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1.
Nat Commun ; 12(1): 7327, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1585856

ABSTRACT

The global disruption caused by the 2020 coronavirus pandemic stressed the supply chain of many products, including pharmaceuticals. Multiple drug repurposing studies for COVID-19 are now underway. If a winning therapeutic emerges, it is unlikely that the existing inventory of the medicine, or even the chemical raw materials needed to synthesize it, will be available in the quantities required. Here, we utilize retrosynthetic software to arrive at alternate chemical supply chains for the antiviral drug umifenovir, as well as eleven other antiviral and anti-inflammatory drugs. We have experimentally validated four routes to umifenovir and one route to bromhexine. In one route to umifenovir the software invokes conversion of six C-H bonds into C-C bonds or functional groups. The strategy we apply of excluding known starting materials from search results can be used to identify distinct starting materials, for instance to relieve stress on existing supply chains.


Subject(s)
Antiviral Agents/chemistry , COVID-19/drug therapy , Indoles/chemistry , Software , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Drug Repositioning , Humans , Indoles/therapeutic use , SARS-CoV-2/drug effects
3.
Anal Bioanal Chem ; 413(29): 7195-7204, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1482198

ABSTRACT

The pandemic of the novel coronavirus disease 2019 (COVID-19) has caused severe harm to the health of people all around the world. Molecular detection of the pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), played a crucial role in the control of the disease. Reverse transcription digital PCR (RT-dPCR) has been developed and used in the detection of SARS-CoV-2 RNA as an absolute quantification method. Here, an interlaboratory assessment of quantification of SARS-CoV-2 RNA was organized by the National Institute of Metrology, China (NIMC), using in vitro transcribed RNA samples, among ten laboratories on six different dPCR platforms. Copy number concentrations of three genes of SARS-CoV-2 were measured by all participants. Consistent results were obtained with dispersion within 2.2-fold and CV% below 23% among different dPCR platforms and laboratories, and Z' scores of all the reported results being satisfactory. Possible reasons for the dispersion included PCR assays, partition volume, and reverse transcription conditions. This study demonstrated the comparability and applicability of RT-dPCR method for quantification of SARS-CoV-2 RNA and showed the capability of the participating laboratories at SARS-CoV-2 test by RT-dPCR platform.


Subject(s)
Laboratories/organization & administration , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2/genetics , COVID-19/virology , Humans , Limit of Detection
4.
Front Immunol ; 12: 735125, 2021.
Article in English | MEDLINE | ID: covidwho-1441109

ABSTRACT

Background: The global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR+CD38+ CD8+ T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38+HLA-DR+ CD8+ T population was reported to play contradictory roles in SARS-CoV-2 infection. Methods: A total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3-7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally. Results: We revealed that the HLA-DR+CD38+ CD8+ T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR+CD38dim and HLA-DR+CD38hi. We observed a persistent accumulation of HLA-DR+CD38hi CD8+ T cells in severe COVID-19 patients. These HLA-DR+CD38hi CD8+ T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR+CD38dim CD8+ T cells. Moreover, the clinical and laboratory data supported that only HLA-DR+CD38hi CD8+ T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients. Conclusions: Our findings indicated that HLA-DR+CD38hi CD8+ T cells were correlated with disease severity of COVID-19 rather than HLA-DR+CD38dim population.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immune System Diseases/immunology , SARS-CoV-2 , Adult , Aged , CD8 Antigens/immunology , Cytokines/immunology , Female , HLA-DR Antigens/immunology , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Young Adult
5.
J Virol Methods ; 298: 114285, 2021 12.
Article in English | MEDLINE | ID: covidwho-1401675

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency. Although many reverse-transcription PCR (RT-PCR) assays have been developed, their performance, especially sensitivity assessment, has been insufficiently tested. In this study, a preliminary comparison of the analytical sensitivity of nine RT-qPCR kits from different manufacturers was first conducted using a certified reference material derived from the genomic RNA of SARS-CoV-2 as the template. Subsequently, three of the nine kits, comprising two highly sensitive kits (DAAN, Huirui) and one less sensitive kit (Geneodx), were selected for further sensitivity and specificity validation. The results revealed variations in the performance between kits of the two groups. For the two highly sensitive kits, the limits of detection at 95 % probability (LOD95%) were 5.6 copies of the N gene and 3.5 copies of the ORF 1ab per reaction (DAAN), and 6.4 (N) and 4.6 (ORF 1ab) copies per reaction (Huirui). These LOD95% values were approximately 3 to 4-fold better than those of the Geneodx Kit. However, none of these three Kits showed cross-reactivity against 6 other types of human coronaviruses or respiratory viruses. Because most of these commercial kits are approved as in vitro diagnostics (testing specimens without direct human contact), it would be beneficial for their manufacturers to improve the diagnostic capability of these kits and thus reduce the clinical risks associated with false-negative results.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Pandemics , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity
6.
Risk Manag Healthc Policy ; 14: 3589-3596, 2021.
Article in English | MEDLINE | ID: covidwho-1389043

