Cryo-EM structure of SARS-CoV-2 postfusion spike in membrane.

The entry of SARS-CoV-2 into host cells depends on the refolding of the virus-encoded spike protein from a prefusion conformation, which is metastable after cleavage, to a lower-energy stable postfusion conformation1,2. This transition overcomes kinetic barriers for fusion of viral and target cell membranes3,4. Here we report a cryogenic electron microscopy (cryo-EM) structure of the intact postfusion spike in a lipid bilayer that represents the single-membrane product of the fusion reaction. The structure provides structural definition of the functionally critical membrane-interacting segments, including the fusion peptide and transmembrane anchor. The internal fusion peptide forms a hairpin-like wedge that spans almost the entire lipid bilayer and the transmembrane segment wraps around the fusion peptide at the last stage of membrane fusion. These results advance our understanding of the spike protein in a membrane environment and may guide development of intervention strategies.

Multi-omic and comparative analyses revealed monocyte-derived alpha-defensin-1 correlated with COVID-19 severity and inhibited SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological pathogen of coronavirus disease 2019 (COVID-19), a highly contagious disease, spreading quickly and threatening global public health. The symptoms of COVID-19 vary from mild reactions to severe respiratory distress or even fatal outcomes probably due to the different status of host immunity against the virus. Here in the study, we unveiled plasma proteomic signatures and transcriptional patterns of peripheral blood mononuclear cells (PBMCs) using blood samples of 10 COVID-19 patients with different severity. Through systemic analysis, α-defensin-1 (DEFA1) was identified to be elevated in both plasma and PBMCs, and correlated with disease severity and stages. In vitro study demonstrated that DEFA1 was secreted from immunocytes and suppressed SARS-CoV-2 infection of both original and mutated strains with dose dependency. By using sequencing data, we discovered that DEFA1 was activated in monocytes through NF-κB signaling pathway after infection, and secreted into circulation to perturb SARS-CoV-2 infection by interfering protein kinase C expression. It worked mainly during virus replication instead of entry in host cells. Together, the anti-SARS-CoV-2 mechanism of DEFA1 has unveiled a corner of how innate immunity is against SARS-CoV-2 and explored its clinical potential in disease prognosis and therapeutic intervention.

ACE2 in male genitourinary and endocrine systems: Does COVID-19 really affect these systems?

The virus that causes COVID-19(Corona Virus Disease 2019), SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2), is causing a worldwide pandemic, posing a substantial threat to human health. Patients show signs of pneumonia, ARDS, shock, acute cardiac injury, acute kidney injury and other complications. The SARS-CoV-2 receptor is angiotensin converting enzyme 2 (ACE2), which is an important component of the renin-angiotensin system (RAS). In addition, TMPRSS2 or other cofactors are needed to allow the virus to enter the host. Clinical patients have exhibited varying degrees of genitourinary and endocrine system damage, and some studies have also reported potential risks to the genitourinary and endocrine systems. This article reviews the mechanism underlying SARS-CoV-2 infection and the current studies on the male genitourinary and endocrine systems and proposes that more attention should be directed towards human reproductive and endocrine health during the SARS-CoV-2 epidemic.

More susceptible psychological status of front-line medical staff than temporary workers in China during a public health emergency: a cross-sectional study (preprint)

Background Our study aimed to investigate the psychological status of medical staff and temporary workers during a public health emergency in China and analyze the relevant factors affecting the psychological symptoms.Methods A total of 380 participants were included in a cross-sectional online survey in a fangcang shelter hospital in Hangzhou, China, during a wave of the COVID-19 pandemic.The Psychological Questionnaires for Emergent Events of Public Health (PQEEPH) was applied to investigate psychological status of medical staff and temporary workers. Multiple linear regression models were built to analyze the relevant factors affecting the psychological symptoms.Results Of 380 participants, women accounted for a high proportion of medical staff, and the majority of temporary workers were men. Medical staff had higher psychological symptom scores in depression, fear, neurasthenia and hypochondria than temporary workers. Multiple linear regression analysis indicated that higher risk perception and occupational exposure of medical staff were significantly related to worse psychological symptoms, and emergency management capacity was negatively correlated with psychological symptoms of medical staff.Conclusion Our findings indicated that medical staff experienced more serious psychological symptoms than temporary workers during public health emergency, and protecting medical staff from psychological disturbance would be of great importance to the development of medical system. Our study suggest that risk perception and protective actions should be actively improved to reduce information avoidance and develop positive psychological status, which provide scientific basis for developing psychological intervention measures when there is emergent event of public health in the future.

