\ 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
5301Maternal Mental Health under COVID-19 Pandemic in Thailand  

Numerous nations have implemented lockdown measures in response to the COVID-19 pandemic. As a consequence of the lockdown on daily living, social participation, and health service accessibility, vulnerable people, for example, new mothers, may experience an increase in mental health problems. This cross-sectional survey was conducted to investigate the impact of the COVID-19 pandemic lockdown on Thai new mothers and the variables affecting their mental health. The survey data were collected from 903 Thai mothers with infants aged 0–12 months using an online platform and a face-to-face interview questionnaire survey between 17 July and 17 October 2020, during the first nationwide COVID-19 lockdown period. For the final analysis, there were 862 participants who completed all of the questions. The full exploratory analysis was performed by multivariable linear regression to identify the variables influencing maternal mental health. Our study demonstrated that new mothers reported feeling a high extent to some extent of worry (44.9%), increased appetite (40.4%), becoming easily annoyed or irritable (39.1%), and feeling down (33.5%), whereas 82.7% felt able to cope with the first lockdown situation. Practiced relaxation techniques were associated with positive maternal mental health (adjusted β = 1.05, 95% CI 0.57 to 1.52, p < 0.001). The perceived impact of the COVID-19 lockdown was on the household’s ability to pay for rent, to make mortgage payments (adjusted β = −1.59, 95% CI −2.87 to −0.36, p = 0.011), the household’s ability to pay for other essentials, such as utilities and medication (adjusted β = −1.99, 95% CI −3.16 to −0.81, p = 0.001), household crowding after lockdown (adjusted β = −3.46, 95% CI −4.86 to −2.06, p < 0.001), and not going outside or doing outdoor activities (adjusted β = −2.22, 95% CI −3.35 to −1.08, p < 0.001). These impacts were significantly associated with negative mental health. In conclusion, our results emphasize the critical need for continuous monitoring of maternal mental health and developing an effective response strategy and activity for promoting maternal mental health under the stress of repetitive lockdowns and increased economic pressures.

Int J Environ Res Public Healt2021       LitCov and CORD-19
5302Rapid response to the COVID-19 pandemic: Vietnam government's experience and preliminary success  

BACKGROUND: The COVID-19 pandemic has hit all corners of the world, challenging governments to act promptly in controlling the spread of the pandemic. Due to limited resources and inferior technological capacities, developing countries including Vietnam have faced many challenges in combating the pandemic. Since the first cases were detected on 23 January 2020, Vietnam has undergone a 3-month fierce battle to control the outbreak with stringent measures from the government to mitigate the adverse impacts. In this study, we aim to give insights into the Vietnamese government’s progress during the first three months of the outbreak. Additionally, we relatively compare Vietnam’s response with that of other Southeast Asia countries to deliver a clear and comprehensive view on disease control strategies. METHODS: The data on the number of COVID-19 confirmed and recovered cases in Vietnam was obtained from the Dashboard for COVID-19 statistics of the Ministry of Health (https://ncov.vncdc.gov.vn/). The review on Vietnam’s country-level responses was conducted by searching for relevant government documents issued on the online database ‘Vietnam Laws Repository’ (https://thuvienphapluat.vn/en/index.aspx), with the grey literature on Google and relevant official websites. A stringency index of government policies and the countries’ respective numbers of confirmed cases of nine Southeast Asian countries were adapted from the Oxford COVID-19 Government Response Tracker (https://www.bsg.ox.ac.uk/research/research-projects/coronavirus-government-response-tracker). All data was updated as of 24 April 2020. RESULTS: Preliminary positive results have been achieved given that the nation confirmed no new community-transmitted cases since 16 April and zero COVID-19 – related deaths throughout the 3-month pandemic period. To date, the pandemic has been successfully controlled thanks to the Vietnamese government’s prompt, proactive and decisive responses including mobilization of the health care systems, security forces, economic policies, along with a creative and effective communication campaign corresponding with crucial milestones of the epidemic’s progression. CONCLUSIONS: Vietnam could be one of the role models in pandemic control for low-resource settings. As the pandemic is still ongoing in an unpredictable trajectory, disease control measures should continue to be put in place in the foreseeable short term.

J Glob Health2020       LitCov and CORD-19
5303General surgery practice under the COVID-19 pandemic: The experience of a pandemic hospital in Istanbul  

N/A

Ulus Travma Acil Cerrahi Derg2022       LitCov and CORD-19
5304Determinants of COVID-19 vaccine acceptance and hesitancy: a cross-sectional study in Saudi Arabia  

N/A

Hum Vaccin Immunother2021       LitCov and CORD-19
5305The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and proteases of the human airways  

The high transmissibility of SARS-CoV-2 is related to abundant replication in the upper airways, which is not observed for the other highly pathogenic coronaviruses SARS-CoV and MERS-CoV. We here reveal features of the coronavirus spike (S) protein, which optimize the virus towards the human respiratory tract. First, the S proteins exhibit an intrinsic temperature preference, corresponding with the temperature of the upper or lower airways. Pseudoviruses bearing the SARS-CoV-2 spike (SARS-2-S) were more infectious when produced at 33°C instead of 37°C, a property shared with the S protein of HCoV-229E, a common cold coronavirus. In contrast, the S proteins of SARS-CoV and MERS-CoV favored 37°C, in accordance with virus preference for the lower airways. Next, SARS-2-S-driven entry was efficiently activated by not only TMPRSS2, but also the TMPRSS13 protease, thus broadening the cell tropism of SARS-CoV-2. Both proteases proved relevant in the context of authentic virus replication. TMPRSS13 appeared an effective spike activator for the virulent coronaviruses but not the low pathogenic HCoV-229E virus. Activation of SARS-2-S by these surface proteases requires processing of the S1/S2 cleavage loop, in which both the furin recognition motif and extended loop length proved critical. Conversely, entry of loop deletion mutants is significantly increased in cathepsin-rich cells. Finally, we demonstrate that the D614G mutation increases SARS-CoV-2 stability, particularly at 37°C, and, enhances its use of the cathepsin L pathway. This indicates a link between S protein stability and usage of this alternative route for virus entry. Since these spike properties may promote virus spread, they potentially explain why the spike-G614 variant has replaced the early D614 variant to become globally predominant. Collectively, our findings reveal adaptive mechanisms whereby the coronavirus spike protein is adjusted to match the temperature and protease conditions of the airways, to enhance virus transmission and pathology.

PLoS Pathog2021       LitCov and CORD-19
5306The effect of the COVID-19 pandemic on emergency department visits for serious cardiovascular conditions  

OBJECTIVE: We examine how emergency department (ED) visits for serious cardiovascular conditions evolved in the coronavirus (COVID-19) pandemic over January–October 2020, compared to 2019, in a large sample of U.S. EDs. METHODS: We compared 2020 ED visits before and during the COVID-19 pandemic, relative to 2019 visits in 108 EDs in 18 states in 115,716 adult ED visits with diagnoses for five serious cardiovascular conditions: ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), ischemic stroke (IS), hemorrhagic stroke (HS), and heart failure (HF). We calculated weekly ratios of ED visits in 2020 to visits in 2019 in the pre-pandemic (Jan 1-March 10), early-pandemic (March 11–April 21), and later-pandemic (April 22–October 31) periods. RESULTS: ED visit ratios show that NSTEMI, IS, and HF visits dropped to lows of 56%, 64%, and 61% of 2019 levels, respectively, in the early-pandemic and gradually returned to 2019 levels over the next several months. HS visits also dropped early pandemic period to 60% of 2019 levels, but quickly rebounded. We find mixed evidence on whether STEMI visits fell, relative to pre-pandemic rates. Total adult ED visits nadired at 57% of 2019 volume during the early-pandemic period and have only party recovered since, to approximately 84% of 2019 by the end of October 2020. CONCLUSION: We confirm prior studies that ED visits for serious cardiovascular conditions declined early in the COVID-19 pandemic for NSTEMI, IS, HS, and HF, but not for STEMI. Delays or non-receipt in ED care may have led to worse outcomes.

