\ BIP! Finder for COVID-19 - Impact-based ranking

BIP! Finder for COVID-19

This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.

Last Update: 18 - 01 - 2023 (628506 entries)

Provided impact measures:
Popularity: Citation-based measure reflecting the current impact.
Influence: Citation-based measure reflecting the total impact.
Reader Attention: The current number of Mendeley readers.
Social Media Attention: The number of recent tweets related to this article.
*More details on these impact measures can be found here.
Score interpretations:
Exceptional score (in top 0.01%).
Substantial score (in top 1%).
Average score (in bottom 99%).
Score not available.
Main data sources:
CORD-19 dataset(1) (list of papers)
LitCovid hub(2) (list of papers)
PMC & PubMed (citations)
Mendeley (number of readers)
COVID-19-TweetIDs(3) (tweets)

Use:  Impact  Relevance & Impact
TitleVenueYearImpactSource
5551COVID-19 vaccination hesitancy among Healthcare workers, communication and policy-making  

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine hesitancy in healthcare workers (HCWs) contributes to personal and patient risk in contracting COVID-19. Reasons behind hesitancy and how best to improve vaccination rates in HCWs are not clear. METHODS: We adapted a survey using the Health Belief Model framework to evaluate HCW vaccine hesitancy and reasons for choosing for or against COVID-19 vaccination. The survey was sent to three large academic medical centers in the Chicagoland area between March and May 2021. RESULTS: We received 1974 completed responses with 85% of HCWs receiving or anticipating receiving COVID-19 vaccination. Multivariable logistic regression found HCWs were less likely to receive COVID-19 vaccination if they were Black (OR 0.34, 95% CI 0.15-0.80), Republican (OR 0.54, 95% CI 0.31-0.91), or allergic to any vaccine component (OR 0.27, 95% CI 0.10-0.70) and more likely to receive if they believed people close to them thought it was important for them to receive the vaccine (OR 5.2, 95% CI 3-8). CONCLUSIONS: A sizable number of HCWs remain vaccine hesitant one year into the COVID-19 pandemic. As HCWs are positively influenced by colleagues who believe COVID-19 vaccination, development of improved communication across HCW departments and roles may improve vaccination rates.

Am J Infect Control2021       LitCov and CORD-19
5552Does peritraumatic distress predict PTSD, depression and anxiety symptoms during and after COVID-19 lockdown in France? A prospective longitudinal study  

BACKGROUND: COVID-19 peritraumatic distress (CPD), an emerging trauma-related psychopathology, involves immediate physiological arousal as well as emotional and cognitive responses to the threat of the COVID-19 outbreak. This study examined the prevalence of and temporal changes in CPD, its early and follow-up predictors and the extent to which it was predictive of mental health problems. METHODS: The study took a two-wave design approach and was conducted during and 3-4 months after the nationwide lockdown in France. Baseline participants were 1,123 (79.5% women; M age = 33.82; range: 18-80). They completed validated measures assessing CPD, posttraumatic stress (PTS), depression, and anxiety symptoms. Descriptive, correlational, and path model analyses were used. FINDINGS: Both baseline and follow-up groups presented similar psychosocial profiles. Overall, 35.5% (95% Confidence Interval [CI]: 32.7-38.4) baseline participants and 17.2% (95% CI: 12.6-22.7) follow-up participants developed clinical cases of CPD. The baseline CPD levels predicted 14 to 20% of the variances of PTS (b = 0.55), depression (b = 0.16) and anxiety symptoms (b = 0.16). After accounting for the effect of the baseline CPD levels, the current CPD levels predicted the three investigated mental health outcomes in high proportions (43 to 47%). Further findings revealed important temporal changes in baseline predictors of CPD. However, the chronic CPD and PTS symptoms were prevalent among students and individuals developing worries about the COVID-19 crisis while depression and anxiety symptoms were prevalent among single people and those with pre-existing mental health problems. LIMITATIONS: Data from self-report measures of mental health were used. The dropout rate between the two time assessments was relatively high. CONCLUSIONS: These longitudinal findings call for clinical efforts in assessment of and intervention in trauma-related distress. These efforts should be put into the predictive role of CPD in subsequent development of PTS symptoms and comorbidities as long as the health, social and economic consequences of the pandemic linger.

J Psychiatr Res2021       LitCov and CORD-19
5553Understanding on the possible routes for SARS CoV-2 invasion via ACE2 in the host linked with multiple organs damage  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accountable for causing the coronavirus diseases 2019 (COVID-19), is already declared as a pandemic disease globally. Like previously reported SARS-CoV strain, the novel SARS-CoV-2 also initiates the viral pathogenesis via docking viral spike-protein with the membranal angiotensin-converting enzyme 2 (ACE2) — a receptor on variety of cells in the human body. Therefore, COVID-19 is broadly characterized as a disease that targets multiple organs, particularly causing acute complications via organ-specific pathogenesis accompanied by destruction of ACE2(+) cells, including alveolus, cardiac microvasculature, endothelium, and glomerulus. Under such circumstances, the high expression of ACE2 in predisposing individuals associated with anomalous production of the renin-angiotensin system (RAS) may promote enhanced viral load in COVID-19, which comparatively triggers excessive apoptosis. Furthermore, multi-organ injuries were found linked to altered ACE2 expression and inequality between the ACE2/angiotensin-(1–7)/mitochondrial Ang system (MAS) and renin-angiotensin-system (RAS) in COVID-19 patients. However, the exact pathogenesis of multi-organ damage in COVID-19 is still obscure, but several perspectives have been postulated, involving altered ACE2 expression linked with direct/indirect damages by the virus-induced immune responses, such as cytokinin storm. Thus, insights into the invasion of a virus with respect to ACE2 expression site can be helpful to simulate or understand the possible complications in the targeted organ during viral infection. Hence, this review summarizes the multiple organs invasion by SARS CoV-2 linked with ACE2 expression and their consequences, which can be helpful in the management of the COVID-19 pathogenesis under life-threatening conditions.

Infect Genet Evol2022       LitCov and CORD-19
5554COVIDiagnosis-Net: Deep Bayes-SqueezeNet based diagnosis of the COVID-19 from X-ray images  

Abstract The COVID-19 outbreak has a tremendous impact on global health and the daily life of people still living in more than two hundred countries. The crucial action to gain the force in the fight of COVID-19 is to have powerful monitoring of the site forming infected patients. Most of the initial tests rely on detecting the genetic material of the coronavirus, and they have a poor detection rate with the time-consuming operation. In the ongoing process, radiological imaging is also preferred where chest X-rays are highlighted in the diagnosis. Early studies express the patients with an abnormality in chest X-rays pointing to the presence of the COVID-19. On this motivation, there are several studies cover the deep learning-based solutions to detect the COVID-19 using chest X-rays. A part of the existing studies use non-public datasets, others perform on complicated Artificial Intelligent (AI) structures. In our study, we demonstrate an AI-based structure to outperform the existing studies. The SqueezeNet that comes forward with its light network design is tuned for the COVID-19 diagnosis with Bayesian optimization additive. Fine-tuned hyperparameters and augmented dataset make the proposed network perform much better than existing network designs and to obtain a higher COVID-19 diagnosis accuracy.

Med Hypotheses2020       LitCov and CORD-19
5555Preserving Organizational Resilience, Patient Safety and Staff Retention during COVID-19 Requires a Holistic Consideration of the Psychological Safety of Healthcare Workers  

During the COVID-19 pandemic, healthcare workers are fighting a lethal virus with acute shortages of Personal Protective Equipment (PPE). These unprecedented circumstances have amplified the sources of emotional distress and worker burnout. However, many healthcare organizations (HCOs) in the United States, have opted for a “stoic approach” to healthcare worker support, i.e., no additional support beyond federal and state policy protections for the licensing and liability of healthcare workers. In this scenario, a key public health concern is sustaining an adequate healthcare workforce, both by way of quantity (adequate numbers) and quality (maximizing clinician resilience to provide safe care to large volumes of patients under challenging conditions). Therefore, it is imperative for HCO leaders to recognize that a limited view of worker psychological safety, without due consideration for the broader emotional distress created by the pandemic, could have the effect of restricting organizational resilience and adversely impacting patient safety and staff retention during and beyond the pandemic. This paper uses the organizational resilience framework to discuss the potential impact of a stoic approach to healthcare worker support on patient safety and staff retention in a hospital intensive care unit (ICU) during COVID-19. The discussion in turn, helps to develop recommendations for HCOs to overcome these challenges.

Int J Environ Res Public Healt2020       LitCov and CORD-19
5556Use of face masks to limit the spread of the COVID-19 among western Ugandans: Knowledge, attitude and practices  

BACKGROUND: The world is grappling with an ever-changing COVID-19 pandemic using preventive measures such as personal hygiene, face masks, restrictions on travel and gatherings in communities, in addition to a race to find a vaccine. The purpose of this study was to evaluate the knowledge, attitudes and practices of the western Uganda community on the proper use of face masks to mitigate the spread of COVID-19. METHODS: A cross-sectional study using a structured questionnaire was carried out from 1(st) July to 10(th) July 2020 among western Ugandans of consent age of 18 years and above. Data was analysed using Stata version 14.2. RESULTS: Among the respondents (n = 1114), the mean age was 30.7 (SD 11.1), 51% were males, 53.9% married and 43% had attained secondary education. Most participants (60.1%, n = 670) had satisfactory knowledge on the use of face masks and participants at a tertiary education level [AOR 2.6 (95% CI: 1.42–4.67; p = 0.002)] were likely to have satisfactory knowledge than participants who had not education. On attitude, most respondents (69.4%) were confident enough to correctly put on a face mask; 83.4% believed that a face mask can protect against COVID-19 and 75.9% of respondents had never shared their face mask. The majority of respondents (95.2%) agreed wearing face masks in public places was important to protect themselves against COVID-19; 60.3% reported washing their hands before wearing and after removing the face mask. Unfortunately, 51.5% reported removing the face mask if they needed to talk to someone. CONCLUSION: Despite the satisfactory knowledge, good attitude and practices, there is still much more to be done in terms of knowledge, attitude and practices among participants. Government, non-governmental organizations and civil society should improve sensitization of populations on how to behave with face masks while talking to avoid the spread of the COVID-19 among western Ugandans.

