LC-MS/MS Determination of 88 Psychotropic Drugs in 1865 Hair Samples From Addicts in Drug Abstinence.

The emergence of novel drugs and the continuous expansion of the scope of the types of drugs under control have greatly increased requests for screening of a range of drugs in hair. Here, a multi-analyte method for the detection and quantification of 88 psychotropic drugs in the hair of addicts in drug abstinence was developed and fully validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hair samples (25 mg) were washed, cut into pieces, cryogenically ground, and extracted in methanol. The extracted analytes were separated on an Allure PFPP column (100×2.1 mm, 5 mm i.d., Restek, USA) and analyzed by LC-MS/MS in multiple reaction monitoring mode. The limits of detection and limits of quantification ranged from 0.1 to 20 pg/mg and 0.2 to 50 pg/mg, respectively. The intra- and inter-assay precisions (RSD) of all analysis ranged from 0.9 to 14.9% and 1.9 to 15.9%, respectively. Accuracy values were 100±20%. The extraction recovery of quality control samples ranged from 50.9% to 99.6% for all analytes. The matrix effects for all analytes ranged from 46.8% to 99.7%. The method was successfully used to analyze 1,865 hair samples from addicts in drug rehabilitation at their own communities.. Among the samples, 129 cases were positive; the majority of positive cases were from males (78.29%), 92.25% of whom were over 35 years old. Traditional drugs, like methamphetamine and opioids, accounted for most positive cases, and 27 of the abstinence cases with a use history of methamphetamine were still positive. In addition to abused drugs, like methamphetamine, morphine, and cocaine, the sedative hypnotic and psychotherapeutic drugs, including clonazepam, alprazolam, estazolam, zolpidem, and quetiapine, were detected in 26% of the hair samples, suggesting that these addicts may have insomnia and mental problems such as depression and psychosis, probably due to the long-term effects of drugs and withdrawal reactions. Three synthetic cannabinoids were also detected in 4 (2.7%) cases. A total of 37 cases were positive for methadone, tramadol, and dextromethorphan, reflecting a new trend of alternative drug use when traditional drugs were not easy to obtain during the COVID-19 outbreak.

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial.

BACKGROUND: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. METHODS: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. FINDINGS: Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57-0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. INTERPRETATION: Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19. FUNDING: Sponsored by the University of Dundee and supported through an Investigator Initiated Research award from Insmed, Bridgewater, NJ; STOP-COVID19 trial.

Eugenol Alleviates TGEV-Induced Intestinal Injury via Suppressing ROS/NLRP3/GSDMD-Dependent Pyroptosis.

Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Pyroptosis is involved in the pathogenesis of coronavirus, but its role in TGEV-induced intestinal injury has yet to be fully elucidated. Eugenol, an essential plant oil, plays a vital role in antiviral innate immune responses. We demonstrate the preventive effect of eugenol on TGEV infection. Eugenol alleviates TGEV-induced intestinal epithelial cell pyroptosis and reduces intestinal injury in TGEV-infected piglets. Mechanistically, eugenol reduces the activation of NLRP3 inflammasome, thereby inhibiting TGEV-induced intestinal epithelial cell pyroptosis. In addition, eugenol scavenges TGEV-induced reactive oxygen species (ROS) increase, which in turn prevents TGEV-induced NLRP3 inflammasome activation and pyroptosis. Overall, eugenol protects the intestine by reducing TGEV-induced pyroptosis through inhibition of NLRP3 inflammasome activation, which may be mediated through intracellular ROS levels. These findings propose that eugenol may be an effective strategy to prevent TGEV infection.

Hepatitis of unknown etiology in children: Current evidence and association.

Two years after the coronavirus disease 2019 (COVID-19) pandemic, acute hepatitis of unknown etiology in children (AHUCD) began to be reported worldwide. The novel coronavirus and adenovirus were found in pathogen and antibody tests in AHUCD cases reported by the World Health Organization. Children are not exposed to the viruses that children are generally exposed to owing to COVID-19 infection preventive measures such as isolation and wearing masks; therefore, some researchers have speculated that this disease is related to reduced exposure to pathogens. Some scientists have also speculated that the disease is related to liver injury and adenoviral hepatitis, which are the sequelae of COVID-19. Some evidence also suggests a weak association between the disease and COVID-19 vaccination. Therefore, further research and investigation of the pathogenesis, preventive measures, and early treatment of hepatitis of unknown etiology are required. This study aimed to synthesize available evidence to further elucidate this disease in order to treat and prevent it effectively.

