The prevalence of pre-diabetes and diabetes in people with and without past history of COVID-19 in northeastern Nigeria (preprint)

Background An increased risk of diabetes mellitus (DM) after COVID-19 has been reported in the United States, Europe, and Asia. The burden of COVID-related DM has not been described in Africa, where the overall risk of DM has been increasing rapidly. Our objective was to compare the prevalence of pre-DM and DM in Nigerian individuals with a history of COVID-19 to individuals without known COVID-19 infection.Methods We identified 256 individuals with a past medical history of COVID-19 with no history of pre-DM or DM and 256 individuals without a history of COVID-19 or pre-DM/DM. Participants were categorized as pre-DM (fasting capillary glucose 100–125 mg/dL) or DM (fasting capillary glucose ≥ 126 mg/dL). We used multivariate multinomial logistic regression to determine the odds of pre-DM and DM in those with and without a history of COVID-19 after adjustment for age, gender, the presence of hypertension, physical activity, central adiposity, and family history of DM.Results Compared to the control group, those with a history of COVID-19 had a similar median age (38 vs 40 years, p = 0.84), had a higher proportion of men (63% vs 49%), and had a lower prevalence of central adiposity (waist: hip ratio ≥ 0.90 for males and WHR ≥ 0.85 for females) (48% vs 56.3%, p = 0.06). Of the 256 with a history of COVID-19, 44 (17%) required inpatient care. The median (interquartile range) time interval between COVID-19 diagnosis and the glycaemic assessment was 19 (14, 24) months. Pre-DM prevalence was 27% in the post-COVID-19 group and 4% in the control group, whereas the prevalence of DM was 7% in the post-COVID-19 group and 2% in the control group. After multivariable adjustment, the odds of pre-DM were 8.12 (95% confidence interval (CI): 33.98, 16.58; p < 0.001) higher, and the odds of DM were 3.97 (95% CI: 1.16, 13.63) higher in those with a history of COVID-19 compared to controls.Conclusion Previous COVID-19 was found to be a risk factor for prevalent pre-diabetes and diabetes mellitus in Nigeria. More intensive screening for DM in those with a history of COVID-19 should be considered.

Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19: a systematic review and meta-analysis (preprint)

Several clinical trials have evaluated the efficacy and safety of baricitinib in COVID-19 patients. Recently, there have been reports on critical patients, which are different from previous research results. Studies were searched in PubMed, Embase, and Cochrane Library databases on January 31, 2023. We performed a meta-analysis to estimate the efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19. This study is registered with INPLASY , number 202310086. A total of 3010 patients were included in our analyses. All included studies were randomized controlled trials or prospective study. There was no difference in 14-day mortality between the two groups (OR 0.23 [95% CI 0.03–1.84], I²=72%, P=0.17). In subgroup analyses we found that baricitinib did not seem to improve significantly in 24-day mortality critically ill patients (OR 0.60 [95% CI 0.35–1.02], I²=0%, P=0.06). Fortunately, baricitinib have led to faster recovery and shorter hospital stays for COVID-19 patients. There were no difference in infections and infestations, major adverse cardiovascular events, deep vein thrombosis and pulmonary embolism. Baricitinib is safe. At the same time, we can find that it reduces the mortality of COVID-19 patients, but the prognosis of the critically ill patients is not significantly improved.

Negative conversion, lymphocyte/monocyte ratio, and bilirubinemia in COVID-19 with mental disorders (preprint)

This retrospective study explored the changes in biomarkers indicators and prognosis in COVID-19 patients with mental disorders (n = 60) from the author’ Hospital between 2/13/2020 and 4/15/2020. Significant differences before and after negative conversion were observed in lymphocytes, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, aspartate aminotransferase, albumin, albumin/globulin ratio, direct bilirubin, alkaline phosphatase, uric acid, high-density lipoprotein cholesterol, and ApoA1 (all P < 0.05). Compared with the patients who had a negative conversion within 3 weeks, those who did not turn negative within 3 weeks had a higher frequency of cardiovascular diseases (27.3% vs. 4.2%, P = 0.040), a higher lymphocyte-to-monocyte ratio (median, 4.72 vs. 3.35, P = 0.003), and higher total bilirubin levels (median, 12.0 vs. 8.6 µmol/L, P = 0.031). The results present the changes in laboratory parameters in COVID-19 patients with a mental disorder. Cardiovascular diseases and higher lymphocyte-to-monocyte ratio, and total bilirubin levels could be associated with the amount of time required for negative conversion.

