David C. Lye

Prof. David C. Lye

orcid

Research Focus & Metrics

Academic Career Length

22Years (2005-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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5 November 2020 in New England Journal of Medicine
Verified
Journal Article
Closed access
PDF file
JBJohn H. Beigel
John H. Beigel
KTKay M. Tomashek
Kay M. Tomashek
LDLori E. Dodd
Lori E. Dodd
AMAneesh K. Mehta
Aneesh K. Mehta
BZBarry S. Zingman
Barry S. Zingman
HLH. Clifford Lane
H. Clifford Lane
Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 ClinicalTrials.gov number, NCT04280705.)

21 April 2020 in JAMA
Verified
Journal Article
Open access
PDF file
BYBarnaby Edward Young
Barnaby Edward Young
SOSean Wei Xiang Ong
Sean Wei Xiang Ong
SKShirin Kalimuddin
Shirin Kalimuddin
JLJenny G. Low
Jenny G. Low
STSeow Yen Tan
Seow Yen Tan
DLDavid C. Lye
David C. Lye
The third novel coronavirus in 17 years emerged in Wuhan, China, in December 2019.1 Phylogenetics has indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is closely related to bat-derived SARS-like coronaviruses.2 Early reports from Wuhan described the associated coronavirus disease 2019 (COVID-19) as a SARS-like atypical pneumonia in which 26% to 33% of patients required intensive care and 4% to 15% died.1,3,4 A large case series of 72 314 infected individuals has since refined these initial estimates in China to severe disease in 14% and a case-fatality rate of 2.3%.5

21 August 2020 in Science
Verified
Journal Article
Open access
PDF file
JHJohanna Hansen
Johanna Hansen
ABAlina Baum
Alina Baum
KPKristen E. Pascal
Kristen E. Pascal
VRVincenzo Russo
Vincenzo Russo
SGStephanie Giordano
Stephanie Giordano
CKChristos A. Kyratsous
Christos A. Kyratsous
An antibody cocktail against SARS-CoV-2: There is an urgent focus on antibodies that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral spike and prevent the virus from entering host cells. Hansen et al. generated a large panel of antibodies against the spike protein from humanized mice and recovered patients. From this panel, they identified several neutralizing antibodies, including pairs that do not compete for binding to the receptor binding domain. Baum et al. focused in on four of these antibodies. All four are effective against known spike variants. However, by growing a pseudovirus that expresses the spike in the presence of individual antibodies, the authors were able to select for spike mutants resistant to that antibody. In contrast, escape mutants are not selected when pseudovirus is grown in the presence of pairs of antibodies that either do not compete or only partially compete for binding to the RBD. Such a pair might be used in a therapeutic antibody cocktail. Science , this issue p. 1010 , p. 1014

23 July 2020 in Nature Biotechnology
Verified
Journal Article
Open access
PDF file
CTChee Wah Tan
Chee Wah Tan
WCWan Ni Chia
Wan Ni Chia
XQXijian Qin
Xijian Qin
PLPei Liu
Pei Liu
MCMark I.-C. Chen
Mark I.-C. Chen
LWLin-Fa Wang
Lin-Fa Wang
A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95–100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.

29 May 2020 in Nature Communications
Verified
Journal Article
Open access
PCPo Ying Chia
Po Ying Chia
KCKristen Kelli Coleman
Kristen Kelli Coleman
YTYian Kim Tan
Yian Kim Tan
SOSean Wei Xiang Ong
Sean Wei Xiang Ong
MGMarcus Gum
Marcus Gum
DMDaniela Moses
Daniela Moses
Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ2 test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1–4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.

11 September 2018 in JAMA
Verified
Journal Article
Open access
PDF file
PHPatrick Harris
Patrick Harris
PTPaul A. Tambyah
Paul A. Tambyah
DLDavid C. Lye
David C. Lye
YMYin Mo
Yin Mo
TLTau H. Lee
Tau H. Lee
F(for the MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN)
for the MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN)
Quiz Ref ID Gram-negative bacteria that produce extended-spectrum β-lactamase (ESBL) enzymes are a global public health concern.1 Based on national surveillance data from 2011, the US Centers for Disease Control and Prevention estimated that ESBL producers accounted for at least 26 000 infections and 1700 deaths annually.2 A key feature of ESBL-producing Enterobacteriaceae is phenotypic resistance to oxyiminocephalosporins, in addition to penicillins.3 ESBL producers are increasingly commonplace in both community and health care settings.4 Carbapenems have been regarded as the treatment of choice for serious infections caused by ESBL producers.3,5 However, increased use of carbapenems may select for carbapenem resistance in gram-negative bacilli,6,7 which currently represents the greatest threat in terms of antibiotic resistance.