The impact of pandemic mental cognition on cultural values: an empirical study based on social media.

BACKGROUND: COVID-19 has triggered a global public health crisis, and had an impact on economies, societies, and politics around the world. Based on the pathogen prevalence hypothesis suggested that residents of areas with higher infection rates are more likely to be collectivists as compared with those of areas with lower infection rates. Many researchers had studied the direct link between infectious diseases and individualism/collectivism (infectious diseases→ cultural values), but no one has focused on the specific psychological factors between them: (infectious diseases→ cognition of the pandemic→ cultural values). To test and develop the pathogen prevalence hypothesis, we introduced pandemic mental cognition and conducted an empirical study on social media (Chinese Sina Weibo), hoping to explore the psychological reasons behind in cultural value changes in the context of a pandemic. METHODS: We downloaded all posts from active Sina Weibo users in Dalian during the pandemic period (January 2020 to May 2022) and used dictionary-based approaches to calculate frequency of words from two domains (pandemic mental cognition and collectivism/individualism), respectively. Then we used the multiple log-linear regression analysis method to establish the relationship between pandemic mental cognition and collectivism/individualism. RESULTS: Among three dimensions of pandemic mental cognition, only the sense of uncertainty had a significant positive relationship with collectivism, and also had a marginal significant positive relationship with individualism. There was a significant positive correlation between the first-order lag term AR(1) and individualism, which means the individualism tendency was mainly affected by its previous level. CONCLUSIONS: The study found that more collectivist regions are associated with a higher pathogen burden, and recognized the sense of uncertainty as its underlying cause. Results of this study validated and further developed the pathogen stress hypothesis in the context of the COVID-19 pandemic.

Nonlinear effects of pandemic uncertainty on depression, pandemic preventive behavior intentions, and positive life attitudes: Moderating effects of high and low uncertainty grouping

Backgrounds COVID-19 is difficult to end in a short time and people are still facing huge uncertainties. Since people's lives are gradually returning to normal, the sense of control and intolerance of uncertainty, which were mainly focused by past studies, are not specific to COVID-19 and will be more influenced by some factors unrelated to the pandemic. Therefore, they may be difficult to accurately reflect the individuals' perceptions of uncertainty. Besides, past research just after the outbreak mainly investigated people in high levels of uncertainty, we don't know the impact of uncertainties on individuals' psychological states when people gradually recovered their sense of control. To solve these problems, we proposed the concept of "pandemic uncertainty” and investigated its impact on people's daily lives. Methods During October 20, 2021 to October 22, 2021, this study obtained data about uncertainty, depression, positive attitude, pandemic preventive behavior intentions, personality, and social support from 530 subjects using convenient sampling. The subjects were all college students from the Dalian University of Technology and Dalian Vocational and Technical College. According to the distribution of uncertainty, we divided the dataset into high and low groups. Subsequently, by using uncertainty as the independent variable, the grouping variable as the moderating variable, and other variables as the control variables, the moderating effects were analyzed for depression, positive attitude, and pandemic preventive behavior intentions, respectively. Results The results showed that the grouping variable significantly moderate the influence of uncertainty on positive attitude and pandemic preventive behavior intentions but had no significant effect on depression. Simple slope analysis revealed that high grouping uncertainty significantly and positively predicted positive attitude and pandemic preventive behavior intentions, while low grouping effects were not significant. Conclusion These results reveal a nonlinear effect of pandemic uncertainty on the pandemic preventive behavior intentions and positive life attitudes and enlighten us about the nonlinear relationship of psychological characteristics during a pandemic.

Nonlinear effects of pandemic uncertainty on depression, pandemic preventive behavior intentions, and positive life attitudes: Moderating effects of high and low uncertainty grouping.

