Immunogenicity and safety of heterologous mRNA-1273/MVC-COV1901 vaccination versus homologous mRNA1273 vaccination: A randomized, double-blind controlled study.

BACKGROUND/PURPOSE: MVC-COV1901 is a protein vaccine based on the same SARS-CoV-2 strain used in mRNA vaccine mRNA-1273. Data are lacking on immunogenicity and safety of MVC-COV1901 as heterologous boost for people already received one dose of mRNA-1273. METHODS: This is a randomized, double-blind trial that recruited adults aged 20-70 years who previously received a single dose of mRNA-1273 vaccine and were randomly assigned in a 1:1 ratio to receive a second dose with the homologous vaccine or protein-based MVC-COV1901 8-12 weeks after the first dose. The primary outcome was neutralizing antibody titers in terms of the geometric mean titer (GMT) 14 days after the second dose. Safety was assessed in all participants who received a dose of the study vaccine. The study is registered with ClinicalTrials.gov (NCT05079633). RESULTS: From September 30 to November 5, 2021, 144 participants were enrolled and randomly assigned to the MVC-COV1901 boost group (n = 72) or the mRNA-1273 boost group (n = 72). The neutralizing antibodies on Day 15 and the anti-SARS-CoV-2 IgG titers on Day 15 and 29 of homologous mRNA-1273 were significantly higher than those of heterologous mRNA-1273/MVC-COV1901. Cellular immune responses were comparable in both groups. However, adverse events were much more frequent after the mRNA-1273 boost than after the MVC-COV1901 boost. CONCLUSION: Our results show that heterologous boost with MVC-COV1901 yielded an inferior immunogenicity but significantly fewer adverse events, compared with homologous boost with mRNA-1273. In people experienced severe adverse events after prime dose of mRNA-1273, as well as in periods when the supply of mRNA-1273 is limited, MVC-COV1901 could serve as an acceptable alternative heterologous boost.

[Appropriate Use and Abuse of Sedative-Hypnotic Drugs].

The incidence of insomnia has been increasing in recent years. In addition, due to the impact of the COVID-19 pandemic, more and more people are experiencing a variety of insomniac problems, including having difficulty in sleep initation, waking up too early, and short sleep duration. Chronic insomnia may seriously affect patients' life and work, increase their risks of developing physical and mental illnesses, and cause crushing social and economic burdens. Sedative-hypnotics, including benzodiazepine agonists, melatonin receptor agonists, orexin receptor antagonists, and antidepressants with hypnotic effects, are widely used to treat most patients suffering from insomnia. However, there is the phenomenon of the non-medical use and abuse of sedative-hypnotic drugs, especially benzodiazepine receptor agonists. The abuse of sedative-hypnotic drugs may lead to mental and physical dependence, cognitive impairment, depression and anxiety, as well as an increased risks of falls and death. Therefore, drug regulatory authorities in China and other countries have issued relevant policies to reinforce regulation. Herein, we reviewed the prevalent use and safety of sedative-hypnotic drugs and proposed suggestions concerning their appropriate use. Both the efficacy and safety of sedative-hypnotic drugs should be carefully considered so that patients suffering from insomnia receive thorough and prompt treatment and the problem of potential abuse of sedative-hypnotic drugs is assessed in an objective and scientific manner. We also hope to provide references for the standardized clinical use of insomnia drugs.

Factors associated with viral rebound among COVID-19 patients receiving oral antivirals.

