Student close contact behavior and COVID-19 transmission in China's classrooms.

Classrooms are high-risk indoor environments, so analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in classrooms is important for determining optimal interventions. Due to the absence of human behavior data, it is challenging to accurately determine virus exposure in classrooms. A wearable device for close contact behavior detection was developed, and we recorded >250,000 data points of close contact behaviors of students from grades 1 to 12. Combined with a survey on students' behaviors, we analyzed virus transmission in classrooms. Close contact rates for students were 37 ± 11% during classes and 48 ± 13% during breaks. Students in lower grades had higher close contact rates and virus transmission potential. The long-range airborne transmission route is dominant, accounting for 90 ± 3.6% and 75 ± 7.7% with and without mask wearing, respectively. During breaks, the short-range airborne route became more important, contributing 48 ± 3.1% in grades 1 to 9 (without wearing masks). Ventilation alone cannot always meet the demands of COVID-19 control; 30 m3/h/person is suggested as the threshold outdoor air ventilation rate in a classroom. This study provides scientific support for COVID-19 prevention and control in classrooms, and our proposed human behavior detection and analysis methods offer a powerful tool to understand virus transmission characteristics and can be employed in various indoor environments.

Clinical predictors and RT-PCR profile of prolonged viral shedding in patients with SARS-CoV-2 Omicron variant in Shanghai: A retrospective observational study

Objective To evaluate determinants of prolonged viral RNA shedding in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. Materials and methods Hospitalized patients tested SARS-CoV-2 positive by nasopharyngeal real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were included in the single-center, retrospective study. Patients were divided into 2 groups according to the timing of viral clearance (≤ 8 days, “early clearance” and ≥15 days, “late clearance”). Results 4,084 patients were included in the study (1,023 late clearance, 3,061 early clearance), with median age of 50 years and a higher proportion (61.4%) of male. Univariate analyses showed that comorbidities (including hypertension, diabetes, and coronary heart disease), receiving vaccine, the number of vaccinations, cycle threshold (Ct) open reading frame 1ab (ORF 1ab), and nucleocapsid protein (N) gene values on admission were associated with late viral clearance. In the multivariable analysis, the number of vaccinations (P = 0.010) and Ct ORF 1ab gene (P < 0.001) values on admission were significantly associated with late viral clearance. Generalized Estimating Equations (GEE) analysis showed that the Ct value of ORF 1ab gene and N gene remained unchanged within 3 days, and showed progressively higher values with increasing days during late viral RNA clearance. Conclusion The number of vaccinations and Ct values of ORF 1ab gene were independently associated with a prolonged SARS-CoV-2 RNA shedding.

Discovery of honokiol thioethers containing 1,3,4-oxadiazole moieties as potential α-glucosidase and SARS-CoV-2 entry inhibitors.

Honokiol, isolated from a traditional Chinese medicine (TCM) Magnolia officinalis, is a biphenolic compound with several biological activities. To improve and broaden its biological activity, herein, two series of honokiol thioethers bearing 1,3,4-oxadiazole moieties were prepared and assessed for their α-glucosidase and SARS-CoV-2 entry inhibitory activities. Among all the honokiol thioethers, compound 7l exhibited the strongest α-glucosidase inhibitory effect with an IC50 value of 18.9 ± 2.3 µM, which was superior to the reference drug acarbose (IC50 = 24.4 ± 0.3 µM). Some interesting results of structure-activity relationships (SARs) have also been discussed. Enzyme kinetic study demonstrated that 7l was a noncompetitive α-glucosidase inhibitor, which was further supported by the results of molecular docking. Moreover, honokiol thioethers 7e, 9a, 9e, and 9r exhibited potent antiviral activity against SARS-CoV-2 pseudovirus entering into HEK-293 T-ACE2h. Especially 9a displayed the strongest inhibitory activity against SARS-CoV-2 pseudovirus entry with an IC50 value of 16.96 ± 2.45 µM, which was lower than the positive control Evans blue (21.98 ± 1.98 µM). Biolayer interferometry (BLI) binding and docking studies suggested that 9a and 9r may effectively block the binding of SARS-CoV-2 to the host ACE2 receptor through dual recognition of SARS-CoV-2 spike RBD and human ACE2. Additionally, the potent honokiol thioethers 7l, 9a, and 9r displayed relatively no cytotoxicity to normal cells (LO2). These findings will provide a theoretical basis for the discovery of honokiol derivatives as potential both α-glucosidase and SARS-CoV-2 entry inhibitors.

