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1.
Signal Transduct Target Ther ; 7(1): 172, 2022 Jun 06.
Article in English | MEDLINE | ID: covidwho-1878517

ABSTRACT

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01-63.85 folds on day 28 after vaccination, whereas only 4.20-16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Humans , SARS-CoV-2
2.
Frontiers in public health ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-1872014

ABSTRACT

Background: Although coronavirus disease 2019 (COVID-19) is considered to be a disease that mainly involves the respiratory system, an increasing number of studies have reported that COVID-19 patients had pancreatic enzymes (PE) elevation and even pancreatic injury. The study aims to determine the prevalence of PE elevation, and the relationship between elevated PE and prognosis in COVID-19 patients. Methods A comprehensive literature search was conducted according to the PRISMA guideline in PubMed, Embase, Scopus, Web of Science, and Google Scholar for studies reporting PE elevation in patients with COVID-19 from 1st January 2020 to 24th November 2021. Results A total of 13 studies (24,353 participants) were included in our review. The pooled prevalence of PE elevation in COVID-19 patients was 24% (18%–31%), the pooled odds ratio (OR) of mortality was 2.5 (1.7–3.6), the pooled OR of ICU admission was 4.4 (2.8–6.8), and the pooled OR of kidney injury, respiratory failure and liver injury were 3.5 (1.6–7.4), 2.0 (0.5–8.7), and 2.3 (1.4–3.9) respectively. In addition, the subgroup analysis revealed that although PE elevated to > 3 × upper normal limit (ULN) was significantly related to the mortality (OR = 4.4, 2.1–9.4), it seemed that mild elevation of PE to 1–3 ULN also had a considerable risk of mortality (OR = 2.3, 1.5–3.5). Conclusions PE elevation was a common phenomenon in patients with COVID-19, and was associated with poor clinical outcomes. However, due to the limited numbers of included studies, the result of our study still needed to be validated. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=295630, identifier: CRD42021295630.

3.
Seizure ; 99: 71-74, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1852058

ABSTRACT

PURPOSE: To assess the safety of inactivated coronavirus 2019 disease (COVID-19) vaccine in tuberous sclerosis complex (TSC) patients with epilepsy. METHODS: All patients with epilepsy were selected from Efficacy and Safety of Sirolimus in Pediatric Patients with Tuberous Sclerosis (ESOSPIT) project and younger than 17 years old. The patients were treated with mTOR inhibitors (rapamycin). A total of 44 patients who completed the two-dose inactivated COVID-19 vaccine between July 7, 2021, and January 1, 2022, were enrolled. RESULTS: The median age of seizure onset was 23 months. About two-thirds of patients have focal seizures. Thirty-three patients use antiseizure medications. The mean duration of rapamycin treatment was 55.59 ± 18.42 months. Adverse reactions within 28 days after injection occurred in 11 patients (25%), all were under 12 years old. Injection site pain was the most reported event (20.45%), which was mild in severity and improved within one day. All patients had no seizure-related changes after vaccination. CONCLUSION: This study shows that the inactivated COVID-19 vaccine was well tolerated and safe in TSC patients with epilepsy, as well as for those treated with mTOR inhibitors.


Subject(s)
COVID-19 , Epilepsy , Tuberous Sclerosis , Adolescent , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Child , Child, Preschool , Epilepsy/chemically induced , Epilepsy/drug therapy , Humans , Infant , Seizures/drug therapy , Sirolimus/adverse effects , TOR Serine-Threonine Kinases , Tuberous Sclerosis/complications , Tuberous Sclerosis/drug therapy
5.
Environ Res ; 212(Pt B): 113297, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1796872

