Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients.

The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.

Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway.

BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines in TBEV-mediated neurological disease are poorly understood. METHODS: BALB/c mice were intracerebrally injected with TBEV, followed by evaluation of chemokine and cytokine profiles using protein array analysis. The virus-infected mice were treated with the CC chemokine antagonist Met-RANTES or anti-RANTES mAb to determine the role of RANTES in affecting TBEV-induced neurological disease. The underlying signaling mechanisms were delineated using RANTES promoter luciferase reporter assay, siRNA-mediated knockdown, and pharmacological inhibitors in human brain-derived cell culture models. RESULTS: In a mouse model, pathological features including marked inflammatory cell infiltrates were observed in brain sections, which correlated with a robust up-regulation of RANTES within the brain but not in peripheral tissues and sera. Antagonizing RANTES within CNS extended the survival of mice and reduced accumulation of infiltrating cells in the brain after TBEV infection. Through in vitro studies, we show that virus infection up-regulated RANTES production at both mRNA and protein levels in human brain-derived cell lines and primary progenitor-derived astrocytes. Furthermore, IRF-3 pathway appeared to be essential for TBEV-induced RANTES production. Site mutation of an IRF-3-binding motif abrogated the RANTES promoter activity in virus-infected brain cells. Moreover, IRF-3 was activated upon TBEV infection as evidenced by phosphorylation of TBK1 and IRF-3, while blockade of IRF-3 activation drastically reduced virus-induced RANTES expression. CONCLUSIONS: Our findings together provide insights into the molecular mechanism underlying RANTES production induced by TBEV, highlighting its potential importance in the process of neuroinflammatory responses to TBEV infection.

Serum lipid levels and suicidality: a meta-analysis of 65 epidemiological studies.

BACKGROUND: We conducted a systematic review and meta-analysis to determine the association between serum lipid levels and suicidality, as evidence from previous studies has been inconsistent. METHODS: We identified relevant studies by searching Medline, Web of Science, EMBASE, and the Cochrane Database of Systematic Reviews (1980 to Dec. 5, 2014). Studies assessing the association between serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) levels and suicidality were included. We used a random-effects model to take into account heterogeneity among studies. RESULTS: We included 65 studies with a total of 510 392 participants in our analysis. Compared with the nonsuicidal patients, suicidal patients had significantly lower serum TC (weighted mean difference [WMD] -22.35, 95% confidence interval [CI] -27.95 to -16.75), LDL-C (WMD -19.56, 95% CI -26.13 to -12.99) and TG (WMD -23.40, 95% CI -32.38 to -14.42) levels, while compared with the healthy controls, suicidal patients had significantly lower TC (WMD -24.75, 95% CI -27.71 to -21.78), HDL-C (WMD -1.75, 95% CI -3.01 to -0.48) and LDL-C (WMD -3.85, 95% CI -7.45 to -0.26) levels. Furthermore, compared with the highest serum TC level category, a lower serum TC level was associated with a 112% (95% CI 40%-220%) higher risk of suicidality, including a 123% (95% CI 24%-302%) higher risk of suicide attempt and an 85% (95 CI 7%-221%) higher risk of suicide completion. The cut-off values for low and high serum TC level were in compliance with the categories reported in the original studies. LIMITATIONS: A major limitation of our study is the potential heterogeneity in most of the analyses. In addition, the suicidal behaviour was examined using different scales or methods across studies, which may further explain heterogeneity among the studies. CONCLUSION: We identified an inverse association between serum lipid levels and suicidality. More mechanistic studies are needed to further explain this association.

Human bocavirus VP2 upregulates IFN-ß pathway by inhibiting ring finger protein 125-mediated ubiquitination of retinoic acid-inducible gene-I.