Close contact behavior-based COVID-19 transmission and interventions in a subway system.

During COVID-19 pandemic, analysis on virus exposure and intervention efficiency in public transports based on real passenger's close contact behaviors is critical to curb infectious disease transmission. A monitoring device was developed to gather a total of 145,821 close contact data in subways based on semi-supervision learning. A virus transmission model considering both short- and long-range inhalation and deposition was established to calculate the virus exposure. During rush-hour, short-range inhalation exposure is 3.2 times higher than deposition exposure and 7.5 times higher than long-range inhalation exposure of all passengers in the subway. The close contact rate was 56.1 % and the average interpersonal distance was 0.8 m. Face-to-back was the main pattern during close contact. Comparing with random distribution, if all passengers stand facing in the same direction, personal virus exposure through inhalation (deposition) can be reduced by 74.1 % (98.5 %). If the talk rate was decreased from 20 % to 5 %, the inhalation (deposition) exposure can be reduced by 69.3 % (73.8 %). In addition, we found that virus exposure could be reduced by 82.0 % if all passengers wear surgical masks. This study provides scientific support for COVID-19 prevention and control in subways based on real human close contact behaviors.

Impact of the COVID-19 Pandemic on ST-Elevation Myocardial Infarction Management in Hunan Province, China: A Multi-Center Observational Study.

Background: This study aimed to investigate the impact of the COVID-19 pandemic on ST-segment elevation myocardial infarction (STEMI) care in China. Methods: We conducted a multicenter, retrospective cohort study in Hunan province (adjacent to the epidemic center), China. Consecutive patients presenting with STEMI within 12 h of symptom onset and receiving primary percutaneous coronary intervention, pharmaco-invasive strategy and only thrombolytic treatment, were enrolled from January 23, 2020 to April 8, 2020 (COVID-19 era group). The same data were also collected for the equivalent period of 2019 (pre-COVID-19 era group). Results: A total of 610 patients with STEMI (COVID-19 era group n = 286, pre-COVID-19 era group n = 324) were included. There was a decline in the number of STEMI admissions by 10.5% and STEMI-related PCI procedures by 12.7% in 2020 compared with the equivalent period of 2019. The key time intervals including time from symptom onset to first medical contact, symptom onset to door, door-to-balloon, symptom onset to balloon and symptom onset to thrombolysis showed no significant difference between these two groups. There were no significant differences for in-hospital death and major adverse cardiovascular events between these two groups. Conclusion: During the COVID-19 pandemic outbreak in China, we observed a decline in the number of STEMI admissions and STEMI-related PCI procedures. However, the key quality indicators of STEMI care were not significantly affected. Restructuring health services during the COVID-19 pandemic has not significantly adversely influenced the in-hospital outcomes.

A multi-zone spatial flow impact factor model for evaluating and layout optimization of infection risk in a Fangcang shelter hospital

Respiratory infectious diseases have caused several pandemics and scarcity of medical resources. As a temporary hospital for infectious disease patients, the Fangcang shelter hospital requires effective air distribution. We developed the multi-zone SFIF (SFIFM) model by combing a natural ventilation multi-zone model (MIX: Multi-zone Infiltration and eXfiltration) and spatial flow impact factor (SFIF) model, which can calculate the contribution of other zones to the risk of infection in the target zone. Compared with the experimental data in the reference, the model can be used to characterize the influence between zones. A three-zone large building was used for the analysis of the relationship between ventilation rate and SFIFM. An existed Fangcang shelter hospital was evaluated and the layout was optimized with this model. The results showed that both mechanical and natural ventilation would influence SFIFM. By optimizing the layout, the weighted SFIFM on health care worker zone could be reduced by 0.022, and the infection risk could be reduced by 14.42%. This model could more clearly show the relationship between zones, ventilation rate, concentration, and infection risk. It could be applied to evaluate and optimize the location of infectious sources, susceptibles, mechanical ventilation, and purifiers under variable conditions. This model may be helpful in reducing the risk of infection in large space buildings and providing guidance for ensuring public health safety.