PLoS One2021       LitCov and CORD-19
5557FDA-authorized mRNA COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system  

Background Two FDA-authorized mRNA COVID-19 vaccines, BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna), have demonstrated high efficacies in large Phase 3 randomized clinical trials. It is important to assess their effectiveness in a real-world setting. Methods This is a retrospective analysis of 136,532 individuals in the Mayo Clinic health system (Arizona, Florida, Iowa, Minnesota, Wisconsin) with PCR testing data between December 1, 2020 and April 20, 2021. We compared clinical outcomes for a vaccinated cohort of 68,266 individuals who received at least one dose of either vaccine (nBNT162b2 = 51,795; nmRNA-1273 = 16,471) and an unvaccinated control cohort of 68,266 individuals propensity-matched based on relevant demographic, clinical, and geographic features. We estimated real-world vaccine effectiveness by comparing incidence rates of positive SARS-CoV-2 PCR testing and COVID-19 associated hospitalization and ICU admission starting 7 days after the second vaccine dose. Findings The real-world vaccine effectiveness in preventing SARS-CoV-2 infection was 86.1% (95% CI: 82.4-89.1%) for BNT162b2 and 93.3% (95% CI: 85.7-97.4%) for mRNA-1273. BNT162b2 and mRNA-1273 were 88.8% (95% CI: 75.5-95.7%) and 86.0% (95% CI: 71.6-93.9%) effective in preventing COVID-19 associated hospitalization. Both vaccines were 100% effective (95% CIBNT162b2: 51.4-100%; 95% CImRNA-1273: 43.3-100%) in preventing COVID-19 associated ICU admission. Conclusions BNT162b2 and mRNA-1273 are both effective in a real-world setting and are associated with reduced rates of SARS-CoV-2 infection and decreased burden of COVID-19 on the healthcare system.

Med (N Y)2021       LitCov and CORD-19
5558Remdesivir for the Treatment of Severe COVID-19: A Community Hospital's Experience  

N/A

J Am Osteopath Assoc2020       LitCov and CORD-19
5559Myocarditis and Pericarditis After Vaccination for COVID-19  

N/A

JAMA2021       LitCov and CORD-19
5560Case report: Variant-specific pre-exposure prophylaxis of SARS-CoV-2 infection in multiple sclerosis patients lacking vaccination responses  

N/A

Front Immunol2022       LitCov
5561SARS-CoV-2 Infections and Impact of the COVID-19 Pandemic in Pregnancy and Breastfeeding: Results from an Observational Study in Primary Care in Belgium  

COVID-19 also affects pregnant and breastfeeding women. Hence, clinicians and policymakers require reliable evidence on COVID-19 epidemiology and consequences in this population. We aimed to assess the susceptibility of pregnant women to SARS-CoV-2 and women’s perceived impact of the pandemic on their breastfeeding practices, medical counseling and social support. We performed a cross-sectional study using an online survey in primary care in Belgium. Pregnant and breastfeeding women and women who breastfed in the preceding four weeks were eligible to participate. The survey was distributed through social media in April 2020. In total, 6470 women participated (i.e., 2647 pregnant and 3823 breastfeeding women). Overall, 0.3% of all respondents reported to have tested positive for SARS-CoV-2, not indicating a higher susceptibility of pregnant women to contracting COVID-19. More than 90% refuted that the pandemic affected their breastfeeding practices, nor indicated that the coronavirus was responsible for breastfeeding cessation. Half of the women even considered giving longer breastmilk because of the coronavirus. In contrast, women’s medical counseling and social support were negatively affected by the lockdown. Women without previous breastfeeding experience and in the early postpartum period experienced a higher burden in terms of reduced medical counseling and support. In the future, more consideration and alternative supportive measures such as tele-visits by midwives or perinatal organizations are required for these women.

Int J Environ Res Public Healt2020       LitCov and CORD-19
5562Clinical features and treatment of COVID-19 patients in northeast Chongqing  

The outbreak of the novel coronavirus in China (SARS‐CoV‐2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID‐19 were enrolled. The median age was 47 years (interquartile range, 36‐55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty‐three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d‐dimer, lactate dehydrogenase, PCT, ALB, C‐reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID‐19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID‐19.

J Med Virol2020       LitCov and CORD-19
5563Preterm birth among women with and without SARS-CoV-2 infection  

INTRODUCTION: Studies directly comparing preterm birth rates in women with and without severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection are limited. Our objective was to determine whether preterm birth was affected by SARS‐CoV‐2 infection within a large integrated health system in New York with a universal testing protocol. MATERIAL AND METHODS: This retrospective cohort study evaluated data from seven hospitals in New York City and Long Island between March 2020 and June 2021, incorporating both the first and second waves of the coronavirus disease 2019 (COVID‐19) pandemic in the USA. All patients with live singleton gestations who had SARS‐CoV‐2 polymerase chain reaction (PCR) testing at delivery were included. Deliveries before 20 weeks of gestation were excluded. The rate of preterm birth (before 37 weeks) was compared between patients with positive and negative SARS‐CoV‐2 test results. This analysis was performed separately for resolved prenatal infections and infections at delivery, with the latter group subdivided by symptom status. Multiple logistic regression analysis was used to examine the association between SARS‐CoV‐2 infection and preterm birth, adjusting for maternal age, race‐ethnicity, parity, history of preterm birth, body mass index, marital status, insurance type, medical co‐morbidities, month of delivery, and wave of pandemic. RESULTS: A total of 31 550 patients were included and 2473 (7.8%) had laboratory‐confirmed infection. Patients with symptomatic COVID‐19 at delivery were more likely to deliver preterm (19.0%; adjusted odds ratio 2.76, 95% CI 1.92–3.88) compared with women with asymptomatic infection (8.8%) or without infection (7.1%). Among preterm births associated with symptomatic infection, 72.5% were medically indicated compared with 44.1% among women without infection (p < 0.001). Risk of preterm birth in patients with resolved prenatal infection was unchanged when compared with women without infection. Among women with infection at delivery, preterm birth occurred more frequently during the second wave compared with the first wave (13.6% vs. 8.7%, respectively; p < 0.006). However, this was not significant on multiple regression analysis after adjusting for other explanatory variables. CONCLUSIONS: Pregnant women with symptomatic COVID‐19 are more than twice as likely to have a preterm delivery than patients without infection. Asymptomatic infection and resolved prenatal infection are not associated with increased risk.

Acta Obstet Gynecol Scand2021       LitCov and CORD-19
5564Efficacy of Licensed Monoclonal Antibodies and Antiviral Agents against the SARS-CoV-2 Omicron Sublineages BA.1 and BA.2  

N/A

Viruses2022       LitCov
5565Acute Stroke Care Is at Risk in the Era of COVID-19: Experience at a Comprehensive Stroke Center in Barcelona  

BACKGROUND AND PURPOSE: The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center. METHODS: On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic. Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19. From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona. We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes. Data were compared with March 2019 using parametric or nonparametric methods as appropriate. RESULTS: At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity. Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426). Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population. Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64–73] versus 75 [73–80] years, P=0.009). In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge. CONCLUSIONS: The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics. During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients. Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic.

Stroke2020       LitCov and CORD-19
5566Analysis of the Effectiveness of the Ad26.COV2.S Adenoviral Vector Vaccine for Preventing COVID-19  

IMPORTANCE: Continuous assessment of the effectiveness and safety of the US Food and Drug Administration–authorized SARS-CoV-2 vaccines is critical to amplify transparency, build public trust, and ultimately improve overall health outcomes. OBJECTIVE: To evaluate the effectiveness of the Johnson & Johnson Ad26.COV2.S vaccine for preventing SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness research study used large-scale longitudinal curation of electronic health records from the multistate Mayo Clinic Health System (Minnesota, Arizona, Florida, Wisconsin, and Iowa) to identify vaccinated and unvaccinated adults between February 27 and July 22, 2021. The unvaccinated cohort was matched on a propensity score derived from age, sex, zip code, race, ethnicity, and previous number of SARS-CoV-2 polymerase chain reaction tests. The final study cohort consisted of 8889 patients in the vaccinated group and 88 898 unvaccinated matched patients. EXPOSURE: Single dose of the Ad26.COV2.S vaccine. MAIN OUTCOMES AND MEASURES: The incidence rate ratio of SARS-CoV-2 infection in the vaccinated vs unvaccinated control cohorts, measured by SARS-CoV-2 polymerase chain reaction testing. RESULTS: The study was composed of 8889 vaccinated patients (4491 men [50.5%]; mean [SD] age, 52.4 [16.9] years) and 88 898 unvaccinated patients (44 748 men [50.3%]; mean [SD] age, 51.7 [16.7] years). The incidence rate ratio of SARS-CoV-2 infection in the vaccinated vs unvaccinated control cohorts was 0.26 (95% CI, 0.20-0.34) (60 of 8889 vaccinated patients vs 2236 of 88 898 unvaccinated individuals), which corresponds to an effectiveness of 73.6% (95% CI, 65.9%-79.9%) and a 3.73-fold reduction in SARS-CoV-2 infections. CONCLUSIONS AND RELEVANCE: This study’s findings are consistent with the clinical trial–reported efficacy of Ad26.COV2.S and the first retrospective analysis, suggesting that the vaccine is effective at reducing SARS-CoV-2 infection, even with the spread of variants such as Alpha or Delta that were not present in the original studies, and reaffirm the urgent need to continue mass vaccination efforts globally.

