Potential core genes associated with COVID-19 identified via weighted gene co-expression network analysis.

AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus belonging to the Coronaviridae family that causes coronavirus disease (COVID-19). This disease rapidly reached pandemic status, presenting a serious threat to global health. However, the detailed molecular mechanism contributing to COVID-19 has not yet been elucidated. METHODS: The expression profiles, including the mRNA levels, of samples from patients infected with SARS-CoV-2 along with clinical data were obtained from the GSE152075 dataset in the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules, which were then implemented to evaluate the relationships between fundamental modules and clinical traits. The differentially expressed genes (DEGs), gene ontology (GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were evaluated using R software packages. RESULTS: A total of 377 SARS-CoV-2-infected samples and 54 normal samples with available clinical and genetic data were obtained from the GEO database. There were 1444 DEGs identified between the sample types, which were used to screen out 11 co-expression modules in the WGCNA. Six co-expression modules were significantly associated with three clinical traits (SARS-CoV-2 positivity, age, and sex). Among the DEGs in two modules significantly correlated with SARS-CoV-2 positivity, enrichment was observed in the biological process of viral infection strategies (viral translation) in the GO analysis. The KEGG signalling pathway analysis demonstrated that the DEGs in the two modules were commonly enriched in oxidative phosphorylation, ribosome, and thermogenesis pathways. Moreover, a five-core gene set (RPL35A, RPL7A, RPS15, RPS20, and RPL17) with top connectivity with other genes was identified in the SARS-CoV-2 infection modules, suggesting that these genes may be indispensable in viral transcription after infection. CONCLUSION: The identified core genes and signalling pathways associated with SARS-CoV-2 infection can significantly supplement the current understanding of COVID-19. The five core genes encoding ribosomal proteins may be indispensable in viral protein biosynthesis after SARS-CoV-2 infection and serve as therapeutic targets for COVID-19 treatment. These findings can be used as a basis for creating a hypothetical model for future experimental studies regarding associations of SARS-CoV-2 infection with ribosomal protein function.

Hepatic dysfunctions in COVID-19 patients infected by the omicron variant of SARS-CoV-2.

Background: Presently, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dominates amid the coronavirus disease 2019 (COVID-19) pandemic, but its clinical characteristics with intrinsic severity and organ tropism remain understudied. Methods: We reported 1,001 mild COVID-19 patients that were infected with the omicron variant of SARS-CoV-2 and hospitalized in China from February to June 2022, including their demographic information, medical/immunization history, clinical symptom, and hematological profile. Patients with one-, two- and three-dose vaccination were compared to assess the vaccine effectiveness. Importantly, liver damage caused by the omicron variant infection was evaluated, in comparison to that caused by the wild-type or the delta variant SARS-CoV-2 infection. Results: For the reported COVID-19 patients infected by the omicron variant of SARS-CoV-2, their median age was 36.0 [interquartile range (IQR): 26.0-50.0] and 49.7% were female. Hypertension, diabetes, and bronchitis were the leading comorbidities, and asymptomatic patients took up a major portion (61.2%). While most hematological parameters revealed the alleviated pathogenicity, full vaccination or booster shot showed effective protection against clinical severity. Furthermore, liver damages caused by viral infection of the omicron variant were largely attenuated when compared to those by infection of the wild-type or the delta variant SARS-CoV-2. Conclusions: Our results supported that the viremic effect of the omicron variant tended to be modest, while the liver damage caused by this strain became milder than the previous circulating variants.

Association Between Red Blood Cell Distribution Width and COVID-19 Severity in Delta Variant SARS-CoV-2 Infection.

Studies have discovered that wild-type SARS-CoV-2 infections are commonly linked to abnormalities in the hematological profiles of COVID-19 patients, one such abnormality being characterized by elevations in red blood cell distribution width (RDW). Whether this linkage reoccurs in delta variant SARS-CoV-2 infection remains unexamined. Here we compared baseline blood parameters in COVID-19 patients infected by wild type and its delta variant, respectively. Our results here point to that although the delta variant has shown increased virulence, transmissibility, and vaccine escape, it has a minimally negative impact on RDW values that were previously found prognostic for COVID-19 severity.