Am J Emerg Med2021       LitCov and CORD-19
5307Excess deaths associated with covid-19 pandemic in 2020: age and sex disaggregated time series analysis in 29 high income countries  

OBJECTIVE: To estimate the direct and indirect effects of the covid-19 pandemic on mortality in 2020 in 29 high income countries with reliable and complete age and sex disaggregated mortality data. DESIGN: Time series study of high income countries. SETTING: Austria, Belgium, Czech Republic, Denmark, England and Wales, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, the Netherlands, New Zealand, Northern Ireland, Norway, Poland, Portugal, Scotland, Slovakia, Slovenia, South Korea, Spain, Sweden, Switzerland, and United States. PARTICIPANTS: Mortality data from the Short-term Mortality Fluctuations data series of the Human Mortality Database for 2016-20, harmonised and disaggregated by age and sex. INTERVENTIONS: Covid-19 pandemic and associated policy measures. MAIN OUTCOME MEASURES: Weekly excess deaths (observed deaths versus expected deaths predicted by model) in 2020, by sex and age (0-14, 15-64, 65-74, 75-84, and ≥85 years), estimated using an over-dispersed Poisson regression model that accounts for temporal trends and seasonal variability in mortality. RESULTS: An estimated 979 000 (95% confidence interval 954 000 to 1 001 000) excess deaths occurred in 2020 in the 29 high income countries analysed. All countries had excess deaths in 2020, except New Zealand, Norway, and Denmark. The five countries with the highest absolute number of excess deaths were the US (458 000, 454 000 to 461 000), Italy (89 100, 87 500 to 90 700), England and Wales (85 400, 83 900 to 86 800), Spain (84 100, 82 800 to 85 300), and Poland (60 100, 58 800 to 61 300). New Zealand had lower overall mortality than expected (−2500, −2900 to −2100). In many countries, the estimated number of excess deaths substantially exceeded the number of reported deaths from covid-19. The highest excess death rates (per 100 000) in men were in Lithuania (285, 259 to 311), Poland (191, 184 to 197), Spain (179, 174 to 184), Hungary (174, 161 to 188), and Italy (168, 163 to 173); the highest rates in women were in Lithuania (210, 185 to 234), Spain (180, 175 to 185), Hungary (169, 156 to 182), Slovenia (158, 132 to 184), and Belgium (151, 141 to 162). Little evidence was found of subsequent compensatory reductions following excess mortality. CONCLUSION: Approximately one million excess deaths occurred in 2020 in these 29 high income countries. Age standardised excess death rates were higher in men than women in almost all countries. Excess deaths substantially exceeded reported deaths from covid-19 in many countries, indicating that determining the full impact of the pandemic on mortality requires assessment of excess deaths. Many countries had lower deaths than expected in children <15 years. Sex inequality in mortality widened further in most countries in 2020.

BMJ2021       LitCov and CORD-19
5308Economic impact of government interventions during the COVID-19 pandemic: International evidence from financial markets  

The outbreak of COVID-19 pandemic came as a rare, unprecedented event and governments around the globe scrambled with emergency actions including social distancing measures, public awareness programs, testing and quarantining policies, and income support packages. In this paper, we examine the expected economic impact of government actions by analyzing the effect of such actions on stock market returns. Using daily data from January 22 to April 17, 2020 from 77 countries, we find announcements of government social distancing measures have a direct negative effect on stock market returns due to their adverse effect on economic activity, while an indirect positive effect through the reduction in COVID-19 confirmed cases. Government announcements regarding public awareness programs, testing and quarantining policies, and income support packages largely result in positive market returns. Our findings have important policy implications, primarily by showing that government social distancing measures have both positive and negative economic impact.

J Behav Exp Finance2020       LitCov and CORD-19
5309Inhaled corticosteroids for the treatment of COVID-19  

N/A

Cochrane Database Syst Rev2022       LitCov and CORD-19
5310Quality and Adoption of COVID-19 Tracing Apps and Recommendations for Development: Systematic Interdisciplinary Review of European Apps  

BACKGROUND: Simulation study results suggest that COVID-19 contact tracing apps have the potential to achieve pandemic control. Concordantly, high app adoption rates were a stipulated prerequisite for success. Early studies on potential adoption were encouraging. Several factors predicting adoption rates were investigated, especially pertaining to user characteristics. Since then, several countries have released COVID-19 contact tracing apps. OBJECTIVE: This study’s primary aim is to investigate the quality characteristics of national European COVID-19 contact tracing apps, thereby shifting attention from user to app characteristics. The secondary aim is to investigate associations between app quality and adoption. Finally, app features contributing to higher app quality were identified. METHODS: Eligible COVID-19 contact tracing apps were those released by national health authorities of European Union member states, former member states, and countries of the European Free Trade Association, all countries with comparable legal standards concerning personal data protection and app use voluntariness. The Mobile App Rating Scale was used to assess app quality. An interdisciplinary team, consisting of two health and two human–computer interaction scientists, independently conducted Mobile App Rating Scale ratings. To investigate associations between app quality and adoption rates and infection rates, Bayesian linear regression analyses were conducted. RESULTS: We discovered 21 national COVID-19 contact tracing apps, all demonstrating high quality overall and high-level functionality, aesthetics, and information quality. However, the average app adoption rate of 22.9% (SD 12.5%) was below the level recommended by simulation studies. Lower levels of engagement-oriented app design were detected, with substantial variations between apps. By regression analyses, the best-case adoption rate was calculated by assuming apps achieve the highest ratings. The mean best-case adoption rates for engagement and overall app quality were 39.5% and 43.6%, respectively. Higher adoption rates were associated with lower cumulative infection rates. Overall, we identified 5 feature categories (symptom assessment and monitoring, regularly updated information, individualization, tracing, and communication) and 14 individual features that contributed to higher app quality. These 14 features were a symptom checker, a symptom diary, statistics on COVID-19, app use, public health instructions and restrictions, information of burden on health care system, assigning personal data, regional updates, control over tracing activity, contact diary, venue check-in, chats, helplines, and app-sharing capacity. CONCLUSIONS: European national health authorities have generally released high quality COVID-19 contact tracing apps, with regard to functionality, aesthetics, and information quality. However, the app’s engagement-oriented design generally was of lower quality, even though regression analyses results identify engagement as a promising optimization target to increase adoption rates. Associations between higher app adoption and lower infection rates are consistent with simulation study results, albeit acknowledging that app use might be part of a broader set of protective attitudes and behaviors for self and others. Various features were identified that could guide further engagement-enhancing app development.

J Med Internet Res2021       LitCov and CORD-19
5311Antigenic characterization of the SARS-CoV-2 Omicron subvariant BA.2.75  

N/A

Cell Host Microbe2022       LitCov
5312Seroprevalence of antibodies to SARS-CoV-2 in healthcare workers & implications of infection control practice in India  

BACKGROUND & OBJECTIVES: Healthcare workers (HCWs) are considered to be at a high risk of contracting COVID-19 infection. Besides, control of nosocomial infections transmitted from HCWs to the patients is also a cause of concern. This study was undertaken to investigate the seroprevalence of antibodies against the SARS-CoV-2 virus among the hospital staff of a tertiary care health facility in north India. METHODS: The HCWs were tested for SARS-CoV-2 serology (IgG+IgM) using chemiluminescence immunoassay between June 22 and July 24, 2020. Venous blood (2 ml) was collected and tested for SARS-CoV-2 IgG and IgM antibodies. RESULTS: Of the 3739 HCWs tested, 487 (13%) were positive for total SARS-CoV-2 antibodies. The highest seroprevalence was observed in administrative staff (19.6%) and least in physicians (5.4%). The staff who used public (20%) and hospital transportation (16.9%) showed higher seroprevalence compared to staff using personal transportation (12.4%). No difference was observed between HCWs posted in COVID versus non-COVID areas. All seropositive symptomatic HCWs in our study (53.6%) had mild symptoms, and the remaining 46.4 per cent were asymptomatic. The antibody positivity rate progressively increased from 7.0 per cent in the first week to 18.6 per cent in the fourth week during the study. INTERPRETATION & CONCLUSIONS: The presence of antibodies to SARS-CoV-2 in a significant number of asymptomatic HCWs, association with the use of public transport, relatively lower seroprevalence compared with the non-HCWs and rising trend during the period of the study highlight the need for serosurveillance, creating awareness for infection control practices including social distancing and study of infection dynamics in the community for effective control of an infectious pandemic.

