\ 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
2001Mental health impacts among health workers during COVID-19 in a low resource setting: a cross-sectional survey from Nepal  

BACKGROUND: Health care workers exposed to COVID-19 might be at increased risk of developing mental health problems. The study aimed to identify factors associated with anxiety, depression and insomnia among health workers involved in COVID-19 response in Nepal. METHODS: This was a cross-sectional web-based survey conducted between April 26 and May 12, 2020. A total of 475 health workers participated in the study. Anxiety and depression were measured using a 14-item Hospital Anxiety and Depression Scale (HADS: 0–21) and insomnia was measured by using a 7-item Insomnia Severity Index (ISI: 0–28). Multivariable logistic regression analysis was done to determine the risk factors of mental health outcomes. RESULTS: Overall, 41.9% of health workers had symptoms of anxiety, 37.5% had depression symptoms and 33.9% had symptoms of insomnia. Stigma faced by health workers was significantly associated with higher odds of experiencing symptoms of anxiety (AOR: 2.47; 95% CI: 1.62–3.76), depression (AOR: 2.05; 95% CI: 1.34–3.11) and insomnia (AOR: 2.37; 95% CI: 1.46–3.84). History of medication for mental health problems was significantly associated with a higher likelihood of experiencing symptoms of anxiety (AOR: 3.40; 95% CI:1.31–8.81), depression (AOR: 3.83; 95% CI: 1.45–10.14) and insomnia (AOR: 3.82; 95% CI: 1.52–9.62) while inadequate precautionary measures in the workplace was significantly associated with higher odds of exhibiting symptoms of anxiety (AOR: 1.89; 95% CI: 1.12–3.19) and depression (AOR: 1.97; 95% CI: 1.16–3.37). Nurses (AOR: 2.33; 95% CI: 1.21–4.47) were significantly more likely to experience anxiety symptoms than other health workers. CONCLUSION: The study findings revealed a considerate proportion of anxiety, depression and insomnia symptoms among health workers during the early phase of the pandemic in Nepal. Health workers facing stigma, those with history of medication for mental health problems, and those reporting inadequate precautionary measures in their workplace were more at risk of developing mental health outcomes. A focus on improving mental wellbeing of health workers should be immediately initiated with attention to reduction of stigma, ensuring an adequate support system such as personal protective equipments, and family support for those with history of mental health problems.

Global Health2020       LitCov and CORD-19
2002Characterization of a novel coronavirus associated with severe acute respiratory syndrome  

N/A

Science2003       CORD-19
2003Trajectories of depression and anxiety symptoms during the COVID-19 pandemic in a representative Australian adult cohort  

OBJECTIVES: To estimate initial levels of symptoms of depression and anxiety, and their changes during the early months of the COVID‐19 pandemic in Australia; to identify trajectories of symptoms of depression and anxiety; to identify factors associated with these trajectories. DESIGN, SETTING, PARTICIPANTS: Longitudinal cohort study; seven fortnightly online surveys of a representative sample of 1296 Australian adults from the beginning of COVID‐19‐related restrictions in late March 2020 to mid‐June 2020. MAIN OUTCOME MEASURES: Symptoms of depression and anxiety, measured with the Patient Health Questionnaire (PHQ‐9) depression and Generalised Anxiety Disorder (GAD‐7) scales; trajectories of symptom change. RESULTS: Younger age, being female, greater COVID‐19‐related work and social impairment, COVID‐19‐related financial distress, having a neurological or mental illness diagnosis, and recent adversity were each significantly associated with higher baseline depression and anxiety scores. Growth mixture models identified three latent trajectories for depression symptoms (low throughout the study, 81% of participants; moderate throughout the study, 10%; initially severe then declining, 9%) and four for anxiety symptoms (low throughout the study, 77%; initially moderate then increasing, 10%; initially moderate then declining, 5%; initially mild then increasing before again declining, 8%). Factors statistically associated with not having a low symptom trajectory included mental disorder diagnoses, COVID‐19‐related financial distress and social and work impairment, and bushfire exposure. CONCLUSION: Our longitudinal data enabled identification of distinct symptom trajectories during the first three months of the COVID‐19 pandemic in Australia. Early intervention to ensure that vulnerable people are clinically and socially supported during a pandemic should be a priority.

Med J Aust2021       LitCov and CORD-19
2004Emergency Physician Twitter Use in the COVID-19 Pandemic as a Potential Predictor of Impending Surge: Retrospective Observational Study  

BACKGROUND: The early conversations on social media by emergency physicians offer a window into the ongoing response to the COVID-19 pandemic. OBJECTIVE: This retrospective observational study of emergency physician Twitter use details how the health care crisis has influenced emergency physician discourse online and how this discourse may have use as a harbinger of ensuing surge. METHODS: Followers of the three main emergency physician professional organizations were identified using Twitter’s application programming interface. They and their followers were included in the study if they identified explicitly as US-based emergency physicians. Statuses, or tweets, were obtained between January 4, 2020, when the new disease was first reported, and December 14, 2020, when vaccination first began. Original tweets underwent sentiment analysis using the previously validated Valence Aware Dictionary and Sentiment Reasoner (VADER) tool as well as topic modeling using latent Dirichlet allocation unsupervised machine learning. Sentiment and topic trends were then correlated with daily change in new COVID-19 cases and inpatient bed utilization. RESULTS: A total of 3463 emergency physicians produced 334,747 unique English-language tweets during the study period. Out of 3463 participants, 910 (26.3%) stated that they were in training, and 466 of 902 (51.7%) participants who provided their gender identified as men. Overall tweet volume went from a pre-March 2020 mean of 481.9 (SD 72.7) daily tweets to a mean of 1065.5 (SD 257.3) daily tweets thereafter. Parameter and topic number tuning led to 20 tweet topics, with a topic coherence of 0.49. Except for a week in June and 4 days in November, discourse was dominated by the health care system (45,570/334,747, 13.6%). Discussion of pandemic response, epidemiology, and clinical care were jointly found to moderately correlate with COVID-19 hospital bed utilization (Pearson r=0.41), as was the occurrence of “covid,” “coronavirus,” or “pandemic” in tweet texts (r=0.47). Momentum in COVID-19 tweets, as demonstrated by a sustained crossing of 7- and 28-day moving averages, was found to have occurred on an average of 45.0 (SD 12.7) days before peak COVID-19 hospital bed utilization across the country and in the four most contributory states. CONCLUSIONS: COVID-19 Twitter discussion among emergency physicians correlates with and may precede the rising of hospital burden. This study, therefore, begins to depict the extent to which the ongoing pandemic has affected the field of emergency medicine discourse online and suggests a potential avenue for understanding predictors of surge.

J Med Internet Res2021       LitCov and CORD-19
2005Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients  

BACKGROUND: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19–related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19–related medically attended visit or death from any cause by day 28. RESULTS: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19–related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P=0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19–related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.)

N Engl J Med2021       LitCov and CORD-19
2006Mental Health-Related Emergency Department Visits Among Children Aged <18 Years During the COVID-19 Pandemic-United States, January 1-October 17, 2020  

Published reports suggest that the coronavirus disease 2019 (COVID-19) pandemic has had a negative effect on children's mental health (1,2). Emergency departments (EDs) are often the first point of care for children experiencing mental health emergencies, particularly when other services are inaccessible or unavailable (3). During March 29-April 25, 2020, when widespread shelter-in-place orders were in effect, ED visits for persons of all ages declined 42% compared with the same period in 2019; during this time, ED visits for injury and non-COVID-19-related diagnoses decreased, while ED visits for psychosocial factors increased (4). To assess changes in mental health-related ED visits among U.S. children aged <18 years, data from CDC's National Syndromic Surveillance Program (NSSP) from January 1 through October 17, 2020, were compared with those collected during the same period in 2019. During weeks 1-11 (January 1-March 15, 2020), the average reported number of children's mental health-related ED visits overall was higher in 2020 than in 2019, whereas the proportion of children's mental health-related visits was similar. Beginning in week 12 (March 16) the number of mental health-related ED visits among children decreased 43% concurrent with the widespread implementation of COVID-19 mitigation measures; simultaneously, the proportion of mental health-related ED visits increased sharply beginning in mid-March 2020 (week 12) and continued into October (week 42) with increases of 24% among children aged 5-11 years and 31% among adolescents aged 12-17 years, compared with the same period in 2019. The increased proportion of children's mental health-related ED visits during March-October 2020 might be artefactually inflated as a consequence of the substantial decrease in overall ED visits during the same period and variation in the number of EDs reporting to NSSP. However, these findings provide initial insight into children's mental health in the context of the COVID-19 pandemic and highlight the importance of continued monitoring of children's mental health throughout the pandemic, ensuring access to care during public health crises, and improving healthy coping strategies and resiliency among children and families.