Precise regulation of innate immunity is crucial for maintaining optimal immune responses against infections. Whereas positive regulation of IFN signaling elicits rapid type I IFNs, negative regulation is equally important in preventing the production of superfluous IFNs that can be hazardous to the host. The positive regulators of IFN pathway are known to be the main targets of viruses to antagonize the innate immune system. Whether viruses target the negative regulators of IFN pathway remains to be fully investigated. In this study, we report that the structural protein VP2 of human Bocavirus modulates IFN pathway by targeting the ring finger protein 125 (RNF125), a negative regulator of type I IFN signaling, which conjugates Lys(48)-linked ubiquitination to retinoic acid-inducible gene-I (RIG-I) and subsequently leads to the proteasome-dependent degradation of RIG-I. VP2 not only upregulated Sendai virus (SeV)-induced IFNB promoter activity, but also enhanced SeV-induced IFN-ß production at both mRNA and protein levels. In agreement, the level of Ser(396)-phosphorylated IFN regulatory factor 3 stimulated by SeV was enhanced in the presence of VP2. Furthermore, VP2 was demonstrated to physically interact with RNF125, resulting in the reduction of RNF125-mediated ubiquitination and proteasome-dependent degradation of RIG-I. Additional study indicated that endogenous RIG-I degradation was decreased in VP2-expressing cells. Our study delineates a unique phenomenon for aberrant activation of IFN regulatory factor 3 pathway and may represent a new mechanism underlying viral manipulation of the host immune system.

Usefulness of serum thyroid-stimulation hormone (TSH) as a prognostic indicator for acute-on-chronic liver failure.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: To investigate thyroid function in patients with acute-on-chronic liver failure (ACLF) caused by hepatitis B virus infection and to determine whether thyroid hormone levels can be used as prognostic markers for assessing severity and prognosis of ACLF patients. We enrolled 75 patients with ACLF and70 patients with chronic hepatitis B (CHB). Continual serum samples were collected during hospitalization from the ACLF patients. The serum thyroid hormone levels (triiodothyronine [T3], thyroxine [T4], free (F)-T3, FT4, and thyroid stimulation hormone [TSH]) were measured by chemiluminescence. The Model for End-stage Liver Disease (MELD) score was used to assess severity. RESULTS: ACLF patients showed significantly (p < 0.001) lower values of serum T3, T4, FT3/FT4 and TSH than CHB patients. The T3, T4, and TSH levels in ACLF patients were negatively correlated with the MELD score (T3: r = -0.495, p < 0.001; T4: r = -0.281, p < 0.001; TSH: r = -0.498, p < 0.001), suggesting that serum thyroid hormone levels reflect disease severity. At 1 year, 31 patients died. The T3 (p = 0.016), T4 (p = 0.008), and TSH (p = 0.003) levels in non-survivors were significantly lower than in survivors. The serum TSH level was a significant factor for predicting mortality in ACLF patients (optimal cutoff value = 0.38 IU/mL). The cumulative survival rate was decreased significantly when the serum TSH level was < 0.38 IU/mL (39.2%, p < 0.001). CONCLUSION: Serum TSH level may be a useful indicator for assessing severity and prognosis in ACLF patients.

Human astrocytic cells support persistent coxsackievirus B3 infection.

Enteroviruses can frequently target the human central nervous system to induce a variety of neurological diseases. Although enteroviruses are highly cytolytic, emerging evidence has shown that these viruses can establish persistent infections both in vivo and in vitro. Here, we investigated the susceptibility of three human brain cell lines, CCF-STTG1, T98G, and SK-N-SH, to infection with three enterovirus serotypes: coxsackievirus B3 (CVB3), enterovirus 71, and coxsackievirus A9. Persistent infection was observed in CVB3-infected CCF-STTG1 cells, as evidenced by prolonged detection of infectious virions, viral RNA, and viral antigens. Of note, infected CCF-STTG1 cells expressed the nonfunctional canonical viral receptors coxsackievirus-adenovirus receptor and decay-accelerating factor, while removal of cell surface chondroitin sulfate from CCF-STTG1 cells inhibited the replication of CVB3, suggesting that receptor usage was one of the major limiting factors in CVB3 persistence. In addition, CVB3 curtailed the induction of beta interferon in infected CCF-STTG1 cells, which likely contributed to the initiation of persistence. Furthermore, proinflammatory chemokines and cytokines, such as vascular cell adhesion molecule 1, interleukin-8 (IL-8), and IL-6, were upregulated in CVB3-infected CCF-STTG1 cells and human progenitor-derived astrocytes. Our data together demonstrate the potential of CCF-STTG1 cells to be a novel cell model for studying CVB3-central nervous system interactions, providing the basis toward a better understanding of CVB3-induced chronic neuropathogenesis.

Human bocavirus NP1 inhibits IFN-ß production by blocking association of IFN regulatory factor 3 with IFNB promoter.

