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1.
Cell Rep ; 36(7): 109530, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1330686

ABSTRACT

A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2 and do not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolve 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV)-positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions by ONT sequencing. That we find no evidence of SARS-CoV-2 integration suggests that such events are, at most, extremely rare in vivo and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus.


Subject(s)
COVID-19/virology , DNA, Viral/genetics , Genome, Human , SARS-CoV-2/genetics , Sequence Analysis, DNA , Virus Integration , Aged , Animals , COVID-19/diagnosis , Carcinoma, Hepatocellular/virology , Chlorocebus aethiops , HEK293 Cells , Hepatitis B virus/genetics , Host-Pathogen Interactions , Humans , Liver Neoplasms/virology , Long Interspersed Nucleotide Elements , Male , Nanopore Sequencing , Vero Cells
2.
Viruses ; 13(7)2021 06 25.
Article in English | MEDLINE | ID: covidwho-1289021

ABSTRACT

The current COVID-19 pandemic has highlighted the urgent need to develop effective therapeutic strategies. We evaluated the in vitro antiviral effect against SARS-CoV-2 of a hepatitis B virus (HBV) hexamer peptide, Poly6, which is capable of eliciting an antiviral effect against human immunodeficiency virus -1 (HIV-1), as a novel HIV-1 integrase inhibitor, and a strong anticancer immune response in an IFN-I-dependent manner, as a novel potential adjuvant in anticancer immunotherapy. Here, we report that Poly6 exerts an anti-SARS-CoV-2 effect, with an estimated 50% inhibitory concentration of 2.617 µM, in the human bronchial epithelial cell line, Calu-3 but not in Vero-E6 cells, which are deficient in type 1 interferon (IFN-I) signaling. We proved via assays based on mRNA profiles, inhibitors, or blocking antibodies that Poly6 can exert an anti-SARS-CoV-2 effect in an IFN-I-dependent manner. We also found that Poly6 inhibits IL-6 production enhanced by SARS-CoV-2 in infected Calu-3 cells at both the transcription and the translation levels, mediated via IL-10 induction in an IFN-I-dependent manner. These results indicate the feasibility of Poly6 as an IFN-I-inducing COVID-19 drug with potent antiviral and anti-inflammatory activities.


Subject(s)
Antiviral Agents/pharmacology , Epithelial Cells/drug effects , Hepatitis B virus/chemistry , Interferon Type I/immunology , Peptides/pharmacology , SARS-CoV-2/drug effects , Virus Replication/drug effects , Animals , Bronchi/cytology , Bronchi/virology , Chlorocebus aethiops , Epithelial Cells/immunology , Epithelial Cells/virology , Hepatitis B virus/genetics , Humans , Lung/cytology , Lung/virology , Peptides/immunology , SARS-CoV-2/immunology , Vero Cells
3.
Hepatology ; 74(4): 1750-1765, 2021 10.
Article in English | MEDLINE | ID: covidwho-1274697

ABSTRACT

BACKGROUND AND AIMS: We compared risk of acute liver injury and mortality in patients with COVID-19 and current, past, and no HBV infection. APPROACH AND RESULTS: This was a territory-wide retrospective cohort study in Hong Kong. Patients with COVID-19 between January 23, 2020, and January 1, 2021, were identified. Patients with hepatitis C or no HBsAg results were excluded. The primary outcome was mortality. Acute liver injury was defined as alanine aminotransferase or aspartate aminotransferase ≥2 × upper limit of normal (ULN; i.e., 80 U/L), with total bilirubin ≥2 × ULN (i.e., 2.2 mg/dL) and/or international normalized ratio ≥1.7. Of 5,639 patients included, 353 (6.3%) and 359 (6.4%) had current and past HBV infection, respectively. Compared to patients without known HBV exposure, current HBV-infected patients were older and more likely to have cirrhosis. Past HBV-infected patients were the oldest, and more had diabetes and cardiovascular disease. At a median follow-up of 14 (9-20) days, 138 (2.4%) patients died; acute liver injury occurred in 58 (1.2%), 8 (2.3%), and 11 (3.1%) patients with no, current, and past HBV infection, respectively. Acute liver injury (adjusted HR [aHR], 2.45; 95% CI, 1.52-3.96; P < 0.001), but not current (aHR, 1.29; 95% CI, 0.61-2.70; P = 0.507) or past (aHR, 0.90; 95% CI, 0.56-1.46; P = 0.681) HBV infection, was associated with mortality. Use of corticosteroid, antifungal, ribavirin, or lopinavir-ritonavir (adjusted OR [aOR], 2.55-5.63), but not current (aOR, 1.93; 95% CI, 0.88-4.24; P = 0.102) or past (aOR, 1.25; 95% CI, 0.62-2.55; P = 0.533) HBV infection, was associated with acute liver injury. CONCLUSION: Current or past HBV infections were not associated with more liver injury and mortality in COVID-19.