Label-free integrated microfluidic plasmonic biosensor from vertical-cavity surface-emitting lasers for SARS-CoV-2 receptor binding domain protein detection.

The nanoplasmonic sensor of the nanograting array has a remarkable ability in label-free and rapid biological detection. The integration of the nanograting array with the standard vertical-cavity surface-emitting lasers (VCSEL) platform can achieve a compact and powerful solution to provide on-chip light sources for biosensing applications. Here, a high sensitivity and label-free integrated VCSELs sensor was developed as a suitable analysis technique for COVID-19 specific receptor binding domain (RBD) protein. The gold nanograting array is integrated on VCSELs to realize the integrated microfluidic plasmonic biosensor of on-chip biosensing. The 850 nm VCSELs are used as a light source to excite the localized surface plasmon resonance (LSPR) effect of the gold nanograting array to detect the concentration of attachments. The refractive index sensitivity of the sensor is 2.99 × 106 nW/RIU. The aptamer of RBD was modified on the surface of the gold nanograting to detect the RBD protein successfully. The biosensor has high sensitivity and a wide detection range of 0.50 ng/mL - 50 µg/mL. This VCSELs biosensor provides an integrated, portable, and miniaturized idea for biomarker detection.

Analysing transcriptomic signatures and identifying potential genes for the protective effect of inactivated COVID-19 vaccines.

Inactivated vaccines are one of the most effective strategies for controlling the coronavirus disease 2019 (COVID-19) pandemic. However, the response genes for the protective effect of inactivated vaccines are still unclear. Herein, we analysed the neutralization antibody responses elicited by vaccine serum and carried out transcriptome sequencing of RNAs isolated from the PBMCs of 29 medical staff receiving two doses of the CoronaVac vaccine. The results showed that SARS-CoV-2 neutralization antibody titers varied considerably among individuals, and revealed that many innate immune pathways were activated after vaccination. Furthermore, the blue module revealed that NRAS, YWHAB, SMARCA5, PPP1CC and CDC5L may be correlated with the protective effect of the inactivated vaccine. Additionally, MAPK1, CDC42, PPP2CA, EP300, YWHAZ and NRAS were demonstrated as the hub genes having a significant association with vaccines. These findings provide a basis for understanding the molecular mechanism of the host immune response induced by inactivated vaccines.

More susceptible psychological status of front-line medical staff than temporary workers in China during public health emergency related to COVID-19: a cross-sectional study (preprint)

Our study aimed to investigate the psychological status of medical staff and temporary workers in a fangcang shelter hospital in China and analyze the relevant factors affecting the psychological symptoms. A total of 380 participants were included in a cross-sectional online survey in a fangcang shelter hospital in Hangzhou, China, during a wave of the COVID-19 pandemic.The Psychological Questionnaires for Emergent Events of Public Health (PQEEPH) was applied to investigate psychological status of medical staff and temporary workers. Multiple linear regression models were built to analyze the relevant factors affecting the psychological symptoms. Of 380 participants, women accounted for a high proportion of medical staff, and the majority of temporary workers were men. Medical staff had higher psychological symptom scores in depression, fear, neurasthenia and hypochondria than temporary workers. Multiple linear regression analysis indicated that higher risk perception and occupational exposure of medical staff were significantly related to worse psychological symptoms, and emergency management capacity was negatively correlated with psychological symptoms of medical staff. Our findings indicated that medical staff experienced more serious psychological symptoms than temporary workers during public health emergency, and protecting medical staff from psychological disturbance is of great importance to the development of medical system. Our study suggested that risk perception and protective actions should be actively improved to reduce information avoidance and develop positive psychological status, which provided scientific basis for developing psychological intervention measures when there is emergent event of public health in the future.