Human bocavirus (HBoV) mainly infects young children. Although many infected children suffer from respiratory or gastroenteric tract diseases, an association between HBoV and these diseases is not definite. Because modulation of type I IFN is crucial for viruses to establish efficient replication, in this study, we tested whether HBoV modulates type I IFN production. We observed that a nearly full-length HBoV clone significantly reduced both Sendai virus (SeV)- and poly(deoxyadenylic-thymidylic) acid-induced IFN-ß production. Further study showed that NP1 blocked IFN-ß activation in response to SeV, poly(deoxyadenylic-thymidylic) acid, and IFN-ß pathway inducers, including retinoic acid-inducible protein I, mitochondrial antiviral signaling protein, inhibitor of κB kinase ε, and TANK-binding kinase 1. In addition, NP1 interfered with IRF-3-responsive PRD(III-I) promoter activated by SeV and a constitutively active mutant of IRF-3 (IRF-3/5D). Although NP1 suppressed the IRF-3 pathway, it did not affect IRF-3 activation processes, including phosphorylation, dimerization, and nuclear translocation. Coimmunoprecipitation assays confirmed the interaction between NP1 and IRF-3. Additional deletion mutagenesis and coimmunoprecipitation assays revealed that NP1 bound to the DNA-binding domain of IRF-3, resulting in the interruption of an association between IRF-3 and IFNB promoter. Altogether, our results indicate that HBoV NP1 blocks IFN production through a unique mechanism. To our knowledge, this is the first study to investigate the modulation of innate immunity by HBoV. Our findings suggest a potential immune-evasion mechanism used by HBoV and provide a basis for better understanding HBoV pathogenesis.

A neonatal mouse model of coxsackievirus A16 for vaccine evaluation.

To evaluate vaccine efficacy in protecting against coxsackievirus A16 (CA16), which causes human hand, foot, and mouth disease (HFMD), we established the first neonatal mouse model. In this article, we report data concerning CA16-induced pathological changes, and we demonstrate that anti-CA16 antibody can protect mice against lethal challenge and that the neonatal mouse model could be used to evaluate vaccine efficacy. To establish a mouse model, a BJCA08/CA16 strain (at 260 50% lethal doses [LD(50)]) was isolated from a patient and used to intracerebrally (i.c.) inoculate neonatal mice. The infection resulted in wasting, hind-limb paralysis, and even death. Pathological examination and immunohistochemistry (IHC) staining indicated that BJCA08 had a strong tropism to muscle and caused severe necrosis in skeletal and cardiac muscles. We then found that BJCA08 pretreated with goat anti-G10/CA16 serum could significantly lose its lethal effect in neonatal mice. When the anti-G10 serum was intraperitoneally (i.p.) injected into the neonatal mice and, within 1 h, the same mice were intracerebrally inoculated with BJCA08, there was significant passive immunization protection. In a separate experiment, female mice were immunized with formaldehyde-inactivated G10/CA16 and BJCA08/CA16 and then allowed to mate 1 h after the first immunization. We found that there was significant protection against BJCA08 for neonatal mice born to the immunized dams. These data demonstrated that anti-CA16 antibody may block virus invasion and protect mice against lethal challenge, and that the neonatal mouse model was a viable tool for evaluating vaccine efficacy.

A complete genomic analysis of hepatitis B virus isolated from 516 Chinese patients with different clinical manifestations.

This study investigated features and clinical implications of HBV mutations in patients with different clinical manifestations. In total, 516 patients were enrolled in this study, including 131 patients with acute hepatitis B, 239 patients with chronic hepatitis B, and 146 patients with acute-on-chronic liver failure. HBV genotypes and mutations were analyzed by direct sequencing of complete viral genomes. Genotypes B2, C1, C2, and D1 accounted for 22.2%, 1.6%, 74.6%, and 1.6%, respectively. Genotype B was more frequently detected in patients with acute hepatitis B than those with chronic hepatitis B and acute-on-chronic liver failure. Deletion mutations were detected mostly in preS1 and preS2 regions and the detection rates were 3.8%, 19.7%, and 24.7% for acute hepatitis B, chronic hepatitis B and acute-on-chronic liver failure patients, respectively. Incidences of point mutation T53C (preS1F53L), G1613A (polR841K), G1775A and A1762T + G1764A in the basal core promoter region, G1896A and G1899A in precore region and A2189C (coreI97L) in core region increased along with acute hepatitis B, chronic hepatitis B, and acute-on-chronic liver failure. The mutation G1896A was independently associated with poor survival of patients with acute-on-chronic liver failure. The gradual increase of viral mutation incidences was also observed in three HLA-A2-restricted cytotoxic T lymphocyte epitopes from HLA-A2-positive patients, that is env188-196 (5.8%, 10.1%, 22.5%), core107-115 (4.3%, 4.6%, 19.7%), and x92-100 (1.4%, 20.2%, 33.8%). In conclusion, certain viral mutations in various regions of HBV genome are associated with disease progression of HBV infection.