Subject(s)
Acute Lung Injury/epidemiology , COVID-19/mortality , Hepatitis B, Chronic/epidemiology , Acute Lung Injury/blood , Acute Lung Injury/diagnosis , Acute Lung Injury/virology , Adult , Age Factors , Aged , Alanine Transaminase , Aspartate Aminotransferases , COVID-19/complications , COVID-19/diagnosis , COVID-19/virology , Female , Hepatitis B Surface Antigens/isolation & purification , Hepatitis B virus/immunology , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/virology , Hong Kong/epidemiology , Humans , Male , Medical History Taking/statistics & numerical data , Middle Aged , Retrospective Studies , Risk Assessment/statistics & numerical data , Risk Factors
4.
Int J Clin Pract ; 75(9): e14412, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1258935

ABSTRACT

OBJECTIVE: We aimed to determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/hepatitis B virus (HBV) coinfection affects liver function and the outcome of the disease. METHODS: One hundred fifty-six laboratories confirmed SARS-CoV-2 positive patients were followed up between 1 July and 31 December 2020 and analysed retrospectively. Continuous variables were compared with the independent samples t-test. Categorical variables were compared using the Pearson's chi-square or Fisher's exact test. A P value of less than .05 was considered statistically significant. RESULTS: The age range of the cohort was from 40 to 78 and 73 (46.8%) of 156 patients were male. There was no significant difference in age and gender distribution between 20 patients (12.8%) with SARS-CoV-2/HBV coinfection and 136 patients without HBV infection (87.2%) (P > .05). Liver function tests were higher in the SARS-CoV-2/HBV coinfected patient group but were not statistically significant. The levels of creatine kinase (CK) were significantly higher in coronavirus disease 2019 (COVID-19) patients without HBV infection compared with the SARS-CoV-2/HBV coinfected patient group (P = .0047). Severe/critical illness was less common in the SARS-CoV-2/HBV coinfected patient group, and no deaths were observed. CONCLUSIONS: SARS-CoV-2/HBV coinfection did not change the severity and outcome of COVID-19. However, the patients with SARS-CoV-2/HBV coinfection should be closely monitored for liver complications.


Subject(s)
COVID-19 , Coinfection , Coinfection/epidemiology , Hepatitis B virus , Humans , Male , Retrospective Studies , SARS-CoV-2
5.
J Hepatol ; 75(4): 848-855, 2021 10.
Article in English | MEDLINE | ID: covidwho-1228070

ABSTRACT

BACKGROUND & AIMS: The impact of chronic liver disease on outcomes in patients with COVID-19 is uncertain. Hence, we aimed to explore this association. METHODS: We explored the outcomes of all adult inpatients with COVID-19 in France, in 2020. We computed adjusted odds ratios to measure the associations between chronic liver disease, alcohol use disorders, mechanical ventilation and day-30 in-hospital mortality. RESULTS: The sample comprised 259,110 patients (median [IQR] age 70 (54-83) years; 52% men), including 15,476 (6.0%) and 10,006 (3.9%) patients with chronic liver disease and alcohol use disorders, respectively. Death occurred in 38,203 (15%) patients, including 7,475 (28%) after mechanical ventilation, and 2,941 (19%) with chronic liver disease. The adjusted odds ratios for mechanical ventilation and day-30 mortality were 1.54 (95% CI 1.44-1.64, p <0.001) and 1.79 (1.71-1.87, p <0.001) for chronic liver disease; 0.55 (0.47-0.64, p <0.001) and 0.54 (0.48-0.61, p <0.001) for mild liver disease; 0.64 (0.53-0.76; p <0.001) and 0.71 (0.63-0.80, p <0.001) for compensated cirrhosis; 0.65 (0.52-0.81, p <0.001) and 2.21 (1.94-2.51, p <0.001) for decompensated cirrhosis; 0.34 (0.24-0.50; p <0.001) and 1.38 (1.17-1.62, p <0.001) for primary liver cancer; and 0.82 (0.76-0.89; p <0.001) and 1.11 (1.05-1.17; p <0.001) for alcohol use disorders. Chronic viral hepatitis; non-viral, non-alcoholic chronic hepatitis; organ, including liver, transplantation, and acquired immunodeficiency syndrome were not associated with COVID-19-related death. CONCLUSION: Chronic liver disease increased the risk of COVID-19-related death in France in 2020. Therapeutic effort limitation may have contributed to COVID-19-related death in French residents with a liver-related complication or an alcohol use disorder. LAY SUMMARY: We studied the outcomes, including mechanical ventilation and day-30 mortality, of all adults with COVID-19 who were discharged from acute and post-acute care in France in 2020 (N = 259,110). Patients with mild liver disease; compensated cirrhosis; organ, including liver, transplantation; or acquired immunodepression syndrome were not at increased risk of COVID-19-related mortality. Patients with alcohol use disorders, decompensated cirrhosis, or primary liver cancer were at increased risk of COVID-19-related mortality but were less likely to receive mechanical ventilation. Our results suggest that therapeutic effort limitation may have contributed to the excess mortality in French residents with a liver-related complication or an alcohol use disorder.