Eugenol Attenuates Transmissible Gastroenteritis Virus-Induced Oxidative Stress and Apoptosis Via ROS-NRF2-ARE Signaling.

Transmissible gastroenteritis virus (TGEV), a coronavirus that causes severe diarrhea due to oxidative stress in the piglet intestine, is a major cause of economic loss in the livestock industry. However, limited interventions have been shown to be effective in the treatment of TGEV. Here, we demonstrate the therapeutic activity of eugenol in TGEV-induced intestinal oxidative stress and apoptosis. Our data show that eugenol supplementation protects intestine and IPEC-J2 cells from TGEV-induced damage. Mechanistically, eugenol reduces TGEV-induced oxidative stress in intestinal epithelial cells by reducing reactive oxygen species levels. Interestingly, eugenol also inhibits TGEV-induced intestinal cell apoptosis in vitro and in vivo. In conclusion, our data suggest that eugenol prevents TGEV-induced intestinal oxidative stress by reducing ROS-mediated damage to antioxidant signaling pathways. Therefore, eugenol may be a promising therapeutic strategy for TGEV infection.

Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-κB signaling pathway.

Increasing evidence supports the ability of eugenol to maintain intestinal barrier integrity and anti-inflammatory in vitro and in vivo; however, whether eugenol alleviates virus-mediated intestinal barrier damage and inflammation remains a mystery. Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Here, we found that eugenol could alleviate TGEV-induced intestinal functional impairment and inflammatory responses in piglets. Our results indicated that eugenol improved feed efficiency in TGEV-infected piglets. Eugenol not only increased serum immunoglobulin concentration (IgG) but also significantly decreased serum inflammatory cytokine concentration (TNF-α) in TGEV-infected piglets. In addition, eugenol also significantly decreased the expression of NF-κB mRNA and the phosphorylation level of NF-κB P65 protein in the jejunum mucosa of TGEV-infected piglets. Eugenol increased villus height and the ratio of villus height to crypt depth in the jejunum and ileum, and decreased serum D-lactic acid levels. Importantly, eugenol increased tight junction protein (ZO-1) and mRNA expression levels of nutrient transporter-related genes (GluT-2 and CaT-1) in the jejunum mucosa of TGEV-infected piglets. Meanwhile, compared with TGEV-infected IPEC-J2 cells, treatment with eugenol reduced the cell cytopathic effect, attenuated the inflammatory response. Interestingly, eugenol did not increase the expression of ZO-1 and Occludin in IPEC-J2 cells. However, western blot and immunofluorescence results showed that eugenol restored TGEV-induced down-regulation of ZO-1 and Occludin, while BAY11-7082 (The NF-κB specific inhibitor) enhanced the regulatory ability of eugenol. Our findings demonstrated that eugenol attenuated TGEV-induced intestinal injury by increasing the expression of ZO-1 and Occludin, which may be related to the inhibition of NF-κB signaling pathway. Eugenol may offer some therapeutic opportunities for coronavirus-related diseases.

Neutrophil proteomics identifies temporal changes and hallmarks of delayed recovery in COVID19 (preprint)