Backgrounds: COVID-19 is difficult to end in a short time and people are still facing huge uncertainties. Since people's lives are gradually returning to normal, the sense of control and intolerance of uncertainty, which were mainly focused by past studies, are not specific to COVID-19 and will be more influenced by some factors unrelated to the pandemic. Therefore, they may be difficult to accurately reflect the individuals' perceptions of uncertainty. Besides, past research just after the outbreak mainly investigated people in high levels of uncertainty, we don't know the impact of uncertainties on individuals' psychological states when people gradually recovered their sense of control. To solve these problems, we proposed the concept of "pandemic uncertainty" and investigated its impact on people's daily lives. Methods: During October 20, 2021 to October 22, 2021, this study obtained data about uncertainty, depression, positive attitude, pandemic preventive behavior intentions, personality, and social support from 530 subjects using convenient sampling. The subjects were all college students from the Dalian University of Technology and Dalian Vocational and Technical College. According to the distribution of uncertainty, we divided the dataset into high and low groups. Subsequently, by using uncertainty as the independent variable, the grouping variable as the moderating variable, and other variables as the control variables, the moderating effects were analyzed for depression, positive attitude, and pandemic preventive behavior intentions, respectively. Results: The results showed that the grouping variable significantly moderate the influence of uncertainty on positive attitude and pandemic preventive behavior intentions but had no significant effect on depression. Simple slope analysis revealed that high grouping uncertainty significantly and positively predicted positive attitude and pandemic preventive behavior intentions, while low grouping effects were not significant. Conclusion: These results reveal a nonlinear effect of pandemic uncertainty on the pandemic preventive behavior intentions and positive life attitudes and enlighten us about the nonlinear relationship of psychological characteristics during a pandemic.

A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry.

It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.

A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice.

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.

The COVID-19 vaccination hesitancy among Chinese individuals with diabetes and the impact on glycemic control of vaccination: a questionnaire study.

OBJECTIVE: The study aimed to investigate the attitudes of people with diabetes mellitus (DM) on COVID-19 vaccination and its influence on the glycemic control. METHODS: Data were collected from a consecutive series of adults (age > 18 years) with type 2 diabetes under regular follow-ups in the Integrated Care Diabetes Outpatient Clinic of Peking University First Hospital from December 1st to December 31st 2021. An online interview questionnaire was conducted, and demographic data including age, sex category, history of drug allergy, history of hypertension, the duration of diabetes, reasons for vaccine hesitancy (VH) and adverse reactions after each injection of vaccines was collected. Glucose levels were collected from medical records. RESULTS: Thirty-nine (22.9%) subjects experienced VH and 131 (77.1%) people living with diabetes received inactivated vaccine against COVID-19. Hesitant individuals had a higher proportion of female gender (vaccinated group vs. VH group, 62/131 vs. 26/39, p = 0.044), higher baseline glycosylated hemoglobin A1c (HbA1c) (vaccinated group vs. VH group, 6.56 ± 0.95% vs. 7.54 ± 2.01%, p < 0.001) and elevated baseline postprandial blood glucose (PBG) (vaccinated group vs. VH group, 8.32 ± 1.97 mmol/L vs. 9.44 ± 2.94 mmol/L, p = 0.015). Subjects of male gender (p = 0.025) and history of hypertension (p = 0.021) were likely to get vaccinated, while higher HbA1c was negatively associated with an elevated propensity to receive anti-COVID-19 vaccine (p = 0.003). Most common reasons for hesitating to receive COVID-19 vaccination were worrying about the possibility of leading to other diseases (30.8%), followed by fearing of glucose variation (17.9%). Systemic adverse reactions were reported in 30.5% individuals after the first injection of inactivated vaccines, and resolved within 3 days in medium. Fasting blood glucose (FBG) decreased significantly after the third injection compared with FBG after the second dose (second vs. third, 6.78 ± 1.24 mmol/L vs. 6.41 ± 1.30 mmol/L, p = 0.027). HbA1c reduced significantly from 6.56% before vaccination to 6.35% after the second injection (p = 0.012). CONCLUSIONS: Our study demonstrated that vaccine hesitancy was lower among male subjects and people with hypertension, while vaccine confidence was reduced in people with poor glycemic control. HbA1c level was lower along with vaccination.

ACE2-Independent Bat Sarbecovirus Entry and Replication in Human and Bat Cells.