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
2007COVID-19 in Heart Transplant Recipients: A Multicenter Analysis of the Northern Italian Outbreak  

Aims The aim of this study was to assess the clinical course and outcomes of all heart transplant recipients affected by COVID-19 who were followed at the leading heart transplant centers of Northern Italy. Method and Results Since February 2020, we enrolled all 47 cases (79% male) in a first cohort of patients, with a mean age of 61.8 ± 14.5 years, who tested positive for SARS-CoV-2, out of 2676 heart transplant recipients alive before the onset of the COVID-19 pandemic at 7 heart transplant centers in Northern Italy. To date, 38 patients required hospitalization while 9 remained self-home quarantined and 14 died. Compared to the general population, prevalence (18 vs 7 cases per 1000) and related case fatality rate (29.7 vs 15.4%) in heart transplant recipients were doubled. Univariable analysis showed older age (p=0.002), diabetes mellitus (p=0.040), extracardiac arteriopathy (p=0.040), previous PCI (p=0.040), CAV score (p=0.039), lower GFR (p=0.004), and higher NYHA classes (p=0.023) were all significantly associated with in-hospital mortality. During the follow-up two patients died and a third patient has prolonged viral-shedding alternating positive and negative swabs. Since 1st July 2020, we had 6 new patients who tested positive for SARS-CoV-2, 5 patients asymptomatic were self-quarantined, while 1 is still hospitalized for pneumonia. A standard therapy was maintained for all, except for the hospitalized patient. Conclusion The prevalence and mortality of SARS-CoV-2 should spur clinicians to immediately refer heart transplant recipients suspected as having SARS-CoV2 infection to centers specializing in the care of this vulnerable population.

JACC Heart Fail2020       LitCov and CORD-19
2008Inflammation and Platelet Activation After COVID-19 Vaccines-Possible Mechanisms Behind Vaccine induced Immune Thrombocytopenia and Thrombosis  

Introduction of vaccines against COVID-19 has provided the most promising chance to control the world-wide COVID-19 pandemic. However, the adenovirus-vector based Oxford/AstraZeneca [ChAdOx1] (AZ) and Johnson & Johnson [Ad26.CoV2.S] COVID-19 vaccines have been linked with serious thromboembolic events combined with thrombocytopenia, denominated Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). The pathogenesis of COVID-19 VITT remain incompletely understood; especially the initial events that trigger platelet activation, platelet factor (PF)4 release, complex formation and PF4 antibody production are puzzling. This is a prospective study investigating the impact of different COVID-19 vaccines on inflammation (CRP, TNF-α, IL-1β, IL-6, IL-8, IL-10), vascular endothelial activation (syndecan-1, thrombomodulin, E-selectin, ICAM-1, ICAM-3, VCAM-1), platelet activation (P-selectin, TGF-β, sCD40L) and aggregation (Multiplate(®) impedance aggregometry), whole blood coagulation (ROTEM(®)), thrombin generation and PF4 antibodies to reveal potential differences between AZ and mRNA vaccines in individuals without VITT. The study included 80 (55 AZ and 55 mRNA) vaccinated individuals and 55 non-vaccinated age- and gender matched healthy controls. The main findings where that both vaccines enhanced inflammation and platelet activation, though AZ vaccination induced a more pronounced increase in several inflammatory and platelet activation markers compared to mRNA vaccination and that post-vaccination thrombin generation was higher following AZ vaccination compared to mRNA vaccination. No difference in neither the PF4 antibody level nor the proportion of individuals with positive PF4 antibodies were observed between the vaccine groups. This is the first study to report enhanced inflammation, platelet activation and thrombin generation following AZ vaccination compared to mRNA vaccination in a head-to-head comparison. We speculate that specific components of the AZ adenovirus vector may serve as initial trigger(s) of (hyper)inflammation, platelet activation and thrombin generation, potentially lowering the threshold for a cascade of events that both trigger complications related to excessive inflammation, platelet and coagulation activation as observed in epidemiological studies and promote development of VITT when combined with high-titer functionally active PF4 antibodies.

Front Immunol2021       LitCov and CORD-19
2009Evaluation of a Novel e-Learning Program for Physiotherapists to Manage Knee Osteoarthritis via Telehealth: Qualitative Study Nested in the PEAK (Physiotherapy Exercise and Physical Activity for Knee Osteoarthritis) Randomized Controlled Trial  

BACKGROUND: The delivery of physiotherapy via telehealth could provide more equitable access to services for patients. Videoconference-based telehealth has been shown to be an effective and acceptable mode of service delivery for exercise-based interventions for chronic knee pain; however, specific training in telehealth is required for physiotherapists to effectively and consistently deliver care using telehealth. The development and evaluation of training programs to upskill health care professionals in the management of osteoarthritis (OA) has also been identified as an important priority to improve OA care delivery. OBJECTIVE: This study aims to explore physiotherapists’ experiences with and perceptions of an e-learning program about best practice knee OA management (focused on a structured program of education, exercise, and physical activity) that includes telehealth delivery via videoconferencing. METHODS: We conducted a qualitative study using individual semistructured telephone interviews, nested within the Physiotherapy Exercise and Physical Activity for Knee Osteoarthritis randomized controlled trial, referred to as the PEAK trial. A total of 15 Australian physiotherapists from metropolitan and regional private practices were interviewed following the completion of an e-learning program. The PEAK trial e-learning program involved self-directed learning modules, a mock video consultation with a researcher (simulated patient), and 4 audited practice video consultations with pilot patients with chronic knee pain. Interviews were audio recorded and transcribed verbatim. Data were thematically analyzed. RESULTS: A total of five themes (with associated subthemes) were identified: the experience of self-directed e-learning (physiotherapists were more familiar with in-person learning; however, they valued the comprehensive, self-paced web-based modules. Unwieldy technological features could be frustrating); practice makes perfect (physiotherapists benefited from the mock consultation with the researcher and practice sessions with pilot patients alongside individualized performance feedback, resulting in confidence and preparedness to implement new skills); the telehealth journey (although inexperienced with telehealth before training, physiotherapists were confident and able to deliver remote care following training; however, they still experienced some technological challenges); the whole package (the combination of self-directed learning modules, mock consultation, and practice consultations with pilot patients was felt to be an effective learning approach, and patient information booklets supported the training package); and impact on broader clinical practice (training consolidated and refined existing OA management skills and enabled a switch to telehealth when the COVID-19 pandemic affected in-person clinical care). CONCLUSIONS: Findings provide evidence for the perceived effectiveness and acceptability of an e-learning program to train physiotherapists (in the context of a clinical trial) on best practice knee OA management, including telehealth delivery via videoconferencing. The implementation of e-learning programs to upskill physiotherapists in telehealth appears to be warranted, given the increasing adoption of telehealth service models for the delivery of clinical care.

J Med Internet Res2021       LitCov and CORD-19
2010The neuroinvasive potential of SARS-CoV-2 may play a role in the respiratory failure of COVID-19 patients  

Following the severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV), another highly pathogenic coronavirus named SARS‐CoV‐2 (previously known as 2019‐nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS‐CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID‐19) with clinical symptoms similar to those reported for SARS‐CoV and MERS‐CoV. The most characteristic symptom of patients with COVID‐19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID‐19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse‐connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS‐CoV and SARS‐CoV2, it remains to make clear whether the potential invasion of SARS‐CoV2 is partially responsible for the acute respiratory failure of patients with COVID‐19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS‐CoV‐2‐induced respiratory failure.

J Med Virol2020       LitCov and CORD-19
2011Seroprevalence of anti-SARS-CoV-2 IgG Antibodies in the Staff of a Public School System in the Midwestern United States  

BACKGROUND: Since March 2020, the United States has lost over 200,000 lives to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. A growing body of literature describes population-level SARS-CoV-2 exposure, but studies of antibody seroprevalence within school systems are critically lacking, hampering evidence-based discussions on school reopenings. The Lake Central School Corporation (LCSC), a public school system in suburban Indiana, USA, assessed SARS-CoV-2 seroprevalence in its staff and identified correlations between seropositivity and subjective histories and demographics. METHODS: This study is a cross-sectional, population-based analysis of the seroprevalence of SARS-CoV-2 in LCSC staff measured in July 2020. We tested for seroprevalence with the Abbott Alinity™ SARS-CoV-2 IgG antibody test. The primary outcome was the total seroprevalence of SARS-CoV-2, and secondary outcomes included trends of antibody presence in relation to baseline attributes. FINDINGS: 753 participants representative of the staff at large were enrolled. 22 participants (2·9%, 95% CI: 1·8% – 4·4%) tested positive for SARS-CoV-2 antibodies. Correcting for test performance parameters, the seroprevalence is estimated at 1·7% (90% Credible Interval: 0·27% – 3·3%). Multivariable logistic regression including mask wearing, travel history, symptom history, and contact history revealed a 48-fold increase in the odds of seropositivity if an individual previously tested positive for COVID-19 (OR: 48.2, 95% CI: 4 – 600). Amongst individuals with no previous positive test, exposure to a person diagnosed with COVID-19 increased the odds of seropositivity by 7-fold (OR: 6.5, 95% CI: 2.06 – 18.9). INTERPRETATION: Assuming the presence of antibodies is associated with immunity against SARS-CoV-2 infection, these results demonstrate a broad lack of herd immunity amongst the school corporation’s staff irrespective of employment role or location. Protective measures like contact tracing face coverings, and social distancing are therefore vital to maintaining the safety of both students and staff as the school year progresses. FUNDING: Lake Central School Corporation

medRxiv2020       CORD-19
2012Birth and Infant Outcomes Following Laboratory-Confirmed SARS-CoV-2 Infection in Pregnancy-SET-NET, 16 Jurisdictions, March 29-October 14, 2020  

Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness and might be at risk for preterm birth (1-3). The full impact of infection with SARS-CoV-2, the virus that causes COVID-19, in pregnancy is unknown. Public health jurisdictions report information, including pregnancy status, on confirmed and probable COVID-19 cases to CDC through the National Notifiable Diseases Surveillance System.* Through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET), 16 jurisdictions collected supplementary information on pregnancy and infant outcomes among 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29-October 14, 2020. Among 3,912 live births with known gestational age, 12.9% were preterm (<37 weeks), higher than the reported 10.2% among the general U.S. population in 2019 (4). Among 610 infants (21.3%) with reported SARS-CoV-2 test results, perinatal infection was infrequent (2.6%) and occurred primarily among infants whose mother had SARS-CoV-2 infection identified within 1 week of delivery. Because the majority of pregnant women with COVID-19 reported thus far experienced infection in the third trimester, ongoing surveillance is needed to assess effects of infections in early pregnancy, as well the longer-term outcomes of exposed infants. These findings can inform neonatal testing recommendations, clinical practice, and public health action and can be used by health care providers to counsel pregnant women on the risks of SARS-CoV-2 infection, including preterm births. Pregnant women and their household members should follow recommended infection prevention measures, including wearing a mask, social distancing, and frequent handwashing when going out or interacting with others or if there is a person within the household who has had exposure to COVID-19.†.

