A Novel Conserved Linear Neutralizing Epitope on the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein.

The continuous emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made it challenging to develop broad-spectrum prophylactic vaccines and therapeutic antibodies. Here, we have identified a broad-spectrum neutralizing antibody and its highly conserved epitope in the receptor-binding domain (RBD) of the spike protein (S) S1 subunit of SARS-CoV-2. First, nine monoclonal antibodies (MAbs) against the RBD or S1 were generated; of these, one RBD-specific MAb, 22.9-1, was selected for its broad RBD-binding abilities and neutralizing activities against SARS-CoV-2 variants. An epitope of 22.9-1 was fine-mapped with overlapping and truncated peptide fusion proteins. The core sequence of the epitope, 405D(N)EVR(S)QIAPGQ414, was identified on the internal surface of the up-state RBD. The epitope was conserved in nearly all variants of concern of SARS-CoV-2. MAb 22.9-1 and its novel epitope could be beneficial for research on broad-spectrum prophylactic vaccines and therapeutic antibody drugs. IMPORTANCE The continuous emergence of new variants of SARS-CoV-2 has caused great challenge in vaccine design and therapeutic antibody development. In this study, we selected a broad-spectrum neutralizing mouse monoclonal antibody which recognized a conserved linear B-cell epitope located on the internal surface of RBD. This MAb could neutralize all variants until now. The epitope was conserved in all variants. This work provides new insights in developing broad-spectrum prophylactic vaccines and therapeutic antibodies.

One Year Later: Family Members of Patients with COVID-19 Experience Persistent Symptoms of Posttraumatic Stress Disorder.

Rationale: Family members of critically ill patients with coronavirus disease (COVID-19) have described increased symptoms of posttraumatic stress disorder (PTSD). Little is known about how these symptoms may change over time. Objectives: We studied changes in PTSD symptoms in family members of critically ill patients with COVID-19 over 12 months. Methods: This prospective, multisite observational cohort study recruited participants at 12 hospitals in five states. Calls were made to participants at 3-4 months, 6 months, and 12 months after patient admission to the intensive care unit. Results: There were 955 eligible family members, of whom 330 (53.3% of those reached) consented to participate. Complete longitudinal data was acquired for 115 individuals (34.8% consented). PTSD symptoms were measured by the IES-6 (Impact of Events Scale-6), with a score of at least 10 identifying significant symptoms. At 3 months, the mean IES-6 score was 11.9 ± 6.1, with 63.6% having significant symptoms, decreasing to 32.9% at 1 year (mean IES-6 score, 7.6 ± 5.0). Three clusters of symptom evolution emerged over time: persistent symptoms (34.8%, n = 40), recovered symptoms (33.0%, n = 38), and nondevelopment of symptoms (32.2%, n = 37). Although participants identifying as Hispanic demonstrated initially higher adjusted IES-6 scores (2.57 points higher [95% confidence interval (CI), 1.1-4.1; P < 0.001]), they also demonstrated a more dramatic improvement in adjusted scores over time (4.7 greater decrease at 12 months [95% CI, 3.2-6.3; P < 0.001]). Conclusions: One year later, some family members of patients with COVID-19 continue to experience significant symptoms of PTSD. Further studies are needed to better understand how various differences contribute to increased risk for these symptoms.

Perinatal mental health and women's lived experience of the COVID-19 pandemic: A scoping review of the qualitative literature 2020-2021.