Case report on cured COVID-19 patients with viral nucleic acid test positive in fecal specimens in Chongqing, China

The outbreak of the novel coronavirus in China (2019-nCoV) has spread to all 31 provinces in China and more than 24 countries in the world. The cure criterion was based on the negative results with respiratory specimens in real-time reverse transcription polymerise chain reaction (RT-PCR) assays with an interval of 24 hrs. This report describes the controversial viral nucleic acid test in 27 cases after hospitalization for medical treatment for various periods. Of 27 cases, 6 cases showed positive results for fecal specimen, and 2 cases showed negative results with respiratory secretion but positive with fecal specimen. In summary, the consistence of results of nucleic acid test with different type of specimens from patients infected with 2019-nCoV varied, deeper research is needed to reveal the criteria of nucleic acid detection during different stages of the 2019-nCoV infection.

Rational Development of a Polysaccharide–Protein-Conjugated Nanoparticle Vaccine Against SARS-CoV-2 Variants and Streptococcus pneumoniae (Adv. Mater. 21/2022)

Nanoparticle Vaccines In article number 2200443, Liangzhi Xie, Chengfeng Qin, and co-workers develop a novel bivalent nanoparticle vaccine that confers protection against infection of multiple SARS-CoV-2 variants and Streptococcus pneumoniae. This universal polysaccharide?protein-conjugated vaccine platform provides a powerful tool to fight against cocirculating viral and bacterial pathogens worldwide.

A population antibody response against SARS-CoV-2 with differential neutralization activities towards the Delta and Omicron variants (preprint)

Population antibody response is believed to be important in selection of new variant viruses. We identified that SARS-CoV-2 infections elicit a population immune response mediated by a lineage of VH1-69 germline antibodies. The representative antibody R1-32 targets a novel semi-cryptic epitope defining a new class of RBD targeting antibodies. Binding to this non-ACE2 competing epitope leading to spike destruction impairing virus entry. Based on epitope location, neutralization mechanism and analysis of antibody binding to spike variants we propose that recurrent substitutions at 452 and 490 are associated with immune evasion of this population antibody response. These substitutions, including L452R found in the Delta variant, disrupt interaction mediated by the VH1-69 specific hydrophobic HCDR2 to impair antibody-antigen association allowing variants to escape. Lacking 452/490 substitutions, the Omicron variant is sensitive to this class of antibodies. Our results provide new insights into SARS-CoV-2 variant genesis and immune evasion.

Fatality assessment and variant risk monitoring for COVID-19 using three new hospital occupancy related metrics (preprint)

Background Though case fatality rate (CFR) and hospital mortality rate (HMR) are used to reflect COVID-19 fatality risk, they are limited by temporal and spatial variation of CFR and availability of HMR. Alternative metrics are needed for COVID-19 fatality measurement and variant risk monitoring. Methods New metrics and their applications in fatality measurements and risk monitoring are proposed here. We also introduce a new mathematical model to estimate average hospital length of stay for death (Ldead) and discharges (Ldis). Multiple data sources were used for our analysis. Findings We propose three new metrics, hospital occupancy mortality rate (HOMR), ratio of total deaths to hospital occupancy (TDHOR) and ratio of hospital occupancy to cases (HOCR), for dynamic assessment of COVID-19 fatality risk. Estimated Ldead and Ldis for 501079 COVID-19 hospitalizations in US 34 states between Aug 7, 2020 and Mar 1, 2021 were 14.0 and 18.2 days, respectively. We found that TDHOR values of 27 countries are less spatially and temporally variable and more capable of detecting changes in COVID-19 fatality risk. The dramatic changes in COVID-19 CFR observed in 27 countries during early stages of the pandemic were mostly caused by undiagnosed cases. Compared to the first week of November, 2021, the week mean HOCRs (mimics hospitalization-to-case ratio) for Omicron variant decreased 34.08% and 65.16% in the United Kingdom and USA respectively as of Jan 16, 2022. Interpretation These new and reliable measurements for COVID-19 that could be expanded as a general index to other fatal infectious diseases for disease fatality risk and variant-associated risk monitoring.

