UBA1-CDK16: A Sex-Specific Chimeric RNA and Its Role in Immune Sexual Dimorphism (preprint)

RNA processing mechanisms, such as alternative splicing and RNA editing, have been recognized as critical means to expand the transcriptome. Chimeric RNAs formed by intergenic splicing provide another potential layer of RNA diversification. By analyzing a large set of RNA-Seq data and validating results in over 1,200 blood samples, we identified UBA1-CDK16, a female-specific chimeric transcript. Intriguingly, both parental genes, are expressed in males and females. Mechanistically, UBA1-CDK16 is produced by cis-splicing between the two adjacent X-linked genes, originating from the inactive X chromosome. A female-specific chromatin loop, formed between the junction sites, facilitates the alternative splicing of its readthrough precursor. This unique chimeric transcript exhibits evolutionary conservation, evolving to be female-specific from non-human primates to humans. Furthermore, our investigation reveals that UBA1-CDK16 is enriched in the myeloid lineage and plays a regulatory role in myeloid differentiation. Notably, female COVID-19 patients who tested negative for this chimeric transcript displayed higher counts of neutrophils, highlighting its potential role in disease pathogenesis. These findings support the notion that chimeric RNAs represent a new repertoire of transcripts that can be regulated independently from the parental genes, and a new class of RNA variance with potential implications in sexual dimorphism and immune responses.

COVID-19 vaccine uptake and hesitancy in Chinese patients with asthma.

OBJECTIVE: Both patients and physicians may be hesitant toward vaccination in patients with asthma, which may result in lower vaccine uptake. The aim of this work was to investigate the vaccination rate, the adverse reactions, as well as the factors associated with vaccine acceptance and hesitancy toward COVID-19 vaccination among asthmatic patients in Beijing. METHODS: A multi-center, cross-sectional face-to-face survey was conducted in patients with asthma consecutively recruited from December 2021 to April 2022. The survey included asthma status, COVID-19 vaccine uptake and adverse reactions, and knowledge of and attitude toward COVID-19 vaccination. RESULTS: A total of 261 patients were enrolled. The rate of COVID-19 vaccination during the study period was 73.6%, as compared to 87.64% in the general population in China. Patients who were currently working, had received other vaccines in the past, and had had no adverse reactions to other vaccines, showed a higher rate of COVID-19 vaccination. Patients believing that the vaccination of family members and colleagues had a positive impact on their decision to get vaccinated, were more likely to get the COVID-19 vaccines. The COVID-19 vaccination rate was lower in those with poorly monitored asthma and those using biologic therapies. The adverse effects of COVID-19 vaccines in asthmatic patients were similar to those in the general population. CONCLUSION: The COVID-19 vaccination rate in asthmatic patients was lower than the general population in China. Active measures should be taken to control asthma and increase vaccination rates in these patients.

Who Sets the Agenda? the Dynamic Agenda Setting of the Wildlife Issue on Social Media

Following the COVID-19's outbreak in China, wildlife-related issues such as wildlife management and conservation made headlines around the world due to the potential zoonotic nature of the newly discovered coronavirus. In our study, we examined the dynamic interaction of the news agenda and public agenda concerning wildlife-related issues on social media after COVID-19's outbreak. Using big data analytics, we automatically extracted the agendas' attributes and networks from 110,549 social media posts made from January 1 to April 8, 2020, and investigated the effect of second- and third-level dynamic agenda setting in a time series analysis. Our findings suggest that the agenda-setting effect of wildlife-related issues on social media was not a single-step, unidirectional action but a reciprocal, dynamic interaction constantly constructed by news outlets and the general public.

"Help Us!": a content analysis of COVID-19 help-seeking posts on Weibo during the first lockdown.

