\ 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
6451Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy  

In December, 2019, reports emerged from Wuhan, China, of a severe acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By the end of April, 2020, over 3 million people had been confirmed infected, with over 1 million in the USA alone, and over 215 000 deaths. The symptoms associated with COVID-19 are diverse, ranging from mild upper respiratory tract symptoms to severe acute respiratory distress syndrome. The major risk factors for severe COVID-19 are shared with idiopathic pulmonary fibrosis (IPF), namely increasing age, male sex, and comorbidities such as hypertension and diabetes. However, the role of antifibrotic therapy in patients with IPF who contract SARS-CoV-2 infection, and the scientific rationale for their continuation or cessation, is poorly defined. Furthermore, several licensed and potential antifibrotic compounds have been assessed in models of acute lung injury and viral pneumonia. Data from previous coronavirus infections such as severe acute respiratory syndrome and Middle East respiratory syndrome, as well as emerging data from the COVID-19 pandemic, suggest there could be substantial fibrotic consequences following SARS-CoV-2 infection. Antifibrotic therapies that are available or in development could have value in preventing severe COVID-19 in patients with IPF, have the potential to treat severe COVID-19 in patients without IPF, and might have a role in preventing fibrosis after SARS-CoV-2 infection.

Lancet Respir Med2020       LitCov and CORD-19
6452COVID-19 pandemic, government responses and public mental health: Investigating consequences through crisis hotline calls in two countries  

N/A

Soc Sci Med2020       LitCov and CORD-19
6453Plasma Biomarkers of Neuropathogenesis in Hospitalized Patients With COVID-19 and Those With Postacute Sequelae of SARS-CoV-2 Infection  

BACKGROUND AND OBJECTIVES: Although patients hospitalized with COVID-19 frequently present with encephalopathy, those with mild initial COVID-19 disease who never required hospitalization also often develop neurologic symptoms as part of postacute sequelae of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection (neuro-PASC). The pathogenic mechanisms of COVID-19 encephalopathy and neuro-PASC are unknown. We sought to establish biochemical evidence of CNS injury in those patients and their association with neuropsychiatric manifestations and SARS-CoV-2 antigenemia. METHODS: We recruited hospitalized, posthospitalized, and nonhospitalized patients with confirmed diagnosis of COVID-19 with neurologic symptoms in addition to healthy control (HC) subjects. Plasma neurofilament light chain (pNfL), plasma glial fibrillary acidic protein (pGFAP), and plasma SARS-CoV-2 Nucleocapsid antigen (pN Ag) were measured by HD-X Simoa analyzer (Quanterix) and compared with neuropsychiatric symptoms, patient-reported quality-of-life measures, and standardized cognitive assessments. Neuroglial scores (pGFAP/pNfL) were calculated to estimate the relative contribution of astroglial and neuronal involvement. RESULTS: We enrolled a total of 64 study participants, including 9 hospitalized patients with COVID-19 encephalopathy (CE), 9 posthospitalization neuro-PASC (PNP) patients, 38 nonhospitalized neuro-PASC (NNP) patients, and 8 HC subjects. Patients with CE were older, had higher pNfL and pGFAP concentrations, and more frequent pN Ag detection than all neuro-PASC groups. PNP and NNP patients exhibited similar PASC symptoms, decreased quality-of-life measures, and cognitive dysfunction, and 1 of the 38 (2.6%) NNP patients had pN Ag detectable 3 weeks postsymptoms onset. Patients with neuro-PASC presenting with anxiety/depression had higher neuroglial scores, which were correlated with increased anxiety on quality-of-life measures. DISCUSSION: pNfL, pGFAP, and pN Ag measurements indicate neuronal dysfunction and systemic involvement in hospitalized COVID-19 patients with encephalopathy. Detection of SARS-CoV-2 N Ag in blood 3 weeks after symptoms onset in a nonhospitalized patient suggests that prolonged antigenic stimulation, or possibly latent infection, may occur. Anxiety was associated with evidence of astroglial activation in patients with neuro-PASC. These data shed new light on SARS-Cov-2 neuropathogenesis and demonstrate the value of plasma biomarkers across the COVID-19 disease spectrum.

Neurol Neuroimmunol Neuroinfla2022       LitCov and CORD-19
6454COVID-19 and comorbidities: Deleterious impact on infected patients  

The pandemic situation with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from China has endangered human lives. Coronavirus disease 2019 (COVID-19) is presented with asymptomatic, mild, or severe pneumonia-like symptoms. COVID-19 patients with diabetes, chronic obstructive pulmonary disease (COPD), cardiovascular diseases (CVD), hypertension, malignancies, HIV, and other comorbidities could develop a life-threatening situation. SARS-CoV-2 utilizes ACE-2 receptors found at the surface of the host cells to get inside the cell. Certain comorbidities are associated with a strong ACE-2 receptor expression and higher release of proprotein convertase that enhance the viral entry into the host cells. The comorbidities lead to the COVID-19 patient into a vicious infectious circle of life and are substantially associated with significant morbidity and mortality. The comorbid individuals must adopt the vigilant preventive measure and requires scrupulous management. In this review, we rigorously focused on the impact of common morbidities in COVID-19 patients and recapitulated the management strategies with recent directions. We found limited resources describing the association of comorbidities in COVID-19; however, our review delineates the broader spectrum of comorbidities with COVID-19 patients.

J Infect Public Health2020       LitCov and CORD-19
6455Clinical characteristics and outcomes of older patients with COVID-19 in Wuhan, China (2019): a single-centered, retrospective study  

BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) emerged in Wuhan city and spread rapidly throughout China and the world. In this study, we aimed to describe the clinical course and outcomes of older patients with COVID-19. METHODS: This is a retrospective investigation of hospitalized older patients with confirmed COVID-19 at Zhongnan Hospital of Wuhan University from January 1, 2020, to February 10, 2020. RESULTS: In total, 203 patients were diagnosed with COVID-19, with a median age of 54 years (interquartile range, 41-68; range, 20-91 years). Men accounted for 108 (53.2%) of the cases, and 55 patients (27.1%) were >65 years of age. Among patients who were 65 years and older, the mortality rate was 34.5% (19/55), which was significantly higher than that of younger patients at 4.7% (7/148). Common symptoms of older patients with COVID-19 included fever (94.5%; n=52), dry cough (69.1%; n=38), and chest distress (63.6%; n=35). Compared with young patients, older patients had more laboratory abnormalities and comorbidities. Through a multivariate analysis of the causes of death in older patients, we found that males, comorbidities, time from disease onset to hospitalization, abnormal kidney function, and elevated procalcitonin levels were all significantly associated with death. CONCLUSIONS: In the recent outbreak of COVID-19, our local hospital in Wuhan found that patients aged 65 and older had greater initial comorbidities, more severe symptoms, and were more likely to experience multi-organ involvement and death, as compared with younger patients.

J Gerontol A Biol Sci Med Sci2020       LitCov and CORD-19
6456Epidemiology of SARS-CoV-2 Infection Evaluated by Immunochromatographic Rapid Testing for the Determination of IgM and IgG Against SARS-CoV-2 in a Cohort of Mask Wearing Workers in the Metal-Mechanical Sector in an Area With a High Incidence of COVID-19  

Background: Although the diagnosis of new coronavirus 2019 (COVID-19) is made through the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory secretions by means of molecular methods, a more accurate estimation of SARS-CoV-2 circulation can be obtained by seroprevalence studies. The main aim of this study was to evaluate the true epidemiology of SARS-CoV-2 infection among workers in the metal-mechanical sector who never stopped working during the pandemic period in an area with a high incidence of COVID-19 and to define whether and how they could continue the work without appreciable risks during a second wave. Methods: A total of 815 metal-mechanical workers who had never stopped working even during the pandemic period in three different factories in the Emilia-Romagna Region, Italy, and who had always used face masks during working hours, underwent a capillary blood rapid test for the determination of IgM and IgG against SARS-CoV-2 (COVID-19 IgG/IgM Rapid test, PrimaLab, Modena, Italy). In the event of a positive test, a nasopharyngeal was performed and tested for the presence of SARS-CoV-2. Results: The detection of serum IgG/IgM against SARS-CoV-2 was significantly more common among workers employed in Parma (21/345, 6.1%) than among those employed in Calerno (7/242, 2.9%) or in Spilamberto (3/228, 1.3%) (p <0.001). The analysis of the role of the different variables as predictors of seropositivity for IgG/IgM against SARS-CoV-2 revealed that the presence of specific antibodies was strictly associated with a previous history of COVID-19-like symptoms (odds ratio [OR] 3.95, 95% confidence interval [CI] 1.9–8.2) and household members with COVID-19-like symptoms (OR 2.20, 95% CI 1.04–4.82). Conclusion: This study shows that seropositivity to SARS-CoV-2 is low even among employees who did not interrupt their work during the lockdown phase in a region with a high incidence of COVID-19. The use of face masks appears effective in the avoidance of the transmission of SARS-CoV-2 in factories even in the presence of asymptomatic or mildly symptomatic workers, suggesting that work activities can continue if adequate infection control measures are used during a second wave.

