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"Chan, Wai"
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Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial
Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir–ritonavir, and ribavirin for treating patients with COVID-19.
This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688.
Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3–7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5–11]) than the control group (12 days [8–15]; hazard ratio 4·37 [95% CI 1·86–10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir–ritonavir because of biochemical hepatitis. No patients died during the study.
Early triple antiviral therapy was safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted.
The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.
Journal Article
The future of translation technology : towards a world without Babel
Technology has revolutionised the field of translation, bringing drastic changes to the way translation is studied and done. To an average user, technology is simply about clicking buttons and storing data. What we need to do is to look beyond a system's interface to see what is at work and what should be done to make it work more efficiently. This book is both macroscopic and microscopic in approach: macroscopic as it adopts a holistic orientation when outlining the development of translation technology in the last 40 years, organising concepts in a coherent and logical way with a theoretical framework, and predicting what is to come in the years ahead; microscopic as it examines in detail the five stages of technology-oriented translation procedure and the strengths and weaknesses of the free and paid systems available to users.
Book
Evaluation of Energy Consumption in Block-Chains with Proof of Work and Proof of Stake
Although there are several special features in block-chain technology such as machine trust, traceability, and security, high energy consumption remains an issue in broadening the applications of block-chain technology. Some researchers proposed the use of proof of stake (PoS) mechanism rather than proof of work (PoW) mechanism to reduce energy consumption of block-chain. However, because PoS cannot guarantee fairness, mixed consensus mechanisms could be a solution and has been adopted in many studies. This paper aims to evaluate the performances of PoW, PoS and mixed consensus mechanisms from three aspects: energy consumption, fairness, and reliability. An agent-based model of a typical block-chain system equipped with different consensus mechanisms is created in NetLogo. This model simulates and evaluates the performances of different consensus mechanisms in the block-chain system.
Journal Article
Neutralizing antibody titres in SARS-CoV-2 infections
The SARS-CoV-2 pandemic poses the greatest global public health challenge in a century. Neutralizing antibody is a correlate of protection and data on kinetics of virus neutralizing antibody responses are needed. We tested 293 sera from an observational cohort of 195 reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections collected from 0 to 209 days after onset of symptoms. Of 115 sera collected ≥61 days after onset of illness tested using plaque reduction neutralization (PRNT) assays, 99.1% remained seropositive for both 90% (PRNT
90
) and 50% (PRNT
50
) neutralization endpoints. We estimate that it takes at least 372, 416 and 133 days for PRNT
50
titres to drop to the detection limit of a titre of 1:10 for severe, mild and asymptomatic patients, respectively. At day 90 after onset of symptoms (or initial RT-PCR detection in asymptomatic infections), it took 69, 87 and 31 days for PRNT
50
antibody titres to decrease by half (T
1/2
) in severe, mild and asymptomatic infections, respectively. Patients with severe disease had higher peak PRNT
90
and PRNT
50
antibody titres than patients with mild or asymptomatic infections. Age did not appear to compromise antibody responses, even after accounting for severity. We conclude that SARS-CoV-2 infection elicits robust neutralizing antibody titres in most individuals.
Here, the authors perform plaque reduction neutralization (PRNT) assays quantitating SARS-CoV-2 specific neutralizing antibodies from 195 patients in different disease states and find that patients with severe disease exhibit higher peaks of neutralizing antibody titres than patients with mild or asymptomatic infections and that serum neutralizing antibody persists for over 6 months in most people.
Journal Article
Multimorbidity and adverse events of special interest associated with Covid-19 vaccines in Hong Kong
Prior research using electronic health records for Covid-19 vaccine safety monitoring typically focuses on specific disease groups and excludes individuals with multimorbidity, defined as ≥2 chronic conditions. We examine the potential additional risk of adverse events 28 days after the first dose of CoronaVac or Comirnaty imposed by multimorbidity. Using a territory-wide public healthcare database with population-based vaccination records in Hong Kong, we analyze a retrospective cohort of patients with chronic conditions. Thirty adverse events of special interest according to the World Health Organization are examined. In total, 883,416 patients are included and 2,807 (0.3%) develop adverse events. Results suggest vaccinated patients have lower risks of adverse events than unvaccinated individuals, multimorbidity is associated with increased risks regardless of vaccination, and the association of vaccination with adverse events is not modified by multimorbidity. To conclude, we find no evidence that multimorbidity imposes extra risks of adverse events following Covid-19 vaccination.
Adverse events resulting from COVID-19 vaccination are a public health concern and it is not known whether pre-existing conditions may impose an increased risk. Here, using electronic health records from Hong Kong, the authors show that adverse events are rare for all groups, and there is no evidence of risk modification due to multimorbidity.
Journal Article
Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments
Plasma consists of DNA released from multiple tissues within the body. Using genome-wide bisulfite sequencing of plasma DNA and deconvolution of the sequencing data with reference to methylation profiles of different tissues, we developed a general approach for studying the major tissue contributors to the circulating DNA pool. We tested this method in pregnant women, patients with hepatocellular carcinoma, and subjects following bone marrow and liver transplantation. In most subjects, white blood cells were the predominant contributors to the circulating DNA pool. The placental contributions in the plasma of pregnant women correlated with the proportional contributions as revealed by fetal-specific genetic markers. The graft-derived contributions to the plasma in the transplant recipients correlated with those determined using donor-specific genetic markers. Patients with hepatocellular carcinoma showed elevated plasma DNA contributions from the liver, which correlated with measurements made using tumor-associated copy number aberrations. In hepatocellular carcinoma patients and in pregnant women exhibiting copy number aberrations in plasma, comparison of methylation deconvolution results using genomic regions with different copy number status pinpointed the tissue type responsible for the aberrations. In a pregnant woman diagnosed as having follicular lymphoma during pregnancy, methylation deconvolution indicated a grossly elevated contribution from B cells into the plasma DNA pool and localized B cells as the origin of the copy number aberrations observed in plasma. This method may serve as a powerful tool for assessing a wide range of physiological and pathological conditions based on the identification of perturbed proportional contributions of different tissues into plasma.
Journal Article