JAMA Netw Open2021       LitCov and CORD-19
5567Proteomics of SARS-CoV-2-infected host cells reveals therapy targets  

N/A

Nature2020       LitCov and CORD-19
5568Trends in Venous Thromboembolism Anticoagulation in Patients Hospitalized With COVID-19  

IMPORTANCE: Venous thromboembolism (VTE) is a common complication of COVID-19. It is not well understood how hospitals have managed VTE prevention and the effect of prevention strategies on mortality. OBJECTIVE: To characterize frequency, variation across hospitals, and change over time in VTE prophylaxis and treatment-dose anticoagulation in patients hospitalized for COVID-19, as well as the association of anticoagulation strategies with in-hospital and 60-day mortality. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of adults hospitalized with COVID-19 used a pseudorandom sample from 30 US hospitals in the state of Michigan participating in a collaborative quality initiative. Data analyzed were from patients hospitalized between March 7, 2020, and June 17, 2020. Data were analyzed through March 2021. EXPOSURES: Nonadherence to VTE prophylaxis (defined as missing ≥2 days of VTE prophylaxis) and receipt of treatment-dose or prophylactic-dose anticoagulants vs no anticoagulation during hospitalization. MAIN OUTCOMES AND MEASURES: The effect of nonadherence and anticoagulation strategies on in-hospital and 60-day mortality was assessed using multinomial logit models with inverse probability of treatment weighting. RESULTS: Of a total 1351 patients with COVID-19 included (median [IQR] age, 64 [52-75] years; 47.7% women, 48.9% Black patients), only 18 (1.3%) had a confirmed VTE, and 219 (16.2%) received treatment-dose anticoagulation. Use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased over time (adjusted odds ratio [aOR], 1.46; 95% CI, 1.31-1.61 per week). Of 1127 patients who ever received anticoagulation, 392 (34.8%) missed 2 or more days of prophylaxis. Missed prophylaxis varied from 11% to 61% across hospitals and decreased markedly over time (aOR, 0.89; 95% CI, 0.82-0.97 per week). VTE nonadherence was associated with higher 60-day (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.03-1.67) but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03). Receiving any dose of anticoagulation (vs no anticoagulation) was associated with lower in-hospital mortality (only prophylactic dose: aHR, 0.36; 95% CI, 0.26-0.52; any treatment dose: aHR, 0.38; 95% CI, 0.25-0.58). However, only the prophylactic dose of anticoagulation remained associated with lower mortality at 60 days (prophylactic dose: aHR, 0.71; 95% CI, 0.51-0.90; treatment dose: aHR, 0.92; 95% CI, 0.63-1.35). CONCLUSIONS AND RELEVANCE: This large, multicenter cohort of patients hospitalized with COVID-19, found evidence of rapid dissemination and implementation of anticoagulation strategies, including use of treatment-dose anticoagulation. As only prophylactic-dose anticoagulation was associated with lower 60-day mortality, prophylactic dosing strategies may be optimal for patients hospitalized with COVID-19.

JAMA Netw Open2021       LitCov and CORD-19
5569Longitudinal characterization of the IgM and IgG humoral response in symptomatic COVID-19 patients using the Abbott Architect  

BACKGROUND: Antibody testing has recently emerged as an option to assist with determining exposure to SARS-CoV-2, the causative agent of COVID-19. Elucidation of the kinetics and duration of the humoral response is important for clinical management and interpreting results from serological surveys. OBJECTIVES: : Here we evaluated the clinical performance of Abbott SARSCoV-2 IgM and IgG assays, as well as the longitudinal dynamics of the antibody response in symptomatic COVID-19 patients. STUDY DESIGN AND RESULTS: The diagnostic specificity was 100% for IgM and 99.67% for IgG using 300 pre-COVID-19 serum specimens. Using 1349 sequential serum samples collected up to 168 days post symptom onset from 427 PCR-confirmed individuals, clinical test sensitivity of the SARS-CoV-2 IgM assay was 24.6% at ≤7 days, 75.3% at 8-14 days, 95.0% at 15-21 days, and 96.0% at 4-5 weeks (peak test sensitivity). The median duration of time for IgM seroconversion was 10 days. IgM levels declined steadily 4-5 weeks after symptom onset, and the positive rate dropped to 30.8% at >3 months. The diagnostic sensitivity for the SARS-CoV-2 IgG assay post symptom onset was 23.2% at ≤7 days, 69.5% at 8-14 days, 93.6% at 15-21 days, and 99.6% at 4-5 weeks (peak test sensitivity). The median duration of time for IgG seroconversion was 11.5 days. During the convalescent phase of the infection, a decline in the IgG level was observed in patients who were followed for >100 days. Despite that decline, 92.3% of the patient cohort remained IgG positive 3-6 months following symptom onset. CONCLUSIONS: This study demonstrates the Abbott IgM assay against SARSCoV-2 is detected slightly earlier compared to IgG, with both tests exhibiting excellent overall sensitivity and specificity. In symptomatic patients who test negative by PCR for a SARS-CoV-2 infection, assessing IgM and IgG antibodies can aid in supporting a diagnosis of COVID-19.

J Clin Virol2020       LitCov and CORD-19
5570Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants  

N/A

J Virol2022       LitCov
5571The structural basis of accelerated host cell entry by SARS-CoV-2  

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the causative agent of the pandemic coronavirus disease 2019 (COVID‐19) that exhibits an overwhelming contagious capacity over other human coronaviruses (HCoVs). This structural snapshot describes the structural bases underlying the pandemic capacity of SARS‐CoV‐2 and explains its fast motion over respiratory epithelia that allow its rapid cellular entry. Based on notable viral spike (S) protein features, we propose that the flat sialic acid‐binding domain at the N‐terminal domain (NTD) of the S1 subunit leads to more effective first contact and interaction with the sialic acid layer over the epithelium, and this, in turn, allows faster viral ‘surfing’ of the epithelium and receptor scanning by SARS‐CoV‐2. Angiotensin‐converting enzyme 2 (ACE‐2) protein on the epithelial surface is the primary entry receptor for SARS‐CoV‐2, and protein–protein interaction assays demonstrate high‐affinity binding of the spike protein (S protein) to ACE‐2. To date, no high‐frequency mutations were detected at the C‐terminal domain of the S1 subunit in the S protein, where the receptor‐binding domain (RBD) is located. Tight binding to ACE‐2 by a conserved viral RBD suggests the ACE2‐RBD interaction is likely optimal. Moreover, the viral S subunit contains a cleavage site for furin and other proteases, which accelerates cell entry by SARS‐CoV‐2. The model proposed here describes a structural basis for the accelerated host cell entry by SARS‐CoV‐2 relative to other HCoVs and also discusses emerging hypotheses that are likely to contribute to the development of antiviral strategies to combat the pandemic capacity of SARS‐CoV‐2.

FEBS J2020       LitCov and CORD-19
5572Infodemia: Another Enemy for Romanian Frontline Healthcare Workers to Fight during the COVID-19 Outbreak  

Background and Objectives: The population has been overwhelmed with false information related to the Coronavirus disease (COVID-19) crisis, spreading rapidly through social media and other channels. We aimed to investigate if frontline healthcare workers affected by infodemia show different psychological consequences than frontline clinicians who do not declare to be affected by false news related to the COVID-19 pandemic. Materials and Methods: One hundred twenty-six frontline healthcare workers from the Intensive Care Unit (ICU) and Emergency Departments in Romania completed a survey to assess stress, depression, anxiety, and sleep disorders, between March and April 2020. We split the sample of frontline healthcare workers into two groups based on the self-evaluated criteria: if they were or were not affected by infodemia in their activity. Results: Considering limitations such as the cross-sectional design, the lack of causality relationship, and the sample size, the results show that, the frontline medical workers who declared to be affected by false news were significantly more stressed, felt more anxiety, and suffered more from insomnia than healthcare workers who are not affected by false information related to pandemic time. Conclusions: The infodemia has significant psychological consequences such as stress, anxiety, and insomnia on already overwhelmed doctors and nurses in the outbreak of the COVID-19 crisis. These findings suggest that medical misinformation’s psychological implications must be considered when different interventions regarding frontline healthcare workers during the COVID-19 pandemic are implemented.

Medicina (Kaunas)2020       LitCov and CORD-19
5573Revised Triage and Surveillance Protocols for Temporary Emergency Department Closures in Tertiary Hospitals as a Response to COVID-19 Crisis in Daegu Metropolitan City  

BACKGROUND: When an emergency-care patient is diagnosed with an emerging infectious disease, hospitals in Korea may temporarily close their emergency departments (EDs) to prevent nosocomial transmission. Since February 2020, multiple, consecutive ED closures have occurred due to the coronavirus disease 2019 (COVID-19) crisis in Daegu. However, sudden ED closures are in contravention of laws for the provision of emergency medical care that enable the public to avail prompt, appropriate, and 24-hour emergency medical care. Therefore, this study ascertained the vulnerability of the ED at tertiary hospitals in Daegu with regard to the current standards. A revised triage and surveillance protocol has been proposed to tackle the current crisis. METHODS: This study was retrospectively conducted at 6 level 1 or 2 EDs in a metropolitan city where ED closure due to COVID-19 occurred from February 18 to March 26, 2020. The present status of ED closure and patient characteristics and findings from chest radiography and laboratory investigations were assessed. Based on the experience from repeated ED closures and the modified systems that are currently used in EDs, revised triage and surveillance protocols have been developed and proposed. RESULTS: During the study period, 6 level 1 or 2 emergency rooms included in the study were shut down 27 times for 769 hours. Thirty-one confirmed COVID-19 cases, of whom 7 died, were associated with the incidence of ED closure. Typical patient presentation with respiratory symptoms of COVID-19 was seen in less than 50% of patients, whereas abnormal findings on chest imaging investigations were detected in 93.5% of the study population. The chest radiography facility, resuscitation rooms, and triage area were moved to locations outside the ED, and a new surveillance protocol was applied to determine the factors warranting quarantine, including symptoms, chest radiographic findings, and exposure to a source of infection. The incidence of ED closures decreased after the implementation of the revised triage and surveillance protocols. CONCLUSION: Triage screening by emergency physicians and surveillance protocols with an externally located chest imaging facility were effective in the early isolation of COVID-19 patients. In future outbreaks of emerging infectious diseases, efforts should be focused toward the provision of continued ED treatment with the implementation of revised triage and surveillance protocols.