Indian J Med Res2021       LitCov and CORD-19
5313COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs  

In the Wuhan Province of China, in December 2019, the novel coronavirus 2019 (COVID-19) has caused a severe involvement of the lower respiratory tract leading to an acute respiratory syndrome. Subsequently, coronavirus 2 (SARS-CoV-2) provoked a pandemic which is considered a life-threatening disease. The SARS-CoV-2, a family member of betacoronaviruses, possesses single-stranded positive-sense RNA with typical structural proteins, involving the envelope, membrane, nucleocapsid and spike proteins that are responsible for the viral infectivity, and nonstructural proteins. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of proinflammatory cytokines “cytokine storm” leading to an acute respiratory distress syndrome. Regretfully, the exact pathophysiology and treatment, especially for the severe COVID-19, is still uncertain. The results of preliminary studies have shown that immune-modulatory or immune-suppressive treatments such as hydroxychloroquine, interleukin (IL)-6 and IL-1 antagonists, commonly used in rheumatology, might be considered as treatment choices for COVID-19, particularly in severe disease. In this review, to gain better information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, we have focused the attention on the structural features of SARS-CoV-2, the host immune response against SARS-CoV-2 and its association with the cytokine storm.

Turk J Med Sci2020       LitCov and CORD-19
5314Demographic Factors Influencing the Impact of Coronavirus-Related Misinformation on WhatsApp: Cross-sectional Questionnaire Study  

BACKGROUND: The risks of misinformation on social networking sites is a global issue, especially in light of the COVID-19 infodemic. WhatsApp is being used as an important source of COVID-19–related information during the current pandemic. Unlike Facebook and Twitter, limited studies have investigated the role of WhatsApp as a source of communication, information, or misinformation during crisis situations. OBJECTIVE: Our study aimed to evaluate the vulnerability of demographic cohorts in a developing country toward COVID-19–related misinformation shared via WhatsApp. We also aimed to identify characteristics of WhatsApp messages associated with increased credibility of misinformation. METHODS: We conducted a web-based questionnaire survey and designed a scoring system based on theories supported by the existing literature. Vulnerability (K) was measured as a ratio of the respondent’s score to the maximum score. Respondents were stratified according to age and occupation, and K(mean) was calculated and compared among each subgroup using single-factor analysis of variance and Hochberg GT2 tests. The questionnaire evaluated the respondents’ opinion of the veracity of coronavirus-related WhatsApp messages. The responses to the false-proven messages were compared using z test between the 2 groups: coronavirus-related WhatsApp messages with an attached link and/or source and those without. RESULTS: We analyzed 1137 responses from WhatsApp users in India. Users aged over 65 years had the highest vulnerability (K(mean)=0.38, 95% CI 0.341-0.419) to misinformation. Respondents in the age group 19-25 years had significantly lower vulnerability (K(mean)=0.31, 95% CI 0.301-0.319) than those aged over 25 years (P<.05). The vulnerability of users employed in elementary occupations was the highest (K(mean)=0.38, 95% CI 0.356-0.404), and it was significantly higher than that of professionals and students (P<.05). Interestingly, the vulnerability of healthcare workers was not significantly different from that of other occupation groups (P>.05). We found that false CRWMs with an attached link and/or source were marked true 6 times more often than false CRWMs without an attached link or source (P<.001). CONCLUSIONS: Our study demonstrates that in a developing country, WhatsApp users aged over 65 years and those involved in elementary occupations were found to be the most vulnerable to false information disseminated via WhatsApp. Health care workers, who are otherwise considered as experts with regard to this global health care crisis, also shared this vulnerability to misinformation with other occupation groups. Our findings also indicated that the presence of an attached link and/or source falsely validating an incorrect message adds significant false credibility, making it appear true. These results indicate an emergent need to address and rectify the current usage patterns of WhatsApp users. This study also provides metrics that can be used by health care organizations and government authorities of developing countries to formulate guidelines to contain the spread of WhatsApp-related misinformation.

JMIR Public Health Surveill2021       LitCov and CORD-19
5315Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial  

N/A

JAMA2020       LitCov and CORD-19
5316COVID-19 cytokine storm: the interplay between inflammation and coagulation  

Lancet Respir Med2020       LitCov and CORD-19
5317Social Support and Optimism as Protective Factors for Mental Health among 7765 Healthcare Workers in Germany during the COVID-19 Pandemic: Results of the VOICE Study  

Background: The COVID-19 pandemic is impacting mental health worldwide, particularly among healthcare workers (HCWs). Risk and protective factors for depression and generalized anxiety in healthcare workers need to be identified to protect their health and ability to work. Social support and optimism are known protective psychosocial resources, but have not been adequately studied in the context of the COVID-19 pandemic among healthcare workers in Germany. Methods: Within the first wave of the VOICE study (n = 7765), a longitudinal web-based survey study among healthcare workers in Germany, we assessed symptoms of depression (PHQ-2) and generalized anxiety (GAD-2), social support (ENRICHD Social Support Inventory; ESSI), and generalized optimism as well as sociodemographic, occupational, and COVID-19 related variables. Multiple linear regression analyses were conducted to examine associations between the constructs. Results: The analyses revealed that higher levels of social support and optimism were associated with lower levels of depression and generalized anxiety. They showed a higher association with depression and generalized anxiety than demographic or occupational risk factors such as female gender and direct contact with infected individuals. Conclusion: Psychosocial resources such as social support and optimism appear to contribute to successful coping with the COVID-19 pandemic and should be considered in future studies.

Int J Environ Res Public Healt2021       LitCov and CORD-19
5318SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects  

N/A

Nat Struct Mol Biol2020       LitCov and CORD-19
5319Evaluation of green tea polyphenols as novel corona virus (SARS CoV-2) main protease (Mpro) inhibitors-an in silico docking and molecular dynamics simulation study  

Coronavirus disease 2019 (COVID-19) is a viral respiratory disease which caused global health emergency and announced as pandemic disease by World Health Organization. Lack of specific drug molecules or treatment strategy against this disease makes it more devastating. Thus, there is an urgent need of effective drug molecules to fight against COVID-19. The main protease (Mpro) of SARS CoV-2, a key component of this viral replication, is considered as a prime target for anti-COVID-19 drug development. In order to find potent Mpro inhibitors, we have selected eight polyphenols from green tea, as these are already known to exert antiviral activity against many RNA viruses. We have elucidated the binding affinities and binding modes between these polyphenols including a well-known Mpro inhibitor N3 (having binding affinity −7.0 kcal/mol) and Mpro using molecular docking studies. All eight polyphenols exhibit good binding affinity toward Mpro (−7.1 to −9.0 kcal/mol). However, only three polyphenols (epigallocatechin gallate, epicatechingallate and gallocatechin-3-gallate) interact strongly with one or both catalytic residues (His41 and Cys145) of Mpro. Molecular dynamics simulations (100 ns) on these three Mpro–polyphenol systems further reveal that these complexes are highly stable, experience less conformational fluctuations and share similar degree of compactness. Estimation of total number of intermolecular H-bond and MM-GBSA analysis affirm the stability of these three Mpro–polyphenol complexes. Pharmacokinetic analysis additionally suggested that these polyphenols possess favorable drug-likeness characteristics. Altogether, our study shows that these three polyphenols can be used as potential inhibitors against SARS CoV-2 Mpro and are promising drug candidates for COVID-19 treatment. Communicated by Ramaswamy H. Sarma

J Biomol Struct Dyn2020       LitCov and CORD-19
5320Computational Analysis of Mutations in the Receptor-Binding Domain of SARS-CoV-2 Spike and Their Effects on Antibody Binding  

Currently, SARS-CoV-2 causing coronavirus disease 2019 (COVID-19) is responsible for one of the most deleterious pandemics of our time. The interaction between the ACE2 receptors at the surface of human cells and the viral Spike (S) protein triggers the infection, making the receptor-binding domain (RBD) of the SARS-CoV-2 S-protein a focal target for the neutralizing antibodies (Abs). Despite the recent progress in the development and deployment of vaccines, the emergence of novel variants of SARS-CoV-2 insensitive to Abs produced in response to the vaccine administration and/or monoclonal ones represent a potential danger. Here, we analyzed the diversity of neutralizing Ab epitopes and assessed the possible effects of single and multiple mutations in the RBD of SARS-CoV-2 S-protein on its binding affinity to various antibodies and the human ACE2 receptor using bioinformatics approaches. The RBD-Ab complexes with experimentally resolved structures were grouped into four clusters with distinct features at sequence and structure level. The performed computational analysis indicates that while single amino acid replacements in RBD may only cause partial impairment of the Abs binding, moreover, limited to specific epitopes, the variants of SARS-CoV-2 with multiple mutations, including some which were already detected in the population, may potentially result in a much broader antigenic escape. Further analysis of the existing RBD variants pointed to the trade-off between ACE2 binding and antigenic escape as a key limiting factor for the emergence of novel SAR-CoV-2 strains, as the naturally occurring mutations in RBD tend to reduce its binding affinity to Abs but not to ACE2. The results provide guidelines for further experimental studies aiming to identify high-risk RBD mutations that allow for an antigenic escape.