Optimization of energy efficiency and COVID-19 pandemic control in different indoor environments.

The COVID-19 pandemic has led to considerable morbidity and mortality, and consumed enormous resources (e.g. energy) to control and prevent the disease. It is crucial to balance infection risk and energy consumption when reducing the spread of infection. In this study, a quantitative human, behavior-based, infection risk-energy consumption model for different indoor environments was developed. An optimal balance point for each indoor environment can be obtained using the anti-problem method. For this study we selected Wangjing Block, one of the most densely populated places in Beijing, as an example. Under the current ventilation standard (30 m3/h/person), prevention and control of the COVID-19 pandemic would be insufficient because the basic reproduction number (R0 ) for students, workers and elders are greater than 1. The optimal required fresh air ventilation rates in most indoor environments are near or below 60 m3/h/person, after considering the combined effects of multiple mitigation measures. In residences, sports buildings and restaurants, the demand for fresh air ventilation rate is relatively high. After our global optimization of infection risk control (R0  ≤ 1), energy consumption can be reduced by 13.7% and 45.1% on weekdays and weekends, respectively, in contrast to a strategy of strict control (R0  = 1 for each indoor environment).

Sedation, Analgesia, and Muscle Relaxation During VV-ECMO Therapy in Patients With Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2): A Single-Center, Retrospective, Observational Study.

Objective: The pharmacokinetics and pharmacodynamics of ECMO-supported sedative, analgesic, and muscle relaxants have changed, but there are insufficient data to determine the optimal dosing strategies for these agents. Sedation, analgesia and muscle relaxation therapy for patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) receiving ECMO support are more specific and have not been fully reported. This study observed and evaluated the use of sedative and analgesic drugs and muscle relaxants in SARS-CoV-2 patients treated with VV-ECMO. Methods: This study was a single-center, retrospective and observational study. Our study includes 8 SARS-CoV-2 patients treated with VV-ECMO in an intensive care unit at Shanghai Public Health Center from February to June 2020. We collected the demographic data from these patients and the dose and course of sedation, analgesia, and muscle relaxants administered during ECMO treatment. Results: The doses of sedative, analgesic and muscle relaxant drugs used in patients with VV-ECMO were significant. Over time, the doses of drugs that were used were increased, and the course of muscle relaxant treatment was extended. Conclusion: Sedation, analgesia, and muscle relaxant use require individualized titration in patients with SARS-CoV-2 who have respiratory failure and who are receiving VV-ECMO.

Interlaboratory assessment of quantification of SARS-CoV-2 RNA by reverse transcription digital PCR.

The pandemic of the novel coronavirus disease 2019 (COVID-19) has caused severe harm to the health of people all around the world. Molecular detection of the pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), played a crucial role in the control of the disease. Reverse transcription digital PCR (RT-dPCR) has been developed and used in the detection of SARS-CoV-2 RNA as an absolute quantification method. Here, an interlaboratory assessment of quantification of SARS-CoV-2 RNA was organized by the National Institute of Metrology, China (NIMC), using in vitro transcribed RNA samples, among ten laboratories on six different dPCR platforms. Copy number concentrations of three genes of SARS-CoV-2 were measured by all participants. Consistent results were obtained with dispersion within 2.2-fold and CV% below 23% among different dPCR platforms and laboratories, and Z' scores of all the reported results being satisfactory. Possible reasons for the dispersion included PCR assays, partition volume, and reverse transcription conditions. This study demonstrated the comparability and applicability of RT-dPCR method for quantification of SARS-CoV-2 RNA and showed the capability of the participating laboratories at SARS-CoV-2 test by RT-dPCR platform.

Eicosanoid Metabolomic Profile of Remdesivir Treatment in Rat Plasma by High-Performance Liquid Chromatography Mass Spectrometry.

