2022年 · 第02卷第03期

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) currently has spread all over the world. However, the dynamic characteristics of SARS-CoV-2 infections have not previously been described in detail. Here, we report a cured patient in West China Hospital, and describe the dynamic detection of SARS-CoV-2-RNA in different specimens and viral specific IgM and IgG antibodies in blood. The findings suggest that the fecal SARS-CoV-2-RNA negativity may be considered as a new standard for de isolation. Serum IgM and IgG antibodies detection were helpful for early diagnosis of SARS-CoV-2 infection and judgment of patients in recovery stage, respectively.

Acquired immunodeficiency syndrome (AIDS) is an important public health problem in China. In 2005, the first edition of the guidelines for the diagnosis and treatment of AIDS was formulated by the AIDS Professional Group of Society of Infectious Diseases of Chinese Medical Association, which was updated in 2011, 2015, and 2018, respectively. The 2021 edition of the guidelines has been revised based on the fourth edition and updated according to the national clinical practice and the latest research findings on opportunistic infections, antiretroviral therapy, post-exposure prophylaxis, pre-exposure prophylaxis (PrEP), whole-course management of human immunodeficiency virus infections, and prevention of mother to child transmission. The 2021 edition also introduces in detail the indications, medication regimen, follow-up and monitoring, and precautions for PrEP. This guide will be updated regularly according to the latest clinical evidence.

End-stage liver disease (ESLD) is a life-threatening clinical syndrome that markedly increases mortality in patients with infections. In patients with ESLD, infections can induce or aggravate the occurrence of liver decompensation. Consequently, infections are among the most common complications of disease progression. There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus. This consensus assembled up-to-date knowledge and experience across Chinese colleagues, providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.

Around 450 cases of acute severe hepatitis of unknown origin in children have been reported in 21 countries and region globally since April 2022, which has exceeded the past annual incidences of related regions, and has aroused wide concern. Affected patients were predominantly children under 16 years of age, presented with symptoms of acute hepatitis with markedly elevated liver enzymes, and had been ruled out of common viral infections such as hepatitis A, B, C, D, and E. Similar cases have not been reported in China yet. However, considering that the severe acute hepatitis has involved worldwide areas, still with unknown origin, and incidences of severity is relatively high, we formulated this recommendation to standardize diagnosis and treatment of acute severe hepatitis of unknown origin in Peking Union Medical College Hospital, to get fully prepared to the possible public health events.

Background: During hepatitis B virus (HBV) infection, virus-infected hepatocytes directly cross-present viral antigens and regulate T cell response within the liver microenvironment. However, little is known regarding the regulatory pathways involved in viral antigen presentation in HBV-infected hepatocytes. This study investigated the underlying mechanism of antigen assembly and the HBV antigen-presenting function of major histocompatibility complex (MHC) class I molecules using heat shock protein gp96. Methods: First, western blotting, flow cytometry, co-immunoprecipitation, GST pull-down, and confocal microscopic assays were performed to determine whether endogenous gp96 affects MHC-I levels via an antigen presentation pathway. Second, the B3Z assay and an AAV/HBV-infected hepatocyte-specific gp96-deficient mouse model were used to determine whether gp96 knockout functionally impaired peptide cross-presentation and produced a weakened antiviral cytotoxic T cell (CTL) response both in vivo and in vitro. Finally, confocal microscopic analysis and the B3Z assay were employed to show that exogenous gp96-associated peptide was present in MHC-I molecules via the endoplasmic reticulum (ER)-Golgi secretory pathway. Results: Compared with the control, gp96 knockdown significantly reduced the cell surface levels of MHC-I by approximately 75% (P < 0.01). Endogenous gp96 interacts with MHC-I and is involved in antigen presentation. Moreover, a weakened antiviral CTL response (34% compared to control mice) has been observed in hepatocyte-specific gp96-deficient mice following HBV infection. gp96 directed exogenous antigen to the ER, and the exogenous gp96-chaperoned peptide was endosome- and proteasome-dependent but not transporter associated with antigen processing dependent. Conclusions: Cellular gp96 promotes the assembly and antigen presentation of MHC class I molecules. In addition, extracellular gp96 served as a natural adjuvant to induce a CTL response in a concerted and regulated manner within different cellular compartments. Our results elucidate the mechanism of assembly of MHC class I molecules by gp96, which may be beneficial for the design of immunotherapy and vaccines.

Background: Many issues, such as severity assessment and antibody responses, remain to be answered eagerly for evaluation and understanding of COVID-19. Immune lesion is one of key pathogenesis of the disease. It would be helpful to understand the disease if an investigation on antigenemia and association was conducted in the patients with SARS-CoV-2 infection. Methods: A total of 156 patients admitted to the First People’s Hospital of Hefei or Anhui Provincial Hospital on January to February 2020 were involved in this study. SARS-CoV-2 nucleocapsid (NP) antigen, specific IgM/IgG antibodies, and RNA were detected in sequential sera from three COVID-19 patients, and additional 153 COVID-19 patients by means of NP-antigen capture enzyme-linked immunosorbent assay, colloidal gold quick diagnosis, and real-time RT-PCR, respectively. The clinical types of COVID-19 patients were classified into asymptomatic, mild, moderate, severe, and critical, following on the Chinese guideline of COVID-19 diagnosis and treatment. The demographic and clinical data of patients were obtained for comparable analysis. Results: NP antigen was detected in 5 of 20 sequential sera collected from three COVID-19 patients with typically clinical symptoms, and 60.13% (92/153) expanded samples collected within 17 days after illness onset. No SARS-CoV-2 RNA segment was detected in these sera. The NP positive proportion reached a peak (84.85%, 28/33) on 6 to 8 days after illness onset. Both NP concentration and positive proportion were increased with the increase of clinical severity of COVID-19. Compared to NP negative patients, NP positive patients had older age [years, medians (interquartile ranges (IQR)), 49 (6) vs. 31 (11)], lower positive proportion of NP specific IgM [27.17% (25/92) vs. 59.02% (36/61)], and IgG [21.74% (20/92) vs. 59.02% (36/61)] antibodies, and longer duration [days, medians (IQR), 24 (10) vs. 21 (13)] from illness to recovery. Conclusions: SARS-CoV-2 NP antigenemia occurred in COVID-19, and presented highly prevalent at early stage of the disease. The antigenemia was related to clinical severity of the disease, and may be responsible for the delay of detectable SARS-Cov-2 IgM.

Recently, an outbreak of severe acute hepatitis of unknown etiology in children has been reported in more than 27 countries worldwide. However, information on its prevalence in different countries and regions is still lacking. The evidence is suggestive of a potential viral infection, but this has not been fully confirmed. Cases of this disease have been reported in children, mainly in those younger than 5 years old. The reason for the age range of the disease requires further investigation.

Hepatocellular carcinoma (HCC) is a highly aggressive cancer that ranks the second leading cause of cancer related death. Hepatitis B virus (HBV) infection is the most prevalent etiological factor, especially in eastern world. However, the underlying mechanism of HBV infection-initialed carcinogenic progression remains largely unknown, making it difficult to improve therapeutic strategies for HBV-associated HCC (HBV+ HCC). The virus drives multi-omics changes in human liver cells, leading to genomic instability, epigenomic modifications, and proteomic alterations. HBV infection also orchestrates the immunosuppressive microenvironment in HBV+ HCC. This review summarized recent research progress with the multimodal methods covering genome, transcriptome, epigenome, and proteome introduced in the mechanistic studies for HBV+ HCC.