ABSTRACT

Meteorological factors have been confirmed to affect the COVID-19 transmission, but current studied conclusions varied greatly. The underlying causes of the variance remain unclear. Here, we proposed two scientific questions: (1) whether meteorological factors have a consistent influence on virus transmission after combining all the data from the studies; (2) whether the impact of meteorological factors on the COVID-19 transmission can be influenced by season, geospatial scale and latitude. We employed a meta-analysis to address these two questions using results from 2813 published articles. Our results showed that, the influence of meteorological factors on the newly-confirmed COVID-19 cases varied greatly among existing studies, and no consistent conclusion can be drawn. After grouping outbreak time into cold and warm seasons, we found daily maximum and daily minimum temperatures have significant positive influences on the newly-confirmed COVID-19 cases in cold season, while significant negative influences in warm season. After dividing the scope of the outbreak into national and urban scales, relative humidity significantly inhibited the COVID-19 transmission at the national scale, but no effect on the urban scale. The negative impact of relative humidity, and the positive impacts of maximum temperatures and wind speed on the newly-confirmed COVID-19 cases increased with latitude. The relationship of maximum and minimum temperatures with the newly-confirmed COVID-19 cases were more susceptible to season, while relative humidity's relationship was more affected by latitude and geospatial scale. Our results suggested that relationship between meteorological factors and the COVID-19 transmission can be affected by season, geospatial scale and latitude. A rise in temperature would promote virus transmission in cold seasons. We suggested that the formulation and implementation of epidemic prevention and control should mainly refer to studies at the urban scale. The control measures should be developed according to local meteorological properties for individual city.


Subject(s)
COVID-19 , COVID-19/epidemiology , Humans , Meteorological Concepts , SARS-CoV-2 , Seasons , Temperature
6.
IEEE Transactions on Automation Science & Engineering ; 19(2):646-662, 2022.
Article in English | Academic Search Complete | ID: covidwho-1788781

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) is a pandemic causing millions of deaths, devastating social and economic disruptions. Testing individuals for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of COVID-19, is critical for mitigating and containing COVID-19. Many countries are implementing group testing strategies against COVID-19 to improve testing capacity and efficiency while saving required workloads and consumables. A group of individuals’ nasopharyngeal/oropharyngeal (NP/OP) swab samples is mixed to conduct one test. However, existing group testing methods neglect the fact that mixing samples usually leads to substantial dilution of viral ribonucleic acid (RNA) of SARS-CoV-2, which seriously impacts the sensitivity of tests. In this paper, we aim to screen individuals infected with COVID-19 with as few tests as possible, under the premise that the sensitivity of tests is high enough. To achieve this goal, we propose an Adaptive Group Testing (AdaGT) method. By collecting information on the number of positive and negative samples that have been identified during the screening process, the AdaGT method can estimate the ratio of positive samples in real-time. Based on this ratio, the AdaGT algorithm adjusts its testing strategy adaptively between an individual testing strategy and a group testing strategy. The group size of the group testing strategy is carefully selected to guarantee that the sensitivity of each test is higher than a predetermined threshold and that this group contains at most one positive sample on average. Theoretical performance analysis on the AdaGT algorithm is provided and then validated in experiments. Experimental results also show that the AdaGT algorithm outperforms existing methods in terms of efficiency and sensitivity. Note to Practitioners—Real-time reverse transcription-polymerase chain reaction (rRT-PCR) tests provide scope for automation and are one of the most widely used laboratory methods for detecting the SARS-CoV-2 virus. This paper is motivated by the following challenges: (1) Many countries are experiencing an acute shortage of professionals and consumables for conducting rRT-PCR tests;(2) Group sizes of existing group testing methods against COVID-19 may not be optimal, which adversely impacts the efficiency of the screening of the SARS-CoV-2 virus;(3) Existing group testing methods do not consider the fact that the sensitivity of rRT-PCR tests usually decreases with the group size. The objective of this paper is to improve the efficiency and sensitivity of large-scale screening against COVID-19. For achieving this goal, we propose an Adaptive Group Testing (AdaGT) algorithm, which has the following advantages: (1) It can improve the efficiency for screening the SARS-CoV-2 virus, mainly by adaptively adjusting its testing strategy between an individual testing strategy and a group testing strategy based upon an estimated ratio of positive samples during the screening process;(2) It can guarantee a high sensitivity of the rRT-PCR tests by determining the group sizes of the group testing strategy based upon some constraints;(3) We derive an appropriate threshold for the estimated ratio of positive samples such that the AdaGT algorithm can achieve a minimum average number of rRT-PCR tests and can be directly employed in practical applications. [ FROM AUTHOR] Copyright of IEEE Transactions on Automation Science & Engineering is the property of IEEE and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

7.
Adv Sci (Weinh) ; 9(14): e2104333, 2022 05.
Article in English | MEDLINE | ID: covidwho-1782562

ABSTRACT

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.