BACKGROUND: Social media is playing an increasingly important role in public emergencies for help-seekers, especially during the global COVID-19 pandemic. Wuhan, China, firstly official reported COVID-19 cases and implemented lockdown measures to prevent the spread of the virus. People during the first lockdown were restricted from seeking help face-to-face. Social media is more prominent as an online tool for people seeking help, especially for patients, than in other stages of the COVID-19 pandemic. OBJECTIVE: This study aimed to explore the urgent needs presented in help-seeking posts in Wuhan during the first COVID-19 lockdown, the content features of these posts, and how they influenced online user engagement. METHODS: This study collected posts from Weibo posted with specific help tags during the first COVID-19 lockdown in Wuhan: from 23 January 2020 to 24 March 2020, and eventually received 2055 data, including textual content, comments, retweets, and publishing location. Content analysis was conducted, and manual coding was performed on help-seeking typology, narrative mode, narrative subject, and emotional valence. RESULTS: The result showed that help-seeking posts primarily were seeking medical (97.7%). Features of these posts were mainly adopting a mixed narrative mode (46.4%), released by relatives of patients (61.7%), and expressing negative emotions (93.2%). Chi-square tests suggested that help-seeking posts with mixed narrative modes released by relatives express more frequent negative emotions. Results of negative binomial regression indicated posts of seeking information (B = 0.52, p < .001, e0.52 = 1.68), with mixed narrative mode (B = 0.63, p < .001, e0.63 = 1.86), released by themselves (as referential groups) and with neutral emotions increased comments. Posts of seeking medical (B = 0.57, p < .01, e0.57 = 1.77), with mixed narrative mode (B = 1.88, p < .001, e1.88 = 6.53), released by people of unrelated patients (B = 0.47, p < .001, e0.47 = 1.60) and with neutral emotions increased retweets. CONCLUSIONS: This study provides evidence of what actual public demands are to be considered and addressed by governments and public administrators before implementing closure and lockdown policies to limit the spread of the virus. Meanwhile, our findings offer strategies for people help-seeking on social media in similar public health emergencies.

Danger control and fear control during public health emergencies: Considering the roles of fear and hope in the EPPM across different levels of trust.

Public health emergencies pose considerable threats to global health and safety. The control of these emergencies requires the efforts of healthcare professionals and calls for the public to take protective actions. The present study not only puts fear back in the extended parallel process model (EPPM) but also considers another similarly productive emotion: hope. We examined the mechanisms behind the effects of four cognitive perceptions on protective actions (i.e., danger control) and information avoidance (i.e., fear control). A national online survey was conducted with 1676 participants during the outbreak of COVID-19 in China from February 1 to 29, 2020. The results revealed that perceived severity and susceptibility could lead to fear, positively affecting protective actions. On the other hand, perceived response efficacy and self-efficacy induced hope, which was positively associated with protective actions but negatively associated with information avoidance. Furthermore, the mechanisms behind the relationships among cognitions, emotions, and behaviors varied across levels of trust in healthcare systems.

Relationship Between Mental Health Education Competency and Interpersonal Trust Among College Counselors: The Mediating Role of Neuroticism.

Objective: Based on the motivated cognition account, this study aimed to explore the relationship between mental health education competency and interpersonal trust among college counselors, as well as the mediating effect of neuroticism. Materials and Methods: A total of 483 college counselors were selected, including 155 men and 328 women. The youngest college counselor was 22 years old and the oldest was 56 years old (M = 31.69, SD = 6.12). The college counselors were asked to fill out the Mental Health Education Competency Scale for College Counselors, a 10-item short version of the Big Five Inventory, and an Interpersonal Trust Scale. Results: (1) This study found a significantly positive correlation between mental health education competency and interpersonal trust. (2) Mental health education competency and interpersonal trust were negatively correlated with neuroticism. (3) The mediating role of neuroticism in the association between mental health education competency and interpersonal trust was significant. Conclusion: Mental health education competency partly affected interpersonal trust via the mediating effect of neuroticism.

Construction of Urban Environmental Performance Evaluation System Based on Multivariate System Theory and Comparative Analysis: A Case Study of Chengdu-Chongqing Twin Cities, China.