A Vaccine with Multiple Receptor-Binding Domain Subunit Mutations Induces Broad-Spectrum Immune Response against SARS-CoV-2 Variants of Concern.

With the emergence of more variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune evasion of these variants from existing vaccines, the development of broad-spectrum vaccines is urgently needed. In this study, we designed a novel SARS-CoV-2 receptor-binding domain (RBD) subunit (RBD5m) by integrating five important mutations from SARS-CoV-2 variants of concern (VOCs). The neutralization activities of antibodies induced by the RBD5m candidate vaccine are more balanced and effective for neutralizing different SARS-CoV-2 VOCs in comparison with those induced by the SARS-CoV-2 prototype strain RBD. Our results suggest that the RBD5m vaccine is a good broad-spectrum vaccine candidate able to prevent disease from several different SARS-CoV-2 VOCs.

Perceived Stigma among Discharged Patients of COVID-19 in Wuhan, China: a Latent Profile Analysis (preprint)

Background Perceived stigma has greatly influenced the life quality of the COVID-19 patients who recovered and were discharged (RD hereafter). It is essential to understand COVID-19 stigma of RD and its related risk factors. The current study aims to identify the characteristics of perceived COVID-19 stigma in RD using latent profile analysis (LPA), to explore its psycho-social influencing factors, and to determine the cut-off point of the stigma scale using receiver operating characteristic (ROC) analysis. Methods A cross-sectional study was conducted among COVID-19 RD in 13 communities in Jianghan District, Wuhan City, Hubei Province, China from June 10 to July 25, 2021, enrolling total 1297 participants. Data were collected on demographic characteristics, COVID-19 perceived stigma, post-traumatic stress disorder (PTSD), anxiety, depression, sleep disorder, fatigue, resilience, social support, and peace of mind. LPA was performed to identify different profiles of perceived COVID-19 stigma level. Univariate analysis and multinominal logistic regression analysis were conducted to explore the influencing factors in different profiles. ROC analyses was carried out to identify the cut-off value of perceived stigma. Results Among the participants, three profiles of perceived stigma were identified: “low perceived COVID-19 stigma” (12.8%), “moderate perceived COVID-19 stigma” (51.1%), and “severe perceived COVID-19 stigma” (36.1%). Multinominal logistic regression analysis revealed that older age, living with other people, anxiety, and sleep disorder were positively associated with moderate perceived COVID-19 stigma, while higher educational level was negatively associated with moderate perceived COVID-19 stigma. Female, older age, living with other people, anxiety, and sleep disorder were positively associated with severe perceived COVID-19 stigma, while higher educational level, social support, and peace of mind were negatively associated with severe perceived COVID-19 stigma. ROC curve of the Short Version of COVID-19 Stigma Scale(CSS-S) for screening perceived COVID-19 stigma showed that the optimal cut-off value was ≥20. Conclusion The study focuses on the issue of perceived COVID-19 stigma and its psycho-socio influencing factors. It provides evidence for implementing relevant psychological interventions to COVID-19 RD.

Implementation and evaluation of the school's COVID-19 prevention website

Purpose The purpose of this study is to investigate the effects of the Perceptions of coronavirus 2019 (COVID-19) questionnaire and the Information System Success Questionnaire on students when using the school's COVID-19 epidemic prevention website. The study is aimed toward analyzing both questionnaires as well as evaluating an epidemic prevention website. Design/methodology/approach The school's COVID-19 prevention website and two questionnaires (Perceptions of COVID-19 and the Information System Success Questionnaire) are examined in order to investigate 73 students' COVID-19 perceptions. An open-ended question was used as the qualitative data to support quantitative data and evaluate a university's COVID-19 epidemic prevention website from a southern university in Taiwan. Findings The findings indicated that most students evaluated the school's COVID-19 website positively and were satisfied. In the open-ended questions, the majority of students rated the quality of the system positively and the need to fix some defects. Students have different COVID-19 perceptions and social distance compliance based on their current situations. Practical implications This study provides researchers and website developers a broader understanding of the construction of the school's COVID-19 prevention website and a better understanding of student's COVID-19 perceptions. Originality/value To the best of the authors' knowledge, this is the first study examining a school's epidemic prevention website, which is measured by the Information Success Questionnaire and the Perceptions of COVID-19 Questionnaire for college students.