Subject(s)
COVID-19 Vaccines , COVID-19 , Globulins , Animals , COVID-19/therapy , Globulins/therapeutic use , Humans , Immunization, Passive , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
8.
Risk management and healthcare policy ; 15:447-456, 2022.
Article in English | EuropePMC | ID: covidwho-1743744

ABSTRACT

Purpose Fever is one of the most typical clinical symptoms of coronavirus disease 2019 (COVID-19), and non-contact infrared thermometers (NCITs) are commonly used to screen for fever. However, there is a lack of authoritative data to define a “fever” when an NCIT is used and previous studies have shown that NCIT readings fluctuate widely depending on ambient temperatures and the body surface site screened. The aim of this study was to establish cut-off points for normal temperatures of different body sites (neck, forehead, temples, and wrist) and investigate the accuracy of NCITs at various ambient temperatures to improve the standardization and accuracy of fever screening. Patients and Methods A prospective investigation was conducted among 904 participants in the outpatient and emergency departments of Chengdu Women’s and Children’s Central Hospital. Body temperature was measured using NCITs and mercury axillary thermometers. A receiver operating characteristic curve was used to determine the accuracy of body temperature detection at the four body surface sites. Data on participant characteristics were also collected. Results Among the four surface sites, the neck temperature detection group had the highest accuracy. When the neck temperature was 37.35°C as the optimum fever diagnostic threshold, the sensitivity was 0.866. The optimum fever diagnostic thresholds for forehead, temporal, and wrist temperature were 36.65°C, 36.65°C, and 36.75°C, respectively. Moreover, triple neck temperature detection had the highest sensitivity, up to 0.998, whereas the sensitivity of triple wrist temperature detections was 0.949. Notably, the accuracy of NCITs significantly reduced when the temperature was lower than 18°C. Conclusion Neck temperature had the highest accuracy among the four NCIT temperature measurement sites, with an optimum fever diagnostic threshold of 37.35°C. Considering the findings reported in our study, we recommend triple neck temperature detection with NCITs as the fever screening standard for COVID-19.

9.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329783

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates ( NCT05069129 ). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67;95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03;95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

10.
Pathogens ; 11(2)2022 Feb 11.
Article in English | MEDLINE | ID: covidwho-1715596

ABSTRACT

Characterized by the high morbidity and mortality and seasonal surge, the influenza virus (IV) remains a major public health challenge. Oseltamivir is commonly used as a first-line antiviral. As a neuraminidase inhibitor, it attenuates the penetration of viruses through the mucus on the respiratory tract and inhibits the release of virus progeny from infected cells. However, over the years, oseltamivir-resistant strains have been detected in the IV surveillance programs. Therefore, new antivirals that circumvent the resistant strains would be of great importance. In this study, two novel secondary amine derivatives of oseltamivir CUHK326 (6f) and CUHK392 (10i), which bear heteroaryl groups of M2-S31 proton channel inhibitors, were designed, synthesized and subjected to biological evaluation using plaque assay. Influenza A virus (A/Oklahoma/447/2008, H1N1), influenza B viruses (B/HongKong/CUHK33261/2012), an oseltamivir-resistant influenza A virus (A/HongKong/CUHK71923/2009, H1N1) and an oseltamivir-resistant influenza B virus (B/HongKong/CUHK33280/2012) were included in the antiviral effect assessment compared to oseltamivir carboxylate (OC). Both novel compounds significantly reduced the plaque size of seasonal IV A and B, and performed similarly to OC at their corresponding half-maximal inhibitory concentration (IC50). CUHK392 (10i) functioned more effectively than CUHK326 (6f). More importantly, these compounds showed an inhibitory effect on the oseltamivir-resistant strain under 10 nM with selective index (SI) of >200.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325221