Based on the related environmental data of Chengdu and Chongqing from 2011 to 2020, this paper constructs a multivariate environment performance evaluation system, combines the self-built indicator system determination criteria and rules, evaluates and compares the environmental performance of Chengdu and Chongqing, and also discusses the impact of COVID-19 on urban environmental performance. The research results show that the overall environmental performance increased from 2011 to 2020, but there are differences between different subsystems, mainly manifested in the best water environment performance, followed by air environment and solid waste; moreover, the noise environment maintains a relatively stable level. By comparing the average levels of various subsystems of the Chengdu-Chongqing dual cities from 2011 to 2020, it can be seen that Chengdu City has better environmental performance in air environment and solid waste, while Chongqing City has better environmental performance in the water environment and noise environment. In addition, this paper also found that the impact of the epidemic on urban environmental performance mainly comes from the impact on the air environment. At present, the overall environmental performance of the two places has shown a trend of environmentally coordinated development. In the future, Chengdu and Chongqing should further optimize and improve their relatively weak environmental subsystems, deepen the joint action mechanism between the two places, and build a green and high-quality development economic circle for the Chengdu-Chongqing twin cities.

Genetic and enzymatic characterization of two novel blaNDM-36, -37 variants in Escherichia coli strains.

The widespread of different NDM variants in clinical Enterobacterales isolates poses a serious public health concern, which requires continuous monitoring. In this study, three E. coli strains carrying two novel blaNDM variants of blaNDM-36, -37 were identified from a patient with refractory urinary tract infection (UTI) in China. We conducted antimicrobial susceptibility testing (AST), enzyme kinetics analysis, conjugation experiment, whole-genome sequencing (WGS), and bioinformatics analysis to characterize the blaNDM-36, -37 enzymes and their carrying strains. The blaNDM-36, -37 harboring E. coli isolates belonged to ST227, O9:H10 serotype and exhibited intermediate or resistance to all ß-lactams tested except aztreonam and aztreonam/avibactam. The genes of blaNDM-36, -37 were located on a conjugative IncHI2-type plasmid. NDM-37 differed from NDM-5 by a single amino acid substitution (His261Tyr). NDM-36 differed from NDM-37 by an additional missense mutation (Ala233Val). NDM-36 had increased hydrolytic activity toward ampicillin and cefotaxime relative to NDM-37 and NDM-5, while NDM-37 and NDM-36 had lower catalytic activity toward imipenem but higher activity against meropenem in comparison to NDM-5. This is the first report of co-occurrence of two novel blaNDM variants in E. coli isolated from the same patient. The work provides insights into the enzymatic function and demonstrates the ongoing evolution of NDM enzymes.

The identification and phylogenetic analysis of SARS-CoV-2 delta variants in Taiwan.

In Taiwan, coronavirus disease 2019 (COVID-19) involving the delta variant occurred after that involving the alpha variant in 2021. In this study, we aimed to analyze the Delta variant. A total of 318 patients in Taiwan infected with delta variants were identified. The case fatality rate (CFR) of patients infected with delta variants was 0.94% in Taiwan compared with that of those infected with alpha variants (5.95%). The possible reasons for the low CFR might be hybrid immunity due to infection and rapid promotion of the COVID-19 vaccination program during the alpha variant outbreak. We identified three 21J delta variants. Two long gene deletions were detected in these severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) isolates: ORF7aΔ91 in KMUH-8 and SpikeΔ30 in KMUH-9. Protein structure prediction indicates that ORF7aΔ91 results in malfunction of NS7a as an interferon antagonist and that SpikeΔ30 results in a truncated spike protein (N679-A688del), resulting in a lower infection rate compared with the delta variant without these deletions. The impact of these two deletions on SARS-CoV-2-associated pathogenesis deserves further investigation. Delta variants still exist in many regions in the omicron era, and the backbone of the delta variant genome possibly spread worldwide in the form of delta-omicron hybrids (deltacron; e.g., XBC.1 and XAY.2), which casts a potential threat to public health. Our study further highlighted the importance of more understanding of the delta variants.

