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1.
Open Forum Infect Dis ; 9(6): ofab356, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1883039

ABSTRACT

[This corrects the article DOI: 10.1093/ofid/ofaa442.].

2.
Archives of Virology ; 165(3):703-707, 2020.
Article in English | ProQuest Central | ID: covidwho-1877434

ABSTRACT

Using viral metagenomics, the complete genome sequence of an infectious bronchitis virus (IBV) strain (named ahysx-1) from a fecal sample from a healthy chicken in Anhui province, China, was determined. The genome sequence of ahysx-1 was found to be very similar to that of IBV strain ck/CH/LLN/131040 (KX252787), except for the spike gene region, which is similar to that of a turkey coronavirus strain (EU022526), suggesting that ahysx-1 is a recombinant. Recombination analysis and phylogenetic analysis based on the genomic sequences of ahysx-1 and other related strains confirmed that ahysx-1 appears to be a recombinant resulting from a recombination event that occurred between a chicken coronavirus and a turkey coronavirus. Further studies need to be performed to determine whether this recombinant IBV strain is pathogenic and whether it is transmitted between chickens and turkeys.

3.
Frontiers in cardiovascular medicine ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1877094

ABSTRACT

Background Heart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly via direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms. Methods We investigated the following mechanisms: (1) the QTc duration in patients with COVID-19 during the active phase and recovery, and its association with C-reactive protein (CRP) and IL-6 levels;(2) the acute impact of IL-6 administration on QTc in an in vivo guinea pig model;and (3) the electrophysiological effects of IL-6 on ventricular myocytes in vitro. Results In patients with active severe COVID-19 and elevated IL-6 levels, regardless of acute myocardial injury/strain and concomitant QT-prolonging risk factors, QTc was significantly prolonged and rapidly normalized in correlation with IL-6 decrease. The direct administration of IL-6 in an in vivo guinea pig model acutely prolongs QTc duration. Moreover, ventricular myocytes incubated in vitro with IL-6 show evident prolongation in the action potential, along with significant inhibition in the rapid delayed rectifier potassium current (IKr). Conclusion For the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies.

4.
Nature Communications ; 13(1), 2022.
Article in English | ProQuest Central | ID: covidwho-1876946

ABSTRACT

Non-pharmaceutical interventions (NPIs) and vaccination are two fundamental approaches for mitigating the coronavirus disease 2019 (COVID-19) pandemic. However, the real-world impact of NPIs versus vaccination, or a combination of both, on COVID-19 remains uncertain. To address this, we built a Bayesian inference model to assess the changing effect of NPIs and vaccination on reducing COVID-19 transmission, based on a large-scale dataset including epidemiological parameters, virus variants, vaccines, and climate factors in Europe from August 2020 to October 2021. We found that (1) the combined effect of NPIs and vaccination resulted in a 53% (95% confidence interval: 42–62%) reduction in reproduction number by October 2021, whereas NPIs and vaccination reduced the transmission by 35% and 38%, respectively;(2) compared with vaccination, the change of NPI effect was less sensitive to emerging variants;(3) the relative effect of NPIs declined 12% from May 2021 due to a lower stringency and the introduction of vaccination strategies. Our results demonstrate that NPIs were complementary to vaccination in an effort to reduce COVID-19 transmission, and the relaxation of NPIs might depend on vaccination rates, control targets, and vaccine effectiveness concerning extant and emerging variants.Non-pharmaceutical interventions (NPIs) and COVID-19 vaccination have been implemented concurrently, making their relative effects difficult to measure. Here, the authors show that effects of NPIs reduced as vaccine coverage increased, but that NPIs could still be important in the context of more transmissible variants.