BACKGROUND: The COVID-19 pandemic resulted in global physical distancing restrictions and lockdown orders. Despite the clear documentation of increased mental distress amongst adult populations during the pandemic, there is limited evidence about the mental health challenges of people in the perinatal period (pregnancy, birth and postpartum). The aim of this review is to summarise the qualitative research about women's lived experience and emotional wellbeing during the COVID-19 pandemic. METHODS: A comprehensive search strategy was developed. Twenty peer-reviewed qualitative research articles published in English from January 1, 2020, to December 15, 2021, were included. Data synthesis outlined the evidence from common themes in a narrative format. RESULTS: Themes during pregnancy included: (1) information seeking: anxiety and fear; (2) experiencing isolation and disruptions to my social support; (3) 'Going it alone' in pregnancy care; (4) anticipatory grieving and despair; (5) finding 'silver linings' in social restrictions. One key theme during birth was "birthing in a crisis". Themes during postpartum included: (1) isolating 'Early motherhood is much like lockdown'; (2) breastfeeding: triumphs and tribulations; (3) facing disruptions during postpartum care; (4) 'Affecting us for years to come' - COVID-19 was not the only trauma; (5) 'silver linings' during postpartum care. CONCLUSIONS: This review provides important insights into how experiences of isolation, decreased social support and adaptions to maternity services affect women's mental health. Maternity services should consider how perinatal mental health support may be integrated into the care of women who may still be required to isolate or have reduced visitors during their perinatal care. STATEMENT OF SIGNIFICANCE: The restrictions and disruptions to maternity care due to the COVID-19 pandemic were likely to impact the mental health of women in the perinatal period (pregnancy, birth and postpartum). What is already known is that public health measures due to COVID-19 increased the prevalence of common perinatal mental disorders (CPMDs) and exacerbated common risk factors for CPMDs (i.e., poor social support). WHAT THIS PAPER ADDS: The qualitative research with women in the perinatal period during the pandemic provides unique insights into how these events impacted perinatal mental and emotional health. In particular, the ways that global physical distancing measures and maternity care adaptations contributed to women's feelings of distress, isolation, and depression/despair. Silver linings such as more uninterrupted time with immediate family were also identified.

Offensive, hateful comment: A networked discourse practice of blame and petition for justice during COVID-19 on Chinese Weibo

Using data from user comments to the official social networking account of the Hubei Red Cross Foundation on a participatory web platform, this study attends to the offensive and hateful comments produced by ordinary Internet users to blame the elite authorities for their malfeasance in managing the donation during the COVID-19 in China. Drawing on Discursive Psychology, we focus on the rhetorical strategies that users employ to legitimise their actions as well-founded evidential blame against a norm-breaking act rather than radical extremist speech. The associated hatred among discussants are moral, social judgements. That said, hate speech also helps construct the moral standards of a normalised society. [ FROM AUTHOR]

Predictors of adverse outcomes in aged patients critically ill with COVID-19: a retrospective study.

Older patients represent an inordinate proportion of intensive care unit (ICU) admissions and ICU mortality associated with coronavirus disease 2019 (COVID-19). In this retrospective cohort study, we examine 198 patients, aged 18 years or older, admitted to the ICU from March to June 2020. We aim to understand the relationships between age, number of comorbidities, and independent living prior to admission on outcomes of mortality, length of stay, renal failure, respiratory failure, and shock. In this cohort, we find that overall mortality was associated with respiratory failure severity (for every decrease of P:F by 50, odds ratio (OR) 2.98 (1.65-6.08)), acute renal failure (OR 4.61 (1.2-19.7)), and age 65 or greater (OR: 3.7 (1.86-7.36)). Surprisingly, increasing age was associated with less severe respiratory failure (R = 0.22, p < 0.01). When adjusting for pre-existing chronic kidney disease, age was not associated with development of acute kidney injury (OR: 1.01 (0.99-1.03)). While chronologic age is associated with mortality, it is not associated independently with severe end organ damage. This is consistent with growing evidence suggesting that a complex interplay between multimorbidity, immunosenescence, and physiologic age is primarily responsible for the vulnerability to COVID-19.

Relationship Between a State-Directed Lockdown on Non-COVID-19-related ICU Admissions and Mortality in a Multicenter Colorado Healthcare System.