Hepatic dysfunctions in COVID-19 patients infected by the omicron variant of SARS-CoV-2

Background Presently, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dominates amid the coronavirus disease 2019 (COVID-19) pandemic, but its clinical characteristics with intrinsic severity and organ tropism remain understudied. Methods We reported 1,001 mild COVID-19 patients that were infected with the omicron variant of SARS-CoV-2 and hospitalized in China from February to June 2022, including their demographic information, medical/immunization history, clinical symptom, and hematological profile. Patients with one-, two- and three-dose vaccination were compared to assess the vaccine effectiveness. Importantly, liver damage caused by the omicron variant infection was evaluated, in comparison to that caused by the wild-type or the delta variant SARS-CoV-2 infection. Results For the reported COVID-19 patients infected by the omicron variant of SARS-CoV-2, their median age was 36.0 [interquartile range (IQR): 26.0-50.0] and 49.7% were female. Hypertension, diabetes, and bronchitis were the leading comorbidities, and asymptomatic patients took up a major portion (61.2%). While most hematological parameters revealed the alleviated pathogenicity, full vaccination or booster shot showed effective protection against clinical severity. Furthermore, liver damages caused by viral infection of the omicron variant were largely attenuated when compared to those by infection of the wild-type or the delta variant SARS-CoV-2. Conclusions Our results supported that the viremic effect of the omicron variant tended to be modest, while the liver damage caused by this strain became milder than the previous circulating variants.

When to become an electronic business venture after the COVID-19 pandemic? The role of strategic orientation and perceived environmental turbulence in determining online market entry timing

After the COVID-19 epidemic, a growing number of commercial entities have decided to enter the online platform and operated as an electronic business venture. However, the timing of entering the online market is a strategically important issue. On the basis of social capital theory and resource-based view, this study attempts to understand the different impacts of two strategic orientations (i.e., Guanxi orientation and entrepreneurial orientation) and perceived environmental turbulence (i.e., market turbulence and political turbulence) on online market entry timing. We test four hypotheses using data collected from 174 Chinese companies. Our results confirm that entrepreneurial orientation negatively impacts online market entry timing, and this effect is moderated by perceived market turbulence such that the negative relationship between entrepreneurial orientation and online market entry timing will be strengthened in higher market turbulence. By contrast, Guanxi orientation positively impacts online market entry timing, and the positive relationship between Guanxi orientation and online market entry timing will be weakened in higher political turbulence. Implications and future research directions are discussed.

Correlation of clinical characteristics between patients with seasonal influenza and patients infected by the wild type or delta variant of SARS-CoV-2.

Background: We compared the clinical characteristics of the patients with COVID-19, infected by the wild type or delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in connection with those of patients with seasonal influenza, all in mild cases. Methods: We retrospectively studied 245 and 115 patients with mild COVID-19 infected by the wild type and the delta variant of SARS-CoV-2, respectively, with their demographic information, medical history, and laboratory data from hospital records, individually compared to 377 patients with mild seasonal influenza, before and after individual treatment. Results: Compared to the influenza cohort, the COVID-19 cohort or the COVID-19 delta variant cohort demonstrated younger median age, lower male ratio, and shorter duration from disease onset to hospitalization. Hypertension remained the top comorbidity among all cohorts. Based on patients' data upon hospitalization, the correlation of clinical characteristics between patients with influenza and those with the wild-type COVID-19 is greater than that between patients with influenza and those with the delta variant COVID-19. Individual treatment in each viral disease alleviated most hematological parameters, but some compromised biomarkers at the time of hospital discharge revealed persistent renal or myocardial impairment among patients with COVID-19 and influenza in recovery. Conclusion: Timely and proper treatment using broad-spectrum antibiotics and antiviral drugs could moderately alleviate the acute viremia and possible bacterial co-infection in patients with mild COVID-19 and influenza, followed by compromised recovery. To prepare for the flu season amid the COVID-19 pandemic, preventive and adequate immunizations of both flu and COVID-19 vaccines, as well as specific therapeutics to effectively reverse viral impairments, are in urgent need.

Comparative characterization of SARS-CoV-2 variants of concern and mouse-adapted strains in mice.

