Impact of COVID-19 Lockdown Measures on Chinese Startups and Local Government Public Finance: Challenges and Policy Implications (preprint)

This paper aims to assess the impact of COVID-19 on the public finance of Chinese local governments, with a particular focus on the effect of lockdown measures on startups during the pandemic. The outbreak has placed significant fiscal pressure on local governments, as containment measures have led to declines in revenue and increased expenses related to public health and social welfare. In tandem, startups have faced substantial challenges, including reduced funding and profitability, due to the negative impact of lockdown measures on entrepreneurship. Moreover, the pandemic has generated short- and long-term economic shocks, affecting both employment and economic recovery. To address these challenges, policymakers must balance health concerns with economic development. In this regard, the government should consider implementing more preferential policies that focus on startups to ensure their survival and growth. Such policies may include financial assistance, tax incentives, and regulatory flexibility to foster innovation and entrepreneurship. By and large, the COVID-19 pandemic has had a profound impact on both the public finance of Chinese local governments and the startup ecosystem. Addressing the challenges faced by local governments and startups will require a comprehensive approach that balances health and economic considerations and includes targeted policies to support entrepreneurship and innovation.

The lung employs an intrinsic surfactant-mediated inflammatory response for viral defense (preprint)

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) causes an acute respiratory distress syndrome (ARDS) that resembles surfactant deficient RDS. Using a novel multi-cell type, human induced pluripotent stem cell (hiPSC)-derived lung organoid (LO) system, validated against primary lung cells, we found that inflammatory cytokine/chemokine production and interferon (IFN) responses are dynamically regulated autonomously within the lung following SARS-CoV-2 infection, an intrinsic defense mechanism mediated by surfactant proteins (SP). Single cell RNA sequencing revealed broad infectability of most lung cell types through canonical (ACE2) and non-canonical (endocytotic) viral entry routes. SARS-CoV-2 triggers rapid apoptosis, impairing viral dissemination. In the absence of surfactant protein B (SP-B), resistance to infection was impaired and cytokine/chemokine production and IFN responses were modulated. Exogenous surfactant, recombinant SP-B, or genomic correction of the SP-B deletion restored resistance to SARS-CoV-2 and improved viability.

A potential alternative systemic treatment option for epithelioid sarcoma (preprint)

Background: Epithelioid sarcoma is a rare soft tissue sarcoma characterized by SMARCB1/INI1 deficiency. Much attention has been paid to the selective EZH2 inhibitor tazemetostat, where other systemic treatments are generally ignored. To explore alternative treatment options, we studied the effects of irinotecan-based chemotherapy in a series of epithelioid sarcoma patients. Methods: We retrospectively reviewed data from patients with metastatic or unresectable epithelioid sarcoma at the Peking University People’s Hospital treated with irinotecan (50 mg/m2/d d1-5 Q3W) in combination with Anlotinib (12 mg Qd, 2 weeks on and 1 week off) from July 2015 to November 2021. Results: A total of 54 courses were administered. With a median follow up of 21.2 months (95% CI, 12.2, 68.1), the 5-year overall survival rate was 83.3%. Five of eight (62.5%) patients presented with unresectable localized lesions, including local tumor thrombosis and lymphatic metastasis. The other patients had unresectable pulmonary metastases. Six of eight (75%) patients had progressed following two lines of systemic therapy. The objective response rate reached 37.5% (three of eight patients) while stabilized disease was observed in 62.5% (five of eight) of patients. No patient had progressed at initial evaluation. At the last follow up, two patients were still using the combination and three patients had ceased the therapy due to toxicities such as diarrhea, nausea, and emesis. One patient changed to tazemetostat for maintenance and one patient stopped treatment due to coronavirus disease 2019 (COVID-19). Another patient stopped therapy as residual lesions had been radiated. Conclusions: The combination of irinotecan and Anlotinib as a salvage regimen may be considered another effective treatment option for refractory epithelioid sarcoma. Trial registration: This trial was approved in the Medical Ethics Committee of Peking University People’s Hospital on October 28, 2022 (No.: 2022PHD015-002). The trial was registered in Clinicaltrials.gov with identifier no. NCT05656222.