J Korean Med Sci2020       LitCov and CORD-19
5574Social Media Use for Health Communication by the CDC in Mainland China: National Survey Study 2009-2020  

BACKGROUND: In recent years, public health incidents that pose a serious threat to public life have occurred frequently in China. The use of social media by public health authorities has helped to reduce these threats by increasing effective risk communication between the government and the public. OBJECTIVE: The aim of this study is to reveal how China’s Center for Disease Control and Prevention (CDC) uses social media to improve three aspects of health communication between the government and the public: adoption, operation, and interaction. METHODS: To analyze the 134 CDC government Weibo accounts at the provincial- and prefecture-level administration regions in mainland China, we collected their account data and extracted 1215 Weibo tweets. We also supplemented the data to reveal the overall performance of the CDC’s government Weibo use during the COVID-19 crisis. RESULTS: The registration rate of the CDC’s government Weibo accounts increased year by year, and the local authorities registered Weibo accounts before the central government authorities. In total, 29.8% (n=134) of the 450 CDC facilities have registered an account. Among the 134 CDC facilities that have registered Weibo accounts, the registration rate in the eastern region (n=68, 50.7%) was higher than those in the central region (n=30, 22.4%) and the western region (n=36, 26.9%). Nearly 90.0% of these Weibo accounts had official certification, but there were dropouts in the specific operating process. One-third of the accounts have not been updated for more than 1 year, and the number of Weibo followers was polarized, with a maximum and minimum difference of 1 million. The response rate to users’ comments was less than 1%. Emergency information, multimedia content, and original content were more helpful in promoting communication between the government and the public. Such interaction was partially improved during the COVID-19 pandemic. The CDC updated the daily epidemic situation and provided popular science information for epidemic prevention and control for the public in a timely manner. CONCLUSIONS: China’s CDC is using more social media to popularize daily health information and has taken the first step to improve communication between the government and the public. However, equal dialogue, two-way interactions, and effective communication with the public still need improvement.

J Med Internet Res2020       LitCov and CORD-19
5575Hydrogel-Based Slow Release of a Receptor-Binding Domain Subunit Vaccine Elicits Neutralizing Antibody Responses Against SARS-CoV-2  

The development of effective vaccines that can be rapidly manufactured and distributed worldwide is necessary to mitigate the devastating health and economic impacts of pandemics like COVID‐19. The receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein, which mediates host cell entry of the virus, is an appealing antigen for subunit vaccines because it is efficient to manufacture, highly stable, and a target for neutralizing antibodies. Unfortunately, RBD is poorly immunogenic. While most subunit vaccines are commonly formulated with adjuvants to enhance their immunogenicity, clinically‐relevant adjuvants Alum, AddaVax, and CpG/Alum are found unable to elicit neutralizing responses following a prime‐boost immunization. Here, it has been shown that sustained delivery of an RBD subunit vaccine comprising CpG/Alum adjuvant in an injectable polymer‐nanoparticle (PNP) hydrogel elicited potent anti‐RBD and anti‐spike antibody titers, providing broader protection against SARS‐CoV‐2 variants of concern compared to bolus administration of the same vaccine and vaccines comprising other clinically‐relevant adjuvant systems. Notably, a SARS‐CoV‐2 spike‐pseudotyped lentivirus neutralization assay revealed that hydrogel‐based vaccines elicited potent neutralizing responses when bolus vaccines did not. Together, these results suggest that slow delivery of RBD subunit vaccines with PNP hydrogels can significantly enhance the immunogenicity of RBD and induce neutralizing humoral immunity.

Adv Mater2021       LitCov and CORD-19
5576Knowledge, socio-cognitive perceptions and the practice of hand hygiene and social distancing during the COVID-19 pandemic: a cross-sectional study of UK university students  

BACKGROUND: During the first wave of the COVID-19 pandemic, social distancing and hand hygiene have been the primary means of reducing transmission in the absence of effective treatments or vaccines, but understanding of their determinants is limited. This study aimed to investigate knowledge and socio-cognitive perceptions, and their associations with such protective behaviours, in UK university students. METHODS: A cross-sectional online survey of 293 students was undertaken on 13 May 2020. Survey questions addressed demographics, knowledge of the disease and effectiveness of the protective measures, risk perception, socio-cognitive perceptions (e.g. attitude, social support, and self-efficacy), habit, time factors and trust, as well as the hand hygiene and social distancing behaviours. Multiple linear regression was used to identify the strongest associations of potential determinants with behaviour. RESULTS: Participants reported high levels of social distancing with 88.9% answering “Mostly” or “Always” for every activity, but only 42.0% reporting the same for all hand hygiene activities. Knowledge of the effectiveness of each activity in preventing transmission was high, with 90.7% and 93.5% respectively identifying at least 7 of 8 hand hygiene or 9 of 10 social distancing activities correctly. Habit (β = 0.39, p = 0.001) and time factors (β = 0.28, p = 0.001) were the greatest contributors to unique variance in hand hygiene behaviour, followed by ethnicity (β = − 0.13, p = 0.014) and risk perception (β = 0.13, p = 0.016). For social distancing behaviour, the determinants were self-efficacy (β = 0.25, p < 0.001), perceived advantages (β = 0.15, p = 0.022), trust in policy (β = 0.14, p = 0.026) and gender (β = − 0.14, p = 0.016). Regression models explained 40% hand hygiene and 25% social distancing variance. CONCLUSIONS: This study indicated that communications about effectiveness of hand hygiene and social distancing behaviours had been effective in terms of knowledge acquisition. However, in the light of likely second waves of COVID-19, attention to maintaining social distancing behaviour and improving hand hygiene behaviour may need to address more difficult areas of changing habits, overcoming time factors and building trust, as well as interventions to increase self-efficacy and address risk perception concerns. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-10461-0.

BMC Public Health2021       LitCov and CORD-19
5577Where Have All the Emergencies Gone? The Impact of the COVID-19 Pandemic on Obstetric and Gynecologic Procedures and Consults at a New York City Hospital  

STUDY OBJECTIVE: The purpose of this study was to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on surgical volume and emergency department (ED) consults across obstetric & gynecologic (OB/GYN) services at a New York City hospital. DESIGN: Retrospective cohort study SETTING: Tertiary-care academic medical center in New York City PATIENTS OR PARTICIPANTS: Women undergoing OB/GYN ED consults or surgeries between February 1(st) to April 15(th). INTERVENTIONS: March 16th institutional moratorium on elective surgeries MEASUREMENTS AND MAIN RESULTS: The volume and types of surgeries and ED consults were compared before and after the COVID-19 moratorium. During the pandemic, the average weekly volume of ED consults and GYN surgeries decreased, while OB surgeries remained stable. The proportions of OBGYN ED consults, GYN surgeries, and OB surgeries relative to all ED consults, all surgeries, and all labor and delivery patients were 1.87%, 13.8%, 54.6% in the pre-COVID timeframe (February 1(st) to March 15(th)) versus 1.53%, 21.3%, 79.7% in the COVID timeframe (March 16(th) to April 15(th)), representing no significant difference in proportions of OBGYN ED consults (p=0.464) and GYN surgeries (p=0.310) before and during COVID, with proportionate increase in OB surgeries (p<.002). The distribution of GYN surgical case types changed significantly during the pandemic with higher proportions of emergent surgeries for ectopics, miscarriages, and concern for cancer (p <.001). Alternatively, the OB surgery distribution of case types remained relatively constant. CONCLUSIONS: This study highlights how the pandemic has impacted the ways OB/GYN patients access and receive care. As expected, institutional policies suspending elective surgeries during the pandemic decreased GYN surgical volume and affected the types of cases performed. This decrease was not appreciated for OB surgical volume reflecting the non-elective and time-sensitive nature of obstetric care. A decrease in ED consults was noted during the pandemic begging the question “Where have all the emergencies gone?”. Although the moratorium on elective procedures was necessary, “elective” GYN surgeries remain medically indicated to address symptoms such as pain and bleeding and to prevent serious medical sequelae such as severe anemia requiring transfusion. As we continue to battle COVID-19, we must not lose sight of those patients whose care has been deferred.

J Minim Invasive Gynecol2020       LitCov and CORD-19
5578Italian Nurses' experiences during the COVID-19 pandemic: a qualitative analysis of internet posts  

AIM: To investigate the experience of Italian nurses during the first wave of the COVID‐19 outbreak by analysing professional social media posts. BACKGROUND: The COVID‐19 outbreak has overwhelmed health care institutions; as a consequence, nurses’ lives and psycho‐physical health have been affected. INTRODUCTION: The COVID‐19 pandemic forced nurses to work in physically and psychologically stressful conditions impacting on their life. METHODS: A qualitative descriptive study. All narratives (texts and videos) posted by nurses from the 23(rd) of February 2020 to the 3(rd) of May (from the start of the outbreak to the end of the first lockdown) were analysed and published on the five most popular Italian professional social media platforms. The Consolidated Criteria for Reporting Qualitative research guidelines were followed. RESULTS: Five themes emerged from the 380 narratives explored: ‘Sharing what is happening within myself’; ‘Experiencing unprecedented working conditions’; ‘Experiencing a deep change’; ‘Failing to rehabilitate the image of nurses in society’; and ‘Do not abandon us’. Even though nurses appreciated the recognition of their communities, they still felt devalued and not recognized as professionals. DISCUSSION: Several psychological, physical, social and professional implications emerged from nurses working during the COVID‐19 pandemic. Despite being highly praised, nurses perceived they had failed in rehabilitating the image of nurses in society. CONCLUSION: The experience of working during the COVID‐19 pandemic represented a traumatic event for nurses but it offered them personal and professional growth opportunities. IMPLICATIONS FOR NURSING PRACTICE, NURSING POLICY AND HEALTH POLICY: Supporting nurses’ mental health is highly recommended, together with a cultural investment on nurses’ role recognition, and a zero‐tolerance policy towards violence and aggression towards nurses.