An LSPR Sensor Integrated with VCSEL and Microfluidic Chip.

The work introduces a localized surface plasmon resonance (LSPR) sensor chip integrated with vertical-cavity surface-emitting lasers (VCSELs). Using VCSEL as the light source, the hexagonal gold nanoparticle array was integrated with anodic aluminum oxide (AAO) as the mask on the light-emitting end face. The sensitivity sensing test of the refractive index solution was realized, combined with microfluidic technology. At the same time, the finite-difference time- domain (FDTD) algorithm was applied to model and simulate the gold nanostructures. The experimental results showed that the output power of the sensor was related to the refractive index of the sucrose solution. The maximum sensitivity of the sensor was 1.65 × 106 nW/RIU, which gives it great application potential in the field of biomolecular detection.

Research trends and hotspots of breast cancer management during the COVID-19 pandemic: A bibliometric analysis

Background The coronavirus disease 2019 (COVID-19) pandemic is disrupting routine medical care of cancer patients, including those who have cancer or are undergoing cancer screening. In this study, breast cancer management during the COVID-19 pandemic (BCMP) is reviewed, and the research trends of BCMP are evaluated by quantitative and qualitative evaluation. Methods In this study, published studies relating to BCMP from 1 January 2020 to 1 April 2022 were searched from the Web of Science database (WoS). Bibliometric indicators consisted of publications, research hotspots, keywords, authors, journals, institutions, nations, and h-index. Results A total of 182 articles investigating BCMP were searched. The United States of America and the University of Rome Tor Vergata were the nation and the institution with the most publications on BCMP. The first three periodicals with leading published BCMP studies were Breast Cancer Research and Treatment, Breast, and In Vivo. Buonomo OC was the most prolific author in this field, publishing nine articles (9/182, 4.94%). The co-keywords analysis of BCMP suggests that the top hotspots and trends in research are screening, surgery, rehabilitation, emotion, diagnosis, treatment, and vaccine management of breast cancer during the pandemic. The hotspot words were divided into six clusters, namely, screening for breast cancer patients in the pandemic, breast cancer surgery in the pandemic, recovery of breast cancer patients in the pandemic, motion effect of the outbreak on breast cancer patients, diagnosis and treatment of breast cancer patients in the pandemic, and vaccination management for breast cancer patients during a pandemic. Conclusion BCMP has received attention from scholars in many nations over the last 3 years. This study revealed significant contributions to BCMP research by nations, institutions, scholars, and journals. The stratified clustering study provided the current status and future trends of BCMP to help physicians with the diagnosis and treatment of breast cancer through the pandemic, and provide a reference for in-depth clinical studies on BCMP.

Epidemic characteristics and spatial analysis of COVID-19 in Zhejiang Province. (Special Issue: Spatio-temporal dynamics analysis, risk assessment and emergency management for COVID-19 epidemic.) [Chinese]

Objective: To explore the temporal and spatial distribution characteristics of confirmed cases of coronavirus disease(COVID-19)in Zhejiang Province and to determine the correlation between number of confirmed cases and geographical demographic factors, so as to provide theoretical basis for the prevention and control of COVID-19.