Viruses2022       LitCov and CORD-19
5321Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA Vaccination Against Multisystem Inflammatory Syndrome in Children Among Persons Aged 12-18 Years-United States, July-December 2021  

Multisystem inflammatory syndrome in children (MIS-C) is a severe postinfectious hyperinflammatory condition, which generally occurs 2-6 weeks after a typically mild or asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19 (1-3). In the United States, the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine is currently authorized for use in children and adolescents aged 5-15 years under an Emergency Use Authorization and is fully licensed by the Food and Drug Administration for persons aged ≥16 years (4). Prelicensure randomized trials in persons aged ≥5 years documented high vaccine efficacy and immunogenicity (5),§ and real-world studies in persons aged 12-18 years demonstrated high vaccine effectiveness (VE) against severe COVID-19 (6). Recent evidence suggests that COVID-19 vaccination is associated with lower MIS-C incidence among adolescents (7); however, VE of the 2-dose Pfizer-BioNTech regimen against MIS-C has not been evaluated. The effectiveness of 2 doses of Pfizer-BioNTech vaccine received ≥28 days before hospital admission in preventing MIS-C was assessed using a test-negative case-control design¶ among hospitalized patients aged 12-18 years at 24 pediatric hospitals in 20 states** during July 1-December 9, 2021, the period when most MIS-C patients could be temporally linked to SARS-CoV-2 B.1.617.2 (Delta) variant predominance. Patients with MIS-C (case-patients) and two groups of hospitalized controls matched to case-patients were evaluated: test-negative controls had at least one COVID-19-like symptom and negative SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) or antigen-based assay results, and syndrome-negative controls were hospitalized patients without COVID-19-like illness. Among 102 MIS-C case-patients and 181 hospitalized controls, estimated effectiveness of 2 doses of Pfizer-BioNTech vaccine against MIS-C was 91% (95% CI = 78%-97%). All 38 MIS-C patients requiring life support were unvaccinated. Receipt of 2 doses of the Pfizer-BioNTech vaccine is associated with a high level of protection against MIS-C in persons aged 12-18 years, highlighting the importance of vaccination among all eligible children.

MMWR Morb Mortal Wkly Rep2022       LitCov and CORD-19
5322Ultra-Sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 21 million people worldwide since August 16, 2020. Compared to PCR and serology tests, SARS-CoV-2 antigen assays are underdeveloped, despite their potential to identify active infection and monitor disease progression. METHODS: We used Single Molecule Array (Simoa) assays to quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the plasma of coronavirus disease (COVID-19) patients. We studied plasma from 64 COVID-19 positive patients, 17 COVID-19 negative patients, and 34 pre-pandemic patients. Combined with Simoa anti-SARS-CoV-2 serological assays, we quantified changes in 31 SARS-CoV-2 biomarkers in 272 longitudinal plasma samples obtained for 39 COVID-19 patients. Data were analyzed by hierarchical clustering and were compared to longitudinal RT-PCR test results and clinical outcomes. RESULTS: SARS-CoV-2 S1 and N antigens were detectable in 41 out of 64 COVID-19 positive patients. In these patients, full antigen clearance in plasma was observed a mean ± 95%CI of 5 ± 1 days after seroconversion and nasopharyngeal RT-PCR tests reported positive results for 15 ± 5 days after viral antigen clearance. Correlation between patients with high concentrations of S1 antigen and ICU admission (77%) and time to intubation (within one day) was statistically significant. CONCLUSIONS: The reported SARS-CoV-2 Simoa antigen assay is the first to detect viral antigens in the plasma of COVID-19 positive patients to date. These data show that SARS-CoV-2 viral antigens in the blood are associated with disease progression, such as respiratory failure, in COVID-19 cases with severe disease.

Clin Chem2020       LitCov and CORD-19
5323Immunothrombotic Dysregulation in COVID-19 Pneumonia Is Associated With Respiratory Failure and Coagulopathy  

BACKGROUND: Severe acute respiratory syndrome corona virus 2 infection causes severe pneumonia (coronavirus disease 2019 [COVID-19]), but the mechanisms of subsequent respiratory failure and complicating renal and myocardial involvement are poorly understood. In addition, a systemic prothrombotic phenotype has been reported in patients with COVID-19. METHODS: A total of 62 subjects were included in our study (n=38 patients with reverse transcriptase polymerase chain reaction–confirmed COVID-19 and n=24 non–COVID-19 controls). We performed histopathologic assessment of autopsy cases, surface marker–based phenotyping of neutrophils and platelets, and functional assays for platelet, neutrophil functions, and coagulation tests, as well. RESULTS: We provide evidence that organ involvement and prothrombotic features in COVID-19 are linked by immunothrombosis. We show that, in COVID-19, inflammatory microvascular thrombi are present in the lung, kidney, and heart, containing neutrophil extracellular traps associated with platelets and fibrin. Patients with COVID-19 also present with neutrophil-platelet aggregates and a distinct neutrophil and platelet activation pattern in blood, which changes with disease severity. Whereas cases of intermediate severity show an exhausted platelet and hyporeactive neutrophil phenotype, patients severely affected with COVID-19 are characterized by excessive platelet and neutrophil activation in comparison with healthy controls and non–COVID-19 pneumonia. Dysregulated immunothrombosis in severe acute respiratory syndrome corona virus 2 pneumonia is linked to both acute respiratory distress syndrome and systemic hypercoagulability. CONCLUSIONS: Taken together, our data point to immunothrombotic dysregulation as a key marker of disease severity in COVID-19. Further work is necessary to determine the role of immunothrombosis in COVID-19.

Circulation2020       LitCov and CORD-19
5324Unexpected high frequency of unspecific reactivities by testing pre-epidemic blood specimens from Europe and Africa with SARS-CoV-2 IgG-IgM antibody rapid tests points to IgM as the Achilles heel  

N/A

J Med Virol2021       LitCov and CORD-19
5325Predictors of impaired SARS-CoV-2 immunity in healthcare workers after vaccination with BNT162b2  

Healthcare workers are at substantially increased risk for infection with SARS-CoV-2. Successful vaccination constitutes a crucial prerequisite to protect this group during the pandemic. Since post vaccination antibody monitoring is not standard of care in all healthcare institutions, data on risk factors of impaired vaccine induced immune response are urgently required. Moreover, there are no data on cellular immune responses in humoral low responders so far. Anti-SARS-CoV-2 spike IgG was assessed after vaccination with BNT162b2 in 1386 employees of three hospitals of a German healthcare provider. Concentrations were compared to those of 45 convalescent employees. Vaccine-induced cellular immunity was measured in employees with reduced humoral response by assessment of frequencies of SARS-CoV-2-reactive CD4(+) and CD8(+) T cell. Anti-SARS-CoV-2 spike IgG were detected in 99.9% of 1386 healthcare workers after completed vaccination. The median antibody concentration was significantly higher after vaccination than after infection with SARS-CoV-2 (p = 0.0001). 10 subjects (0.7%) generated an IgG concentration < 100 IU/ml, and only two persons (0.1%, solid organ recipients) did not produce detectable antibodies at all. T cell responses of those subjects with submaximal or lacking humoral response were comparable to employees with maximal antibody titers. 50% of those individuals with impaired or lacking humoral immune response were on immunosuppression. Vaccination to SARS-CoV-2 with BNT162b2 is very effective in healthcare workers yielding a seroconversion rate of 99.9%. Immunosuppression is the most important risk factor of an impaired immune response. There was no case of vaccination failure without immunosuppression. Thus, post vaccination antibody monitoring is highly recommendable in those employees with immunosuppression.