Hundreds of sarbecoviruses have been found in bats, but only a fraction of them have the ability to infect cells using angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV and -2. To date, only ACE2-dependent sarbecoviruses have been isolated from field samples or grown in the laboratory. ACE2-independent sarbecoviruses, comprising the majority of the subgenus, have not been propagated in any type of cell culture, as the factors and conditions needed for their replication are completely unknown. Given the significant zoonotic threat posed by sarbecoviruses, cell culture models and in vitro tools are urgently needed to study the rest of this subgenus. We previously showed that the exogenous protease trypsin could facilitate cell entry of viral-like particles pseudotyped with spike protein from some of the ACE2-independent sarbecoviruses. Here, we tested if these conditions were sufficient to support bona fide viral replication using recombinant bat sarbecoviruses. In the presence of trypsin, some of the spike proteins from clade 2 viruses were capable of supporting bat sarbecovirus infection and replication in human and bat cells. Protease experiments showed a specific viral dependence on high levels of trypsin, as TMPRSS2 and furin had no effect on clade 2 virus entry. These results shed light on how sarbecoviruses transmit and coexist in their natural hosts, provide key insights for future efforts to isolate and grow these viruses from field samples, and further underscore the need for broadly protective, universal coronavirus vaccines. IMPORTANCE Our studies demonstrate that some unexplored sarbecoviruses are capable of replicating in human and bat cells in an ACE2-independent way but need a high trypsin environment. We found that trypsin is not compensated by other known proteases involved in some coronavirus entry. This work provides important information that the trypsin-dependent entry may be a widely employed mechanism for coronaviruses and will help for further understanding the biological features of the less-studied viruses.

Impacts of COVID-19 Lockdown on Use and Perception of Urban Green Spaces and Demographic Group Differences

The COVID-19 pandemic triggered unprecedented travel restrictions around the world and significantly altered people's daily behaviors. Although previous works have explored the changes in usage and perceptions of urban green spaces (UGS) before and through the pandemic lockdown, there are certain differences in conclusions for various regions, and demographic group differences are not figured out. Our study aimed to evaluate the impacts of the COVID-19 lockdown on the use and perception of urban green spaces in Xuzhou, China and identify the differences across groups through an online survey of 376 respondents. The descriptive statistical results showed that approximately half reduced UGS visits, and one third reported increased importance of UGS's health benefits, especially in mentality. During the lockdown, the city park and community park were the most common destinations and the well-maintained lawn was regarded as the most valued characteristic, followed by sports facilities and seating facilities. Walking was the most frequent means of travel, while public transport was the least common choice. The regression analysis suggested that age, marriage, living pattern and income have significant influences on usage and perception of UGS. The young and the unmarried were more likely to perceive increased social benefits by visiting UGS compared to before the pandemic. People living alone visited the private garden more frequently, and people from three-generation-families preferred green life streets. Richer people unusually spend more time in UGS, benefited more and had more potential to renew green activities. In addition, more perceived risks related to COVID-19 resulted in higher self-reported health benefits. Finally, the suggestions for encouraging UGS visits during the pandemic lockdown are discussed.

Presepsin Predicts Severity and Secondary Bacterial Infection in COVID-19 by Bioinformatics Analysis.

Introduction: Novel coronavirus pneumonia (COVID-19) is an acute respiratory disease caused by the novel coronavirus SARS-CoV-2. Severe and critical illness, especially secondary bacterial infection (SBI) cases, accounts for the vast majority of COVID-19-related deaths. However, the relevant biological indicators of COVID-19 and SBI are still unclear, which significantly limits the timely diagnosis and treatment. Methods: The differentially expressed genes (DEGs) between severe COVID-19 patients with SBI and without SBI were screened through the analysis of GSE168017 and GSE168018 datasets. By performing Gene Ontology (GO) enrichment analysis for significant DEGs, significant biological processes, cellular components, and molecular functions were selected. To understand the high-level functions and utilities of the biological system, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. By analyzing protein-protein interaction (PPI) and key subnetworks, the core DEGs were found. Results: 85 DEGs were upregulated, and 436 DEGs were downregulated. The CD14 expression was significantly increased in the SBI group of severe COVID-19 patients (P < 0.01). The area under the curve (AUC) of CD14 in the SBI group in severe COVID-19 patients was 0.9429. The presepsin expression was significantly higher in moderate to severe COVID-19 patients (P < 0.05). Presepsin has a diagnostic value for moderate to severe COVID-19 with the AUC of 0.9732. The presepsin expression of COVID-19 patients in the nonsurvivors was significantly higher than that in the survivors (P < 0.05). Conclusion: Presepsin predicts severity and SBI in COVID-19 and may be associated with prognosis in COVID-19.

Housing and health: an updated glossary.