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
2013Humoral Response in Hemodialysis Patients Following COVID-19 Vaccination and Breakthrough Infections during Delta and Omicron Variant Predominance  

Background: The advancement of COVID-19 vaccination programs globally has been viewed as an integral strategy to reduce both the number of COVID-19 cases and consequential complications of COVID-19, particularly for high-risk patient groups. There are limited data on the antibody response and protection from disease infection and severity in patients requiring hemodialysis (HD) following COVID-19 vaccination during the Delta and Omicron variant predominance. We conducted a study aiming to evaluate humoral immunity derived from two different COVID-19 vaccines administered to our in-centre HD population and investigated the characteristics of breakthrough COVID-19 infections occurring post-vaccination within this population. Methods: This is a prospective observational study including patients receiving HD at Salford Royal Hospital. The first and second doses of COVID-19 vaccinations (Pfizer BioNTech BNT162b2 or Oxford AstraZeneca ChAdOx1 nCoV-19) were administered to this patient cohort since January 2021. The incidence of any breakthrough COVID-19 infections occurring in double vaccinated patients between 1 April 2021 and 15 January 2022 was recorded. Patients were screened weekly with nasal and pharyngeal nasopharyngeal swabs for real-time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) for COVID-19, whilst SARS-CoV-2 antibody testing was performed alongside monthly routine HD bloods. Results: Four hundred eleven patients receiving HD were included in this study, of which 170 of 178 patients (95.5%) with available data on antibody status following two doses of the Pfizer BioNTech BNT162b2 vaccination had detectable antibody response, whilst this was the case for 97 of 101 patients (96.1%) who received two doses of the Oxford AstraZeneca ChAdOx1 nCoV-19 vaccine. For 12 seronegative patients who received a booster vaccine (third dose), nine seroconverted, while one remained negative and two were not tested. No statistically significant differences were observed with regards to antibody status between those receiving Pfizer BioNTech BNT162b2 and Oxford AstraZeneca ChAdOx1 nCoV-19 vaccines. Sixty-three of 353 patients with two doses of COVID-19 vaccination had breakthrough COVID-19 infection (40 during Delta and 23 during Omicron variant predominance). Of the 40 patients during the delta period, five were admitted into hospital and there were two reported deaths due to COVID-19-related illness. There were no COVID-19 associated hospitalizations or deaths during the Omicron variant predominance. Conclusions: The vast majority of HD patients who received two doses of the Pfizer BioNTech BNT162b2 or Oxford AstraZeneca ChAdOx1 nCoV-19 vaccinations developed detectable antibody responses. Our results support the value of booster vaccination with mRNA-based COVID-19 vaccine in HD patients and highlight the need for ongoing surveillance programmes with rRT-PCR and antibody testing for timely detection of positive cases.

Vaccines (Basel)2022       LitCov and CORD-19
2014The perspective of undergraduate dental students on web-based learning in pediatric dentistry during the COVID-19 pandemic: a Korean multicenter cross-sectional survey  

BACKGROUND: The COVID-19 pandemic changed the world and created a shift in the dental education program. This sudden change in the dental education program may have affected the academic standards of dental students. This study aimed to evaluate the overall satisfaction and effectiveness of online learning in pediatric dentistry of undergraduate dental students’ during the COVID-19 pandemic in South Korea. METHODS: An anonymous online survey was sent to three dental schools, and responses were collected from dental school students. Questions included the demographics, perspectives of online classes, comparison of online and offline pediatric dentistry classes and opinions on how dental schools are handling the pandemic. Students’ perspectives on online classes were evaluated based on satisfaction with online education. Data were analyzed using the Kruskal-Wallis test and the Mann-Whitney U test. RESULTS: Most students took online classes from home (80.9%) using Zoom (50.4%). The majority reported overall program satisfaction (74.1%) and agreed that universities implemented online classes well (55%). Students who were in favor of online classes responded more positively to questions on the effectiveness and safety of online learning (p < 0.05). Regardless of satisfaction with online education, the students agreed that the online education shift was the right decision in pandemic outbreak. CONCLUSIONS: Dental students in South Korea preferred and adapted well to the web-based learning program in pediatric dentistry during COVID-19 pandemic.

BMC Med Educ2021       LitCov and CORD-19
2015Comparison of COVID-19 laboratory diagnosis by commercial kits: Effectivity of RT-PCR to the RT-LAMP  

Coronavirus disease 2019 or COVID‐19 caused by novel coronavirus/severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 or 2019‐nCoV) is an ongoing pandemic that has emerging global effects and requires rapid and reliable diagnostic testing. Quantitative reverse transcription‐polymerase chain reaction (q‐RT‐PCR) is the gold standard method for SARS‐CoV‐2 detections. On the other hand, new approaches remedy the diagnosis difficulties gradually. Reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) as one of these novel approaches may also contribute to faster and cheaper field‐based testing. The present study was designed to evaluate this rapid screening diagnostic test that can give results in 30–45 min and to compare the effectiveness of LAMP to the q‐RT‐PCR. The 30 randomly chosen patient samples were generated by nasopharyngeal swabs with a portion of the SARS‐CoV‐2 nucleic sequence. The sample of quantification cycle (Cq) values was tested using RT‐LAMP as well as by conventional q‐RT‐PCR. The patient samples were tested with four different kits (SENSObiz COVID‐19 [SARS‐CoV‐2] LAMP Assay, the QIAseq DIRECT SARS‐CoV‐2 kit, Biospeedy SARS‐CoV‐2 Variant Plus kit, and CoVirion‐CV19‐2 SARS‐CoV‐2 OneStep RT‐PCR kit) and two different PCR devices (GDS Rotor‐Gene Q Thermocycler and Inovia Technologies GenX series). Based on 30 patient samples, the positive/negative ratio (P/N) was 30/0 as Biospeedy and Covirion (positivity 100%), 28/2 as Qiagen kit (positivity 93.3%) for the samples studied on the Inovia device while the same samples on the Rotor‐Gene device were 30/0 as Biospeedy and Covirion (positivity 100%), 29/1 as Qiagen kit at the first day (96.7%). On the fifth day, the samples were studied in the Inovia device and the respective results were obtained: 27/3 as Biospeedy (positivity 90%), 16/14 as Qiagen (positivity 53.3%), 28/2 as Covirion kit (positivity 93.3%). When these samples were studied in the Rotor‐Gene device, it was 29/1 in Biospeedy and Covirion (positivity 96.7%), 19/11 in the Qiagen kit (positivity 63.3%). When these samples were compared with the LAMP method it was found to be 19/11 (positivity 63.3%) on the first day and 18/12 (positivity 60%) on the fifth day. SARS‐CoV‐2 test studies will contribute to a proactive approach to the development of rapid diagnosis systems. The LAMP approach presents promising results to monitor exposed individuals and also improves screening efforts in potential ports of entry.

J Med Virol2022       LitCov and CORD-19
2016Obesity in patients with COVID-19: a systematic review and meta-analysis  

BACKGROUND: Obesity is common in patients with coronavirus disease 2019 (COVID-19). The effects of obesity on clinical outcomes of COVID-19 warrant systematical investigation. OBJECTIVE: This study explores the effects of obesity with the risk of severe disease among patients with COVID-19. METHODS: Body mass index (BMI) and degree of visceral adipose tissue (VAT) accumulation were used as indicators for obesity status. Publication databases including preprints were searched up to August 10, 2020. Clinical outcomes of severe COVID-19 included hospitalization, a requirement for treatment in an intensive care unit (ICU), invasive mechanical ventilation (IMV), and mortality. Risks for severe COVID-19 outcomes are presented as odds ratios (OR) and 95% confidence interval (95%CI) for cohort studies with BMI-defined obesity, and standardized mean difference (SMD) and 95%CI for controlled studies with VAT-defined excessive adiposity. RESULTS: A total of 45, 650 participants from 30 studies with BMI-defined obesity and 3 controlled studies with VAT-defined adiposity were included for assessing the risk of severe COVID-19. Univariate analyses showed significantly higher ORs of severe COVID-19 with higher BMI: 1.76 (95%: 1.21, 2.56, P = 0.003) for hospitalization, 1.67 (95%CI: 1.26, 2.21, P<0.001) for ICU admission, 2.19 (95%CI: 1.56, 3.07, P<0.001) for IMV requirement, and 1.37 (95%CI: 1.06, 1.75, P = 0.014) for death, giving an overall OR for severe COVID-19 of 1.67 (95%CI: 1.43, 1.96; P<0.001). Multivariate analyses revealed increased ORs of severe COVID-19 associated with higher BMI: 2.36 (95%CI: 1.37, 4.07, P = 0.002) for hospitalization, 2.32 (95%CI: 1.38, 3.90, P = 0.001) for requiring ICU admission, 2.63 (95%CI: 1.32, 5.25, P = 0.006) for IMV support, and 1.49 (95%CI: 1.20, 1.85, P<0.001) for mortality, giving an overall OR for severe COVID-19 of 2.09 (95%CI: 1.67, 2.62; P<0.001). Compared to non-severe COVID-19 patients, severe COVID-19 cases showed significantly higher VAT accumulation with a SMD of 0.49 for hospitalization (95% CI: 0.11, 0.87; P = 0.011), 0.57 (95% CI: 0.33, 0.81; P<0.001) for requiring ICU admission and 0.37 (95% CI: 0.03, 0.71; P = 0.035) for IMV support. The overall SMD for severe COVID-19 was 0.50 (95% CI: 0.33, 0.68; P<0.001). CONCLUSIONS: Obesity increases risk for hospitalization, ICU admission, IMV requirement and death among patients with COVID-19. Further, excessive visceral adiposity appears to be associated with severe COVID-19 outcomes. These findings emphasize the need for effective actions by individuals, the public and governments to increase awareness of the risks resulting from obesity and how these are heightened in the current global pandemic.