5.
Aging (Albany NY) ; 14(10): 4211-4219, 2022 May 18.
Article in English | MEDLINE | ID: covidwho-1856446

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading around the world. The COVID-19 vaccines may improve concerns about the pandemic. However, the roles of inactivated vaccines in older patients (aged ≥60 years) with infection of Delta variant were less studied. METHODS: We classified the older patients with infection of Delta variant into three groups based on the vaccination status: no vaccination (group A, n = 113), one dose of vaccination (group B, n = 46), and two doses of vaccination (group C, n = 22). Two inactivated COVID-19 vaccines (BBIBP-CorV or CoronaVac) were evaluated in this study. The demographic data, laboratory parameters, and clinical severity were recorded. RESULTS: A total of 181 older patients with infection of Delta variant were enrolled. 111 (61.3%) patients had one or more co-morbidities. The days of "turn negative" and hospital stay in Group C were lower than those in the other groups (P < 0.05). The incidences of multiple organ dysfunction syndrome (MODS), septic shock, acute respiratory distress syndrome (ARDS), acute kidney injury, and cardiac injury in Group A were higher than those in the other groups (P < 0.05). The MV-free days and ICU-free days during 28 days in Group A were also lower than those in the other groups (P < 0.05). In patients with co-morbidities, vaccinated cases had lower incidences of MODS (P = 0.015), septic shock (P = 0.015), and ARDS (P = 0.008). CONCLUSIONS: The inactivated COVID-19 vaccines were effective in improving the clinical severity of older patients with infection of Delta variant.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Shock, Septic , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , China/epidemiology , Humans , Multiple Organ Failure , SARS-CoV-2 , Vaccines, Inactivated
6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335494

ABSTRACT

Recent emergence of SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.2.13, BA.4 and BA.5 all contain L452 mutations and show potential higher transmissibility over BA.2. The new variants’ receptor binding and immune evasion capability require immediate investigation, especially on the role of L452 substitutions. Herein, coupled with structural comparisons, we showed that BA.2 sublineages, including BA.2.12.1 and BA.2.13, exhibit increased ACE2-binding affinities compared to BA.1;while BA.4/BA.5 shows the weakest receptor-binding activity due to F486V and R493Q reversion. Importantly, compared to BA.2, BA.2.12.1 and BA.4/BA.5 exhibit stronger neutralization escape from the plasma of 3-dose vaccinees and, most strikingly, from vaccinated BA.1 convalescents. To delineate the underlying evasion mechanism, we determined the escaping mutation profiles, epitope distribution and Omicron sub-lineage neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory and elicits antibodies that neutralize both wild-type and BA.1. These cross-reactive NAbs are significantly enriched on non-ACE2-competing epitopes;and surprisingly, the majority are undermined by R346 and L452 substitutions, namely R346K (BA.1.1), L452M (BA.2.13), L452Q (BA.2.12.1) and L452R (BA.4/BA.5), suggesting that R346K and L452 mutations appeared under the immune pressure of Omicron convalescents. Nevertheless, BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1 but do not respond to wild-type SARS-CoV-2, due to the high susceptibility to N501, N440, K417 and E484. However, these NAbs are largely escaped by BA.2 sublineages and BA.4/BA.5 due to D405N and F486V, exhibiting poor neutralization breadths. As for therapeutic NAbs, LY-CoV1404 (Bamlanivimab) and COV2-2130 (Cilgavimab) can still effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations carried by BA.2/BA.4/BA.5 sublineages would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron can evolve mutations to specifically evade humoral immunity elicited by BA.1 infection. The continuous evolution of Omicron poses great challenges to SARS-CoV-2 herd immunity and suggests that BA.1-derived vaccine boosters may not be ideal for achieving broad-spectrum protection.

