Associations of dyspnea symptoms with lung function in patients with COVID-19 in the acute period (preprint)

Background Currently, the main prevalent strain of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is Omicron, which shows elevated viral load and spread ability, bringing new challenges to pandemic prevention and control.Objective To examine the associations of dyspnea symptoms with lung function in coronavirus disease-19 (COVID-19) patients during the acute period.Methods This study included COVID-19 cases diagnosed by real-time PCR (RT-PCR). These patients were divided into the dyspnea and non-dyspnea groups based on whether they had dyspnea symptoms at the time of admission.Results A total of 29 patients with pulmonary function tests (PFTs) were included in this study. Of all patients, 17.24% (5/29) had severe COVID-19, while the remaining cases were mild or moderate. Lung function was normal, with forced vital capacity (FVC) ≥ 80%, forced expiratory volume in 1 second (FEV1)/FVC ≥ 0.92, and diffusing capacity for carbon monoxide (DLCO) ≥ 80% in 96.55% (28/29), 79.31% (23/29), and 72.41% (21/29) of patients, respectively. Computer tomography (CT) findings were normal in 10.34% (3/29) of patients.Conclusions Multivariate analysis showed that lung function and chest CT parameters are not independently associated with dyspnea persistence in acute COVID-19 patients.

Pandemic Lessons of Sustainability: Higher Covid-19 Mortality in Less Sustainable US States (preprint)

This paper intends to contribute to the current debate over what lessons the United States should take away from the Covid-19 pandemic. It focuses on the role that sustainability played in shaping different pandemic outcomes among the 50 states. By the end of 2021, Mississippi reported the highest death rate from Covid-19 in the country, more than five times higher than Vermont, which reported the lowest death rate. If Mississippi had the same death rate as Vermont, approximately 83% of the lives lost (7,958 individuals) could have been saved. If all 50 states had the same death rate as Vermont, approximately 583,296 individuals (76% of the total deceased) would have survived. Such large variation among the states requires further research to understand. Political ideology is currently a popular possible explanation for discrepancies among states in pandemic outcomes, given that Republican states tended to have higher death rates compared to Democratic ones. Additionally, partisan politics have been criticized for hindering the US pandemic response, especially in the early stages of the pandemic. However, this study demonstrates that indicators of sustainability may actually serve as more significant predictors of Covid-19 death rates among the US states than political affiliation. Using the percentage of votes for Trump per state in 2020 as a proxy variable, this study found that the correlation between political affiliation and Covid-19 death rates is significant only when it is the lone parameter. Its effects are overshadowed when vaccination rates and eco-friendliness are included in the equation. Above all, when the Sustainable Development Goal (SDG) index is added to the regression, it becomes the only significant predictor of death rates from Covid-19 becoming more influential than both partisan politics and vaccination. This suggests that it was not red or blue, but rather green that was the most important factor in determining Covid-19 mortality.

Network structure of family function and self-management in patients with early chronic kidney disease amid the COVID-19 pandemic

Background Family function plays a pivotal role in self-management among patients with early chronic kidney disease (CKD), which has been especially important during the COVID-19 pandemic. Previous studies have investigated the relationships between family function and self-management using total scores through self-report questionnaires while ignoring the different components in both family function and self-management. The specific objective of this study was to explore the network structure of family function and self-management at the component level. Methods A total of 360 patients with early CKD from three tertiary hospitals were enrolled in our cross-sectional survey from September to December 2021 in China. Components of family function were measured by the Family Adaptation Partnership Growth and Resolve Index, and components of self-management were measured by the Chronic Kidney Disease Self-management Instrument. Network analysis was used to establish the network structure. Results Edges across the community of family function and self-management were mainly positive. Edges between F3 "Growth” and M1 "Self-integration”, F2 "Partnership” and M3 "Seeking social support,” F5 "Resolve” and M3 "Seeking social support” were the strongest. F3 "Growth” had the greatest positive bridge expected influence of family function community (0.12), and M3 "Seeking social support” had the greatest positive bridge expected influence of self-management community (0.16). Conclusion We explored the potential pathways between different components of family function and self-management among patients with early CKD during the COVID-19 pandemic and found fine-grained relationships between them. The two nodes F3 "Growth” and M3 "Seeking social support” may provide a new idea from the perspective of family function for interventions to improve self-management.