BACKGROUND: COVID-19 rebound is usually reported among patients experiencing concurrent symptomatic and viral rebound. But longitudinal viral RT-PCR results from early stage to rebound of COVID-19 was less characterized. Further, identifying the factors associated with viral rebound after nirmatrelvir-ritonavir (NMV/r) and molnupiravir may expand understanding of COVID-19 rebound. METHODS: We retrospectively analyzed clinical data and sequential viral RT-PCR results from COVID-19 patients receiving oral antivirals between April and May, 2022. Viral rebound was defined by the degree of viral load increase (ΔCt ≥ 5 units). RESULTS: A total of 58 and 27 COVID-19 patients taking NMV/r and molnupiravir, respectively, were enrolled. Patients receiving NMV/r were younger, had fewer risk factors for disease progression and faster viral clearance rate compared to those receiving molnupiravr (All P < 0.05). The overall proportion of viral rebound (n = 11) was 12.9%, which was more common among patients receiving NMV/r (10 [17.2%] vs. 1 [3.7%], P = 0.16). Of them, 5 patients experienced symptomatic rebound, suggesting the proportion of COVID-19 rebound was 5.9%. The median interval to viral rebound was 5.0 (interquartile range, 2.0-8.0) days after completion of antivirals. Initial lymphopenia (<0.8 × 109/L) was associated with viral rebound among overall population (adjusted odds ratio [aOR], 5.34; 95% confidence interval [CI], 1.33-21.71), and remained significant (aOR, 4.50; 95% CI, 1.05-19.25) even when patients receiving NMV/r were considered. CONCLUSION: Our data suggest viral rebound after oral antivirals may be more commonly observed among lymphopenic individuals in the context of SARS-CoV-2 Omicron BA.2 variant.

A Retrospective Study of the Safety and Immunogenicity of MVC-COV1901 Vaccine for People Living with HIV.

BACKGROUND: This study aimed to assess the safety and immunogenicity of MVC-COV1901, a recombinant COVID-19 protein vaccine, containing S-2P protein adjuvanted with CpG 1018 and aluminum hydroxide, for people living with HIV (PWH). METHODS: A total of 57 PWH of ≥20 years of age who are on stable antiretroviral therapy were compared with 882 HIV-negative participants. Participants received two doses of MVC-COV1901 28 days apart. RESULTS: No vaccine-related serious adverse events (SAEs) were recorded. Seroconversion rates (SCRs) of 100% and 99.8% were achieved in PWH and comparators, respectively, 28 days after the second dose. After adjusting for sex, age, BMI category, and comorbidity, the adjusted GMT ratio of comparator/PWH was 3.2 (95% CI 2.5-4). A higher CD4/CD8 ratio was associated with a higher GMT (R = 0.27, p = 0.039). MVC-COV1901 has shown robust safety but elicited weaker immune responses in PWH. CONCLUSIONS: Further investigations may be needed to determine whether PWH require distinct immunization strategies with improved immunogenicity. The main study is registered at ClinicalTrials.gov (NCT04695652).

Identification of Potential Key Genes and Prognostic Biomarkers of Lung Cancer Based on Bioinformatics.

Objective: To analyze and identify the core genes related to the expression and prognosis of lung cancer including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) by bioinformatics technology, with the aim of providing a reference for clinical treatment. Methods: Five sets of gene chips, GSE7670, GSE151102, GSE33532, GSE43458, and GSE19804, were obtained from the Gene Expression Omnibus (GEO) database. After using GEO2R to analyze the differentially expressed genes (DEGs) between lung cancer and normal tissues online, the common DEGs of the five sets of chips were obtained using a Venn online tool and imported into the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database for Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The protein-protein interaction (PPI) network was constructed by STRING online software for further study, and the core genes were determined by Cytoscape software and KEGG pathway enrichment analysis. The clustering heat map was drawn by Excel software to verify its accuracy. In addition, we used the University of Alabama at Birmingham Cancer (UALCAN) website to analyze the expression of core genes in P53 mutation status, confirmed the expression of crucial core genes in lung cancer tissues with Gene Expression Profiling Interactive Analysis (GEPIA) and GEPIA2 online software, and evaluated their prognostic value in lung cancer patients with the Kaplan-Meier online plotter tool. Results: CHEK1, CCNB1, CCNB2, and CDK1 were selected. The expression levels of these four genes in lung cancer tissues were significantly higher than those in normal tissues. Their increased expression was negatively correlated with lung cancer patients (including LUAD and LUSC) prognosis and survival rate. Conclusion: CHEK1, CCNB1, CCNB2, and CDK1 are the critical core genes of lung cancer and are highly expressed in lung cancer. They are negatively correlated with the prognosis of lung cancer patients (including LUAD and LUSC) and closely related to the formation and prediction of lung cancer. They are valuable predictors and may be predictive biomarkers of lung cancer.