SARS-CoV-2 has evolved into a panel of variants of concern (VOCs) and constituted a sustained threat to global health. The wildtype (WT) SARS-CoV-2 isolates fail to infect mice, while the Beta variant, one of the VOCs, has acquired the capability to infect standard laboratory mice, raising a spreading risk of SARS-CoV-2 from humans to mice. However, the infectivity and pathogenicity of other VOCs in mice remain not fully understood. In this study, we systematically investigated the infectivity and pathogenicity of three VOCs, Alpha, Beta, and Delta, in mice in comparison with two well-understood SARS-CoV-2 mouse-adapted strains, MASCp6 and MASCp36, sharing key mutations in the receptor-binding domain (RBD) with Alpha or Beta, respectively. Our results showed that the Beta variant had the strongest infectivity and pathogenicity among the three VOCs, while the Delta variant only caused limited replication and mild pathogenic changes in the mouse lung, which is much weaker than what the Alpha variant did. Meanwhile, Alpha showed comparable infectivity in lungs in comparison with MASCp6, and Beta only showed slightly lower infectivity in lungs when compared with MASCp36. These results indicated that all three VOCs have acquired the capability to infect mice, highlighting the ongoing spillover risk of SARS-CoV-2 from humans to mice during the continued evolution of SARS-CoV-2, and that the key amino acid mutations in the RBD of mouse-adapted strains may be referenced as an early-warning indicator for predicting the spillover risk of newly emerging SARS-CoV-2 variants.

Association Between Red Blood Cell Distribution Width and COVID-19 Severity in Delta Variant SARS-CoV-2 Infection

Studies have discovered that wild-type SARS-CoV-2 infections are commonly linked to abnormalities in the hematological profiles of COVID-19 patients, one such abnormality being characterized by elevations in red blood cell distribution width (RDW). Whether this linkage reoccurs in delta variant SARS-CoV-2 infection remains unexamined. Here we compared baseline blood parameters in COVID-19 patients infected by wild type and its delta variant, respectively. Our results here point to that although the delta variant has shown increased virulence, transmissibility, and vaccine escape, it has a minimally negative impact on RDW values that were previously found prognostic for COVID-19 severity.

Differences in Clinical Characteristics Between Delta Variant and Wild-Type SARS-CoV-2 Infected Patients.

Background: As delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevailed in the current coronavirus disease 2019 (COVID-19) pandemic, its clinical characteristics with the difference from those of wild-type strains have been little studied. Methods: We reported one cohort of 341 wild-type patients with COVID-19 admitted at Wuhan, China in 2020 and the other cohort of 336 delta variant patients with COVID-19 admitted at Yangzhou, China in 2021, with comparisons of their demographic information, medical history, clinical manifestation, and hematological data. Furthermore, within the delta variant cohort, patients with none, partial, and full vaccination were also compared to assess vaccine effectiveness. Findings: For a total of 677 patients with COVID-19 included in this study, their median age was 53.0 years [interquartile range (IQR): 38.0-66.0] and 46.8% were men. No difference was found in age, gender, and percentage of patients with the leading comorbidity between wild-type and delta variant cohorts, but delta variant cohort showed a lessened time interval between disease onset to hospitalization, a reduced portion of patients with smoking history, and a lowered frequency of clinical symptoms. For hematological parameters, most values demonstrated significant differences between wild-type and delta variant cohorts, while full vaccination rather than partial vaccination alleviated the disease condition. This reflected the viremic effect of delta variant when vaccination succeeds or fails to protect. Interpretation: Delta variant of SARS-CoV-2 may cause severe disease profiles, but timely diagnosis and full vaccination could protect patients with COVID-19 from worsened disease progression.

Exploring the effect of COVID-19 on airline environmental efficiency through an interval epsilon-based measure model.

COVID-19 has dealt an unprecedented blow to the aviation industry since 2020. This paper applies the interval epsilon-based measure (IEBM) model to evaluate the optimal quarterly environmental efficiency of 14 global airlines of passenger and cargo subsystems during 2018-2020. Then, the time series prediction method is applied to forecast the interval data of inputs and outputs from 2021 to 2022. Finally, we can calculate the quarterly efficiency. Thus, the future development trends of airlines can be predicted. The results show that (1) COVID-19 has hit the passenger subsystem harder, while the freight subsystem has become more efficient; (2) the efficiency of the freight subsystem has inevitably declined in the post-epidemic era; and (3) therefore, the airlines will have a "√" shaped recovery curve in the next few years.

