Antibacterial, antiviral, and biodegradable collagen network mask for effective particulate removal and wireless breath monitoring.

Functional face masks that can effectively remove particulate matter and pathogens are critical to addressing the urgent health needs arising from industrial air pollution and the COVID-19 pandemic. However, most commercial masks are manufactured by tedious and complicated network-forming procedures (e.g., meltblowing and electrospinning). In addition, the materials used (e.g., polypropylene) have significant limitations such as a lack of pathogen inactivation and degradability, which can cause secondary infection and serious environmental concerns if discarded. Here, we present a facile and straightforward method for creating biodegradable and self-disinfecting masks based on collagen fiber networks. These masks not only provide superior protection against a wide range of hazardous substances in polluted air, but also address environmental concerns associated with waste disposal. Importantly, collagen fiber networks with naturally existing hierarchical microporous structures can be easily modified by tannic acid to improve its mechanical characteristics and enable the in situ production of silver nanoparticles. The resulting masks exhibit excellent antibacterial (>99.99%, 15 min) and antiviral (>99.999%, 15 min) capabilities, as well as high PM2.5 removal efficiency (>99.9%, 30 s). We further demonstrate the integration of the mask into a wireless platform for respiratory monitoring. Therefore, the smart mask has enormous promise for combating air pollution and contagious viruses, managing personal health, and alleviating waste issues caused by commercial masks.

Synthesis and anti-SARS-CoV-2 evaluation of lipid prodrugs of ß-D-N4-hydroxycytidine (NHC) and a 3'-fluoro-substituted analogue of NHC.

ß-D-N4-hydroxycytidine (NHC, EIDD-1931) is a nucleoside analogue that exhibits broad spectrum antiviral activity against a variety of RNA viruses. Herein, we report the synthesis of a series of lipid prodrugs of NHC and a novel 3'-fluoro modified NHC analogue, and evaluation of their antiviral activity against five variants of SARS-CoV-2. All lipid prodrugs showed potent antiviral activity against the tested SARS-CoV-2 variants with EC50 values in the range of 0.31-3.51 µM, which were comparable to those of NHC or higher than those of remdesivir and molnupiravir. An increase in the cytostatic activity of the lipid prodrugs was found, but prodrug 2d proved equally selective as molnupinavir. The 3'-F analogue of NHC (6) only displayed minor antiviral activity against the SARS-CoV-2 Omicron variant (EC50 = 29.91 µM), while no activity was found for other variants at the highest concentration tested. The promising antiviral data of the lipid prodrugs of NHC suggest that they deserve further investigation as new anti-SARS-CoV-2 drugs.

Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes.

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been widely reported in various cancers. However, the potential therapeutic targets of the Chonglou active ingredients in LUAD patients remain unknown. Here, the network pharmacology and bioinformatics were performed to analyze the associations of the clinical characteristics, immune infiltration factors and m6A-related genes with the EMT-related genes associated with LUAD (EMT-LUAD related genes), and the molecular docking, STRING, GO, and KEGG enrichment for the drug targets of Chonglou active ingredients associated with EMT (EMT-LUAD-Chonglou related genes). And, cell viability analysis and cell invasion and infiltration analysis were used to confirm the theoretical basis of this study. A total of 166 EMT-LUAD related genes were identified and a multivariate Cox proportional hazards regression model with a favorable predictive accuracy was constructed. Meanwhile, the immune cell infiltration, immune cell subsets, checkpoint inhibitors and the expression of m6A-related genes were significantly associated with the risk scores for EMT-LUAD related genes with independent significant prognostic value of all included LUAD patients. Furthermore, 12 EMT-LUAD-Chonglou related genes with five core drug targets were identified, which participated in LUAD development through extracellular matrix disassembly, collagen metabolic process, collagen catabolic process, extracellular matrix organization, extracellular structure organization and inflammatory response. Moreover, we found that the active ingredients of Chonglou could indeed inhibit the progression of lung adenocarcinoma cells. These results are oriented towards EMT-related genes to achieve a better understanding of the role of Chonglou and its targets in osteosarcoma development and metastasis, thus guiding future preclinical studies and facilitating clinical translation of LUAD treatment.