Red media, blue media, and misperceptions: examining a moderated serial mediation model of partisan media use and COVID-19 misperceptions

Misinformation and misperceptions about COVID-19 have undermined democratic system. Partisan media are regarded as one of the culprits for facilitating the spread of misinformation. Grounded in the extended communication mediation model, this study analyzes a U.S. survey sample and examines the conditional indirect effects of partisan media use on COVID-19 related misperceptions. Findings show that using conservative and liberal media both have positive effects on misperceptions and message derogation. Conservative media use has a negative impact on perceived response efficacy, whereas liberal media use positively influenced it. Furthermore, the effect of liberal media use on misperceptions became negative when serially mediated by perceived response efficacy and message derogation. Lastly, discussion network heterogeneity was a significant moderator, such that the indirect effects of partisan media use on misperceptions became weaker among those with a more heterogeneous discussion network. Theoretical and practical implications are discussed. Supplementary Information The online version contains supplementary material available at 10.1007/s12144-022-03772-x.

Social media interactions between government and the public: A Chinese case study of government WeChat official accounts on information related to COVID-19

The concept of a public energy field is central to public administration discourse theory. Its main idea is the facilitation of dialog between government and the public, on the basis of equality, to construct a public policy consensus. In contemporary society, social media provides new and distinctive channels for such interactions. Social media can, therefore, be conceived as a novel type of public energy field. Since the outbreak of the COVID-19 pandemic, interactions between the Chinese government and the Chinese public (whether located in China or abroad) have been acutely reflected through WeChat official accounts. This article focuses on the COVID-19 pandemic and, through social media text mining and processing, analyzes the text topics and emotions covered. Basic principles of discourse validity, regarding this public energy field and two guarantee conditions, are applied to analyze the information exchange and dialog between the government and the public on COVID-19 through WeChat official accounts. It was found that the government’s WeChat official accounts have not yet formed a harmonious dialog space to balance the public energy field, and that the interaction between the government and the public has to be improved. The government’s social discourse had a significant influence on the public’s social discourse. Using text analysis, the study found that the government has published information on 11 topics related to the prevention and control of the pandemic. It can be argued that the public energy field presented by both the government and the public effectively portrayed and reflected the actual situation of the pandemic in China.

Discussion about the prevention of Coronavirus disease 19 based on the thought of treating non-disease and the theory of constitution of traditional Chinese medicine

Objective To summarize and analyze the susceptible constitution of coronavirus disease 19(COVID-19), put forward the diet prescription of traditional Chinese medicine for prevention based on the thought of treating non-disease and the theory of constitution, and to provide reference for COVID-19's prevention. Methods The relevant literatures in the past 5 years were reviewed, and the current situation of COVID-19's clinical manifestations, etiology, pathogenesis, disease location, disease transmission, susceptible physique, physique differentiation and prevention were summarized. Results The symptoms of COVID-19 were similar in the initial stage of infection, which was caused by damp pathogen. People with different physique were different in susceptibility to COVID-19 and the development and outcome of syndrome type after infection. The susceptible constitution was phlegm-dampness, dampness-heat, Qi deficiency and yang deficiency, blood stasis and Qi depression. Invigorating vital Qi, dispelling dampness, and nourishing lung are the basic treatment principles. Combined with physical differences and dialectical prevention, tonifying, invigorating spleen and stomach, and aromatic dampness-transforming drugs are major drugs, which are supplemented by drugs for promoting lung-Qi. Conclusion The formulation of preventive prescriptions of traditional Chinese medicine according to different physique can provide some guidance for the clinical prevention of COVID-19.

Nanobody-Functionalized Cellulose for Capturing and Containing SARS-CoV-2 (preprint)

The highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 217 million people, claiming ~ 4.5 million lives to date. Although mandatory quarantines, lockdowns, and vaccinations help curb viral transmission, safe and effective preventative measures remain urgently needed. Here, we present a generic strategy for containing SARS-CoV-2 by cellulose materials. Specifically, we developed a bifunctional fusion protein consisting of a cellulose-binding domain and a nanobody (Nb) targeting the receptor-binding domain of SARS-CoV-2. The immobilization of the fusion proteins on cellulose substrates enhanced the capture efficiency of Nbs against SARS-CoV-2 pseudoviruses of the wildtype and the D614G variant, the latter of which has been shown to confer higher infectivity. Furthermore, the fusion protein was integrated into a customizable chromatography with highly porous cellulose for neutralizing virus from contaminated fluids in a continuous and cost-effective fashion. Taken together, our work leverages low-cost cellulose materials and recently developed Nbs to provide a complementary approach to addressing the pandemic. IMPORTANCEThe ongoing efforts to address the COVID-19 pandemic center around the development of point-of-care diagnostics, preventative measures, and therapeutic strategies against COVID-19. In contrast to existing work, we have provided a complementary approach to target and contain SARS-CoV-2 from contaminated fluids and surfaces. Specifically, we present a generic strategy for the capture and containing of SARS-CoV-2 by cellulose-based substrates. This was archived by developing a bifunctional fusion protein consisting of both a cellulose-binding domain and a nanobody specific for the receptor-binding domain of SARS-CoV-2. As a proof-of-concept, our fusion protein-coated cellulose substrates exhibited enhanced capture efficiency against SARS-CoV-2 pseudovirus of both wildtype and the D614G mutant variants, the latter of which has been shown to confer higher infectivity. Furthermore, the fusion protein was integrated into a customizable chromatography with highly porous cellulose for neutralizing the virus from contaminated fluids in a highly continuous and cost-effective fashion.

Nanobody-Functionalized Cellulose for Capturing and Containing SARS-CoV-2 (preprint)

The highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 196 million people, claiming ~ 4.2 million lives to date. Although mandatory quarantines, lockdowns, and vaccinations help curb viral transmission, safe and effective preventative measures remain urgently needed. Here, we present a generic strategy for containing SARS-CoV-2 by cellulose materials. Specifically, we developed a bifunctional fusion protein consisting of a cellulose-binding domain and a nanobody (Nb) targeting the receptor-binding domain of SARS-CoV-2. The immobilization of the fusion proteins on cellulose substrates enhanced the capture efficiency of Nbs against SARS-CoV-2 pseudoviruses of both the wildtype and the D614G variant, the latter of which has been shown to confer higher infectivity. Furthermore, the fusion protein was integrated into a customizable chromatography with highly porous cellulose for neutralizing virus from contaminated fluids in a continuous and cost-effective fashion. Taken together, our work leverages low-cost cellulose materials and recently developed Nbs to provide a complementary approach to addressing the pandemic.

Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients (preprint)

BackgroundIncreased inflammation is a hallmark of COVID-19, with pulmonary and systemic inflammation identified in multiple cohorts of patients. Definitive cellular and molecular pathways driving severe forms of this disease remain uncertain. Neutrophils, the most numerous leukocytes in blood circulation, can contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in multiple neutrophil functions and circulating cytokine levels over time during COVID-19 may help define disease severity and guide care and decision making. MethodsBlood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil oxidative burst, neutrophil extracellular trap formation (NETosis), phagocytosis and cytokine levels were assessed ex vivo. Lung tissue was obtained immediately post-mortem for immunostaining. ResultsElevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified in COVID-19 plasma both at the first measurement and at multiple timepoints across hospitalization (p < 0.0001). Neutrophils had exaggerated oxidative burst (p < 0.0001), NETosis (p < 0.0001) and phagocytosis (p < 0.0001) relative to controls. Increased NETosis correlated with both leukocytosis and neutrophilia. Neutrophils and NETs were identified within airways and alveoli in the lung parenchyma of 40% of SARS-CoV-2 infected lungs. While elevations in IL-8 and ANC correlated to COVID-19 disease severity, plasma IL-8 levels alone correlated with death. ConclusionsCirculating neutrophils in COVID-19 exhibit an activated phenotype with increased oxidative burst, NETosis and phagocytosis. Readily accessible and dynamic, plasma IL-8 and circulating neutrophil function may be potential COVID-19 disease biomarkers.

Natural SARS-CoV-2 infection in kept ferrets, Spain (preprint)

We found SARS-CoV-2 RNA in 6 of 71 ferrets (8.4%) and isolated the virus from one rectal swab. Natural SARS-CoV-2 infection does occur in kept ferrets, at least under circumstances of high viral circulation in the human population. However, small ferret collections are probably unable to maintain prolonged virus circulation.