Sci Rep2022       LitCov and CORD-19
5326Non-COVID-19 patients in times of pandemic: Emergency department visits, hospitalizations and cause-specific mortality in Northern Italy  

The COVID-19 pandemic forced healthcare services organization to adjust to mutating healthcare needs. Not exhaustive data are available on the consequences of this on non-COVID-19 patients. The aim of this study was to assess the impact of the pandemic on non-COVID-19 patients living in a one-million inhabitants’ area in Northern Italy (Bologna Metropolitan Area-BMA), analyzing time trends of Emergency Department (ED) visits, hospitalizations and mortality. We conducted a retrospective observational study using data extracted from BMA healthcare informative systems. Weekly trends of ED visits, hospitalizations, in- and out-of-hospital, all-cause and cause-specific mortality between December 1(st), 2019 to May 31(st), 2020, were compared with those of the same period of the previous year. Non-COVID-19 ED visits and hospitalizations showed a stable trend until the first Italian case of COVID-19 has been recorded, on February 19(th), 2020, when they dropped simultaneously. The reduction of ED visits was observed in all age groups and across all severity and diagnosis groups. In the lockdown period a significant increase was found in overall out-of-hospital mortality (43.2%) and cause-specific out-of-hospital mortality related to neoplasms (76.7%), endocrine, nutritional and metabolic (79.5%) as well as cardiovascular (32.7%) diseases. The pandemic caused a sudden drop of ED visits and hospitalizations of non-COVID-19 patients during the lockdown period, and a concurrent increase in out-of-hospital mortality mainly driven by deaths for neoplasms, cardiovascular and endocrine diseases. As recurrencies of the COVID-19 pandemic are underway, the scenario described in this study might be useful to understand both the population reaction and the healthcare system response at the early phases of the pandemic in terms of reduced demand of care and systems capability in intercepting it.

PLoS One2021       LitCov and CORD-19
5327Evaluation of SARS-CoV-2 antigen-based rapid diagnostic kits in Pakistan: formulation of COVID-19 national testing strategy  

Rapid diagnosis of SARS-CoV-2 during pandemic enables timely treatment and prevention of COVID-19. Evaluating the accuracy and reliability of rapid diagnostic testing kits is crucial for surveillance and diagnosis of SARS-CoV-2 infections in general population, injection drug users, multi-transfused populations, healthcare workers, prisoners, barbers and other high risk populations. The aim of this study was to evaluate performance and effectiveness of nasopharyngeal swab (NSP) and saliva based rapid antigen detection testing kits in comparison with USFDA approved triple target gold standard real-time polymerase chain reaction. A cross-sectional study was conducted on 33,000 COVID-19 suspected patients. From RT-PCR positive patients, nasopharyngeal swab (NSP) and saliva samples were obtained for evaluation of rapid COVID-19 testing kits (RDT). 100/33,000 (0.3%) of specimens were RT-PCR positive for SARS-CoV-2. Among RT-PCR positive, 62% were males, 34% were females, and 4% were children. The NSP-RDT (Lepu Medical China) analysis revealed 53% reactivity among males, 58% reactivity among females, and 25% reactivity among children. However saliva based RDT (Lepu Medical China) analysis showed 21% reactivity among males and 23% among females, and no reactivity in children. False negative results were significantly more pronounced in saliva based RDT as compared to NSP-RDT. The sensitivity of these NSP-RDT and saliva based RDT were 52% and 21% respectively. The RDTs evaluated in this study showed limited sensitivities in comparison to gold standard RT-PCR, indicating that there is a dire need in Pakistan for development of suitable testing to improve accurate COVID-19 diagnosis in line with national demands.

Virol J2021       LitCov and CORD-19
5328An evidence-based systematic review on emerging therapeutic and preventive strategies to treat novel coronavirus during an outbreak scenario  

N/A

J Basic Clin Physiol Pharmacol2020       LitCov and CORD-19
5329Mucocutaneous disease and related clinical characteristics in hospitalized children and adolescents with COVID-19 and multisystem inflammatory syndrome in children  

Background Little is known about mucocutaneous disease in acutely-ill children and adolescents with COVID-19 and MIS-C. Objective To characterize mucocutaneous disease and its relation to clinical course among hospitalized patients with COVID-19 and MIS-C. Methods Descriptive cohort study of prospectively and consecutively hospitalized eligible patients between May 11, 2020 and June 5, 2020. Results In COVID-19 patients, 4/12 (33%) had rash and/or mucositis, including erythema, morbilliform pattern, and lip mucositis. In MIS-C patients, 9/19 (47%) had rash and/or mucositis, including erythema, morbilliform, retiform purpura, targetoid and urticarial patterns, along with acral edema, lip mucositis, tongue papillitis, and conjunctivitis. COVID-19 patients with rash had less frequent respiratory symptoms, PICU admission, and invasive ventilation, as well as shorter stay (vs COVID-19 without rash). MIS-C patients with rash had less frequent PICU admission, shock, ventilation, as well as lower levels of CRP, ferritin, D-dimer, and troponin (vs MIS-C without rash). Neutrophil-to-lymphocyte ratio was similar for patients with and without rash in both groups. None of the MIS-C patients met criteria for Kawasaki disease. Limitations Small sample sizes. Conclusions Mucocutaneous disease is common among children and adolescents with COVID-19 and MIS-C. Laboratory trends observed in patients with rash may prognosticate a less severe course.

J Am Acad Dermatol2020       LitCov and CORD-19
5330Social Media as an Early Proxy for Social Distancing Indicated by the COVID-19 Reproduction Number: Observational Study  

BACKGROUND: The magnitude and time course of the COVID-19 epidemic in the United States depends on early interventions to reduce the basic reproductive number to below 1. It is imperative, then, to develop methods to actively assess where quarantine measures such as social distancing may be deficient and suppress those potential resurgence nodes as early as possible. OBJECTIVE: We ask if social media is an early indicator of public social distancing measures in the United States by investigating its correlation with the time-varying reproduction number (R(t)) as compared to social mobility estimates reported from Google and Apple Maps. METHODS: In this observational study, the estimated R(t) was obtained for the period between March 5 and April 5, 2020, using the EpiEstim package. Social media activity was assessed using queries of “social distancing” or “#socialdistancing” on Google Trends, Instagram, and Twitter, with social mobility assessed using Apple and Google Maps data. Cross-correlations were performed between R(t) and social media activity or mobility for the United States. We used Pearson correlations and the coefficient of determination (ρ) with significance set to P<.05. RESULTS: Negative correlations were found between Google search interest for “social distancing” and R(t) in the United States (P<.001), and between search interest and state-specific R(t) for 9 states with the highest COVID-19 cases (P<.001); most states experienced a delay varying between 3-8 days before reaching significance. A negative correlation was seen at a 4-day delay from the start of the Instagram hashtag “#socialdistancing” and at 6 days for Twitter (P<.001). Significant correlations between R(t) and social media manifest earlier in time compared to social mobility measures from Google and Apple Maps, with peaks at –6 and –4 days. Meanwhile, changes in social mobility correlated best with R(t) at –2 days and +1 day for workplace and grocery/pharmacy, respectively. CONCLUSIONS: Our study demonstrates the potential use of Google Trends, Instagram, and Twitter as epidemiological tools in the assessment of social distancing measures in the United States during the early course of the COVID-19 pandemic. Their correlation and earlier rise and peak in correlative strength with R(t) when compared to social mobility may provide proactive insight into whether social distancing efforts are sufficiently enacted. Whether this proves valuable in the creation of more accurate assessments of the early epidemic course is uncertain due to limitations. These limitations include the use of a biased sample that is internet literate with internet access, which may covary with socioeconomic status, education, geography, and age, and the use of subtotal social media mentions of social distancing. Future studies should focus on investigating how social media reactions change during the course of the epidemic, as well as the conversion of social media behavior to actual physical behavior.

