Risk tradeoffs between nitrogen dioxide and ozone pollution during the COVID-19 lockdowns in the Greater Bay area of China.

Photochemical regime for ozone (O3) formation is complicated in the sense that reducing emission of nitrogen oxides (NOx) may increase O3 concentration. The lockdown due to COVID-19 pandemic affords a unique opportunity to use real observations to explore the O3 formation regime and the effectiveness of NOx emission control strategies. In this study, observations from ground networks during the lockdowns were used to assess spatial disparity of the Ratio of Ozone Formation (ROF) for nitrogen dioxide (NO2) reduction in the Greater Bay Area (GBA) of China. The health risk model from Air Quality Health Index (AQHI) system in Hong Kong was adopted to evaluate the risk tradeoffs between NO2 and O3. Results show that the levels of O3 increase and NO2 reduction were comparable due to high ROF values in urban areas of central GBA. The ozone reactivity to NO2 reduction gradually declined outwards from central GBA. Despite the O3 increases, the NOx emission controls reduced the Integrated Health Risk (IHR) of NO2 and O3 in most regions of the GBA. When risk coefficients from the AQHI in Canada or the global review were adopted in the risk analyses, the results are extremely encouraging because the controls of NOx emission reduced the IHR of NO2 and O3 almost everywhere in the GBA. Our results underscore the importance of using a risk-based method to assess the effectiveness of emission control measures and the overall health benefit from NOx emission controls in the GBA.

[International multi-center evaluation of a rapid antigen test based on gold immunochromatographic assay for detection of severe acute respiratory syndrome coronavirus 2].

Objective: The gold immunochromatographic assay for detection of SARS-CoV-2 antigen was evaluated by international multi-center clinical trial. Methods: A total of 1 855 clinical parallel samples with valid test results (for nucleic acid and antigen tests, respectively) were collected from nine countries, including Germany, the United Kingdom, Ukraine, France, India, Thailand, Malaysia, the United States of America and Brazil, with sampling period from January 3, 2021 to September 22, 2021. These samples were detected by SARS-CoV-2 antigen test kit (colloidal gold immunochromatography assay) and nucleic acid detection kit (real-time fluorescent quantitative reverse transcription polymerase chain reaction). Positive coincidence rates [(number of antigen-positive cases/nucleic acid-positive cases)×100%], negative coincidence rates [(number of antigen-negative cases/nucleic acid-negative cases)×100%], total coincidence rates [(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases) ×100%], as well as Kappa values were calculated. The differences of the above indictors among different countries were evaluated by the coefficient of variation. The detection rates of the antigen test for samples with different cycle threshold values (Ct values) for the nucleic acid detection, different characteristics and different mutant strains were analyzed. Results: For all samples, the positive, negative, and total coincidence rate between the antigen test and nucleic acid assay was 90.8% (569/627), 99.7% (1 224/1 228) and 96.7% (1 793/1 855), respectively, and the consistency coefficient Kappa value was 0.924. Among these countries, the coefficient of variation for positive coincidence rates (except for Malaysia with a lot of samples with Ct value>30), negative coincidence rates (except for France without negative samples) and total coincidence rates (except for France) was 6%,<1%, and 6%, respectively. When Ct values were less than 25, the detection rates of antigen test were 83.3%-100% for each countries (the coefficient of variation was 6%); The total detection rate and the coefficient of variation was 93.4% (428/458) and 5%, respectively, for asymptomatic infected persons and cases within 7 days post onset of symptoms; the total detection rate for various SARS-CoV-2 mutant strains was 97.5% (119/122); and it showed negative results for samples from cases infected with other viruses, including influenza A virus subtype H1N1, influenza B virus, respiratory syncytial virus subgroups A and B, coxsackievirus 16, human metapneumovirus, parainfluenza virus types 1 and 4, Epstein-Barr virus and adenovirus. Conclusion: The SARS-CoV-2 antigen test kit showed excellent authenticity, and there were few differences for its indictors among nine countries, therefore it can meet the needs of large-scale early screening of SARS-CoV-2 infection.

GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia.

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.

Physical distancing implementation, ambient temperature and Covid-19 containment: An observational study in the United States.