Publication trends of research on COVID-19 and host immune response: A bibliometric analysis

Introduction As the first bibliometric analysis of COVID-19 and immune responses, this study will provide a comprehensive overview of the latest research advances. We attempt to summarize the scientific productivity and cooperation across countries and institutions using the bibliometric methodology. Meanwhile, using clustering analysis of keywords, we revealed the evolution of research hotspots and predicted future research focuses, thereby providing valuable information for the follow-up studies. Methods We selected publications on COVID-19 and immune response using our pre-designed search strategy. Web of Science was applied to screen the eligible publications for subsequent bibliometric analyses. GraphPad Prism 8.0, VOSviewer, and CiteSpace were applied to analyze the research trends and compared the contributions of countries, authors, institutions, and journals to the global publications in this field. Results We identified 2,200 publications on COVID-19 and immune response published between December 1, 2019, and April 25, 2022, with a total of 3,154 citations. The United States (611), China (353), and Germany (209) ranked the top three in terms of the number of publications, accounting for 53.3% of the total articles. Among the top 15 institutions publishing articles in this area, four were from France, four were from the United States, and three were from China. The journal Frontiers in Immunology published the most articles (178) related to COVID-19 and immune response. Alessandro Sette (31 publications) from the United States were the most productive and influential scholar in this field, whose publications with the most citation frequency (3,633). Furthermore, the development and evaluation of vaccines might become a hotspot in relevant scope. Conclusions The United States makes the most indispensable contribution in this field in terms of publication numbers, total citations, and H-index. Although publications from China also take the lead regarding quality and quantity, their international cooperation and preclinical research need to be further strengthened. Regarding the citation frequency and the total number of published articles, the latest research progress might be tracked in the top-ranking journals in this field. By analyzing the chronological order of the appearance of retrieved keywords, we speculated that vaccine-related research might be the novel focus in this field.

Effects of face shield on an emitter during a cough process: A large-eddy simulation study.

Face shield is a common personal protection equipment for pandemic. In the present work, three-dimensional computational fluid dynamic (CFD) method is used to simulate a cough jet from an emitter who wears a face shield. A realistic manikin model with a simplified mouth cavity is employed. A large eddy simulation with a dynamic structure subgrid scale model is applied to model the turbulence. An Eulerian-Lagrangian approach is adopted to model the two-phase flows, with which the droplets are represented by a cloud of particles. The droplet breakup, evaporation, dispersion, drag force, and wall impingement are considered in this model. An inlet velocity profile that is based on a variable mouth opening area is considered. Special attentions have been put the vortex structure and droplet re-distribution induced by the face shield. It is found that the multiple vortices are formed when the cough jet impinges on the face shield. Some droplets move backward and others move downward after the impinging. It is also found that a small modification of the face shield significantly modifies the flow field and droplet distribution. We conclude that face shield significantly reduces the risk factor in the front of the emitter, meanwhile the risk factor in the back of the emitter increases. When the receiver standing in front of the emitter is shorter than the emitter, the risk is still very high. More attentions should be paid on the design of the face field, clothes cleaning and floor cleaning of the emitters with face shields. Based on the predicted droplet trajectory, a conceptual model for droplet flux is proposed for the scenario with the face shield.

Heavy Metal, Waste, COVID-19, and Rapid Industrialization in This Modern Era-Fit for Sustainable Future

Heavy metal contamination, waste, and COVID-19 are hazardous to all living things in the environment. This review examined the effects of heavy metals, waste, and COVID-19 on the ecosystem. Scientists and researchers are currently working on ways to extract valuable metals from waste and wastewater. We prefer Tessier sequential extraction for future use for heavy metal pollution in soil. Results indicated that population growth is another source of pollution in the environment. Heavy metal pollution wreaks havoc on soil and groundwater, especially in China. COVID-19 has pros and cons. The COVID-19 epidemic has reduced air pollution in China and caused a significant reduction in CO2 releases globally due to the lockdown but has a harmful effect on human health and the economy. Moreover, COVID-19 brings a huge amount of biomedical waste. COVID-19's biomedical waste appears to be causing different health issues. On the other hand, it was discovered that recycling has become a new source of pollution in south China. Furthermore, heavy metal contamination is the most severe ecological effect. Likewise, every problem has a remedy to create new waste management and pollution monitoring policy. The construction of a modern recycling refinery is an important aspect of national waste disposal.

Global Research Status of Multiple Organ Dysfunction Syndrome During 2001-2021: A 20-Year Bibliometric Analysis.

