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  • Oxford University Press (OUP)  (6)
  • 1
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    Online Resource
    Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity
    Oxford University Press (OUP) ; 2021
    In:  Clinical Infectious Diseases Vol. 73, No. 9 ( 2021-11-02), p. e2932-e2942
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 73, No. 9 ( 2021-11-02), p. e2932-e2942
    Abstract: Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was & gt;30 or & gt;14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. Conclusions We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciaa1280
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2002229-3
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  • 2
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    Clinical and Virological Features of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern: A Retrospective Cohort Study Comparing B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta)
    Oxford University Press (OUP) ; 2022
    In:  Clinical Infectious Diseases Vol. 75, No. 1 ( 2022-08-24), p. e1128-e1136
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 75, No. 1 ( 2022-08-24), p. e1128-e1136
    Abstract: The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared the outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with wild-type strains from early 2020. Methods National surveillance data from January to May 2021 were obtained and outcomes in relation to VOCs were explored. Detailed patient-level data from all patients with VOC infection admitted to our center between December 2020 and May 2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January to April 2020. Results A total of 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, intensive care unit admission, or death (adjusted odds ratio [aOR], 4.90; 95% confidence interval [CI] : 1.43-30.78). Of these patients, 157 were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, the aOR for pneumonia with B.1.617.2 was 1.88 (95% CI: .95-3.76) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower polymerase chain reaction cycle threshold (Ct) values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). Conclusions B.1.617.2 was associated with increased severity of illness, and with lower Ct values and longer viral shedding. These findings provide impetus for the rapid implementation of vaccination programs.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciab721
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2002229-3
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  • 3
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    The Effect of Sample Site, Illness Duration, and the Presence of Pneumonia on the Detection of SARS-CoV-2 by Real-time Reverse Transcription PCR
    Oxford University Press (OUP) ; 2020
    In:  Open Forum Infectious Diseases Vol. 7, No. 9 ( 2020-09-01)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 7, No. 9 ( 2020-09-01)
    Abstract: The performance of real-time reverse transcription polymerase chain reaction (rRT-PCR) for SARS-CoV-2 varies with sampling site(s), illness stage, and infection site. Methods Unilateral nasopharyngeal, nasal midturbinate, throat swabs, and saliva were simultaneously sampled for SARS-CoV-2 rRT-PCR from suspected or confirmed cases of COVID-19. True positives were defined as patients with at least 1 SARS-CoV-2 detected by rRT-PCR from any site on the evaluation day or at any time point thereafter, until discharge. Diagnostic performance was assessed and extrapolated for site combinations. Results We evaluated 105 patients; 73 had active SARS-CoV-2 infection. Overall, nasopharyngeal specimens had the highest clinical sensitivity at 85%, followed by throat, 80%, midturbinate, 62%, and saliva, 38%–52%. Clinical sensitivity for nasopharyngeal, throat, midturbinate, and saliva was 95%, 88%, 72%, and 44%–56%, respectively, if taken ≤7 days from onset of illness, and 70%, 67%, 47%, 28%–44% if & gt;7 days of illness. Comparing patients with upper respiratory tract infection (URTI) vs pneumonia, clinical sensitivity for nasopharyngeal, throat, midturbinate, and saliva was 92% vs 70%, 88% vs 61%, 70% vs 44%, 43%–54% vs 26%–45%, respectively. A combination of nasopharyngeal plus throat or midturbinate plus throat specimen afforded overall clinical sensitivities of 89%–92%; this rose to 96% for persons with URTI and 98% for persons ≤7 days from illness onset. Conclusions Nasopharyngeal specimens, followed by throat specimens, offer the highest clinical sensitivity for COVID-19 diagnosis in early illness. Clinical sensitivity improves and is similar when either midturbinate or nasopharyngeal specimens are combined with throat specimens. Upper respiratory specimens perform poorly if taken after the first week of illness or if there is pneumonia.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofaa335
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2757767-3
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  • 4