ABSTRACT

Objective: To implement epidemic prevention among entry personnel, Shanghai has launched a number of Medical Observation Sites (Observation Site) for which high expectations are set. Ours is one such Observation Site. Methods: As part of a novel project, we did not have any previous experience to use as reference. Despite some challenges, we achieved satisfactory outcomes by establishing a stepwise approach to inbound passenger management, including the division of the working area of the Observation Site, dynamic management of the rooms, closed-loop management of the isolated personnel. Results: As of May 14, 2020, a total of 42 Observation Sites were operational in Pudong New Area. The following are the detailed descriptions of our Temporary Medical Observation Site set up and work flow. Conclusion: Early screening of inbound passengers as well as prompt and dynamic management of information about passengers' close contacts play an active role in preventing an influx of cases. As a pilot program, we have a model that is effective despite some limitations.

7.
PLoS Comput Biol ; 17(8): e1009351, 2021 08.
Article in English | MEDLINE | ID: covidwho-1378132

ABSTRACT

Decision-making about pandemic mitigation often relies upon simulation modelling. Models of disease transmission through networks of contacts-between individuals or between population centres-are increasingly used for these purposes. Real-world contact networks are rich in structural features that influence infection transmission, such as tightly-knit local communities that are weakly connected to one another. In this paper, we propose a new flow-based edge-betweenness centrality method for detecting bottleneck edges that connect nodes in contact networks. In particular, we utilize convex optimization formulations based on the idea of diffusion with p-norm network flow. Using simulation models of COVID-19 transmission through real network data at both individual and county levels, we demonstrate that targeting bottleneck edges identified by the proposed method reduces the number of infected cases by up to 10% more than state-of-the-art edge-betweenness methods. Furthermore, the proposed method is orders of magnitude faster than existing methods.


Subject(s)
COVID-19/prevention & control , Computer Simulation , Models, Biological , Algorithms , COVID-19/epidemiology , COVID-19/transmission , Humans , Oregon/epidemiology , Pandemics , Quebec/epidemiology , Social Media
8.
Sens Actuators B Chem ; 345: 130411, 2021 Oct 15.
Article in English | MEDLINE | ID: covidwho-1294241

ABSTRACT

The outbreak of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic. The high infectivity of SARS-CoV-2 highlights the need for sensitive, rapid and on-site diagnostic assays of SARS-CoV-2 with high-throughput testing capability for large-scale population screening. The current detection methods in clinical application need to operate in centralized labs. Though some on-site detection methods have been developed, few tests could be performed for high-throughput analysis. We here developed a gold nanoparticle-based visual assay that combines with CRISPR/Cas12a-assisted RT-LAMP, which is called Cas12a-assisted RT-LAMP/AuNP (CLAP) assay for rapid and sensitive detection of SARS-CoV-2. In optimal condition, we could detect down to 4 copies/µL of SARS-CoV-2 RNA in 40 min. by naked eye. The sequence-specific recognition character of CRISPR/Cas12a enables CLAP a superior specificity. More importantly, the CLAP is easy for operation that can be extended to high-throughput test by using a common microplate reader. The CLAP assay holds a great potential to be applied in airports, railway stations, or low-resource settings for screening of suspected people. To the best of our knowledge, this is the first AuNP-based colorimetric assay coupled with Cas12 and RT-LAMP for on-site diagnosis of COVID-19. We expect CLAP assay will improve the current COVID-19 screening efforts, and make contribution for control and mitigation of the pandemic.

9.
Health Policy ; 125(8): 957-971, 2021 08.
Article in English | MEDLINE | ID: covidwho-1252927

ABSTRACT

Coronavirus 2019 (COVID-19) has had a significant impact on the world. Different countries introduced various public health and social measures (PHSMs) against the coronavirus. This paper aims to (a) examine how national policies on PHSMs were framed and which PHSMs were adopted; (b) compare the similarities and differences of PHSMs advocated by different countries; and (c) examine whether these measures have changed with time. We performed a content analysis of 160 COVID-19 policy documents on the websites of the WHO and ten countries' government websites on COVID-19 between December 1, 2019 and May 31, 2020. Results showed that although the initial responses to COVID-19 in different countries varied, there was a homogenization of PHSMs over time: by May 31, 2020, almost all the countries we studied implemented the major PHSMs that the WHO recommended, except Sweden, which applied only part of the major PHSMs recommended by the WHO. The differences among countries were in the speediness, strictness and resourcefulness of the PHSMs implementation. We suggest that a timely and effective utilization of the integrated package of health measures with the support of adequate resources may help the efficient implementation of PHSMs.