Background: Multiple Organ Dysfunction Syndrome (MODS) is a major cause of high morbidity and mortality among patients in intensive care units (ICU). Although numerous basic and clinical researches on MODS have been conducted, there is still a long way to go to prevent patients from entering this stage. To our knowledge, no bibliometric analyses of MODS have been reported, this study, therefore, was conducted to reveal MODS research status and trends during 2001-2021. Methods: All relevant literature covering MODS during 2001-2021 were extracted from Web of Science. An online analysis platform of literature metrology was used to analyze the publication trends. VOSviewer software was used to collect and analyze the keywords and research hotspots related to MODS. Results: As of July 31, 2021, a total of 994 MODS-related articles from 2001 to 2021 were identified. The United States accounted for the largest number of publications (31.1%), followed by China and Germany, with 186 and 75 publications, respectively. Among all the institutions, the University of Pittsburgh published the most papers related to MODS (21). Critical Care Medicine published the most papers in this field (106). Professor Moore EE, who had the most citation frequency (1847), made great achievements in MODS research. Moreover, analysis of the keywords identified three MODS research hotspot clusters: "mechanism-related research," "clinical research," and "diagnostic research." Conclusions: The United States maintained a top position worldwide and made the most outstanding contribution in the MODS field. In terms of publication, China was next only to the United States, but there was a disproportion between the quantity of publications and citation frequency. The institution University of Pittsburgh and journal Critical Care Medicine represent the highest level of research in this field. During the 20 years from 2001 to 2021, basic MODS research has been in-depth yet progressed relatively slowly recently, but the outbreak of COVID-19 has to some extent set off an upsurge of clinical research in MODS field.

Undergraduates' perceptions on emergency remote learning in ecology in the post-pandemic era.

The COVID-19 pandemic has strongly disrupted academic activities, particularly in disciplines with a strong empirical component among other reasons by limiting our mobility. It is thus essential to assess emergency remote teaching plans by surveying learners' opinions and perceptions during these unusual circumstances. To achieve this aim, we conducted a survey during the spring semester of 2021 in an environmental science program to ascertain learners' perceptions on online and onsite learning activities in ecology-based modules. We were particularly interested not only in comparing the performance of these two types of activities but also in understanding the role played by learners' perceptions about nature in shaping this pattern. Environmental science programs are rather heterogeneous from a conceptual point of view and, thus, learners may also be more diverse than in traditional ecology programs, which may affect their interest for ecology-based modules. We assessed connectedness to nature by computing the reduced version of the Nature Relatedness Scale. Here, we found that online activities systematically obtained significantly lower scores than onsite activities regardless of the wording employed, and that altruistic behaviors were prevalent among learners. Interestingly, scores for both onsite and online activities were strongly influenced by learners' connectedness to nature, as learners with a stronger connection to nature gave higher scores to both types of activities. Our results suggest that an effort to improve the efficacy of remote learning activities should be the focus of research about teaching methodologies in predominantly empirical scientific disciplines.

Development and validation of prognosis model of mortality risk in patients with COVID-19.

This study aimed to identify clinical features for prognosing mortality risk using machine-learning methods in patients with coronavirus disease 2019 (COVID-19). A retrospective study of the inpatients with COVID-19 admitted from 15 January to 15 March 2020 in Wuhan is reported. The data of symptoms, comorbidity, demographic, vital sign, CT scans results and laboratory test results on admission were collected. Machine-learning methods (Random Forest and XGboost) were used to rank clinical features for mortality risk. Multivariate logistic regression models were applied to identify clinical features with statistical significance. The predictors of mortality were lactate dehydrogenase (LDH), C-reactive protein (CRP) and age based on 500 bootstrapped samples. A multivariate logistic regression model was formed to predict mortality 292 in-sample patients with area under the receiver operating characteristics (AUROC) of 0.9521, which was better than CURB-65 (AUROC of 0.8501) and the machine-learning-based model (AUROC of 0.4530). An out-sample data set of 13 patients was further tested to show our model (AUROC of 0.6061) was also better than CURB-65 (AUROC of 0.4608) and the machine-learning-based model (AUROC of 0.2292). LDH, CRP and age can be used to identify severe patients with COVID-19 on hospital admission.

Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases.

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.

Glycomics-informed glycoproteomic analysis of site-specific glycosylation for SARS-CoV-2 spike protein.

This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry. Glycoproteomics analyzes intact glycopeptides to examine site-specific microheterogeneity of glycoproteins. Glycomics provides structural characterization on any glycan assignments by glycoproteomics. This procedure can be modified and applied to a variety of N- and/or O-linked glycoproteins. Combined with bioinformatics, the glycomics-informed glycoproteomics may be useful in generating 3D molecular dynamics simulations of certain glycoproteins alone or interacting with one another. For complete details on the use and execution of this protocol, please refer to Zhao et al. (2020).