Metabolism2020       LitCov and CORD-19
2017Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients  

PURPOSE: The length of time a critically ill coronavirus disease 2019 (COVID-19) patient remains infectious and should therefore be isolated remains unknown. This prospective study was undertaken in critically ill patients to evaluate the reliability of single negative real-time polymerase chain reaction (RT-PCR) in lower tracheal aspirates (LTA) in predicting a second negative test and to analyze clinical factors potentially influencing the viral shedding. METHODS: From April 9, 2020 onwards, intubated COVID-19 patients treated in the intensive care unit were systematically evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR of nasopharyngeal swabs and LTA. The time to negativity was defined as the time between the onset of symptoms and the viral clearance in LTA. In order to identify risk factors for prolonged viral shedding, we used univariate and multivariate Cox proportional hazards models. RESULTS: Forty-eight intubated SARS-CoV-2 patients were enrolled. Overall, we observed that the association of the first negative RT-PCR with a second negative result was 96.7%. Median viral shedding was 25 (IQR: 21.5–28) days since symptoms’ onset. In the univariate Cox model analysis, type 2 diabetes mellitus was associated with a prolonged viral RNA shedding (hazard ratio [HR]: 0.41, 95% CI: 0.06–3.11, p = 0.04). In the multivariate Cox model analysis, type 2 diabetes was associated with a prolonged viral RNA shedding (HR: 0.31, 95% CI: 0.11–0.89, p = 0.029). CONCLUSION: Intubated patients with type 2 diabetes mellitus may have prolonged SARS-CoV-2 shedding. In critically ill COVID-19 patients, one negative LTA should be sufficient to assess and exclude infectivity.

Endocrine2020       LitCov and CORD-19
2018Analysis of a persistent viral shedding patient infected with SARS-CoV-2 by RT-qPCR, FilmArray Respiratory Panel v2.1 and antigen detection  

Various diagnostic tests utilizing different principles are currently under development for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, these tests can occasionally produce discrepant results, causing confusion in their interpretation. Here, we evaluated the performance and features of three diagnostic assays: quantitative reverse transcription polymerase chain reaction (RT-qPCR), FilmArray Respiratory Panel (RP) v2.1, and the LUMIPULSE antigen test. Twenty-seven serial nasopharyngeal swabs were collected from a prolonged viral shedding patient who had been hospitalized for 51 days. We examined the SARS-CoV-2 detection rates of the three tests. The overall agreement rate was 81% between RT-qPCR and FilmArray RP v2.1, 63% between the antigen test and FilmArray RP v2.1, and 59% between the antigen test and RT-qPCR. We obtained concordant results in samples with high viral loads (low threshold cycle values) by all three tests. RT-qPCR and FilmArray RP v2.1 accurately detected SARS-CoV-2 at the early to intermediate phases of infection, but the results varied at the late phase. The antigen test also produced a positive result at the early phase but varied at the intermediate phase and consistently produced negative results at late phase of infection. These results demonstrated FilmArray RP v2.1 could detect SARS-CoV-2 with accuracy comparable to RT-qPCR. Further, there were discrepant results using different types of diagnostic tests during the clinical course of prolonged viral shedding patient. We provided insights into how to utilize different types of kits to assess and manage SARS-CoV-2 infections.

J Infect Chemother2020       LitCov and CORD-19
2019Performance of Abbott ID Now COVID-19 Rapid Nucleic Acid Amplification Test Using Nasopharyngeal Swabs Transported in Viral Transport Media and Dry Nasal Swabs in a New York City Academic Institution  

The recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real-time reverse transcription-PCR (RT-PCR) platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. The two platforms demonstrate comparable performances; however, the run times for each assay are 3.5 h and 45 min, respectively. In search for a platform with a shorter turnaround time, we sought to evaluate the recently released Abbott ID Now COVID-19 assay, which is capable of producing positive results in as little as 5 min. We present here the results of comparisons between Abbott ID Now COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID Now COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID Now. Regardless of method of collection and sample type, Abbott ID Now COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.

J Clin Microbiol2020       LitCov and CORD-19
2020Headaches Associated With Personal Protective Equipment-A Cross-Sectional Study Among Frontline Healthcare Workers During COVID-19  

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Headache2020       LitCov and CORD-19
2021Reduced humoral response 3 months following BNT162b2 vaccination in SARS-CoV-2 uninfected residents of long-term care facilities  

BACKGROUND: SARS-CoV-2 vaccination is the most effective strategy to protect older residents of long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterised the humoral responses of institutionalised seniors 3 months after they had received the mRNA/BNT162b2 vaccine. METHODS: plasma levels of SARS-CoV-2-specific total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in older residents of LTCF. Neutralisation capacity was assessed in a pseudovirus neutralisation assay against the original WH1 and later B.1.617.2/Delta variants. A group of younger adults was used as a reference group. RESULTS: three months after vaccination, uninfected older adults presented reduced SARS-CoV-2-specific IgG levels and a significantly lower neutralisation capacity against the WH1 and Delta variants compared with vaccinated uninfected younger individuals. In contrast, COVID-19-recovered older adults showed significantly higher SARS-CoV-2-specific IgG levels after vaccination than their younger counterparts, whereas showing similar neutralisation activity against the WH1 virus and an increased neutralisation capacity against the Delta variant. Although, similarly to younger individuals, previously infected older adults elicit potent cross-reactive immune responses, higher quantities of SARS-CoV-2-specific IgG antibodies are required to reach the same neutralisation levels. CONCLUSIONS: although hybrid immunity seems to be active in previously infected older adults 3 months after mRNA/BNT162b2 vaccination, humoral immune responses are diminished in COVID-19 uninfected but vaccinated older residents of LTCF. These results suggest that a vaccine booster dose should be prioritised for this particularly vulnerable population.

Age Ageing2022       LitCov and CORD-19
2022Coronavirus as a possible cause of severe acute respiratory syndrome  

BACKGROUND: An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. METHODS: We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. FINDINGS: Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. INTERPRETATION: A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.

Lancet2003       CORD-19
2023Knowledge, attitudes and practices towards COVID-19 among Chinese residents during the rapid rise period of the COVID-19 outbreak: a quick online cross-sectional survey  

Unprecedented measures have been adopted to control the rapid spread of the ongoing COVID-19 epidemic in China. People's adherence to control measures is affected by their knowledge, attitudes, and practices (KAP) towards COVID-19. In this study, we investigated Chinese residents' KAP towards COVID-19 during the rapid rise period of the outbreak. An online sample of Chinese residents was successfully recruited via the authors' networks with residents and popular media in Hubei, China. A self-developed online KAP questionnaire was completed by the participants. The knowledge questionnaire consisted of 12 questions regarding the clinical characteristics and prevention of COVID-19. Assessments on residents' attitudes and practices towards COVID-19 included questions on confidence in winning the battle against COVID-19 and wearing masks when going out in recent days. Among the survey completers (n=6910), 65.7% were women, 63.5% held a bachelor degree or above, and 56.2% engaged in mental labor. The overall correct rate of the knowledge questionnaire was 90%. The majority of the respondents (97.1%) had confidence that China can win the battle against COVID-19. Nearly all of the participants (98.0%) wore masks when going out in recent days. In multiple logistic regression analyses, the COVID-19 knowledge score (OR: 0.75-0.90, P<0.001) was significantly associated with a lower likelihood of negative attitudes and preventive practices towards COVID-2019. Most Chinese residents of a relatively high socioeconomic status, in particular women, are knowledgeable about COVID-19, hold optimistic attitudes, and have appropriate practices towards COVID-19. Health education programs aimed at improving COVID-19 knowledge are helpful for Chinese residents to hold optimistic attitudes and maintain appropriate practices. Due to the limited sample representativeness, we must be cautious when generalizing these findings to populations of a low socioeconomic status.

