\ 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
501Intestinal Collinsella may mitigate infection and exacerbation of COVID-19 by producing ursodeoxycholate  

The mortality rates of COVID-19 vary widely across countries, but the underlying mechanisms remain unelucidated. We aimed at the elucidation of relationship between gut microbiota and the mortality rates of COVID-19 across countries. Raw sequencing data of 16S rRNA V3-V5 regions of gut microbiota in 953 healthy subjects in ten countries were obtained from the public database. We made a generalized linear model (GLM) to predict the COVID-19 mortality rates using gut microbiota. GLM revealed that low genus Collinsella predicted high COVID-19 mortality rates with a markedly low p-value. Unsupervised clustering of gut microbiota in 953 subjects yielded five enterotypes. The mortality rates were increased from enterotypes 1 to 5, whereas the abundances of Collinsella were decreased from enterotypes 1 to 5 except for enterotype 2. Collinsella produces ursodeoxycholate. Ursodeoxycholate was previously reported to inhibit binding of SARS-CoV-2 to angiotensin-converting enzyme 2; suppress pro-inflammatory cytokines like TNF-α, IL-1β, IL-2, IL-4, and IL-6; have antioxidant and anti-apoptotic effects; and increase alveolar fluid clearance in acute respiratory distress syndrome. Ursodeoxycholate produced by Collinsella may prevent COVID-19 infection and ameliorate acute respiratory distress syndrome in COVID-19 by suppressing cytokine storm syndrome.

PLoS One2021       LitCov and CORD-19
502Long covid in children and adolescents  

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BMJ2022       LitCov and CORD-19
503Mental health and well-being during the second wave of COVID-19: longitudinal analyses of the UK COVID-19 Mental Health and Wellbeing study (UK COVID-MH)  

N/A

BJPsych Open2022       LitCov
504Early COVID-19 therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in outpatient settings significantly improved COVID-19 outcomes compared to known outcomes in untreated patients  

In a prospective observational study (pre-AndroCoV Trial), the use of nitazoxanide, ivermectin and hydroxychloroquine demonstrated unexpected improvements in COVID-19 outcomes, when compared to untreated patients. The apparent yet likely positive results raised ethical concerns on the employment of further full placebo84 controlled studies in early stage COVID-19. The present analysis aimed to elucidate whether full placebo-control randomized clinical trials (RCTs) on early-stage COVID-19 are still ethically acceptable, through a comparative analysis with two control87 groups. Active group (AG) consisted of patients enrolled in the Pre AndroCoV-Trial (n = 585). Control Group 1 (CG1) consisted of a retrospectively obtained group of untreated patients of the same population (n = 137), and Control Group 2 (CG2) resulted from a precise prediction of clinical outcomes based on a thorough and structured review of indexed articles and official statements. Patients were matched for sex, age, comorbidities and disease severity at baseline. Compared to CG1 and CG2 AG showed reduction of 31.5-36.5% in viral shedding (p < 0.0001), 70-85% in disease duration (p < 0.0001), and 100% in respiratory complications, hospitalization, mechanical ventilations, and deaths (p < 0.0001 for all). For every 1,000 confirmed cases for COVID-19, at least 70 hospitalizations, 50 mechanical ventilations and five deaths were prevented. Benefits from the combination of early COVID-19 detection and early pharmacological approaches were consistent and overwhelming when compared to untreated groups, which, together with and well-established safety profile of the drug combinations tested in the Pre-AndroCoV Trial, precluded our study to continue employing full placebo in early COVID-19.

New Microbes New Infect2021       LitCov and CORD-19
505Preseptal cellulitis and infraorbital abscess as a complication of a routine COVID-19 swab  

This case report describes a significant complication of a routine COVID-19 swab in a previously fit and well young patient who developed preseptal cellulitis and an infraorbital abscess as a consequence of the mentioned nasal swabbing. Other authors have previously reported various complications in connection with the use of nasal swabs, including retained swab fragments, epistaxis and cerebrospinal fluid leakage. To our knowledge, to date, this is the first reported case of an abscess as a consequence of COVID-19 swabbing. There has been a clear growth in the use of nasal swabbing worldwide over the last 9 months and many healthcare workers involved in COVID-19 prevention may not be aware of the potential risks of nasopharyngeal swabbing. The presented case highlights the need for better awareness of the complications of these routine tests and we hope that it will also lead to their safer implementation.