Front Public Health2021       LitCov and CORD-19
6457Baricitinib as potential treatment for 2019-nCoV acute respiratory disease  

Lancet2020       LitCov and CORD-19
6458SARS-CoV-2 Omicron Variant: Epidemiological Features, Biological Characteristics and Clinical Significance  

The SARS-CoV-2 Omicron (B.1.1529) variant was designated as a variant of concern (VOC) by the World Health Organization (WHO) on November 26, 2021. Within two months, it had replaced the Delta variant and had become the dominant circulating variant around the world. The Omicron variant possesses an unprecedented number of mutations, especially in the spike protein, which may be influencing its biological and clinical aspects. Preliminary studies have suggested that increased transmissibility and the reduced protective effects of neutralizing antibodies have contributed to the rapid spread of this variant, posing a significant challenge to control the coronavirus disease 2019 (COVID-19) pandemic. There is, however, a silver lining for this wave of the Omicron variant. A lower risk of hospitalization and mortality has been observed in prevailing countries. Booster vaccination also has ameliorated a significant reduction in neutralization. Antiviral drugs are minimally influenced. Moreover, the functions of Fc-mediated and T-cell immunity have been retained to a great extent, both of which play a key role in preventing severe disease.

Front Immunol2022       LitCov and CORD-19
6459Neutralization of SARS-CoV-2 variants by convalescent and BNT162b2 vaccinated serum  

SARS-CoV-2 and its variants continue to infect hundreds of thousands every day despite the rollout of effective vaccines. Therefore, it is essential to understand the levels of protection that these vaccines provide in the face of emerging variants. Here, we report two demographically balanced cohorts of BNT162b2 vaccine recipients and COVID-19 patients, from which we evaluate neutralizing antibody titers against SARS-CoV-2 as well as the B.1.1.7 (alpha) and B.1.351 (beta) variants. We show that both B.1.1.7 and B.1.351 are less well neutralized by serum from vaccinated individuals, and that B.1.351, but not B.1.1.7, is less well neutralized by convalescent serum. We also find that the levels of variant-specific anti-spike antibodies are proportional to neutralizing activities. Together, our results demonstrate the escape of the emerging SARS-CoV-2 variants from neutralization by serum antibodies, which may lead to reduced protection from re-infection or increased risk of vaccine breakthrough.

Nat Commun2021       LitCov and CORD-19
6460Hesitancy in COVID-19 vaccine uptake and its associated factors among the general adult population: a cross-sectional study in six Southeast Asian countries  

BACKGROUND: Vaccines are effective and reliable public health interventions against viral outbreaks and pandemics. However, hesitancy regarding the Coronavirus disease (COVID-19) vaccine is evident worldwide. Therefore, understanding vaccination-related behavior is critical in expanding the vaccine coverage to flatten the infection curve. This study explores the public perception regarding COVID-19 vaccination and identifies factors associated with vaccine hesitancy among the general adult populations in six Southeast Asian countries. METHODS: Using a snowball sampling approach, we conducted a descriptive cross-sectional study among 5260 participants in Indonesia, Malaysia, Myanmar, Philippines, Thailand, and Vietnam between February and May 2021. Binary logistic regression analysis with a backward conditional approach was applied to identify factors associated with COVID-19 vaccine hesitancy. RESULTS: Of the total, 50.6% were female, and the median age was 30 years (range: 15–83 years). The majority of the participants believed that vaccination effectively prevents and controls COVID-19 (81.2%), and 84.0% would accept COVID-19 vaccines when they become available. They agreed that health providers’ advice (83.0%), vaccination convenience (75.6%), and vaccine costs (62.8%) are essential for people to decide whether to accept COVID-19 vaccines. About half (49.3%) expressed their hesitancy to receive the COVID-19 vaccines. After adjustment for other covariates, COVID-19 vaccine hesitancy was significantly associated with age, residential area, education levels, employment status, and family economic status. Participants from Indonesia, Myanmar, Thailand, and Vietnam were significantly more likely to express hesitancy in receiving COVID-19 vaccines than those from Philippines. CONCLUSIONS: In general, participants in this multi-country study showed their optimistic perception of COVID-19 vaccines’ effectiveness and willingness to receive them. However, about half of them still expressed their hesitancy in getting vaccinated. The hesitation was associated with several socioeconomic factors and varied by country. Therefore, COVID-19 vaccination programs should consider these factors essential for increasing vaccine uptake in the populations.

Trop Med Health2022       LitCov and CORD-19
6461Artificial intelligence-enabled rapid diagnosis of patients with COVID-19  

N/A

Nat Med2020       LitCov and CORD-19
6462SARS-CoV-2 antibody and T-cell responses one year after COVID-19 and the booster effect of vaccination: A prospective cohort study  

OBJECTIVES: : First, to describe SARS-CoV-2 T cell and antibody responses in a prospective cohort of healthcare workers that suffered from mild to moderate COVID-19 approximately one year ago. Second, to assess COVID-19 vaccine-induced immune responses in these prior-infected individuals. METHODS: : SARS-CoV-2-specific T cell and anti-SARS-CoV-2-Spike-RBD immunoglobulin G (IgG) responses in blood were determined before COVID-19 vaccination with mRNA-1273, BNT162b2, Ad26.CoV2-S or ChAdOx1-S, two weeks after first vaccination, and after second vaccination. RESULTS: : 55 prior SARS-CoV-2 infected and seroconverted individuals were included. S1-specific T cell responses and anti-RBD IgG were detectable one year post SARS-CoV-2 infection: 24 spot-forming cells per 10(6) peripheral blood mononuclear cells (SFCs/10(6) PBMCs) after S1 stimulation and anti-RBD IgG concentration of 74 (IQR 36-158) IU/mL. Responses after the first and second vaccination were comparable with S1-specfic T cell responses of 198 (IQR 137-359) and 180 (IQR 103-347) SFCs/10(6) PBMCs, and IgG concentrations of 6792 (IQR 3386-15180) and 6326 (IQR 2336-13440) IU/mL, respectively. These responses retained up to four months after vaccination. CONCLUSIONS: : Both T cell and IgG responses against SARS-CoV-2 persist for up to one year after COVID-19. A second COVID-19 vaccination in prior-infected individuals did not further increase immune responses in comparison to one vaccination.

J Infect2021       LitCov and CORD-19
6463Factors associated with anti-SARS-CoV-2 spike antibody titers after a second BNT162b2 mRNA COVID-19 vaccination in Japanese hemodialysis patients  

BACKGROUND: We investigated factors associated with the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody titer after the second dose of the BNT162b2 messenger RNA coronavirus disease 2019 (COVID-19) vaccine in Japanese patients undergoing hemodialysis. METHODS: Overall, 75 patients (41 men, 34 women; mean age 71.4 ± 12.2 years) with a hemodialysis duration of 5.7 ± 6.1 [interquartile range, 1.0–8.5] years were enrolled in this single-center, prospective, cross-sectional study. We used multiple linear regression analysis to determine the relationships of the anti-SARS-CoV-2 spike antibody titer with patient demographic and clinical parameters. We also compared the anti-SARS-CoV-2 spike antibody titer between hemodialysis patients and 22 healthcare workers (10 men, 12 women; mean age 48.5 ± 14.4 years). RESULTS: Autoimmune disease presence (standard coefficient [β] = − 0.290, p = 0.018), lymphocyte counts (β = 0.261, p = 0.015), hemoglobin levels (β = 0.290, p = 0.009), and blood urea nitrogen concentrations (β = 0.254, p = 0.033) were significantly and independently correlated with the log-anti-SARS-CoV-2 spike antibody titer. The anti-SARS-CoV-2 spike antibody titer was significantly lower in hemodialysis patients than in healthcare workers (3589 ± 3921 [813–4468] vs. 12,634 ± 18,804 [3472–10,257] AU/mL; p < 0.002). CONCLUSIONS: Autoimmune disease presence, lymphocyte counts, hemoglobin levels, and blood urea nitrogen concentrations were associated with the anti-SARS-CoV-2 spike antibody titer after the second dose of the BNT162b2 messenger RNA COVID-19 vaccine in Japanese patients undergoing hemodialysis.