Int J Biol Sci2020       LitCov and CORD-19
2024The Development and Validation of Simplified Machine Learning Algorithms to Predict Prognosis of Hospitalized Patients With COVID-19: Multicenter, Retrospective Study  

BACKGROUND: The current COVID-19 pandemic is unprecedented; under resource-constrained settings, predictive algorithms can help to stratify disease severity, alerting physicians of high-risk patients; however, there are only few risk scores derived from a substantially large electronic health record (EHR) data set, using simplified predictors as input. OBJECTIVE: The objectives of this study were to develop and validate simplified machine learning algorithms that predict COVID-19 adverse outcomes; to evaluate the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and calibration of the algorithms; and to derive clinically meaningful thresholds. METHODS: We performed machine learning model development and validation via a cohort study using multicenter, patient-level, longitudinal EHRs from the Optum COVID-19 database that provides anonymized, longitudinal EHR from across the United States. The models were developed based on clinical characteristics to predict 28-day in-hospital mortality, intensive care unit (ICU) admission, respiratory failure, and mechanical ventilator usages at inpatient setting. Data from patients who were admitted from February 1, 2020, to September 7, 2020, were randomly sampled into development, validation, and test data sets; data collected from September 7, 2020, to November 15, 2020, were reserved as the postdevelopment prospective test data set. RESULTS: Of the 3.7 million patients in the analysis, 585,867 patients were diagnosed or tested positive for SARS-CoV-2, and 50,703 adult patients were hospitalized with COVID-19 between February 1 and November 15, 2020. Among the study cohort (n=50,703), there were 6204 deaths, 9564 ICU admissions, 6478 mechanically ventilated or EMCO patients, and 25,169 patients developed acute respiratory distress syndrome or respiratory failure within 28 days since hospital admission. The algorithms demonstrated high accuracy (AUC 0.89, 95% CI 0.89-0.89 on the test data set [n=10,752]), consistent prediction through the second wave of the pandemic from September to November (AUC 0.85, 95% CI 0.85-0.86) on the postdevelopment prospective test data set [n=14,863], great clinical relevance, and utility. Besides, a comprehensive set of 386 input covariates from baseline or at admission were included in the analysis; the end-to-end pipeline automates feature selection and model development. The parsimonious model with only 10 input predictors produced comparably accurate predictions; these 10 predictors (age, blood urea nitrogen, SpO(2), systolic and diastolic blood pressures, respiration rate, pulse, temperature, albumin, and major cognitive disorder excluding stroke) are commonly measured and concordant with recognized risk factors for COVID-19. CONCLUSIONS: The systematic approach and rigorous validation demonstrate consistent model performance to predict even beyond the period of data collection, with satisfactory discriminatory power and great clinical utility. Overall, the study offers an accurate, validated, and reliable prediction model based on only 10 clinical features as a prognostic tool to stratifying patients with COVID-19 into intermediate-, high-, and very high-risk groups. This simple predictive tool is shared with a wider health care community, to enable service as an early warning system to alert physicians of possible high-risk patients, or as a resource triaging tool to optimize health care resources.

J Med Internet Res2022       LitCov and CORD-19
2025Students' Perceptions towards the Experience, Quality, Challenges and Effectiveness of Online Teaching-Learning during Covid-19 Pandemic in Riyadh Elm University, Saudi Arabia  

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Mymensingh Med J2022       LitCov and CORD-19
2026Understanding COVID-19 Vaccine Hesitancy in Ethnic Minorities Groups in the UK  

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Front Public Health2022       LitCov
2027Changes in attitudes to vaccination as a result of the COVID-19 pandemic: A longitudinal study of older adults in the UK  

BACKGROUND: The rapid development of COVID-19 vaccines has brought an unprecedented focus on public attitudes to vaccines, with intention to accept a COVID-19 vaccine fluctuating during the pandemic. However, it is unclear how the pandemic may influence attitudes and behaviour in relation to vaccines in general. The aim of the current study is to examine older adults’ changes in vaccination attitudes and behaviour over the first year of the pandemic. METHODS: In February-March 2020 (before the first COVID-19 national lockdown in the UK), 372 older adults (aged 65+) provided sociodemographic information, self-reported influenza vaccine uptake, and completed two measures of vaccination attitudes: the 5C scale and the Vaccination Attitudes Examination Scale. One-year later, following rollout of COVID-19 vaccines to older adults, participants provided information on their COVID-19 and influenza vaccine uptake in the previous 12 months, and completed the 5C and VAX scales again. Paired samples t-tests were used to examine changes in vaccination attitudes over time. RESULTS: Almost all participants (98.7%) had received at least one dose of a COVID-19 vaccine, and a significant increase in influenza uptake was identified (83.6% in 2020 to 91.6% in 2021). Complacency, mistrust of vaccine benefit, concerns about commercial profiteering, and constraints to vaccination had significantly decreased between Time 1 and Time 2, and collective responsibility had significant increased. However, calculation and worries about unforeseen future effects had increased, indicating that participants now perceived higher risks related to vaccination and were taking a more deliberative information-seeking approach. CONCLUSION: The results show significant changes in vaccination attitudes across the pandemic. These changes suggest that while older adults became less complacent about the importance of vaccines, concerns about potential risks associated with vaccination increased. It will be important for public health communication to address these concerns for all vaccines offered to this group.

PLoS One2021       LitCov and CORD-19
2028PERSPECTIVE: A Mental Health Services Research Agenda in the Era of COVID-19: Steadfast Commitment to Addressing Evolving Challenges  

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J Ment Health Policy Econ2021       LitCov and CORD-19
2029SARS-CoV-2 Neutralization in Convalescent Plasma and Commercial Lots of Plasma-Derived Immunoglobulin  

INTRODUCTION: Patients with primary or secondary immunodeficiency (PID or SID) face increased insecurity and discomfort in the light of the COVID-19 pandemic, not knowing if and to what extent their comorbidities may impact the course of a potential SARS-CoV-2 infection. Furthermore, recently available vaccination options might not be amenable or effective for all patients in this heterogeneous population. Therefore, these patients often rely on passive immunization with plasma-derived, intravenous or subcutaneous immunoglobulin (IVIG/SCIG). Whether the ongoing COVID-19 pandemic and/or the progress in vaccination programs lead to increased and potentially protective titers in plasma-derived immunoglobulins (Ig) indicated (e.g., for humoral immunodeficiency) remains a pressing question for this patient population. PURPOSE: We investigated SARS-CoV-2 reactivity of US plasma-derived IVIG/SCIG products from the end of 2020 until June 2021 as well as in convalescent plasma (CP) from May 2020 to August 2020 to determine whether potentially neutralizing antibody titers may be present. METHODS: Final containers of IVIG/SCIG and CP donations were analyzed by commercial ELISA for anti-SARS-CoV-2 S1-receptor binding domain (RBD) IgG as well as microneutralization assay using a patient-derived SARS-CoV-2 (D614G) isolate. Neutralization capacities of 313 single plasma donations and 119 plasma-derived IVIG/SCIG lots were determined. Results obtained from both analytical methods were normalized against the WHO International Standard. Finally, based on dense pharmacokinetic profiles of an IVIG preparation from previously published investigations, possible steady-state plasma levels of SARS-CoV-2 neutralization capacities were approximated based on currently measured anti-SARS-CoV-2 potencies in IVIG/SCIG preparations. RESULTS: CP donations presented with high variability with regards to anti-SARS-CoV-2 reactivity in ELISA as well as in neutralization testing. While approximately 50% of convalescent donations were not/low neutralizing, approximately 10% were at or above 600 IU/mL. IVIG/SCIG lots derived from pre-pandemic plasma donations did not show neutralizing capacities for SARS-CoV-2. Lots produced between December 2020 and June 2021 entailing plasma donations after the emergence of SARS-CoV-2 showed a rapid and constant increase in anti-SARS-CoV-2 reactivity and neutralization capacity over time. While lot-to-lot variability was substantial, neutralization capacity increased from a mean of 21 IU/mL in December 2020 to 506 IU/mL in June 2021 with a maximum of 864 IU/mL for the most recent lots. Pharmacokinetic extrapolations, based on non-compartmental superposition principles using steady-state reference profiles from previously published pharmacokinetic investigations on IVIG in PID, yielded potential steady-state trough plasma levels of 16 IU/mL of neutralizing SARS-CoV-2 IgG based on the average final container concentration from May 2021 of 216 IU/mL. Maximum extrapolated trough levels could reach 64 IU/mL based on the latest maximal final container potency tested in June 2021. CONCLUSIONS: SARS-CoV-2 reactivity and neutralization capacity in IVIG/SCIG produced from US plasma rapidly and in part exponentially increased in the first half of 2021. The observed increase of final container potencies is likely trailing the serological status of the US donor population in terms of COVID-19 convalescence and vaccination by at least 5 months due to production lead times and should in principle continue at least until Fall 2021. In summary, the data support rapidly increasing levels of anti-SARS-CoV-2 antibodies in IVIG/SCIG products, implicating that a certain level of protection could be possible against COVID-19 for regularly substituted PID/SID patients. Nevertheless, more research is still needed to confirm which plasma levels are needed to provide protection against SARS-CoV-2 infection in immune-compromised patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40259-021-00511-9.