JMIR Public Health Surveill2020       LitCov and CORD-19
5331COVID-19 and ENT SLT services, workforce and research in the UK: A discussion paper  

BACKGROUND: The COVID‐19 pandemic and the UK government's subsequent coronavirus action plan have fundamentally impacted on every aspect of healthcare. One area that is severely affected is ear, nose and throat (ENT)/laryngology where speech and language therapists (SLTs) engage in a diverse range of practice with patients with a range of conditions, including voice disorders, airway problems, and head and neck cancers (HNCs). A large majority of these patients are in high‐risk categories, and many specialized clinical practices are vulnerable. In addition, workforce and research issues are challenged in both the immediate context and the future. AIMS: To discuss the threats and opportunities from the COVID‐19 pandemic for SLTs in ENT/laryngology with specific reference to clinical practice, workforce and research leadership. METHODS & PROCEDURES: The relevant sections of the World Health Organisation's (WHO) health systems building blocks framework (2007) were used to structure the study. Expert agreement was determined by an iterative process of multiple‐group discussions, the use of all recent relevant policy documentation, and other literature and shared documentation/writing. The final paper was verified and agreed by all authors. MAIN CONTRIBUTION: The main threats to ENT/laryngology SLT clinical services include increased patient complexity related to COVID‐19 voice and airway problems, delayed HNC diagnosis, reduced access to instrumental procedures and inequitable care provision. The main clinical opportunities include the potential for new modes of service delivery and collaborations, and harnessing SLT expertise in non‐instrumental assessment. There are several workforce issues, including redeployment (and impact on current services), training implications and psychological impact on staff. Workforce opportunities exist for service innovation and potential extended ENT/SLT practice roles. Research is threatened by a reduction in immediate funding calls and high competition. Current research is affected by very limited access to participants and the ability to conduct face‐to‐face and instrumental assessments. However, research opportunities may result in greater collaboration, and changes in service delivery necessitate robust investigation and evaluation. A new national set of research priorities is likely to emerge. CONCLUSIONS & IMPLICATIONS: The immediate impact of the pandemic has resulted in major disruption to all aspects of clinical delivery, workforce and research for ENT/laryngology SLT. It is unclear when any of these areas will resume operations and whether permanent changes to clinical practice, professional remits and research priorities will follow. However, significant opportunity exists in the post‐COVID era to re‐evaluate current practice, embrace opportunities and evaluate new ways of working. WHAT THIS PAPER ADDS: WHAT IS ALREADY KNOWN ON THE SUBJECT: ENT/laryngology SLTs manage patients with a range of conditions, including voice disorders, airway problems and HNCs. The diverse scope of clinical practice involves highly specialized assessment and treatment practices in patients in high‐risk categories. A large majority of active research projects in this field are patient focused and involve instrumental assessment. The COVID‐19 pandemic has created both opportunities and threats for ENT SLT clinical services, workforce and research. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE: This study provides a discussion of the threats and opportunities from the COVID‐19 pandemic for ENT/laryngology SLT with specific reference to clinical practice, workforce and research leadership. WHAT ARE THE POTENTIAL OR ACTUAL CLINICAL IMPLICATIONS OF THIS WORK? The COVID‐19 pandemic has resulted in major disruption to all aspects of clinical delivery, workforce and research for ENT/laryngology SLT. Changes to clinical practice, professional remits and research priorities are of indeterminant duration at this time, and some components could be permanent. Significant clinical practice, workforce and research opportunities may exist in the post‐COVID era.

Int J Lang Commun Disord2020       LitCov and CORD-19
5332A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia  

BACKGROUND: Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials. METHODS: We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient’s clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. RESULTS: A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200]. No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83 (95% confidence interval [CI], 0.52 to 1.35; P=0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of −0.46 percentage points (95% CI, −7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups. CONCLUSIONS: No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535.)

N Engl J Med2020       LitCov and CORD-19
5333Knowledge, Attitude and Practices Towards SARS-COV-2 Infection in the United Arab Emirates Population: An Online Community-Based Cross-Sectional Survey  

Population's preventive practices and self-isolation is determinantal in the prevention and mitigation. This study explored the adult population's knowledge, attitude, and practice toward COVID-19 in UAE between the 4th and 14th of April 2020. The study was a community-based, cross-sectional study using a self-administered electronic questionnaire covering five different aspects: demographics, knowledge, practice, attitude, source, and trust of information, and a patient health questionnaire (PHQ-2) for depression screening. Results were analyzed using frequencies, cross-tabulation, and regression analysis. A total of 1,867 people responded to the survey. The mean age of participants was 36.0 years S.D. 10.8. Males were 19.3% and female (80.7%). Knowledge was significantly better in people with higher educational levels (B 0.17, P-value < 0.001), good preventive practice (B 0.12, P-value < 0.001), and higher perceived risk scores (B 0.053, P-value = 0.025). The best practice scores were shown by participants with older age (B 0.097, P-value < 0.05), with good knowledge (B 0.086, P-value < 0.05), were of non-UAE nationalities (B −0.08, P-value < 0.05), with jobs that cannot be practiced from home, military and health care employees (B −0.104, P-value < 0.05), had a personal history of contact with COVID-19 patients (B 0.053, P-value < 0.05), higher educational levels (B 0.052, P-value < 0.05), and a positive attitude toward taking a vaccine (B 0.088, P-value < 0.05). Depression risk was significantly higher in men, non-UAE nationals, in those with lower knowledge scores, and younger ages. The most followed practices were staying home, handwashing, avoiding social gatherings, limiting three people per vehicle, and avoiding public transportation. The least practiced measures were covering the face while sneezing or coughing and wearing masks. Although staying home was reported by 92.5% of participants, 22.6% mentioned that they were visited by more than two people and visited others in 18.4% during the last week. Social media was the source of information for 82.1% of the participants and most trusted doctors and healthcare providers. Depression risk was present in 18.9% of the participants, and most respondents (89%) agreed that SARS-COV-2 infection would be finally be successfully controlled. An encouraging finding is the willingness of two-third of the participants (64.5%) to take the COVID-19 vaccine and if it was developed, although it was very early in the pandemic. Only 14.6% said they would not take the vaccine, and 20.9% were not sure. The obtained results on knowledge and practices, although satisfactory, could be insufficient to prevent this pandemic from being contained. Therefore, we recommend the intensification of awareness programs and good practices. In addition, mental health is an area worth further studies.

Front Public Health2021       LitCov and CORD-19
5334Development and comparison of novel multiple cross displacement amplification (MCDA) assays with other nucleic acid amplification methods for SARS-CoV-2 detection  

The development of alternative isothermal amplification assays including multiple cross displacement amplification (MCDA) may address speed and portability limitations of real-time PCR (rt-PCR) methods for SARS-CoV-2 detection. We developed a novel SARS-CoV-2 MCDA assay and compared its speed and sensitivity to loop-mediated isothermal amplification (LAMP) and rt-PCR. Two MCDA assays targeting SARS-CoV-2 N gene and ORF1ab were designed. The fastest time to detection and sensitivity of MCDA was compared to LAMP and rt-PCR using DNA standards and transcribed RNA. For the N gene, MCDA was faster than LAMP and rt-PCR by 10 and 20 min, respectively with fastest time to detection at 5.2 min. rt-PCR had the highest sensitivity with the limit of detection at 10 copies/µl compared with MCDA (100 copies/µl) and LAMP (500 copies/µl). For ORF1ab, MCDA and LAMP had similar speed with fastest time to detection at 9.7 and 8.4 min, respectively. LAMP was more sensitive for ORF1ab detection with 50 copies/µl compared to MCDA (500 copies/µl). In conclusion, different nucleic acid amplification methods provide different advantages. MCDA is the fastest nucleic acid amplification method for SARS-CoV-2 while rt-PCR is the most sensitive. These advantages should be considered when determining the most suitable nucleic acid amplification methods for different applications.

Sci Rep2021       LitCov and CORD-19
5335Neonatal management and outcomes during the COVID-19 pandemic: an observation cohort study  

BACKGROUND: The risk of vertical and perinatal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, which causes COVID-19), the most appropriate management, and the neonate's risk of developing COVID-19 during the perinatal period are unknown. Therefore, we aimed to elucidate best practices regarding infection control in mother–newborn dyads, and identify potential risk factors associated with transmission. METHODS: In this observational cohort study, we identified all neonates born between March 22 and May 17, 2020, at three New York Presbyterian Hospitals in New York City (NY, USA) to mothers positive for SARS-CoV-2 at delivery. Mothers could practice skin-to-skin care and breastfeed in the delivery room, but had to wear a surgical mask when near their neonate and practice proper hand hygiene before skin-to-skin contact, breastfeeding, and routine care. Unless medically required, neonates were kept in a closed Giraffe isolette in the same room as their mothers, and were held by mothers for feeding after appropriate hand hygiene, breast cleansing, and placement of a surgical mask. Neonates were tested for SARS-CoV-2 by use of real-time PCR on nasopharyngeal swabs taken at 24 h, 5–7 days, and 14 days of life, and were clinically evaluated by telemedicine at 1 month of age. We recorded demographics, neonatal, and maternal clinical presentation, as well as infection control practices in the hospital and at home. FINDINGS: Of 1481 deliveries, 116 (8%) mothers tested positive for SARS-CoV-2; 120 neonates were identified. All neonates were tested at 24 h of life and none were positive for SARS-CoV-2. 82 (68%) neonates completed follow-up at day 5–7 of life. Of the 82 neonates, 68 (83%) roomed in with the mothers. All mothers were allowed to breastfeed; at 5–7 days of life, 64 (78%) were still breastfeeding. 79 (96%) of 82 neonates had a repeat PCR at 5–7 days of life, which was negative in all; 72 (88%) neonates were also tested at 14 days of life and none were positive. None of the neonates had symptoms of COVID-19. INTERPRETATION: Our data suggest that perinatal transmission of COVID-19 is unlikely to occur if correct hygiene precautions are undertaken, and that allowing neonates to room in with their mothers and direct breastfeeding are safe procedures when paired with effective parental education of infant protective strategies. FUNDING: None.