7.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335258

ABSTRACT

The recently emerged SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.2.13, BA.4 and BA.5 all contain L452 mutations and show potential higher transmissibility over BA.2 1 . The new variants’ receptor binding and immune evasion capability require immediate investigation, especially on the role of L452 substitutions. Herein, coupled with structural comparisons, we show that BA.2 sublineages, including BA.2.12.1 and BA.2.13, exhibit increased ACE2-binding affinities compared to BA.1;while BA.4/BA.5 displays the weakest receptor-binding activity due to F486V and R493Q reversion. Importantly, compared to BA.2, BA.2.12.1 and BA.4/BA.5 exhibit stronger neutralization evasion against the plasma of 3-dose vaccinees and, most strikingly, of vaccinated BA.1 convalescents. To delineate the underlying evasion mechanism, we determined the escaping mutation profiles 2 , epitope distribution 3 and Omicron sublineage neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype (WT) induced humoral memory and elicits antibodies that neutralize both WT and BA.1. These cross-reactive NAbs are significantly enriched on non-ACE2-competing epitopes;and surprisingly, the majority are undermined by R346 and L452 substitutions, namely R346K (BA.1.1), L452M (BA.2.13), L452Q (BA.2.12.1) and L452R (BA.4/BA.5), suggesting that R346K and L452 mutations appeared under the immune pressure induced by Omicron convalescents. Nevertheless, BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1 but do not respond to WT SARS-CoV-2 due to the high susceptibility to N501, N440, K417 and E484. However, these NAbs are largely escaped by BA.2 sublineages and BA.4/BA.5 due to D405N and F486V, exhibiting poor neutralization breadths. As for therapeutic NAbs, LY-CoV1404 (Bebtelovimab 4 ) and COV2-2130 (Cilgavimab 5 ) can still effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations carried by BA.2/BA.4/BA.5 sublineages would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron can evolve mutations to specifically evade humoral immunity elicited by BA.1 infection. The continuous evolution of Omicron poses great challenges to SARS-CoV-2 herd immunity and suggests that BA.1-derived vaccine boosters may not be ideal for achieving broad-spectrum protection.

8.
J Virol ; 96(10): e0007022, 2022 05 25.
Article in English | MEDLINE | ID: covidwho-1832352

ABSTRACT

In global infection and serious morbidity and mortality, porcine epidemic diarrhea virus (PEDV) has been regarded as a dreadful porcine pathogen, but the existing commercial vaccines are not enough to fully protect against the epidemic strains. Therefore, it is of great necessity to feature the PEDV-host interaction and develop efficient countermeasures against viral infection. As an RNA/DNA protein, the trans-active response DNA binding protein (TARDBP) plays a variety of functions in generating and processing RNA, including transcription, splicing, transport, and mRNA stability, which have been reported to regulate viral replication. The current work aimed to detect whether and how TARDBP influences PEDV replication. Our data demonstrated that PEDV replication was significantly suppressed by TARDBP, regulated by KLF16, which targeted its promoter. We observed that through the proteasomal and autophagic degradation pathway, TARDBP inhibited PEDV replication via the binding as well as degradation of PEDV-encoded nucleocapsid (N) protein. Moreover, we found that TARDBP promoted autophagic degradation of N protein via interacting with MARCHF8, an E3 ubiquitin ligase, as well as NDP52, a cargo receptor. We also showed that TARDBP promoted host antiviral innate immune response by inducing interferon (IFN) expression through the MyD88-TRAF3-IRF3 pathway during PEDV infection. In conclusion, these data revealed a new antiviral role of TARDBP, effectively suppressing PEDV replication through degrading virus N protein via the proteasomal and autophagic degradation pathway and activating type I IFN signaling via upregulating the expression of MyD88. IMPORTANCE PEDV refers to the highly contagious enteric coronavirus that has quickly spread globally and generated substantial financial damage to the global swine industry. During virus infection, the host regulates the innate immunity and autophagy process to inhibit virus infection. However, the virus has evolved plenty of strategies with the purpose of limiting IFN-I production and autophagy processes. Here, we identified that TARDBP expression was downregulated via the transcription factor KLF16 during PEDV infection. TARDBP could inhibit PEDV replication through the combination as well as degradation of PEDV-encoded nucleocapsid (N) protein via proteasomal and autophagic degradation pathways and promoted host antiviral innate immune response by inducing IFN expression through the MyD88-TRAF3-IRF3 pathway. In sum, our data identify a novel antiviral function of TARDBP and provide a better grasp of the innate immune response and protein degradation pathway against PEDV infection.