Int Nurs Rev2021       LitCov and CORD-19
5579Seroprevalence of SARS-CoV-2 IgG Antibodies and Factors Associated with SARS-CoV-2 IgG Neutralizing Activity among Primary Healthcare Workers 6 Months after Vaccination Rollout in France  

We aimed to investigate the immunoglobulin G response and neutralizing activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among primary health care workers (PHCW) in France and assess the association between the neutralizing activity and several factors, including the coronavirus disease 2019 (COVID-19) vaccination scheme. A cross-sectional survey was conducted between 10 May 2021 and 31 August 2021. Participants underwent capillary blood sampling and completed a questionnaire. Sera were tested for the presence of antibodies against the nucleocapsid (N) protein and the S-1 portion of the spike (S) protein and neutralizing antibodies. In total, 1612 PHCW were included. The overall seroprevalences were: 23.6% (95% confidence interval (CI) 21.6–25.7%) for antibodies against the N protein, 94.7% (93.6–95.7%) for antibodies against the S protein, and 81.3% (79.4–83.2%) for neutralizing antibodies. Multivariate regression analyses showed that detection of neutralizing antibodies was significantly more likely in PHCW with previous SARS-CoV-2 infection than in those with no such history among the unvaccinated (odds ratio (OR) 16.57, 95% CI 5.96–59.36) and those vaccinated with one vaccine dose (OR 41.66, 95% CI 16.05–120.78). Among PHCW vaccinated with two vaccine doses, the detection of neutralizing antibodies was not significantly associated with previous SARS-CoV-2 infection (OR 1.31, 95% CI 0.86–2.07), but was more likely in those that received their second vaccine dose within the three months before study entry than in those vaccinated more than three months earlier (OR 5.28, 95% CI 3.51–8.23). This study highlights that previous SARS-CoV-2 infection and the time since vaccination should be considered when planning booster doses and the design of COVID-19 vaccine strategies.

Viruses2022       LitCov and CORD-19
5580A randomised, double-blind, placebo-controlled, pilot trial of intravenous plasma purified alpha-1 antitrypsin for SARS-CoV-2 induced Acute Respiratory Distress Syndrome: a structured summary of a study protocol for a randomised, controlled trial  

OBJECTIVES: The primary objective is to demonstrate that, in patients with PCR-confirmed SARS-CoV-2 resulting in Acute Respiratory Distress Syndrome (ARDS), administration of 120mg/kg of body weight of intravenous Prolastin®(plasma-purified alpha-1 antitrypsin) reduces circulating plasma levels of interleukin-6 (IL-6). Secondary objectives are to determine the effects of intravenous Prolastin® on important clinical outcomes including the incidence of adverse events (AEs) and serious adverse events (SAEs). TRIAL DESIGN: Phase 2, randomised, double-blind, placebo-controlled, pilot trial. PARTICIPANTS: The study will be conducted in Intensive Care Units in hospitals across Ireland. Patients with a laboratory-confirmed diagnosis of SARS-CoV-2-infection, moderate to severe ARDS (meeting Berlin criteria for a diagnosis of ARDS with a PaO(2)/FiO(2) ratio <200 mmHg), >18 years of age and requiring invasive or non-invasive mechanical ventilation. All individuals meeting any of the following exclusion criteria at baseline or during screening will be excluded from study participation: more than 96 hours has elapsed from onset of ARDS; age < 18 years; known to be pregnant or breastfeeding; participation in a clinical trial of an investigational medicinal product (other than antibiotics or antivirals) within 30 days; major trauma in the prior 5 days; presence of any active malignancy (other than nonmelanoma skin cancer) which required treatment within the last year; WHO Class III or IV pulmonary hypertension; pulmonary embolism prior to hospital admission within past 3 months; currently receiving extracorporeal life support (ECLS); chronic kidney disease receiving dialysis; severe chronic liver disease with Child-Pugh score > 12; DNAR (Do Not Attempt Resuscitation) order in place; treatment withdrawal imminent within 24 hours; Prisoners; non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available; IgA deficiency. INTERVENTION AND COMPARATOR: Intervention: Either a once weekly intravenous infusion of Prolastin® at 120mg/kg of body weight for 4 weeks or a single dose of Prolastin® at 120mg/kg of body weight intravenously followed by once weekly intravenous infusion of an equal volume of 0.9% sodium chloride for a further 3 weeks. Comparator (placebo): An equal volume of 0.9% sodium chloride intravenously once per week for four weeks. MAIN OUTCOMES: The primary effectiveness outcome measure is the change in plasma concentration of IL-6 at 7 days as measured by ELISA. Secondary outcomes include: safety and tolerability of Prolastin® in the respective groups (as defined by the number of SAEs and AEs); PaO(2)/FiO(2) ratio; respiratory compliance; sequential organ failure assessment (SOFA) score; mortality; time on ventilator in days; plasma concentration of alpha-1 antitrypsin (AAT) as measured by nephelometry; plasma concentrations of interleukin-1β (IL-1β), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble TNF receptor 1 (sTNFR1, a surrogate marker for TNF-α) as measured by ELISA; development of shock; acute kidney injury; need for renal replacement therapy; clinical relapse, as defined by the need for readmission to the ICU or a marked decline in PaO(2)/FiO(2) or development of shock or mortality following a period of sustained clinical improvement; secondary bacterial pneumonia as defined by the combination of radiographic findings and sputum/airway secretion microscopy and culture. RANDOMISATION: Following informed consent/assent patients will be randomised. The randomisation lists will be prepared by the study statistician and given to the unblinded trial personnel. However, the statistician will not be exposed to how the planned treatment will be allocated to the treatment codes. Randomisation will be conducted in a 1:1:1 ratio, stratified by site and age. BLINDING (MASKING): The investigator, treating physician, other members of the site research team and patients will be blinded to treatment allocation. The clinical trial pharmacy personnel and research nurses will be unblinded to facilitate intervention and placebo preparation. The unblinded individuals will keep the treatment information confidential. The infusion bag will be masked at the time of preparation and will be administered via a masked infusion set to maintain blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 36 patients will be recruited and randomised in a 1:1:1 ratio to each of the trial arms. TRIAL STATUS: In March 2020, version 1.0 of the trial protocol was submitted to the local research ethics committee (REC), Health Research Consent Declaration Committee (HRCDC) and the Health Products regulatory Authority (HPRA). REC approval was granted on April 1(st) 2020, HPRA approval was granted on April 24(th) 2020 and the HRCDC provided a conditional declaration on April 17(th) 2020. In July 2020 a substantial amendment (version 2.0) was submitted to the REC, HRCDC and HPRA. Protocol changes in this amendment included: the addition of trial sites; extending the duration of the trial to 12 months from 3 months; removal of inclusion criteria requiring the need for vasopressors; amendment of randomisation schedule to stratify by age only and not BMI and sex; correction of grammatical error in relation to infusion duration; to allow for inclusion of subjects who may have been enrolled in a clinical trial involving either antibiotics or anti-virals in the past 30 days; to allow for inclusion of subjects who may be currently enrolled in a clinical trial involving either antibiotics or anti-virals; to remove the need for exclusion based on alpha-1 antitrypsin phenotype; removal of mandatory isoelectric focusing of plasma to confirm Pi*MM status at screening; removal of need for mandatory echocardiogram at screening; amendment on procedures around plasma analysis to reflect that this will be conducted at the central site laboratory (as trial is multi-site and no longer single site); wording amended to reflect that interim analysis of cytokine levels taken at 7 days may be conducted. HRCDC approved version 2.0 on September 14th 2020, and HPRA approved on October 22nd 2020. REC approved the substantial amendment on November 23(rd). In November 2020, version 3.0 of the trial protocol was submitted to the REC and HPRA. The rationale for this amendment was to allow for patients with moderate to severe ARDS from SARS-CoV-2 with non-invasive ventilation. HPRA approved this amendment on December 1st 2020 and the REC approved the amendment on December 8th 2020. Patient recruitment commenced in April 2020 and the last patient will be recruited to the trial in April 2021. The last visit of the last patient is anticipated to occur in April 2021. At time of writing, patient recruitment is now complete, however follow-up patient visits and data collection are ongoing. TRIAL REGISTRATION: EudraCT 2020-001391-15 (Registered 31 Mar 2020). FULL PROTOCOL: The full protocol (version 3.0 23.11.2020) is attached as an additional file accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05254-0.