Governments may relax physical distancing interventions for coronavirus disease 2019 (Covid-19) containment in warm seasons/areas to prevent economic contractions. However, it is not clear whether higher temperature may offset the transmission risk posed by this relaxation. This study aims to investigate the associations of the effective reproductive number (Rt) of Covid-19 with ambient temperature and the implementation of physical distancing interventions in the United States (US). This study included 50 states and one territory of the US with 4,532,650 confirmed cases between 29 January and 31 July 2020. We used an interrupted time-series model with a state-level random intercept for data analysis. An interaction term of 'physical distancing×temperature' was included to examine their interactions. Stratified analyses by temperature and physical distancing implementation were also performed to analyse the modifying effects. The overall median (interquartile range) Rt was 1.2 (1.0-2.3). The implementation of physical distancing was associated with a 12% decrease in the risk of Rt (relative risk [RR]: 0.88, 95% confident interval [CI]: 0.86-0.89), and each 5 °C increase in temperature was associated with a 2% decrease (RR: 0.98, 95%CI: 0.97-0.98). We observed a statistically significant interaction between temperature and physical distancing implementation, but all the RRs were small (close to one). The containing effects of high temperature were attenuated by 5.1% when physical distancing was implemented. The association of COVID-19 Rt with physical distancing implementation was more stable (0.88 vs. 0.89 in days when temperature was low and high, respectively). Increased temperature did not offset the risk of Covid-19 Rt posed by the relaxation of physical distancing implementation. Our study does not recommend relaxing the implementation of physical distancing interventions in warm seasons/areas.

Factors Influencing Viral Clearance in Mild COVID-19 and Clinical Characteristics of Asymptomatic Patients.

BACKGROUND: The outbreak of coronavirus disease (COVID-19) has become a global public health emergency. OBJECTIVE: To evaluate the characteristics and outcomes of patients with COVID-19 in Anhui and to identify predictors of viral clearance. METHODS: We retrospectively analyzed the data collected from discharged patients with laboratory-confirmed SARS-CoV-2 infections. We compared clinical features between viral clearance and viral persistence, and evaluated factors associated with SARS-CoV-2 shedding using multiple linear regression. RESULTS: Among the 83 patients involved in the study, the median age was 43 years, while 60.2% were male, 35.4% had comorbidities, and the mortality was zero. The median time from illness onset to admission was 5 days (interquartile range (IQR), 2-7 days), and the median time from the illness onset to SARS-CoV-2 RNA detection was 16 days (IQR, 13-18 days). The factors influencing viral clearance were as follows: (1) delayed admission (beta 1.057, 95% CI 0.810-1.304; p ≤ 0.001) and (2) underlying comorbidities (beta 1.907, 95% CI 0.198-3.616; p = 0.029). No significant differences were observed in the length of stay (p = 0.246) and pneumonia between asymptomatic and symptomatic patients based on computed tomography (CT) (p = 0.124). CONCLUSIONS: Delayed admission and underlying comorbidities may effectively predict SARS-CoV-2 RNA clearance. For those infected with SARS-CoV-2, even asymptomatic patients without any clinical symptoms should be traced and isolated. This practice may reduce the spread of SARS-CoV-2 and slow the COVID-19 pandemic caused by the virus. Clinical Trial Registration Number: This trial is registered with 2020-051.

An improved decomposition method to differentiate meteorological and anthropogenic effects on air pollution: A national study in China during the COVID-19 lockdown period.

Although the effects of meteorological factors on severe air pollution have been extensively investigated, quantitative decomposition of the contributions of meteorology and anthropogenic factors remains a big challenge. The novel coronavirus disease 2019 (COVID-19) pandemic affords a unique opportunity to test decomposition method. Based on a wind decomposition method, this study outlined an improved method to differentiate complex meteorological and anthropogenic effects. The improved method was then applied to investigate the cause of unanticipated haze pollution in China during the COVID-19 lockdown period. Results from the wind decomposition method show that weakened winds increased PM2.5 concentrations in the Beijing-Tianjin area and northeastern China (e.g., by 3.19 µg/m3 in Beijing). Using the improved decomposition method, we found that the combined meteorological effect (e.g., drastically elevated humidity levels and weakened airflow) substantially increased PM2.5 concentrations in northern China: the most substantial increases were in the Beijing-Tianjin-Hebei region (e.g., by 26.79 µg/m3 in Beijing). On excluding the meteorological effects, PM2.5 concentrations substantially decreased across China (e.g., by 21.84 µg/m3 in Beijing), evidencing that the strict restrictions on human activities indeed decreased PM2.5 concentrations. The unfavorable meteorological conditions, however, overwhelmed the beneficial effects of emission reduction, causing the severe haze pollution. These results indicate that the integrated meteorological effects should be considered to differentiate the meteorological and anthropogenic effects on severe air pollution.

Effectiveness of non-pharmaceutical interventions on COVID-19 transmission in 190 countries from 23 January to 13 April 2020.

BACKGROUND: To evaluate and compare the effectiveness of four types of non-pharmaceutical interventions (NPIs) to contain the time-varying effective reproduction number (Rt) of coronavirus disease-2019 (COVID-19). METHODS: This study included 1,908,197 confirmed COVID-19 cases from 190 countries between 23 January and 13 April 2020. The implemented NPIs were categorised into four types: mandatory face mask in public, isolation or quarantine, social distancing and traffic restriction (referred to as mandatory mask, quarantine, distancing and traffic hereafter, respectively). RESULTS: The implementations of mandatory mask, quarantine, distancing and traffic were associated with changes (95% confidence interval, CI) of -15.14% (from -21.79% to -7.93%), -11.40% (from -13.66% to -9.07%), -42.94% (from -44.24% to -41.60%) and -9.26% (from -11.46% to -7.01%) in the Rt of COVID-19 when compared with those without the implementation of the corresponding measures. Distancing and the simultaneous implementation of two or more types of NPIs seemed to be associated with a greater decrease in the Rt of COVID-19. CONCLUSION: Our study indicates that NPIs can significantly contain the COVID-19 pandemic. Distancing and the simultaneous implementation of two or more NPIs should be the strategic priorities for containing COVID-19.

