Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses.
We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection.
Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years range 37–75). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R2>0·9). No genome mutations were detected on serial samples.
Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis.
Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.
The novel SARS-CoV-2 Omicron variant (B.1.1.529), first found in early November 2021, has sparked considerable global concern and it has >50 mutations, many of which are known to affect ...transmissibility or cause immune escape. In this study, we sought to investigate the virological characteristics of the Omicron variant and compared it with the Delta variant which has dominated the world since mid-2021. Omicron variant replicated more slowly than the Delta variant in transmembrane serine protease 2 (TMPRSS2)-overexpressing VeroE6 (VeroE6/TMPRSS2) cells. Notably, the Delta variant replicated well in Calu3 cell line which has robust TMPRSS2 expression, while the Omicron variant replicated poorly in this cell line. Competition assay showed that Delta variant outcompeted Omicron variant in VeroE6/TMPRSS2 and Calu3 cells. To confirm the difference in entry pathway between the Omicron and Delta variants, we assessed the antiviral effect of bafilomycin A1, chloroquine (inhibiting endocytic pathway), and camostat (inhibiting TMPRSS2 pathway). Camostat potently inhibited the Delta variant but not the Omicron variant, while bafilomycin A1 and chloroquine could inhibit both Omicron and Delta variants. Moreover, the Omicron variant also showed weaker cell-cell fusion activity when compared with Delta variant in VeroE6/TMPRSS2 cells. Collectively, our results suggest that Omicron variant infection is not enhanced by TMPRSS2 but is largely mediated via the endocytic pathway. The difference in entry pathway between Omicron and Delta variants may have an implication on the clinical manifestations or disease severity.
Abstract
Background
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant, designated as a variant of concern by the World Health Organization, carries numerous spike ...mutations that are known to evade neutralizing antibodies elicited by coronavirus disease 2019 (COVID-19) vaccines. A deeper understanding of the susceptibility of omicron variant to vaccine-induced neutralizing antibodies is urgently needed for risk assessment.
Methods
Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the omicron, delta and beta variants to sera from 25 BNT162b2 and 25 CoronaVac vaccine recipients was determined using a live virus microneutralization assay.
Results
The omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains deposited in the GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the omicron variant HKU691 and HKU344-R346K, respectively, whereas none of the CoronaVac recipients had detectable neutralizing antibody titer against either omicron isolate. For BNT162b2 recipients, the geometric mean neutralization antibody titers (GMTs) of the omicron variant isolates (5.43 and 6.42) were 35.7–39.9-fold lower than that of the ancestral virus (229.4), and the GMTs of both omicron variant isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMTs between HKU691 and HKU344-R346K.
Conclusions
Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the omicron variant may be associated with lower COVID-19 vaccine effectiveness.
Immune sera from BNT162b2 and Coronavac recipients had substantially reduced neutralizing antibody titers against the omicron variant. There was no statistically significant difference between the geometric mean neutralization titers against omicron variant strains with or without spike R346K mutation.
As the most populous country in the world, China has made strides in health promotion in the past few decades. With the aging population, the burden of cancer in China continues to grow. Changes in ...risk factors for cancer, especially diet, obesity, diabetes, and air pollution, continue to fuel the shift of cancer transition in China. The burden of upper gastrointestinal cancer in China is decreasing, but still heavy. The rising burden of colorectal, prostate, and breast cancers is also significant. Lung cancer became the top cause of cancer-related deaths, together with smoking as the most important contributor to cancer deaths. The Chinese government has taken several approaches to control cancer and cancer-related risk factors. Many achievements have been made, but some challenges remain. Health China 2030 is ambitious and depicts a bright vision of the future for cancer control in China. The decrease in the cancer burden in China will require cross-sector collaboration and coordinated efforts on primary and secondary preventions by governments, public health organizations, and individuals. In this review, we describe the trends of cancer burden and discuss cancer-related risk factors in China, identifying strategies to reduce the burden of cancer in China.
