Blood unconjugated bilirubin and tacrolimus are negative predictors of specific cellular immunity in kidney transplant recipients after SAR-CoV-2 inactivated vaccination.

The immunogenicity of SARS-CoV-2 vaccines is poor in kidney transplant recipients (KTRs). The factors related to poor immunogenicity to vaccination in KTRs are not well defined. Here, observational study demonstrated no severe adverse effects were observed in KTRs and healthy participants (HPs) after first or second dose of SARS-CoV-2 inactivated vaccine. Different from HPs with excellent immunity against SARS-CoV-2, IgG antibodies against S1 subunit of spike protein, receptor-binding domain, and nucleocapsid protein were not effectively induced in a majority of KTRs after the second dose of inactivated vaccine. Specific T cell immunity response was detectable in 40% KTRs after the second dose of inactivated vaccine. KTRs who developed specific T cell immunity were more likely to be female, and have lower levels of total bilirubin, unconjugated bilirubin, and blood tacrolimus concentrations. Multivariate logistic regression analysis found that blood unconjugated bilirubin and tacrolimus concentration were significantly negatively associated with SARS-CoV-2 specific T cell immunity response in KTRs. Altogether, these data suggest compared to humoral immunity, SARS-CoV-2 specific T cell immunity response are more likely to be induced in KTRs after administration of inactivated vaccine. Reduction of unconjugated bilirubin and tacrolimus concentration might benefit specific cellular immunity response in KTRs following vaccination.

NSUN2-mediated M5c methylation of IRF3 mRNA negatively regulates type I interferon responses during various viral infections.

5-Methylcytosine (m5C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m5C methyltransferase, negatively regulates type I interferon responses during various viral infections, including SARS-CoV-2. NSUN2 specifically mediates m5C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-ß production. Knockout or knockdown of NSUN2 enhanced type I interferon and downstream ISGs during various viral infection in vitro. And in vivo, the antiviral innate response is more dramatically enhanced in Nsun2+/- mice than in Nsun2+/+ mice. The highly m5C methylated cytosines in IRF3 mRNA were identified, and their mutation enhanced cellular IRF3 mRNA levels. Moreover, infection with Sendai virus (SeV), vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), or Zika virus (ZIKV) resulted in a reduction of endogenous NSUN2 levels. Especially, SARS-CoV-2 infection (WT strain and BA.1 omicron variant) also decreased endogenous levels of NSUN2 in COVID-19 patients and K18-hACE2 KI mice, further increasing type I interferon and downstream ISGs. Together, our findings reveal that NSUN2 serves as a negative regulator of interferon response by accelerating the fast turnover of IRF3 mRNA, while endogenous NSUN2 levels decrease during SARS-CoV-2 and various viral infections to boost antiviral responses for effective elimination of viruses.

Antibodies Induced by Homologous or Heterologous Inactivated (CoronaVac/BBIBP-CorV) and Recombinant Protein Subunit Vaccines (ZF2001) Dramatically Enhanced Inhibitory Abilities against B.1.351, B.1.617.2, and B.1.1.529 Variants.

Safe and effective vaccines for Corona Virus Disease 2019 (COVID-19) can prevent the virus from infecting human populations and treat patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we discuss the inhibitory abilities of primary and booster vaccine-induced antibodies inhibitory ability toward the SARS-CoV-2 wild-type strain, as well as B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529. We confirmed these antibodies had the strongest inhibitory effects on the wild-type strain and cross-inhibition activities against other mutant strains after two inactivated vaccine doses. However, the B.1.351, B.1.617.2 and B.1.1.529 mutants exhibit antibody resistance in the vaccine serum. Antibodies induced by homologous inactivated vaccines (n = 92) presented more effective inhibition against tested SARS-CoV-2 strains (p < 0.0001), especially B.1.351, B.1.617.2, and B.1.1.529 mutant strains, which had strong immune escape characteristics. In addition, a heterologous booster vaccination (n = 50) of a protein subunit vaccine ZifiVax (ZF2001) significantly restored humoral immune responses and even showed an increasing response against wild-type, B.1.351, B.1.617.2, and B.1.1.529 than homologous inactivated vaccines. Our analysis of the humoral immune response elicited by the different vaccine regimens, including inhibiting antibodies, indicated that a booster, whether homologous or heterologous, could be essential for achieving greater efficacy against SARS-CoV-2.