RationaleNeutrophils are important in the pathophysiology of COVID19 but the molecular changes contributing to altered neutrophil phenotypes following SARS-CoV-2 infection are not fully understood. ObjectivesTo use quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes following acute SARS-CoV-2 infection and during recovery. MethodsProspective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May 2020-December 2020). Patients were enrolled within 96 hours of admission, with longitudinal sampling up to 29 days. Control groups comprised non-COVID19 acute lower respiratory tract infection (LRTI) and age-matched non-infected controls. Neutrophils isolated from peripheral blood were processed for mass spectrometry. COVID19 severity and recovery were defined using the WHO ordinal scale. Measurements and Main Results84 COVID19 patients were included and compared to 91 LRTI patients and 42 controls. 5,800 neutrophil proteins were identified and 1,748 proteins were significantly different (q-value<0.05) in neutrophils from COVID19 patients compared to those of non-infected controls, including a robust interferon response at baseline, which was lost in severe patients one week after enrolment. Neutrophil changes associated with COVID19 disease severity and prolonged illness were characterized and candidate targets for modulation of neutrophil function were identified. Delayed recovery from COVID19 was associated with changes in metabolic and signalling proteins, complement, chemokine and leukotriene receptors, integrins and inhibitory receptors. ConclusionsSARS-CoV-2 infection results in the sustained presence of recirculating neutrophils with distinct metabolic profiles and altered capacities to respond to migratory signals and cues from other immune cells, pathogens or cytokines. Scientific Knowledge on the SubjectInflammation is the primary driver of morbidity and mortality in severe COVID19. Type I interferon responses, T-cell exhaustion, cytokine storm, emergency myelopoiesis, myeloid compartment dysregulation and procoagulant pathway activation are well established contributors to COVID19 disease severity. Neutrophils play an important role in COVID19, with elevated neutrophil-to-lymphocyte ratios and the emergence of a circulating immature neutrophil population in individuals with severe symptoms. Neutrophil infiltration in the lungs coupled with the release of neutrophil extracellular traps has also been reported in severe and fatal COVID19. The aim of this study was to quantitatively map the proteomes of peripheral blood neutrophils from a cohort of hospitalised COVID19 patients to understand how SARS-CoV-2 infection changes neutrophil phenotypes and functional capacity. What this study adds to the fieldHigh-resolution mass spectrometry was used to characterise the proteomes of peripheral blood neutrophils from >200 individuals at different stages of disease. This work has comprehensively mapped neutrophil molecular changes associated with mild and severe COVID19 and identified significant quantitative changes in more than 1700 proteins in neutrophils from patients hospitalised with COVID19 versus patients with non-COVID19 acute respiratory infections. The study identifies neutrophil protein signatures associated with COVID19 disease severity. The data also show that alterations in neutrophil proteomes can persist in fully recovered patients and identify distinct neutrophil proteomes in recovered versus non recovered patients. Our study provides novel insights into neutrophil responses during acute COVID19 and reveals that altered neutrophil phenotypes persist in convalescent COVID19 patients.

Pharmacokinetic Study of Coadministration with Cefuroxime Sodium for Injection Influencing ReDuNing Injection-Derived Seven Phytochemicals and Nine Metabolites in Rats.

According to the sixth edition of China's "New Coronavirus Diagnosis and Treatment Plan (NCDTP)," ReDuNing injection (RDN) was firstly introduced to treat severe and critical COVID-19, whereas its combination with broad-spectrum antibiotics was suggested to take with extreme caution and full reasons. Therefore, we aim to describe the pharmacokinetics of seven active phytochemicals and semiquantification of nine relevant metabolites in ReDuNing injection (RDN) after combining with cefuroxime sodium (CNa) for injection in rat plasma. Male Sprague-Dawley rats were randomly assigned to six groups, and they were intravenously administered, respectively, with different prescriptions of RDN (2 mL/kg) and CNa (225 mg/kg). At different time points (0.03, 0.08, 0.17, 0.24, 0.33, 0.50, 0.67, 1, and 6 h) after administration, the drug concentrations of iridoids glycosides, organic acids, and metabolites in rat plasma were determined using ultrahigh-pressure liquid chromatography coupled with linear ion rap-orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS), and main pharmacokinetic parameters were estimated by noncompartment model. The results showed that there were differences in pharmacokinetic parameters, AUC(0-t), T1/2, C max, CL of iridoids glycosides, and organic acids, after the intravenous administration of the different combinations of RDN and CNa. Moreover, different combinations of the injections also resulted in different curves of relative changes of each metabolite. The obtained results suggested that RDN and CNa existed pharmacokinetic drug-herb interactions in rats. The findings not only lay the foundation for evaluating the safety of RDN injection combined with CNa but also make contributions to clinically applying RDN injection combined with CNa, which works potentially against severe forms of COVID-19.

Impact of COVID-19 on paediatric admissions to a Chinese hospital: a single-centre retrospective chart review.

