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BACKGROUND The recent identification of a novel coronavirus, also known as SARS-CoV-2, has caused a global outbreak of respiratory illnesses. The rapidly developing pandemic has posed great challenges to diagnosis of this novel infection. However, little is known about the metatranscriptomic characteristics of patients with Coronavirus Disease 2019 (COVID-19). METHODS We analyzed metatranscriptomics in 187 patients (62 cases with COVID-19 and 125 with non-COVID-19 pneumonia). Transcriptional aspects of three core elements – pathogens, the microbiome, and host responses – were interrogated. Based on the host transcriptional signature, we built a host gene classifier and examined its potential for diagnosing COVID-19 and indicating disease severity. RESULTS The airway microbiome in COVID-19 patients had reduced alpha diversity, with 18 taxa of differential abundance. Potentially pathogenic microbes were also detected in 47% of the COVID-19 cases, 58% of which were respiratory viruses. Host gene analysis revealed a transcriptional signature of 36 differentially expressed genes significantly associated with immune pathways such as cytokine signaling. The host gene classifier built on such a signature exhibited potential for diagnosing COVID-19 (AUC of 0.75-0.89) and indicating disease severity. CONCLUSIONS Compared to those with non-COVID-19 pneumonias, COVID-19 patients appeared to have a more disrupted airway microbiome with frequent potential concurrent infections, and a special trigger host immune response in certain pathways such as interferon gamma signaling. The immune-associated host transcriptional signatures of COVID-19 hold promise as a tool for improving COVID-19 diagnosis and indicating disease severity.

Virus-like particles encapsulating HBV-RNA represent a serum biomarker for assessing viral replication activity in clinical practice. However, baseline levels of serum HBV-RNA and their associations with viral replicative intermediates and liver disease in phases of chronic hepatitis B remain unknown. In this cross-sectional study, 102 patients were categorized into immune-tolerant (IT), HBeAg-positive immune active (HBeAg+IA), inactive carrier (IC) and HBeAg-negative immune active (HBeAg-IA) phases. HBV-RNA in serum samples and in 66 paired liver biopsies were quantified and correlated with serum ALT levels, histopathological scores and the levels of other viral replicative intermediates. Mean levels of serum HBV-RNA differed among phases, with the highest levels among IT (6.78 ± 0.83 log copies mL ) patients, followed by HBeAg+IA (5.73 ± 1.16 log copies mL ), HBeAg-IA (4.52 ± 1.25 log copies mL ) and IC (2.96 ± 0.40 log copies mL ) patients. Serum HBV-RNA levels correlated with HBV DNA in all phases, although correlations with other viral replicative intermediates weakened or disappeared when cases were stratified into phases. Distinct compositions of viral products were found among phases: the ratio of HBsAg to serum HBV-RNA was highest in IC patients, while the ratio of serum HBV-RNA to intrahepatic HBV-RNA and the ratio of intrahepatic HBV-DNA to intrahepatic HBV-RNA were significantly higher in IT patients. In conclusion, baseline levels of HBV-RNA and the composition of viral replicative intermediates differ significantly across the natural course of chronic HBV infection. These findings shed light on the nature of viral replication and pathogenesis of disease among different phases of chronic HBV infection.

COVID-19 caused by a novel coronavirus SARS-CoV-2 emerged in Wuhan, Hubei province since December 2019, and caused a rapid outbreak throughout China and globally. Cities outside Hubei are also facing great challenge and require implementing of effective and feasible strategy in precision diagnosing novel coronavirus pneumonia (NCP).We described a multicenter prospective study on diagnostic strategy of suspected NCP patients from January 22 nd to February 9 th , 2020 in Eastern China cities. Nasopharyngeal swabs were collected from the patients. The epidemiological characteristics, clinical symptoms, laboratory assessments, and computed tomographic (CT) scans were obtained. Pathogen screen were performed including RT-PCR, multiplex PCR, rapid flu antigen tests and mNGS.We enrolled 53 suspected NCP patients, among whom 20 were laboratory-confirmed. Fourteen (70%) and 3 (15%) patients were positive for the first and second SARS-CoV-2 RT-PCR test, respectively. All NCP patients were positive for mNGS. Chest CT images and the symptoms of early stage NCP patients were similar to other viral pneumonia patients. We identified 11 of 20 co-infections in NCP cases, including regular respiratory virus, fungi and bacteria synchronously. Genomic analysis showed that 8 of 10 cases had no mutation in virus genome, while 2 cases had only one single mutation in N gene.Our study discovered that a combination of chest CT, SARS-CoV-2 RT-PCR and multi-plex PCR is recommended in regions outside Hubei province. Co-infection of other pathogens with SARS-CoV-2 exists and should be acknowledged. Repeated sampling, change of specimen type or metagenomics sequencing could further facilitate during critical clinical cases.