Coronavirus disease 2019 (COVID-19) has a wide spectrum of disease severity from mild upper respiratory symptoms to respiratory failure. The role of neutralizing antibody (NAb) response in disease ...progression remains elusive. This study determined the seroprevalence of 733 non-COVID-19 individuals from April 2018 to February 2020 in the Hong Kong Special Administrative Region and compared the neutralizing antibody (NAb) responses of eight COVID-19 patients admitted to the intensive care unit (ICU) with those of 42 patients not admitted to the ICU. We found that NAb against SARS-CoV-2 was not detectable in any of the anonymous serum specimens from the 733 non-COVID-19 individuals. The peak serum geometric mean NAb titer was significantly higher among the eight ICU patients than the 42 non-ICU patients (7280 95% confidence interval (CI) 1468-36099) vs (671 95% CI, 368-1223). Furthermore, NAb titer increased significantly at earlier infection stages among ICU patients than among non-ICU patients. The median number of days to reach the peak Nab titers after symptoms onset was shorter among the ICU patients (17.6) than that of the non-ICU patients (20.1). Multivariate analysis showed that oxygen requirement and fever during admission were the only clinical factors independently associated with higher NAb titers. Our data suggested that SARS-CoV-2 was unlikely to have silently spread before the COVID-19 emergence in Hong Kong. ICU patients had an accelerated and augmented NAb response compared to non-ICU patients, which was associated with disease severity. Further studies are required to understand the relationship between high NAb response and disease severity.
This letter proposes an improved nearest-level modulation (NLM) method to enhance the quality of output voltage of a modular multilevel converter (MMC) with the low amount of submodules, as well as ...restrain the voltage fluctuation of the submodules. By adding a small offset, which is alternating at the double fundamental frequency to the reference signals, a small phase shift of the step-changing moment between upper and lower arms' voltage emerges. As a result, an odd-level difference between the output voltage of lower arm and that of upper arm occurs, which can increase the level number of output voltage from N + 1 to 2N + 1, where N is the number of submodules per arm. With the proposed method, the total harmonic distortion (THD) of the output voltage is mitigated without increasing the switching frequency of IGBTs or changing the average voltage of submodules' capacitor. In addition, within a special range of power factor angle, the circulating current can be reduced by choosing the proper phase between the fundamental and the double fundamental frequency. Simulation and experimental results verify the effectiveness and validity of the proposed NLM scheme.
Cancer has become the most common cause of death in China. Owing to rapid economic development, improved livelihood, and shifts in risk factors, cancer epidemiology has experienced substantial ...changes during the past several decades. In this review, we aim to describe the current cancer epidemiology of the main types of cancer in China, report major risk factors associated with cancer development, and summarize the contributions of the Chinese government to controlling the cancer burden. A total of 4,064,000 new cases were diagnosed in China in 2016. The most frequent types are lung cancer (828,100; 20.4％), colorectal cancer (408,000; 10.0％), and gastric cancer (396,500; 9.8％). Lung (657,000; 27.2％), liver (336,400, 13.9％), and stomach (288,500; 12.0％) cancers are the 3 most deadly cancers in the general population. The 5-year survival rate for cancer has dramatically increased in recent decades. However, liver and particularly pancreatic cancers still have the poorest prognosis. The main modifiable risk factors associated with cancer development include infectious agents, smoking, alcohol consumption, obesity, unhealthful dietary habits, and inadequate physical activity. The Chinese government has made unremitting efforts to decrease the cancer burden, including cancer education and investment in cancer screening programs.
Evidence on the role of physical activity (PA) on healthcare utilization and expenditure is limited in China. We aimed to examine the association between the total physical activity (TPA) per week, ...healthcare service use and expenditure.
We extracted the data from China Health and Retirement Longitudinal Study (CHARLS) 2011, 2013, and 2015. Participants more than 50 years old who completed the follow-up for the three waves were enrolled. We converted the volume of vigorous physical activity (VPA) into an equivalent volume of moderate physical activity (MPA) and calculated the TPA per week for each participant. 12,927 of the 17,708 participants in CHARLS were included in our analysis. More than one-third of participants over 50 years old never participate in any moderate or intensity activity, and the median of self-reported moderate or intensity PA was about 525 (IQR 0-1680) MET-minutes per week in 2015.
Compared to inactive subjects, the highest level of TPA was significantly related to the decreased risk number of inpatient visits (IRR: 0.58; 95% CI:0.50-0.67, p < 0.001), inpatient hospital days (IRR: 0.60; 95% CI: 0.42-0.84, p < 0.01), healthcare expenditure (IRR: 0.71; 95% CI: 0.65-0.79, p < 0.001) and catastrophic health expenditures (OR: 0.57; 95% CI: 0.45-0.72, p < 0.001) after adjusting for covariates.
Engaging in moderate-to-vigorous PA may drive a potential decrease in healthcare utilization, healthcare expenditure and household financial risk with a dose-response relationship in China, and some possible policy implications in public health may be considered to promote exercise in the middle-aged and elderly to reduce the medical burden on individuals and healthcare systems.
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