Evolution of anti-SARS-CoV-2 spike protein titers after two-dose of COVID-19 vaccination among people living with HIV.

Background: A community COVID-19 outbreak caused by the B.1.1.7 SARS-CoV-2 variant occurred in Taiwan in May 2021. High-risk populations such as people living with HIV (PLWH) were recommended to receive two doses of COVID-19 vaccines. While SARS-CoV-2 vaccines have demonstrated promising results in general population, real-world information on the serological responses remains limited among PLWH. Methods: PLWH receiving the first dose of SARS-CoV-2 vaccine from 2020 to 2021 were enrolled. Determinations of anti-SARS-CoV-2 spike IgG titers were performed every one to three months, the third dose of the SARS-CoV-2 vaccine or confirmed SARS-CoV-2 infection. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from analysis. Results: A total of 1189 PLWH were enrolled: 829 (69.7%) receiving two doses of the AZD1222 vaccine, 232 (19.5%) of the mRNA-1273 vaccine, and 128 (10.8%) of the BNT162b2 vaccine. At all time-points, PLWH receiving two doses of mRNA vaccines had consistently higher antibody levels than those receiving the AZD1222 vaccine (p <0.001 for all time-point comparisons). Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/mL within 12 weeks, included type 2 diabetes mellitus (DM) (adjusted odds ratio [aOR], 2.24; 95% CI, 1.25-4), a CD4 T cell count <200 cells/mm3 upon receipt of the first dose of vaccination (aOR, 3.43; 95% CI, 1.31-9) and two homologous AZD1222 vaccinations (aOR, 16.85; 95%CI, 10.13-28). For those receiving two doses of mRNA vaccines, factors associated with failure to achieve an anti-spike IgG titer >899 BAU/mL within 12 weeks were a CD4 T cell count <200 cells/mm3 on first-dose vaccination (aOR, 3.95; 95% CI, 1.08-14.42) and dual BNT162b2 vaccination (aOR, 4.21; 95% CI, 2.57-6.89). Conclusions: Two doses of homologous mRNA vaccination achieved significantly higher serological responses than vaccination with AZD1222 among PLWH. Those with CD4 T cell counts <200 cells/mm3 and DM had consistently lower serological responses.

Impact of the initial wave of COVID-19 pandemic in Taiwan on local HIV services: Results from a cross-sectional online survey.

PURPOSE: This study aimed to investigate the impact of the initial wave of the COVID-19 pandemic on HIV services in Taiwan. METHODS: An online, cross-sectional survey was conducted among people living with HIV (PLWH), individuals at risk of HIV infection (IAR), and service prescribers between 20th October and 30th November, 2020. Representatives from patient advocacy groups were interviewed. RESULTS: In total, 66 PLWH, 104 IAR, and 32 prescribers from Taiwan completed the survey. Mild to moderate disruptions to HIV-related services (including medical consultation, HIV-related testing, and medications) were found by the survey, with IAR appearing more affected than PLWH. Nine (13.6%) PLWH and 31 (29.8%) IAR reported disruptions in hospital/clinic visits and two (3.0%) PLWH and 25 (24.0%) IAR reported decreased frequency of HIV testing. Similar observations were also made by four patient advocacy group representatives interviewed. Telehealth services were received by only limited proportions of PLWH and IAR who participated in the survey. CONCLUSION: HIV services in Taiwan were not severely affected by the initial wave of COVID-19, but notable disruptions were still observed in HIV screening and prevention services. Multi-pronged strategies, including telehealth services, are warranted to overcome new challenges in HIV care in the COVID-19 era.

Evolution of neutralizing antibodies and cross-activity against different variants of SARS-CoV-2 in patients recovering from COVID-19.

