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Nat Commun ; 13(1): 1687, 2022 03 30.
Article in English | MEDLINE | ID: covidwho-1768823


Rapid and sensitive diagnostics of infectious diseases is an urgent and unmet need as evidenced by the COVID-19 pandemic. Here, we report a strategy, based on DIgitAl plasMONic nanobubble Detection (DIAMOND), to address this need. Plasmonic nanobubbles are transient vapor bubbles generated by laser heating of plasmonic nanoparticles (NPs) and allow single-NP detection. Using gold NPs as labels and an optofluidic setup, we demonstrate that DIAMOND achieves compartment-free digital counting and works on homogeneous immunoassays without separation and amplification steps. DIAMOND allows specific detection of respiratory syncytial virus spiked in nasal swab samples and achieves a detection limit of ~100 PFU/mL (equivalent to 1 RNA copy/µL), which is competitive with digital isothermal amplification for virus detection. Therefore, DIAMOND has the advantages including one-step and single-NP detection, direct sensing of intact viruses at room temperature, and no complex liquid handling, and is a platform technology for rapid and ultrasensitive diagnostics.

COVID-19 , Pandemics , COVID-19/diagnosis , DNA Viruses , Gold , Humans , Lasers
Sci Rep ; 11(1): 24442, 2021 12 24.
Article in English | MEDLINE | ID: covidwho-1577650


Therapeutic interventions targeting viral infections remain a significant challenge for both the medical and scientific communities. While specific antiviral agents have shown success as therapeutics, viral resistance inevitably develops, making many of these approaches ineffective. This inescapable obstacle warrants alternative approaches, such as the targeting of host cellular factors. Respiratory syncytial virus (RSV), the major respiratory pathogen of infants and children worldwide, causes respiratory tract infection ranging from mild upper respiratory tract symptoms to severe life-threatening lower respiratory tract disease. Despite the fact that the molecular biology of the virus, which was originally discovered in 1956, is well described, there is no vaccine or effective antiviral treatment against RSV infection. Here, we demonstrate that targeting host factors, specifically, mTOR signaling, reduces RSV protein production and generation of infectious progeny virus. Further, we show that this approach can be generalizable as inhibition of mTOR kinases reduces coronavirus gene expression, mRNA transcription and protein production. Overall, defining virus replication-dependent host functions may be an effective means to combat viral infections, particularly in the absence of antiviral drugs.

Coronavirus/metabolism , Respiratory Syncytial Virus, Human/metabolism , TOR Serine-Threonine Kinases/metabolism , Viral Proteins/metabolism , A549 Cells , Coronavirus/drug effects , Coronavirus/genetics , Gene Expression Regulation, Viral/drug effects , Humans , Protein Biosynthesis/drug effects , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , RNA Interference , RNA, Small Interfering/metabolism , Rapamycin-Insensitive Companion of mTOR Protein/antagonists & inhibitors , Rapamycin-Insensitive Companion of mTOR Protein/genetics , Rapamycin-Insensitive Companion of mTOR Protein/metabolism , Regulatory-Associated Protein of mTOR/antagonists & inhibitors , Regulatory-Associated Protein of mTOR/genetics , Regulatory-Associated Protein of mTOR/metabolism , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/pathology , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus, Human/drug effects , Respiratory Syncytial Virus, Human/isolation & purification , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/genetics , Viral Proteins/genetics
Children (Basel) ; 8(9)2021 Aug 30.
Article in English | MEDLINE | ID: covidwho-1390545


BACKGROUND: The lack of SARS-CoV-2 antigen surveillance testing in the pediatric population has inhibited accurate infection and hospitalization prevalence estimates. We aim to report the estimated prevalence of and risk factors for COVID-19 infection, hospitalization, and intensive care unit (ICU) admission across the three United States (US) waves in one of the largest pediatric healthcare systems in the nation. METHODS: Retrospective electronic health record (EHR) review of all COVID-19 surveillance data among children aged 0-19 years seeking healthcare at one pediatric healthcare system that serves predominantly Medicaid-dependent families from 1 March 2020 to 31 March 2021. COVID-19 infection status (Y/N), hospital admission (Y/N), and ICU admission (Y/N) are the main outcomes. RESULTS: Of 22,377 children aged ≤ 19 years tested for SARS-CoV-2 infection from March 2020-March 2021, 3126 were positive (14.0%), and out of those positive, 53.7% were hospitalized and 2.9% were admitted to the ICU. Compared to Wave 1 (1 March 2020-31 May 2020), the risk of a positive test increased from 16% (RR 1.16, 95% CI, 1.07-1.26) in Wave 2 (1 June 2020-31 October 2020) to 33% (RR 1.33, 95% CI, 1.23-1.44) in Wave 3 (1 November 2020-31 March 2021). Similarly, compared to Wave 1, the risk for hospitalization increased 86% (RR 1.86, 95% CI, 1.86-2.06) in Wave 2 and 89% in Wave 3 (RR 1.89, 95% CI, 1.70-2.08), and the risk for ICU admission increased from 10% in Wave 2 (RR 1.10, 95% CI, 0.39-3.01) to 310% in Wave 3 (RR 3.10, 95% CI, 1.21-7.80). Children with asthma, depressive disorders, type 1 or 2 diabetes, and anemia were more likely to be hospitalized while children with diabetes, obesity, cardiac malformations, and hypertension were more likely to be admitted to the ICU versus children without these conditions. CONCLUSIONS: Children were cumulatively impacted by the COVID-19 pandemic through the three US waves with more than a third hospitalized in Wave 3. Children with underlying health conditions were particularly at risk for severe illness and should be monitored for any long-term impacts.