Lancet Child Adolesc Health2020       LitCov and CORD-19
5336Adherence to personal protective equipment use among healthcare workers caring for confirmed COVID-19 and alleged non-COVID-19 patients  

Adherence observations of health care workers (HCW) revealed deficiencies in the use of recommended personal protective equipment (PPE) among HCW caring in COVID-19 and non-COVID-19 wards during the first period of the SARS-CoV-2 pandemic in a university hospital in Germany. The adherence to wearing surgical face or FFP2-masks and disinfecting hands prior to donning and after doffing the PPE was significantly higher in COVID-19 wards However, there was no total adherence of 100% in COVID-19 wards.

Antimicrob Resist Infect Contr2020       LitCov and CORD-19
5337Sociodemographic Predictors of Health Risk Perception, Attitude and Behavior Practices Associated with Health-Emergency Disaster Risk Management for Biological Hazards: The Case of COVID-19 Pandemic in Hong Kong, SAR China  

In addition to top-down Health-Emergency and Disaster Risk Management (Health-EDRM) efforts, bottom-up individual and household measures are crucial for prevention and emergency response of the COVID-19 pandemic, a Public Health Emergency of International Concern (PHEIC). There is limited scientific evidence of the knowledge, perception, attitude and behavior patterns of the urban population. A computerized randomized digital dialing, cross-sectional, population landline-based telephone survey was conducted from 22 March to 1 April 2020 in Hong Kong Special Administrative Region, China. Data were collected for socio-demographic characteristics, knowledge, attitude and risk perception, and various self-reported Health-EDRM behavior patterns associated with COVID-19. The final study sample was 765. Although the respondents thought that individuals (68.6%) had similar responsibilities as government (67.5%) in infection control, less than 50% had sufficient health risk management knowledge to safeguard health and well-being. Among the examined Health-EDRM measures, significant differences were found between attitude and practice in regards to washing hands with soap, ordering takeaways, wearing masks, avoidance of visiting public places or using public transport, and travel avoidance to COVID-19-confirmed regions. Logistic regression indicated that the elderly were less likely to worry about infection with COVID-19. Compared to personal and household hygiene practices, lower compliance was found for public social distancing.

Int J Environ Res Public Healt2020       LitCov and CORD-19
5338Vaccine induced systemic and mucosal T-cell immunity to SARS-CoV-2 viral variants  

N/A

Proc Natl Acad Sci U S A2022       LitCov and CORD-19
5339Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19  

BACKGROUND: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P=1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P=1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.)

N Engl J Med2020       LitCov and CORD-19
5340Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines  

The Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or prior infection. Despite the dramatic global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc-effector mechanisms. Here we probed the ability of vaccine-induced antibodies to drive Fc-effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant Receptor Binding Domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of cross RBD-specific antibody Fcγ receptor (FcγR) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific FcγR2a and FcγR3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein-specific antibodies exhibited persistent but reduced binding to FcγRs across all three vaccines, though higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of FcγR2a and FcγR3a binding antibodies and maintenance of Spike protein-specific antibody-dependent natural killer cell activating antibodies. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein-specific antibodies continue to drive Fc-effector functions, suggesting a capacity for extra-neutralizing antibodies to contribute to disease control.

Sci Transl Med2022       LitCov and CORD-19
5341Detection of IFNgamma-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2  

Background: New coronavirus SARS-CoV-2, a causative agent of the COVID-19 pandemic, has been circulating among humans since November 2019. Multiple studies have assessed the qualitative and quantitative characteristics of virus-specific immunity in COVID-19 convalescents, however, some aspects of the development of memory T-cell responses after natural SARS-CoV-2 infection remain uncovered. Methods: In most of published studies T-cell immunity to the new coronavirus is assessed using peptides corresponding to SARS-CoV-1 or SARS-CoV-2 T-cell epitopes, or with peptide pools covering various parts of the viral proteins. Here, we determined the level of CD4(+) and CD8(+) memory T-cell responses in COVID-19 convalescents by stimulating PBMCs collected 1 to 6 months after recovery with sucrose gradient-purified live SARS-CoV-2. IFNγ production by the central and effector memory helper and cytotoxic T cells was assessed by intracellular cytokine staining assay and flow cytometry. Results: Stimulation of PBMCs with live SARS-CoV-2 revealed IFNγ-producing T-helper effector memory cells with CD4(+)CD45RA(−)CCR7(−) phenotype, which persisted in circulation for up to 6 month after COVID-19. In contrast, SARS-CoV-2-specific IFNγ-secreting cytotoxic effector memory T cells were found at significant levels only shortly after the disease, but rapidly decreased over time. Conclusion: The stimulation of immune cells with live SARS-CoV-2 revealed a rapid decline in the pool of effector memory CD8(+), but not CD4(+), T cells after recovery from COVID-19. These data provide additional information on the development and persistence of cellular immune responses after natural infection, and can inform further development of T cell-based SARS-CoV-2 vaccines.

Viruses2021       LitCov and CORD-19
5342Boosting with Multiple Doses of mRNA Vaccine after Priming with Two Doses of Protein Subunit Vaccine MVC-COV1901 Elicited Robust Humoral and Cellular Immune Responses against Emerging SARS-CoV-2 Variants  

N/A

Microbiol Spectr2022       LitCov
5343Predictors of COVID-19 vaccine hesitancy in the UK household longitudinal study  

Vaccine hesitancy could undermine efforts to control COVID-19. We investigated the prevalence of COVID-19 vaccine hesitancy in the UK and identified vaccine hesitant subgroups. The ‘Understanding Society’ COVID-19 survey asked participants (n=12,035) their likelihood of vaccine uptake and reason for hesitancy. Cross-sectional analysis assessed vaccine hesitancy prevalence and logistic regression calculated odds ratios. Overall vaccine hesitancy was low (18% unlikely/very unlikely). Vaccine hesitancy was higher in women (21.0% vs 14.7%), younger age groups (26.5% in 16-24 year olds vs 4.5% in 75+) and those with lower education levels (18.6% no qualifications vs 13.2% degree qualified). Vaccine hesitancy was high in Black (71.8%) and Pakistani/Bangladeshi (42.3%) ethnic groups. Odds ratios for vaccine hesitancy were 13.42 (95% CI:6.86, 26.24) in Black and 2.54 (95% CI:1.19, 5.44) in Pakistani/Bangladeshi groups (compared to White British/Irish) and 3.54 (95%CI:2.06, 6.09) for people with no qualifications versus degree. Urgent action to address hesitancy is needed for some but not all ethnic minority groups.