Recent crises have underscored the importance that housing has in sustaining good health and, equally, its potential to harm health. Considering this and building on Howden-Chapman's early glossary of housing and health and the WHO Housing and Health Guidelines, this paper introduces a range of housing and health-related terms, reflecting almost 20 years of development in the field. It defines key concepts currently used in research, policy and practice to describe housing in relation to health and health inequalities. Definitions are organised by three overarching aspects of housing: affordability (including housing affordability stress (HAS) and fuel poverty), suitability (including condition, accessibility and sustainable housing) and security (including precarious housing and homelessness). Each of these inter-related aspects of housing can be either protective of, or detrimental to, health. This glossary broadens our understanding of the relationship between housing and health to further promote interdisciplinarity and strengthen the nexus between these fields.

The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint.

The spike protein on sarbecovirus virions contains two external, protruding domains: an N-terminal domain (NTD) with unclear function and a C-terminal domain (CTD) that binds the host receptor, allowing for viral entry and infection. While the CTD is well studied for therapeutic interventions, the role of the NTD is far less well understood for many coronaviruses. Here, we demonstrate that the spike NTD from SARS-CoV-2 and other sarbecoviruses binds to unidentified glycans in vitro similarly to other members of the Coronaviridae family. We also show that these spike NTD (S-NTD) proteins adhere to Calu3 cells, a human lung cell line, although the biological relevance of this is unclear. In contrast to what has been shown for Middle East respiratory syndrome coronavirus (MERS-CoV), which attaches sialic acids during cell entry, sialic acids present on Calu3 cells inhibited sarbecovirus infection. Therefore, while sarbecoviruses can interact with cell surface glycans similarly to other coronaviruses, their reliance on glycans for entry is different from that of other respiratory coronaviruses, suggesting sarbecoviruses and MERS-CoV have adapted to different cell types, tissues, or hosts during their divergent evolution. Our findings provide important clues for further exploring the biological functions of sarbecovirus glycan binding and adds to our growing understanding of the complex forces that shape coronavirus spike evolution. IMPORTANCE Spike N-terminal domains (S-NTD) of sarbecoviruses are highly diverse; however, their function remains largely understudied compared with the receptor-binding domains (RBD). Here, we show that sarbecovirus S-NTD can be phylogenetically clustered into five clades and exhibit various levels of glycan binding in vitro. We also show that, unlike some coronaviruses, including MERS-CoV, sialic acids present on the surface of Calu3, a human lung cell culture, inhibit SARS-CoV-2 and other sarbecoviruses. These results suggest that while glycan binding might be an ancestral trait conserved across different coronavirus families, the functional outcome during infection can vary, reflecting divergent viral evolution. Our results expand our knowledge on the biological functions of the S-NTD across diverse sarbecoviruses and provide insight on the evolutionary history of coronavirus spike.

Demographic Groups' Differences in Restorative Perception of Urban Public Spaces in COVID-19

The health-promoting functions of one's spatial environment have been widely recognized. Facing the huge loss of mental resources caused by the COVID-19 pandemic, visiting and perception of urban public spaces with restorative potential should be encouraged. However perceived, restorativeness differs from individual features. Moreover, the COVID-19 pandemic has considerable effects on residents' leisure travel and psychological states. Therefore, the aim of our research is to identify the demographic variables influencing restorative perception of typical urban public spaces under the social background of the COVID-19 pandemic. The research consists of 841 residents' restorative evaluation of four kinds of urban public spaces according to the Chinese version of the Perceived Restorativeness Scale, including urban green spaces, exhibition spaces, commercial spaces and sports spaces. Then, 10 individual factors were recorded which represented their demographic features and the influence of COVID-19. Then, the relationship between individual features and perceived restoration of different urban public spaces was analyzed, respectively, by using One-way ANOVA and regression analysis. The results show that the urban green spaces were ranked as the most restorative, followed by commercial spaces, sports spaces and exhibition spaces. Further, the findings indicate that significant factors affect the restoration of four typical urban public spaces.

Single-Cell Landscape of Lungs Reveals Key Role of Neutrophil-Mediated Immunopathology during Lethal SARS-CoV-2 Infection.