Colorado issued a month long statewide lockdown on March 26, 2020, during the initial surge of the COVID-19 pandemic. The impact of this mandate on non-COVID-19 ICU admission rates and outcomes is unclear. DESIGN: We performed a retrospective analysis of all medical ICU admissions in the University of Colorado Health System in four predefined periods: 1) prepandemic (2 mo prior to lockdown period 1); 2) mandated lockdown from March 26 to April 26, 2020 (period 2); 3) between surges (period 3); and 4) nonmandated lockdown surge (between November 1, 2020, and March 31, 2021, period 4). SETTING: Nonsurgical ICU admissions at the University of Colorado Health Systems, including 10 hospitals throughout Colorado. SUBJECTS: All ICU admissions in four predefined time periods. MEASUREMENTS AND MAIN RESULTS: We included 13,787 patients who were admitted during the four study periods. The 28-day mortality rates for non-COVID-19 ICU admissions following index ICU admission were 13.6%, 18.0%, 13.5%, and 16.0% across periods 1-4, respectively. However, the increased odds in non-COVID-19 ICU mortality during the mandated lockdown period relative to prepandemic 1 (odds ratio [OR], 1.39; 95% CI, 1.11-1.72; p = 0.0.04) was attenuated and nonsignificant after adjustment for demographics, comorbidities, diagnosis flags, and severity (OR, 1.15; 95% CI, 0.89-1.48; p = 0.27). Similar results were found in time-to-event analyses. The most common diagnosis in each time period was acute respiratory failure (ARF), and we found it to have increased during lockdown (p < 0.001), whereas sepsis admissions increased during and decreased after lockdown (p = 0.004). Admissions for alcohol withdrawal syndrome (AWS) increased during lockdown and 6 months afterwards (p = 0.005). CONCLUSIONS: For non-COVID-19-related ICU admissions, mortality rate was similar before, during, and after Colorado's month long lockdown after confounder adjustment, including typical ICU admission flags. Primary admission diagnoses shifted throughout the predefined study periods with more admissions for severe critical diagnoses (i.e., ARF, sepsis, AWS) occurring during the mandated lockdown and nonmandated lockdown periods compared with the prepandemic and between surge period. This would suggest that the perceived increase in mortality during the lockdown for non-COVID-19 ICU admissions may be related to a shift inpatient demographics.

The evolution of structural resilience of global oil and gas resources trade network

This paper establishes anetwork resilience evaluation framework of the global oil and gas resourcetrade network in 2010, 2015 and 2020. The results are as follows: The links of the oil trade network present a gradually shrinking trend, and the gas tradenetwork presents a trend of close connection first and then reduced. In termsof network density, network centrality, network connectivity and network size, the structural resilience of the oil and gas resource trade network displays ashrinking trend, and the gas trade network is superior. Concerninginvulnerability and recovery, the resilience of the oil trade network issuperior to the natural gas trade network. In simulated attacks, the oil tradenetwork reveals a higher resilience towards intentional attacks, and the gastrade network shows a higher resilience towards random attacks. The Strait ofHormuz and the Strait of Malacca are critical chokepoints in the networks.

COVID-19: Presumed Infection Routes and Psychological Impact on Staff in Administrative and Logistics Departments in a Designated Hospital in Wuhan, China.

Objective: Our aim was to explore the presumed infection routes and psychological impact of COVID-19 on staff in administrative and logistics departments (ALDs). Methods: We gathered data from all 18 staff members with COVID-19 in ALDs in Zhongnan Hospital of Wuhan University, China. The baseline, job before diagnosis, presumed infection environment, use of protective equipment, and psychological status before and after diagnosis were collected and analyzed. A total of 18 uninfected staff members working alongside them in the same environment and 18 random matched infected doctors and nurses formed two control groups; the psychological impact of these three groups was then compared. Results: Of the 18 members of staff, 88.89% were infected due to the working environment (hospital), and nine had face-to-face conversations with doctors and nurses in their daily work. Many staff members did not take any protective measures in their routine work. Before they were diagnosed, 12 staff members were aware of the seriousness of the epidemic, and most of the staff maintained a neutral attitude to the COVID-19 outbreak. A total of 77.78% of the staff experienced psychological stress or emotional changes after diagnosis, which were mainly caused by family health and disease related issues. Most of them managed their emotions by self-control and video calls with their families. There was no significant difference in psychological impact among the three groups, but uninfected staff members were fully aware of the seriousness of the epidemic. Conclusions: Effective protective measures should be taken for staff members in ALDs. Psychological interventions are very important to help infected staff members in ALDs cope with psychological distress.

Stress-Related Disorders of Family Members of Patients Admitted to the Intensive Care Unit With COVID-19.