An credible traceability system for cold chain logistics developed for China's agricultural products in the context of COVID-19

Cold chain logistics is important for reducing post-harvest losses of agricultural products and ensuring the safety of agricultural products. COVID-19 cases related to cold chains have occasionally occurred, prompting considerable and widespread attention to cold chain logistics. The establishment of an effective traceability system for agricultural products within cold chain logistics is vital for ensuring their safety during the COVID-19 pandemic and achieving accurate traceability and recall. A study was conducted to assess the developmental status of cold chain logistics for China's agriculture products and identify challenges associated with cold chain logistics in the context of COVID-19. The study highlighted the advantages of blockchain-based traceability of agricultural products within cold chain logistics. Accordingly, a blockchain-based system was constructed for ensuring effective traceability of agricultural products within cold chain logistics extending from the production to the sales areas (i.e., from the field to the table). First, the demand for a traceability system was analyzed in detail from the perspective of the government, enterprises, and consumers. Second, six layers of the system architecture, comprising perceptions, data, networks, and the core, application, and user layers were delineated. Next, a storage mechanism and the system flow were designed and analyzed, and the on-chain and off-chain storage mechanisms of the "Inter Planetary File System+ blockchain" were applied for data storage, thereby addressing the deficiency of the blockchain and improving the operation and query efficiency of the traceability system. Lastly, the main functions of three respective ports for the government, enterprises, and consumers were introduced. This system can effectively resolve various challenges, such as tracing the entire process of cold chain logistics for agricultural products and a lack of clarity regarding assigned responsibility. Thus, the traceability of the entire process of cold chain logistics for agricultural products can be achieved, thereby enhancing the effectiveness of oversight of agricultural production, which ensures the quality and safety of agricultural products and strengthens consumers' trust in food safety.

Engagement of the G3BP2-TRIM25 Interaction by Nucleocapsid Protein Suppresses the Type I Interferon Response in SARS-CoV-2-Infected Cells.

The nucleocapsid (N) protein contributes to key steps of the SARS-CoV-2 life cycle, including packaging of the virus genome and modulating interactions with cytoplasmic components. Expanding knowledge of the N protein acting on cellular proteins and interfering with innate immunity is critical for studying the host antiviral strategy. In the study on SARS-CoV-2 infecting human bronchial epithelial cell line s1(16HBE), we identified that the N protein can promote the interaction between GTPase-activating protein SH3 domain-binding protein 2 (G3BP2) and tripartite motif containing 25 (TRIM25), which is involved in formation of the TRIM25-G3BP2-N protein interactome. Our findings suggest that the N protein is enrolled in the inhibition of type I interferon production in the process of infection. Meanwhile, upgraded binding of G3BP2 and TRIM25 interferes with the RIG-I-like receptor signaling pathway, which may contribute to SARS-CoV-2 escaping from cellular innate immune surveillance. The N protein plays a critical role in SARS-CoV-2 replication. Our study suggests that the N protein and its interacting cellular components has potential for use in antiviral therapy, and adding N protein into the vaccine as an antigen may be a good strategy to improve the effectiveness and safety of the vaccine. Its interference with innate immunity should be strongly considered as a target for SARS-CoV-2 infection control and vaccine design.

Longitudinal analyses reveal distinct immune response landscapes in lung and intestinal tissues from SARS-CoV-2-infected rhesus macaques.

The pathological and immune response of individuals with COVID-19 display different dynamics in lung and intestine. Here, we depict the single-cell transcriptional atlas of longitudinally collected lung and intestinal tissue samples from SARS-CoV-2-infected monkeys at 3 to 10 dpi. We find that intestinal enterocytes are degraded at 3 days post-infection but recovered rapidly, revealing that infection has mild effects on the intestine. Crucially, we observe suppression of the inflammatory response and tissue damage related to B-cell and Paneth cell accumulation in the intestines, although T cells are activated in the SARS-CoV-2 infection. Compared with that in the lung, the expression of interferon response-related genes is inhibited, and inflammatory factor secretion is reduced in the intestines. Our findings indicate an imbalance of immune dynamic in intestinal mucosa during SARS-CoV-2 infection, which may underlie ongoing rectal viral shedding and mild tissue damage.