Clin Exp Nephrol2022       LitCov and CORD-19
6464SARS-CoV-2 Antibody Rapid Tests: Valuable Epidemiological Tools in Challenging Settings  

During the last year, mass screening campaigns have been carried out to identify immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and establish a possible seroprevalence. The obtained results gained new importance with the beginning of the SARS-CoV-2 vaccination campaign, as the lack of doses has persuaded several countries to introduce different policies for individuals who had a history of COVID-19. Lateral flow assays (LFAs) may represent an affordable tool to support population screening in low-middle-income countries, where diagnostic tests are lacking and epidemiology is still widely unknown. However, LFAs have demonstrated a wide range of performance, and the question of which one could be more valuable in these settings still remains. We evaluated the performance of 11 LFAs in detecting SARS-CoV-2 infection, analyzing samples collected from 350 subjects. In addition, samples from 57 health care workers collected at 21 to 24 days after the first dose of the Pfizer-BioNTech vaccine were also evaluated. LFAs demonstrated a wide range of specificity (92.31% to 100%) and sensitivity (50% to 100%). The analysis of postvaccination samples was used to describe the most suitable tests to detect IgG response against S protein receptor binding domain (RBD). Tuberculosis (TB) therapy was identified as a potential factor affecting the specificity of LFAs. This analysis identified which LFAs represent a valuable tool not only for the detection of prior SARS-CoV-2 infection but also for the detection of IgG elicited in response to vaccination. These results demonstrated that different LFAs may have different applications and the possible risks of their use in high-TB-burden settings. IMPORTANCE Our study provides a fresh perspective on the possible employment of SARS-CoV-2 LFA antibody tests. We developed an in-depth, large-scale analysis comparing LFA performance to enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECLIA) and evaluating their sensitivity and specificity in identifying COVID-19 patients at different time points from symptom onset. Moreover, for the first time, we analyzed samples of patients undergoing treatment for endemic poverty-related diseases, especially tuberculosis, and we evaluated the impact of this therapy on test specificity in order to assess possible performance in TB high-burden countries.

Microbiol Spectr2021       LitCov and CORD-19
6465SARS-CoV-2 by the numbers  

The COVID-19 pandemic is a harsh reminder of the fact that, whether in a single human host or a wave of infection across continents, viral dynamics is often a story about the numbers. In this article we provide a one-stop, curated graphical source for the key numbers (based mostly on the peer-reviewed literature) about the SARS-CoV-2 virus that is responsible for the pandemic. The discussion is framed around two broad themes: i) the biology of the virus itself; ii) the characteristics of the infection of a single human host.

Elife2020       LitCov and CORD-19
6466Therapeutic options for the 2019 novel coronavirus (2019-nCoV)  

N/A

Nat Rev Drug Discov2020       LitCov and CORD-19
6467Angiotensin-Converting Enzyme Gene Polymorphism and Severe Lung Injury in Patients with COVID-19  

COVID-19 has markedly varied clinical presentations, with the majority of patients being asymptomatic or having mild symptoms. However, severe acute respiratory disease caused by SARS-CoV-2 is common and associated with mortality in patients who require hospitalization. The etiology of susceptibility to severe lung injury remains unclear. Angiotensin II, converted by angiotensin-converting enzyme (ACE) from angiotensin I and metabolized by angiotensin converting enzyme 2 (ACE2), plays a pivotal role in the pathogenesis of lung injury. ACE2 is identified as an essential receptor for SARS-COV-2 to enter the cell. The binding of ACE2 and SARS-COV-2 leads to the exhaustion of ACE2 and down-regulation of ACE2. The interaction and imbalance between ACE and ACE2 result in an unopposed angiotensin II. Considering that the ACE insertion/deletion (I/D) gene polymorphism contributes to the ACE level variability in general population, in which mean ACE level in DD carriers are approximately twice that in II carriers, we propose a hypothesis of genetic predisposition to severe lung injury in patients with COVID-19. It is plausible that the ACE inhibitors and ACE receptor blockers (ARBs) may have the potential to prevent and to treat the acute lung injury after SARS-COV-2 infection especially for those with the ACE genotype associated with high ACE level.

Am J Pathol2020       LitCov and CORD-19
6468COVID-19 Pandemic: Disparate Health Impact on the Hispanic/Latinx Population in the United States  

In December 2019, a novel coronavirus known as SARS-CoV-2, emerged in Wuhan, China, causing the Coronavirus disease 2019 we now refer to as COVID-19. The World Health Organization declared COVID-19 a pandemic on March 12th, 2020. In the United States, the COVID-19 pandemic has exposed pre-existing social and health disparities among several historically vulnerable populations, with stark differences in the proportion of minority individuals diagnosed with and dying from COVID-19. In this article we will describe the emerging disproportionate impact of COVID-19 on the Hispanic/Latinx (henceforth: Hispanic or Latinx) community in the U.S., discuss potential antecedents and consider strategies to address the disparate impact of COVID-19 on this population.

J Infect Dis2020       LitCov and CORD-19
6469Disparities in COVID-19 Vaccination Coverage Between Urban and Rural Counties-United States, December 14, 2020-April 10, 2021  

Approximately 60 million persons in the United States live in rural counties, representing almost one fifth (19.3%) of the population.* In September 2020, COVID-19 incidence (cases per 100,000 population) in rural counties surpassed that in urban counties (1). Rural communities often have a higher proportion of residents who lack health insurance, live with comorbidities or disabilities, are aged ≥65 years, and have limited access to health care facilities with intensive care capabilities, which places these residents at increased risk for COVID-19-associated morbidity and mortality (2,3). To better understand COVID-19 vaccination disparities across the urban-rural continuum, CDC analyzed county-level vaccine administration data among adults aged ≥18 years who received their first dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine, or a single dose of the Janssen COVID-19 vaccine (Johnson & Johnson) during December 14, 2020-April 10, 2021 in 50 U.S. jurisdictions (49 states and the District of Columbia [DC]). Adult COVID-19 vaccination coverage was lower in rural counties (38.9%) than in urban counties (45.7%) overall and among adults aged 18-64 years (29.1% rural, 37.7% urban), those aged ≥65 years (67.6% rural, 76.1% urban), women (41.7% rural, 48.4% urban), and men (35.3% rural, 41.9% urban). Vaccination coverage varied among jurisdictions: 36 jurisdictions had higher coverage in urban counties, five had higher coverage in rural counties, and five had similar coverage (i.e., within 1%) in urban and rural counties; in four jurisdictions with no rural counties, the urban-rural comparison could not be assessed. A larger proportion of persons in the most rural counties (14.6%) traveled for vaccination to nonadjacent counties (i.e., farther from their county of residence) compared with persons in the most urban counties (10.3%). As availability of COVID-19 vaccines expands, public health practitioners should continue collaborating with health care providers, pharmacies, employers, faith leaders, and other community partners to identify and address barriers to COVID-19 vaccination in rural areas (2).

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
6470Structural Basis of the Potential Binding Mechanism of Remdesivir to SARS-CoV-2 RNA-Dependent RNA Polymerase  

[Image: see text] Starting from late 2019, the coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures, and supporting apparatuses. Recently, because of its positive results in clinical trials, remdesivir was approved by the Food and Drug Administration to treat COVID-19 through Emergency Use Authorization. Here, we used molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). We first constructed the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identity of 95.8%). We then built a putative preinsertion binding structure by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp without the RNA template. The putative binding structure was further optimized with molecular dynamics simulations. The resulting stable preinsertion state of remdesivir appeared to form hydrogen bonds with the RNA template when aligned with the newly solved cryo-EM structure of SARS-CoV-2 RdRp. The relative binding free energy between remdesivir and ATP was calculated to be −2.80 ± 0.84 kcal/mol, where remdesivir bound much stronger to SARS-CoV-2 RdRp than the natural substrate ATP. The ∼100-fold improvement in the K(d) from remdesivir over ATP indicates an effective replacement of ATP in blocking of the RdRp preinsertion site. Key residues D618, S549, and R555 are found to be the contributors to the binding affinity of remdesivir. These findings suggest that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA replication, with key residues also identified for future lead optimization and/or drug resistance studies.