Subject(s)
COVID-19/epidemiology , Hepacivirus , Hepatitis B virus , Hepatitis B, Chronic/epidemiology , Hepatitis C, Chronic/epidemiology , Liver Cirrhosis/epidemiology , Liver Diseases, Alcoholic/epidemiology , Liver Neoplasms/epidemiology , Liver Transplantation , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , Alcoholism/epidemiology , COVID-19/mortality , COVID-19/virology , Comorbidity , Disease Progression , Female , France/epidemiology , Hepatitis B, Chronic/virology , Hepatitis C, Chronic/virology , Hospital Mortality , Humans , Male , Middle Aged , Prognosis , Respiration, Artificial , Retrospective Studies , Risk Factors , Young Adult
6.
Clin Immunol ; 227: 108727, 2021 06.
Article in English | MEDLINE | ID: covidwho-1193258

ABSTRACT

With the global spread of coronavirus disease 2019 (COVID-19), the important role of natural killer (NK) cells in the control of various viral infections attracted more interest, via non-specific activation, such as antibody-dependent cell-mediated cytotoxicity (ADCC) and activating receptors, as well as specific activation, such as memory-like NK generation. In response to different viral infections, NK cells fight viruses in different ways, and different NK subsets proliferate. For instance, cytomegalovirus (CMV) induces NKG2C + CD57 + KIR+ NK cells to expand 3-6 months after hematopoietic stem cell transplantation (HSCT), but human immunodeficiency virus (HIV) induces KIR3DS1+/KIR3DL1 NK cells to expand in the acute phase of infection. However, the similarities and differences among these processes and their molecular mechanisms have not been fully discussed. In this article, we provide a summary and comparison of antiviral mechanisms, unique subset expansion and time periods in peripheral blood and tissues under different conditions of CMV, HIV, Epstein-Barr virus (EBV), COVID-19 and hepatitis B virus (HBV) infections. Accordingly, we also discuss current clinical NK-associated antiviral applications, including cell therapy and NK-related biological agents, and we state the progress and future prospects of NK cell antiviral treatment.


Subject(s)
COVID-19/immunology , COVID-19/virology , Host Microbial Interactions/immunology , Killer Cells, Natural/immunology , Antibody-Dependent Cell Cytotoxicity , COVID-19/blood , Cytomegalovirus/immunology , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Epstein-Barr Virus Infections/blood , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/virology , HIV/immunology , HIV Infections/blood , HIV Infections/immunology , HIV Infections/virology , Hepatitis B/blood , Hepatitis B/immunology , Hepatitis B/virology , Hepatitis B virus/immunology , Herpesvirus 4, Human/immunology , Humans , SARS-CoV-2/immunology , Toll-Like Receptors/metabolism
7.
Rheumatology (Oxford) ; 60(9): 4418-4427, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1193773

