiviral therapy and the serum biomarkers associated with it. We found the viral loads had different trends and peaked at different time among COVID-19 patients. Combining the detection of IgM anti-SARS-CoV-2, C-reactive protein and Serum amyloid A may give suggestions on the viral load and condition judgment of COVID-19 patients at different stages of illness. The changes of viral load among patients of different clinical severity and different time after onset also can be tracked and used to inform public health policies to prevent the spread of SARS-CoV-2. The findings may facilitate the prevention and control of COVID-19.