J Phys Chem B2020       LitCov and CORD-19
6471Performance of a Severity Score on Admission Chest Radiography in Predicting Clinical Outcomes in Hospitalized Patients With Coronavirus Disease  

N/A

AJR Am J Roentgenol2021       LitCov and CORD-19
6472Exploring Quality Differences in Telemedicine Between Hospital Outpatient Departments and Community Clinics: Cross-sectional Study  

BACKGROUND: Telemedicine is a care delivery modality that has the potential to broaden the reach and flexibility of health care services. In the United Arab Emirates, telemedicine services are mainly delivered through either integrated hospital outpatient department (OPDs) or community clinics. However, it is unknown if patients’ perceptions of, and satisfaction with, telemedicine services differ between these two types of health care systems during the COVID-19 pandemic. OBJECTIVE: We aimed to explore the differences in patients’ perceptions of, and satisfaction with, telemedicine between hospital OPDs and community clinics during the COVID-19 pandemic. We also aimed to identify patient- or visit-related characteristics contributing to patient satisfaction with telemedicine. METHODS: In this cross-sectional study that was conducted at Abu Dhabi health care centers, we invited outpatients aged 18 years or over, who completed a telemedicine visit during the COVID-19 pandemic, to participate in our study. Patients’ perceptions of, and satisfaction with, telemedicine regarding the two system types (ie, hospital OPDs and community clinics) were assessed using an online survey that was sent as a link through the SMS system. Regression models were used to describe the association between patient- and visit-related characteristics, as well as the perception of, and satisfaction with, telemedicine services. RESULTS: A total of 515 patients participated in this survey. Patients’ satisfaction with telemedicine services was equally high among the settings, with no statistically significant difference between the two setting types (hospital OPDs: 253/343, 73.8%; community clinics: 114/172, 66.3%; P=.19). Video consultation was significantly associated with increased patient satisfaction (odds ratio [OR] 2.57, 95% CI 1.04-6.33; P=.04) and patients’ support of the transition to telemedicine use during and after the pandemic (OR 2.88, 95% CI 1.18-7.07; P=.02). Patients who used video consultations were more likely to report that telemedicine improved access to health care services (OR 3.06, 95% CI 1.71-8.03; P=.02), reduced waiting times and travel costs (OR 4.94, 95% CI 1.15-21.19; P=.03), addressed patients’ needs (OR 2.63, 95% CI 1.13-6.11; P=.03), and eased expression of patients’ medical concerns during the COVID-19 pandemic (OR 2.19, 95% CI 0.89-5.38; P=.09). Surprisingly, middle-aged patients were two times more likely to be satisfied with telemedicine services (OR 2.12, 95% CI 1.09-4.14; P=.03), as compared to any other age group in this study. CONCLUSIONS: These findings suggest that patient satisfaction was unaffected by the health system setting in which patients received the teleconsultations, whether they were at hospitals or community clinics. Video consultation was associated with increased patient satisfaction with telemedicine services. Efforts should be focused on strategic planning for enhanced telemedicine services, video consultation in particular, for both emergent circumstances, such as the COVID-19 pandemic, and day-to-day health care delivery.

JMIR Med Inform2022       LitCov and CORD-19
6473A spatiotemporally resolved infection risk model for airborne transmission of COVID-19 variants in indoor spaces  

The classic Wells-Riley model is widely used for estimation of the transmission risk of airborne pathogens in indoor spaces. However, the predictive capability of this zero-dimensional model is limited as it does not resolve the highly heterogeneous spatiotemporal distribution of airborne pathogens, and the infection risk is poorly quantified for many pathogens. In this study we address these shortcomings by developing a novel spatiotemporally resolved Wells-Riley model for prediction of the transmission risk of different COVID-19 variants in indoor environments. This modelling framework properly accounts for airborne infection risk by incorporating the latest clinical data regarding viral shedding by COVID-19 patients and SARS-CoV-2 infecting human cells. The spatiotemporal distribution of airborne pathogens is determined via computational fluid dynamics (CFD) simulations of airflow and aerosol transport, leading to an integrated model of infection risk associated with the exposure to SARS-CoV-2, which can produce quantitative 3D infection risk map for a specific SARS-CoV-2 variant in a given indoor space. Application of this model to airborne COVID-19 transmission within a hospital ward demonstrates the impact of different virus variants and respiratory PPE upon transmission risk. With the emergence of highly contagious SARS-CoV-2 variants such as the Delta and Omicron strains, respiratory PPE alone may not provide effective protection. These findings suggest a combination of optimal ventilation and respiratory PPE must be developed to effectively control the transmission of COVID-19 in healthcare settings and indoor spaces in general. This generalised risk estimation framework has the flexibility to incorporate further clinical data as such becomes available, and can be readily applied to consider a wide range of factors that impact transmission risk, including location and movement of infectious persons, virus variant and stage of infection, level of PPE and vaccination of infectious and susceptible individuals, impacts of coughing, sneezing, talking and breathing, and natural and mechanised ventilation and filtration.

Sci Total Environ2021       LitCov and CORD-19
6474Coronavirus conspiracy beliefs, mistrust and compliance with government guidelines in England  

BACKGROUND: An invisible threat has visibly altered the world. Governments and key institutions have had to implement decisive responses to the danger posed by the coronavirus pandemic. Imposed change will increase the likelihood that alternative explanations take hold. In a proportion of the general population there may be strong scepticism, fear of being misled, and false conspiracy theories. Our objectives were to estimate the prevalence of conspiracy thinking about the pandemic and test associations with reduced adherence to government guidelines. METHODS: A non-probability online survey with 2501 adults in England, quota sampled to match the population for age, gender, income, and region. RESULTS: Approximately 50% of this population showed little evidence of conspiracy thinking, 25% showed a degree of endorsement, 15% showed a consistent pattern of endorsement, and 10% had very high levels of endorsement. Higher levels of coronavirus conspiracy thinking were associated with less adherence to all government guidelines and less willingness to take diagnostic or antibody tests or to be vaccinated. Such ideas were also associated with paranoia, general vaccination conspiracy beliefs, climate change conspiracy belief, a conspiracy mentality, and distrust in institutions and professions. Holding coronavirus conspiracy beliefs was also associated with being more likely to share opinions. CONCLUSIONS: In England there is appreciable endorsement of conspiracy beliefs about coronavirus. Such ideas do not appear confined to the fringes. The conspiracy beliefs connect to other forms of mistrust and are associated with less compliance with government guidelines and greater unwillingness to take up future tests and treatment.

Psychol Med2020       LitCov and CORD-19
6475The effect of COVID-19 on the characteristics of adult emergency department visits: A retrospective cohort tertiary hospital experience in Riyadh  

BACKGROUND: On March 2, 2020, Saudi Arabia identified the first positive COVID-19 case. Since then, several aspects of the COVID-19 impact on Emergency Departments (EDs) use have been reported. The objective of this study is to describe the pattern and characteristics of Emergency Department visits during the COVID-19 pandemic period, compared with the same period in the previous year, including the patients’ demographic information, acuity level, length of stay, and admission rate. METHODS: Data were collected from King Abdulaziz Medical City in Riyadh, Saudi Arabia. The health records of all the patients who presented at the Emergency Department from January 2019 to September 2020 were retrospectively reviewed. The variations in the patient and the visit characteristics were described for the periods before and during COVID-19. RESULTS: The records of 209,954 patients who presented at the Emergency Department were retrieved. In contrast to 2019, the number of visits during the pandemic period reduced by 23%. A dramatic decrease was observed after the announcement of the first COVID-19 diagnosed case in Saudi Arabia, and subsequently the numbers gradually increased. The patients who presented at the Emergency Department during the pandemic period were slightly older (mean age, 43.1 versus 44.0 years), more likely to be older, more urgent and had a higher admission rate compared to the pre-pandemic period. There was a slight increase in visits during the daytime curfew hours and a decrease during the nighttime. CONCLUSION: We report a considerable decrease in the number of Emergency Department visits. The reduction was higher in non-urgent and less urgent cases. Patients presenting at the Emergency Department during the curfew times were more likely to stay longer in the Emergency Department and more likely to be admitted, compared with the pre-pandemic period.