BACKGROUND: Patients recovering from COVID-19 may need vaccination against SARS-CoV-2 because acquired immunity from primary infection may wane, given the emergence of new SARS-CoV-2 variants. Understanding the trends of anti-spike IgG and neutralizing antibody titers in patients recovering from COVID-19 may inform the decision made on the appropriate interval between recovery and vaccination. METHODS: Participants aged 20 years or older and diagnosed with COVID-19 between January and December, 2020 were enrolled. Serum specimens were collected every three months from 10 days to 12 months after the onset of symptom for determinations of anti-spike IgG and neutralizing antibody titers against SARS-CoV-2 Wuhan strain with D614G mutation, alpha, gamma and delta variants. RESULTS: Of 19 participants, we found a decreasing trend of geometric mean titers of anti-spike IgG from 560.9 to 217 and 92 BAU/mL after a 4-month and a 7-month follow-up, respectively. The anti-spike IgG titers declined more quickly in the ten participants with severe or critical disease than the nine participants with only mild to moderate disease between one month and seven months after SARS-CoV-2 infection (-8.49 vs - 2.34-fold, p < 0.001). The neutralizing activity of the convalescent serum specimens collected from participants recovering from wild-type SARS-CoV-2 infection against different variants was lower, especially against the delta variants (p < 0.01 for each variant with Wuhan strain as reference). CONCLUSION: Acquired immunity from primary infection with SARS-CoV-2 waned within 4-7 months in COVID-19 patients, and neutralizing cross-activities against different SARS-CoV-2 variants were lower compared with those against wild-type strain.

Impact of coronavirus disease on the HIV testing and health care delivery at a university hospital in Taiwan, 2020-2021

Background To contain the coronavirus disease 2019 (Covid-19) pandemic, non-pharmacologic interventions, including lockdown and social distancing, may have adverse impact on access to HIV testing and care. This study investigated the impact of Covid-19 on HIV testing and care at a major hospital in Taiwan in 2020-2021. Methods The numbers of clients seeking anonymous HIV voluntary counseling and testing were compared 2 years before (2018-2019) and 2 years after Covid-19 outbreak (2020-2021). People living with HIV (PLWH) who sought care at the hospital during 2018-2021 were included to examine the status of HIV care delivery and disposition. Results The annual number of HIV screening tests performed had significantly decreased from 2,507 and 2,794 in 2018 and 2019, respectively, to 2,161 and 1,737 in 2020 and 2021, respectively. The rate of discontinuation of HIV care among PLWH was 3.7% in 2019, which remained unchanged in 2020 (3.7%) and 2021 (3.8%). The respective percentage of annual plasma HIV RNA testing <2 times increased from 8.4% and 7.8% in 2018 and 2019 to 7.0% and 10.7% in 2020 and 2021, so was that of annual syphilis testing <2 times (10.1% and 8.8% to 7.9% and 12.0%). The rates of plasma HIV RNA <200 copies/ml ranged from 97.0% to 98.1% in 2018-2021. Conclusions During the Covid-19 pandemic, access to HIV counseling and testing was significantly limited. While the number of HIV-related testing decreased, the impact of Covid-19 on the continuity of antiretroviral therapy and viral suppression among PLWH appeared to be minimal in Taiwan.

Hepatitis C microelimination among people living with HIV in Taiwan.

To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39-7.12%) in 2018 to 2.09% (95% CI, 1.60-2.77%) in 2021 (decline by 66.4% [95% CI, 55.4-74.7%]); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44-32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14-17.44) (decline by 53.2% [95% CI, 27.3-70.6%]). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.

Effectiveness of COVID-19 vaccination among people living with HIV during a COVID-19 outbreak.

COVID-19 vaccination is recommended for at-risk populations, but the vaccine effectiveness in people living with HIV (PLWH) remains incompletely understood. Here we demonstrate that COVID-19 vaccination was clinically effective among PLWH during the outbreak setting with a low endemicity of COVID-19 where non-pharmaceutical interventions were strictly implemented.