OBJECTIVE: To explore the impact of the COVID-19 on the distribution, type and patterns of diseases in hospitalised children under local antiepidemic measures. DESIGN: Retrospective chart review. SETTING: Electronic medical records of patients hospitalised in the paediatric department of a tertiary hospital in South China from 21 January 2019 to 20 January 2021. PARTICIPANTS: Records of 2139 patients. OUTCOME MEASURES: Data were analysed before and during the COVID-19 pandemic. Disease characteristics were analysed based on the 10th revision of the International Statistical Classification of Diseases and Related Health Problems. Features of the length of hospital stay were investigated. Categorical variables involving more than three groups were analysed using an overall χ2 test, followed by pairwise comparisons. RESULTS: During the COVID-19 outbreak period, paediatric hospitalisation was reduced by 29.6%, from 1255 to 884. The proportions of infection-related diseases (36.3% (455 cases) vs 20.8% (184 cases)), respiratory system-related diseases (22.5% (283 cases) vs 9.4% (83 cases)); and endocrine, nutritional and metabolic diseases (17.1% (214 cases) vs 9.2% (81 cases)) decreased significantly, whereas that of musculoskeletal and connective tissue diseases increased from 11.0% (138 cases) to 20.1% (178 cases), thereby becoming the most common reason for hospitalisation. The proportions of diseases of the nervous system (12.4% (156 cases) to 18.8% (166 cases)) and mental and behavioural disorders (0.2% (3 cases) to 2.1% (19 cases)) increased significantly. The average length of hospital stay increased after the outbreak (7.57±6.53 vs 8.36±6.87). CONCLUSION: The number of hospitalisation cases decreased during the COVID-19 period. The prominent decreases in hospitalisation associated with infections and respiratory system diseases were likely attributed to the improved epidemic prevention work, enhancement of people's health awareness and fear of possible exposure to COVID-19. Describing the impact of COVID-19 on disease patterns may provide a reference for resource planning during the pandemic.

Epidemiological and virological surveillance of influenza viruses in China during 2020-2021.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, seasonal influenza activity declined globally and remained below previous seasonal levels, but intensified in China since 2021. Preventive measures to COVID-19 accompanied by different epidemic characteristics of influenza in different regions of the world. To better respond to influenza outbreaks under the COVID-19 pandemic, we analyzed the epidemiology, antigenic and genetic characteristics, and antiviral susceptibility of influenza viruses in the mainland of China during 2020-2021. METHODS: Respiratory specimens from influenza like illness cases were collected by sentinel hospitals and sent to network laboratories in Chinese National Influenza Surveillance Network. Antigenic mutation analysis of influenza virus isolates was performed by hemagglutination inhibition assay. Next-generation sequencing was used for genetic analyses. We also conducted molecular characterization and phylogenetic analysis of circulating influenza viruses. Viruses were tested for resistance to antiviral medications using phenotypic and/or sequence-based methods. RESULTS: In the mainland of China, influenza activity recovered in 2021 compared with that in 2020 and intensified during the traditional influenza winter season, but it did not exceed the peak in previous years. Almost all viruses isolated during the study period were of the B/Victoria lineage and were characterized by genetic diversity, with the subgroup 1A.3a.2 viruses currently predominated. 37.8% viruses tested were antigenically similar to reference viruses representing the components of the vaccine for the 2020-2021 and 2021-2022 Northern Hemisphere influenza seasons. In addition, China has a unique subgroup of 1A.3a.1 viruses. All viruses tested were sensitive to neuraminidase inhibitors and endonuclease inhibitors, except two B/Victoria lineage viruses identified to have reduced sensitivity to neuraminidase inhibitors. CONCLUSIONS: Influenza activity increased in the mainland of China in 2021, and caused flu season in the winter of 2021-2022. Although the diversity of influenza (sub)type decreases, B/Victoria lineage viruses show increased genetic and antigenic diversity. The world needs to be fully prepared for the co-epidemic of influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus globally.

Natural Language Processing to Identify Digital Learning Tools in Postgraduate Family Medicine: Protocol for a Scoping Review.