ABSTRACT

Background: The clinical significance of cardiac troponin measurement in patients hospitalised for coronavirus disease-2019 (covid-19) is uncertain. We investigated the prevalence of elevated troponins in these patients and its prognostic value for predicting mortality. Methods: : Studies were identified by searching electronic databases and preprint servers. We included studies of hospitalised covid-19 patients that reported the frequency of troponin elevations above the upper reference limit and/or the association between troponins and mortality. Meta-analyses were performed using random-effects models. Results: : Forty-four studies were included. Elevated troponins were found in 21.3% (95% confidence interval [CI] 18.0-24.9 %) of patients who received troponin test on hospital admission. Elevated troponins on admission were associated with a higher risk of subsequent death (risk ratio 2.81, 95% CI 2.01-3.93) after adjusting for confounders in multivariable analysis. The pooled sensitivity of elevated admission troponins for predicting death was 0.64 (95% CI 0.58-0.70), and the specificity was 0.88 (0.82-0.92). The post-test probability of death was about 50% for patients with elevated admission troponins, and was about 7% for those with non-elevated troponins on admission. There were significant heterogeneity and publication bias in the analyses, and many included studies were at risk of selection bias due to the lack of systematic troponin measurement and inadequate follow-up. Conclusion: Elevated troponins were relatively common in patients hospitalised for covid-19. Troponin measurement on admission might help in risk stratification, especially in identifying patients at high risk of death when troponin levels are elevated. High-quality prospective studies are needed to validate these findings. Systematic Review Registration: PROSPERO (CRD42020176747).

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324821

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has become a world-wide pandemic. Hospitalized patients of COVID-19 suffer from a high mortality rate, motivating the development of convenient and practical methods for clinicians to promptly identify high-risk patients. Here we developed a risk score using clinical data from 1,479 inpatients admitted to Tongji Hospital, Wuhan, China (development cohort) and externally validated with data from two other centers: 141 inpatients from Jinyintan Hospital in Wuhan (validation cohort 1) and 432 inpatients from the Third People’s Hospital Shenzhen (validation cohort 2). The risk score is based on three biomarkers readily available in routine blood samples and can be easily translated into a probability of death. The risk score can predict the mortality of individual patients more than 12 days in advance with more than 90% accuracy across all cohorts. Moreover, the Kaplan-Meier score shows that patients upon admission can clearly be differenciated into low, medium or high risk, with an AUC score of 0.9551. In summary, a simple risk score was validated to predict death in patients infected with COVID-19 and was validated in independent cohorts.

13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323767

ABSTRACT

The SARS-CoV-2 variant VUI/202012/01 has been reported to spread unexpectedly fast in the United Kingdom. It is estimated that its transmissibility may increase by 70%. In this study, the top five variants circulating in the UK including D614G+L18F+A222V, D614G+A222V, D614G+S477N, VUI/202012/01 and D614G+69-70del+439K were analyzed for their infective and neutralizing characteristics. The pseudotyped viruses were constructed for the five variants and 12 single mutants composed those variants. We found that the VUI/202012/01 variant does enhance its infectivity due to the cumulative effect of multiple mutations including 69-70del and 144/145del mutations in NTD, A570D in RBD, and S982A in S2. Meanwhile, mutations N501Y, N439K and S477N in RBD can cause a significant decrease in the neutralization activity for some mAbs. Although VUI/202012/01 did not affect the neutralization effect of convalescent sera, it affected the neutralization activity of animal immunized sera by RBD protein or recombinant spike DNA to some extent.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315338

ABSTRACT

The coronavirus disease (COVID-19) is currently prevalent worldwide. We analysed the occurrence of diarrhoea of these patients after treatment. All patients were treated with nebulised α-interferon and oral administration of Lopinavir/Ritonavir tablets. Of the 62 patients, 38 (61.3%) developed diarrhoea after treatment. Of these 38 cases, 63.2% (24/38 cases) had their first diarrhoea within 24 hours after medication. Only 13.2% (5/38 cases) had more than 5 bowel movements per day with a maximum of 10 per day. Patients with diarrhoea had lower white blood cell counts. Leukopenia was a risk factor for the development of diarrhoea. We conclude that COVID-19 patients had a relatively high rate of diarrhoea after treatment. Lopinavir/Ritonavir was speculated to contribute to diarrhea, which is a common adverse drug reaction to Lopinavir/Ritonavir. Patients with reduced white blood cell counts at admission may be more likely to develop diarrhoea after admission.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314409