Single-cell epigenomic landscape of peripheral immune cells reveals establishment of trained immunity in individuals convalescing from COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes severe complications and even death. However, asymptomatic infection has also been reported, highlighting the difference in immune responses among individuals. Here we performed single-cell chromatin accessibility and T cell-receptor analyses of peripheral blood mononuclear cells collected from individuals convalescing from COVID-19 and healthy donors. Chromatin remodelling was observed in both innate and adaptive immune cells in the individuals convalescing from COVID-19. Compared with healthy donors, recovered individuals contained abundant TBET-enriched CD16+ and IRF1-enriched CD14+ monocytes with sequential trained and activated epigenomic states. The B-cell lineage in recovered individuals exhibited an accelerated developmental programme from immature B cells to antibody-producing plasma cells. Finally, an integrated analysis of single-cell T cell-receptor clonality with the chromatin accessibility landscape revealed the expansion of putative SARS-CoV-2-specific CD8+ T cells with epigenomic profiles that promote the differentiation of effector or memory cells. Overall, our data suggest that immune cells of individuals convalescing from COVID-19 exhibit global remodelling of the chromatin accessibility landscape, indicative of the establishment of immunological memory.

SARS-CoV-2 spillover into hospital outdoor environments.

Facing the ongoing coronavirus infectious disease-2019 (COVID-19) pandemic, many studies focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in indoor environment, on solid surface or in wastewater. It remains unclear whether SARS-CoV-2 can spill over into outdoor environments and impose transmission risks to surrounding people and communities. In this study, we investigated the presence of SARS-CoV-2 by measuring viral RNA in 118 samples from outdoor environment of three hospitals in Wuhan. We detected SARS-CoV-2 in soils (205-550 copies/g), aerosols (285-1,130 copies/m3) and wastewaters (255-18,744 copies/L) in locations close to hospital departments receiving COVID-19 patients or in wastewater treatment sectors. These findings revealed a significant viral spillover in hospital outdoor environments that was possibly caused by respiratory droplets from patients or aerosolized particles from wastewater containing SARS-CoV-2. In contrast, SARS-CoV-2 was not detected in other areas or on surfaces with regular implemented disinfection. Soils may behave as viral warehouse through deposition and serve as a secondary source spreading SARS-CoV-2 for a prolonged time. For the first time, our findings demonstrate that there are high-risk areas out of expectation in hospital outdoor environments to spread SARS-CoV-2, calling for sealing of wastewater treatment unit and complete sanitation to prevent COVID-19 transmission risks.

Organoid: a powerful tool to study lung regeneration and disease.

Organoids are three-dimensional self-organizing structures formed by adult tissue stem cells or pluripotent stem cells. They recapitulate cell-cell, cell-niche interactions in tissue development, homeostasis, regeneration and disease, and provide an in vitro model for drug screening. This review summarizes the recent advances of organoid cultures derived from adult lung stem cells and human pluripotent stem cells, especially focusing on the organoids of the distal airway stem/progenitor cells. We also discuss the applications of organoids in studying lung regeneration and pulmonary diseases, including pulmonary fibrosis, airway diseases and Coronavirus disease 2019 (COVID-19).

Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression. METHODS: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ2 test or the Fisher exact test (categorical variables) and independent group t test or Mann-Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19. RESULTS: The mean incubation was 8.67 (95% confidence interval, 6.78-10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86-12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8+ T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4+ T cells, and CD8+ T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocyte count in pneumonia patients did not recover when discharged. CONCLUSIONS: Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8+ cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.

Clinical Manifestation and Neonatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China.