BMJ Case Rep2021       LitCov and CORD-19
506Massive image-based single-cell profiling reveals high levels of circulating platelet aggregates in patients with COVID-19  

A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. In fact, COVID-19 autopsy reports have shown widespread thrombotic microangiopathy characterized by extensive diffuse microthrombi within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure. However, the underlying process of COVID-19-associated microvascular thrombosis remains elusive due to the lack of tools to statistically examine platelet aggregation (i.e., the initiation of microthrombus formation) in detail. Here we report the landscape of circulating platelet aggregates in COVID-19 obtained by massive single-cell image-based profiling and temporal monitoring of the blood of COVID-19 patients (n = 110). Surprisingly, our analysis of the big image data shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients. Furthermore, results indicate strong links between the concentration of platelet aggregates and the severity, mortality, respiratory condition, and vascular endothelial dysfunction level of COVID-19 patients.

Nat Commun2021       LitCov and CORD-19
507Covid-19: Children born during the pandemic score lower on cognitive tests, study finds  

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BMJ2021       LitCov and CORD-19
508Covid-19: 40% of patients with weakened immune system mount lower response to vaccines  

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BMJ2021       LitCov and CORD-19
509SARS-CoV-2 failure to infect or replicate in mosquitoes: an extreme challenge  

This research addresses public speculation that SARS-CoV-2 might be transmitted by mosquitoes. The World Health Organization has stated “To date there has been no information nor evidence to suggest that the new coronavirus could be transmitted by mosquitoes”. Here we provide the first experimental data to investigate the capacity of SARS-CoV-2 to infect and be transmitted by mosquitoes. Three widely distributed species of mosquito; Aedes aegypti, Ae. albopictus and Culex quinquefasciatus, representing the two most significant genera of arbovirus vectors that infect people, were tested. We demonstrate that even under extreme conditions, SARS-CoV-2 virus is unable to replicate in these mosquitoes and therefore cannot be transmitted to people even in the unlikely event that a mosquito fed upon a viremic host.

Sci Rep2020       LitCov and CORD-19
510In Vitro Effect of Taraxacum officinale Leaf Aqueous Extract on the Interaction between ACE2 Cell Surface Receptor and SARS-CoV-2 Spike Protein D614 and Four Mutants  

To date, there have been rapidly spreading new SARS-CoV-2 “variants of concern”. They all contain multiple mutations in the ACE2 receptor recognition site of the spike protein, compared to the original Wuhan sequence, which is of great concern, because of their potential for immune escape. Here we report on the efficacy of common dandelion (Taraxacum officinale) to block protein–protein interaction of SARS-COV-2 spike to the human ACE2 receptor. This could be shown for the wild type and mutant forms (D614G, N501Y, and a mix of K417N, E484K, and N501Y) in human HEK293-hACE2 kidney and A549-hACE2-TMPRSS2 lung cells. High-molecular-weight compounds in the water-based extract account for this effect. Infection of the lung cells using SARS-CoV-2 spike D614 and spike Delta (B.1.617.2) variant pseudotyped lentivirus particles was efficiently prevented by the extract and so was virus-triggered pro-inflammatory interleukin 6 secretion. Modern herbal monographs consider the usage of this medicinal plant as safe. Thus, the in vitro results reported here should encourage further research on the clinical relevance and applicability of the extract as prevention strategy for SARS-CoV-2 infection in terms of a non-invasive, oral post-exposure prophylaxis.

Pharmaceuticals (Basel)2021       LitCov and CORD-19
511Covid-19: Two million people in the UK are estimated to be experiencing long covid, says ONS  

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BMJ2022       LitCov
512Therapeutic vaccine for chronic diseases after the COVID-19 Era  

There is currently a respiratory disease outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After rapid development, RNA vaccines and adenoviral vector vaccines were approved within a year, which has demonstrated the strong impact of preventing infectious diseases using gene therapy technology. Furthermore, intensive immunological analysis has been performed to evaluate the efficiency and safety of these vaccines, potentially allowing for rapid progress in vaccine technology. After the coronavirus disease 2019 (COVID-19) era, the novel vaccine technology developed will expand to other vaccines. We have been developing vaccines for chronic diseases, such as hypertension, for >10 years. Regarding the development of vaccines against self-antigens (i.e., angiotensin II), the vaccine should efficiently induce a blocking antibody response against the self-antigen without activating cytotoxic T cells. Therefore, the epitope vaccine approach has been proposed to induce antibody production in response to a combination of a B cell epitope and exogenous T cell epitopes through major histocompatibility complex molecules. When these vaccines are established as therapeutic options for hypertension, their administration regimen, which might be a few times per year, will replace daily medication use. Thus, therapeutic vaccines for hypertension may be a novel option to control the progression of cerebrovascular diseases. Hopefully, the accumulation of immunological findings and vaccine technology advances due to COVID-19 will provide a novel concept for vaccines for chronic diseases.