Enterovirus 71 2C protein inhibits TNF-α-mediated activation of NF-κB by suppressing IκB kinase ß phosphorylation.

Enterovirus 71 (EV71), a single, positive-stranded RNA virus, has been regarded as the most important neurotropic enterovirus after the eradication of the poliovirus. EV71 infection can cause hand, foot, and mouth disease or herpangina. Cytokine storm with elevated levels of proinflammatory and inflammatory cytokines, including TNF-α, has been proposed to explain the pathogenesis of EV71-induced disease. TNF-α-mediated NF-κB signaling pathway plays a key role in inflammatory response. We hypothesized that EV71 might also moderate host inflammation by interfering with this pathway. In this study, we tested this hypothesis and identified EV71 2C protein as an antagonist of TNF-α-mediated activation of NF-κB signaling pathway. Expression of 2C protein significantly reduced TNF-α-mediated NF-κB activation in 293T cells as measured by gene reporter and gel mobility shift assays. Furthermore, overexpression of TNFR-associated factor 2-, MEK kinase 1-, IκB kinase (IKK)α-, or IKKß-induced NF-κB activation, but not constitutively active mutant of IKKß (IKKß SS/EE)-induced NF-κB activation, was inhibited by 2C protein. These data together suggested that the activation of IKKß is most likely targeted by 2C; this notion was further strengthened by immunoblot detection of IKKß phosphorylation and IκBα phosphorylation and degradation. Coimmunoprecipitation and colocalization of 2C and IKKß expressed in mammalian cells provided compelling evidence that 2C interacts with IKKß. Collectively, our data indicate that EV71 2C protein inhibits IKKß activation and thus blocks NF-κB activation.

Laboratory features throughout the disease course of influenza A (H1N1) virus infection.

BACKGROUND: Influenza has emerged every year but a complete profile of laboratory indices throughout the disease course remains unknown. METHODS: Clinical data was collected from 28 confirmed cases of the pandemic influenza H1N1 2009. The levels of serum iron (Fe), carbon dioxide combining power (CO2-CP), total complement hemolytic activity (CH50), C-reactive protein (CRP), and white blood cell (WBC) and differential count were analyzed. RESULTS: Major laboratory abnormalities recokled for patients upon admission were lymphopenia (96.4%), eosinopenia (50.0%), hypoferremia (92.9%), decreased levels of serum CO2-CP (60.7%), increased levels of serum CRP (84.6%) and serum CH50 (71.4%). The serum iron and CO2-CP concentration and the counts for lymphocytes, eosinophils, and basophils were significantly increased four days after sickness was noticed compared with the first three days of illness (p < 0.05). The total WBC and neutrophil counts were significantly decreased four days after onset of illness compared with the counts over the first three days (p < 0.05). The monocyte count and CRP concentration was significantly decreased 7 days after onset of illness compared with first 3 days after illness onset (p < 0.05). The serum CH50 concentrations were higher than the normal range during disease course and significantly elevated 7 days after onset of illness compared with the first 6 days after illness onset (p < 0.05). CONCLUSIONS: The serum levels of iron, CO2-CP, CH50, CRP, and WBC and differential count Were significantly varied during the whole pandemic influenza (H1N1) 2009. The development of WBC count in patients with influenza may be an effective predictor for severity of illness.

Induction of significant neutralizing antibodies against SARS-CoV-2 by a highly attenuated pangolin coronavirus variant with a 104nt deletion at the 3'-UTR.