Subject(s)
COVID-19 , Public Health , Government , Humans , SARS-CoV-2 , Sweden
10.
Front Public Health ; 9: 648360, 2021.
Article in English | MEDLINE | ID: covidwho-1221994

ABSTRACT

The clinical spectrum of COVID-19 pneumonia is varied. Thus, it is important to identify risk factors at an early stage for predicting deterioration that require transferring the patients to ICU. A retrospective multicenter study was conducted on COVID-19 patients admitted to designated hospitals in China from Jan 17, 2020, to Feb 17, 2020. Clinical presentation, laboratory data, and quantitative CT parameters were also collected. The result showed that increasing risks of ICU admission were associated with age > 60 years (odds ratio [OR], 12.72; 95% confidence interval [CI], 2.42-24.61; P = 0.032), coexisting conditions (OR, 5.55; 95% CI, 1.59-19.38; P = 0.007) and CT derived total opacity percentage (TOP) (OR, 8.0; 95% CI, 1.45-39.29; P = 0.016). In conclusion, older age, coexisting conditions, larger TOP at the time of hospital admission are associated with ICU admission in patients with COVID-19 pneumonia. Early monitoring the progression of the disease and implementing appropriate therapies are warranted.


Subject(s)
COVID-19 , Aged , China/epidemiology , Humans , Intensive Care Units , Middle Aged , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
11.
Med Sci Monit ; 27: e929708, 2021 Apr 11.
Article in English | MEDLINE | ID: covidwho-1148368

ABSTRACT

BACKGROUND Since the outbreak of COVID-19 in December 2019, there have been 96 623 laboratory-confirmed cases and 4784 deaths by December 29 in China. We aimed to analyze the risk factors and the incidence of thrombosis from patients with confirmed COVID-19 pneumonia. MATERIAL AND METHODS Eighty-eight inpatients with confirmed COVID-19 pneumonia were reported (31 critical cases, 33 severe cases, and 24 common cases). The thrombosis risk factor assessment, laboratory results, ultrasonographic findings, and prognoses of these patients were analyzed, and compared among groups with different severity. RESULTS Nineteen of the 88 cases developed DVT (12 critical cases, 7 severe cases, and no common cases). In addition, among the 18 patients who died, 5 were diagnosed with DVT. Positive correlations were observed between the increase in D-dimer level (≥5 µg/mL) and the severity of COVID-19 pneumonia (r=0.679, P<0.01), and between the high Padua score (≥4) and the severity (r=0.799, P<0.01). In addition, the CRP and LDH levels on admission had positive correlations with the severity of illness (CRP: r=0.522, P<0.01; LDH: r=0.600, P<0.01). A negative correlation was observed between the lymphocyte count on admission and the severity of illness (r=-0.523, P<0.01). There was also a negative correlation between the lymphocyte count on admission and mortality in critical patients (r=-0.499, P<0.01). Univariable logistic regression analysis showed that the occurrence of DVT was positively correlated with disease severity (crude odds ratio: 3.643, 95% CI: 1.218-10.896, P<0.05). CONCLUSIONS Our report illustrates that critically or severely ill patients have an associated high D-dimer value and high Padua score, and illustrates that a low threshold to screen for DVT may help improve detection of thromboembolism in these groups of patients, especially in asymptomatic patients. Our results suggest that early administration of prophylactic anticoagulant would benefit the prognosis of critical patients with COVID-19 pneumonia and would likely reduce thromboembolic rates.


Subject(s)
COVID-19/complications , Fibrin Fibrinogen Degradation Products/analysis , Venous Thrombosis/epidemiology , Adult , Aged , Asymptomatic Diseases , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , China/epidemiology , Female , Hospital Mortality , Humans , Incidence , Lower Extremity/blood supply , Lower Extremity/diagnostic imaging , Male , Middle Aged , Patient Admission , Prognosis , Retrospective Studies , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Ultrasonography , Venous Thrombosis/blood , Venous Thrombosis/diagnosis , Venous Thrombosis/etiology
12.
Health, Risk & Society ; : 1-18, 2021.
Article in English | Taylor & Francis | ID: covidwho-1142576
13.
International Journal of Hospitality Management ; 95:102910, 2021.
Article in English | ScienceDirect | ID: covidwho-1126843

ABSTRACT

This paper investigates the effects of crowdedness and in-restaurant safety measures on consumers’ restaurant patronage choices (eat-in vs. order takeaway vs. not patronize) and their perceptions during the COVID-19 pandemic. In an online experiment with 593 US consumers and 591 Australian consumers, we assess the effects of three levels of crowdedness (low vs. medium vs. high crowdedness) and four types of in-restaurant safety measures (none vs. partition vs. increasing distances between tables vs. not using in-between tables) by showing participants an image of the restaurant setting. Results show that US consumers are more sensitive to crowdedness, whereas Australian consumers are more sensitive to different types of safety measures, which greatly influence their patronage choices. In general, safety measures featuring social distancing are preferred over partitions, and there is no preferential difference between the measure of increasing distances between tables and the measure of not using in-between tables.