J Infect Public Health2021       LitCov and CORD-19
6476Factors affecting Iranian nurses' intention to leave or stay in the profession during the COVID-19 pandemic  

AIM: This study was conducted to explore the factors affecting nurses’ intentions to leave or stay in their profession during the coronavirus pandemic in Iran. INTRODUCTION: Because the effectiveness of a healthcare response to a disaster depends on an available, skilled, and motivated healthcare workforce, it is essential to understand and address potential barriers to and reasons for the intentions of medical staff to leave or stay in their profession. METHODS: A qualitative study with a conventional content analysis approach was conducted. The participants included nurses working in hospitals during the COVID‐19 pandemic, and nurses who had previously left their job or had been absent from work for a period of time. The participants were selected using a purposeful sampling strategy. Data were collected through 19 in‐depth, individual semi‐structured interviews with 16 nurses. The COnsolidated criteria for REporting Qualitative research checklist was used to report the study. FINDINGS: Three categories; commitment and work conscience (with a subcategory of risk‐taking), fear (with two subcategories of fear of family infection and fear of protective equipment shortages), and organizational factors (with two subcategories of organizational atmosphere of the hospital and motivational factors), emerged from the analysis. CONCLUSION: The reasons for quitting a nursing job or to keep working as a nurse during the pandemic include both personal and organizational factors. Commitment and work conscience in pandemic conditions is one of the main factors for keeping nurses in their profession. IMPLICATION FOR NURSING PRACTICE AND POLICY: Gaining insight into nurses’ understanding of the situation and perspectives is the key to being able to provide appropriate support and keep them in the workforce. Peer support can play an important role in supporting novice nurses in facing challenges posed by a pandemic and should be improved. Also, programs and strategies need to be planned to improve resilience among nurses and to help them to manage their stress and fear.

Int Nurs Rev2021       LitCov and CORD-19
6477COVID-19 Reporting and Data System: A Categorical CT Assessment Scheme for Patients Suspected of Having COVID-19-Definition and Evaluation  

PURPOSE: To introduce the COVID-19 Reporting and Data System (CO-RADS) for standardized assessment of pulmonary involvement of COVID-19 on non-enhanced chest CT and report its initial interobserver agreement and performance. METHODS: The Dutch Radiological Society (NVvR) developed CO-RADS based on other efforts for standardization, such as Lung-RADS or BI-RADS. CO-RADS assesses the suspicion for pulmonary involvement of COVID-19 on a scale from 1 (very low) to 5 (very high). The system is meant to be used in patients presenting with moderate to severe symptoms of COVID-19. The system was evaluated using 105 chest CTs of patients admitted to the hospital with clinical suspicion of COVID-19 in whom RT-PCR was performed (62 +/- 16 years, 61 men, 53 with positive RT-PCR). Eight observers assessed the scans using CO-RADS. Fleiss’ kappa was calculated, and scores of individual observers were compared to the median of the remaining seven observers. The resulting area under the receiver operating characteristics curve (AUC) was compared to results from RT-PCR and clinical diagnosis of COVID-19. RESULTS: There was absolute agreement among observers in 573 (68.2%) of 840 observations. Fleiss’ kappa was 0.47 (95% confidence interval (CI) 0.45-0.47), with the highest kappa for CO-RADS categories 1 (0.58, 95% CI 0.54-0.62) and 5 (0.68, 95% CI 0.65-0.72). The average AUC was 0.91 (95% CI 0.85-0.97) for predicting RT-PCR outcome and 0.95 (95% CI 0.91-0.99) for clinical diagnosis. The false negative rate for CO-RADS 1 was 9/161 (5.6%, 95% CI 1.0-10%), and the false positive rate for CO-RADS 5 was 1/286 (0.3%, 95% CI 0-1.0%). CONCLUSIONS: CO-RADS is a categorical assessment scheme for pulmonary involvement of COVID-19 on non-enhanced chest CT providing very good performance for predicting COVID-19 in patients with moderate to severe symptoms and has a substantial interobserver agreement, especially for categories 1 and 5.

Radiology2020       LitCov and CORD-19
6478The experience of European hospital-based Healthcare workers on following infection prevention and control procedures and their wellbeing during the first wave of the COVID-19 pandemic  

BACKGROUND: Working under pandemic conditions exposes health care workers (HCWs) to infection risk and psychological strain. A better understanding of HCWs’ experiences of following local infection prevention and control (IPC) procedures during COVID-19 is urgently needed to inform strategies for protecting the psychical and psychological health of HCWs. The objective of this study was therefore to capture the perceptions of hospital HCWs on local IPC procedures and the impact on their emotional wellbeing during the first wave of the COVID-19 pandemic in Europe. METHODS: Participants were recruited in two sampling rounds of an international cross-sectional survey. Sampling took place between 31 March and 17 April 2020 via existing research networks and between 14 May and 31 August 2020 via online convenience sampling. Main outcome measures were behavioural determinants of HCWs’ adherence to IPC guidelines and the WHO-5 Well-Being Index, a validated scale of 0–100 reflecting emotional wellbeing. The WHO-5 was interpreted as a score below or above 50 points, a cut-off score used in previous literature to screen for depression. RESULTS: 2289 HCWs from 40 countries in Europe participated. Mean age was 42 (±11) years, 66% were female, 47% and 39% were medical doctors and nurses, respectively. 74% (n = 1699) of HCWs were directly treating patients with COVID-19, of which 32% (n = 527) reported they were fearful of caring for these patients. HCWs reported high levels of concern about COVID-19 infection risk to themselves (71%) and their family (82%) as a result of their job. 40% of HCWs considered that getting infected with COVID-19 was not within their control. This feeling was more common among junior than senior HCWs (46% versus 38%, P value < .01). Sufficient COVID-19-specific IPC training, confidence in PPE use and institutional trust were positively associated with the feeling that becoming infected with COVID-19 was within their control. Female HCWs were more likely than males to report a WHO-5 score below 50 points (aOR 1.5 (95% confidence interval (CI) 1.2–1.8). CONCLUSIONS: In Europe, the COVID-19 pandemic has had a differential impact on those providing direct COVID-19 patient care, junior staff and women. Health facilities must be aware of these differential impacts, build trust and provide tailored support for this vital workforce during the current COVID-19 pandemic.

PLoS One2022       LitCov and CORD-19
6479Induction of Potent and Durable Neutralizing Antibodies Against SARS-CoV-2 Using a Receptor Binding Domain-Based Immunogen  

A novel betacoronavirus (SARS-CoV-2) that causes severe pneumonia emerged through zoonosis in late 2019. The disease, referred to as COVID-19, has an alarming mortality rate and it is having a devastating effect on the global economy and public health systems. A safe, effective vaccine is urgently needed to halt this pandemic. In this study, immunogenicity of the receptor binding domain (RBD) of spike (S) glycoprotein was examined in mice. Animals were immunized with recombinant RBD antigen intraperitoneally using three different adjuvants (Zn-chitosan, Alhydrogel, and Adju-Phos), and antibody responses were followed for over 5 months. Results showed that potent neutralizing antibodies (nAbs) can be induced with 70% neutralization titer (NT(70)) of ~14,580 against live, infectious viruses. Although antigen-binding antibody titers decreased gradually over time, sufficiently protective levels of nAbs persisted (NT(80) >2,430) over the 5-month observation period. Results also showed that adjuvants have profound effects on kinetics of nAb induction, total antibody titers, antibody avidity, antibody longevity, and B-cell epitopes targeted by the immune system. In conclusion, a recombinant subunit protein immunogen based on the RBD is a highly promising vaccine candidate. Continued evaluation of RBD immunogenicity using different adjuvants and vaccine regimens could further improve vaccine efficacy.