ABSTRACT

OBJECTIVES: The biomarkers of an immunological dysregulation due to a chronic HBV infection are indeed understudied. If untreated, this condition may evolve into liver impairment co-occurring with extrahepatic involvements. Here, we aim to identify a new panel of biomarkers [including immunoglobulin G (IgG) subclasses, RF, and Free Light Chains (FLCs)] that may be useful and reliable for clinical evaluation of HBV-related cryoglobulinemia. METHODS: We retrospectively analysed clinical data from 44 HBV-positive patients. The patients were stratified (according to the presence/absence of mixed cryoglobulinemia) into two groups: 22 with cryoglobulins (CGs) and 22 without CGs. Samples from 20 healthy blood donors (HDs) were used as negative controls. Serum samples were tested for IgG subclasses, RF (-IgM, -IgG, and -IgA type), and FLCs. RESULTS: We detected a strikingly different distribution of serum IgG subclasses between HDs and HBV-positive patients, together with different RF isotypes; in addition, FLCs were significantly increased in HBV-positive patients compared with HDs, while no significant difference was shown between HBV-positive patients with/without mixed cryoglobulinemia. CONCLUSION: The immune-inflammatory response triggered by HBV may be monitored by a peculiar profile of biomarkers. Our results open a new perspective in the precision medicine era; in these challenging times, they could also be employed to monitor the clinical course of those COVID-19 patients who are at high risk of HBV reactivation due to liver impairment and/or immunosuppressive therapies.


Subject(s)
Biomarkers/blood , COVID-19/immunology , Cryoglobulinemia/immunology , Cryoglobulinemia/virology , Hepatitis B virus/immunology , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2
8.
Molecules ; 26(5)2021 Mar 09.
Article in English | MEDLINE | ID: covidwho-1143539

ABSTRACT

A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(E)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound 15j, a hexadecyloxypropyl (HDP)/(isopropyloxycarbonyl-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 µM, without significant cytotoxicity (IC50 = 66.4 µM in HepG2 cells, IC50 = 43.1 µM in HepG2 cells) at 10 µM.


Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Azo Compounds/chemistry , Nucleosides/chemistry , Organophosphonates/chemistry , Prodrugs/chemical synthesis , Prodrugs/pharmacology , Alkenes/chemistry , Animals , Cell Line, Tumor , Chlorocebus aethiops , HIV-1/drug effects , Hepatitis B virus/drug effects , Humans , Magnetic Resonance Spectroscopy , Methylation , SARS-CoV-2/drug effects , Structure-Activity Relationship , Triazoles/chemistry , Vero Cells
9.
Immunol Rev ; 299(1): 108-117, 2021 01.
Article in English | MEDLINE | ID: covidwho-1072592

ABSTRACT

Humoral immunity is a critical component of the coordinated response required to resolve viral infections and mediate protection following pathogen clearance or vaccination. A better understanding of factors shaping the memory B cell response will allow tailored development of efficient preventative vaccines against emerging acute viral infections, therapeutic vaccines, and immunotherapies for chronic viral infections. Here, we use recent data obtained by profiling antigen-specific B cell responses in hepatitis B as a framework to explore lessons that can be learnt from different viral infections about the diverse influences on humoral immunity. Hepatitis B provides a paradigm where successful B cell responses in resolved or vaccinated individuals can be contrasted to the failed response in chronic infection, while also exemplifying the degree to which B cell responses within infected individuals can differ to two antigens from the same virus. Drawing on studies in other human and murine infections, including emerging data from COVID-19, we consider the influence of antigen quantity and structure on the quality of the B cell response, the role of differential CD4 help, the importance of germinal center vs extrafollicular responses and the emerging concept that responses residing in non-lymphoid organs can participate in B cell memory.


Subject(s)
Antibodies, Viral/metabolism , B-Lymphocytes/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Hepatitis B virus/physiology , Hepatitis B/immunology , SARS-CoV-2/physiology , T-Lymphocytes, Helper-Inducer/immunology , Antibody Formation , Antigens, Viral/immunology , Humans , Immunity, Humoral , Immunodominant Epitopes/immunology , Immunologic Memory
10.
Nature ; 591(7850): 482-487, 2021 03.
Article in English | MEDLINE | ID: covidwho-1049967