BioDrugs2021       LitCov and CORD-19
2030Positive impact of the pandemic: the effect of post-COVID-19 virtual visit implementation on departmental efficiency and patient satisfaction in a quaternary care center  

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Neurosurg Focus2022       LitCov
2031SARS-CoV-2 Evolutionary Adaptation toward Host Entry and Recognition of Receptor O-Acetyl Sialylation in Virus-Host Interaction  

The recently emerged SARS-CoV-2 is the cause of the global health crisis of the coronavirus disease 2019 (COVID-19) pandemic. No evidence is yet available for CoV infection into hosts upon zoonotic disease outbreak, although the CoV epidemy resembles influenza viruses, which use sialic acid (SA). Currently, information on SARS-CoV-2 and its receptors is limited. O-acetylated SAs interact with the lectin-like spike glycoprotein of SARS CoV-2 for the initial attachment of viruses to enter into the host cells. SARS-CoV-2 hemagglutinin-esterase (HE) acts as the classical glycan-binding lectin and receptor-degrading enzyme. Most β-CoVs recognize 9-O-acetyl-SAs but switched to recognizing the 4-O-acetyl-SA form during evolution of CoVs. Type I HE is specific for the 9-O-Ac-SAs and type II HE is specific for 4-O-Ac-SAs. The SA-binding shift proceeds through quasi-synchronous adaptations of the SA-recognition sites of the lectin and esterase domains. The molecular switching of HE acquisition of 4-O-acetyl binding from 9-O-acetyl SA binding is caused by protein–carbohydrate interaction (PCI) or lectin–carbohydrate interaction (LCI). The HE gene was transmitted to a β-CoV lineage A progenitor by horizontal gene transfer from a 9-O-Ac-SA–specific HEF, as in influenza virus C/D. HE acquisition, and expansion takes place by cross-species transmission over HE evolution. This reflects viral evolutionary adaptation to host SA-containing glycans. Therefore, CoV HE receptor switching precedes virus evolution driven by the SA-glycan diversity of the hosts. The PCI or LCI stereochemistry potentiates the SA–ligand switch by a simple conformational shift of the lectin and esterase domains. Therefore, examination of new emerging viruses can lead to better understanding of virus evolution toward transitional host tropism. A clear example of HE gene transfer is found in the BCoV HE, which prefers 7,9-di-O-Ac-SAs, which is also known to be a target of the bovine torovirus HE. A more exciting case of such a switching event occurs in the murine CoVs, with the example of the β-CoV lineage A type binding with two different subtypes of the typical 9-O-Ac-SA (type I) and the exclusive 4-O-Ac-SA (type II) attachment factors. The protein structure data for type II HE also imply the virus switching to binding 4-O acetyl SA from 9-O acetyl SA. Principles of the protein–glycan interaction and PCI stereochemistry potentiate the SA–ligand switch via simple conformational shifts of the lectin and esterase domains. Thus, our understanding of natural adaptation can be specified to how carbohydrate/glycan-recognizing proteins/molecules contribute to virus evolution toward host tropism. Under the current circumstances where reliable antiviral therapeutics or vaccination tools are lacking, several trials are underway to examine viral agents. As expected, structural and non-structural proteins of SARS-CoV-2 are currently being targeted for viral therapeutic designation and development. However, the modern global society needs SARS-CoV-2 preventive and therapeutic drugs for infected patients. In this review, the structure and sialobiology of SARS-CoV-2 are discussed in order to encourage and activate public research on glycan-specific interaction-based drug creation in the near future.

Int J Mol Sci2020       LitCov and CORD-19
2032Zilucoplan in patients with acute hypoxic respiratory failure due to COVID-19 (ZILU-COV): A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: Zilucoplan (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms that lead to improvement in lung oxygenation parameters. The purpose of this study is to investigate the efficacy and safety of Zilucoplan in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure. TRIAL DESIGN: This is a phase 2 academic, prospective, 2:1 randomized, open-label, multi-center interventional study. PARTICIPANTS: Adult patients (≥18y old) will be recruited at specialized COVID-19 units and ICUs at 9 Belgian hospitals. The main eligibility criteria are as follows: 1) Inclusion criteria: a. Recent (≥6 days and ≤16 days) SARS-CoV-2 infection. b. Chest CT scan showing bilateral infiltrates within the last 2 days prior to randomisation. c. Acute hypoxia (defined as PaO(2)/FiO(2) below 350 mmHg or SpO2 below 93% on minimal 2 L/min supplemental oxygen). d. Signs of cytokine release syndrome characterized by either high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those. 2) Exclusion criteria: e. Mechanical ventilation for more than 24 hours prior to randomisation. f. Active bacterial or fungal infection. g. History of meningococcal disease (due to the known high predisposition to invasive, often recurrent meningococcal infections of individuals deficient in components of the alternative and terminal complement pathways). INTERVENTION AND COMPARATOR: Patients in the experimental arm will receive daily 32,4 mg Zilucoplan subcutaneously and a daily IV infusion of 2g of the antibiotic ceftriaxone for 14 days (or until hospital discharge, whichever comes first) in addition to standard of care. These patients will receive additional prophylactic antibiotics until 14 days after the last Zilucoplan dose: hospitalized patients will receive a daily IV infusion of 2g of ceftriaxone, discharged patients will switch to daily 500 mg of oral ciprofloxacin. The control group will receive standard of care and a daily IV infusion of 2g of ceftriaxone for 1 week (or until hospital discharge, whichever comes first), to control for the effects of antibiotics on the clinical course of COVID-19. MAIN OUTCOMES: The primary endpoint is the improvement of oxygenation as measured by mean and/or median change from pre-treatment (day 1) to post-treatment (day 6 and 15 or at discharge, whichever comes first) in PaO(2)/FiO(2) ratio, P(A-a)O(2) gradient and a/A PO(2) ratio. (PAO(2)= Partial alveolar pressure of oxygen, PaO(2)=partial arterial pressure of oxygen, FiO(2)=Fraction of inspired oxygen). RANDOMISATION: Patients will be randomized in a 2:1 ratio (Zilucoplan: control). Randomization will be done using an Interactive Web Response System (REDCap). BLINDING (MASKING): In this open-label trial neither participants, caregivers, nor those assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 81 patients will be enrolled: 54 patients will be randomized to the experimental arm and 27 patients to the control arm. TRIAL STATUS: ZILU-COV protocol Version 4.0 (June 10 2020). Participant recruitment started on June 23 2020 and is ongoing. Given the uncertainty of the pandemic, it is difficult to predict the anticipated end date. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on May 11(th), 2020 (ClinicalTrials.gov Identifier: NCT04382755) and on EudraCT (Identifier: 2020-002130-33). FULL PROTOCOL: The full protocol 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-020-04884-0.

Trials2020       LitCov and CORD-19
2033The Prevalence of Depression, Anxiety and Associated Factors among the General Public during COVID-19 Pandemic: a Cross-sectional Study in Korea  

BACKGROUND: Since its first case confirmed on January 20, 2020, Korea has been through three waves of the COVID-19 pandemic. Fears of the fourth wave persist as new cases continue to emerge. In such unpredictable times, the mental well-being of people is of crucial importance. This study examined the levels of depression and anxiety and their predictors among the Korean general public in Busan, Korea, during the COVID-19 pandemic. METHODS: We conducted a cross-sectional study via a self-reported questionnaire administered to 2,288 adult residents (aged 19–60 years) of Busan, Korea. Participants' depression and anxiety were assessed using the Korean version of the Patient Health Questionnaire-4 (PHQ-4), which consists of PHQ-2 and Generalized Anxiety Disorder-2 (GAD-2), with the cutoff score of 3. RESULTS: The mean age of the participants was 39.71 years. COVID-19 had several psychosocial impacts on people. It was revealed that 80.3% had restrictions in outside activities, 47.3% reported financial difficulties, and 53.6% had a fear of death or fatal outcome when infected with COVID-19. We performed logistic regression analysis to identify the factors associated with depression and anxiety. A total of 30.7% participants were classified as at risk of depression based on cutoff score of 3 on PHQ-2. Logistic regression analysis revealed that changes in sleep pattern due to COVID-19 were most strongly associated with depression, followed by restrictions in outside activities due to social distancing and increased family conflicts due to COVID-19. Also, 22.6% participants were classified as at risk of anxiety based on a cutoff score of 3 on GAD-2. Analysis revealed that changes in sleep pattern due to COVID-19 were most strongly associated with anxiety, followed by spending a lot of time searching for COVID-19-related information and having a fear of death or fatal outcome when infected with COVID-19. CONCLUSION: The results are alarming; 30.7% had a PHQ-2 score of 3 or higher, indicating depression, and 22.6% had a GAD-2 score of 3 or higher, indicating anxiety. Changes in sleep pattern had the strongest association with both depression and anxiety. Our results can be used to formulate mental health policies tailored to the context of the city. Our findings suggest the high prevalence of depression and anxiety in the society during the COVID-19 pandemic, which places growing importance on early intervention for mental health problems during these times.

J Korean Med Sci2021       LitCov and CORD-19
2034Comparative 6-Month Wild-Type and Delta-Variant Antibody Levels and Surrogate Neutralization for Adults Vaccinated with BNT162b2 vs mRNA-1273  

While mRNA vaccines are highly efficacious against short-term COVID-19, long-term immunogenicity is less clear. We compared humoral immunogenicity between BNT162b2 and mRNA-1273 vaccines 6 months after the first vaccine dose, examining the wild-type strain and multiple Delta-variant lineages. Using samples from a prospective observational cohort study of adult paramedics, we included COVID-19-negative participants who received two BNT162b2 or mRNA-1273 vaccines, and provided a blood sample 170 to 190 days post first vaccine dose. We compared wild-type spike IgG concentrations using the Mann-Whitney U test. We also compared secondary outcomes of: receptor binding domain (RBD) wild-type antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to spike proteins from the wild-type strain and five Delta-variant lineages. We included 571 adults: 475 BNT162b2 (83%) and 96 mRNA-1273 (17%) vaccinees, with a mean age of 39 (SD = 10) and 43 (SD = 10) years, respectively. Spike IgG antibody concentrations were significantly higher (P < 0.0001) for those who received mRNA-1273 (GM 601 BAU/mL [GSD 2.05]) versus BNT162b2 (GM 375 BAU/mL [GSD 2.33) vaccines. Results of RBD antibody comparisons (P < 0.0001), and inhibition of ACE-2 binding to the wild-type strain and all tested Delta lineages (all P < 0.0001), were consistent. Adults who received two doses of mRNA-1273 vaccines demonstrated improved wild-type and Delta variant-specific humoral immunity outcomes at 6 months compared with those who received two doses of the BNT162b2 vaccine. IMPORTANCE The BNT162b2 and mRNA-1273 mRNA SARS-CoV-2 vaccines have demonstrated high efficacy for preventing short-term COVID-19. However, comparative long-term effectiveness is unclear, especially pertaining to the Delta variant. We tested virus-specific antibody responses 6 months after the first vaccine dose and compared individuals who received the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines. We found that individuals who received the mRNA-1273 vaccine demonstrated superior serological markers at 6 months in comparison with those who received the BNT162b2 vaccine.