Meteorological factors and COVID-19 incidence in 190 countries: An observational study.

Novel corona virus disease 2019 (COVID-19), which first emerged in December 2019, has become a pandemic. This study aimed to investigate the associations between meteorological factors and COVID-19 incidence and mortality worldwide. This study included 1,908,197 confirmed cases of and 119,257 deaths from COVID-19 from 190 countries between 23 January and 13 April, 2020. We used a distributed lag non-linear model with city-/country-level random intercept to investigate the associations between COVID19 incidence and daily temperature, relative humidity, and wind speed. A series of confounders were considered in the analysis including demographics, socioeconomics, geographic locations, and political strategies. Sensitivity analyses were performed to examine the robustness of the associations. The COVID-19 incidence showed a stronger association with temperature than with relative humidity or wind speed. An inverse association was identified between the COVID-19 incidence and temperature. The corresponding 14-day cumulative relative risk was 1.28 [95% confidence interval (CI), 1.20-1.36] at 5 °C, and 0.75 (95% CI, 0.65-0.86) at 22 °C with reference to the risk at 11 °C. An inverse J-shaped association was observed between relative humidity and the COVID-19 incidence, with the highest risk at 72%. A higher wind speed was associated with a generally lower incidence of COVID-19, although the associations were weak. Sensitivity analyses generally yielded similar results. The COVID-19 incidence decreased with the increase of temperature. Our study suggests that the spread of COVID-19 may slow during summer but may increase during winter.

Development and evaluation of a serological test for diagnosis of COVID-19 with selected recombinant spike proteins.

Serological test is a valuable diagnostic tool for coronavirus disease 2019 (COVID-19). However, considerable improvements to these tests are needed, especially in the detection sensitivity. In this study, six recombinant nucleocapsid and spike proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were prepared and evaluated, including three prokaryotic expression nucleocapsid proteins (rN, rN1, rN2) and three eukaryotic expression spike proteins (rS1, rS-RBD, rS-RBD-mFc). The recombinant proteins with the highest ELISA titers (rS1 and rS-RBD-mFc) were selected to develop a double-antigen sandwich colloidal gold immunochromatography assay (GICA) to detect total antibodies against SARS-CoV-2. The clinical evaluation results showed that the sensitivity and specificity of GICA were 92.09% (419/455) and 99.44% (706/710), respectively. Moreover, a significant number (65.63%, 21/32) of COVID-19 patients with undetectable viral RNA were correctly diagnosed by the GICA method. In conclusion, the eukaryotic expression spike proteins (rS1 and rS-RBD-mFc) are more suitable than the prokaryotic expression nucleocapsid proteins for serological diagnosis of SARS-CoV-2. The proposed GICA for detection of total antibodies could be a powerful complement to the current RNA tests for COVID-19.

A mechanism-based parameterisation scheme to investigate the association between transmission rate of COVID-19 and meteorological factors on plains in China.

The novel coronavirus disease 2019 (COVID-19), which first emerged in Hubei province, China, has become a pandemic. However, data regarding the effects of meteorological factors on its transmission are limited and inconsistent. A mechanism-based parameterisation scheme was developed to investigate the association between the scaled transmission rate (STR) of COVID-19 and the meteorological parameters in 20 provinces/municipalities located on the plains in China. We obtained information on the scale of population migrated from Wuhan, the world epicentre of the COVID-19 outbreak, into the study provinces/municipalities using mobile-phone positioning system and big data techniques. The highest STRs were found in densely populated metropolitan areas and in cold provinces located in north-eastern China. Population density had a non-linear relationship with disease spread (linearity index, 0.9). Among various meteorological factors, only temperature was significantly associated with the STR after controlling for the effect of population density. A negative and exponential relationship was identified between the transmission rate and the temperature (correlation coefficient, -0.56; 99% confidence level). The STR increased substantially as the temperature in north-eastern China decreased below 0 °C (the STR ranged from 3.5 to 12.3 when the temperature was between -9.41 °C and -13.87 °C), whilst the STR showed less temperature dependence in the study areas with temperate weather conditions (the STR was 1.21 ± 0.57 when the temperature was above 0 °C). Therefore, a higher population density was linearly whereas a lower temperature (<0 °C) was exponentially associated with an increased transmission rate of COVID-19. These findings suggest that the mitigation of COVID-19 spread in densely populated and/or cold regions will be a great challenge.

Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19.

Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500 mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. Although randomized trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.