BACKGROUND: Clinical manifestation and neonatal outcomes of pregnant women with coronavirus disease 2019 (COVID-19) were unclear in Wuhan, China. METHODS: We retrospectively analyzed clinical characteristics of pregnant and nonpregnant women with COVID-19 aged from 20 to 40, admitted between January 15 and March 15, 2020 at Union Hospital, Wuhan, and symptoms of pregnant women with COVID-19 and compared the clinical characteristics and symptoms to historic data previously reported for H1N1. RESULTS: Among 64 patients, 34 (53.13%) were pregnant, with higher proportion of exposure history (29.41% vs 6.67%) and more pulmonary infiltration on computed tomography test (50% vs 10%) compared to nonpregnant women. Of pregnant patients, 27 (79.41%) completed pregnancy, 5 (14.71%) had natural delivery, 18 (52.94%) had cesarean section, and 4 (11.76%) had abortion; 5 (14.71%) patients were asymptomatic. All 23 newborns had negative reverse-transcription polymerase chain results, and an average 1-minute Apgar score was 8-9 points. Pregnant and nonpregnant patients show differences in symptoms such as fever, expectoration, and fatigue and on laboratory tests such as neurophils, fibrinogen, D-dimer, and erythrocyte sedimentation rate. Pregnant patients with COVID-19 tend to have more milder symptoms than those with H1N1. CONCLUSIONS: Clinical characteristics of pregnant patients with COVID-19 are less serious than nonpregnant. No evidence indicated that pregnant women may have fetal infection through vertical transmission of COVID-19. Pregnant patients with H1N1 had more serious condition than those with COVID-19.

The impact of COVID-19 on gastric cancer surgery: a single-center retrospective study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been declared a global pandemic by the World Health Organization. Patients with cancer are more likely to incur poor clinical outcomes. Due to the prevailing pandemic, we propose some surgical strategies for gastric cancer patients. METHODS: The 'COVID-19' period was defined as occurring between 2020 and 01-20 and 2020-03-20. The enrolled patients were divided into two groups, pre-COVID-19 group (PCG) and COVID-19 group (CG). A total of 109 patients with gastric cancer were enrolled in this study. RESULTS: The waiting time before admission increased by 4 days in the CG (PCG: 4.5 [IQR: 2, 7.8] vs. CG: 8.0 [IQR: 2,20]; p = 0.006). More patients had performed chest CT scans besides abdominal CT before admission during the COVID-19 period (PCG: 22 [32%] vs. CG: 30 [73%], p = 0.001). After admission during the COVID period, the waiting time before surgery was longer (PCG: 3[IQR: 2,5] vs. CG: 7[IQR: 5,9]; p < 0.001), more laparoscopic surgeries were performed (PCG: 51[75%] vs. CG: 38[92%], p = 0.021), and hospital stay period after surgery was longer (7[IQR: 6,8] vs.9[IQR:7,11]; p < 0.001). In addition, the total cost of hospitalization increased during this period, (PCG: 9.22[IQR:7.82,10.97] vs. CG: 10.42[IQR:8.99,12.57]; p = 0.006). CONCLUSION: This study provides an opportunity for our surgical colleagues to reflect on their own services and any contingency plans they may have to tackle the COVID-19 crisis.

Risk factors for prolonged viral clearance in adult patients with COVID-19 in Beijing, China: A prospective observational study.

Clearance of COVID-19 from the human body has not been established. Our study collected the laboratory test results from patients and analyzed the correlation between early changes in serum indices and the virus clearance by univariable and multivariable COX regression models, with an aim to explore the risk factors for prolonged viral clearance. The study included 61 patients with COVID-19 treated at the Fifth Medical Center of PLA General Hospital in Beijing from 20 January 2020 to 20 February 2020. We set the total observation of the disease course to 20 days and the patients were divided into two groups (prolonged group, > 20d vs. normal group, ≤ 20d). The 48 patients with COVID-19 included in this study, 13 remained positive for viral nucleic acid monitoring 20 days after onset. The median for virus clearance was 16 days (range, 6-35 days). The results showed that hypertension, a lactate dehydrogenase level > 211.5 U/L, an interleukin 6 (IL-6) level > 12.5 pg/ml, and a NK lymphocyte percentage > 0.5% were associated with prolonged viral clearance. Therefore, we showed that a history of hypertension, an elevated IL-6 level, and an elevated percentage of NK cells were risk factors for prolonged viral clearance.

Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor.

The SARS-CoV-2 betacoronavirus uses its highly glycosylated trimeric Spike protein to bind to the cell surface receptor angiotensin converting enzyme 2 (ACE2) glycoprotein and facilitate host cell entry. We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mimetic immunogen and for a soluble version of human ACE2. We combined this information with bioinformatics analyses of natural variants and with existing 3D structures of both glycoproteins to generate molecular dynamics simulations of each glycoprotein both alone and interacting with one another. Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions. Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation. Taken together, these data can facilitate immunogen design to achieve antibody neutralization and inform therapeutic strategies to inhibit viral infection.