Due to the limitation of human studies with respect to individual difference or the accessibility of fresh tissue samples, how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in pathological complications in lung, the main site of infection, is still incompletely understood. Therefore, physiologically relevant animal models under realistic SARS-CoV-2 infection conditions would be helpful to our understanding of dysregulated inflammation response in lung in the context of targeted therapeutics. Here, we characterized the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicates human symptoms, including severe lung pathology and lymphopenia. We showed a reduction of lymphocyte populations and an increase of neutrophils in lung and then demonstrated the key role of neutrophil-mediated lung immunopathology in both mice and humans. Under severe conditions, neutrophils recruited by a chemokine-driven positive feedback produced elevated "fatal signature" proinflammatory genes and pathways related to neutrophil activation or releasing of granular content. In addition, we identified a new Cd177high cluster that is undergoing respiratory burst and Stfahigh cluster cells that may dampen antigen presentation upon infection. We also revealed the devastating effect of overactivated neutrophil by showing the highly enriched neutrophil extracellular traps in lung and a dampened B-cell function in either lung or spleen that may be attributed to arginine consumption by neutrophil. The current study helped our understanding of SARS-CoV-2-induced pneumonia and warranted the concept of neutrophil-targeting therapeutics in COVID-19 treatment. IMPORTANCE We demonstrated the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicated human symptoms, including severe lung pathology and lymphopenia. Our comprehensive study revealed the key role of neutrophil-mediated lung immunopathology in SARS-CoV-2-induced severe pneumonia, which not only helped our understanding of COVID-19 but also warranted the concept of neutrophil targeting therapeutics in COVID-19 treatment.

Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice.

Severe acute respiratory syndrome coronavirus (SARS-CoV-1) and SARS-CoV-2 are highly pathogenic to humans and have caused pandemics in 2003 and 2019, respectively. Genetically diverse SARS-related coronaviruses (SARSr-CoVs) have been detected or isolated from bats, and some of these viruses have been demonstrated to utilize human angiotensin-converting enzyme 2 (ACE2) as a receptor and to have the potential to spill over to humans. A pan-sarbecovirus vaccine that provides protection against SARSr-CoV infection is urgently needed. In this study, we evaluated the protective efficacy of an inactivated SARS-CoV-2 vaccine against recombinant SARSr-CoVs carrying two different spike proteins (named rWIV1 and rRsSHC014S, respectively). Although serum neutralizing assays showed limited cross-reactivity between the three viruses, the inactivated SARS-CoV-2 vaccine provided full protection against SARS-CoV-2 and rWIV1 and partial protection against rRsSHC014S infection in human ACE2 transgenic mice. Passive transfer of SARS-CoV-2-vaccinated mouse sera provided low protection for rWIV1 but not for rRsSHC014S infection in human ACE2 mice. A specific cellular immune response induced by WIV1 membrane protein peptides was detected in the vaccinated animals, which may explain the cross-protection of the inactivated vaccine. This study shows the possibility of developing a pan-sarbecovirus vaccine against SARSr-CoVs for future preparedness. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlight the necessity of developing wide-spectrum vaccines against infection of various SARSr-CoVs. In this study, we tested the protective efficacy of the SARS-CoV-2 inactivated vaccine (IAV) against two SARSr-CoVs with different spike proteins in human ACE2 transgenic mice. We demonstrate that the SARS-CoV-2 IAV provides full protection against rWIV1 and partial protection against rRsSHC014S. The T-cell response stimulated by the M protein may account for the cross protection against heterogeneous SARSr-CoVs. Our findings suggest the feasibility of the development of pan-sarbecovirus vaccines, which can be a strategy of preparedness for future outbreaks caused by novel SARSr-CoVs from wildlife.

SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network.

BACKGROUND: Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical manifestations. However, the underlying mechanism of how SARS-CoV-2 interacts with host and develops multiple symptoms is largely unexplored. METHODS: Bioinformatics analysis determined the sequence similarity between SARS-CoV-2 and human genomes. Diverse fragments of SARS-CoV-2 genome containing Human Identical Sequences (HIS) were cloned into the lentiviral vector. HEK293T, MRC5 and HUVEC were infected with laboratory-packaged lentivirus or transfected with plasmids or antagomirs for HIS. Quantitative RT-PCR and chromatin immunoprecipitation assay detected gene expression and H3K27ac enrichment, respectively. UV-Vis spectroscopy assessed the interaction between HIS and their target locus. Enzyme-linked immunosorbent assay evaluated the hyaluronan (HA) levels of culture supernatant and plasma of COVID-19 patients. FINDINGS: Five short sequences (24-27 nt length) sharing identity between SARS-CoV-2 and human genome were identified. These RNA elements were highly conserved in primates. The genomic fragments containing HIS were predicted to form hairpin structures in silico similar to miRNA precursors. HIS may function through direct genomic interaction leading to activation of host enhancers, and upregulation of adjacent and distant genes, including cytokine genes and hyaluronan synthase 2 (HAS2). HIS antagomirs and Cas13d-mediated HIS degradation reduced HAS2 expression. Severe COVID-19 patients displayed decreased lymphocytes and elevated D-dimer, and C-reactive proteins, as well as increased plasma hyaluronan. Hymecromone inhibited hyaluronan production in vitro, and thus could be further investigated as a therapeutic option for preventing severe outcome in COVID-19 patients. INTERPRETATION: HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. FUNDING: The National Key R&D Program of China (2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101), and the National Natural Science Foundation of China (31872814, 32000505).