Trials2021       LitCov and CORD-19
5581Antibody response against SARS-CoV-2 variants of concern in children infected with pre-Omicron variants: An observational cohort study  

N/A

EBioMedicine2022       LitCov
5582Expression of ACE2 and TMPRSS2 Proteins in the Upper and Lower Aerodigestive Tracts of Rats: Implications on COVID-19 Infections  

N/A

Laryngoscope2021       LitCov and CORD-19
5583COVID-19: The World Community Expects the World Health Organization to Play a Stronger Leadership and Coordination Role in Pandemics Control  

The coronavirus disease 2019 (COVID-19) pandemic has been accompanied by the return of the concept of national state and exhibited signs of crisis of globalism and liberalism. The pandemic affected most aspects of society and human activity, including socioeconomic impact. Economic problems, shortages of medical supplies and personnel, xenophobic sentiments, and misinformation led to the use of unethical practices and human rights violations. To navigate through this crisis, many countries resorted to traditional diplomacy in the absence of effective international instruments. Thus, the world faced the urgent need in functioning global governance. The pandemic also manifested the increasing importance of international organizations as sources of technical expertise, providing scientific basis for politicians to legitimize their decisions and actions. The article addresses the topic of implications of the pandemic for governance and forecasting a post-pandemic future. The research focus of this paper, therefore, is the assessment of the role of the World Health Organization (WHO) in prevention and response to pandemics. The work is aimed at identifying the functions of the WHO and assessing its activities in prevention and control of pandemics and response to the COVID-19 pandemic in particular. Furthermore, the objective of this article is to identify gaps in the WHO pandemic control efforts and formulate recommendations on addressing them.

Front Public Health2020       LitCov and CORD-19
5584Emerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia  

BACKGROUND: The chest CT findings of patients with 2019 Novel Coronavirus (2019-nCoV) pneumonia have not previously been described in detail. PURPOSE: To investigate the clinical, laboratory, and imaging findings of emerging 2019-nCoV pneumonia in humans. MATERIALS AND METHODS: Fifty-one patients (25 men and 26 women; age range 16–76 years) with laboratory-confirmed 2019-nCoV infection by using real-time reverse transcription polymerase chain reaction underwent thin-section CT. The imaging findings, clinical data, and laboratory data were evaluated. RESULTS: Fifty of 51 patients (98%) had a history of contact with individuals from the endemic center in Wuhan, China. Fever (49 of 51, 96%) and cough (24 of 51, 47%) were the most common symptoms. Most patients had a normal white blood cell count (37 of 51, 73%), neutrophil count (44 of 51, 86%), and either normal (17 of 51, 35%) or reduced (33 of 51, 65%) lymphocyte count. CT images showed pure ground-glass opacity (GGO) in 39 of 51 (77%) patients and GGO with reticular and/or interlobular septal thickening in 38 of 51 (75%) patients. GGO with consolidation was present in 30 of 51 (59%) patients, and pure consolidation was present in 28 of 51 (55%) patients. Forty-four of 51 (86%) patients had bilateral lung involvement, while 41 of 51 (80%) involved the posterior part of the lungs and 44 of 51 (86%) were peripheral. There were more consolidated lung lesions in patients 5 days or more from disease onset to CT scan versus 4 days or fewer (431 of 712 lesions vs 129 of 612 lesions; P < .001). Patients older than 50 years had more consolidated lung lesions than did those aged 50 years or younger (212 of 470 vs 198 of 854; P < .001). Follow-up CT in 13 patients showed improvement in seven (54%) patients and progression in four (31%) patients. CONCLUSION: Patients with fever and/or cough and with conspicuous ground-glass opacity lesions in the peripheral and posterior lungs on CT images, combined with normal or decreased white blood cells and a history of epidemic exposure, are highly suspected of having 2019 Novel Coronavirus (2019-nCoV) pneumonia. © RSNA, 2020

Radiology2020       LitCov and CORD-19
5585Comparison of seven commercial SARS-CoV-2 rapid point-of-care antigen tests: a single-center laboratory evaluation study  

BACKGROUND: Antigen point-of-care tests (AgPOCTs) can accelerate SARS-CoV-2 testing. As some AgPOCTs have become available, interest is growing in their utility and performance. Here we aimed to compare the analytical sensitivity and specificity of seven commercially available AgPOCT devices. METHODS: In a single-centre, laboratory evaluation study, we compared AgPOCT products from seven suppliers: the Abbott Panbio COVID-19 Ag Rapid Test, the RapiGEN BIOCREDIT COVID-19 Ag, the Healgen Coronavirus Ag Rapid Test Cassette (Swab), the Coris BioConcept COVID-19 Ag Respi-Strip, the R-Biopharm RIDA QUICK SARS-CoV-2 Antigen, the nal von minden NADAL COVID-19 Ag Test, and the Roche-SD Biosensor SARS-CoV Rapid Antigen Test. Tests were evaluated on recombinant SARS-CoV-2 nucleoprotein, cultured endemic and emerging coronaviruses, stored respiratory samples with known SARS-CoV-2 viral loads, stored samples from patients with respiratory pathogens other than SARS-CoV-2, and self-sampled swabs from healthy volunteers. We estimated analytical sensitivity in terms of approximate viral concentrations (quantified by real-time RT-PCR) that yielded positive AgPOCT results, and specificity in terms of propensity to generate false-positive results. FINDINGS: In 138 clinical samples with quantified SARS-CoV-2 viral load, the 95% limit of detection (concentration at which 95% of test results were positive) in six of seven AgPOCT products ranged between 2·07 × 10(6) and 2·86 × 10(7) copies per swab, with an outlier (RapiGEN) at 1·57 × 10(10) copies per swab. The assays showed no cross-reactivity towards cell culture or tissue culture supernatants containing any of the four endemic human coronaviruses (HCoV‑229E, HCoV‑NL63, HCoV‑OC43, or HCoV‑HKU1) or MERS-CoV, with the exception of the Healgen assay in one repeat test on HCoV-HKU1 supernatant. SARS-CoV was cross-detected by all assays. Cumulative specificities among stored clinical samples with non-SARS-CoV-2 infections (n=100) and self-samples from healthy volunteers (n=35; cumulative sample n=135) ranged between 98·5% (95% CI 94·2–99·7) and 100·0% (97·2–100·0) in five products, with two outliers at 94·8% (89·2–97·7; R-Biopharm) and 88·9% (82·1–93·4; Healgen). False-positive results did not appear to be associated with any specific respiratory pathogen. INTERPRETATION: The sensitivity range of most AgPOCTs overlaps with SARS-CoV-2 viral loads typically observed in the first week of symptoms, which marks the infectious period in most patients. The AgPOCTs with limit of detections that approximate virus concentrations at which patients are infectious might enable shortcuts in decision making in various areas of health care and public health. FUNDING: EU's Horizon 2020 research and innovation programme, German Ministry of Research, German Federal Ministry for Economic Affairs and Energy, German Ministry of Health, and Bill & Melinda Gates Foundation.

Lancet Microbe2021       LitCov and CORD-19
5586Real-Time Digital Contact Tracing: Development of a System to Control COVID-19 Outbreaks in Nursing Homes and Long-Term Care Facilities  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread rapidly in nursing homes and long-term care (LTC) facilities. Symptoms-based screening and manual contact tracing have limitations that render them ineffective for containing the viral spread in LTC facilities. Symptoms-based screening alone cannot identify asymptomatic people who are infected, and the viral spread is too fast in confined living quarters to be contained by slow manual contact tracing processes. OBJECTIVE: We describe the development of a digital contact tracing system that LTC facilities can use to rapidly identify and contain asymptomatic and symptomatic SARS-CoV-2 infected contacts. A compartmental model was also developed to simulate disease transmission dynamics and to assess system performance versus conventional methods. METHODS: We developed a compartmental model parameterized specifically to assess the coronavirus disease (COVID-19) transmission in LTC facilities. The model was used to quantify the impact of asymptomatic transmission and to assess the performance of several intervention groups to control outbreaks: no intervention, symptom mapping, polymerase chain reaction testing, and manual and digital contact tracing. RESULTS: Our digital contact tracing system allows users to rapidly identify and then isolate close contacts, store and track infection data in a respiratory line listing tool, and identify contaminated rooms. Our simulation results indicate that the speed and efficiency of digital contact tracing contributed to superior control performance, yielding up to 52% fewer cases than conventional methods. CONCLUSIONS: Digital contact tracing systems show promise as an effective tool to control COVID-19 outbreaks in LTC facilities. As facilities prepare to relax restrictions and reopen to outside visitors, such tools will allow them to do so in a surgical, cost-effective manner that controls outbreaks while safely giving residents back the life they once had before this pandemic hit.

JMIR Public Health Surveill2020       LitCov and CORD-19
5587Willingness of Long-Term Care Staff to Receive a COVID-19 Vaccine: A Single State Survey  

N/A

J Am Geriatr Soc2021       LitCov and CORD-19
5588Bean Extract-Based Gargle for Efficient Diagnosis of Active COVID-19 Infection Using Rapid Antigen Tests  

The antigen-based rapid diagnostic test (Ag-RDT) using saliva specimens is fast, noninvasive, and suitable for SARS-CoV-2 self-testing, unlike nasopharyngeal swab (NPS) testing. We evaluated a novel Beanguard gargle (BG)-based virus collection method that can be applied to Ag-RDT as an alternative to the current RT-PCR with an NPS for early diagnosis of COVID-19. This clinical trial comprised 102 COVID-19-positive patients hospitalized after a governmental screening process and 100 healthy individuals. Paired NPS and BG-based saliva specimens from COVID-19 patients and healthy individuals were analyzed using NPS-RT-PCR, BG-RT-PCR, and BG-Ag-RDTs, whose diagnostic performance for detecting SARS-CoV-2 was compared. BG-Ag-RDTs showed high sensitivity (97.8%) and specificity (100%) in 45 patients within 6 days of illness and detected all cases of SARS-CoV-2 Alpha and Delta variants. In 11 asymptomatic active COVID-19 cases, both BG-Ag-RDTs and BG-RT-PCR showed sensitivities and specificities of 100%. Sensitivities of BG-Ag-RDT and BG-RT-PCR toward salivary viral detection were highly concordant, with no discrimination between symptomatic (97.0%), asymptomatic (100%), or SARS-CoV-2 variant (100%) cases. The intermolecular interactions between SARS-CoV-2 spike proteins and truncated canavalin, an active ingredient from the bean extract (BE), were observed in terms of physicochemical properties. The detachment of the SARS-CoV-2 receptor-binding domain from hACE2 increased as the BE concentration increased, allowing the release of the virus from hACE2 for early diagnosis. Using BG-based saliva specimens remarkably enhances the Ag-RDT diagnostic performance as an alternative to NPS and enables noninvasive, rapid, and accurate COVID-19 self-testing and mass screening, supporting efficient COVID-19 management. IMPORTANCE An Ag-RDT is less likely to be accepted as an initial test method for early diagnosis owing to its low sensitivity. However, our self-collection method, Ag-RDT using BG-based saliva specimens, showed significantly enhanced detection sensitivity and specificity toward SARS-CoV-2 including the Alpha and Delta variants in all patients tested within 6 days of illness. The method represents an attractive alternative to nasopharyngeal swabs for the early diagnosis of symptomatic and asymptomatic COVID-19 cases. The evidence suggests that the method could have a potential for mass screening and monitoring of COVID-19 cases.