Influence of positive and negative affect on self-management among patients with early chronic kidney disease during the COVID-19 pandemic: The mediating and suppressing effect of ego depletion

Background Self-management in patients with early chronic kidney disease (CKD) can effectively delay damage to renal function. However, with the continuous spread of COVID-19, patients cannot receive timely treatment, which can lead to different affects, resulting in ego depletion and serious challenges to self-management. This study aimed to investigate the mediating and suppressing roles of ego depletion on the relationship between positive and negative affect and self-management among patients with early CKD during the COVID-19 pandemic in China. Methods A total of 383 patients with early CKD from three tertiary hospitals were enrolled by convenience sampling in our cross-sectional study from September 2021 to March 2022. Participants completed the Sociodemographic Questionnaire, Positive Affect and Negative Affect Scale, Self-Regulating Fatigue Scale and Chronic Kidney Disease Self-Management Instrument. A structural equation model was conducted to test the mediating and suppressing effects of ego depletion on the relationship between positive and negative affect and self-management. Results The average score of the participants' self-management was 84.54 (SD: 19.72), and nearly 60% of them were at low and moderate levels. The mediating effect of positive affect on self-management through ego depletion was significant (β = 0.248, 95% CI: 0.170 to 0.376), accounting for 53.22% of the total effect. The suppressing effect of negative affect on self-management through ego depletion was significant (β = −0.191, 95% CI: −0.310 to −0.118), and the absolute value of the ratio of the suppressing effect to the direct effect was 66.55%. Conclusions Ego depletion partially mediated the relationship between positive affect and self-management while suppressing the relationship between negative affect and self-management among patients with early CKD during the COVID-19 pandemic. The reduction of patients' ego depletion must be taken as the intervention target to improve self-management and delay the progression of CKD.

Fair Assignment for Reserved Nucleic Acid Testing

Corona Virus Disease 2019 (COVID-19) is now treating the health of millions of people worldwide. The Chinese government now applies nucleic acid testing as a tool to detect patients from healthy people to control the spread of COVID-19. However, people may come to the nucleic acid testing stations simultaneously, leading to long queues and wasting time. In this paper, we proposed the reserved nucleic acid testing method, which could be easily implemented via Web applications associated with nucleic acid testing. Its key idea is to assign people to different pre-scheduled time slots so that the number of people arriving at a certain time slot can be controlled under the capacity, and thus congestion can be relieved. The key question is how to assign people in a fair manner. We propose a concise model to formalize and analyze the minimum total envy and pairwise fairness assignment problem for a variety of reservation-based applications, including nuclear acid testing. Its objective is to maximize the sum of each person's utility under the capacity constraints of time slots. The decision variables are the time slot assignment of each person. We show that the envy-freeness solution is usually unavailable. However, we can minimize the total envy through appropriate arrangements and realize pairwise fairness with equal-chance shuffling.

Comparison between emerging adults and adults in terms of contamination fear, post-COVID-19 PTSD and psychiatric comorbidity

The present study compared Chinese emerging adults and adults regarding the association between contamination fear, posttraumatic stress disorder post-COVID-19 and psychiatric comorbidity after controlling for demographic and trauma exposure variables. 1089 Chinese civilians (M = 382;F = 707) with a mean age of 26 years (M = 26.36, SD = 8.58) were recruited from different provinces in China via an online survey posted on mainstream Chinese social networking platforms. They completed a demographic page with questions on trauma exposure, the Vancouver Obsessional Compulsive Inventory, the Posttraumatic Stress Disorder Checklist for DSM-5 and the General Health Questionnaire-28. Results showed that 12.7%, 68.7% and 18.6% met criteria for full, partial and no PTSD, respectively. Emerging adults reported significantly lower levels of symptoms of re-experiencing, avoidance, somatic problems, anxiety and fear of contamination than adults. In both emerging adults and adults, contamination fear was correlated with PTSD and psychiatric comorbidity. High educational attainment was significantly correlated with psychiatric comorbidity in emerging adults, but with PTSD in adults. Length of quarantine was correlated with psychiatric comorbidity only in adults. In conclusion, both emerging adults and adults developed varying levels of contamination fear, posttraumatic stress and general psychological symptoms following the outbreak of COVID-19. Emerging adults were more resilient than adults in coping with distress.