A Multi-Period Curve Fitting Model for Short-Term Prediction of the COVID-19 Spread in the U.S. Metropolitans.

The COVID-19 has wreaked havoc upon the world with over 248 million confirmed cases and a death toll of over 5 million. It is alarming that the United States contributes over 18% of these confirmed cases and 14% of the deaths. Researchers have proposed many forecasting models to predict the spread of COVID-19 at the national, state, and county levels. However, due to the large variety in the mitigation policies adopted by various state and local governments; and unpredictable social events during the pandemic, it is incredibly challenging to develop models that can provide accurate long-term forecasting for disease spread. In this paper, to address such a challenge, we introduce a new multi-period curve fitting model to give a short-term prediction of the COVID-19 spread in Metropolitan Statistical Areas (MSA) within the United States. Since most counties/cities within a single MSA usually adopt similar mitigation strategies, this allows us to substantially diminish the variety in adopted mitigation strategies within an MSA. At the same time, the multi-period framework enables us to incorporate the impact of significant social events and mitigation strategies in the model. We also propose a simple heuristic to estimate the COVID-19 fatality based on our spread prediction. Numerical experiments show that the proposed multi-period curve model achieves reasonably high accuracy in the prediction of the confirmed cases and fatality.

Potential Associations Between Microbiome and COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis. The disease is characterized by strong infectivity, high morbidity, and high mortality. It is still spreading in some countries. Microbiota and their metabolites affect human physiological health and diseases by participating in host digestion and nutrition, promoting metabolic function, and regulating the immune system. Studies have shown that human microecology is associated with many diseases, including COVID-19. In this research, we first reviewed the microbial characteristics of COVID-19 from the aspects of gut microbiome, lung microbime, and oral microbiome. We found that significant changes take place in both the gut microbiome and airway microbiome in patients with COVID-19 and are characterized by an increase in conditional pathogenic bacteria and a decrease in beneficial bacteria. Then, we summarized the possible microecological mechanisms involved in the progression of COVID-19. Intestinal microecological disorders in individuals may be involved in the occurrence and development of COVID-19 in the host through interaction with ACE2, mitochondria, and the lung-gut axis. In addition, fecal bacteria transplantation (FMT), prebiotics, and probiotics may play a positive role in the treatment of COVID-19 and reduce the fatal consequences of the disease.

Rapid electrochemical detection of COVID-19 genomic sequence with dual-function graphene nanocolloids based biosensor

Discovered in December 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (aka SARS-CoV-2 or 2019-nCoV) has attracted worldwide attention and concerns due to its high transmissibility and the severe health consequences experienced upon its infection, particularly by elderly people. Over 272 million people have been infected till date and over 5.33 million people could not survive the respiratory illness known as COVID-19 syndrome. Rapid and low-cost detection methods are of utmost importance to monitor the diffusion of the virus and to aid in the global fight against the pandemic. We propose here the use of graphene oxide nanocolloids (GONC) as an electroactive nanocarbon material that can act simultaneously as a transducing platform as well as the electroactive label for the detection of 2019-nCoV genomic sequences. The ability of GONC to provide an intrinsic electrochemical signal arising from the reduction of the electrochemically reducible oxygen functionalities present on its surface, allows GONC to be used as a simple and sensitive biosensing platform. Different intrinsic electroactivity of the material was obtained at each step of the genosensing process, starting from the immobilization of a short-stranded DNA probe and followed by the incubation with different concentrations of the target 2019-nCoV DNA strand. Monitoring such variations enabled the quantification of the target analyte over a wide dynamic range between 10−10 and 10−5 M. All in all, this proof-of-concept system serves as a stepping stone for the development of a rapid, sensitive and selective analytical tool for the detection of 2019-nCoV as well as other similar viral vectors. The use of cost-effective electrochemical detection methods coupled with the vast availability and suitability of carbon-based nanomaterials make this sensing system a valid candidate for low-cost and point-of-care analysis.