Microbiol Spectr2022       LitCov and CORD-19
5589The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung injury in Κ18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells  

Acute lung injury (ALI) leading to acute respiratory distress syndrome is the major cause of COVID-19 lethality. Cell entry of SARS-CoV-2 occurs via the interaction between its surface spike protein (SP) and angiotensin-converting enzyme-2 (ACE2). It is unknown if the viral spike protein alone is capable of altering lung vascular permeability in the lungs or producing lung injury in vivo. To that end, we intratracheally instilled the S1 subunit of SARS-CoV-2 spike protein (S1SP) in K18-hACE2 transgenic mice that overexpress human ACE2 and examined signs of COVID-19-associated lung injury 72 h later. Controls included K18-hACE2 mice that received saline or the intact SP and wild-type (WT) mice that received S1SP. K18-hACE2 mice instilled with S1SP exhibited a decline in body weight, dramatically increased white blood cells and protein concentrations in bronchoalveolar lavage fluid (BALF), upregulation of multiple inflammatory cytokines in BALF and serum, histological evidence of lung injury, and activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways in the lung. K18-hACE2 mice that received either saline or SP exhibited little or no evidence of lung injury. WT mice that received S1SP exhibited a milder form of COVID-19 symptoms, compared with the K18-hACE2 mice. Furthermore, S1SP, but not SP, decreased cultured human pulmonary microvascular transendothelial resistance (TER) and barrier function. This is the first demonstration of a COVID-19-like response by an essential virus-encoded protein by SARS-CoV-2 in vivo. This model of COVID-19-induced ALI may assist in the investigation of new therapeutic approaches for the management of COVID-19 and other coronaviruses.

Am J Physiol Lung Cell Mol Phy2021       LitCov and CORD-19
5590Booster dose of COVID-19 mRNA vaccine does not increase risks of myocarditis and pericarditis compared with primary vaccination: New insights from the vaccine adverse event reporting system  

N/A

Front Immunol2022       LitCov
5591Demographic and clinical characteristics associated with variations in antibody response to BNT162b2 COVID-19 vaccination among healthcare workers at an academic medical centre: a longitudinal cohort analysis  

OBJECTIVES: We sought to understand the demographic and clinical factors associated with variations in longitudinal antibody response following completion of two-dose regiment of BNT162b2 vaccination. DESIGN: This study is a 10-month longitudinal cohort study of healthcare workers and serially measured anti-spike protein IgG (IgG-S) antibody levels using mixed linear models to examine their associations with participant characteristics. SETTING: A large, multisite academic medical centre in Southern California, USA. PARTICIPANTS: A total of 843 healthcare workers met inclusion criteria including completion of an initial two-dose course of BNT162b2 vaccination, complete clinical history and at least two blood samples for analysis. Patients had an average age of 45±13 years, were 70% female and 7% with prior SARS-CoV-2 infection. RESULTS: Vaccine-induced IgG-S levels remained in the positive range for 99.6% of individuals up to 10 months after initial two-dose vaccination. Prior SARS-CoV-2 infection was the primary correlate of sustained higher postvaccination IgG-S levels (partial R(2)=0.133), with a 1.74±0.11 SD higher IgG-S response (p<0.001). Female sex (beta 0.27±0.06, p<0.001), younger age (0.01±0.00, p<0.001) and absence of hypertension (0.17±0.08, p=0.003) were also associated with persistently higher IgG-S responses. Notably, prior SARS-CoV-2 infection augmented the associations of sex (−0.42 for male sex, p=0.08) and modified the associations of hypertension (1.17, p=0.001), such that infection-naïve individuals with hypertension had persistently lower IgG-S levels whereas prior infected individuals with hypertension exhibited higher IgG-S levels that remained augmented over time. CONCLUSIONS: While the IgG-S antibody response remains in the positive range for up to 10 months following initial mRNA vaccination in most adults, determinants of sustained higher antibody levels include prior SARS-CoV-2 infection, female sex, younger age and absence of hypertension. Certain determinants of the longitudinal antibody response appear significantly modified by prior infection status. These findings offer insights regarding factors that may influence the ‘hybrid’ immunity conferred by natural infection combined with vaccination.

BMJ Open2022       LitCov and CORD-19
5592Digital Health Strategies to Fight COVID-19 Worldwide: Challenges, Recommendations and a Call for Papers  

The coronavirus disease (COVID-19) pandemic has created an urgent need for coordinated mechanisms to respond to the outbreak across health sectors, and digital health solutions have been identified as promising approaches to address this challenge. This editorial discusses the current situation regarding digital health solutions to fight COVID-19 as well as the challenges and ethical hurdles to broad and long-term implementation of these solutions. To decrease the risk of infection, telemedicine has been used as a successful health care model in both emergency and primary care. Official communication plans should promote facile and diverse channels to inform people about the pandemic and to avoid rumors and reduce threats to public health. Social media platforms such as Twitter and Google Trends analyses are highly beneficial to model pandemic trends as well as to monitor the evolution of patients’ symptoms or public reaction to the pandemic over time. However, acceptability of digital solutions may face challenges due to potential conflicts with users’ cultural, moral, and religious backgrounds. Digital tools can provide collective public health benefits; however, they may be intrusive and can erode individual freedoms or leave vulnerable populations behind. The COVID-19 pandemic has demonstrated the strong potential of various digital health solutions that have been tested during the crisis. More concerted measures should be implemented to ensure that future digital health initiatives will have a greater impact on the epidemic and meet the most strategic needs to ease the life of people who are at the forefront of the crisis.

J Med Internet Res2020       LitCov and CORD-19
5593Virtual screening of approved drugs as potential SARS-CoV-2 main protease inhibitors  

The global emergency caused by COVID-19 makes the discovery of drugs capable of inhibiting SARS-CoV-2 a priority, to reduce the mortality and morbidity of this disease. Repurposing approved drugs can provide therapeutic alternatives that promise rapid and ample coverage because they have a documented safety record, as well as infrastructure for large-scale production. The main protease of SARS-CoV-2 (Mpro) is an excellent therapeutic target because it is critical for viral replication; however, Mpro has a highly flexible active site that must be considered when performing computer-assisted drug discovery. In this work, potential inhibitors of the main protease (Mpro) of SARS-Cov-2 were identified through a docking-assisted virtual screening procedure. A total of 4384 drugs, all approved for human use, were screened against three conformers of Mpro. The ligands were further studied through molecular dynamics simulations and binding free energy analysis. A total of nine currently approved molecules are proposed as potential inhibitors of SARS-CoV-2. These molecules can be further tested to speed the development of therapeutics against COVID-19.

Comput Biol Chem2020       LitCov and CORD-19
5594Reduction in ST-Segment Elevation Cardiac Catheterization Laboratory Activations in the United States During COVID-19 Pandemic  

J Am Coll Cardiol2020       LitCov and CORD-19
5595Unmuting Medical Students' Education: Utilizing Telemedicine During the COVID-19 Pandemic and Beyond  

Due to the coronavirus disease (COVID-19) pandemic, medical schools have paused traditional clerkships, eliminating direct patient encounters from medical students’ education for the immediate future. Telemedicine offers opportunities in a variety of specialties that can augment student education during this time. The projected growth of telemedicine necessitates that students learn new skills to be effective providers. In this viewpoint, we delineate specific telehealth opportunities that teach core competencies for patient care, while also teaching telemedicine-specific skills. Schools can further augment student education through a variety of telemedicine initiatives across multiple medical fields. The explosion of telemedicine programs due to the pandemic can be a catalyst for schools to integrate telemedicine into their current curricula. The depth and variety of telemedicine opportunities allow schools to continue providing high-quality medical education while maintaining social distancing policies.