BACKGROUND: The COVID-19 pandemic has highlighted the growing need for digital learning tools in postgraduate family medicine training. Family medicine departments must understand and recognize the use and effectiveness of digital tools in order to integrate them into curricula and develop effective learning tools that fill gaps and meet the learning needs of trainees. OBJECTIVE: This scoping review will aim to explore and organize the breadth of knowledge regarding digital learning tools in family medicine training. METHODS: This scoping review follows the 6 stages of the methodological framework outlined first by Arksey and O'Malley, then refined by Levac et al, including a search of published academic literature in 6 databases (MEDLINE, ERIC, Education Source, Embase, Scopus, and Web of Science) and gray literature. Following title and abstract and full text screening, characteristics and main findings of the included studies and resources will be tabulated and summarized. Thematic analysis and natural language processing (NLP) will be conducted in parallel using a 9-step approach to identify common themes and synthesize the literature. Additionally, NLP will be employed for bibliometric and scientometric analysis of the identified literature. RESULTS: The search strategy has been developed and launched. As of October 2021, we have completed stages 1, 2, and 3 of the scoping review. We identified 132 studies for inclusion through the academic literature search and 127 relevant studies in the gray literature search. Further refinement of the eligibility criteria and data extraction has been ongoing since September 2021. CONCLUSIONS: In this scoping review, we will identify and consolidate information and evidence related to the use and effectiveness of existing digital learning tools in postgraduate family medicine training. Our findings will improve the understanding of the current landscape of digital learning tools, which will be of great value to educators and trainees interested in using existing tools, innovators looking to design digital learning tools that meet current needs, and researchers involved in the study of digital tools. TRIAL REGISTRATION: OSF Registries osf.io/wju4k; https://osf.io/wju4k INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34575.

The Contribution of Psychological Distress to Resting Palpitations in Patients Who Recovered from Severe COVID-19.

BACKGROUND: Increasing numbers of patients have recovered from severe coronavirus disease 2019 (COVID-19) in Wuhan, China. This study aimed to evaluate the association of psychological distress with resting palpitations in recovered patients. METHODS: In this prospective cohort study, consecutive patients who recovered from severe COVID-19 and complained of resting palpitations were included. Dynamic electrocardiogram (ECG) was continuously monitored for 2 hours while patients were at rest. A survey using a palpitation frequency scale and the Hospital Anxiety and Depression Scale (HADS) was administered to all participants. RESULTS: Of the 289 consecutive patients who recovered from severe COVID-19, 24 patients (8.3%) suffered resting palpitation symptoms, and 22 patients were finally included. Two-hour Holter monitoring showed that 18 (81.8%) patients had tachyarrhythmias, of which the most common was sinus tachycardia (17/22, 77.3%). However, patients with sinus tachycardia showed a similar frequency of palpitation episodes compared to those without sinus tachycardia. Anxiety (68.2%) and depression (59.1%) were prevalent among these recovered patients. Patients with anxiety or depression symptoms had a higher frequency of palpitation episodes than those without anxiety or depression symptoms. In addition, both the HADS-anxiety score (r =0.609, P<0.01) and HADS-depression score (r =0.516, P=0.01) were positively related to the frequency of palpitation episodes. CONCLUSION: Symptoms of resting palpitations, manifested mainly by sinus tachycardia, are not uncommon in patients who recovered from severe COVID-19. Psychological distress (anxiety and depression) may be responsible, at least in part, for resting palpitation symptoms.

Exploring Tourism Recovery in the Post-COVID-19 Period: An Evolutionary Game Theory Approach

This study aims to explore the process of tourism recovery in the post-COVID-19 period and the role of stakeholders in promoting such a process. Using evolutionary game theory, this study analyzes the behavior interactions and game equilibrium of stakeholders in the development of tourism by constructing an evolutionary game model amongst governments, tourists and tourism enterprises. Then, the influences of different evolution paths and major parameters affecting stakeholders’ strategy selection are discussed. With the aim of illustrating the role of the stakeholders in the tourism sector’s economic recovery under the impact of the coronavirus pandemic, the numerical experiment was conducted using the MATLAB 2016 software. The results show that the development and change of the emergent public health events affect tourism stakeholders’ behavior strategy. Moreover, the strategic choices of each player, including governments, tourism enterprises and tourists, are also constantly evolving at different stages of the pandemic.