Research on Default Prediction for Credit Card Users Based on XGBoost-LSTM Model

The credit card business has become an indispensable financial service for commercial banks. With the development of credit card business, commercial banks have achieved outstanding results in maintaining existing customers, tapping potential customers, and market share. During credit card operations, massive amounts of data in multiple dimensions—including basic customer information;billing, installment, and repayment information;transaction flows;and overdue records—are generated. Compared with preloan and postloan links, user default prediction of the on-loan link has a huge scale of data, which makes it difficult to identify signs of risk. With the recent growing maturity and practicality of technologies such as big data analysis and artificial intelligence, it has become possible to further mine and analyze massive amounts of transaction data. This study mined and analyzed the transaction flow data that best reflected customer behavior. XGBoost, which is widely used in financial classification models, and Long-Short Term Memory (LSTM), which is widely used in time-series information, were selected for comparative research. The accuracy of the XGBoost model depends on the degree of expertise in feature extraction, while the LSTM algorithm can achieve higher accuracy without feature extraction. The resulting XGBoost-LSTM model showed good classification performance in default prediction. The results of this study can provide a reference for the application of deep learning algorithms in the field of finance.

Single Extracellular Vesicles (EV) Proteomic Profiling Altered and Identifies Co-Localization of SARS-CoV-2 Nucleocapsid Protein with CD81/Integrin-Rich EV Subpopulation in Sputum Samples of COVID-19 Patients (preprint)

Understanding the pathogenesis of SARS-CoV-2 is crucial to respond to the current coronavirus disease 2019 (COVID-19) pandemic. Sputum samples from 20 COVID-19 patients and healthy controls were collected, respectively. During the isolation of infectious SARS-CoV-2 virus, EV-like vesicles were associated with virions under a transmission electron microscope. Next, the expression of IL6 and TGF-β increased in EVs derived from the sputum of patients, and these were highly correlated with the expression of the SARS-CoV-2 N protein. Further, proximity barcoding assay (PBA) was used to investigate the immune-related proteins in the EVs, and the relationship between EVs and SARS-CoV-2 N protein in COVID-19 patients’ samples. Particularly, to investigate the differential contribution of the specific EV subsets, the protein expression of a single EV was detected and analyzed for the first time. Among the 40 EV subpopulations, 18 were found to have significant differences. The EV subpopulation regulated by CD81 were most likely to correlate with the changes in the pulmonary microenvironment after SARS-CoV-2 infection. This study provides evidence on the association between EVs and the SARS-CoV-2 virus, give a deep insight into the possible pathogenesis of SARS-CoV-2 infection and the possibility of nanoparticles drug intervention in viral infection.

Epidemic Spreading in Trajectory Networks

Epidemics of infectious diseases, such as the one caused by the rapid spread of the coronavirus disease 2019 (COVID-19), have tested the world's more advanced health systems and have caused an enormous societal and economic damage. The mechanism of contagion is well understood. As people move around, over time, they regularly engage in social interactions. The spatiotemporal network representing these interactions constitutes the backbone on which an epidemic spreads, causing outbreaks. At the same time, advanced technological responses have claimed some success in controlling the epidemic based on digital contact tracing technologies. Motivated by these observations, we design, develop and evaluate a stochastic agent-based SEIR model of epidemic spreading in spatiotemporal networks informed by mobility data of individuals (trajectories). The model focuses on individual variation in mobility patterns that affects the degree of exposure to the disease. Understanding the role that individual nodes play in the process of disease spreading through network effects is fundamental as it allows to (i) assess the risk of infection of individuals, (ii) assess the size of a disease outbreak due to specific individuals, and (iii) assess targeted intervention strategies that aim to control the epidemic spreading. We perform a comprehensive analysis of the model employing COVID-19 as a use case. The results indicate that simple individual-based intervention strategies that exhibit significant network effects can effectively control the spread of an epidemic. We have also demonstrated that targeted interventions can outperform generic intervention strategies. Overall, our work provides an evidence-based data-driven model to support decision making and inform public policy regarding intervention strategies for containing or mitigating the epidemic spread.