Impact of the Initial Wave of COVID-19 Pandemic in Taiwan on Local HIV Services: Results from a Cross-Sectional Online Survey

Purpose This study aimed to investigate the impact of the initial wave of the COVID-19 pandemic on HIV services in Taiwan. Methods An online, cross-sectional survey was conducted among people living with HIV (PLWH), individuals at risk of HIV infection (IAR), and service prescribers between 20th October and 30th November, 2020. Representatives from patient advocacy groups were interviewed. Results In total, 66 PLWH, 104 IAR, and 32 prescribers from Taiwan completed the survey. Mild to moderate disruptions to HIV-related services (including medical consultation, HIV-related testing, and medications) were found by the survey, with IAR appearing more affected than PLWH. Nine (13.6%) PLWH and 31 (29.8%) IAR reported disruptions in hospital/clinic visits and two (3.0%) PLWH and 25 (24.0%) IAR reported decreased frequency of HIV testing. Similar observations were also made by four patient advocacy group representatives interviewed. Telehealth services were received by only limited proportions of PLWH and IAR who participated in the survey. Conclusion HIV services in Taiwan were not severely affected by the initial wave of COVID-19, but notable disruptions were still observed in HIV screening and prevention services. Multi-pronged strategies, including telehealth services, are warranted to overcome new challenges in HIV care in the COVID-19 era.

Treatment efficacy of Lianhua Qingwen capsules for eraly-stage COVID-19

Objective: To systematically determine the effect of Lianhua Qingwen Capsules on the early antiviral and anti-inflammatory action against COVID-19 (Coronavirus 2019) and its applicational value in the treatment of COVID-19. Methods: The clinical data of 66 early-mid-stage COVID-19 patients admitted to hospitals in Guangzhou between January 2020 and April 2020 were retrospectively analyzed. The patients receiving Lianhua Qingwen Capsule treatment were assigned to the observation group (n=33) and those given conventional therapy were included in the control group (n=33). The two groups were compared in terms of clinical effects and main symptom (fever, cough and fatigue) disappearance rate. Results: In comparison with the control group, 1) the total effective rate was significantly higher in the observation group (P<0.05);2) the disappearance rates of fever, cough and fatigue were statistically higher in the observation group;3) the treatment time was significantly shorter and patient recovery was significantly better in the observation group;4) the laboratory index levels [white blood cell (WBC), interleukin-6 (IL-6), serum amyloid A (SAA)] were better in the observation group. Conclusion: Lianhua Qingwen Capsules can significantly improve the total effective rate for COVID-19 patients, as well as shorten the hospital stay and treatment time, which is worth of promotion in the clinic.

An acceptable methodological evaluation method of real-time fluorescent RT-PCR targeting SARS-CoV-2 (preprint)

Background: it is necessary to evaluate real-time fluorescent reverse-transcription PCR (RT-PCR) methods to detect the nucleic acids of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: considering lack of positive specimens in some particular locations in China, the specimens from healthy individuals were used to perform the methodology evaluations, in which the indexes were the differences of quantification cycle values (ΔCq) between human-derived internal reference control (IRC) genes of a specimen and quality control gene (QC). A series of experiments was conducted to evaluate various factors that might affect the results, such as types of virus transport media, methods of specimen pretreatment and template preparation, specimen vortex strength, specimen storage temperature, and duration. Results: it was better to store specimens in normal saline (NS) transport medium, release more virus particles from swabs by vortex mixing, extract nucleic acids with centrifugation methods, and perform amplification assays timely. The above-mentioned options and optimum conditions were further confirmed using SARS-CoV-2 pseudoviruses and positive clinical specimens. Conclusions: this study provides a solution for the accurate detection of SARS-CoV-2. Specifically, this study also indicates that the routine specimens from healthy individuals could be used to methodological evaluation of real-time fluorescent RT-PCR targeting SARS-CoV-2, of which the indexes were the ΔCq values.

Exploring the Potential Targets and Mechanisms of Huang Lian Jie Du Decoction in the Treatment of Coronavirus Disease 2019 Based on Network Pharmacology.