Effects of Infection with SARS-CoV-2 on the Male and Female Reproductive Systems: A Review.

Coronavirus Disease-2019 (COVID-19) is a rapidly spreading pandemic that began at the end of 2019. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Reproductive health has always been one of the most important healthcare problems, and the impacts of COVID-19 on the reproductive systems have become an emerging topic. The effects of infection with SARS-CoV-2 on males are more harmful than on females. The outcomes of pregnancy also can show the condition of male and female reproductive system health. The vertical transmission of SARS-CoV-2 significantly affects pregnancy healthy. SARS-CoV-2, antibody, and other factors, such as the decline of lymphocyte counts, and increased erythrocyte sedimentation rate, C-reactive protein, and D-dimer levels, are evidence of SARS-CoV-2 vertical transmission. Angiotensin-converting enzyme 2 (ACE2) is regarded as a virus receptor in the reproductive system. The expression and activity of ACE2 are influenced by sex hormones, especially the male sex hormones. The strength of immunity is crucial to fighting off viral infection. Antibodies against SARS-CoV-2 show different expression in male and female patients, and the antibodies have been regarded as having potential applications in COVID-19 prevention and treatment. This review aims to present the current status of what is known about the involvement of the male and female reproductive systems, as well as the effects on pregnancy health, during infection with SARS-CoV-2, and discusses the implications for future fertility.

The protective effect of SARS-CoV-2 antibodies in Scottish healthcare workers.

BACKGROUND: Healthcare workers (HCWs) are believed to be at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is not known to what extent the natural production of antibodies to SARS-CoV-2 is protective against re-infection. METHODS: A prospective observational study of HCWs in Scotland (UK) from May to September 2020 was performed. The Siemens SARS-CoV-2 total antibody assay was used to establish seroprevalence in this cohort. Controls, matched for age and sex to the general local population, were studied for comparison. New infections (up to 2 December 2020) post antibody testing were recorded to determine whether the presence of SARS-CoV-2 antibodies protects against re-infection. RESULTS: A total of 2063 health and social care workers were recruited for this study. At enrolment, 300 HCWs had a positive antibody test (14.5%). 11 out of 231 control sera tested positive (4.8%). HCWs therefore had an increased likelihood of a positive test (OR 3.4, 95% CI 1.85-6.16; p<0.0001). Dentists were most likely to test positive. 97.3% of patients who had previously tested positive for SARS-CoV-2 by reverse transcriptase (RT)-PCR had positive antibodies. 18.7% had an asymptomatic infection. There were 38 new infections with SARS-CoV-2 in HCWs who were previously antibody negative, and one symptomatic RT-PCR-positive re-infection. The presence of antibodies was therefore associated with an 85% reduced risk of re-infection with SARS-CoV-2 (hazard ratio 0.15, 95% CI 0.06-0.35; p=0.026). CONCLUSION: HCWs were three times more likely to test positive for SARS-CoV-2 than the general population. Almost all infected individuals developed an antibody response, which was 85% effective in protecting against re-infection with SARS-CoV-2.

Nonlinear dynamic mechanism of regional air pollution during the COVID-19 lockdown

Based on hourly concentration of PM2.5 and O3 during the epidemic period（January 24, 2020 to May 31, 2020） in Changsha, Zhuzhou and Xiangtan, the diurnal patterns, long-term persistence, multifractality and self-organization evolution dynamics of these two pollutants were studied to reveal the internal dynamic mechanism of the occurrence and evolution of heavy pollution events during the epidemic period. Firstly, the diurnal patterns of PM2.5 and O3 concentrations were investigated. It showed that O3 showed a single peak of high concentration in the daytime and low in the night, while PM2.5 showed a single lowest peak concentration in the day and high in the night, which was different from the pattern in non-epidemic periods. Furthermore, detrended fluctuation analysis（DFA）, the multifractal detrended fluctuation analysis（MFDFA） and probability statistical analysis were applied to study the long-term persistence, multi-fractal structure of PM2.5 and O3 series. The results showed that PM2.5 and O3 series had significant long-term persistence characteristics and strong multi-fractal structures for the three cities. Meanwhile, detrended cross-correlation analysis（DCCA） and multifractal detrended cross-correlation analysis（MFDCCA） were conducted to estimate the cross-correlations between PM2.5 and O3 series. Long-term persistence as well as multifractal features at different time scales was also observed in PM2.5-O3 cross-correlations. Next, nonlinear analysis results obtained during epidemic period were compared with those obtained in the same periods of non-epidemic years of 2019 and 2018. Finally, based on the self-organized criticality（SOC） theory, the internal dynamic law of spatial and temporal evolution of PM2.5 and O3 series was discussed. Combined with the typical regional meteorological characteristics, it was found that the intrinsic dynamic mechanism of SOC may be one of the leading mechanisms of heavy air pollution episodes during the COVID-19 lockdown period. During the epidemic period, PM2.5 and O3 concentrations did not evolve independently but remained complex interactions. Under the stable meteorological conditions, the nonlinear coupling effect inside the air combined pollution might reach the dynamic critical state, thus, lead to the risk of heavy air pollution in Greater Changsha Metropolitan Region during the epidemic period.