Microbiol Spectr2022       LitCov and CORD-19
2035Human Factor Considerations in Using Personal Protective Equipment in the COVID-19 Pandemic Context: Binational Survey Study  

BACKGROUND: Full level 1 personal protective equipment (PPE) is used in various domains and contexts. Prior research has shown influences of such equipment on performance, comfort, and contamination levels. The coronavirus disease (COVID-19) pandemic forced a pervasive requirement of PPE, with little preparation, rushed deployment, inadequate time for training, and massive use by personnel who are inexperienced or not qualified in its effective use. OBJECTIVE: This study aims to examine the key human factors (physical and ergonomic, perceptual and cognitive) that influence the use of level 1 PPE when attending to patients with suspected or confirmed COVID-19. METHODS: The research approach consisted of a short survey disseminated to health care professionals in two countries, Israel and Portugal, with similar demographics and health care systems. The survey included 10 items with a 5-point Likert scale regarding the key human factors involved in level 1 PPE, as identified in prior research. RESULTS: A total of 722 respondents from Israel and 301 respondents from Portugal were included in the analysis. All the respondents reported using level 1 PPE with patients with COVID-19 in the range of several hours daily to several hours weekly. The Cronbach α was .73 for Israel and .75 for Portugal. Responses showed high levels of difficulty, with medians of 4 for items related to discomfort (n=539/688, 78% in Israel; n=328/377, 87% in Portugal), hearing (n=236/370, 64% in Portugal; n=321/642, 50% in Israel), seeing (n=697/763, 89% in Israel; n=317/376, 84% in Portugal), and doffing (n=290/374, 77% in Portugal; n=315/713, 44% in Israel). A factor analysis showed a set of strongly related variables consisting of hearing, understanding speech, and understanding the situation. This suggests that degradation in communication was strongly associated with degradation in situational awareness. A subsequent mediation analysis showed a direct effect of PPE discomfort on situational awareness (P<.001); this was also influenced (mediated) by difficulties in communicating, namely in hearing and understanding speech. CONCLUSIONS: In 2020, the COVID-19 pandemic is paving the way for updating PPE design. The use of already deployed technology affords ample opportunities to improve, adapt, and overcome caveats. The findings here suggest that the use of level 1 PPE with patients with COVID-19 has perceptual and cognitive effects, in addition to physical and ergonomic influences. Efforts should be taken to mitigate the harmful effects of such influences, both regarding the performance of medical actions and the risk of contamination to health care workers. Such efforts involve the design of PPE; the introduction of technologies to enhance vision, hearing, and communicating during the use of PPE; and training staff in using the equipment and in effective communication and teamwork protocols.

J Med Internet Res2020       LitCov and CORD-19
2036Clinical Characteristics of Covid-19 in New York City  

N Engl J Med2020       LitCov and CORD-19
2037A qualitative study of experiences of NHS mental healthcare workers during the Covid-19 pandemic  

BACKGROUND: The Covid-19 pandemic has imposed extraordinary strains on healthcare workers. But, in contrast with acute settings, relatively little attention has been given to those who work in mental health settings. We aimed to characterise the experiences of those working in English NHS secondary mental health services during the first wave of the pandemic. METHODS: The design was a qualitative interview-based study. We conducted semi-structured, remote (telephone or online) interviews with 35 members of staff from NHS secondary (inpatient and community) mental health services in England. Analysis was based on the constant comparative method. RESULTS: Participants reported wide-ranging changes in the organisation of secondary mental health care and the nature of work in response to the pandemic, including pausing of all services deemed to be “non-essential”, deployment of staff across services to new and unfamiliar roles, and moves to remote working. The quality of participants’ working life was impaired by increasing levels of daily challenge associated with trying to provide care in trying and constrained circumstances, the problems of forging new ways of working remotely, and constraints on ability to access informal support. Participants were confronted with difficult dilemmas relating to clinical decision-making, prioritisation of care, and compromises in ability to perform the therapeutic function of their roles. Other dilemmas centred on trying to balance the risks of controlling infection with the need for human contact. Many reported features of moral injury linked to their perceived failures in providing the quality or level of care that they felt service users needed. They sometimes sought to compensate for deficits in care through increased advocacy, taking on additional tasks, or making exceptions, but this led to further personal strain. Many experienced feelings of grief, helplessness, isolation, distress, and burnout. These problems were compounded by sometimes poor communication about service changes and by staff feeling that they could not take time off because of the potential impact on others. Some reported feeling poorly supported by organisations. CONCLUSIONS: Mental health workers faced multiple adversities during the pandemic that were highly consequential for their wellbeing. These findings can help in identifying targets for support.

BMC Psychiatry2021       LitCov and CORD-19
2038Clinical Characteristics and Viral RNA Detection in Children With COVID-19 in the Republic of Korea  

Importance There is limited information describing the full spectrum of coronavirus disease 2019 (COVID-19) and the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection in children. Objective To analyze the full clinical course and the duration of SARS-CoV-2 RNA detectability in children confirmed with COVID-19 in the Republic of Korea, where rigorous public health interventions have been implemented. Design, Setting, and Participants This case series of children with COVID-19 was conducted in 20 hospitals and 2 nonhospital isolation facilities across the country from February 18, 2020, to March 31, 2020. Children younger than 19 years who had COVID-19 were included. Exposures Confirmed COVID-19, detected via SARS-CoV-2 RNA in a combined nasopharyngeal and oropharyngeal swab or sputum by real-time reverse transcription-polymerase chain reaction. Main Outcomes and Measures Clinical manifestations during the observation period, including the time and duration of symptom occurrence. The duration of SARS-CoV-2 RNA detection was also analyzed. Results A total of 91 children with COVID-19 were included (median [range] age, 11 [0-18] years; 53 boys [58%]). Twenty children (22%) were asymptomatic during the entire observation period. Among 71 symptomatic cases, 47 children (66%) had unrecognized symptoms before diagnosis, 18 (25%) developed symptoms after diagnosis, and only 6 (9%) were diagnosed at the time of symptom onset. Twenty-two children (24%) had lower respiratory tract infections. The mean (SD) duration of the presence of SARS-CoV-2 RNA in upper respiratory samples was 17.6 (6.7) days. Virus RNA was detected for a mean (SD) of 14.1 (7.7) days in asymptomatic individuals. There was no difference in the duration of virus RNA detection between children with upper respiratory tract infections and lower respiratory tract infections (mean [SD], 18.7 [5.8] days vs 19.9 [5.6] days; P = .54). Fourteen children (15%) were treated with lopinavir-ritonavir and/or hydroxychloroquine. All recovered, without any fatal cases. Conclusions and Relevance In this case series study, inapparent infections in children may have been associated with silent COVID-19 transmission in the community. Heightened surveillance using laboratory screening will allow detection in children with unrecognized SARS-CoV-2 infection.

JAMA Pediatr2020       LitCov and CORD-19
2039Immunogenicity of BNT162b2, BBIBP-CorV and Gam-COVID-Vac vaccines and immunity after natural SARS-CoV-2 infection-A comparative study from Novi Sad, Serbia  

BACKGROUND: Mass vaccination is the key element in controlling current COVID-19 pandemic. Studies comparing immunogenicity of different COVID-19 vaccines are largely lacking. We aimed at measuring anti-S antibody (Ab) levels in individuals fully vaccinated with BNT162b2, BBIBP-CorV and Gam-COVID-Vac, as well as in COVID-19 convalescents. METHODS: In this cross-sectional study, serum was collected from 400 age- and sex-matched participants, 100 fully vaccinated with BNT162b2, 100 with BBIBP-CorV and 100 with Gam-COVID-Vac on the 28(th) day after the second vaccine dose, and 100 recovered from COVID-19 at least 28 days after symptom(s) resolution. Sera were analyzed using the LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy). Wilcoxon rank-sum or Kruskal–Wallis tests was used for comparison of Ab levels. RESULTS: Highest mean value (210.11, SD = 100.42) was measured in the BNT162b2 group, followed by Gam-COVID-Vac (171.11, SD = 120.69) and BBIBP-CorV (68.50, SD = 72.78) AU/mL (p<0.001). Significant differences in antibody levels were found between BNT162b2 and BBIBP-CorV (p<0.001), BNT162b2 and Gam-COVID-Vac (p = 0.001), as well as BBIBP-CorV and Gam-COVID-Vac groups (p<0.001). Percentage of seropositive was 81% in the convalescent group, 83% in BBIBP-CorV vaccinated and 100% in BNT162b2 and Gam-COVID-Vac. When comparing measured antibody levels in vaccinated to those in COVID-19 recovered, significantly higher antibody levels were found for vaccinated with BNT162b2 (p<0.001), and with Gam-COVID-Vac (p<0.001), while for BBIBP-CorV there was no statistically significant difference (p = 0.641). CONCLUSIONS: All three investigated vaccines, BNT162b2, BBIBP-CorV and Gam-COVID-Vac, provide robust immune response 28 days after the second dose of vaccine, in the majority of participants. All individuals vaccinated with BNT162b2 and Gam-COVID-Vac seroconverted, while in vaccinated with BBIBP-CorV and COVID-19 recovered seroconversion rates were lower. Although less potent compared to other two vaccines, immune response after BBIBP-CorV was similar to response measured in convalescents. Challenge still remains to examine dynamics and durability of immunoprotection.