Non-stop industries were the main source of air pollution during the 2020 coronavirus lockdown in the North China Plain.

Despite large decreases of emissions of air pollution during the coronavirus disease 2019 (COVID-19) lockdown in 2020, an unexpected regional severe haze has still occurred over the North China Plain. To clarify the origin of this pollution, we studied air concentrations of fine particulate matter (PM2.5), NO2, O3, PM10, SO2, and CO in Beijing, Hengshui and Baoding during the lockdown period from January 24 to 29, 2020. Variations of PM2.5 composition in inorganic ions, elemental carbon and organic matter were also investigated. The HYSPLIT model was used to calculate backward trajectories and concentration weighted trajectories. Results of the cluster trajectory analysis and model simulations show that the severe haze was caused mainly by the emissions of northeastern non-stopping industries located in Inner Mongolia, Liaoning, Hebei, and Tianjin. In Beijing, Hengshui and Baoding, the mixing layer heights were about 30% lower and the maximum relative humidity was 83% higher than the annual averages, and the average wind speeds were lower than 1.5 m s-1. The concentrations of NO3 -, SO4 2-, NH4 +, organics and K+ were the main components of PM2.5 in Beijing and Hengshui, while organics, K+, NO3 -, SO4 2-, and NH4 + were the main components of PM2.5 in Baoding. Contrary to previous reports suggesting a southerly transport of air pollution, we found that northeast transport caused the haze formation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10311-021-01314-8.

The spatiotemporal transmission dynamics of COVID-19 among multiple regions: a modeling study in Chinese provinces.

Current explosive outbreak of COVID-19 around the world is a complex spatiotemporal process with hidden interactions between viruses and humans. This study aims at clarifying the transmission patterns and the driving mechanism that contributed to the COVID-19 prevalence across the provinces of China. Thus, a new dynamical transmission model is established by an ordinary differential system. The model takes into account the hidden circulation of COVID-19 virus among/within humans, which incorporates the spatial diffusion of infection by parameterizing human mobility. Theoretical analysis indicates that the basic reproduction number is a unique epidemic threshold, which can unite infectivity in each region by human mobility and can totally determine whether COVID-19 proceeds among multiple regions. By validating the model with real epidemic data in China, it is found that (1) if without any intervention, COVID-19 would overrun China within three months, resulting in more than 1.1 billion clinical infections and 0.2 billion subclinical infections; (2) high frequency of human mobility can trigger COVID-19 diffusion across each province in China, no matter where the initial infection locates; (3) travel restrictions and other non-pharmaceutical interventions must be implemented simultaneously for disease control; and (4) infection sites in central and east (rather than west and northeast) of China would easily stimulate quick diffusion of COVID-19 in the whole country. Supplementary Information: The online version supplementary material available at 10.1007/s11071-021-07001-1.

Non-stop industries were the main source of air pollution during the 2020 coronavirus lockdown in the North China Plain

Despite large decreases of emissions of air pollution during the coronavirus disease 2019 (COVID-19) lockdown in 2020, an unexpected regional severe haze has still occurred over the North China Plain. To clarify the origin of this pollution, we studied air concentrations of fine particulate matter (PM2.5), NO2, O3, PM10, SO2, and CO in Beijing, Hengshui and Baoding during the lockdown period from January 24 to 29, 2020. Variations of PM2.5 composition in inorganic ions, elemental carbon and organic matter were also investigated. The HYSPLIT model was used to calculate backward trajectories and concentration weighted trajectories. Results of the cluster trajectory analysis and model simulations show that the severe haze was caused mainly by the emissions of northeastern non-stopping industries located in Inner Mongolia, Liaoning, Hebei, and Tianjin. In Beijing, Hengshui and Baoding, the mixing layer heights were about 30% lower and the maximum relative humidity was 83% higher than the annual averages, and the average wind speeds were lower than 1.5 m s−1. The concentrations of NO3−, SO42−, NH4+, organics and K+ were the main components of PM2.5 in Beijing and Hengshui, while organics, K+, NO3−, SO42−, and NH4+ were the main components of PM2.5 in Baoding. Contrary to previous reports suggesting a southerly transport of air pollution, we found that northeast transport caused the haze formation. Supplementary Information The online version contains supplementary material available at 10.1007/s10311-021-01314-8.