SARS-CoV-2 related coronaviruses (SARS-CoV-2r) from Guangdong and Guangxi pangolins have been implicated in the emergence of SARS-CoV-2 and future pandemics. We previously reported the culture of a SARS-CoV-2r GX_P2V from Guangxi pangolins. Here we report the GX_P2V isolate rapidly adapted to Vero cells by acquiring two genomic mutations: an alanine to valine substitution in the nucleoprotein and a 104-nucleotide deletion in the hypervariable region (HVR) of the 3'-terminus untranslated region (3'-UTR). We further report the characterization of the GX_P2V variant (renamed GX_P2V(short_3UTR)) in in vitro and in vivo infection models. In cultured Vero, BGM and Calu-3 cells, GX_P2V(short_3UTR) had similar robust replication kinetics, and consistently produced minimum cell damage. GX_P2V(short_3UTR) infected golden hamsters and BALB/c mice but was highly attenuated. Golden hamsters infected intranasally had a short duration of productive infection in pulmonary, not extrapulmonary, tissues. These productive infections induced neutralizing antibodies against pseudoviruses of GX_P2V and SARS-CoV-2. Collectively, our data show that the GX_P2V(short_3UTR) is highly attenuated in in vitro and in vivo infection models. Attenuation of the variant is likely partially due to the 104-nt deletion in the HVR in the 3'-UTR. This study furthers our understanding of pangolin coronaviruses pathogenesis and provides novel insights for the design of live attenuated vaccines against SARS-CoV-2.

Anti-Coronaviral Nanocluster Restrain Infections of SARS-CoV-2 and Associated Mutants through Virucidal Inhibition and 3CL Protease Inactivation.

Antivirals that can combat coronaviruses, including SARS-CoV-2 and associated mutants, are urgently needed but lacking. Simultaneously targeting the viral physical structure and replication cycle can endow antivirals with sustainable and broad-spectrum anti-coronavirus efficacy, which is difficult to achieve using a single small-molecule antiviral. Thus, a library of nanomaterials on GX_P2V, a SARS-CoV-2-like coronavirus of pangolin origin, is screened and a surface-functionalized gold nanocluster (TMA-GNC) is identified as the top hit. TMA-GNC inhibits transcription- and replication-competent SARS-CoV-2 virus-like particles and all tested pseudoviruses of SARS-CoV-2 variants. TMA-GNC prevents viral dissemination through destroying membrane integrity physically to enable a virucidal effect, interfering with viral replication by inactivating 3CL protease and priming the innate immune system against coronavirus infection. TMA-GNC exhibits biocompatibility and significantly reduces viral titers, inflammation, and pathological injury in lungs and tracheas of GX_P2V-infected hamsters. TMA-GNC may have a role in controlling the COVID-19 pandemic and inhibiting future emerging coronaviruses or variants.

Immunologic changes during Pandemic (H1N1) 2009, China.

We analyzed changes in immunologic values over time for 28 hospitalized patients with pandemic (H1N1) 2009. Levels of interleukin-6, interferon-y, and interleukin-10 increased 1 day after illness onset and then decreased to baseline levels. Levels of virus-specific antibody were undetectable 1 day after illness onset and peaked 36 days later.

Mimotopes selected with neutralizing antibodies against multiple subtypes of influenza A.

BACKGROUND: The mimotopes of viruses are considered as the good targets for vaccine design. We prepared mimotopes against multiple subtypes of influenza A and evaluate their immune responses in flu virus challenged Balb/c mice. METHODS: The mimotopes of influenza A including pandemic H1N1, H3N2, H2N2 and H1N1 swine-origin influenza virus were screened by peptide phage display libraries, respectively. These mimotopes were engineered in one protein as multi- epitopes in Escherichia coli (E. coli) and purified. Balb/c mice were immunized using the multi-mimotopes protein and specific antibody responses were analyzed using hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). The lung inflammation level was evaluated by hematoxylin and eosin (HE). RESULTS: Linear heptopeptide and dodecapeptide mimotopes were obtained for these influenza virus. The recombinant multi-mimotopes protein was a 73 kDa fusion protein. Comparing immunized infected groups with unimmunized infected subsets, significant differences were observed in the body weight loss and survival rate. The antiserum contained higher HI Ab titer against H1N1 virus and the lung inflammation level were significantly decreased in immunized infected groups. CONCLUSIONS: Phage-displayed mimotopes against multiple subtypes of influenza A were accessible to the mouse immune system and triggered a humoral response to above virus.