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    SnRK1A-Interacting Negative Regulators Modulate the Nutrient Starvation Signaling Sensor SnRK1 in Source-Sink Communication in Cereal Seedlings under Abiotic Stress  
    Oxford University Press (OUP) ; 2014
    In:  The Plant Cell Vol. 26, No. 2 ( 2014-03-26), p. 808-827
    Details
    In: The Plant Cell, Oxford University Press (OUP), Vol. 26, No. 2 ( 2014-03-26), p. 808-827
    Abstract: In plants, source-sink communication plays a pivotal role in crop productivity, yet the underlying regulatory mechanisms are largely unknown. The SnRK1A protein kinase and transcription factor MYBS1 regulate the sugar starvation signaling pathway during seedling growth in cereals. Here, we identified plant-specific SnRK1A-interacting negative regulators (SKINs). SKINs antagonize the function of SnRK1A, and the highly conserved GKSKSF domain is essential for SKINs to function as repressors. Overexpression of SKINs inhibits the expression of MYBS1 and hydrolases essential for mobilization of nutrient reserves in the endosperm, leading to inhibition of seedling growth. The expression of SKINs is highly inducible by drought and moderately by various stresses, which is likely related to the abscisic acid (ABA)–mediated repression of SnRK1A under stress. Overexpression of SKINs enhances ABA sensitivity for inhibition of seedling growth. ABA promotes the interaction between SnRK1A and SKINs and shifts the localization of SKINs from the nucleus to the cytoplasm, where it binds SnRK1A and prevents SnRK1A and MYBS1 from entering the nucleus. Our findings demonstrate that SnRK1A plays a key role regulating source-sink communication during seedling growth. Under abiotic stress, SKINs antagonize the function of SnRK1A, which is likely a key factor restricting seedling vigor.
    Type of Medium: Online Resource
    ISSN: 1532-298X , 1040-4651
    URL: Article
    DOI: 10.1105/tpc.113.121939
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2014
    detail.hit.zdb_id: 623171-8
    detail.hit.zdb_id: 2004373-9
    SSG: 12
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  • 5
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    Ribavirin Reduces Mortality in Enterovirus 71–Infected Mice by Decreasing Viral Replication
    Oxford University Press (OUP) ; 2008
    In:  The Journal of Infectious Diseases Vol. 197, No. 6 ( 2008-03-15), p. 854-857
    Details
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 197, No. 6 ( 2008-03-15), p. 854-857
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Issue
    URL: Article
    DOI: 10.1086/587999
    DOI: 10.1086/527326
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2008
    detail.hit.zdb_id: 1473843-0
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  • 6
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    Epidemiological and Clinical Predictors of COVID-19
    Oxford University Press (OUP) ; 2020
    In:  Clinical Infectious Diseases Vol. 71, No. 15 ( 2020-07-28), p. 786-792
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 71, No. 15 ( 2020-07-28), p. 786-792
    Abstract: Rapid identification of COVID-19 cases, which is crucial to outbreak containment efforts, is challenging due to the lack of pathognomonic symptoms and in settings with limited capacity for specialized nucleic acid–based reverse transcription polymerase chain reaction (PCR) testing. Methods This retrospective case-control study involves subjects (7–98 years) presenting at the designated national outbreak screening center and tertiary care hospital in Singapore for SARS-CoV-2 testing from 26 January to 16 February 2020. COVID-19 status was confirmed by PCR testing of sputum, nasopharyngeal swabs, or throat swabs. Demographic, clinical, laboratory, and exposure-risk variables ascertainable at presentation were analyzed to develop an algorithm for estimating the risk of COVID-19. Model development used Akaike’s information criterion in a stepwise fashion to build logistic regression models, which were then translated into prediction scores. Performance was measured using receiver operating characteristic curves, adjusting for overconfidence using leave-one-out cross-validation. Results The study population included 788 subjects, of whom 54 (6.9%) were SARS-CoV-2 positive and 734 (93.1%) were SARS-CoV-2 negative. The median age was 34 years, and 407 (51.7%) were female. Using leave-one-out cross-validation, all the models incorporating clinical tests (models 1, 2, and 3) performed well with areas under the receiver operating characteristic curve (AUCs) of 0.91, 0.88, and 0.88, respectively. In comparison, model 4 had an AUC of 0.65. Conclusions Rapidly ascertainable clinical and laboratory data could identify individuals at high risk of COVID-19 and enable prioritization of PCR testing and containment efforts. Basic laboratory test results were crucial to prediction models.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciaa322
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2002229-3
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