PLoS One2022       LitCov and CORD-19
2040Safety and immunogenicity of a live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine in adults: randomised, double-blind, placebo-controlled, phase 1 and 2 trials  

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Lancet Respir Med2022       LitCov
2041Effect of Different Disease-Modifying Therapies on Humoral Response to BNT162b2 Vaccine in Sardinian Multiple Sclerosis Patients  

OBJECTIVES: Vaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients. METHODS: We obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine. RESULTS: MS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients. CONCLUSION: Humoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.

Front Immunol2021       LitCov and CORD-19
2042Outcomes for Out-of-Hospital Cardiac Arrest in the United States During the COVID-19 Pandemic  

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JAMA Cardiol2021       LitCov and CORD-19
2043Limited neutralisation of the SARS-CoV-2 Omicron subvariants BA.1 and BA.2 by convalescent and vaccine serum and monoclonal antibodies  

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EBioMedicine2022       LitCov
2044Development of an inactivated vaccine candidate for SARS-CoV-2  

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are currently no SARS-CoV-2-specific treatments or vaccines available due to the novelty of the virus. Hence, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.

Science2020       LitCov and CORD-19
2045Assessing the Impact of a Rapidly Scaled Virtual Urgent Care in New York City During the COVID-19 Pandemic  

Abstract Background The COVID-19 pandemic quickly challenged New York City healthcare systems. Telemedicine has been suggested to manage acute complaints and divert patients from in-person care. Objectives The objective of this study was to describe and assess the impact of a rapidly scaled virtual urgent care during the COVID-19 pandemic. Methods This was a retrospective cohort study of all patients who presented to a virtual urgent care platform over one month during the COVID-19 pandemic surge. We described scaling our telemedicine urgent care capacity, described patient clinical characteristics, assessed for emergency department (ED) referrals, and analyzed post-visit surveys. Results During the study period, a total of 17,730 patients were seen via virtual urgent care. 454 (2.56%) were referred to an ED. The most frequent diagnoses were COVID-19 related or upper respiratory symptoms. Geospatial analysis indicated a wide catchment area. 251 providers were onboarded to the platform; at peak, 62 providers supplied 364 hours of coverage in one day. The average patient satisfaction score was 4.4/5. 2,668 patients (15.05%) responded to the post-visit survey; 1,236 (49.35%) would have sought care in an ED (11.86%) or in-person urgent care (37.49%). Conclusions A virtual urgent care was scaled to manage a volume of more than 800 patients a day across a large catchment area during the pandemic surge. About half of patients would have otherwise presented to an ED or urgent care in-person. Virtual urgent care is an option for appropriate patients while minimizing in-person visits during the COVID-19 pandemic.

J Emerg Med2020       LitCov and CORD-19
2046Threat, Coping and Social Distance Adherence During COVID-19: Cross-Continental Comparison Using an Online Cross-Sectional Survey  

BACKGROUND: Social distancing is an effective preventative policy for COVID-19 that is enforced by governments worldwide. However, significant variations are observed in adherence to social distancing across individuals and countries. Due to the lack of treatment, rapid spread, and prevalence of COVID-19, panic and fear associated with the disease causes great stress. Subsequent effects will be a variation around the coping and mitigation strategies for different individuals following different paths to manage the situation. OBJECTIVE: This study aims to explore how threat and coping appraisal processes work as mechanisms between information and citizens’ adherence to COVID-19–related recommendations (ie, how the information sources and social media influence threat and coping appraisal processes with COVID-19 and how the threat and coping appraisal processes influence adherence to policy guidelines). In addition, this study aims to explore how citizens in three different countries (the United States, Kuwait, and South Korea), randomly sampled, are effectively using the mechanisms. METHODS: Randomly sampled online survey data collected by a global firm in May 2020 from 162 citizens of the United States, 185 of Kuwait, and 71 of South Korea were analyzed, resulting in a total sample size of 418. A seemingly unrelated regression model, controlling for several counterfactuals, was used for analysis. The study’s focal estimated effects were compared across the three countries using the weighted distance between the parameter estimates. RESULTS: The seemingly unrelated regression model estimation results suggested that, overall, the intensity of information source use for the COVID-19 pandemic positively influenced the threat appraisal for the disease (P<.001). Furthermore, the intensity of social media use for the COVID-19 pandemic positively influenced the coping appraisal for the disease (P<.001). Higher COVID-19 threat appraisal had a positive effect on social distancing adherence (P<.001). Higher COVID-19 coping appraisal had a positive effect on social distancing adherence (P<.001). Higher intensity of COVID-19 knowledge positively influenced social distancing adherence (P<.001). There were country-level variations. Broadly, we found that the United States had better results than South Korea and Kuwait in leveraging the information to threat and coping appraisal to the adherence process, indicating that individuals in countries like the United States and South Korea may be more pragmatic to appraise the situation before making any decisions. CONCLUSIONS: This study’s findings suggest that the mediation of threat and coping strategies are essential, in varying effects, to shape the information and social media strategies for adherence outcomes. Accordingly, coordinating public service announcements along with information source outlets such as mainstream media (eg, TV and newspaper) as well as social media (eg, Facebook and Twitter) to inform citizens and, at the same time, deliver balanced messages about the threat and coping appraisal is critical in implementing a staggered social distancing and sheltering strategy.

J Med Internet Res2020       LitCov and CORD-19
2047The Disproportionate Impact of COVID-19 on Racial and Ethnic Minorities in the United States  

The COVID-19 pandemic has disproportionately affected racial and ethnic minority groups, with high rates of death in African American, Native American, and LatinX communities. While the mechanisms of these disparities are being investigated, they can be conceived as arising from biomedical factors as well as social determinants of health. Minority groups are disproportionately affected by chronic medical conditions and lower access to healthcare that may portend worse COVID-19 outcomes. Furthermore, minority communities are more likely to experience living and working conditions that predispose them to worse outcomes. Underpinning these disparities are long-standing structural and societal factors that the COVID-19 pandemic has exposed. Clinicians can partner with patients and communities to reduce the short-term impact of COVID-19 disparities while advocating for structural change.

Clin Infect Dis2020       LitCov and CORD-19
2048Effective treatment of severe COVID-19 patients with tocilizumab  

After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People’s Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.

Proc Natl Acad Sci U S A2020       LitCov and CORD-19
2049An 11-Year-Old Saudi Arabian Girl Who Presented with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 Infection with Coronary Artery Aneurysm and Cardiac Involvement: A Case Report  

Patient: Female, 11-year-old Final Diagnosis: Pediatrics multisystem inflammatory syndrome Symptoms: Cough • fever • shortness of breath Medication: — Clinical Procedure: — Specialty: Infectious Diseases OBJECTIVE: Unusual clinical course BACKGROUND: Early in the COVID-19 pandemic, children who were infected with severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) with vascular inflammation were described as having a vasculitis similar to Kawasaki’s disease. There are now consensus clinical guidelines that have described the presentation and diagnosis of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection. This report aims to describe a case of MIS-C in an 11-year-old Saudi Arabian girl who presented with coronary artery aneurysm and cardiac involvement. CASE REPORT: We describe an 11-year-old Saudi girl who was asymptomatic for 3 weeks after contracting SARS-CoV-2. Three weeks after suffering a mild flulike illness, she developed a high fever, cough, and severe clinical deterioration within 12 h of admission, including shock, rash, pleural effusion, high inflammatory markers, and a coronary aneurysm. As per current practice, the diagnosis was confirmed as multisystem inflammatory syndrome based on a SARS-CoV-2 test with reverse transcription polymerase chain reaction (RT-PCR) from 2 nasopharyngeal aspirates. Her condition was successfully treated with antibiotics, inotropes, IVIG, aspirin, and Tocilizumab, in addition to high-flow oxygen therapy. Eventually, she was able to return home after fully recovering. CONCLUSIONS: The findings in this report suggest that children with MIS-C due to SARS-CoV-2 infection can have a good prognosis, even when they suffer from coronary artery and cardiac involvement. The increasing number of emerging SARS-CoV-2 variants that affect children supports the importance of RT-PCR for the COVID-19 diagnostic test for children with multisystem or cardiovascular inflammation, which may guide the most appropriate clinical management of the variants of MIS-C.

Am J Case Rep2021       LitCov and CORD-19
2050Parents' intent to vaccinate against influenza during the COVID-19 pandemic in two regions in Switzerland  

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Swiss Med Wkly2021       LitCov and CORD-19

(1) COVID-19 Open Research Dataset (CORD-19). 2020. Version 2022-06-02. Retrieved from https://ai2-semanticscholar-cord-19.s3-us-west-2.amazonaws.com/historical_releases.html. Accessed 2022-06-05. doi:10.5281/zenodo.3715506
(2) Chen Q, Allot A, & Lu Z. (2020) Keep up with the latest coronavirus research, Nature 579:193 and Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Research. 2020. (version 2023-01-10)
(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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