Human liver organoid derived intra-hepatic bile duct cells support SARS-CoV-2 infection and replication and its comparison with SARS-CoV (preprint)

BackgroundAlthough the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by deranged parenchymal liver enzymes. Furthermore, patients with severe liver disease have been shown to have higher mortality. Overall, the mechanism behind the liver injury remains unclear. Approach and resultsWe showed that intra-hepatic bile duct cells could be grown using a human liver organoid platform. The cholangiocytes were not only susceptible to SARS-CoV-2 infection, they also supported efficient viral replication. We also showed that SARS-CoV-2 replication was much higher than SARS-CoV. ConclusionOur findings suggested direct cytopathic viral damage being a mechanism for SARS-CoV-2 liver injury.

The Protective Effect of SARS-CoV-2 Antibodies in Scottish Healthcare Workers (preprint)

Background: Healthcare workers (HCW) are believed to be at increased risk of SARS-CoV-2 infection. The extent of that increased risk compared to the general population and the groups most at risk have not been extensively studied. It is also not known to what extent the natural production of antibodies to SARS-CoV-2 is protective against re-infection.Methods: A prospective observational study of health and social care workers in NHS Tayside (Scotland, UK) from May to September 2020. The Siemens SARS-CoV-2 total antibody assay was used to establish seroprevalence in this cohort. Controls, matched for age and sex to the general Tayside population, were studied for comparison. New infections post antibody testing were recorded to determine if the presence of SARS-CoV-2 antibodies protect against re-infection.Results: A total of 2063 health and social care workers were recruited for this study. 300 HCW had a positive antibody test (14.5%). 11/231 control sera tested positive (4.8%). HCW therefore had an increased likelihood of a positive test (Odds ratio 3.4 95% CI 1.85-6.16, p<0.0001). Dentists, healthcare assistants and porters were the job roles most likely to test positive. Those working in front-line roles with COVID-19 patients were more likely to test positive (17.4% vs. 13.4%, p=0.02). 97.3% of patients who had previously tested positive for SARS-CoV-2 by RT-PCR had positive antibodies. 18.7% of HCW had an asymptomatic infection. There were 38 new infections with SARS-CoV-2 in HCW who were previously antibody negative and 1 symptomatic RT-PCR positive re-infection in a HCW who had detectable antibodies 76 days prior to re-infection. The presence of antibodies was therefore associated with an 85% reduced risk of re-infection with SARS-CoV-2 (HR 0.15, 95% CI 0.06 to 0.35, p=0.026).Conclusion: In this study, HCW were three times more likely to test positive for SARS-CoV-2 than the general population. Almost all of the infected individuals developed an antibody response and this was 85% effective in protecting against re-infection with SARS-CoV-2.Funding Statement: NHS Tayside COVID-19 Research Fund, JDC is supported by the British Lung Foundation Chair of Respiratory Research.Declaration of Interests: JDC reports grants and personal fees from GlaxoSmithKline, Boehringer-Ingelheim, Astrazeneca, Pfizer, Bayer Healthcare, Grifols, Napp, Insmed and Zambon outside the submitted work; All other authors report no conflicts of interest.Ethics Approval Statement: West of Scotland Research Ethics committee, approval number 20/WS/0078.