Birds carry a diversity of significant viruses in their virome (preprint)

Birds can carry and transmit viruses to humans and other animals. Thus, understanding the viral community hosted by birds could help us predict future outbreaks of human disease. A recent metagenomics study took a broad look at the viruses found in the gut of wild and captive birds. The dataset included samples from over 3,000 birds that represented over 87 species and 10 different phylogenetic orders and the researchers characterized genomes from numerous viral families including astroviruses, coronaviruses, parvoviruses, and adenoviruses. Examining trends, they found that wild birds had higher viral diversity than captive birds. There was also evidence of potential cross-species transmission between wild birds and domestic poultry. Further analysis of the viral genomic sequences revealed differences in virus distribution patterns between wild and captive birds. Different phylogenetic orders of birds and geographic sites also had distinct distribution patterns. Interestingly, there were no significant differences in virus distribution patterns between migratory and resident birds. While further studies are needed to explore the diversity and potential pathogenicity of these viruses in more detail, this study expanded our understanding of viral diversity in birds.

How Risky if China Moves Away from Its Zero-COVID Policy? (preprint)

There are two contrary opinions regarding the risk if mainland China (MC) moves away from its zero-COVID policy. Some experts think the risk shall be much lower than influenza as per MC’s own COVID-19 case fatality rate (CFR), while some other experts think the risk shall be much higher than influenza as per the COVID-19 CFRs of other regions. We elucidate here that this and multiple other striking differences in the CFR between various scenarios all support and substantially resulted from the view that good IDM is highly powerful to mitigate COVID-19, where IDM (isolation-disinfection-maintenance) means isolation of COVID-19 cases from other people, disinfection of their living environments, and health maintenance (e.g., rest, nutrition, breathing). The high effect of good IDM is also supported by the theoretic functions of IDM in minimizing co-infections and maintaining body functions, and the fact that all the 505 COVID-19 deaths reported in MC in 2022 before May 5 died directly of severe underlying diseases with COVID-19. Although it is tough for people in poverty to obtain good IDM, good IDM can be feasible at home for the most mild cases and in hospitals for the most severe cases. Therefore, good IDM can be crucial to mitigating COVID-19 worldwide. It also suggests that the risk for China to end its zero-COVID policy depends on China’s control policies or measures. Based on the effect of IDM, the cautious co-existence policy was proposed for COVID-19 control. This policy could reduce the whole death toll in MC because good IDM is non-specific and can reduce deaths of various other diseases. The cautious co-existence policy (non-specific) and the vaccination policy (specific) aid each other to mitigate COVID-19, and they cannot replace each other. Those who are qualified in health for vaccination should be vaccinated against COVID-19 timely.

The Role of Mitophagy in Viral Infection.

Mitophagy, which is able to selectively clear excess or damaged mitochondria, plays a vital role in the quality control of mitochondria and the maintenance of normal mitochondrial functions in eukaryotic cells. Mitophagy is involved in many physiological and pathological processes, including apoptosis, innate immunity, inflammation, cell differentiation, signal transduction, and metabolism. Viral infections cause physical dysfunction and thus pose a significant threat to public health. An accumulating body of evidence reveals that some viruses hijack mitophagy to enable immune escape and self-replication. In this review, we systematically summarize the pathway of mitophagy initiation and discuss the functions and mechanisms of mitophagy in infection with classical swine fever virus and other specific viruses, with the aim of providing a theoretical basis for the prevention and control of related diseases.

Monetary incentives and peer referral in promoting secondary distribution of HIV self-testing among men who have sex with men in China: A randomized controlled trial.