The adenosine analogue prodrug ATV006 is orally bioavailable and has potent preclinical efficacy against SARS-CoV-2 and its variants (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the COVID-19 pandemic, is rapidly evolving. Due to the limited efficacy of vaccination in prevention of SARS-CoV-2 transmission and continuous emergence of variants of concern (VOC), including the currently most prevalent Delta variant, orally bioavailable and broadly efficacious antiviral drugs are urgently needed. Previously we showed that adenosine analogue 69-0 (also known as GS-441524), possesses potent anti-SARS-CoV-2 activity. Herein, we report that esterification of the 5-hydroxyl moieties of 69-0 markedly improved the antiviral potency. The 5-hydroxyl -isobutyryl prodrug, ATV006, showed excellent oral bioavailability in rats and cynomolgus monkeys and potent antiviral efficacy against different VOCs of SARS-CoV-2 in cell culture and three mouse models. Oral administration of ATV006 significantly reduced viral loads, alleviated lung damage and rescued mice from death in the K18-hACE2 mouse model challenged with the Delta variant. Moreover, ATV006 showed broad antiviral efficacy against different mammal-infecting coronaviruses. These indicate that ATV006 represents a promising oral drug candidate against SARS-CoV-2 VOCs and other coronaviruses.

COVID-19 Disease Severity among People with HIV Infection or Solid Organ Transplant in the United States: A Nationally-representative, Multicenter, Observational Cohort Study (preprint)

Background Individuals with immune dysfunction, including people with HIV (PWH) or solid organ transplant recipients (SOT), might have worse outcomes from COVID-19. We compared odds of COVID-19 outcomes between patients with and without immune dysfunction. Methods We evaluated data from the National COVID-19 Cohort Collaborative (N3C), a multicenter retrospective cohort of electronic medical record (EMR) data from across the United States, on. 1,446,913 adult patients with laboratory-confirmed SARS-CoV-2 infection. HIV, SOT, comorbidity, and HIV markers were identified from EMR data prior to SARS-CoV-2 infection. COVID-19 disease severity within 45 days of SARS-CoV-2 infection was classified into 5 categories: asymptomatic/mild disease with outpatient care; mild disease with emergency department (ED) visit; moderate disease requiring hospitalization; severe disease requiring ventilation or extracorporeal membrane oxygenation (ECMO); and death. We used multivariable, multinomial logistic regression models to compare odds of COVID-19 outcomes between patients with and without immune dysfunction. Findings Compared to patients without immune dysfunction, PWH and SOT had a greater likelihood of having ED visits (adjusted odds ratio [aOR]: 1.28, 95% confidence interval [CI] 1.27-1.29; aOR: 2.61, CI: 2.58-2.65, respectively), requiring ventilation or ECMO (aOR: 1.43, CI: 1.43-1.43; aOR: 4.82, CI: 4.78-4.86, respectively), and death (aOR: 1.20, CI: 1.19-1.20; aOR: 3.38, CI: 3.35-3.41, respectively). Associations were independent of sociodemographic and comorbidity burden. Compared to PWH with CD4>500 cells/mm3, PWH with CD4<350 cells/mm3 were independently at 4.4-, 5.4-, and 7.6-times higher odds for hospitalization, requiring ventilation, and death, respectively. Increased COVID-19 severity was associated with higher levels of HIV viremia. Interpretation Individuals with immune dysfunction have greater risk for severe COVID-19 outcomes. More advanced HIV disease (greater immunosuppression and HIV viremia) was associated with higher odds of severe COVID-19 outcomes. Appropriate prevention and treatment strategies should be investigated to reduce the higher morbidity and mortality associated with COVID-19 among PWH and SOT.