Subject(s)
Coronavirus Infections , DNA-Binding Proteins , Interferon Type I , Porcine epidemic diarrhea virus , Virus Replication , Animals , Coronavirus Infections/veterinary , DNA-Binding Proteins/metabolism , Immunity, Innate , Interferon Regulatory Factor-3/metabolism , Interferon Type I/metabolism , Myeloid Differentiation Factor 88/metabolism , Nucleocapsid Proteins/metabolism , Porcine epidemic diarrhea virus/genetics , Porcine epidemic diarrhea virus/physiology , RNA/metabolism , Signal Transduction , Swine , TNF Receptor-Associated Factor 3/metabolism
9.
Chin J Integr Med ; 2022 May 04.
Article in English | MEDLINE | ID: covidwho-1820982

ABSTRACT

OBJECTIVE: To evaluate the effectiveness and safety of Baidu Jieduan Granules (BDJDG) to treat common type coronavirus disease 2019 (COVID-19). METHODS: This multicenter, retrospective, and observational clinical trial included 230 common COVID-19 patients in Leishenshan, Huangshi, and Laohekou Hospitals in Wuhan from January 21 to March 26, 2020. The included patients were further divided into two subgroups according to the use of supplemental oxygen, mild and moderate groups. During the first 14 d of hospitalization, all patients were administered BDJDG combined with conventional Western medicine, and observed for continuous 28 d. Primary outcomes were disease progression rate and discharge rate. Secondary outcomes included negative conversion time of nucleic acid, hospitalization duration, clinical symptom subsidence time, and symptom regression rate. RESULTS: A total of 230 common COVID-19 patients were analyzed (138 in moderate group and 92 in mild group). By day 28, the disease progression rate was 4.3% and the discharge rate was 95.7%. All mild cases recovered and were discharged from hospital. The median negative conversion time of nucleic acid of all 230 COVID-19 patients was 12 d [inter-quartile range (IQR) 3.5-17], the median hospitalization duration was 15 d (IQR 12-20). The median time to fever, cough, and fatigue recovery was 4 d (IQR 2-6), 8 d (IQR 5-12), and 8 d (IQR 5-11). The recovery rate of fever, cough, and fatigue was 94.6%, 90.5%, and 93.5%. The median time to clinical improvement was 12 d (IQR 10-17). Compared with the baseline, total leukocyte counts, neutrophil counts, lymphocyte counts, and platelet counts were increased significantly on days 7 and 14 (P<0.01). C-reactive protein markedly increased on day 3 and significantly decreased on days 7 and 14 (P<0.01). No serious adverse events occurred during treatment. CONCLUSION: BDJDG may be effective and safe for treatment of common type COVID-19. (Registration No. ChiCTR2000030836).

10.
Clin Immunol ; 239: 109022, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1803761

ABSTRACT

In March 2020, when coronavirus disease 2019 (COVID-19) was just beginning to spread around the world, we presented the potential benefits and controversies of anti-inflammatory therapy in COVID-19 patients based on the limited experience and proposed some types of anti-inflammatory drugs with potential therapeutic value, while without evidence-based data. In the past one more year, many clinical trials or real-world studies have been performed, either confirm or deny the efficacy of certain anti-inflammatory drugs in the treatment of COVID-19. In this review we summarize the progress of anti-inflammatory and immune therapy in COVID-19, including glucocorticoids, IL-6 antagonist, IL-1 inhibitor, kinase inhibitors, non-steroidal anti-inflammatory drugs and chloroquine/hydroxychloroquine.