Brain Behav Immun2021       LitCov and CORD-19
5344Older Adults Hospitalized with Covid-19: Clinical Characteristics and Early Outcomes from a Single Center in Istanbul, Turkey  

OBJECTIVE: Older adults have been continuously reported to be at higher risk for adverse outcomes of Covid-19. We aimed to describe clinical characteristics and early outcomes of the older Covid-19 patients hospitalized in our center comparatively with the younger patients, and also to analyze the triage factors that were related to the in-hospital mortality of older adults. DESIGN: Retrospective; observational study. SETTING: Istanbul Faculty of Medicine hospital, Turkey. PARTICIPANTS: 362 hospitalized patients with laboratory-confirmed Covid-19 from March 11 to May 11, 2020. MEASUREMENTS: The demographic information; associated comorbidities; presenting clinical, laboratory, radiological characteristics on admission and outcomes from the electronic medical records were analyzed comparatively between the younger (<65 years) and older (≥65 years) adults. Factors associated with in-hospital mortality of the older adults were analyzed by multivariate regression analyses. RESULTS: The median age was 56 years (interquartile range [IQR], 46–67), and 224 (61.9%) were male. There were 104 (28.7%) patients ≥65 years of age. More than half of the patients (58%) had one or more chronic comorbidity. The three most common presenting symptoms in the older patients were fatigue/myalgia (89.4%), dry cough (72.1%), and fever (63.5%). Cough and fever were significantly less prevalent in older adults compared to younger patients (p=0.001 and 0.008, respectively). Clinically severe pneumonia was present in 31.5% of the study population being more common in older adults (49% vs. 24.4%) (p<0.001). The laboratory parameters that were significantly different between the older and younger adults were as follows: the older patients had significantly higher CRP, D-dimer, TnT, pro-BNP, procalcitonin levels, higher prevalence of lymphopenia, neutrophilia, increased creatinine, and lower hemoglobin, ALT, albumin level (p<0.05). In the radiological evaluation, more than half of the patients (54.6%) had moderate-severe pneumonia, which was more prevalent in older patients (66% vs. 50%) (p=0.006). The adverse outcomes were significantly more prevalent in older adults compared to the younger patients (ICU admission, 28.8% vs. 8.9%; mortality, 23.1% vs. 4.3%, p<0.001). Among the triage evaluation parameters, the only factor associated with higher mortality was the presence of clinically severe pneumonia on admission (Odds Ratio=12.3, 95% confidence interval=2.7–55.5, p=0.001). CONCLUSION: Older patients presented with more prevalent chronic comorbidities, less prevalent symptomatology but more severe respiratory signs and laboratory abnormalities than the younger patients. Among the triage assessment factors, the clinical evaluation of pulmonary involvement came in front to help clinicians to stratify the patients for mortality risk.

J Nutr Health Aging2020       LitCov and CORD-19
5345Isolation of SARS-CoV-2 Related coronavirus from Malayan pangolins  

N/A

Nature2020       LitCov and CORD-19
5346T-cell responses to SARS-CoV-2 Omicron spike epitopes with mutations after the third booster dose of an inactivated vaccine  

The rapidly spreading severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron variant contains more than 30 mutations that mediate escape from antibody responses elicited by prior infection or current vaccines. Fortunately, T‐cell responses are highly conserved in most individuals, but the impacts of mutations are not clear. Here, we showed that the T‐cell responses of individuals who underwent booster vaccination with CoronaVac were largely protective against the SARS‐CoV‐2 Omicron spike protein. To specifically estimate the impact of Omicron mutations on vaccinated participants, 16 peptides derived from the spike protein of the ancestral virus or Omicron strain with mutations were used to stimulate peripheral blood mononuclear cells (PBMCs) from the volunteers. Compared with the administration of two doses of vaccine, booster vaccination substantially enhanced T‐cell activation in response to both the ancestral and Omicron epitopes, although the enhancement was slightly weakened by the Omicron mutations. Then, the peptides derived from these spike proteins were used separately to stimulate PBMCs. Interestingly, compared with the ancestral peptides, only the peptides with the G339D or N440K mutation were detected to significantly destabilize the T‐cell response. Although more participants need to be evaluated to confirm this conclusion, our study nonetheless estimates the impacts of mutations on T‐cell responses to the SARS‐CoV‐2 Omicron variant.

J Med Virol2022       LitCov and CORD-19
5347An App-Based Intervention to Support First Responders and Essential Workers During the COVID-19 Pandemic: Needs Assessment and Mixed Methods Implementation Study  

BACKGROUND: The COVID-19 pandemic has created unprecedented challenges for first responders (eg, police, fire, and emergency medical services) and nonmedical essential workers (eg, workers in food, transportation, and other industries). Health systems may be uniquely suited to support these workers given their medical expertise, and mobile apps can reach local communities despite social distancing requirements. Formal evaluation of real-world mobile appbased interventions is lacking. OBJECTIVE: We aimed to evaluate the adoption, acceptability, and appropriateness of an academic medical centersponsored app-based intervention (COVID-19 Guide App) designed to support access of first responders and essential workers to COVID-19 information and testing services. We also sought to better understand the COVID-19related needs of these workers early in the pandemic. METHODS: To understand overall community adoption, views and download data of the COVID-19 Guide App were described. To understand the adoption, appropriateness, and acceptability of the app and the unmet needs of workers, semistructured qualitative interviews were conducted by telephone, by video, and in person with first responders and essential workers in the San Francisco Bay Area who were recruited through purposive, convenience, and snowball sampling. Interview transcripts and field notes were qualitatively analyzed and presented using an implementation outcomes framework. RESULTS: From its launch in April 2020 to September 2020, the app received 8262 views from unique devices and 6640 downloads (80.4% conversion rate, 0.61% adoption rate across the Bay Area). App acceptability was mixed among the 17 first responders interviewed and high among the 10 essential workers interviewed. Select themes included the need for personalized and accurate information, access to testing, and securing personal safety. First responders faced additional challenges related to interprofessional coordination and a culture of heroism that could both protect against and exacerbate health vulnerability. CONCLUSIONS: First responders and essential workers both reported challenges related to obtaining accurate information, testing services, and other resources. A mobile app intervention has the potential to combat these challenges through the provision of disease-specific information and access to testing services but may be most effective if delivered as part of a larger ecosystem of support. Differentiated interventions that acknowledge and address the divergent needs between first responders and nonfirst responder essential workers may optimize acceptance and adoption.

J Med Internet Res2021       LitCov and CORD-19
5348COVID-19 vaccines: modes of immune activation and future challenges  

The new vaccines against SARS-CoV-2 are novel in terms of specificity, their wide dissemination across the global population and the inclusion of newly licensed mRNA platforms. We discuss here how the approved vaccines trigger innate immunity to promote durable immunological memory and consider the future implications of protecting populations with these vaccines.

Nat Rev Immunol2021       LitCov and CORD-19
5349Increase in prevalence of current mental disorders in the context of COVID-19: analysis of repeated nationwide cross-sectional surveys  

AIMS: The United Nations warned of COVID-19-related mental health crisis; however, it is unknown whether there is an increase in the prevalence of mental disorders as existing studies lack a reliable baseline analysis or they did not use a diagnostic measure. We aimed to analyse trends in the prevalence of mental disorders prior to and during the COVID-19 pandemic. METHODS: We analysed data from repeated cross-sectional surveys on a representative sample of non-institutionalised Czech adults (18+ years) from both November 2017 (n = 3306; 54% females) and May 2020 (n = 3021; 52% females). We used Mini International Neuropsychiatric Interview (MINI) as the main screening instrument. We calculated descriptive statistics and compared the prevalence of current mood and anxiety disorders, suicide risk and alcohol-related disorders at baseline and right after the first peak of COVID-19 when related lockdown was still in place in CZ. In addition, using logistic regression, we assessed the association between COVID-19-related worries and the presence of mental disorders. RESULTS: The prevalence of those experiencing symptoms of at least one current mental disorder rose from a baseline of 20.02 (95% CI = 18.64; 21.39) in 2017 to 29.63 (95% CI = 27.9; 31.37) in 2020 during the COVID-19 pandemic. The prevalence of both major depressive disorder (3.96, 95% CI = 3.28; 4.62 v. 11.77, 95% CI = 10.56; 12.99); and suicide risk (3.88, 95% CI = 3.21; 4.52 v. 11.88, 95% CI = 10.64; 13.07) tripled and current anxiety disorders almost doubled (7.79, 95% CI = 6.87; 8.7 v. 12.84, 95% CI = 11.6; 14.05). The prevalence of alcohol use disorders in 2020 was approximately the same as in 2017 (10.84, 95% CI = 9.78; 11.89 v. 9.88, 95% CI = 8.74; 10.98); however, there was a significant increase in weekly binge drinking behaviours (4.07% v. 6.39%). Strong worries about both, health or economic consequences of COVID-19, were associated with an increased odds of having a mental disorder (1.63, 95% CI = 1.4; 1.89 and 1.42, 95% CI = 1.23; 1.63 respectively). CONCLUSIONS: This study provides evidence matching concerns that COVID-19-related mental health problems pose a major threat to populations, particularly considering the barriers in service provision posed during lockdown. This finding emphasises an urgent need to scale up mental health promotion and prevention globally.

Epidemiol Psychiatr Sci2020       LitCov and CORD-19
5350Atypical Manifestations of SARS-CoV-2 Infection in Children: A Systematic Review  

N/A

Curr Pediatr Rev2021       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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