Remdesivir, a nucleotide analog prodrug, has displayed pharmacological activity against SARS-CoV-2. Recently, eicosanoids are widely involved in regulating immunity and inflammation for COVID-19 patients. Rats were intravenously administered remdesivir at a dose of 5 mg/kg, and series of blood samples were collected before and after treatment. Targeted metabolomics regarding the eicosanoid profile were investigated and quantitated simultaneously using the previously reported reliable HPLC-MS/MS method. Additionally, interplay relationship between metabolomics and pharmacokinetic parameters was performed using the Pearson correlation analysis and PLS model. For the longitudinal metabolomics of remdesivir, metabolic profiles of the same rat were comparatively substantial at discrete sampling points. The metabolic fingerprints generated by individual discrepancy of rats were larger than metabolic disturbance caused by remdesivir. As for the transversal metabolomics, the prominent metabolic profile variation was observed between the baseline and treatment status. Except for TXB2, the inflammatory- and immunology-related eicosanoids of resolvin D2, 5-HEPE, 5-HETE, and DHA were significantly disturbed and reduced after single administration of remdesivir (p < 0.05, p < 0.001). Moreover, the metabolite of PGE2 correlated with GS-441524 (active metabolite of remdesivir) concentration and pharmacokinetic parameters of Cmax, AUC0-t, AUC0-infinity, and CL significantly. Eicosanoid metabolic profiles of remdesivir at both longitudinal and transversal levels were first revealed using the robust HPLC-MS/MS method. This initial observational eicosanoid metabolomics may lighten the therapy for fighting COVID-19 and further provide mechanistic insights of SARS-CoV-2 virus infection.

Applications of digital PCR in COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has led to a public health crisis and global panic. This infectious disease is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Digital polymerase chain reaction (dPCR), which is an emerging nucleic acid amplification technology that allows absolute quantification of nucleic acids, plays an important role in the detection of SARS-CoV-2. In this review, we introduce the principle and advantages of dPCR, and review the applications of dPCR in the COVID-19 pandemic, including detection of low copy number viruses, measurement of the viral load, preparation of reference materials, monitoring of virus concentration in the environment, detection of viral mutations, and evaluation of anti-SARS-CoV-2 drugs. We also discuss the challenges of dPCR in clinical practice.

Effects of Human Behavior Changes During the Coronavirus Disease 2019 (COVID-19) Pandemic on Influenza Spread in Hong Kong.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to threaten human life worldwide. We explored how human behaviors have been influenced by the COVID-19 pandemic in Hong Kong, and how the transmission of other respiratory diseases (eg, influenza) has been influenced by human behavior. METHODS: We focused on the spread of COVID-19 and influenza infections based on the reported COVID-19 cases and influenza surveillance data and investigated the changes in human behavior due to COVID-19 based on mass transit railway data and the data from a telephone survey. We did the simulation based on a susceptible-exposed-infected-recovered (SEIR) model to assess the risk reduction of influenza transmission caused by the changes in human behavior. RESULTS: During the COVID-19 pandemic, the number of passengers fell by 52.0% compared with the same period in 2019. Residents spent 32.2% more time at home. Each person, on average, came into close contact with 17.6 and 7.1 people per day during the normal and pandemic periods, respectively. Students, workers, and older people reduced their daily number of close contacts by 83.0%, 48.1%, and 40.3%, respectively. The close contact rates in residences, workplaces, places of study, restaurants, shopping centers, markets, and public transport decreased by 8.3%, 30.8%, 66.0%, 38.5%, 48.6%, 41.0%, and 36.1%, respectively. Based on the simulation, these changes in human behavior reduced the effective reproduction number of influenza by 63.1%. CONCLUSIONS: Human behaviors were significantly influenced by the COVID-19 pandemic in Hong Kong. Close contact control contributed more than 47% to the reduction in infection risk of COVID-19.

Synthesis and Biological Evaluation of Honokiol Derivatives Bearing 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones as Potential Viral Entry Inhibitors against SARS-CoV-2.