ABSTRACT

Naturally occurring protein switches have been repurposed for the development of biosensors and reporters for cellular and clinical applications1. However, the number of such switches is limited, and reengineering them is challenging. Here we show that a general class of protein-based biosensors can be created by inverting the flow of information through de novo designed protein switches in which the binding of a peptide key triggers biological outputs of interest2. The designed sensors are modular molecular devices with a closed dark state and an open luminescent state; analyte binding drives the switch from the closed to the open state. Because the sensor is based on the thermodynamic coupling of analyte binding to sensor activation, only one target binding domain is required, which simplifies sensor design and allows direct readout in solution. We create biosensors that can sensitively detect the anti-apoptosis protein BCL-2, the IgG1 Fc domain, the HER2 receptor, and Botulinum neurotoxin B, as well as biosensors for cardiac troponin I and an anti-hepatitis B virus antibody with the high sensitivity required to detect these molecules clinically. Given the need for diagnostic tools to track the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)3, we used the approach to design sensors for the SARS-CoV-2 spike protein and antibodies against the membrane and nucleocapsid proteins. The former, which incorporates a de novo designed spike receptor binding domain (RBD) binder4, has a limit of detection of 15 pM and a luminescence signal 50-fold higher than the background level. The modularity and sensitivity of the platform should enable the rapid construction of sensors for a wide range of analytes, and highlights the power of de novo protein design to create multi-state protein systems with new and useful functions.


Subject(s)
Antibodies, Viral/analysis , Biosensing Techniques/methods , Hepatitis B virus/immunology , SARS-CoV-2/chemistry , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/analysis , Troponin I/analysis , Antibodies, Viral/immunology , Biosensing Techniques/standards , Botulinum Toxins/analysis , Coronavirus Nucleocapsid Proteins/immunology , Immunoglobulin G/analysis , Immunoglobulin G/immunology , Limit of Detection , Luminescence , Phosphoproteins/immunology , Proto-Oncogene Proteins c-bcl-2/analysis , Receptor, ErbB-2/analysis , Sensitivity and Specificity , Viral Matrix Proteins/immunology
11.
AIDS Rev ; 22(4): 227-228, 2020 12 23.
Article in English | MEDLINE | ID: covidwho-1006729

ABSTRACT

The clinical spectrum of "Severe Acute Respiratory Syndrome Coronavirus type 2" (SARS-CoV-2) infection is wider than initially thought. The coronavirus does not establish a chronic cellular infection, in contrast with HIV or the hepatitis B virus, that keeps their genomes, respectively, as proviruses integrated within the chromosomes or as episomes (Soriano et al. J Antimicrob Chemother 2014).


Subject(s)
COVID-19/virology , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , HIV-1/genetics , HIV-1/pathogenicity , Hepatitis B virus/genetics , Hepatitis B virus/pathogenicity , Humans
12.
Dig Dis Sci ; 66(11): 4026-4034, 2021 11.
Article in English | MEDLINE | ID: covidwho-1002116

ABSTRACT

BACKGROUND AND AIM: To investigate the risk of hepatitis B virus reactivation in patients undergoing long-term tocilizumab therapy for rheumatoid arthritis. METHOD: From January 2011 through August 2019, a total of 97 patients were enrolled in this retrospective study. Clinical data, comedications, and the occurrence of HBV reactivation were recorded. RESULTS: Seven patients were HBsAg+ (7.2%), 64 were HBsAg-/HBcAb+ (65.9%), and 26 were HBsAg-/HBcAb- (26.8%). The median disease follow-up time was 9 years. TCZ was administered for a median of 29 months. Four patients (4.1%) experienced HBV reactivation after tocilizumab therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients did not receive antiviral prophylaxis, and all 3 (100%) experienced HBV reactivation and hepatitis flare-up. Hyperbilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg-/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 107 IU/mL) after 18 months of tocilizumab treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare-up. CONCLUSIONS: Tocilizumab is widely used in treating rheumatoid arthritis and has the potential to reduce the mortality rate among severe COVID-19 patients. However, HBV reactivation needs to be considered. HBsAg+ patients have a high risk of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg-/HBcAb+ patients, strict monitoring is necessary.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Hepatitis B, Chronic/drug therapy , Virus Activation/drug effects , Antibodies, Monoclonal, Humanized/adverse effects , Antirheumatic Agents/adverse effects , Antiviral Agents/therapeutic use , Guanine/analogs & derivatives , Guanine/therapeutic use , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/blood , Hepatitis B virus/physiology , Humans , Retrospective Studies , Risk Factors , Virus Latency/drug effects
13.
J Viral Hepat ; 28(1): 80-88, 2021 01.
Article in English | MEDLINE | ID: covidwho-979832