Front Immunol2021       LitCov and CORD-19
6480Identification of SARS-CoV-2 variants using viral sequencing for the Centers for Disease Control and Prevention genomic surveillance program  

BACKGROUND: The Centers for Disease Control and Prevention contracted with laboratories to sequence the SARS-CoV-2 genome from positive samples across the United States to enable public health officials to investigate the impact of variants on disease severity as well as the effectiveness of vaccines and treatment. Herein we present the initial results correlating RT-PCR quality control metrics with sample collection and sequencing methods from full SARS-CoV-2 viral genomic sequencing of 24,441 positive patient samples between April and June 2021. METHODS: RT-PCR confirmed (N Gene Ct value < 30) positive patient samples, with nucleic acid extracted from saliva, nasopharyngeal and oropharyngeal swabs were selected for viral whole genome SARS-CoV-2 sequencing. Sequencing was performed using Illumina COVIDSeq™ protocol on either the NextSeq550 or NovaSeq6000 systems. Informatic variant calling, and lineage analysis were performed using DRAGEN COVID Lineage applications on Illumina’s Basespace cloud analytical system. All sequence data and variant calls were uploaded to NCBI and GISAID. RESULTS: An association was observed between higher sequencing coverage, quality, and samples with a lower Ct value, with < 27 being optimal, across both sequencing platforms and sample collection methods. Both nasopharyngeal swabs and saliva samples were found to be optimal samples of choice for SARS-CoV-2 surveillance sequencing studies, both in terms of strain identification and sequencing depth of coverage, with NovaSeq 6000 providing higher coverage than the NextSeq 550. The most frequent variants identified were the B.1.617.2 Delta (India) and P.1 Gamma (Brazil) variants in the samples sequenced between April 2021 and June 2021. At the time of submission, the most common variant > 99% of positives sequenced was Omicron. CONCLUSION: These initial analyses highlight the importance of sequencing platform, sample collection methods, and RT-PCR Ct values in guiding surveillance efforts. These surveillance studies evaluating genetic changes of SARS-CoV-2 have been identified as critical by the CDC that can affect many aspects of public health including transmission, disease severity, diagnostics, therapeutics, and vaccines. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-022-07374-7.

BMC Infect Dis2022       LitCov and CORD-19
6481Gender-related time course of sleep disturbances and psychological symptoms during the COVID-19 lockdown: A longitudinal study on the Italian population  

Italy was the first western hotspot of the COVID-19 pandemic. In order to contain the spread of the virus, the Italian Government imposed home confinement to the entire population for almost two months. The present study is the first large-scale longitudinal report of the sleep and mental health changes during the prolonged lockdown due to the COVID-19 outbreak. We focused on the gendered vulnerability in a sample of the Italian population since cross-sectional research identified women to be more at-risk than men during this unprecedented situation. 2701 individuals (mean age ± standard deviation, 32.37 ± 11.62; range, 18–82) participated in a web-based longitudinal survey consisting of two measurements. Participants were first-time recruited on social networks and via telephone messages through a snowball sampling and tested during the third week of the lockdown period. Subsequently, a follow-up evaluation was carried out during the seventh week of lockdown. The survey assessed perceived stress, sleep quality, insomnia and depression symptoms, and anxiety, using the following questionnaires: the 10-item Perceived Stress Scale, the Pittsburgh Sleep Quality Index, the Insomnia Severity Index, the Beck Depression Inventory-second edition, and the State-Anxiety Inventory. Women showed the worst condition for all the examined dimensions in both the assessments. Nevertheless, at the follow-up women reported a reduction in perceived stress, insomnia and depression severity symptoms, and anxiety. On the other hand, male participants showed a worsening of perceived stress, sleep quality, and insomnia symptoms. Consequently, the gender prevalence gap of clinical conditions such as insomnia and depression was largely reduced under lockdown. Our investigation pointed to a different time course of sleep and mental health between genders during the home confinement period. Women seemed to show greater long-term resilience during the lockdown. Meanwhile, the male gender emerges as the most vulnerable category to the extension of the restraining measures. Our results suggest that there is no “weaker gender” after a prolonged lockdown. Indeed, the Italian population transversely presented signs of psychological suffering and significant sleep disturbances after the protracted and stressful lockdown period due to the COVID-19 pandemic.

Neurobiol Stress2020       LitCov and CORD-19
6482Management of COVID-19 Respiratory Distress  

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JAMA2020       LitCov and CORD-19
6483Sewage surveillance for the presence of SARS-CoV-2 genome as a useful wastewater based epidemiology (WBE) tracking tool in India  

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Water Sci Technol2020       LitCov and CORD-19
6484The Impact of COVID-19 on nurses working in a University Health System in Singapore: A qualitative descriptive study  

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Int J Ment Health Nurs2021       LitCov and CORD-19
6485Intracerebral Hemorrhage due to Thrombosis with Thrombocytopenia Syndrome after Vaccination against COVID-19: the First Fatal Case in Korea  

Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4). This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein. Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis. A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination. He developed severe headache with vomiting 9 days after the vaccination. Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage. Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzyme-linked immunosorbent assay antibody test was reported to be strongly positive. Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination. Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients. Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis.

J Korean Med Sci2021       LitCov and CORD-19
6486Different efficacies of neutralizing antibodies and antiviral drugs on SARS-CoV-2 Omicron subvariants, BA.1 and BA.2  

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Antiviral Res2022       LitCov
6487Long-term cardiovascular outcomes of COVID-19  

The cardiovascular complications of acute coronavirus disease 2019 (COVID-19) are well described, but the post-acute cardiovascular manifestations of COVID-19 have not yet been comprehensively characterized. Here we used national healthcare databases from the US Department of Veterans Affairs to build a cohort of 153,760 individuals with COVID-19, as well as two sets of control cohorts with 5,637,647 (contemporary controls) and 5,859,411 (historical controls) individuals, to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes. We show that, beyond the first 30 d after infection, individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. These risks and burdens were evident even among individuals who were not hospitalized during the acute phase of the infection and increased in a graded fashion according to the care setting during the acute phase (non-hospitalized, hospitalized and admitted to intensive care). Our results provide evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of those surviving the acute episode of COVID-19 should include attention to cardiovascular health and disease.

Nat Med2022       LitCov and CORD-19
6488COVID-19: the vasculature unleashed  

On the basis of emerging evidence from patients with COVID-19, we postulate that endothelial cells are essential contributors to the initiation and propagation of severe COVID-19. Here, we discuss current insights into the link between endothelial cells, viral infection and inflammatory changes and propose novel therapeutic strategies.

Nat Rev Immunol2020       LitCov and CORD-19
6489Coronaviruses post-SARS: update on replication and pathogenesis  

While coronaviruses were first identified nearly 60 years ago, they received notoriety in 2003 when one of their members was identified as the etiological agent of the Severe Acute Respiratory Syndrome (SARS-CoV) 1. Previously these viruses were known to be important agents of respiratory and enteric infections of domestic and companion animals and to cause approximately 15% of all cases of the common cold. This Review focuses on recent advances in our understanding of the mechanisms of coronavirus replication, interactions with the host immune response and disease pathogenesis and highlights the recent identification of numerous novel coronaviruses and the propensity of this virus family to cross species barriers.

Nat Rev Microbiol2009       CORD-19
6490Provisioning of personal protective equipment in hospitals in preparation for a pandemic  

BACKGROUND: At the beginning of the SARS-CoV‑2 outbreak, personal protective equipment (PPE) was scarce worldwide, leading to the treatment of patients partially without sufficient protection for the medical personnel. In order to be prepared for a new epidemic or pandemic or a “second wave” of COVID-19 outbreak and to meet a renewed deficiency of PPE, considerations were made on how personnel and patients can be better protected by appropriate provisioning. OBJECTIVE: The aim of this study was to develop a tool to predict the necessary amount of PPE to be in stock at a transregional university hospital for a certain period of time during a pandemic. MATERIAL AND METHODS: The consumption of PPE needed for every patient was calculated based on the following data of the Ulm University Hospital: the total consumption of healthcare workers’ PPE for April 2020 recorded by the materials management department and the number of patients suffering from COVID-19 and their treatment days. From the amount of PPE necessary for every patient in the intensive care unit (ICU) or in an infection ward, a PPE calculator was created in which the estimated amount of PPE can be calculated with the input variables “patients in intensive care unit”, “patients in infection ward” and “treatment days”. To validate the PPE calculator, the actual consumption of PPE for May 2020 at the Ulm University hospital was compared to the theoretically calculated demand by the PPE calculator. RESULTS: In April 2020 PPE consisting of 18 different items were kept in stock at Ulm University Hospital and in total 1,995,500 individual items were used. 22 intensive care patients with 257 nursing days and in the infection ward 39 patients with 357 nursing days were treated for COVID-19 disease, leading to a total of 603.2 man-days. A total of 34,550 KN95 masks, 1,558,780 gloves and 1100 goggles or protective visors were used, with a daily average of 49 NK95 masks and 2216 gloves required per ICU patient. In May 2020, 6 ICU patients and 19 patients in infection wards were treated for COVID-19 with 34 nursing days in intensive care and 201 nursing days in infection wards. The use of PPE material was 39% lower than in the previous month but in absolute terms 82% and on average 39% higher than calculated. CONCLUSION: The developed tool allows our hospital to estimate the necessary amount of PPE to be kept in stock for future pandemics. By taking local conditions into account this tool can also be helpful for other hospitals.