The spatiotemporal transmission dynamics of COVID-19 among multiple regions: a modeling study in Chinese provinces

Current explosive outbreak of COVID-19 around the world is a complex spatiotemporal process with hidden interactions between viruses and humans. This study aims at clarifying the transmission patterns and the driving mechanism that contributed to the COVID-19 prevalence across the provinces of China. Thus, a new dynamical transmission model is established by an ordinary differential system. The model takes into account the hidden circulation of COVID-19 virus among/within humans, which incorporates the spatial diffusion of infection by parameterizing human mobility. Theoretical analysis indicates that the basic reproduction number is a unique epidemic threshold, which can unite infectivity in each region by human mobility and can totally determine whether COVID-19 proceeds among multiple regions. By validating the model with real epidemic data in China, it is found that (1) if without any intervention, COVID-19 would overrun China within three months, resulting in more than 1.1 billion clinical infections and 0.2 billion subclinical infections;(2) high frequency of human mobility can trigger COVID-19 diffusion across each province in China, no matter where the initial infection locates;(3) travel restrictions and other non-pharmaceutical interventions must be implemented simultaneously for disease control;and (4) infection sites in central and east (rather than west and northeast) of China would easily stimulate quick diffusion of COVID-19 in the whole country. Supplementary Information The online version supplementary material available at 10.1007/s11071-021-07001-1.

Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions.

The coronavirus disease 2019 (COVID-19) pandemic has caused large-scale economic and social losses and worldwide deaths. Although most COVID-19 patients have initially complained of respiratory insufficiency, the presence of neuropsychiatric manifestations is also reported frequently, ranging from headache, hyposmia/anosmia, and neuromuscular dysfunction to stroke, seizure, encephalopathy, altered mental status, and psychiatric disorders, both in the acute phase and in the long term. These neuropsychiatric complications have emerged as a potential indicator of worsened clinical outcomes and poor prognosis, thus contributing to mortality in COVID-19 patients. Their etiology remains largely unclear and probably involves multiple neuroinvasive pathways. Here, we summarize recent animal and human studies for neurotrophic properties of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and elucidate potential neuropathogenic mechanisms involved in the viral invasion of the central nervous system as a cause for brain damage and neurological impairments. We then discuss the potential therapeutic strategy for intervening and preventing neuropsychiatric complications associated with SARS-CoV-2 infection. Time-series monitoring of clinical-neurochemical-radiological progress of neuropsychiatric and neuroimmune complications need implementation in individuals exposed to SARS-CoV-2. The development of a screening, intervention, and therapeutic framework to prevent and reduce neuropsychiatric sequela is urgently needed and crucial for the short- and long-term recovery of COVID-19 patients.

Live attenuated coronavirus vaccines deficient in N7-Methyltransferase activity induce both humoral and cellular immune responses in mice.