An Improved Corpus-Based NLP Method for Facilitating Keyword Extraction: An Example of the COVID-19 Vaccine Hesitancy Corpus

In the current COVID-19 post-pandemic era, COVID-19 vaccine hesitancy is hindering the herd immunity generated by widespread vaccination. It is critical to identify the factors that may cause COVID-19 vaccine hesitancy, enabling the relevant authorities to propose appropriate interventions for mitigating such a phenomenon. Keyword extraction, a sub-field of natural language processing (NLP) applications, plays a vital role in modern medical informatics. When traditional corpus-based NLP methods are used to conduct keyword extraction, they only consider a word's log-likelihood value to determine whether it is a keyword, which leaves room for concerns about the efficiency and accuracy of this keyword extraction technique. These concerns include the fact that the method is unable to (1) optimize the keyword list by the machine-based approach, (2) effectively evaluate the keyword's importance level, and (3) integrate the variables to conduct data clustering. Thus, to address the aforementioned issues, this study integrated a machine-based word removal technique, the i10-index, and the importance-performance analysis (IPA) technique to develop an improved corpus-based NLP method for facilitating keyword extraction. The top 200 most-cited Science Citation Index (SCI) research articles discussing COVID-19 vaccine hesitancy were adopted as the target corpus for verification. The results showed that the keywords of Quadrant I (n = 98) reached the highest lexical coverage (9.81%), indicating that the proposed method successfully identified and extracted the most important keywords from the target corpus, thus achieving more domain-oriented and accurate keyword extraction results.

Immunological and metabolic characteristics of the Omicron variants infection.

The Omicron variants of SARS-CoV-2, primarily authenticated in November 2021 in South Africa, has initiated the 5th wave of global pandemics. Here, we systemically examined immunological and metabolic characteristics of Omicron variants infection. We found Omicron resisted to neutralizing antibody targeting receptor binding domain (RBD) of wildtype SARS-CoV-2. Omicron could hardly be neutralized by sera of Corona Virus Disease 2019 (COVID-19) convalescents infected with the Delta variant. Through mass spectrometry on MHC-bound peptidomes, we found that the spike protein of the Omicron variants could generate additional CD8 + T cell epitopes, compared with Delta. These epitopes could induce robust CD8 + T cell responses. Moreover, we found booster vaccination increased the cross-memory CD8 + T cell responses against Omicron. Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted the response of memory T cells. Consistently, a greater fraction of memory CD8 + T cells existed in Omicron stimulated peripheral blood mononuclear cells (PBMCs). In addition, CD147 was also a receptor for the Omicron variants, and CD147 antibody inhibited infection of Omicron. CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia. Taken together, our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron.

Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Investigation on the spatial and temporal patterns of coupling sustainable development posture and economic development in World Natural Heritage Sites: A case study of Jiuzhaigou, China

To continue directing global sustainable development efforts from 2015 to 2030, the United Nations adopted 17 global development goals known as the Sustainable Development Goals (SDGs) when the Millennium Development Goals (MDGs) from 2000 to 2015 expired. Sustainable development of World Natural Heritage Sites is one of these 17 MDGs and a crucial step toward achieving global sustainability. A scientific and systematic indicator system that can measure the sustainable development of natural World Heritage Sites more objectively and fairly is urgently needed to support the establishment of SDG11.4 on a Chinese scale and to help with the subsequent promotion of the development of natural World Heritage Sites. This study proposes a comprehensive assessment indicator system for the sustainable development of natural heritage sites based on the theoretical framework of "value contribution-environmental effect” to quantify the sustainable development of natural heritage sites. The study is based on the ecological environment and regional economic and social data of Jiuzhaigou World Natural Heritage Site from 2010 to 2020. Finally, the degree of coupling and coordination between the natural environment and economic development is assessed and studied. The results show that tourism to the World Heritage Site drove rapid economic development in Jiuzhaigou County between 2010 and 2020. As the fame of the World Heritage Site Jiuzhaigou has grown, so has the per capita income of local locals, making them unduly reliant on tourists for a living. Meanwhile, both the 2017 earthquake and the COVID-19 epidemic in 2019 have had substantial detrimental effects on the local economy. Furthermore, the Jiuzhaigou sustainable development trend from 2010 to 2020 exhibits a "W-shaped” curve, and there is a high level of positive coupling between the Jiuzhaigou sustainable development trend and economic development, and the two are mutually reinforcing.