J Med Internet Res2020       LitCov and CORD-19
5596A radiomics-boosted deep-learning model for COVID-19 and non-COVID-19 pneumonia classification using chest x-ray images  

PURPOSE: To develop a deep learning model design that integrates radiomics analysis for enhanced performance of COVID‐19 and non‐COVID‐19 pneumonia detection using chest x‐ray images. METHODS: As a novel radiomics approach, a 2D sliding kernel was implemented to map the impulse response of radiomic features throughout the entire chest x‐ray image; thus, each feature is rendered as a 2D map in the same dimension as the x‐ray image. Based on each of the three investigated deep neural network architectures, including VGG‐16, VGG‐19, and DenseNet‐121, a pilot model was trained using x‐ray images only. Subsequently, two radiomic feature maps (RFMs) were selected based on cross‐correlation analysis in reference to the pilot model saliency map results. The radiomics‐boosted model was then trained based on the same deep neural network architecture using x‐ray images plus the selected RFMs as input. The proposed radiomics‐boosted design was developed using 812 chest x‐ray images with 262/288/262 COVID‐19/non‐COVID‐19 pneumonia/healthy cases, and 649/163 cases were assigned as training‐validation/independent test sets. For each model, 50 runs were trained with random assignments of training/validation cases following the 7:1 ratio in the training‐validation set. Sensitivity, specificity, accuracy, and ROC curves together with area‐under‐the‐curve (AUC) from all three deep neural network architectures were evaluated. RESULTS: After radiomics‐boosted implementation, all three investigated deep neural network architectures demonstrated improved sensitivity, specificity, accuracy, and ROC AUC results in COVID‐19 and healthy individual classifications. VGG‐16 showed the largest improvement in COVID‐19 classification ROC (AUC from 0.963 to 0.993), and DenseNet‐121 showed the largest improvement in healthy individual classification ROC (AUC from 0.962 to 0.989). The reduced variations suggested improved robustness of the model to data partition. For the challenging non‐COVID‐19 pneumonia classification task, radiomics‐boosted implementation of VGG‐16 (AUC from 0.918 to 0.969) and VGG‐19 (AUC from 0.964 to 0.970) improved ROC results, while DenseNet‐121 showed a slight yet insignificant ROC performance reduction (AUC from 0.963 to 0.949). The achieved highest accuracy of COVID‐19/non‐COVID‐19 pneumonia/healthy individual classifications were 0.973 (VGG‐19)/0.936 (VGG‐19)/ 0.933 (VGG‐16), respectively. CONCLUSIONS: The inclusion of radiomic analysis in deep learning model design improved the performance and robustness of COVID‐19/non‐COVID‐19 pneumonia/healthy individual classification, which holds great potential for clinical applications in the COVID‐19 pandemic.

Med Phys2022       LitCov and CORD-19
5597Radiomics Analysis of Computed Tomography helps predict poor prognostic outcome in COVID-19  

Rationale: Given the rapid spread of COVID-19, an updated risk-stratify prognostic tool could help clinicians identify the high-risk patients with worse prognoses. We aimed to develop a non-invasive and easy-to-use prognostic signature by chest CT to individually predict poor outcome (death, need for mechanical ventilation, or intensive care unit admission) in patients with COVID-19. Methods: From November 29, 2019 to February 19, 2020, a total of 492 patients with COVID-19 from four centers were retrospectively collected. Since different durations from symptom onsets to the first CT scanning might affect the prognostic model, we designated the 492 patients into two groups: 1) the early-phase group: CT scans were performed within one week after symptom onset (0-6 days, n = 317); and 2) the late-phase group: CT scans were performed one week later after symptom onset (≥7 days, n = 175). In each group, we divided patients into the primary cohort (n = 212 in the early-phase group, n = 139 in the late-phase group) and the external independent validation cohort (n = 105 in the early-phase group, n = 36 in the late-phase group) according to the centers. We built two separate radiomics models in the two patient groups. Firstly, we proposed an automatic segmentation method to extract lung volume for radiomics feature extraction. Secondly, we applied several image preprocessing procedures to increase the reproducibility of the radiomics features: 1) applied a low-pass Gaussian filter before voxel resampling to prevent aliasing; 2) conducted ComBat to harmonize radiomics features per scanner; 3) tested the stability of the features in the radiomics signature by several image transformations, such as rotating, translating, and growing/shrinking. Thirdly, we used least absolute shrinkage and selection operator (LASSO) to build the radiomics signature (RadScore). Afterward, we conducted a Fine-Gray competing risk regression to build the clinical model and the clinic-radiomics signature (CrrScore). Finally, performances of the three prognostic signatures (clinical model, RadScore, and CrrScore) were estimated from the two aspects: 1) cumulative poor outcome probability prediction; 2) 28-day poor outcome prediction. We also did stratified analyses to explore the potential association between the CrrScore and the poor outcomes regarding different age, type, and comorbidity subgroups. Results: In the early-phase group, the CrrScore showed the best performance in estimating poor outcome (C-index = 0.850), and predicting the probability of 28-day poor outcome (AUC = 0.862). In the late-phase group, the RadScore alone achieved similar performance to the CrrScore in predicting poor outcome (C-index = 0.885), and 28-day poor outcome probability (AUC = 0.976). Moreover, the RadScore in both groups successfully stratified patients with COVID-19 into low- or high-RadScore groups with significantly different survival time in the training and validation cohorts (all P < 0.05). The CrrScore in both groups can also significantly stratify patients with different prognoses regarding different age, type, and comorbidities subgroups in the combined cohorts (all P < 0.05). Conclusions: This research proposed a non-invasive and quantitative prognostic tool for predicting poor outcome in patients with COVID-19 based on CT imaging. Taking the insufficient medical recourse into account, our study might suggest that the chest CT radiomics signature of COVID-19 is more effective and ideal to predict poor outcome in the late-phase COVID-19 patients. For the early-phase patients, integrating radiomics signature with clinical risk factors can achieve a more accurate prediction of individual poor prognostic outcome, which enables appropriate management and surveillance of COVID-19.

Theranostics2020       LitCov and CORD-19
5598Covid-19 vaccines and variants of concern: A review  

Since the outbreak of coronavirus disease 2019 (Covid‐19) in December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the number of confirmed infections has risen to more than 242 million worldwide, with nearly 5 million deaths. Currently, nine Covid‐19 vaccine candidates based on the original Wuhan‐Hu‐1 strain are at the forefront of vaccine research. All nine had an efficacy over 50% against symptomatic Covid‐19 disease: NVX‐CoV2373 (∼96%), BNT162b2 (∼95%), mRNA‐1273 (∼94%), Sputnik V (∼92%), AZD1222 (∼81%), BBIBP‐CorV (∼79%), Covaxin (∼78%), Ad26.CoV.S (∼66%) and CoronaVac (∼51%). However, vaccine efficacy (VE) can be jeopardised by the rapid emergence and spread of SARS‐CoV‐2 variants of concern (VOCs) that could escape from neutralising antibodies and/or cell‐mediated immunity. Rare adverse events have also been reported soon after administration of viral vector and mRNA vaccines. Although many Covid‐19 vaccines have been developed, additional effective vaccines are still needed to meet the global demand. Promising Covid‐19 vaccines such as WIBP‐CorV, AD5‐nCOV, ZyCoV‐D, CVnCoV, EpiVacCorona and ZF2001 have advanced to clinical studies. This review describes the most relevant mutations in the SARS‐CoV‐2 spike protein, discusses VE against VOCs, presents rare adverse events after Covid‐19 vaccination and introduces some promising Covid‐19 vaccine candidates.

Rev Med Virol2021       LitCov and CORD-19
5599Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships  

The linkage of individuals with obesity and COVID‐19 is controversial and lacks systematic reviews. After a systematic search of the Chinese and English language literature on COVID‐19, 75 studies were used to conduct a series of meta‐analyses on the relationship of individuals with obesity–COVID‐19 over the full spectrum from risk to mortality. A systematic review of the mechanistic pathways for COVID‐19 and individuals with obesity is presented. Pooled analysis show individuals with obesity were more at risk for COVID‐19 positive, >46.0% higher (OR = 1.46; 95% CI, 1.30–1.65; p < 0.0001); for hospitalization, 113% higher (OR = 2.13; 95% CI, 1.74–2.60; p < 0.0001); for ICU admission, 74% higher (OR = 1.74; 95% CI, 1.46–2.08); and for mortality, 48% increase in deaths (OR = 1.48; 95% CI, 1.22–1.80; p < 0.001). Mechanistic pathways for individuals with obesity are presented in depth for factors linked with COVID‐19 risk, severity and their potential for diminished therapeutic and prophylactic treatments among these individuals. Individuals with obesity are linked with large significant increases in morbidity and mortality from COVID‐19. There are many mechanisms that jointly explain this impact. A major concern is that vaccines will be less effective for the individuals with obesity.

Obes Rev2020       LitCov and CORD-19
5600Surviving a global pandemic: The experience of depression, anxiety and loneliness among individuals with multiple sclerosis  

BACKGROUND: The world has been experiencing one of the most significant worldwide health pandemics in modern history. The result has been increased depression, anxiety, and loneliness in the general population. However, populations who demonstrated pre-pandemic emotional disturbance and social isolation, such as individuals with multiple sclerosis (MS), are likely uniquely vulnerable to such symptoms. OBJECTIVE: The purpose of the present investigation was to examine the emotional outcomes, including reports of loneliness, in individuals with MS during the COVID-19 pandemic. We additionally sought to examine how individuals’ experiences during the pandemic may contribute to a specific COVID-19-related depression or anxiety. METHODS: 142 individuals with MS who previously participated in a national, online, survey-based study were asked to complete an online survey assessing their current level of depression, anxiety, loneliness, and perceived impact of the COVID-19 pandemic. RESULTS: Increases in the rates of depression and anxiety were noted, with approximately 54% and 33% reporting “new” depression or anxiety, respectively. Given this increase, we examined how individuals with “new” depression or anxiety differed from those without depression and anxiety and those with pre-pandemic depression and/or anxiety. Significant differences in person-specific factors (e.g., personality, self-efficacy) were noted between the groups. Increased loneliness was also found among both those with depression or anxiety regardless of whether “new” or pre-pandemic. Finally, all those depressed or anxious reported greater disruption and distress related to the COVID-19 pandemic with a trend for increased anxiety specifically related to the pandemic (e.g., fear or dying due to COVID-19) among those with new depression or anxiety when compared to those with existing depression or anxiety, suggesting an influence of the pandemic that is specific to reports of new depression or anxiety. CONCLUSION: Findings suggest increased depression, anxiety, and loneliness among individuals with MS following the COVID-19 pandemic, with reports of “new” depression or anxiety, which appears to be related to the pandemic, specifically. Moreover, factors commonly associated with depression or anxiety in MS (e.g., personality, self-efficacy) were more common among those with existing depression or anxiety but not among those experiencing new depression or anxiety. These differences should be considered when attempting to ameliorate the impact of the COVID-19 among those experiencing emotional distress.

Mult Scler Relat Disord2022       LitCov and CORD-19

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(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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