e Nucleos(t)ide analogues rarely result in a durable off-treatment response in chronic hepatitis B infection, whereas pegylated interferon (Peg-IFN) induces a long-lasting response only in a subset of patients. We assessed the effect of sequential combination therapy with Peg-IFN-␣2a and entecavir in hepatitis B e antigen (HBeAg)-positive patients with prior long-term entecavir therapy and investigated the predictors of response to treatment. HBeAg-positive individuals who did not achieve HBeAg seroconversion during previous long-term entecavir therapy, receiving Peg-IFN-␣2a added to ongoing entecavir therapy (sequential combination [S-C] therapy; n ‫؍‬ 81) for 48 weeks or remaining on entecavir monotherapy (n ‫؍‬ 116), were retrospectively included. A matched pair was created at a 1:1 ratio from each treatment group. The primary endpoint was HBeAg seroconversion at week 48. Subgroup analysis of response prediction was conducted for 81 patients with S-C therapy. More patients in the S-C therapy group achieved HBeAg seroconversion than those in the entecavir group (44% versus 6%; P < 0.0001). An HBeAg level of <200 signal-to-cutoff ratio (S/CO) at baseline was a strong predictor for higher HBeAg seroconversion than that achieved when HBeAg was >200 S/CO (64.2% versus 17.9%; P < 0.0001). Hepatitis B surface antigen (HBsAg) levels at baseline and the decrease in HBsAg levels predicted HBsAg loss in the S-C therapy group. The combination of baseline HBeAg of <200 S/CO and HBsAg of <1,000 IU/ml and an HBsAg decline at week 12 of >0.5 log 10 IU/ml provided the highest rate of HBeAg seroconversion (92.31%) and HBsAg loss (83.3%) at week 48. Patients receiving sequential combination therapy have a higher rate of HBeAg seroconversion and are more likely to experience HBsAg clearance than do those continuing entecavir monotherapy. Sequential combination therapy can be guided by baseline HBsAg/HBeAg levels and on-treatment HBsAg dynamics. Hepatitis B virus (HBV) infection is endemic in Asia, the Pacific islands, Africa, Southern Europe, and Latin America, and chronic hepatitis B (CHB) is a global health threat. There are approximately 350 million chronic HBV surface antigen (HBsAg) carriers worldwide (1). Patients with CHB have an increased risk of developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), which results in about 1 million deaths per year (2). Antiviral treatment is effective in halting progression of CHB in many patients. Two classes of antiviral agents are available: nucleos(t)ide analogues (NUCs), such as entecavir (ETV), which inhibit the viral polymerase and interfere with viral replication, and interferon alpha (IFN-␣), including conventional and pegylated forms, which has antiviral and immunomodulatory effects (3). NUCs are effective in most patients but must be continued indefinitely in the patients that do not achieve hepatitis B e antigen (HBeAg) seroconversion. In contrast, a finite course of pegylated IFN-␣ (Peg-IFN-␣) can induce a long-lasting therapeutic response, but on...

This study demonstrated a significant increase in TB risk in patients with RA treated with TNF-α antagonists; among them, ETN is least likely to cause active TB. The study also proposes the necessity of LTBI prophylaxis in patients with RA.

The aims of this paper are to report hepatitis B virus reactivation in 12 patients with rheumatic disease undergoing immunosuppressive therapy and to evaluate whether pre-emptive antiviral therapy is necessary in patients receiving disease-modifying anti-rheumatic drugs. From January 2008 to March 2012, a total of 12 HBV-infected patients with rheumatic diseases were consecutively enrolled in the long-term follow-up. Liver function, HBV DNA, and serum aminotransferase level were tested during the follow-up. We also reviewed the published reports and summarized the clinical characteristics of HBV reactivation during immunosuppressive therapy in patients with rheumatic diseases. The medium duration of follow-up was 41 months (range 16–48). Patients were treated with prednisone, disease-modifying anti-rheumatic drugs (DMARDs) or tumor necrosis factor-alpha-blocking agents (TNFBA). HBV reactivation was only documented in two patients treated with prednisone without pre-emptive antiviral therapy. One hundred patients from literature review were identified as having HBV reactivation; 20.8 % of the patients receiving prednisone experienced HBV reactivation compared to only 4.46 and 9.52 % of patients treated with DMARDs or TNFBA, respectively. This long-term follow-up of serial cases suggests that pre-emptive antiviral therapy should be administered in patients receiving prednisone therapy for rheumatic disease. In contrast, DMARDs and TNFBA are relatively safe to HBV-infected patients with rheumatic diseases. Close monitoring of HBV DNA and ALT levels is necessary in the management of HBV reactivation.

Critically ill patients with coronavirus diseases 2019 (COVID-19) are of grave concern. Those patients usually underwent a stage of excessive inflammation before developing acute respiratory distress syndrome. In this study, we test the hypothesis that short-term, low-to-moderate-dose corticosteroids would benefit patients when used in the early phase of excessive inflammation, namely, the therapeutic window. Among a Shanghai cohort and a validation cohort, we enrolled COVID-19 patients showing marked radiographic progression. Short-term, low-to-moderate-dose corticosteroids were considered for them. After identifying the possible markers for the therapeutic window, we then divided the patients, based on whether they were treated with corticosteroids within the therapeutic window, into the early-start group and control group. We identified that the therapeutic window for corticosteroids was characterized by a marked radiographic progression and lactase dehydrogenase (LDH) less than two times the upper limit of normal (ULN). The Shanghai cohort comprised of 68 patients, including 47 in the early-start group and 21 in the control group. The proportion of patients requiring invasive mechanical ventilation was significantly lower in the early-start group than in the control group (10.6% vs. 33.3%, difference, 22.7%, 95% confidence interval 2.6-44.8%). Among the validation cohort of 51 patients, similar difference of the primary outcome was observed (45.0% vs. 74.2%, P = 0.035). Among COVID-19 patients with marked radiologic progression, short-term, low-to-moderate-dose corticosteroids benefits patients with LDH levels of less than two times the ULN, who may be in the early phase of excessive inflammation.