Importance: The psychological symptoms associated with having a family member admitted to the intensive care unit (ICU) during the COVID-19 pandemic are not well defined. Objective: To examine the prevalence of symptoms of stress-related disorders, primarily posttraumatic stress disorder (PTSD), in family members of patients admitted to the ICU with COVID-19 approximately 90 days after admission. Design, Setting, and Participants: This prospective, multisite, mixed-methods observational cohort study assessed 330 family members of patients admitted to the ICU (except in New York City, which had a random sample of 25% of all admitted patients per month) between February 1 and July 31, 2020, at 8 academic-affiliated and 4 community-based hospitals in 5 US states. Exposure: Having a family member in the ICU with COVID-19. Main Outcomes and Measures: Symptoms of PTSD at 3 months, as defined by a score of 10 or higher on the Impact of Events Scale 6 (IES-6). Results: A total of 330 participants (mean [SD] age, 51.2 [15.1] years; 228 [69.1%] women; 150 [52.8%] White; 92 [29.8%] Hispanic) were surveyed at the 3-month time point. Most individuals were the patients' child (129 [40.6%]) or spouse or partner (81 [25.5%]). The mean (SD) IES-6 score at 3 months was 11.9 (6.1), with 201 of 316 respondents (63.6%) having scores of 10 or higher, indicating significant symptoms of PTSD. Female participants had an adjusted mean IES-6 score of 2.6 points higher (95% CI, 1.4-3.8; P < .001) than male participants, whereas Hispanic participants scored a mean of 2.7 points higher compared with non-Hispanic participants (95% CI, 1.0-4.3; P = .002). Those with graduate school experience had an adjusted mean score of 3.3 points lower (95% CI, 1.5-5.1; P < .001) compared with those with up to a high school degree or equivalent. Qualitative analyses found no substantive differences in the emotional or communication-related experiences between those with high vs low PTSD scores, but those with higher scores exhibited more distrust of practitioners. Conclusions and Relevance: In this cohort study, symptoms of PTSD among family members of ICU patients with COVID-19 were high. Hispanic ethnicity and female gender were associated with higher symptoms. Those with higher scores reported more distrust of practitioners.

Healthcare worker stress, anxiety and burnout during the COVID-19 pandemic in Singapore: A 6-month multi-centre prospective study.

AIM: The long-term stress, anxiety and job burnout experienced by healthcare workers (HCWs) are important to consider as the novel coronavirus disease (COVID-19) pandemic stresses healthcare systems globally. The primary objective was to examine the changes in the proportion of HCWs reporting stress, anxiety, and job burnout over six months during the peak of the pandemic in Singapore. The secondary objective was to examine the extent that objective job characteristics, HCW-perceived job factors, and HCW personal resources were associated with stress, anxiety, and job burnout. METHOD: A sample of HCWs (doctors, nurses, allied health professionals, administrative and operations staff; N = 2744) was recruited via invitation to participate in an online survey from four tertiary hospitals. Data were gathered between March-August 2020, which included a 2-month lockdown period. HCWs completed monthly web-based self-reported assessments of stress (Perceived Stress Scale-4), anxiety (Generalized Anxiety Disorder-7), and job burnout (Physician Work Life Scale). RESULTS: The majority of the sample consisted of female HCWs (81%) and nurses (60%). Using random-intercept logistic regression models, elevated perceived stress, anxiety and job burnout were reported by 33%, 13%, and 24% of the overall sample at baseline respectively. The proportion of HCWs reporting stress and job burnout increased by approximately 1·0% and 1·2% respectively per month. Anxiety did not significantly increase. Working long hours was associated with higher odds, while teamwork and feeling appreciated at work were associated with lower odds, of stress, anxiety, and job burnout. CONCLUSIONS: Perceived stress and job burnout showed a mild increase over six months, even after exiting the lockdown. Teamwork and feeling appreciated at work were protective and are targets for developing organizational interventions to mitigate expected poor outcomes among frontline HCWs.

A dynamic microsimulation model for epidemics.