BACKGROUND: Digital network-based methods may enhance peer distribution of HIV self-testing (HIVST) kits, but interventions that can optimize this approach are needed. We aimed to assess whether monetary incentives and peer referral could improve a secondary distribution program for HIVST among men who have sex with men (MSM) in China. METHODS AND FINDINGS: Between October 21, 2019 and September 14, 2020, a 3-arm randomized controlled, single-blinded trial was conducted online among 309 individuals (defined as index participants) who were assigned male at birth, aged 18 years or older, ever had male-to-male sex, willing to order HIVST kits online, and consented to take surveys online. We randomly assigned index participants into one of the 3 arms: (1) standard secondary distribution (control) group (n = 102); (2) secondary distribution with monetary incentives (SD-M) group (n = 103); and (3) secondary distribution with monetary incentives plus peer referral (SD-M-PR) group (n = 104). Index participants in 3 groups were encouraged to order HIVST kits online and distribute to members within their social networks. Members who received kits directly from index participants or through peer referral links from index MSM were defined as alters. Index participants in the 2 intervention groups could receive a fixed incentive ($3 USD) online for the verified test result uploaded to the digital platform by each unique alter. Index participants in the SD-M-PR group could additionally have a personalized peer referral link for alters to order kits online. Both index participants and alters needed to pay a refundable deposit ($15 USD) for ordering a kit. All index participants were assigned an online 3-month follow-up survey after ordering kits. The primary outcomes were the mean number of alters motivated by index participants in each arm and the mean number of newly tested alters motivated by index participants in each arm. These were assessed using zero-inflated negative binomial regression to determine the group differences in the mean number of alters and the mean number of newly tested alters motivated by index participants. Analyses were performed on an intention-to-treat basis. We also conducted an economic evaluation using microcosting from a health provider perspective with a 3-month time horizon. The mean number of unique tested alters motivated by index participants was 0.57 ± 0.96 (mean ± standard deviation [SD]) in the control group, compared with 0.98 ± 1.38 in the SD-M group (mean difference [MD] = 0.41),and 1.78 ± 2.05 in the SD-M-PR group (MD = 1.21). The mean number of newly tested alters motivated by index participants was 0.16 ± 0.39 (mean ± SD) in the control group, compared with 0.41 ± 0.73 in the SD-M group (MD = 0.25) and 0.57 ± 0.91 in the SD-M-PR group (MD = 0.41), respectively. Results indicated that index participants in intervention arms were more likely to motivate unique tested alters (control versus SD-M: incidence rate ratio [IRR = 2.98, 95% CI = 1.82 to 4.89, p-value < 0.001; control versus SD-M-PR: IRR = 3.26, 95% CI = 2.29 to 4.63, p-value < 0.001) and newly tested alters (control versus SD-M: IRR = 4.22, 95% CI = 1.93 to 9.23, p-value < 0.001; control versus SD-M-PR: IRR = 3.49, 95% CI = 1.92 to 6.37, p-value < 0.001) to conduct HIVST. The proportion of newly tested testers among alters was 28% in the control group, 42% in the SD-M group, and 32% in the SD-M-PR group. A total of 18 testers (3 index participants and 15 alters) tested as HIV positive, and the HIV reactive rates for alters were similar between the 3 groups. The total costs were $19,485.97 for 794 testers, including 450 index participants and 344 alter testers. Overall, the average cost per tester was $24.54, and the average cost per alter tester was $56.65. Monetary incentives alone (SD-M group) were more cost-effective than monetary incentives with peer referral (SD-M-PR group) on average in terms of alters tested and newly tested alters, despite SD-M-PR having larger effects. Compared to the control group, the cost for one more alter tester in the SD-M group was $14.90 and $16.61 in the SD-M-PR group. For newly tested alters, the cost of one more alter in the SD-M group was $24.65 and $49.07 in the SD-M-PR group. No study-related adverse events were reported during the study. Limitations include the digital network approach might neglect individuals who lack internet access. CONCLUSIONS: Monetary incentives alone and the combined intervention of monetary incentives and peer referral can promote the secondary distribution of HIVST among MSM. Monetary incentives can also expand HIV testing by encouraging first-time testing through secondary distribution by MSM. This social network-based digital approach can be expanded to other public health research, especially in the era of the Coronavirus Disease 2019 (COVID-19). TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR1900025433.

The incidence of influenza in children was decreased in the first flu season after COVID-19 pandemic in Wuhan.

Wuhan, China was the first city to discover COVID-19. With the government's macro-control and the active cooperation of the public, the spread of COVID-19 has been effectively controlled. In order to understand the additional impact of these measures on the prevalence of common influenza, we have collected flu test data from the Pediatric Clinic of Zhongnan Hospital of Wuhan University from September to December 2020, and compared them with the same period in 2018 and 2019. It is found that compared with the same period in 2018 and 2019, the rate of children's influenza activity in 2020 has significantly decreased, which indicates that the protective measures against COVID-19 have effectively reduced the level of influenza activity.