Evaluation of a novel fully automated and ELISA- based assays for detecting anti- SARS- CoV-2 neutralizing antibodies (preprint)

Background: Rapid and accurate measurement of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-specific neutralizing antibodies (nAbs) is paramount for monitoring immunity in infected and vaccinated subjects. The current gold standard relies on pseudovirus neutralization tests which require sophisticated skills and facilities. Alternatively, recent competitive immunoassays measuring anti-SARS-CoV-2 nAbs are proposed as a quick and commercially available surrogate virus neutralization test (sVNT). Here, we report the performance evaluation of three sVNTs, including two ELISA-based assays and a novel automated bead-based immunoassay for detecting nAbs against SARS-CoV-2. Method: The performance of three sVNTs, including GenScript cPass, Dynamiker, and Mindray NTAb was assessed in samples collected from SARS-CoV-2 infected patients (n=160), COVID-19 vaccinated individuals (n=163), and pre-pandemic controls (n=70). Samples were collected from infected patients and vaccinated individuals 2-24 weeks after symptoms onset or second dose administration. Correlation analysis with pseudovirus neutralization test (pVNT) and immunoassays detecting anti-SARS-CoV-2 binding antibodies was performed. Receiver operating characteristic (ROC) curve analysis was generated to assess the optimal threshold for detecting nAbs by each assay. Results: All three sVNTs showed an excellent performance in terms of specificity (100%) and sensitivity (100%, 97.0%, and 97.1% for GenScript, Dynamiker, and Mindray, respectively) in samples collected from vaccinated subjects. GenScript demonstrated the strongest correlation with pVNT (r=0.743, R2=0.552), followed by Mindray (r=0.718, R2=0.515) and Dynamiker (r=0.608, R2=0.369). Correlation with anti-SARS-CoV-2 binding antibodies was variable, but the strongest correlations were observed between anti-RBD IgG antibodies and Mindray (r=0.952, R2=0.907). ROC curve analyses demonstrated excellent performance for all three sVNT assays in both groups, with an AUC ranging between 0.99 and 1.0 (p <0.0001). Also, it was shown that the manufacturer’s recommended cutoff values could be modified based on the tested cohort without significantly affecting the sVNT performance.Conclusion: The sVNT provides a rapid, low-cost, and scalable alternative to conventional neutralization assays for measuring and expanding nAbs testing across a wide range of research and clinical settings. Also, it could aid in evaluating actual protective immunity at the population level and assessing vaccine effectiveness to lay a foundation for boosters’ requirements.

Three-dose vaccination-induced immune responses protect against SARS-CoV-2 Omicron BA.2 (preprint)

Background: The ongoing outbreak of SARS-CoV-2 Omicron BA.2 infections in Hong Kong, the world model city of universal masking, has resulted in a major public health crisis. Although the third heterologous BNT162b2 vaccination after 2-dose CoronaVac generated higher neutralizing antibody responses than the third homologous CoronaVac booster, vaccine efficacy and corelates of immune protection against the major circulating Omicron BA.2 remains to be investigated. Methods: : We investigated the vaccine efficacy against the Omicron BA.2 breakthrough infection among 481 public servants who had been received with SARS-CoV-2 vaccines including two-dose BNT162b2 (2×BNT, n=169), three-dose BNT162b2 (2×BNT, n=175), two-dose CoronaVac (2×CorV, n=37), three-dose CoronaVac (3×CorV, n=68) and third-dose BNT162b2 following 2×CorV (2×CorV+1BNT, n=32). Humoral and cellular immune responses after three-dose vaccination were characterized and correlated with clinical characteristics of BA.2 infection. Results: : During the BA.2 outbreak, 29.3% vaccinees were infected. Three-dose vaccination provided protection with lower incidence rates of breakthrough infections (2×BNT 49.2% vs 3×BNT 16.6%, p<0.0001; 2×CorV 48.6% vs 3×CoV 20.6%, p=0.003). The third heterologous vaccination showed the lowest incidence (2×CorV+1×BNT 6.3%). Although BA.2 conferred the highest neutralization resistance compared with variants of concern tested, the third dose vaccination-activated spike-specific memory B and Omicron cross-reactive T cell responses contributed to reduced frequencies of breakthrough infection and disease severity. Conclusions: : Our results have implications to timely boost vaccination and immune responses likely required for vaccine-mediated protection against Omicron BA.2 pandemic.