Effects of novel Coronavirus pneumonia pandemic on the spread of multidrug-resistant Acinetobacter in ICU

OBJECTIVE: To investigate the effect of novel coronavirus pneumonia pandemic on multidrug-resistant Acinetobacter baumannii transmission in intensive care units(ICU) and to provide reference for the guidance of nosocomial infection prevention and control. METHODS: Data of multidrug-resistant A. baumannii in ICU1, ICU2 and neurosurgery ICU from Jan. 2019 to Aug. 2020 were collected. Contact times between healthcare workers and environmental surfaces, clearance rate of fluorescent marker in the culture of environment specimens before and after the novel coronavirus pneumonia outbreak, number of free colonies and number of MDR-AB were detected, and the correlation between MDR-AB detection rate of the environment and MDR-AB the infection rate were analyzed by using Pearson correlation analysis. RESULTS: The high-frequency contact surfaces in ICU were bed bars(43.59 times), quilts(39.58 times), treatment vehicles(30.83 times), vein tubes(27.46 times), nursing station table tops(27.20 times) and hand sterilized buttons(26.40 times). The clearance rate of fluorescent marker after novel coronavirus pneumonia outbreak was 81.35%, which was significantly higher than that before the new coronavirus-infected pneumonia epidemic outbreak(P<0.001), with the rate of 56.57%. The detection rate and infection rate of MDR-AB in the environment after new coronavirus-infected pneumonia epidemic were 5.40% and 1.80%, respectively, which were significantly lower than that before the epidemic(P<0.001). Pearson correlation analysis showed that the detection rate of MDR-AB in the ICU environment was positively correlated with the MDR-AB infection rate of patients(r=0.850, P=0.002). CONCLUSION: Methods of novel coronavirus pneumonia epidemic prevention promoted the implementation of environmental sanitation, disinfection and isolation measures, cut off the transmission route of multidrug-resistant A. baumannii, and played a positive role in the prevention and control of infection.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant (preprint)

We report the first local transmission of the SARS-CoV-2 Delta variant in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of the quarantined subjects indicated that the viral loads of Delta infections, when they first become PCR+, were on average ~1000 times greater compared to A/B lineage infections during initial epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. We performed high-quality sequencing on samples from 126 individuals. Reliable epidemiological data meant that, for 111 transmission events, the donor and recipient cases were known. The estimated transmission bottleneck size was 1-3 virions with most minor intra-host single nucleotide variants (iSNVs) failing to transmit to the recipients. However, transmission heterogeneity of SARS-CoV-2 was also observed. The transmission of minor iSNVs resulted in at least 4 of the 30 substitutions identified in the outbreak, highlighting the contribution of intra-host variants to population level viral diversity during rapid spread. Disease control activities, such as the frequency of population testing, quarantine during pre-symptomatic infection, and level of virus genomic surveillance should be adjusted in order to account for the increasing prevalence of the Delta variant worldwide.

Plasma cell-free DNA promise disease monitoring and tissue injury assessment of COVID-19 (preprint)

COVID-19 is a huge threat to global health. Due to the lack of definitive etiological therapeutics currently, effective disease monitoring is of high clinical value for better healthcare and management of the large number of COVID-19 patients. In this study, we recruited 37 COVID-19 patients, collected 176 blood samples upon diagnosis and during treatment, and analyzed cell-free DNA (cfDNA) in these samples. We report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA characteristics reflect patient-specific physiological conditions during treatment. Further analysis on tissue origin tracing of cfDNA reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, we demonstrate the translational merit of cfDNA as valuable analyte for effective disease monitoring, as well as tissue injury assessment in COVID-19 patients.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant (preprint)

Summary We report the first local transmission of the SARS-CoV-2 Delta variant in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of the quarantined subjects indicated that the viral loads of Delta infections, when they first become PCR+, were on average ∼1000 times greater compared to A/B lineage infections during initial epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. We performed high-quality sequencing on samples from 126 individuals. Reliable epidemiological data meant that, for 111 transmission events, the donor and recipient cases were known. The estimated transmission bottleneck size was 1-3 virions with most minor intra-host single nucleotide variants (iSNVs) failing to transmit to the recipients. However, transmission heterogeneity of SARS-CoV-2 was also observed. The transmission of minor iSNVs resulted in at least 4 of the 30 substitutions identified in the outbreak, highlighting the contribution of intra-host variants to population level viral diversity during rapid spread. Disease control activities, such as the frequency of population testing, quarantine during pre-symptomatic infection, and level of virus genomic surveillance should be adjusted in order to account for the increasing prevalence of the Delta variant worldwide.