Coronaviruses (CoVs) can infect a variety of hosts, including humans, livestock and companion animals, and pose a serious threat to human health and the economy. The current COVID-19 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has killed millions of people. Unfortunately, effective treatments for CoVs infection are still lacking, suggesting the importance of coronavirus vaccines. Our previous work showed that CoV nonstuctural protein 14 (nsp14) functions as (guanine-N7)-methyltransferase (N7-MTase), which is involved in RNA cap formation. Moreover, we found that N7-MTase is well conserved among different CoVs and is a universal target for developing antivirals against CoVs. Here, we show that N7-MTase of CoVs can be an ideal target for designing live attenuated vaccines. Using murine hepatitis virus strain A59 (MHV-A59), a representative and well-studied model of coronaviruses, we constructed N7-MTase-deficient recombinant MHV D330A and Y414A. These two mutants are highly attenuated in mice and exhibit similar replication efficiency to the wild-type (WT) virus in the cell culture. Furthermore, a single dose immunization of D330A or Y414A can induce long-term humoral immune responses and robust CD4+ and CD8+ T cell responses, which can provide full protection against the challenge of a lethal-dose of MHV-A59. Collectively, this study provides an ideal strategy to design live attenuated vaccines for coronavirus by abolishing viral RNA N7-MTase activity. This approach may apply to other RNA viruses that encode their own conservative viral N7-methyltransferase.

Switching to electric vehicles can lead to significant reductions of PM2.5 and NO2 across China

Summary Transportation contributes to around one-fifth of global greenhouse gas emissions, while also causing severe air pollution. The conversion to electric vehicles (EVs) represents a major path to decarbonize the transport sector, with potentially significant co-benefits for human health. However, the scale of such co-benefits largely remains an empirical question and lacks observational evidence. The full lockdown in China during the coronavirus disease 2019 (COVID-19) pandemic provides an unprecedented real-world experiment to evaluate emission reduction potentials of a large-scale transition to EVs. Here, we utilize ground and satellite observations of air quality during the full lockdown to constrain predictions of a comprehensive chemical transport model and find that the substantial traffic reductions are near-linearly linked to reductions of PM2.5 (particles with an aerodynamic diameter ≤2.5 μm) and NO2. A further extrapolation of a full conversion to EVs shows a significant reduction of PM2.5 (30%–70%) and NO2 (30%–80%) in most of China. Our findings provide fact-based evidence of potential environmental benefits generated by fully switching to EVs.

Hospitalization Costs of COVID-19 Cases and Their Associated Factors in Guangdong, China: A Cross-Sectional Study.

Background: The ongoing COVID-19 pandemic has brought significant challenges to health system and consumed a lot of health resources. However, evidence on the hospitalization costs and their associated factors in COVID-19 cases is scarce. Objectives: To describe the total and components of hospitalization costs of COVID-19 cases, and investigate the associated factors of costs. Methods: We included 876 confirmed COVID-19 cases admitted to 33 designated hospitals from January 15th to April 27th, 2020 in Guangdong, China, and collected their demographic and clinical information. A multiple linear regression model was performed to estimate the associations of hospitalization costs with potential associated factors. Results: The median of total hospitalization costs of COVID-19 cases was $2,869.4 (IQR: $3,916.8). We found higher total costs in male (% difference: 29.7, 95% CI: 15.5, 45.6) than in female cases, in older cases than in younger ones, in severe cases (% difference: 344.8, 95% CI: 222.5, 513.6) than in mild ones, in cases with clinical aggravation than those without, in cases with clinical symptoms (% difference: 47.7, 95% CI: 26.2, 72.9) than those without, and in cases with comorbidities (% difference: 21.1%, 21.1, 95% CI: 4.4, 40.6) than those without. We also found lower non-pharmacologic therapy costs in cases treated with traditional Chinese medicine (TCM) therapy (% difference: -47.4, 95% CI: -64.5 to -22.0) than cases without. Conclusion: The hospitalization costs of COVID-19 cases in Guangdong were comparable to the national level. Factors associated with higher hospitalization costs included sex, older age, clinical severity and aggravation, clinical symptoms and comorbidities at admission. TCM therapy was found to be associated with lower costs for some non-pharmacologic therapies.

Reduction of air pollutants and associated mortality during and after the COVID-19 lockdown in China: Impacts and implications.