ABSTRACT

The interaction between existing chronic liver diseases caused by hepatitis B virus (HBV) infection and COVID-19 has not been studied. We analysed 70 COVID-19 cases combined with HBV infection (CHI) to determine the epidemiological, clinical characteristics, treatment and outcome. We investigated clinical presentation, imaging and laboratory parameters of COVID-19 patients of seven hospitals from Jan 20 to March 20, 2020. Multivariate analysis was used to analyse risk factors for progression of patients with COVID-19 combined with HBV infection. Compared with COVID-19 without HBV infection (WHI) group, patients with dual infection had a higher proportion of severe/critically ill disease (32.86% vs. 15.27%, P = .000), higher levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and activated partial thromboplastin (APTT) [50(28-69)vs 21(14-30), P = .000; 40(25-54) vs 23(18-30), P = .000; 34.0(27.2-38.7) vs 37.2(31.1-41.4), P = .031]. The utilization rates of Arbidol and immunoglobulin were significantly higher than those in the co-infected group [48.57% vs. 35.64%, P < .05; 21.43% vs. 8.18%, P < .001], while the utilization rate of chloroquine phosphate was lower (1.43% vs 14.00%, P < .05) in the co-infected patients group. Age and c-reactive protein (CRP) level were independent risk factors for recovery of patients with COVID-19 combined with HBV infection. The original characteristics of COVID-19 cases combined with HBV infection were higher rate of liver injury, coagulation disorders, severe/critical tendency and increased susceptibility. The elderly and patients with higher level of CRP were more likely to experience a severe outcome of COVID-19.


Subject(s)
COVID-19/epidemiology , COVID-19/pathology , Hepatitis B/epidemiology , Hepatitis B/pathology , Adult , COVID-19/complications , COVID-19/therapy , China/epidemiology , Coinfection/complications , Coinfection/epidemiology , Coinfection/pathology , Coinfection/therapy , Female , Hepatitis B/complications , Hepatitis B/therapy , Hepatitis B virus , Humans , Liver/injuries , Liver/pathology , Liver/physiopathology , Male , Middle Aged , Risk Factors , SARS-CoV-2 , Treatment Outcome
14.
Am J Gastroenterol ; 116(6): 1357-1358, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-892538
15.
Am J Case Rep ; 21: e925932, 2020 Oct 13.
Article in English | MEDLINE | ID: covidwho-854650

ABSTRACT

BACKGROUND Coronavirus disease 2019 (COVID-19) is a newly emerging disease that is still not fully characterized. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that can be transmitted easily from human to human mainly by the respiratory route. Currently, there is no specific treatment for COVID-19 or a vaccine for prevention. The disease has various degrees of severity. It often presents with nonspecific symptoms such as fever, headache, and fatigue, accompanied by respiratory symptoms (e.g., cough and dyspnea) and other systemic involvement. Severe disease is associated with hemophagocytic syndrome and cytokine storm due to altered immune response. Patients with severe disease are more likely to have increased liver enzymes. The disease can affect the liver through various mechanisms. CASE REPORT We report an unusual case of SARS-CoV-2 infection in a 24-year-old man with no previous medical illness, who presented with mild respiratory involvement. He had no serious lung injury during the disease course. However, he experienced acute fulminant hepatitis B infection and cytokine release syndrome that led to multiorgan failure and death. CONCLUSIONS It is uncommon for SARS-CoV-2 infection with mild respiratory symptoms to result in severe systemic disease and organ failure. We report an unusual case of acute hepatitis B infection with concomitant SARS-CoV-2 leading to fulminant hepatitis, multiorgan failure, and death.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Hepatitis B virus , Hepatitis B/epidemiology , Liver Failure, Acute/etiology , Pneumonia, Viral/epidemiology , COVID-19 , Comorbidity , Humans , Liver Failure, Acute/diagnosis , Male , Pandemics , SARS-CoV-2 , Young Adult
16.
Vaccine ; 38(33): 5212-5218, 2020 07 14.
Article in English | MEDLINE | ID: covidwho-828034

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) has had a negative economic impact on the global swine industry for decades since its first emergence in the 1970s in Europe. In 2013, PEDV emerged for the first time in the United States, causing immense economic losses to the swine industry. Efforts to protect U.S. swine herds from PEDV infection and limit PEDV transmission through vaccination had only limited success so far. Following the previous success in our virus-like particle (VLP) based vaccine in mouse model, in this study we determined the immunogenicity and protective efficacy of a VLP-based vaccine containing B-cell epitope 748YSNIGVCK755 from the spike protein of PEDV incorporated into the hepatitis B virus core capsid (HBcAg), in a comprehensive pregnant gilt vaccination and piglet challenge model. The results showed that the vaccine was able to induce significantly higher virus neutralization response in gilt milk, and provide alleviation of clinical signs for piglets experimentally infected with PEDV. Piglets from pregnant gilt that was vaccinated with the VLP vaccine had faster recovery from the clinical disease, less small intestinal lesions, and higher survival rate at 10 days post-challenge (DPC).