Hypertens Res2021       LitCov and CORD-19
513SARS-CoV-2 Omicron subvariants evolved to promote further escape from MHC-I recognition  

N/A

bioRxiv2022       CORD-19
514Serological markers of SARS-CoV-2 infection; anti-nucleocapsid antibody positivity may not be the ideal marker of natural infection in vaccinated individuals  

J Infect2021       LitCov and CORD-19
515Rapid and sensitive multiplex detection of COVID-19 antigens and antibody using electrochemical immunosensor-/aptasensor-enabled biochips  

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Chem Commun (Camb)2022       LitCov
516Impact of war on the dynamics of COVID-19 in Ukraine  

BMJ Glob Health2022       LitCov and CORD-19
517Prolonged fever and exaggerated hypercoagulopathy in malaria vivax relapse and COVID-19 coinfection: a case report  

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Malar J2022       LitCov
518Merits and Limitations of Mathematical Modeling and Computational Simulations in Mitigation of COVID-19 Pandemic: A Comprehensive Review  

Mathematical models have assisted in describing the transmission and propagation dynamics of various viral diseases like MERS, measles, SARS, and Influenza; while the advanced computational technique is utilized in the epidemiology of viral diseases to examine and estimate the influences of interventions and vaccinations. In March 2020, the World Health Organization (WHO) has declared the COVID-19 as a global pandemic and the rate of morbidity and mortality triggers unprecedented public health crises throughout the world. The mathematical models can assist in improving the interventions, key transmission parameters, public health agencies, and countermeasures to mitigate this pandemic. Besides, the mathematical models were also used to examine the characteristics of epidemiological and the understanding of the complex transmission mechanism. Our literature study found that there were still some challenges in mathematical modeling for the case of ecology, genetics, microbiology, and pathology pose; also, some aspects like political and societal issues and cultural and ethical standards are hard to be characterized. Here, the recent mathematical models about COVID-19 and their prominent features, applications, limitations, and future perspective are discussed and reviewed. This review can assist in further improvement of mathematical models that will consider the current challenges of viral diseases.

Arch Comput Methods Eng2021       LitCov and CORD-19
519Covid-19: Spreading vaccine "misinformation" puts licence at risk, US boards tell physicians  

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BMJ2021       LitCov
520Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?  

Glutathione peroxidases (GPX), a family of antioxidant selenoenzymes, functionally link selenium and glutathione, which both show correlations with clinical outcomes in COVID-19. Thus, it is highly significant that cytosolic GPX1 has been shown to interact with an inactive C145A mutant of M(pro), the main cysteine protease of SARS-CoV-2, but not with catalytically active wild-type M(pro). This seemingly anomalous result is what might be expected if GPX1 is a substrate for the active protease, leading to its fragmentation. We show that the GPX1 active site sequence is substantially similar to a known M(pro) cleavage site, and is identified as a potential cysteine protease site by the Procleave algorithm. Proteolytic knockdown of GPX1 is highly consistent with previously documented effects of recombinant SARS-CoV M(pro) in transfected cells, including increased reactive oxygen species and NF-κB activation. Because NF-κB in turn activates many pro-inflammatory cytokines, this mechanism could contribute to increased inflammation and cytokine storms observed in COVID-19. Using web-based protease cleavage site prediction tools, we show that M(pro) may be targeting not only GPX1, but several other selenoproteins including SELENOF and thioredoxin reductase 1, as well as glutamate-cysteine ligase, the rate-limiting enzyme for glutathione synthesis. This hypothesized proteolytic knockdown of components of both the thioredoxin and glutaredoxin systems is consistent with a viral strategy to inhibit DNA synthesis, to increase the pool of ribonucleotides for RNA synthesis, thereby enhancing virion production. The resulting “collateral damage” of increased oxidative stress and inflammation would be exacerbated by dietary deficiencies of selenium and glutathione precursors.