ABSTRACT

2019 novel coronavirus (2019-nCoV) is firstly found in Wuhan and has caused over 14,000 infections all over the world. We retrospectively investigated the presence of 2019-nCoV among influenza-like illness patients in Wuhan. Nine cases in January 2020 were 2019-nCoV positive, suggesting the virus has established community transmission in Wuhan, the origin and center of this epidemic.Authors Wen-Hua Kong, Yao Li, and Ming-Wei Peng contributed equally to this work.

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-307411

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of novel coronavirus disease 2019 (COVID-19)1. SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as a cellular receptor and enters cells via clathrin-mediated endocytosis (CME)2-4. However, the key molecules involved in internalizing and facilitating CME for virus entry remain unknown. Here, we found metabotropic glutamate receptor subtype 2 (mGluR2) is a key entry receptor for SARS-CoV-2 infection. mGluR2 directly interacts with the SARS-CoV-2 spike protein. Knockdown of mGluR2 decreases endocytosis of SARS-CoV-2 but not cell binding. mGluR2 cooperates with ACE2 to facilitate SARS-CoV-2 entry through CME. Knockout of the mGluR2 gene in mice abolished SARS-CoV-2 infection in the nasal turbinates and significantly reduced viral infection in the lungs. Importantly, mGluR2 also is important for severe acute respiratory syndrome coronavirus spike protein and Middle East respiratory syndrome coronavirus spike protein mediated endocytosis. Our study provides important insights into SARS-CoV-2 infection and reveals an important target for the development of novel approaches to limit coronavirus infection.

17.
Journal of Intensive Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-1665214

ABSTRACT

Background The coronavirus disease 2019 (COVID-19) is an ongoing pandemic since December 2019. Invasive mechanical ventilation (IMV) is essential for the management of COVID-19 with acute respiratory distress syndrome (ARDS). We aimed to assess the impact of compliance with a respiratory decision support system on the outcomes of patients with COVID-19-associated ARDS who required IMV. Methods In this retrospective, single-center, case series, 46 patients with COVID-19-associated ARDS who required IMV at Zhongnan Hospital of Wuhan University, China, from January 8, 2020, to March 24, 2020, with the final follow-up date of April 20, 2020, were included. Demographic, clinical, laboratory, imaging, and management information were collected and analyzed. Compliance with the respiratory support decision system was documented, and its relationship with 28-day mortality was evaluated. Results The median age of the 46 patients with COVID-19-associated ARDS requiring IMV was 68.5 years, and 31 were men. The partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio at intensive care unit (ICU) admission was 104 mmHg. The median total length of IMV was 12.0 (interquartile range [IQR], 6.0–27.3) days, and the median respiratory support decision score was 11.0 (IQR, 7.8–16.0). To 28 days after ICU admission, 18 (39.1%) patients died. Survivors had a significantly higher respiratory support decision score than non-survivors (15.0 [10.3–17.0] vs. 8.5 (6.0–10.3), P = 0.001). Using receiver operating characteristic (ROC) curve to assess the discrimination of respiratory support decision score to 28-day mortality, the area under the curve (AUC) was 0.796 (95% confidence interval [CI]: 0.657–0.934, P = 0.001) and the cut-off was 11.5 (sensitivity = 0.679, specificity = 0.889). Patients with a higher score (>11.5) were more likely to survive at 28 days after ICU admission (log-rank test, P < 0.001). Conclusions For severe COVID-19-associated ARDS with IMV, following the respiratory support decision and assessing completion would improve the progress of ventilation. With a decision score of >11.5, the mortality at 28 days after ICU admission showed an obvious decrease.