Anaesthesist2020       LitCov and CORD-19
6491COVID-19 Associated Multisystem Inflammatory Syndrome: A Systematic Review and Meta-analysis  

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Iran J Allergy Asthma Immunol2020       LitCov and CORD-19
6492Household Secondary Attack Rates of SARS-CoV-2 by Variant and Vaccination Status: An Updated Systematic Review and Meta-analysis  

IMPORTANCE: An overall household secondary attack rate (SAR) of 18.9% (95% CI, 16.2%-22.0%) through June 17, 2021 was previously reported for SARS-CoV-2. Emerging variants of concern and increased vaccination have affected transmission rates. OBJECTIVE: To evaluate how reported household SARs changed over time and whether SARs varied by viral variant and index case and contact vaccination status. DATA SOURCES: PubMed and medRxiv from June 18, 2021, through March 8, 2022, and reference lists of eligible articles. Preprints were included. STUDY SELECTION: Articles with original data reporting the number of infected and total number of household contacts. Search terms included SARS-CoV-2, COVID-19, variant, vaccination, secondary attack rate, secondary infection rate, household, index case, family contacts, close contacts, and family transmission. DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline was followed. Meta-analyses used generalized linear mixed models to obtain SAR estimates and 95% CIs. MAIN OUTCOMES AND MEASURES: SAR stratified by covariates according to variant, index case and contact vaccination status, and index case identification period. SARs were used to estimate vaccine effectiveness on the basis of the transmission probability for susceptibility to infection (VE(S,p)), infectiousness given infection (VE(I,p)), and total vaccine effectiveness (VE(T,p)). RESULTS: Household SARs were higher for 33 studies with midpoints in 2021 to 2022 (37.3%; 95% CI, 32.7% to 42.1%) compared with 63 studies with midpoints through April 2020 (15.5%; 95% CI, 13.2% to 18.2%). Household SARs were 42.7% (95% CI, 35.4% to 50.4%) for Omicron (7 studies), 36.4% (95% CI, 33.4% to 39.5%) for Alpha (11 studies), 29.7% (95% CI, 23.0% to 37.3%) for Delta (16 studies), and 22.5% (95% CI, 18.6% to 26.8%) for Beta (3 studies). For full vaccination, VE(S,p) was 78.6% (95% CI, 76.0% to 80.9%) for Alpha, 56.4% (95% CI, 54.6% to 58.1%) for Delta, and 18.1% (95% CI, −18.3% to 43.3%) for Omicron; VE(I,p) was 75.3% (95% CI, 69.9% to 79.8%) for Alpha, 21.9% (95% CI, 11.0% to 31.5%) for Delta, and 18.2% (95% CI, 0.6% to 32.6%) for Omicron; and VE(T,p) was 94.7% (95% CI, 93.3% to 95.8%) for Alpha, 64.4% (95% CI, 58.0% to 69.8%) for Delta, and 35.8% (95% CI, 13.0% to 52.6%) for Omicron. CONCLUSIONS AND RELEVANCE: These results suggest that emerging SARS-CoV-2 variants of concern have increased transmissibility. Full vaccination was associated with reductions in susceptibility and infectiousness, but more so for Alpha than Delta and Omicron. The changes in estimated vaccine effectiveness underscore the challenges of developing effective vaccines concomitant with viral evolution.

JAMA Netw Open2022       LitCov and CORD-19
6493Student-senior isolation prevention partnership: a Canada-wide programme to mitigate social exclusion during the COVID-19 pandemic  

Amidst the pandemic, Canada has taken critical steps to curb the transmission of the 2019 novel coronavirus disease (COVID-19). A key intervention has been physical distancing. Although physical distancing may protect older adults and other at-risk groups from COVID-19, research suggests quarantine and isolation may worsen mental health. Among older adults, social exclusion and social safety nets are social determinants of health (SDOH) that may be uniquely affected by the COVID-19 physical distancing measures. Health promotion programmes designed to reduce social exclusion and enhance social safety nets are one way to mitigate the potential mental health implications of this pandemic. The Student–Senior Isolation Prevention Partnership (SSIPP) is a student-led, community health promotion initiative that has scaled into a nation-wide effort to improve social connection among older adults. This initiative began with in-person visits and transformed into a tele-intervention guided by health promotion principles due to COVID-19. SSIPP continued to target the SDOH of social exclusion and social safety nets by pairing student volunteers with older adults to engage in weekly phone- and video-based interactions. Informed by the community partnership model by Best et al., SSIPP is built on the three orientations of empowerment, behaviour and organization, which are achieved through cross-disciplinary collaboration. This article reviews the importance of the adaptability of health promotion programmes, such as SSIPP during a pandemic, placing an emphasis on the lessons learned and future steps.

Health Promot Int2021       LitCov and CORD-19
6494Plant-derived natural polyphenols as potential antiviral drugs against SARS-CoV-2 via RNA-dependent RNA polymerase (RdRp) inhibition: an in-silico analysis  

The sudden outburst of Coronavirus disease (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a massive threat to global public health. Currently, no therapeutic drug or vaccine exists to treat COVID-19. Due to the time taking process of new drug development, drug repurposing might be the only viable solution to tackle COVID-19. RNA‐dependent RNA polymerase (RdRp) catalyzes SARS-CoV-2 RNA replication and hence, is an obvious target for antiviral drug design. Interestingly, several plant-derived polyphenols effectively inhibit the RdRp of other RNA viruses. More importantly, polyphenols have been used as dietary supplementations for a long time and played beneficial roles in immune homeostasis. We were curious to study the binding of polyphenols with SARS-CoV-2 RdRp and assess their potential to treat COVID-19. Herein, we made a library of polyphenols that have shown substantial therapeutic effects against various diseases. They were successfully docked in the catalytic pocket of RdRp. The investigation reveals that EGCG, theaflavin (TF1), theaflavin-3’-O-gallate (TF2a), theaflavin-3’-gallate (TF2b), theaflavin 3,3'-digallate (TF3), hesperidin, quercetagetin, and myricetin strongly bind to the active site of RdRp. Further, a 150-ns molecular dynamic simulation revealed that EGCG, TF2a, TF2b, TF3 result in highly stable bound conformations with RdRp. The binding free energy components calculated by the MM-PBSA also confirm the stability of the complexes. We also performed a detailed analysis of ADME prediction, toxicity prediction, and target analysis for their druggability. Overall, our results suggest that EGCG, TF2a, TF2b, TF3 can inhibit RdRp and represent an effective therapy for COVID-19. Communicated by Ramaswamy H. Sarma

J Biomol Struct Dyn2020       LitCov and CORD-19
6495A new era for nuclear medicine  

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Hell J Nucl Med2020       LitCov and CORD-19
6496Role of booster with BNT162b2 mRNA in SARS-CoV-2 vaccination in patients with rheumatoid arthritis  

Only case reports and small clinical series report the effects of booster vaccination with BNT162b2 in patients with rheumatoid arthritis (RA). We studied 200 patients with RA in clinical remission evaluated with the DAS28. All patients were vaccinated for SARS CoV-2 with the BNT162b2 mRNA vaccine. The value of anti-SARS-CoV 2 Spike RBD IgG antibodies was determined at T1 (3 weeks after first vaccination) and T2 (3 weeks after booster). In addition, patients underwent assessment of lymphocyte subpopulations by flow cytometry analysis before starting the vaccination cycle (T0). Furthermore, the serum antibody levels of 96 health care workers (HCWs) were analyzed for comparison. DAS28 values at T0, T1, and T2 indicated remission or low disease activity in all patients. Levels of anti-SARS CoV-2 IgG at T1 were higher in HCWs than in patients’ groups: 1562.00 BAU WHO/mL [975.00–1632.00] vs 416.00 BAU WHO/mL [110.00, 1581.00], p <0.001. Anti-SARS COV2 IgG levels at T1 and at T2 were slightly lower in patients taking b/tsDMARDs than in patients under csDMARDs. Regression analysis evidenced age, treatment with abatacept (ABA), JAK inhibitors, and rituximab (RTX) as negative predictors of higher anti-SARS CoV-2 IgG levels at T1. Moreover, treatment with anti-IL6, anti-JAK, and anti-tumor necrosis factor (TNF) emerged as positive predictors of higher levels of anti-SARS CoV-2 IgG at T2. Our data show that despite the booster vaccine with BNT162b2, seroconversion in patients with rheumatoid arthritis is influenced by the background therapy, particularly for patients being treated with ABA and RTX. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12026-022-09283-y.