A large evidence base demonstrates that the outcomes of COVID-19 and national and local interventions are not distributed equally across different communities. The need to inform policies and mitigation measures aimed at reducing the spread of COVID-19 highlights the need to understand the complex links between our daily activities and COVID-19 transmission that reflect the characteristics of British society. As a result of a partnership between academic and private sector researchers, we introduce a novel data driven modelling framework together with a computationally efficient approach to running complex simulation models of this type. We demonstrate the power and spatial flexibility of the framework to assess the effects of different interventions in a case study where the effects of the first UK national lockdown are estimated for the county of Devon. Here we find that an earlier lockdown is estimated to result in a lower peak in COVID-19 cases and 47% fewer infections overall during the initial COVID-19 outbreak. The framework we outline here will be crucial in gaining a greater understanding of the effects of policy interventions in different areas and within different populations.

An integrated method for hybrid distribution with estimation of demand matching degree.

Timely and effective distribution of relief materials is one of the most important aspects when fighting with a natural or a man-made disaster. Due to the sudden and urgent nature of most disasters, it is hard to make the exact prediction on the demand information. Meanwhile, timely delivery is also a problem. In this paper, taking the COVID-19 epidemic as an example, we propose an integrated method to fulfill both the demand estimation and the relief material distribution. We assume the relief supply is directed by government, so it is possible to arrange experts to evaluate the situation from aspects and coordinate supplies of different sources. The first part of the integrated method is a fuzzy decision-making process. The demand degrees on relief materials are estimated by extending COPRAS under interval 2-tuple linguistic environment. The second part includes the demand degrees as one of the inputs, conducts a hybrid distribution model to decide the allocation and routing. The key point of hybrid distribution is that each demand point could be visited by different vehicles and each vehicle could visit different demand points. Our method can also be extended to include both relief materials and medical staffs. A real-life case study of Wuhan, China is provided to illustrate the presented method.

Optimizing the Performance of Pure ALOHA for LoRa-Based ESL.

(1) Background: The scientific development in the field of industrialization demands the automization of electronic shelf labels (ESLs). COVID-19 has limited the manpower responsible for the frequent updating of the ESL system. The current ESL uses QR (quick response) codes, NFC (near-field communication), and RFID (radio-frequency identification). These technologies have a short range or need more manpower. LoRa is one of the prominent contenders in this category as it provides long-range connectivity with less energy harvesting and location tracking. It uses many gateways (GWs) to transmit the same data packet to a node, which causes collision at the receiver side. The restriction of the duty cycle (DC) and dependency of acknowledgment makes it unsuitable for use by the common person. The maximum efficiency of pure ALOHA is 18.4%, while that of slotted ALOHA is 36.8%, which makes LoRa unsuitable for industrial use. It can be used for applications that need a low data rate, i.e., up to approximately 27 Kbps. The ALOHA mechanism can cause inefficiency by not eliminating fast saturation even with the increasing number of gateways. The increasing number of gateways can only improve the global performance for generating packets with Poisson law having a uniform distribution of payload of 1~51 bytes. The maximum expected channel capacity usage is similar to the pure ALOHA throughput. (2) Methods: In this paper, the improved ALOHA mechanism is used, which is based on the orthogonal combination of spreading factor (SF) and bandwidth (BW), to maximize the throughput of LoRa for ESL. The varying distances (D) of the end nodes (ENs) are arranged based on the K-means machine learning algorithm (MLA) using the parameter selection principle of ISM (industrial, scientific and medical) regulation with a 1% DC for transmission to minimize the saturation. (3) Results: The performance of the improved ALOHA degraded with the increasing number of SFs and as well ENs. However, after using K-mapping, the network changes and the different number of gateways had a greater impact on the probability of successful transmission. The saturation decreased from 57% to 1~2% by using MLA. The RSSI (Received Signal Strength Indicator) plays a key role in determining the exact position of the ENs, which helps to improve the possibility of successful transmission and synchronization at higher BW (250 kHz). In addition, a high BW has lower energy consumption than a low BW at the same DC with a double-bit rate and almost half the ToA (time on-air).

Review of oral ulcerative lesions in COVID-19 patients: A comprehensive study of 51 cases.