Three-dose vaccination-induced immune responses protect against SARS-CoV-2 Omicron-BA.2 (preprint)

The ongoing outbreak of SARS-CoV-2 Omicron BA.2 infections in Hong Kong, the world model city of universal masking, has resulted in a major public health crisis. In this study, we investigate public servants who had been vaccinated with two dose (82.7%) or three dose (14%) of either CoronaVac (CorV) or BNT162b2 (BNT). During the BA.2 outbreak, 29.3% vaccinees were infected. Three-dose vaccination provided protection with lower incidence rates of breakthrough infections (2xBNT 49.2% vs 3xBNT 16.6%, p<0.0001; 2xCorV 48.6% vs 3xCoV 20.6%, p=0.003). The third heterologous vaccination showed the lowest incidence (2xCorV+1xBNT 6.3%). Although BA.2 conferred the highest neutralization resistance compared with variants of concern tested, the third dose vaccination-activated spike-specific memory B and Omicron cross-reactive T cell responses contributed to reduced frequencies of breakthrough infection and disease severity. Our results have implications to timely boost vaccination and immune responses likely required for vaccine-mediated protection against Omicron BA.2 pandemic.

High but Short-lived anti-SARS-CoV2 neutralizing, IgM, IgA, and IgG levels among mRNA-vaccinees compared to naturally-infected participants (preprint)

1. Background Waning of protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited due to current vaccination or natural infection is a global concern. Whether this is due to waning of immunity to SARS-COV-2 remains unclear. Aim We aimed to investigate dynamics of antibody isotype responses among vaccinated naïve (VN) and naturally infected (NI) individuals. Methods We followed up antibody levels in COVID-19 mRNA-vaccinated subjects without prior infection (VN, n=100) at two phases: phase-I (P-I) at ∼1.4 and phase-II (P-II) at ∼5.3 months. Antibody levels were compared to those of unvaccinated and naturally infected subjects (NI, n=40) at ∼1.7 (P-1) and 5.2 (P-II) months post-infection. Neutralizing antibodies (NTAb), anti-S-RBD-IgG, -IgM, and anti-S-IgA isotypes were measured. Results VN group produced significantly greater antibody responses ( p <0.001) than NI group at P-I except for IgM. In VN group, a significant waning in antibody response was observed in all isotypes. There was about ∼ a 4-fold decline in NTAb levels ( p <0.001), anti-S-RBD-IgG (∼5-folds, p <0.001), anti-S-RBD-IgM (∼6-folds, p <0.001), and anti-S1-IgA (2-folds, p <0.001). In NI group, a significant but less steady decline was notable in NTAb (∼1-folds, p <0.001), anti-S-RBD IgG (∼1-fold, p =0.005), and S-RBD-IgM (∼2-folds, p <0.001). Unlike VN group, NI group mounted a lasting anti-S1-IgA response with no significant decline. Anti-S1-IgA levels which were ∼3 folds higher in VN subjects compared to NI in P-1 ( p <0.001), dropped to almost same levels, with no significant difference observed between the two groups in P-II. Conclusion While double dose mRNA vaccination boosted antibody levels, this “boost” was relatively short-lived in vaccinated individuals.