Platelet-driven coagulopathy in COVID-19 patients: in comparison to seasonal influenza cases.

BACKGROUND: One year into the coronavirus diseases 2019 (COVID-19) pandemic we analyzed the blood coagulopathy in severe and non-severe COVID-19 patients and linked to those of influenza patients for a comparative study. METHODS: We reported 461 COVID-19 patients and 409 seasonal influenza patients admitted at separated medical centers. With their demographic data and medical history, hematological profiles with coagulation characters were emphasized, and compared between two cohorts before and after treatment. RESULTS: For 870 patients included in this study, their median age was (64.0, 51.0-76.0), and among them 511 (58.7%) were male. Hypertension, diabetes, cardiovascular diseases, and bronchitis constituted the leading comorbidities. Upon hospital admission blood test results differentiated COVID-19 patients from influenza cases, and for COVID-19 patients, leukocytosis, neutrophilia, lymphocytopenia, and thrombocytopenia were associated with disease severity and mortality. In addition, COVID-19 cohort demonstrated a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), increased INR, shortened thrombin time and decreased fibrinogen, compared to those in influenza cohort, leaving D-dimer levels indistinguishably high between both cohorts. Platelet hyperreactivity in COVID-19 is more evident, associated with worse hyper-inflammatory response and more refractory coagulopathy. For severe COVID-19 patients administered with anticoagulants, bleeding incidence was substantially higher than others with no anticoagulant medications. CONCLUSIONS: Comparison of coagulation characteristics between COVID-19 and influenza infections provides an insightful view on SARS-CoV-2 pathogenesis and its coagulopathic mechanism, proposing for therapeutic improvement.

Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain.

The emerging new lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have marked a new phase of coronavirus disease 2019 (COVID-19). Understanding the recognition mechanisms of potent neutralizing monoclonal antibodies (NAbs) against the spike protein is pivotal for developing new vaccines and antibody drugs. Here, we isolated several monoclonal antibodies (MAbs) against the SARS-CoV-2 spike protein receptor-binding domain (S-RBD) from the B cell receptor repertoires of a SARS-CoV-2 convalescent. Among these MAbs, the antibody nCoV617 demonstrates the most potent neutralizing activity against authentic SARS-CoV-2 infection, as well as prophylactic and therapeutic efficacies against the human angiotensin-converting enzyme 2 (ACE2) transgenic mouse model in vivo. The crystal structure of S-RBD in complex with nCoV617 reveals that nCoV617 mainly binds to the back of the "ridge" of RBD and shares limited binding residues with ACE2. Under the background of the S-trimer model, it potentially binds to both "up" and "down" conformations of S-RBD. In vitro mutagenesis assays show that mutant residues found in the emerging new lineage B.1.1.7 of SARS-CoV-2 do not affect nCoV617 binding to the S-RBD. These results provide a new human-sourced neutralizing antibody against the S-RBD and assist vaccine development. IMPORTANCE COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has posed a serious threat to global health and the economy, so it is necessary to find safe and effective antibody drugs and treatments. The receptor-binding domain (RBD) in the SARS-CoV-2 spike protein is responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor. It contains a variety of dominant neutralizing epitopes and is an important antigen for the development of new coronavirus antibodies. The significance of our research lies in the determination of new epitopes, the discovery of antibodies against RBD, and the evaluation of the antibodies' neutralizing effect. The identified antibodies here may be drug candidates for the development of clinical interventions for SARS-CoV-2.

Comparative Study of Acute Lung Injury in COVID-19 and Non-COVID-19 Patients.