Subject(s)
COVID-19 , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Chloroquine/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2
11.
Microbiome ; 10(1): 60, 2022 04 12.
Article in English | MEDLINE | ID: covidwho-1789144

ABSTRACT

BACKGROUND: Wild birds may harbor and transmit viruses that are potentially pathogenic to humans, domestic animals, and other wildlife. RESULTS: Using the viral metagenomic approach, we investigated the virome of cloacal swab specimens collected from 3182 birds (the majority of them wild species) consisting of > 87 different species in 10 different orders within the Aves classes. The virus diversity in wild birds was higher than that in breeding birds. We acquired 707 viral genomes from 18 defined families and 4 unclassified virus groups, with 265 virus genomes sharing < 60% protein sequence identities with their best matches in GenBank comprising new virus families, genera, or species. RNA viruses containing the conserved RdRp domain with no phylogenetic affinity to currently defined virus families existed in different bird species. Genomes of the astrovirus, picornavirus, coronavirus, calicivirus, parvovirus, circovirus, retrovirus, and adenovirus families which include known avian pathogens were fully characterized. Putative cross-species transmissions were observed with viruses in wild birds showing > 95% amino acid sequence identity to previously reported viruses in domestic poultry. Genomic recombination was observed for some genomes showing discordant phylogenies based on structural and non-structural regions. Mapping the next-generation sequencing (NGS) data respectively against the 707 genomes revealed that these viruses showed distribution pattern differences among birds with different habitats (breeding or wild), orders, and sampling sites but no significant differences between birds with different behavioral features (migratory and resident). CONCLUSIONS: The existence of a highly diverse virome highlights the challenges in elucidating the evolution, etiology, and ecology of viruses in wild birds. Video Abstract.


Subject(s)
RNA Viruses , Viruses , Animals , Animals, Wild , Birds , Cloaca , Phylogeny , RNA Viruses/genetics , Virome/genetics , Viruses/genetics
12.
Environ Sci Pollut Res Int ; 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1782915

ABSTRACT

Because of global lock-downs caused by the unexpected COVID-19, the interactions between emission trading and related markets have changed significantly compared to the pre-COVID-19 period. Considering the pandemic effect, this paper established an integrated system to identify the relationship trajectories between carbon trading market and impact factors. A noise-assisted multivariate empirical mode decomposition (N-A MEMD) method was utilized to simultaneously decompose the original multi-dimensional time series into intrinsic mode functions (IMFs), after which the Lempel-Ziv (LZ) complexity algorithm was applied to reconstruct the IMFs into high-frequency (HF), low-frequency (LF), and trend modules. Vector autoregression (VAR) and vector error correction (VEC) models were then used to systematically simulate the correlations. The time span was split into pre-COVID-19 and post-COVID-19 periods for comparison, and the mobility trends data during the outbreak period released by the Apple company was chosen to reflect the pandemic effects. The empirical analysis results revealed the energy prices, macroeconomic index, and exchange rate are the main external impact factors of carbon price in the short term. Summarizing from the cointegration models over the long term, the market stability reserve (MSR) mechanism was found to have ability on stabilizing the carbon price under the epidemic shock. Furthermore, the COVID-19 was found to complicate the relationships between carbon price and influence factors, which resulted in fluctuating markets.

13.
Transbound Emerg Dis ; 2022 Apr 02.
Article in English | MEDLINE | ID: covidwho-1774901

ABSTRACT

The ongoing enzootic circulation of the Middle East respiratory syndrome coronavirus (MERS-CoV) in the Middle East and North Africa is increasingly raising the concern about the possibility of its recombination with other human-adapted coronaviruses, particularly the pandemic SARS-CoV-2. We aim to provide an updated picture about ecological niches of MERS-CoV and associated socio-environmental drivers. Based on 356 confirmed MERS cases with animal contact reported to the WHO and 63 records of animal infections collected from the literature as of 30 May 2020, we assessed ecological niches of MERS-CoV using an ensemble model integrating three machine learning algorithms. With a high predictive accuracy (area under receiver operating characteristic curve = 91.66% in test data), the ensemble model estimated that ecologically suitable areas span over the Middle East, South Asia and the whole North Africa, much wider than the range of reported locally infected MERS cases and test-positive animal samples. Ecological suitability for MERS-CoV was significantly associated with high levels of bareland coverage (relative contribution = 30.06%), population density (7.28%), average temperature (6.48%) and camel density (6.20%). Future surveillance and intervention programs should target the high-risk populations and regions informed by updated quantitative analyses.