Front Nutr2020       LitCov and CORD-19
521Orthodoxy, illusio and playing the scientific game: a Bourdieusian analysis of infection control science in the COVID-19 pandemic  

Background: Scientific and policy bodies’ failure to acknowledge and act on the evidence base for airborne transmission of SARS-CoV-2 in a timely way is both a mystery and a scandal. In this study, we applied theories from Bourdieu to address the question, “How was a partial and partisan scientific account of SARS-CoV-2 transmission constructed and maintained, leading to widespread imposition of infection control policies which de-emphasised airborne transmission?”. Methods: From one international case study (the World Health Organisation) and four national ones (UK, Canada, USA and Japan), we selected a purposive sample of publicly available texts including scientific evidence summaries, guidelines, policy documents, public announcements, and social media postings. To analyse these, we applied Bourdieusian concepts of field, doxa, scientific capital, illusio, and game-playing. We explored in particular the links between scientific capital, vested interests, and policy influence. Results: Three fields—political, state (policy and regulatory), and scientific—were particularly relevant to our analysis. Political and policy actors at international, national, and regional level aligned—predominantly though not invariably—with medical scientific orthodoxy which promoted the droplet theory of transmission and considered aerosol transmission unproven or of doubtful relevance. This dominant scientific sub-field centred around the clinical discipline of infectious disease control, in which leading actors were hospital clinicians aligned with the evidence-based medicine movement. Aerosol scientists—typically, chemists, and engineers—representing the heterodoxy were systematically excluded from key decision-making networks and committees. Dominant discourses defined these scientists’ ideas and methodologies as weak, their empirical findings as untrustworthy or insignificant, and their contributions to debate as unhelpful. Conclusion: The hegemonic grip of medical infection control discourse remains strong. Exit from the pandemic depends on science and policy finding a way to renegotiate what Bourdieu called the ‘rules of the scientific game’—what counts as evidence, quality, and rigour.

Wellcome Open Res2021       LitCov and CORD-19
522Is there any role of intermittent fasting in the prevention and improving clinical outcomes of COVID-19?: intersection between inflammation, mTOR pathway, autophagy and calorie restriction  

The coronavirus disease 2019 (COVID-19) pandemic is provoking a global public health crisis. Even though the academic world is intensively pursuing new therapies, there is still no “game changer” in the management of COVID 19. The Mammalian Target of Rapamycin (mTOR) is an ancient signaling system that has been proposed as a molecular tool used by coronaviruses and other RNA and DNA viruses in order to replicate and persist in the host cell. In recent years, Intermittent Fasting (IF), a practice consisting on a strict calorie restriction during a prolonged period of time during the day, has gained popularity due to its potential benefits in multiple health systems and in regulating inflammation. IF inhibits the mTOR pathway which is similar to the effects of Rapamycin in some animal models. mTOR inhibition and promotion of autophagy could potentially be the link between the possible direct benefits of IF in COVID-19 due to the interruption of the viral cycle (protein synthesis). Besides, IF has shown to be a strong anti-inflammatory in multiple prior studies, and may play a role in attenuating COVID -19 severity. This review hypothesizes the possible intersection between viral, immunological, and metabolic pathways related to mTOR and the potential mechanisms through which IF may improve clinical outcomes. Future prospective randomized controlled clinical trials to evaluate intermittent fasting (IF) regimens in order to prevent and treat moderate to severe forms of COVID-19 in humans are needed.

Virusdisease2021       LitCov and CORD-19
523Comparing COVID-19-related hospitalization rates among individuals with infection induced and vaccine induced immunity in Israel  

With the COVID-19 pandemic ongoing, accurate assessment of population immunity and the effectiveness of booster and enhancer vaccine doses is critical. We compare COVID-19-related hospitalization incidence rates in 2,412,755 individuals across four exposure levels: non-recent vaccine immunity (two BNT162b2 COVID-19 vaccine doses five or more months prior), boosted vaccine immunity (three BNT162b2 doses), infection-induced immunity (previous COVID-19 without a subsequent BNT162b2 dose), and enhanced infection-induced immunity (previous COVID-19 with a subsequent BNT162b2 dose). Rates, adjusted for potential demographic, clinical and health-seeking-behavior confounders, were assessed from July-November 2021 when the Delta variant was predominant. Compared with non-recent vaccine immunity, COVID-19-related hospitalization incidence rates were reduced by 89% (87–91%) for boosted vaccine immunity, 66% (50–77%) for infection-induced immunity and 75% (61–83%) for enhanced infection-induced immunity. We demonstrate that infection-induced immunity (enhanced or not) provides more protection against COVID-19-related hospitalization than non-recent vaccine immunity, but less protection than booster vaccination. Additionally, our results suggest that vaccinating individuals with infection-induced immunity further enhances their protection.