Increased IL-8, Neutrophil Activation Phenotypes and NETosis in Critically Ill COVID-19 Patients (preprint)

Background: Increased inflammation is a hallmark of COVID-19, with pulmonary and systemic inflammation identified in multiple cohorts of patients. Definitive cellular and molecular pathways driving severe forms of this disease remain uncertain. Neutrophils, the most numerous leukocytes in blood circulation, can contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Neutrophilia, elevated neutrophil:lymphocyte ratios, and elevated neutrophil-associated cytokines are present in COVID-19, but changes in neutrophil functions have not been characterized. Here we analyzed the functional state of circulating neutrophils in COVID-19.Methods: Blood was obtained from critically ill COVID-19 patients over two weeks and healthy controls across multiple timepoints. Plasma cytokine profiles were assessed by bead array. Neutrophils were isolated and tested ex vivo for oxidative burst, neutrophil extracellular trap formation (NETosis) and phagocytosis. Lung tissue was obtained immediately post-mortem from COVID-19 patients for immunostaining.Results: Elevations in neutrophil-associated cytokines IL-8 and IL-6 were identified in COVID-19 plasma both at the first measurement and across their hospitalization (p < 0.0001). Elevations in cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF were also present at the first measurement and across hospital stays. Functionally, circulating neutrophils from COVID-19 patients had exaggerated oxidative burst (p < 0.0001), NETosis (p < 0.0001) and phagocytosis (p < 0.0001) relative to controls. Increased NETosis was found to be correlated with both leukocytosis and neutrophilia in COVID-19 patients. Neutrophils and NETs were identified within airways and alveoli in lung parenchyma. While elevations in IL-8 and ANC correlated to COVID-19 disease severity, plasma IL-8 levels alone correlated with death.Conclusions: Circulating neutrophils in COVID-19 exhibit an activated phenotype with increased oxidative burst, NETosis and phagocytosis. Readily accessible and dynamic, plasma IL-8 and circulating neutrophil function can be explored as potential COVID-19 disease biomarkers.Funding Statement: This work was supported by the Department of Veterans Affairs (salary support and VA Merit Award, PI Crotty Alexander) and NIH NHLBI (PI Crotty Alexander).Declaration of Interests: The authors report no conflicts of interest.Ethics Approval Statement: The research protocol was approved by the UCSD, VASDHS and Rady Children’s Hospital institutional review boards (IRBs) and all participants or designated family member gave written informed consent.

Quantifying the impacts of human mobility restriction on the spread of COVID-19: an empirical analysis from 344 cities of China (preprint)

Abstract Objective Since the outbreak of novel coronavirus pneumonia (COVID-19), human mobility restriction measures have raised controversies, partly due to inconsistent findings. Empirical study is urgently needed to reliably assess the causal effects of mobility restriction. Methods Our study applied the difference-in-difference (DID) model to assess declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time, after adjusting for confounders. Results The DID model showed that a continual expansion of the relative declines over time in 2020. After four weeks, population mobility declined by 54.81% (interquartile ranges, -65.50% to -43.56%). The accrued population mobility declines were associated with significant reduction of cumulative COVID-19 cases throughout six weeks (i.e., 1% decline of population mobility was associated with 0.72% (95%CI 0.50% to 0.93%) reduce of cumulative cases for one week, 1.42% two weeks, 1.69% three weeks, 1.72% four weeks,1.64% five weeks and 1.52% six weeks). The impact on weekly new cases seemed greater in the first four weeks, but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities. Conclusion Persistent population mobility restrictions are well deserved. However, a change in the degree of mobility restriction may be warranted over time, particularly after several weeks of rigorous mobility restriction. Implementation of mobility restrictions in major cities with large population sizes may be even more important.

Single Nucleus Multiomic Profiling Reveals Age-Dynamic Regulation of Host Genes Associated with SARS-CoV-2 Infection (preprint)

Respiratory failure is the leading cause of COVID-19 death and disproportionately impacts adults more than children. Here, we present a large-scale snATAC-seq dataset (90,980 nuclei) of the human lung, generated in parallel with snRNA-seq (46,500 nuclei), from healthy donors of ~30 weeks, ~3 years and ~30 years of age. Focusing on genes implicated in SARS-CoV-2 cell entry, we observed an increase in the proportion of alveolar epithelial cells expressing ACE2 and TMPRSS2 in adult compared to young lungs. Consistent with expression dynamics, 10 chromatin peaks linked to TMPRSS2 exhibited significantly increased activity with age and harbored IRF and STAT binding sites. Furthermore, we identified 14 common sequence variants in age-increasing peaks with predicted regulatory function, including several associated with respiratory traits and TMPRSS2 expression. Our findings reveal a plausible contributor to why children are more resistant to COVID-19 and provide an epigenomic basis for transferring this resistance to older populations.