Numerous oral manifestations of COVID-19 have been reported in the literatures. Common oral lesions in COVID-19 patients included ulcerations, xerostomia, dysgeusia, gingival inflammation, and erythema. Among them, oral ulceration is the most frequent finding and is present as various but distinct patterns. Thus, we conducted a comprehensive review of 51 COVID-19 patients with oral ulcerative lesions to further analyze the various oral ulcerative lesions in COVID-19 patients. There were a median age of 41.4 years and a slight female predilection in these patients. Most oral lesions manifested as an aphtha-like ulceration but lack of an evidence of recurrent aphthous stomatitis. Some of them were present as herpetiform ulcerations without HSV infection. Widespread ulcerations accompanied with necrosis were observed in the more severe and immunosuppressed older patients. Although some reported patients were asymptomatic, most of them had systemic symptoms concurring or slightly preceding the oral ulcerative lesions and the latency from the onset of systemic symptoms to oral ulcerative lesions were under 10 days, suggesting that oral ulceration was one of the early symptoms of COVID-19. Therefore, the oral ulcerative lesions may be considered as oral markers for early diagnosis of the underlying COVID-19 infection in the asymptomatic patients.

Quality of and Recommendations for Relevant Clinical Practice Guidelines for COVID-19 Management: A Systematic Review and Critical Appraisal.

Background: The morbidity and mortality of coronavirus disease 2019 (COVID-19) are still increasing. This study aimed to assess the quality of relevant COVID-19 clinical practice guidelines (CPGs) and to compare the similarities and differences between recommendations. Methods: A comprehensive search was conducted using electronic databases (PubMed, Embase, and Web of Science) and representative guidelines repositories from December 1, 2019, to August 11, 2020 (updated to April 5, 2021), to obtain eligible CPGs. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to evaluate the quality of CPGs. Four authors extracted relevant information and completed data extraction forms. All data were analyzed using R version 3.6.0 software. Results: In total, 39 CPGs were identified and the quality was not encouragingly high. The median score (interquartile range, IQR) of every domain from AGREE II for evidence-based CPGs (EB-CPGs) versus (vs.) consensus-based CPG (CB-CPGs) was 81.94% (75.00-84.72) vs. 58.33% (52.78-68.06) in scope and purpose, 59.72% (38.89-75.00) vs. 36.11% (33.33-36.11) in stakeholder involvement, 64.58% (32.29-71.88) vs. 22.92% (16.67-26.56) in rigor of development, 75.00% (52.78-86.81) vs. 52.78% (50.00-63.89) in clarity of presentation, 40.63% (22.40-62.50) vs. 20.83% (13.54-25.00) in applicability, and 58.33% (50.00-100.00) vs. 50.00% (50.00-77.08) in editorial independence, respectively. The methodological quality of EB-CPGs were significantly superior to the CB-CPGs in the majority of domains (P < 0.05). There was no agreement on diagnosis criteria of COVID-19. But a few guidelines show Remdesivir may be beneficial for the patients, hydroxychloroquine +/- azithromycin may not, and there were more consistent suggestions regarding discharge management. For instance, after discharge, isolation management and health status monitoring may be continued. Conclusions: In general, the methodological quality of EB-CPGs is greater than CB-CPGs. However, it is still required to be further improved. Besides, the consistency of COVID-19 recommendations on topics such as diagnosis criteria is different. Of them, hydroxychloroquine +/- azithromycin may be not beneficial to treat patients with COVID-19, but remdesivir may be a favorable risk-benefit in severe COVID-19 infection; isolation management and health status monitoring after discharge may be still necessary. Chemoprophylaxis, including SARS-CoV 2 vaccines and antiviral drugs of COVID-19, still require more trials to confirm this.

Spatial distributive effects of public green space and COVID-19 infection in London.

While public green spaces (PGS) are opined to be central in the pandemic recovery, higher accessibility to PGS also mean a higher risk of infection spread from the raised possibility of people encountering each other. This study explores the distributive effects of accessibility of PGS on the COVID-19 cases distribution using a geo-spatially varying network-based risk model at the borough level in London. The coupled effect of social deprivation with accessibility of the PGS was used as an adjustment factor to identify vulnerability. Results indicate that highly connected green spaces with high choice measure were associated with high risk of infection transmission. Socially deprived areas demonstrated higher possibility of infection spread even with moderate connectivity of the PGS. The study demonstrated that only applying a uniform social distancing measure without characterising the infrastructure and social conditions may lead to higher infection transmission.