Vaccine-breakthrough infection by the SARS-CoV-2 Omicron variant elicits broadly cross-reactive immune responses (preprint)

Highly transmissible SARS-CoV-2 Omicron variant has posted a new crisis for COVID-19 pandemic control. Within a month, Omicron is dominating over Delta variant in several countries probably due to immune evasion. It remains unclear whether vaccine-induced memory responses can be recalled by Omicron infection. Here, we investigated host immune responses in the first vaccine-breakthrough case of Omicron infection in Hong Kong. We found that the breakthrough infection rapidly recruited potent cross-reactive broad neutralizing antibodies (bNAbs) against current VOCs, including Alpha, Beta, Gamma, Delta and Omicron, from unmeasurable IC50 values to mean 1:2929 at around 9-12 days, which were higher than the mean peak IC50 values of BioNTech-vaccinees. Cross-reactive spike- and nucleocapsid-specific CD4 and CD8 T cell responses were detected. Similar results were also obtained in the second vaccine-breakthrough case of Omicron infection. Our preliminary findings may have timely implications to booster vaccine optimization and preventive strategies of pandemic control.

Waning immune responses against SARS-CoV-2 among vaccinees in Hong Kong (preprint)

Background: Nearly 4 billion doses of the BioNTech-mRNA and Sinovac-inactivated vaccines have been administrated globally, yet different vaccine-induced immunity against SARS-CoV-2 variants of concern (VOCs) remain incompletely investigated. Methods: We compare the immunogenicity and durability of these two vaccines among fully vaccinated Hong Kong people. Findings: Standard BioNTech and Sinovac vaccinations were tolerated and induced neutralizing antibody (NAb) (100% and 85.7%) and spike-specific CD4 T cell responses (96.7% and 82.1%), respectively. The geometric mean NAb IC 50 and median frequencies of reactive CD4 subsets were consistently lower among Sinovacvaccinees than BioNTech-vaccinees. Against VOCs, NAb response rate and geometric mean IC 50 against B1.351 and B.1.617.2 were significantly lower for Sinovac (14.3%, 15 and 50%, 23.2) than BioNTech (79.4%, 107 and 94.1%, 131). Three months after vaccinations, NAbs to VOCs dropped near to detection limit, along with waning memory T cell responses, mainly among Sinovac-vaccinees. Interpretation: Our results indicate that Sinovac-vaccinees may face higher risk to pandemic VOCs breakthrough infection.

Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination (preprint)

Background Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. Methods Since mucosal immunity is critical for nasal prevention, we investigated an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. Findings Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. Interpretation Our results demonstrated that intranasal influenza-based boost vaccination is required for inducing mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. Funding This study was supported by the Research Grants Council Collaborative Research Fund (C7156-20G, C1134-20G and C5110-20G), General Research Fund (17107019) and Health and Medical Research Fund (19181052 and 19181012) in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program (JSGG20200225151410198); the Health@InnoHK, Innovation and Technology Commission of Hong Kong; and National Program on Key Research Project of China (2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); and donations from the Friends of Hope Education Fund. Z.C.’s team was also partly supported by the Theme-Based Research Scheme (T11-706/18-N).

SARS-CoV-2 hijacks neutralizing dimeric IgA for enhanced nasal infection and injury (preprint)

Robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) accounts for high viral transmissibility, yet whether neutralizing IgA antibodies can control it remains unknown. Here, we evaluated receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1 and B8-dIgA2 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparably potent neutralization against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viruses in lungs, pre-exposure intranasal B8-dIgA1 or B8-dIgA2 led to 81-fold more infectious viruses and severer damage in NT than placebo. Virus-bound B8-dIgA1 and B8-dIgA2 could engage CD209 as an alternative receptor for entry into ACE2-negative cells and allowed viral cell-to-cell transmission. Cryo-EM revealed B8 as a class II neutralizing antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Therefore, RBD-specific neutralizing dIgA engages an unexpected action for enhanced SARS-CoV-2 nasal infection and injury in Syrian hamsters.