Nat Commun2022       LitCov and CORD-19
524Production of a functionally active recombinant SARS-CoV-2 3C-like protease and a soluble inactive 3C-like protease-RBD chimeric in a prokaryotic expression system  

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Epidemiol Infect2022       LitCov
525Gastrointestinal viral shedding in children with SARS-CoV-2: a systematic review and meta-analysis  

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World J Pediatr2022       LitCov
526Modelling the potential acute and post-acute burden of COVID-19 under the Australian border re-opening plan  

BACKGROUND: Concerns have grown that post-acute sequelae of COVID-19 may affect significant numbers of survivors. However, the analyses used to guide policy-making for Australia’s national and state re-opening plans have not incorporated non-acute illness in their modelling. We, therefore, develop a model by which to estimate the potential acute and post-acute COVID-19 burden using disability-adjusted life years (DALYs) associated with the re-opening of Australian borders and the easing of other public health measures, with particular attention to longer-term, post-acute consequences and the potential impact of permanent functional impairment following COVID-19. METHODS: A model was developed based on the European Burden of Disease Network protocol guideline and consensus model to estimate the burden of COVID-19 using DALYs. Data inputs were based on publicly available sources. COVID-19 infection and different scenarios were drawn from the Doherty Institute’s modelling report to estimate the likely DALY losses under the Australian national re-opening plan. Long COVID prevalence, post-intensive care syndrome (PICS) and potential permanent functional impairment incidences were drawn from the literature. DALYs were calculated for the following health states: the symptomatic phase, Long COVID, PICS and potential permanent functional impairment (e.g., diabetes, Parkinson’s disease, dementia, anxiety disorders, ischemic stroke). Uncertainty and sensitivity analysis were performed to examine the robustness of the results. RESULTS: Mortality was responsible for 72-74% of the total base case COVID-19 burden. Long COVID and post-intensive care syndrome accounted for at least 19 and 3% of the total base case DALYs respectively. When included in the analysis, potential permanent impairment could contribute to 51-55% of total DALYs lost. CONCLUSIONS: The impact of Long COVID and potential long-term post-COVID disabilities could contribute substantially to the COVID-19 burden in Australia’s post-vaccination setting. As vaccination coverage increases, the share of COVID-19 burden driven by longer-term morbidity rises relative to mortality. As Australia re-opens, better estimates of the COVID-19 burden can assist with decision-making on pandemic control measures and planning for the healthcare needs of COVID-19 survivors. Our estimates highlight the importance of valuing the morbidity of post-COVID-19 sequelae, above and beyond simple mortality and case statistics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-13169-x.

BMC Public Health2022       LitCov and CORD-19
527Implications of testicular ACE2 and the renin-angiotensin system for SARS-CoV-2 on testis function  

Although many studies have focused on SARS-CoV-2 infection in the lungs, comparatively little is known about the potential effects of the virus on male fertility. SARS-CoV-2 infection of target cells requires the presence of furin, angiotensin-converting enzyme 2 (ACE2) receptors, and transmembrane protease serine 2 (TMPRSS2). Thus, cells in the body that express these proteins might be highly susceptible to viral entry and downstream effects. Currently, reports regarding the expression of the viral entry proteins in the testes are conflicting; however, other members of the SARS-CoV family of viruses — such as SARS-CoV — have been suspected to cause testicular dysfunction and/or orchitis. SARS-CoV-2, which displays many similarities to SARS-CoV, could potentially cause similar adverse effects. Commonalities between SARS family members, taken in combination with sparse reports of testicular discomfort and altered hormone levels in patients with SARS-CoV-2, might indicate possible testicular dysfunction. Thus, SARS-CoV-2 infection has the potential for effects on testis somatic and germline cells and experimental approaches might be required to help identify potential short-term and long-term effects of SARS-CoV-2 on male fertility.