Background: Amid the coronavirus disease 2019 (COVID-19) pandemic, we analyzed clinical characteristics of acute lung injury (ALI) in COVID-19 patients and reported their similarity and dissimilarity to those of non-COVID-19 patients in the intensive care unit (ICU). Methods: We reported on 90 COVID-19 and 130 non-COVID-19 ALI patients in the ICUs of multiple centers. Demographic data, medical histories, laboratory findings, and radiological images were analyzed and compared between the two cohorts and within each cohort between survivors and non-survivors. For ALI survivors, clinical characteristics before and after treatment were also compared. Findings: Aberrations in blood parameters, such as leukocytosis, neutrophilia, and thrombocytopenia, were observed in both cohorts. More characteristic abnormalities, including significantly higher red cell distribution width (RDW), C-reactive proteins, and lactic dehydrogenase (LDH) but lower troponin (TnT) and procalcitonin, were observed in the COVID-19 cohort than in the non-COVID-19 cohort, whereas D-dimer levels showed a similar elevation in both cohorts. The COVID-19 cohort also showed more diversified CT patterns where severe features such as consolidations and crazy paving patterns were more frequently observed. Multivariate analysis indicated that age, fever symptom, prothrombin time, procalcitonin, partial pressure of carbon dioxide, oxygenated hemoglobin, and crazy paving patterns in CT scans were independent risk factors associated with COVID-19. Interpretation: Comparison of ALI characteristics between COVID-19 and non-COVID-19 patients in the ICU setting provided insight into the pathogenesis of ALI induced by different risk factors, suggesting distinct treatment plans.

Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection.

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.

Differentiation of COVID-19 from seasonal influenza: A multicenter comparative study.

As coronavirus disease 2019 (COVID-19) crashed into the influenza season, clinical characteristics of both infectious diseases were compared to make a difference. We reported 211 COVID-19 patients and 115 influenza patients as two separate cohorts at different locations. Demographic data, medical history, laboratory findings, and radiological characters were summarized and compared between two cohorts, as well as between patients at the intensive care unit (ICU) andnon-ICU within the COVID-19 cohort. For all 326 patients, the median age was 57.0 (interquartile range: 45.0-69.0) and 48.2% was male, while 43.9% had comorbidities that included hypertension, diabetes, bronchitis, and heart diseases. Patients had cough (75.5%), fever (69.3%), expectoration (41.1%), dyspnea (19.3%), chest pain (18.7%), and fatigue (16.0%), etc. Both viral infections caused substantial blood abnormality, whereas the COVID-19 cohort showed a lower frequency of leukocytosis, neutrophilia, or lymphocytopenia, but a higher chance of creatine kinase elevation. A total of 7.7% of all patients possessed no abnormal sign in chest computed tomography (CT) scans. For both infections, pulmonary lesions in radiological findings did not show any difference in their location or distribution. Nevertheless, compared to the influenza cohort, the COVID-19 cohort presented more diversity in CT features, where certain specific CT patterns showed significantly more frequency, including consolidation, crazy paving pattern, rounded opacities, air bronchogram, tree-in-bud sign, interlobular septal thickening, and bronchiolar wall thickening. Differentiable clinical manifestations and CT patterns may help diagnose COVID-19 from influenza and gain a better understanding of both contagious respiratory illnesses.

CT features of coronavirus disease 2019 (COVID-19) with an emphasis on the vascular enlargement pattern.

PURPOSE: The vascular enlargement (VE) pattern differs from previously described imaging patterns for pneumonia. This study aimed to investigate the incidence, computed tomography (CT) characteristics, and diagnostic value of the VE pattern in coronavirus disease 2019 (COVID-19). METHOD: The CT data of 106 patients with COVID-19 from January 19 to February 29, 2020, and 52 patients with influenza virus pneumonia (IVP) from January 2018 to February 2020 were retrospectively collected. The incidences of the VE pattern between the two groups were compared. The CT manifestations of COVID-19 were analyzed with a particular focus on the VE pattern's specific CT signs, dynamic changes, and relationships with lesion size and disease severity. RESULTS: Peripheral and multilobar ground-glass opacities (GGOs) or mixed GGOs with various sizes and morphologies were typical features of COVID-19 on initial CT. The VE pattern was more common in COVID-19 (88/106, 83.02 %) than in IVP (10/52, 19.23 %) on initial CT (P < 0.001). Three special VE-pattern-specific CT signs, including central vascular sign, ginkgo leaf sign, and comb sign, were identified. Four types of dynamic changes in the VE pattern were observed on initial and follow-up CT, which were closely associated with the evolution of lesions and the time interval from the onset of symptoms to initial CT scan. The VE pattern in COVID-19 was more commonly seen in larger lesions and patients with severe-critical type (all P < 0.001). CONCLUSIONS: The VE pattern is a valuable CT sign for differentiating COVID-19 from IVP, which correlates with more extensive or serious disease. A good understanding of the CT characteristics of the VE pattern may contribute to the early and accurate diagnosis of COVID-19 and prediction of the evolution of lesions.