Altered biliary epithelial cell and monocyte responses to lipopolysaccharide as a TLR ligand in patients with primary biliary cirrhosis.

OBJECTIVE: Lipopolysaccharide (LPS) is suspected to trigger primary biliary cirrhosis (PBC) in susceptible individuals, yet the precise mechanism of its effect in PBC remains largely unknown. The aim of this study was to investigate altered responses to LPS ligand for Toll-like receptors (TLRs) in pathogenesis of PBC in vivo and in vitro. MATERIAL AND METHODS: In vivo, we investigated levels of LPS and pro-inflammatory cytokines in sera and expression of LPS receptors in liver tissues from 162 patients with PBC, 325 patients with other liver diseases and 80 healthy controls. In vitro, altered responses to LPS on monocytes and cultured human biliary epithelial cells (BECs) from patients with PBC were determined. RESULTS: Significantly higher levels of LPS in patients with PBC were detected, compared with patients with other liver diseases and healthy controls. Immunohistochemically, expression of TLR4, CD14, CD68 and NF-κB was significantly enhanced in liver tissues from patients with PBC. Before LPS stimulation, we found significantly higher serum levels of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6 and IL-8 in patients with PBC than those in healthy controls. After LPS stimulation, TLR4 expression and pro-inflammatory cytokine production in CD14-positive monocytes and cultured BEC from patients with PBC increased significantly. CONCLUSIONS: These results indicated that patients with PBC were prone to exhibit higher serum LPS level, hypersensitivity of monocytes and BEC to LPS, and enhanced production of pro-inflammatory cytokines. LPS altered expression of TLR4, CD14 and NF-κB on monocytes and BEC, which may be implicated in the pathogenesis and progression of PBC.

Patient hematology during hospitalization for viral pneumonia caused by SARS-CoV-2 and non-SARS-CoV-2 agents: a retrospective study.

BACKGROUND: Hematological comparison of coronavirus disease (COVID-19) and other viral pneumonias can provide insights into COVID-19 treatment. METHODS: In this retrospective case-control single-center study, we compared the data of 126 patients with viral pneumonia during different outbreaks [severe acute respiratory syndrome (SARS) in 2003, influenza A (H1N1) in 2009, human adenovirus type 7 in 2018, and COVID-19 in 2020]. RESULTS: One of the COVID-19 characteristics was a continuous decline in the hemoglobin level. The neutrophil count was related to the aggravation of COVID-19 and SARS. Thrombocytopenia occurred in patients with SARS and severe COVID-19 even at the recovery stage. Lymphocytes were related to the entire course of adenovirus infection, recovery of COVID-19, and disease development of SARS. CONCLUSIONS: Dynamic changes in hematological counts could provide a reference for the pathogenesis and prognosis of pneumonia caused by respiratory viruses in clinics.

Association between epidermal growth factor 61A/G polymorphism and hepatocellular carcinoma susceptibility in Chinese patients.

BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection is an important risk factor for hepatocellular carcinoma (HCC) development in China, while little is known of the genetic susceptibility to hepatocarcinogenesis. The epidermal growth factor (EGF) pathway plays an important role in tumorigenesis, including HCC. EGF polymorphisms are associated with susceptibility to several types of cancers. Therefore, this study aimed to assess whether EGF genetic polymorphisms can influence HCC development. METHODS: A total of 338 chronic HBV-infected patients (186 HCC patients and 152 cirrhotic patients) and 186 healthy individuals were enrolled in this study. EGF 61A/G polymorphisms of all subjects and 12 cell lines were assayed with polymerase chain reaction-restriction fragment length polymorphism and the sequencing method. Furthermore, EGF protein levels were measured in the serum and the results were compared with the different genotypes. EGF expression in the liver tissue of the HCC patients was detected by immunohistochemical analysis. RESULTS: EGF 61A and 61G allele frequencies in healthy subjects were 28.76 and 71.24%. EGF 61GG and G allele frequencies in the HCC group were higher than those in the cirrhosis group. EGF protein levels with the GG genotype were significantly higher than those with either the GA or the AA genotype. About 59.09% of HCC liver tumour tissues assayed showed EGF protein expression. CONCLUSIONS: The EGF 61 GG genotype might be associated with a high risk for the development of chronic HBV infection-related HCC in Chinese patients.