Nat Rev Urol2021       LitCov and CORD-19
528Lack of inflammatory bowel disease flare-up following two-dose BNT162b2 vaccine: a population-based cohort study  

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Gut2022       LitCov and CORD-19
529Understanding the US failure on coronavirus-an essay by Drew Altman  

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BMJ2020       LitCov and CORD-19
530A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia  

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Infect Dis Ther2022       LitCov and CORD-19
531Adolescent Trauma During the COVID Pandemic: Just Like Adults, Children, or Someone Else?  

COVID-19 stay-at-home (SAH) orders were impactful on adolescence, when social interactions affect development. This has the potential to change adolescent trauma. A post-hoc multicenter retrospective analysis of adolescent (13-17 years-old) trauma patients (ATPs) at 11 trauma centers was performed. Patients were divided into 3 groups based on injury date: historical control (CONTROL:3/19/2019-6/30/2019, before SAH (PRE:1/1/2020-3/18/2020), and after SAH (POST:3/19/2020-6/30/2020). The POST group was compared to both PRE and CONTROL groups in separate analyses. 726 ATPs were identified across the 3 time periods. POST had a similar penetrating trauma rate compared to both PRE (15.8% vs 13.8%, P = .56) and CONTROL (15.8% vs 14.5%, P = .69). POST also had a similar rate of suicide attempts compared to both PRE (1.2% vs 1.5%, P = .83) and CONTROL (1.2% vs 2.1%, P = .43). However, POST had a higher rate of drug positivity compared to CONTROL (28.6% vs 20.6%, P = .032), but was similar in all other comparisons of alcohol and drugs to PRE and POST periods (all P > .05). Hence ATPs were affected differently than adults and children, as they had a similar rate of penetrating trauma, suicide attempts, and alcohol positivity after SAH orders. However, they had increased drug positivity compared to the CONTROL, but not PRE group.

Am Surg2022       LitCov and CORD-19
532Covid-19: How is vaccination affecting hospital admissions and deaths?  

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BMJ2021       LitCov and CORD-19
533Implementing sequence-based antigenic distance calculation into immunological shape space model  

BACKGROUND: In 2009, a novel influenza vaccine was distributed worldwide to combat the H1N1 influenza “swine flu” pandemic. However, antibodies induced by the vaccine display differences in their specificity and cross-reactivity dependent on pre-existing immunity. Here, we present a computational model that can capture the effect of pre-existing immunity on influenza vaccine responses. The model predicts the region of the virus hemagglutinin (HA) protein targeted by antibodies after vaccination as well as the level of cross-reactivity induced by the vaccine. We tested our model by simulating a scenario similar to the 2009 pandemic vaccine and compared the results to antibody binding data obtained from human subjects vaccinated with the monovalent 2009 H1N1 influenza vaccine. RESULTS: We found that both specificity and cross-reactivity of the antibodies induced by the 2009 H1N1 influenza HA protein were affected by the viral strain the individual was originally exposed. Specifically, the level of antigenic relatedness between the original exposure HA antigen and the 2009 HA protein affected antigenic-site immunodominance. Moreover, antibody cross-reactivity was increased when the individual’s pre-existing immunity was specific to an HA protein antigenically distinct from the 2009 pandemic strain. Comparison of simulation data with antibody binding data from human serum samples demonstrated qualitative and quantitative similarities between the model and real-life immune responses to the 2009 vaccine. CONCLUSION: We provide a novel method to evaluate expected outcomes in antibody specificity and cross-reactivity after influenza vaccination in individuals with different influenza HA antigen exposure histories. The model produced similar outcomes as what has been previously reported in humans after receiving the 2009 influenza pandemic vaccine. Our results suggest that differences in cross-reactivity after influenza vaccination should be expected in individuals with different exposure histories.

BMC Bioinformatics2020       CORD-19
534The association between vitamin D status and COVID-19 in England: A cohort study using UK Biobank  

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PLoS One2022       LitCov
535COVID-19 induces neuroinflammation and loss of hippocampal neurogenesis  

Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is associated with onset of neurological and psychiatric symptoms during and after the acute phase of illness(1–4). Acute SARS-CoV-2 disease (COVID-19) presents with deficits of memory, attention, movement coordination, and mood. The mechanisms of these central nervous system symptoms remain largely unknown. In an established hamster model of intranasal infection with SARS-CoV-2(5), and patients deceased from COVID-19, we report a lack of viral neuroinvasion despite aberrant BBB permeability, microglial activation, and brain expression of interleukin (IL)-1β and IL-6, especially within the hippocampus and the inferior olivary nucleus of the medulla, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uremia or trauma. In the hippocampus dentate gyrus of both COVID-19 hamsters and humans, fewer cells expressed doublecortin, a marker of neuroblasts and immature neurons. Despite absence of viral neurotropism, we find SARS-CoV-2-induced inflammation, and hypoxia in humans, affect brain regions essential for fine motor function, learning, memory, and emotional responses, and result in loss of adult hippocampal neurogenesis. Neuroinflammation could affect cognition and behaviour via disruption of brain vasculature integrity, neurotransmission, and neurogenesis, acute effects that may persist in COVID-19 survivors with long-COVID symptoms.