18.
J Hazard Mater ; 425: 127901, 2022 03 05.
Article in English | MEDLINE | ID: covidwho-1573490

ABSTRACT

The aim of this work was to evaluate the adsorption capacity and mechanism of two antiviral drugs AVDs (lopinavir (LOP) and ritonavir (RIT)) on three various sewage sludges (SSLs). The results showed that SSLs differed in the structure and chemical composition and LOP and RIT had a high affinity to the studied SSLs (Kd in ranges 2076-3449 L/kg). The adsorption capacities differed between SSLs and ranged 7.55-8.71 mg/g (RIT) and 8.10-8.64 mg/g (LOP). The Freundlich model provided a best fitting of adsorption isotherms of all AVDs-SSLs. The adsorption kinetics were best described by pseudo-second order kinetic model. The adsorption of LOP and RIT on SSLs was exothermic, spontaneous, and thermodynamically feasible. The sorption of LOP and RIT to SSLs was complex due to the diverse chemical composition of SSLs and the differences in the chemical structure of AVDs. Analysis of binary solution of both AVDs showed the competition effect between AVDs and a decrease in adsorption efficiency (3-17%) compared to single solutions. The amount of desorbed AVDs from all SSLs was low (less than 15%). The findings of the present work are significant in the prediction of fate and persistence of AVDs on SSLs in the context of their further transmission and possible environmental contamination.


Subject(s)
Sewage , Water Pollutants, Chemical , Adsorption , Antiviral Agents , Kinetics , Lopinavir , Ritonavir , Water Pollutants, Chemical/analysis
19.
Brief Bioinform ; 23(2)2022 03 10.
Article in English | MEDLINE | ID: covidwho-1639367

ABSTRACT

Genomic epidemiology is important to study the COVID-19 pandemic, and more than two million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a node-picking rendering strategy. In total, 1,002,739 high-quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, highly efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and ongoing positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB was written in Java and JavaScript. It not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Public Health Surveillance/methods , SARS-CoV-2/genetics , Software , Web Browser , Computational Biology/methods , DNA Mutational Analysis , Databases, Genetic , Genome, Viral , Genomics , Humans , Molecular Epidemiology/methods , Molecular Sequence Annotation , Mutation
20.
Viruses ; 14(1)2021 12 29.
Article in English | MEDLINE | ID: covidwho-1639272

ABSTRACT

Inactivated vaccines based on cell culture are very useful in the prevention and control of many diseases. The most popular strategy for the production of inactivated vaccines is based on monkey-derived Vero cells, which results in high productivity of the virus but has a certain carcinogenic risk due to non-human DNA contamination. Since human diploid cells, such as MRC-5 cells, can produce a safer vaccine, efforts to develop a strategy for inactivated vaccine production using these cells have been investigated using MRC-5 cells. However, most viruses do not replicate efficiently in MRC-5 cells. In this study, we found that rabies virus (RABV) infection activated a robust interferon (IFN)-ß response in MRC-5 cells but almost none in Vero cells, suggesting that the IFN response could be a key limiting factor for virus production. Treatment of the MRC-5 cells with IFN inhibitors increased RABV titers by 10-fold. Additionally, the RABV titer yield was improved five-fold when using IFN receptor 1 (IFNAR1) antibodies. As such, we established a stable IFNAR1-deficient MRC-5 cell line (MRC-5IFNAR1-), which increased RABV production by 6.5-fold compared to normal MRC-5 cells. Furthermore, in a pilot-scale production in 1500 square centimeter spinner flasks, utilization of the MRC-5IFNAR1- cell line or the addition of IFN inhibitors to MRC cells increased RABV production by 10-fold or four-fold, respectively. Thus, we successfully established a human diploid cell-based pilot scale virus production platform via inhibition of IFN response for rabies vaccines, which could also be used for other inactivated virus vaccine production.


Subject(s)
Diploidy , Interferons/pharmacology , Rabies Vaccines/immunology , Rabies virus , Rabies/prevention & control , Animals , Antibodies, Viral , Cell Line , Chlorocebus aethiops , Gene Expression , Humans , Interferons/genetics , Receptor, Interferon alpha-beta/genetics , Vaccines, Inactivated/immunology , Vero Cells
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