The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from Magnoliae officinalis Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, 6a and 6p demonstrated antiviral entry effect with IC50 values of 29.23 and 9.82 µM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC50 value more than 50 µM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that 6p binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of 6p on SARS-CoV-2 spike RBD's binding with ACE2. Importantly, 6a and 6p (TC50 > 100 µM) also had higher biological safety for host cells than honokiol (TC50 of 48.23 µM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although 6p's antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.

Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection.

The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

Cover Picture: Applications of digital PCR in COVID-19 pandemic (View 2/2021)

In article number 20200082, Yong Guo and co-workers have shown the detection of SARS-CoV-2 RNA by digital PCR.

Myoglobin and C-reactive protein are efficient and reliable early predictors of COVID-19 associated mortality.

Since the emergence of SARS-CoV-2, numerous studies have been attempting to determine biomarkers, which could rapidly and efficiently predict COVID-19 severity, however there is lack of consensus on a specific one. This retrospective cohort study is a comprehensive analysis of the initial symptoms, comorbidities and laboratory evaluation of patients, diagnosed with COVID-19 in Huoshenshan Hospital, Wuhan, from 4th February to 12th March, 2020. Based on the data collected from 63 severely ill patients from the onset of symptoms till the full recovery or demise, we found not only age (average 70) but also blood indicators as significant risk factors associated with multiple organ failure. The blood indices of all patients showed hepatic, renal, cardiac and hematopoietic dysfunction with imbalanced coagulatory biomarkers. We noticed that the levels of LDH (85%, P < .001), HBDH (76%, P < .001) and CRP (65%, P < .001) were significantly elevated in deceased patients, indicating hepatic impairment. Similarly, increased CK (15%, P = .002), Cre (37%, P = 0.102) and CysC (74%, P = 0.384) indicated renal damage. Cardiac injury was obvious from the significantly elevated level of Myoglobin (52%, P < .01), Troponin-I (65%, P = 0.273) and BNP (50%, P = .787). SARS-CoV-2 disturbs the hemolymphatic system as WBC# (73%, P = .002) and NEUT# (78%, P < .001) were significantly elevated in deceased patients. Likewise, the level of D-dimer (80%, P < .171), PT (87%, P = .031) and TT (57%, P = .053) was elevated, indicating coagulatory imbalances. We identified myoglobin and CRP as specific risk factors related to mortality and highly correlated to organ failure in COVID-19 disease.

Glucocorticoids Should Be Used With Caution in Patients With SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, and the use of glucocorticoids in clinical practice is controversial. Our clinical experiences with glucocorticoid treatment suggested that, while use was effective in some cases, in other cases, glucocorticoid were ineffective and even resulted in immunosuppression that could lead to deterioration. Therefore, glucocorticoids should be used with caution in patients with SARS-CoV-2.

Analysis of viral load in different specimen types and serum antibody levels of COVID-19 patients.

BACKGROUND: COVID-19 has caused a global pandemic and the death toll is increasing. However, there is no definitive information regarding the type of clinical specimens that is the best for SARS-CoV-2 detection, the antibody levels in patients with different duration of disease, and the relationship between antibody level and viral load. METHODS: Nasopharyngeal swabs, anal swabs, saliva, blood, and urine specimens were collected from patients with a course of disease ranging from 7 to 69 days. Viral load in different specimen types was measured using droplet digital PCR (ddPCR). Meanwhile, anti-nucleocapsid protein (anti-N) IgM and IgG antibodies and anti-spike protein receptor-binding domain (anti-S-RBD) IgG antibody in all serum samples were tested using ELISA. RESULTS: The positive detection rate in nasopharyngeal swab was the highest (54.05%), followed by anal swab (24.32%), and the positive detection rate in saliva, blood, and urine was 16.22%, 10.81%, and 5.41%, respectively. However, some patients with negative nasopharyngeal swabs had other specimens tested positive. There was no significant correlation between antibody level and days after symptoms onset or viral load. CONCLUSIONS: Other specimens could be positive in patients with negative nasopharyngeal swabs, suggesting that for patients in the recovery period, specimens other than nasopharyngeal swabs should also be tested to avoid false negative results, and anal swabs are recommended. The antibody level had no correlation with days after symptoms onset or the viral load of nasopharyngeal swabs, suggesting that the antibody level may also be affected by other factors.