Immunol Res2022       LitCov and CORD-19
6497Knowledge, attitudes and practices of face mask utilization and associated factors in COVID-19 pandemic among Wachemo University Students, Southern Ethiopia: A cross-sectional study  

INTRODUCTION: The widespread use of face masks by the general public may help to prevent the spread of viruses. Face masks are thought to be a good strategy to protect against respiratory diseases such as the Coronavirus. Identifying student knowledge, attitude, and practice about the use of face masks is crucial to detect vulnerabilities and respond rapidly to avoid the spread of the infection. This study aimed to determine the knowledge, attitude, and practices of face mask utilization and associated factors in the COVID-19 pandemic among college students. METHODS: A cross-sectional study was performed from February to March 2021 among 764 students from Wachemo University, Southern Ethiopia. A multistage sampling technique was used in the study. The sample size for each department was allocated in proportion to the number of students in that department, and each respondent was chosen using a simple random sampling procedure. Data were collected using a pre-tested self-administered questionnaire and analyzed using SPSS version 26. To predict the relationship between the predictor and outcome variables, a logistic regression model was used. At a p-value of 0.05, statistical significance was declared. RESULTS: The study showed that the overall knowledge of the students was 223 (29.2%), their attitude was 673 (88.1%), and their practice was 684 (89.5%). The students from the college natural and computational sciences (AOR: 0.23; 95%CI: 0.13, 0.40) and students having good knowledge (AOR = 4.40; 95%CI; 2.13, 9.14) were found to be independently associated with face mask utilization. CONCLUSION: When compared to other researches, the knowledge about the usage of face masks in this study was low, but the attitudes and practices were high. Authorities in areas that are in danger of a COVID-19 pandemic should plan and implement public awareness and education initiatives.

PLoS One2021       LitCov and CORD-19
6498The Australasian COVID-19 Trial (ASCOT) to assess clinical outcomes in hospitalised patients with SARS-CoV-2 infection treated with lopinavir/ritonavir and/or hydroxychloroquine compared to standard of care: A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. TRIAL DESIGN: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. PARTICIPANTS: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently. INTERVENTION AND COMPARATOR: Participants will be randomised 1:1:1:1 to: Group 1: standard of care; Group 2: lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form; Group 3: hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days; Group 4: lopinavir /ritonavir plus hydroxychloroquine. MAIN OUTCOMES: Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated. RANDOMISATION: The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have individual participant allocation provided through a web-based trial enrolment platform. BLINDING (MASKING): This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required sample size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 2440. TRIAL STATUS: ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12620000445976). Prospectively registered April 6, 2020. 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.

Trials2020       LitCov and CORD-19
6499Does Pandemic Anxiety Affect Urology Healthcare Workers?  

PURPOSE: To assess anxiety, stress level, and perception of safety during the coronavirus disease 2019 (COVID-19) pandemic in health care workers (HCWs) of one of Germany's largest urology university clinics. METHODS: A cross-sectional study among urological HCWs was performed. HCWs were surveyed for anxiety about the pandemic, stress level and current workload, fear of coronavirus infection, current perception of safety at work, and attitude towards protective equipment and tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: Sixty-three HCWs filled in the questionnaire. Overall anxiety of infection with CO­VID-19 is at a median of 4.7 with no statistically significant difference between nurses and physicians (p = 0.0749). Safety at work reaches a median of 6 out of 10. In fact, the highest fear in 56.7% (31/63) of the personnel is to get infected by a colleague tested positive for SARS-CoV-2 despite wearing surgical face masks. A proportion of 55.7 and 74.6% highly favor swabs for SARS-CoV-2 on a regular basis in HCWs and patients, respectively (p = 0.0001). Workload in the urology department is clearly reduced during the pandemic (physicians 39.3% vs. nurses 32.2%, p = 0.0001) and 57.4% do not feel distress at all; only 27.9% express mental distress. CONCLUSION: During the pandemic, urology HCWs perceive lower burden by workload and deem themselves at low risk of infection. However, the greatest anxiety is related to infection by a SARS-CoV-2-positive colleague, despite reciprocal protection by surgical face masks. This highlights a relevant mental stress and uncertainty towards management of infected HCWs, calling for increased education and psychological support.

Urol Int2021       LitCov and CORD-19
6500CPAP management of COVID-19 respiratory failure: a first quantitative analysis from an inpatient service evaluation  

OBJECTIVE: To evaluate the role of continuous positive air pressure (CPAP) in the management of respiratory failure associated with COVID-19 infection. Early clinical management with limited use of CPAP (3% of patients) was compared with a later clinical management strategy which had a higher proportion of CPAP use (15%). DESIGN: Retrospective case-controlled service evaluation for a single UK National Health Service (NHS) Trust during March–June 2020 designed and conducted solely to estimate the effects of current care. SETTING: The acute inpatient unit in Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust, a medium-sized English NHS Trust. PARTICIPANTS: 206 patients with antigen confirmed COVID-19 disease and severe acute respiratory syndrome admitted between 17 March 2020 and 3 April 2020 for the early group (controls), and between 10 April 2020 and 11 May 2020 for the late group (cases). Follow-up for all cases was until 11 June by which time all patients had a final outcome of death or discharge. Both groups were composed of 103 patients. Cases and controls were matched by age and sex. OUTCOME MEASURE: The outcome measure was the proportion of patients surviving at time t (time from the positive result of COVID-19 test to discharge/death date). The predictors were CPAP intervention, intubation, residence in care homes and comorbidities (renal, pulmonary, cardiac, hypertension and diabetes). A stratified Cox proportional hazard for clustered data (via generalised estimating equations) and model selection algorithms were employed to identify the effect of CPAP on patients’ survival and the effect on gas exchange as measured by alveolar arterial (A-a) gradient and timing of CPAP treatment on CPAP patients’ survival. RESULTS: CPAP was found to be significantly (HR 0.38, 95% CI 0.36 to 0.40) associated with lower risk of death in patients with hospital stay equal to, or below 7 days. However, for longer hospitalisation CPAP was found to be associated with increased risk of death (HR 1.72, 95% CI 1.40 to 2.12). When CPAP was initiated within 4 days of hospital admission, the survival probability was above 73% (95% CI 53% to 99%). In addition, lower A-a gradient was associated with lower risk of death in CPAP patients (HR 1.011, 95% CI 1.010 to 1.013). The selected model (best fit) was stratified by sex and clustered by case/control groups. The predictors were age, intubation, hypertension and the residency from care homes, which were found to be statistically significantly associated with patient’s death/discharge. CONCLUSIONS: CPAP is a simple and cost-effective intervention. It has been established for care of other respiratory disorders but not for COVID-19 respiratory failure. This evaluation establishes that CPAP as a potentially viable treatment option for this group of patients during the first days of hospital admission. As yet there is limited availability of quantitative research on CPAP use for COVID-19. Whist this work is hampered by both the relatively small sample size and retrospective design (which reduced the ability to control potential confounders), it represents evidence of the significant benefit of early CPAP intervention. This evaluation should stimulate further research questions and larger study designs on the potential benefit of CPAP for COVID-19 infections. Globally, this potentially beneficial low cost and low intensity therapy could have added significance economically for healthcare provision in less developed countries.

BMJ Open Respir Res2020       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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