14.
Biosens Bioelectron ; 209: 114226, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1767929

ABSTRACT

Protein sensors based on allosteric enzymes responding to target binding with rapid changes in enzymatic activity are potential tools for homogeneous assays. However, a high signal-to-noise ratio (S/N) is difficult to achieve in their construction. A high S/N is critical to discriminate signals from the background, a phenomenon that might largely vary among serum samples from different individuals. Herein, based on the modularized luciferase NanoLuc, we designed a novel biosensor called NanoSwitch. This sensor allows direct detection of antibodies in 1 µl serum in 45 min without washing steps. In the detection of Flag and HA antibodies, NanoSwitches respond to antibodies with S/N ratios of 33-fold and 42-fold, respectively. Further, we constructed a NanoSwitch for detecting SARS-CoV-2-specific antibodies, which showed over 200-fold S/N in serum samples. High S/N was achieved by a new working model, combining the turn-off of the sensor with human serum albumin and turn-on with a specific antibody. Also, we constructed NanoSwitches for detecting antibodies against the core protein of hepatitis C virus (HCV) and gp41 of the human immunodeficiency virus (HIV). Interestingly, these sensors demonstrated a high S/N and good performance in the assays of clinical samples; this was partly attributed to the combination of off-and-on models. In summary, we provide a novel type of protein sensor and a working model that potentially guides new sensor design with better performance.


Subject(s)
Biosensing Techniques , COVID-19 , Antibodies, Viral , COVID-19/diagnosis , Humans , Luciferases , SARS-CoV-2
15.
International Journal of Financial Engineering ; 9(1), 2022.
Article in English | ProQuest Central | ID: covidwho-1765139

ABSTRACT

In this paper, we use the permutation entropy algorithm to derive the static and dynamic permutation entropy of commodity futures, and to evaluate the effectiveness of main products in China’s commodity futures market. The intraday data of six varieties belonging to six categories in China’s commodity futures market are taken as samples. We find the following: (1) The return distribution of the main varieties shows high peaks, fat tails and asymmetry, and follows the biased random walk distribution characteristics;(2) The permutation entropy of all varieties decreases significantly in the same time window, during which the price volatility of major commodity markets rises. And the time window coincides with the impact time of COVID-19 epidemic;(3) By comparing the distribution of permutation entropy of main varieties in different stages of event shock, we found that the mean value of permutation entropy decreases significantly during the process of event shock, and the price fluctuates greatly. Therefore, the significant decrease of permutation entropy is a valuable warning signal for regulators and investors.

16.
Acta Pharmacol Sin ; 2022 Mar 16.
Article in English | MEDLINE | ID: covidwho-1747246

ABSTRACT

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo were administered per protocol requirements. Blood samples were collected at the scheduled time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in plasma and calculated for the PK parameters. In SAD, AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25-800 mg. T1/2 was within 4.80-6.95 h. In MAD, the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect on Cmax and AUC of VV116. No serious adverse event occurred in the studies, and no subject withdrew from the studies due to adverse events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which supports the continued investigation of VV116 in patients with COVID-19.

17.
Sustainability ; 14(5):2609, 2022.
Article in English | ProQuest Central | ID: covidwho-1742640

ABSTRACT

The ways people use words online can furnish psychological processes about their beliefs, fears, thinking patterns, and so on. Extracting from online employees’ reviews on the workplace community websites, we can quantify the psychological effects of employees during the phase of the COVID-19 pandemic. We collect the anonymous employees’ reviews of Top 100 digital companies from the Glassdoor website which allows people to evaluate and review the companies they have worked for or are working for. Here, based on the data of numerical evaluations and textual reviews, we firstly use Z-score to investigate the psychological effects of employees in digital companies during the phase of COVID-19 pandemic. Next, we use a text analysis application called Linguistic Inquiry and Word Count (LIWC), which provides an efficient and effective method for studying the various emotional, cognitive, and structural components existing in individuals’ verbal and written speech samples, to mine these reviews to obtain changes in personal pronouns and 10 dimensions of psychological processes. Finally, we use Z-score to count on all aspects of drives and personal concerns in psychological processes.