SARS-CoV-2 hijacks neutralizing dimeric IgA for enhanced nasal infection and injury (preprint)

Robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) accounts for high viral transmissibility, yet whether neutralizing IgA antibodies can control it remains unknown. Here, we evaluated receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1 and B8-dIgA2 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparably potent neutralization against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viruses in lungs, pre-exposure intranasal B8-dIgA1 or B8-dIgA2 led to 81-fold more infectious viruses and severer damage in NT than placebo. Virus-bound B8-dIgA1 and B8-dIgA2 could engage CD209 as an alternative receptor for entry into ACE2-negative cells and allowed viral cell-to-cell transmission. Cryo-EM revealed B8 as a class II neutralizing antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Therefore, RBD-specific neutralizing dIgA engages an unexpected action for enhanced SARS-CoV-2 nasal infection and injury in Syrian hamsters.

BRD2 inhibition blocks SARS-CoV-2 infection in vitro by reducing transcription of the host cell receptor ACE2 (preprint)

SARS-CoV-2 infection of human cells is initiated by the binding of the viral Spike protein to its cell-surface receptor ACE2. We conducted an unbiased CRISPRi screen to uncover druggable pathways controlling Spike protein binding to human cells. We found that the protein BRD2 is an essential node in the cellular response to SARS-CoV-2 infection. BRD2 is required for ACE2 transcription in human lung epithelial cells and cardiomyocytes, and BRD2 inhibitors currently evaluated in clinical trials potently block endogenous ACE2 expression and SARS-CoV-2 infection of human cells. BRD2 also controls transcription of several other genes induced upon SARS-CoV-2 infection, including the interferon response, which in turn regulates ACE2 levels. It is possible that the previously reported interaction between the viral E protein and BRD2 evolved to manipulate the transcriptional host response during SARS-CoV-2 infection. Together, our results pinpoint BRD2 as a potent and essential regulator of the host response to SARS-CoV-2 infection and highlight the potential of BRD2 as a novel therapeutic target for COVID-19.

SARS-CoV-2 infection of circulating immune cells is not responsible for virus dissemination in severe COVID-19 patients (preprint)

In late 2019 a novel coronavirus (SARS-CoV-2) emerged, and has since caused a global pandemic. Understanding the pathogenesis of COVID-19 disease is necessary to inform development of therapeutics, and management of infected patients. Using scRNAseq of blood drawn from SARS-CoV-2 patients, we asked whether SARS-CoV-2 may exploit immune cells as a 'Trojan Horse' to disseminate and access multiple organ systems. Our data suggests that circulating cells are not actively infected with SARS-CoV-2, and do not appear to be a source of viral dissemination.

Sterically-Confined Rearrangements of SARS-CoV-2 Spike Protein Control Cell Invasion (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious, and transmission involves a series of processes that may be targeted by vaccines and therapeutics. During transmission, host cell invasion is controlled by a large-scale conformational change of the Spike protein. This conformational rearrangement leads to membrane fusion, which creates transmembrane pores through which the viral genome is passed to the host. During Spike-protein-mediated fusion, the fusion peptides must be released from the core of the protein and associate with the host membrane. Interestingly, the Spike protein possesses many post-translational modifications, in the form of branched glycans that flank the surface of the assembly. Despite the large number of glycosylation sites, until now, the specific role of glycans during cell invasion has been unclear. Here, we propose that glycosylation is needed to provide sufficient time for the fusion peptides to reach the host membrane, otherwise the viral particle would fail to enter the host. To understand this process, an all-atom model with simplified energetics was used to perform thousands of simulations in which the protein transitions between the prefusion and postfusion conformations. These simulations indicate that the steric composition of the glycans induces a pause during the Spike protein conformational change. We additionally show that this glycan-induced delay provides a critical opportunity for the fusion peptides to capture the host cell. This previously-unrecognized role of glycans reveals how the glycosylation state can regulate infectivity of this pervasive pathogen.

Behavioral and Emotional Disorders in Children during the COVID-19 Epidemic

This article has been published in English before [1]. Эта статья была опубликована ранее на английском языке [1].