14.
J Thromb Haemost ; 19(4): 1038-1048, 2021 04.
Article in English | MEDLINE | ID: covidwho-1061045

ABSTRACT

BACKGROUND: High incidence of asymptomatic venous thromboembolism (VTE) has been observed in severe COVID-19 patients, but the characteristics of symptomatic VTE in general COVID-19 patients have not been described. OBJECTIVES: To comprehensively explore the prevalence and reliable risk prediction for VTE in COVID-19 patients. METHODS/RESULTS: This retrospective study enrolled all COVID-19 patients with a subsequent VTE in 16 centers in China from January 1 to March 31, 2020. A total of 2779 patients were confirmed with COVID-19. In comparison to 23,434 non-COVID-19 medical inpatients, the odds ratios (ORs) for developing symptomatic VTE in severe and non-severe hospitalized COVID-19 patients were 5.94 (95% confidence interval [CI] 3.91-10.09) and 2.79 (95% CI 1.43-5.60), respectively. When 104 VTE cases and 208 non-VTE cases were compared, pulmonary embolism cases had a higher rate for in-hospital death (OR 6.74, 95% CI 2.18-20.81). VTE developed at a median of 21 days (interquartile range 13.25-31) since onset. Independent factors for VTE were advancing age, cancer, longer interval from symptom onset to admission, lower fibrinogen and higher D-dimer on admission, and D-dimer increment (DI) ≥1.5-fold; of these, DI ≥1.5-fold had the most significant association (OR 14.18, 95% CI 6.25-32.18, p = 2.23 × 10-10 ). A novel model consisting of three simple coagulation variables (fibrinogen and D-dimer levels on admission, and DI ≥1.5-fold) showed good prediction for symptomatic VTE (area under the curve 0.865, 95% CI 0.822-0.907, sensitivity 0.930, specificity 0.710). CONCLUSIONS: There is an excess risk of VTE in hospitalized COVID-19 patients. This novel model can aid early identification of patients who are at high risk for VTE.


Subject(s)
Biomarkers/blood , COVID-19/complications , Fibrin Fibrinogen Degradation Products/analysis , Venous Thromboembolism/diagnosis , Venous Thrombosis/epidemiology , Aged , COVID-19/blood , COVID-19/diagnosis , COVID-19/therapy , China/epidemiology , Female , Hospital Mortality , Humans , Immunization, Passive , Male , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/blood , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thrombosis/blood , Venous Thrombosis/etiology
15.
Talanta ; 224: 121726, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-894232

ABSTRACT

The outbreak of COVID-19 caused by a novel Coronavirus (termed SARS-CoV-2) has spread to over 210 countries around the world. Currently, reverse transcription quantitative qPCR (RT-qPCR) is used as the gold standard for diagnosis of SARS-CoV-2. However, the sensitivity of RT-qPCR assays of pharyngeal swab samples are reported to vary from 30% to 60%. More accurate and sensitive methods are urgently needed to support the quality assurance of the RT-qPCR or as an alternative diagnostic approach. A reverse transcription digital PCR (RT-dPCR) method was established and evaluated. To explore the feasibility of RT-dPCR in diagnostic of SARS-CoV-2, a total of 196 clinical pharyngeal swab samples from 103 suspected patients, 77 close contacts and 16 supposed convalescents were analyzed by RT-qPCR and then measured by the proposed RT-dPCR. For the 103 fever suspected patients, 19 (19/25) negative and 42 (42/49) equivocal tested by RT-qPCR were positive according to RT-dPCR. The sensitivity of SARS-CoV-2 detection was significantly improved from 28.2% by RT-qPCR to 87.4% by RT-dPCR. For 29 close contacts (confirmed by additional sample and clinical follow up), 16 (16/17) equivocal and 1 negative tested by RT-qPCR were positive according to RT-dPCR, which is implying that the RT-qPCR is missing a lot of asymptomatic patients. The overall sensitivity, specificity and diagnostic accuracy of RT-dPCR were 91%, 100% and 93%, respectively. RT-dPCR is highly accurate method and suitable for detection of pharyngeal swab samples from COVID-19 suspected patients and patients under isolation and observation who may not be exhibiting clinical symptoms.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2/genetics , Coronavirus Envelope Proteins/genetics , Coronavirus Nucleocapsid Proteins/genetics , Humans , Pharynx/virology , Phosphoproteins/genetics , Polyproteins/genetics , Viral Proteins/genetics
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