18.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329931

ABSTRACT

Background: Home isolation is a generally effective strategy for coronavirus disease control during lockdown periods. This study is to determine the potential adverse consequences of home isolation to mental health among school-aged youth after lifting of major lockdown measures in central China. Methods: : This cohort study assessed the mental health of school-aged children and adolescents enrolled in Wuhan city and nearby areas in Hubei province, China, from July 1 to August 31, 2020. Post-lockdown responses to anxiety, depression, sleep disturbances and post-traumatic stress symptoms were assessed in online questionnaire-based surveys. Participants’ scores for the Zung self-rated anxiety scale, the Patient Health Questionnaire-9, the self-rating scale of sleep and the post-traumatic stress disorder self-rating scale (PTSS) were analyzed. Results: : Questionnaire responses of 730 school children were collected. Among the participants, 6.25% of them had scores above thresholds for PTSS, 5.81% had anxiety, and 48.84% had depression. All subjects reported that they experienced sleep disturbances. Subjects who had anxiety might have a high risk for developing depression [OR: 16.07, p =0.008, 95%CI (2.08-123.94)] and PTSS [OR: 12.97, p <0.001, 95%CI (5.41-31.11)]. Both depression [OR: 17.35, p =0.006, 95%CI (2.28-131.87)] and PTSS [OR: 14.18, p <0.001, 95%CI (6.00-33.47)] were risk factors for developing anxiety among participants. Interestingly, higher educational levels of primary caregivers were a risk factor for developing depression [OR: 1.62, p =0.005, 95%CI (1.16-2.28)] in the participants, but a protective factor against PTSS [OR: 0.47, p =0.048, 95%CI (0.23-0.99)]. Conclusions: : The local youth had less than expected degree of increases in their self-reported PTSS and anxiety, after exiting lockdown-related isolation. As a result of a combination of compensatory mechanisms including internet-based home-schooling and increased intra-familial interactions, home isolation did not affect the mental health of local school-aged youth to an extent as great as expected. Trial registration: The Registration number of this trial is ChiCTR2000033054.

19.
Chin Med J (Engl) ; 133(9): 1039-1043, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722619

ABSTRACT

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/genetics , Pneumonia, Viral/genetics , RNA, Viral/genetics , Adult , Aged , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/rehabilitation , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/rehabilitation , Real-Time Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2
20.
Sci Adv ; 8(7): eabl6242, 2022 02 18.
Article in English | MEDLINE | ID: covidwho-1714333

ABSTRACT

Large segmental osseous defects heal poorly. Recombinant, human bone morphogenetic protein-2 (rhBMP-2) is used clinically to promote bone healing, but it is applied at very high doses that cause adverse side effects and raise costs while providing only incremental benefit. We describe a previously unexplored, alternative approach to bone regeneration using chemically modified messenger RNA (cmRNA). An optimized cmRNA encoding BMP-2 was delivered to critical-sized femoral osteotomies in rats. The cmRNA remained orthotopically localized and generated BMP locally for several days. Defects healed at doses ≥25 µg of BMP-2 cmRNA. By 4 weeks, all animals treated with 50 µg of BMP-2 cmRNA had bridged bone defects without forming the massive callus seen with rhBMP-2. Moreover, such defects recovered normal mechanical strength quicker and initiated bone remodeling faster. cmRNA regenerated bone via endochondral ossification, whereas rhBMP-2 drove intramembranous osteogenesis; cmRNA provides an innovative, safe, and highly translatable technology for bone healing.


Subject(s)
Bone Morphogenetic Protein 2 , Bone Regeneration , Animals , Bone Morphogenetic Protein 2/genetics , Bone Morphogenetic Protein 2/pharmacology , Femur , Osteogenesis , RNA, Messenger/genetics , Rats , Recombinant Proteins/pharmacology , Wound Healing
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