Although strict lockdown measurements implemented during the COVID-19 pandemic have dramatically reduced the anthropogenic-based emissions, changes in air quality and its health impacts remain unclear in China. We comprehensively described air pollution during and after the lockdown periods in 2020 compared with 2018-2019, and estimated the mortality burden indicated by the number of deaths and years of life lost (YLL) related to the air pollution changes. The mean air quality index (AQI), PM10, PM2.5, NO2, SO2 and CO concentrations during the lockdown across China declined by 18.2 (21.2%), 27.0 µg/m3 (28.9%), 10.5 µg/m3 (18.3%), 8.4 µg/m3 (44.2%), 13.1 µg/m3 (38.8%), and 0.3 mg/m3 (27.3%) respectively, when compared to the same periods during 2018-2019. We observed an increase in O3 concentration during the lockdown by 5.5 µg/m3 (10.4%), and a slight decrease after the lockdown by 3.4 µg/m3 (4.4%). As a result, there were 51.3 (95%CI: 32.2, 70.1) thousand fewer premature deaths (16.2 thousand during and 35.1 thousand after the lockdown), and 1066.8 (95%CI: 668.7, 1456.8) thousand fewer YLLs (343.3 thousand during and 723.5 thousand after the lockdown) than these in 2018-2019. Our findings suggest that the COVID-19 lockdown has caused substantial decreases in air pollutants except for O3, and that substantial human health benefits can be achieved when strict control measures for air pollution are taken to reduce emissions from vehicles and industries. Stricter tailored policy solutions of air pollution are urgently needed in China and other countries, especially in well-developed industrial regions, such as upgrading industry structure and promoting green transportation.

Diverse immunoglobulin gene usage and convergent epitope targeting in neutralizing antibody responses to SARS-CoV-2.

It is unclear whether individuals with enormous diversity in B cell receptor repertoires are consistently able to mount effective antibody responses against SARS-CoV-2. We analyzed antibody responses in a cohort of 55 convalescent patients and isolated 54 potent neutralizing monoclonal antibodies (mAbs). While most of the mAbs target the angiotensin-converting enzyme 2 (ACE2) binding surface on the receptor binding domain (RBD) of SARS-CoV-2 spike protein, mAb 47D1 binds only to one side of the receptor binding surface on the RBD. Neutralization by 47D1 is achieved independent of interfering RBD-ACE2 binding. A crystal structure of the mAb-RBD complex shows that the IF motif at the tip of 47D1 CDR H2 interacts with a hydrophobic pocket in the RBD. Diverse immunoglobulin gene usage and convergent epitope targeting characterize neutralizing antibody responses to SARS-CoV-2, suggesting that vaccines that effectively present the receptor binding site on the RBD will likely elicit neutralizing antibody responses in a large fraction of the population.

Role of neutrophil chemoattractant CXCL5 in SARS-CoV-2 infection-induced lung inflammatory innate immune response in an in vivo hACE2 transfection mouse model.

Understanding the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clarifying antiviral immunity in hosts are critical aspects for the development of vaccines and antivirals. Mice are frequently used to generate animal models of infectious diseases due to their convenience and ability to undergo genetic manipulation. However, normal adult mice are not susceptible to SARS-CoV-2. Here, we developed a viral receptor (human angiotensin-converting enzyme 2, hACE2) pulmonary transfection mouse model to establish SARS-CoV-2 infection rapidly in the mouse lung. Based on the model, the virus successfully infected the mouse lung 2 days after transfection. Viral RNA/protein, innate immune cell infiltration, inflammatory cytokine expression, and pathological changes in the infected lungs were observed after infection. Further studies indicated that neutrophils were the first and most abundant leukocytes to infiltrate the infected lungs after viral infection. In addition, using infected CXCL5-knockout mice, chemokine CXCL5 was responsible for neutrophil recruitment. CXCL5 knockout decreased lung inflammation without diminishing viral clearance, suggesting a potential target for controlling pneumonia.

Yidu-toxicity blocking lung decoction ameliorates inflammation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome by eliminating IL-6 and TNF-a.