Efficacy and safety of auto-cross-linked hyaluronic gel to prevent intrauterine adhesion after hysteroscopic electrosurgical resection: a multi-center randomized controlled trial.

Background: The electrothermal effect of hysteroscopic bipolar electrosurgical resection may cause damage to the endometrium, leading to intrauterine adhesion (IUA). Although some studies have demonstrated the efficacy and feasibility of auto-cross-linked hyaluronic (ACP) gel in preventing IUAs, controversy over its use continues. In this randomized controlled multi-center 2-arm parallel trial, we aimed to examine the efficacy and safety of ACP gel in preventing IUA after hysteroscopic electrosurgical resection and facilitate pregnancy in patients. Methods: Patients from 4 centers in China were randomly assigned (1:1) to receive an intrauterine infusion of ACP gel or nothing after hysteroscopic electrosurgical resection. The randomization assignment was generated by computer and kept in a sealed envelope. A second-look hysteroscopy was performed within 3 months of the surgery. Results: From June 2018 to May 2021, 200 patients were recruited. Ultimately, 82 patients in both groups were included in the result analysis. The baseline characteristics were comparable. The outcomes were assessed by using per-protocol analysis. The incidence of IUA in the ACP gel group was lower than that in the control group [3.66% vs. 10.98%, risk ratio (RR) =0.333, 95% confidence interval (CI): 0.094-1.187, P=0.072], and the planned pregnancy rate was higher than that of the control group (60.98% vs. 40.54%, RR =1.504, 95% CI: 0.949-2.384, P=0.071), but the difference was not statistically significant. There was no significant difference in menstruation change. Menstrual volume remained unchanged in most cases (86.59% in ACP gel group vs. 89.02% in the control group, RR =0.877, 95% CI: 0.877-1.109, P=0.815). Menstrual volume decreased in 10 women in the ACP gel group and 8 in the control group (12.20% vs. 9.76%, RR =1.250, 95% CI: 0.520-3.007, P=0.617). No adverse effects were observed after the ACP administration. Conclusions: The present study showed that the use of ACP gel appeared to reduce both the tendency of IUA and American Fertility Society (AFS) scores and improve the subsequent pregnancy rate during hysteroscopic electrosurgical resection when treating polyps, fibroids, and uterine septum. ACP might be recommended to prevent IUA after such surgery. Further studies should be conducted with larger numbers of participants. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100047165.

Anthracyclines inhibit SARS-CoV-2 infection (preprint)

Vaccines and drugs are two effective medical interventions to mitigate SARS-CoV-2 infection. Three SARS-CoV-2 inhibitors, remdesivir, paxlovid, and molnupiravir, have been approved for treating COVID-19 patients, but more are needed, because each drug has its limitation of usage and SARS-CoV-2 constantly develops drug resistance mutations. In addition, SARS-CoV-2 drugs have the potential to be repurposed to inhibit new human coronaviruses, thus help to prepare for future coronavirus outbreaks. We have screened a library of microbial metabolites to discover new SARS-CoV-2 inhibitors. To facilitate this screening effort, we generated a recombinant SARS-CoV-2 Delta variant carrying the nano luciferase as a reporter for measuring viral infection. Six compounds were found to inhibit SARS-CoV-2 at the half maximal inhibitory concentration (IC50) below 1 mM, including the anthracycline drug aclarubicin that markedly reduced viral RNA-dependent RNA polymerase (RdRp)-mediated gene expression, whereas other anthracyclines inhibited SARS-CoV-2 by activating the expression of interferon and antiviral genes. As the most commonly prescribed anti-cancer drugs, anthracyclines hold the promise of becoming new SARS-CoV-2 inhibitors.

Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo.