Subject(s)
Coronavirus Infections , Porcine epidemic diarrhea virus , Swine Diseases , Vaccines, Virus-Like Particle , Viral Vaccines , Animals , Antibodies, Viral , Capsid , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Epitopes, B-Lymphocyte , Europe , Female , Hepatitis B virus , Mice , Pregnancy , Swine , Swine Diseases/prevention & control , United States
17.
J Viral Hepat ; 28(1): 89-94, 2021 01.
Article in English | MEDLINE | ID: covidwho-793304

ABSTRACT

A significant proportion of patients infected with SARS-CoV-2 develop severe respiratory symptoms due to an excessive immune response. Treatment of this condition may include immunosuppressive therapies, such as IL-6 receptor antagonists and corticosteroids, which pose a risk for patients with active or past hepatitis B virus (HBV) infection. In this prospective cohort study, we analysed the risk of HBV reactivation in patients with severe COVID-19 and resolved HBV infection undergoing immunosuppressive therapy. From 15th March to 30th April 2020, 600 patients with severe COVID-19 were admitted to our hospital and treated with immune modulators. Data regarding HBV infection were available in 484, of whom 69 (14%) were HBsAg negative/anti-HBc positive. For these patients, HBV reactivation prophylaxis with entecavir was strongly recommended. Complete follow-up was available in 61 patients: 72% were male, median age was 67 years, and anti-HBs was >10 IU/mL in 72%. The immunosuppressive drug most used was tocilizumab (72%). Despite HBV prophylaxis recommendation, 38 (62%) patients received entecavir and 23 (38%) did not. Baseline features of both groups were similar. At follow-up, we found no cases of HBsAg seroreversion and only 2 (3%) patients (no prophylaxis group) had detectable serum HBV-DNA (<15 IU/mL). Both were anti-HBs negative and had normal aminotransferase levels. Our data show that the risk of HBV reactivation in patients with severe COVID-19 and resolved HBV infection undergoing immunosuppressive treatment is low. However, if a systematic follow-up after hospital discharge is unfeasible in patients without anti-HBs, a short course of antiviral prophylaxis may be a safe option.


Subject(s)
COVID-19/drug therapy , Hepatitis B/virology , Immunosuppressive Agents/therapeutic use , Virus Activation/drug effects , Aged , Antiviral Agents/therapeutic use , COVID-19/complications , DNA, Viral/blood , Female , Hepatitis B/complications , Hepatitis B/prevention & control , Hepatitis B Antibodies/blood , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/blood , Hepatitis B virus/immunology , Hepatitis B virus/physiology , Humans , Male , Middle Aged , Prospective Studies , Risk , SARS-CoV-2
19.
Curr Res Transl Med ; 68(3): 105-110, 2020 08.
Article in English | MEDLINE | ID: covidwho-631298

ABSTRACT

The relative ease of isolation of mesenchymal stem cells (MSCs) from different tissues coupled with their culture expansion in vitro and their differentiation capacity to mesodermal, endodermal and ectodermal lineages have made these cells attractive for a large number of therapeutic applications. In recent years, there has been remarkable progress in the utilization of MSCs in diverse clinical indications both in animal models and human clinical trials. However, the potential of MSCs to control or treat viral diseases is still in its infancy. In this study, we report quantitative data on the MSC-based clinical trials over the last ten years as they appear on the online database of clinical research studies from US National Institutes of Health. In particular, we provide comprehensive review of either completed or ongoing clinical trials using MSCs for virus-associated diseases focusing on HIV, hepatitis B virus and COVID-19 virus.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , Virus Diseases/therapy , Virus Physiological Phenomena , Animals , Betacoronavirus/physiology , COVID-19 , Cell Culture Techniques , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Coronavirus Infections/virology , HIV/physiology , Hepatitis B virus/physiology , Humans , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/trends , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , SARS-CoV-2 , Virus Diseases/epidemiology , Virus Diseases/immunology , Viruses/pathogenicity
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