The present study investigates the differences in inflammatory agents alterations, immune function, and leukocyte differential count evaluation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome after the recommended Chinese medicine prescription of Yidu-toxicity blocking lung decoction. A total of 40 patients with yidu-toxicity blocking lung syndrome, diagnosed as severe pneumonia of SARS-COV-2 following the latest Chinese national recommendations for the diagnosis and treatment of pneumonia caused by SARS-COV-2 (the 5th edition), were recruited. They were randomly divided into the pure western medicine therapy group (PWM) and integrated into Chinese and Western medicine therapy group (ICW). The general strategies were given to both groups according to the national recommendations, and the ICW group was given Yidu-toxicity blocking lung decoction extraorally. A radioimmunoassay method was adopted to detect the content of IL-6, IL-8,IL-2R,TNF-α, procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in sera. Flow cytometry was used to determine the peripheral blood lymphocyte subsets (the levels of CD3+, CD4+, CD8+, and the ratios of CD4+/CD8+). The white blood cell counts (WBC#), neutrophils count(N#), and lymphocyte counts (L#) were measured using a fully automatic blood rheological instrument. The t-test or Rank Sum Test and Spearman analysis were conducted to evaluate the differences. The results showed that IL-6 (P = 0.013) and TNF-α (P = 0.035) levels in the PWM group were significantly higher than those in the ICW group after treatment. Infection related indicators such as WBC#, N#, L#, hs-CRP showed no differences. The analysis showed that there was no statistical difference in the values of CD4 and CD8 between the two groups. By the end of Day 29, all patients were discharged and the final cure rate for both group were 100 %. Taken together, we conclude that Yidu-toxicity blocking lung decoction could relieve inflammation of SARS-COV-2 patients with yidu-toxicity blocking lung syndrome by eliminating inflammatory agents. CM can serve as a complementary medication to western medicine, which should be highlighted in clinical settings.

Unexpected rise of ozone in urban and rural areas, and sulfur dioxide in rural areas during the coronavirus city lockdown in Hangzhou, China: implications for air quality.

The outbreak of coronavirus named COVID-19, initially identified in Wuhan, China in December 2019, has spread rapidly at the global scale. Most countries have rapidly stopped almost all activities including industry, services and transportation of goods and people, thus decreasing air pollution in an unprecedented way, and providing a unique opportunity to study air pollutants. While satellite data have provided visual evidence for the global reduction in air pollution such as nitrogen dioxide (NO2) worldwide, precise and quantitative information is missing at the local scale. Here we studied changes in particulate matter (PM2.5, PM10), carbon monoxide (CO), NO2, sulfur dioxide (SO2) and ozone (O3) at 10 urban sites in Hangzhou, a city of 7.03 million inhabitants, and at 1 rural site, before city lockdown, January 1-23, during city lockdown, January 24-February 15, and during resumption, February 16-28, in 2020. Results show that city lockdown induced a sharp decrease in PM2.5, PM10, CO, and NO2 concentrations at both urban and rural sites. The NO2 decrease is explained by reduction in traffic emissions in the urban areas, and by lower regional transport in rural areas during lockdown, as expected. SO2 concentrations decreased from 6.3 to 5.3 µg m-3 in the city, but increased surprisingly from 4.7 to 5.8 µg m-3 at the rural site: this increase is attributed both to higher coal consumption for heating and emissions from traditional fireworks of the Spring Eve and Lantern Festivals during lockdown. Unexpectedly, O3 concentrations increased by 145% from 24.6 to 60.6 µg m-3 in the urban area, and from 42.0 to 62.9 µg m-3 in the rural area during the lockdown. This finding is explained by the weakening of chemical titration of O3 by NO due to reductions of NOx fresh emissions during the non-photochemical reaction period from 20:00 PM to 9:00 AM (local time). During the lockdown, compared to the same period in 2019, the daily average concentrations in the city decreased by 42.7% for PM2.5, 47.9% for PM10, 28.6% for SO2, 22.3% for CO and 58.4% for NO2, which is obviously explained by the absence of city activities. Overall, we observed not only the expected reduction in some atmospheric pollutants (PM, SO2, CO, NO2), but also unexpected increases in SO2 in the rural areas and of ozone (O3) in both urban and rural areas, the latter being paradoxically due to the reduction in nitrogen oxide levels. In other words, the city lockdown has improved air quality by reducing PM2.5, PM10, CO, and NO2, but has also decreased air quality by augmenting O3 and SO2.