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

Nanoformulations targeting immune cells for cancer therapy: mRNA therapeutics

The approved worldwide use of two messenger RNA (mRNA) vaccines (BNT162b2 and mRNA-1273) in late 2020 has proven the remarkable success of mRNA therapeutics together with lipid nanoformulation technology in protecting people against coronaviruses during COVID-19 pandemic. This unprecedented and exciting dual strategy with nanoformulations and mRNA therapeutics in play is believed to be a promising paradigm in targeted cancer immunotherapy in future. Recent advances in nanoformulation technologies play a prominent role in adapting mRNA platform in cancer treatment. In this review, we introduce the biologic principles and advancements of mRNA technology, and chemistry fundamentals of intriguing mRNA delivery nanoformulations. We discuss the latest promising nano-mRNA therapeutics for enhanced cancer immunotherapy by modulation of targeted specific subtypes of immune cells, such as dendritic cells (DCs) at peripheral lymphoid organs for initiating mRNA cancer vaccine-mediated antigen specific immunotherapy, and DCs, natural killer (NK) cells, cytotoxic T cells, or multiple immunosuppressive immune cells at tumor microenvironment (TME) for reversing immune evasion. We highlight the clinical progress of advanced nano-mRNA therapeutics in targeted cancer therapy and provide our perspectives on future directions of this transformative integrated technology toward clinical implementation.

CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis.

COVID-19 patients can develop clinical and histopathological features associated with fibrosis, but the pathogenesis of fibrosis remains poorly understood. CD147 has been identified as a universal receptor for SARS-CoV-2 and its variants, which could initiate COVID-19-related cytokine storm. Here, we systemically analyzed lung pathogenesis in SARS-CoV-2- and its delta variant-infected humanized CD147 transgenic mice. Histopathology and Transmission Electron Microscopy revealed inflammation, fibroblast expansion and pronounced fibrotic remodeling in SARS-CoV-2-infected lungs. Consistently, RNA-sequencing identified a set of fibrosis signature genes. Furthermore, we identified CD147 as a crucial regulator for fibroblast activation induced by SARS-CoV-2. We found conditional knockout of CD147 in fibroblast suppressed activation of fibroblasts, decreasing susceptibility to bleomycin-induced pulmonary fibrosis. Meplazumab, a CD147 antibody, was able to inhibit the accumulation of activated fibroblasts and the production of ECM proteins, thus alleviating the progression of pulmonary fibrosis caused by SARS-CoV-2. In conclusion, we demonstrated that CD147 contributed to SARS-CoV-2-triggered progressive pulmonary fibrosis and identified CD147 as a potential therapeutic target for treating patients with post-COVID-19 pulmonary fibrosis.

Immunoglobulin Y Specific for SARS-CoV-2 Spike Protein Subunits Effectively Neutralizes SARS-CoV-2 Infectivity and Ameliorates Disease Manifestations In Vivo.

(Background) The coronavirus disease 2019 (COVID-19) that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries high infectivity and mortality. Efficient intervention strategies are urgently needed. Avian immunoglobulin Y (IgY) showed efficacy against viral infection whereas the in vivo efficacy remains unclear. (Methods) We immunized laying hens with S1, S1 receptor-binding domain (S1-RBD), or S2 subunits of the SARS-CoV-2 spike (S) protein. After immunization, IgYs were collected and extracted from the egg yolks. The neutralization potential of IgYs was examined by the plaque reduction neutralization test (PRNT). The bioutility of IgYs was examined in Syrian hamsters in vivo. (Results) IgYs exhibited typical banding patterns in SDS-PAGE and Western blot and were immunoreactive against S1, S1-RBD, and S2 subunits. The plaque reduction neutralization test (PRNT) showed that all purified IgYs potently neutralized different SARS-CoV-2 strains in vitro. In Syrian hamsters, the combination of IgYs for S1-RBD and S2 subunits administered before or after SARS-CoV-2 infection effectively restored body weight loss and reduced intrapulmonary lesions and the amount of immunoreactive N protein-positive cells, which were caused by SARS-CoV-2 infection. (Conclusions) Collectively, IgYs specific for S protein subunits effectively neutralized SARS-CoV-2 in vitro and in vivo and may serve as prophylactic or therapeutic antibodies in the prevention or treatment of COVID-19.