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) caused by a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2; previously known as 2019-nCoV) emerged in Wuhan, China, and caused many infections and deaths. At present, there are no specific drugs for the etiology and treatment of COVID-19. A combination of traditional Chinese and western medicine is proposed to treat COVID-19, in which Huang Lian Jie Du decoction (HLJDD) is recommended for the treatment of COVID-19 in many provinces in China and has been widely used in the clinic. This study explored the potential targets of HLJDD in the treatment of COVID-19 based on network pharmacology. METHODS: First, the chemical composition and targets of HLJDD and COVID-19-related targets were obtained through the TCMSP, UniProt, GeneCards and OMIM databases. Second, HLJDD target and HLJDD-COVID-19 target networks were constructed via the STRING database and Cytoscape software. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the HLJDD-COVID-19 targets was applied via the DAVID database. RESULTS: Our study identified a total of 67 active ingredients of HLJDD and 204 targets of HLJDD. A total of 502 COVID-19-related targets were obtained, of which 47 were intersecting targets of HLJDD and COVID-19. A total of 179 GO terms and 77 KEGG terms, including the TNF signaling pathway, NF-κB signaling pathway and HIF-1 signaling pathway, were identified. CONCLUSION: The present study explored the potential targets and signaling pathways of HLJDD during the treatment of COVID-19, which may provide a basis for the research and development of drugs for the treatment of COVID-19.

Safety and immunogenicity of a Recombinant Stabilized Prefusion SARS-CoV-2 Spike Protein Vaccine (MVC-COV1901) Adjuvanted with CpG 1018 and Aluminum Hydroxide in healthy adults: A Phase 1, dose-escalation study.

BACKGROUND: This was a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC-COV1901, a SARS-CoV-2 S-2P protein vaccine adjuvanted with aluminum hydroxide and CpG 1018. METHODS: Between September 28 and November 13 2020, 77 participants were screened. Of these, 45 healthy adults from 20 to 49 years of age were to be administered two doses of MVC-COV1901 in doses of 5 µg, 15 µg, or 25 µg of spike protein at 28 days apart. There were 15 participants in each dose group; all were followed for 28 days after the second dose at the time of the interim analysis. Adverse events and laboratory data were recorded for the safety evaluation. Blood samples were collected for humoral, and cellular immune response at various time points. Trial Registration: ClinicalTrials.gov NCT04487210. FINDINGS: Solicited adverse events were mostly mild and similar. No subject experienced fever. After the second dose, the geometric mean titers (GMTs) for SARS-CoV-2 spike-specific immunoglobulin G were 7178.2, 7746.1, 11,220.6 in the 5 µg, 15 µg, and 25 µg dose groups, respectively. The neutralizing activity were detected in both methods. (Day 43 GMTs, 538.5, 993.1, and 1905.8 for pseudovirus; and 33.3, 76.3, and 167.4 for wild-type virus). The cellular immune response induced by MVC-COV1901 demonstrated substantially higher numbers of IFN-γ- producing cells, suggesting a Th1-skewed immune response. INTERPRETATION: The MVC-COV1901 vaccine was well tolerated and elicited robust immune responses and is suitable for further development. FUNDING: Medigen Vaccine Biologics Corporation.

Evolution of SARS-CoV-2 neutralizing antibody in an HIV-positive patient with COVID-19.

We presented the clinical course and immune responses of a well-controlled HIV-positive patient with COVID-19. The clinical presentation and antibody production to SARS-CoV-2 were similar to other COVID-19 patients without HIV infection. Neutralizing antibody reached a plateau from 26th to 47th day onset but decreased on 157th day after symptoms.

A Tale of Two Countries: A Longitudinal Cross-Country Study of Mobile Users' Reactions to the COVID-19 Pandemic Through the Lens of App Popularity (preprint)

The ongoing COVID-19 pandemic has profoundly impacted people's life around the world, including how they interact with mobile technologies. In this paper, we seek to develop an understanding of how the dynamic trajectory of a pandemic shapes mobile phone users' experiences. Through the lens of app popularity, we approach this goal from a cross-country perspective. We compile a dataset consisting of six-month daily snapshots of the most popular apps in the iOS App Store in China and the US, where the pandemic has exhibited distinct trajectories. Using this longitudinal dataset, our analysis provides detailed patterns of app ranking during the pandemic at both category and individual app levels. We reveal that app categories' rankings are correlated with the pandemic, contingent upon country-specific development trajectories. Our work offers rich insights into how the COVID-19, a typical global public health crisis, has influence people's day-to-day interaction with the Internet and mobile technologies.

Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13.

Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.