Res Sq2021       CORD-19
536Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain  

Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection. Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection – without neuroinvasion - and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.

bioRxiv2022       CORD-19
537Molnupiravir's authorisation was premature  

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BMJ2022       LitCov and CORD-19
538Changes in laboratory value improvement and mortality rates over the course of the pandemic: an international retrospective cohort study of hospitalised patients infected with SARS-CoV-2  

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BMJ Open2022       LitCov
539Cognitive dysfunction associated with COVID-19: A comprehensive neuropsychological study  

OBJECTIVE: Recent evidence suggests that patients suffering post-acute COVID syndrome frequently report cognitive complaints, but their characteristics and pathophysiology are unknown. This study aims to determine the characteristics of cognitive dysfunction in patients reporting cognitive complaints after COVID-19 and to evaluate the correlation between cognitive function and anxiety, depression, sleep, and olfactory function. METHODS: Cross-sectional study involving 50 patients with COVID-19 reporting cognitive complaints 9.12 ± 3.46 months after the acute infection. Patients were evaluated with a comprehensive neuropsychological protocol, and scales of fatigue, depression, anxiety, sleep and an olfactory test. Normative data and an age- and education matched healthy control group were used for comparison. RESULTS: COVID-19 patients showed a diminished performance on several tests evaluating attention and executive function, with alterations in processing speed, divided attention, selective attention, visual vigilance, intrinsic alertness, working memory, and inhibition; episodic memory; and visuospatial processing. Cognitive performance was correlated with olfactory dysfunction, and sleep quality and anxiety to a lesser extent, but not depression. CONCLUSIONS: Patients with COVID-19 reporting cognitive symptoms showed a reduced cognitive performance, especially in the attention-concentration and executive functioning, episodic memory, and visuospatial processing domains. Future studies are necessary to disentangle the specific mechanisms associated with COVID-19 cognitive dysfunction.

J Psychiatr Res2022       LitCov and CORD-19
540Herpes zoster reactivation after mRNA-1273 (Moderna) SARS-CoV-2 vaccination  

JAAD Case Rep2021       LitCov and CORD-19
541Lactoferrin as Antiviral Treatment in COVID-19 Management: Preliminary Evidence  

Lactoferrin (Lf), a multifunctional cationic glycoprotein synthesized by exocrine glands and neutrophils, possesses an in vitro antiviral activity against SARS-CoV-2. Thus, we conducted an in vivo preliminary study to investigate the antiviral effect of oral and intranasal liposomal bovine Lf (bLf) in asymptomatic and mild-to-moderate COVID-19 patients. From April 2020 to June 2020, a total of 92 mild-to-moderate (67/92) and asymptomatic (25/92) COVID-19 patients were recruited and divided into three groups. Thirty-two patients (14 hospitalized and 18 in home-based isolation) received only oral and intranasal liposomal bLf; 32 hospitalized patients were treated only with standard of care (SOC) treatment; and 28, in home-based isolation, did not take any medication. Furthermore, 32 COVID-19 negative, untreated, healthy subjects were added for ancillary analysis. Liposomal bLf-treated COVID-19 patients obtained an earlier and significant (p < 0.0001) SARS-CoV-2 RNA negative conversion compared to the SOC-treated and untreated COVID-19 patients (14.25 vs. 27.13 vs. 32.61 days, respectively). Liposomal bLf-treated COVID-19 patients showed fast clinical symptoms recovery compared to the SOC-treated COVID-19 patients. In bLf-treated patients, a significant decrease in serum ferritin, IL-6, and D-dimers levels was observed. No adverse events were reported. These observations led us to speculate a potential role of bLf in the management of mild-to-moderate and asymptomatic COVID-19 patients.

Int J Environ Res Public Healt2021       LitCov and CORD-19
542Ambulatory COVID-19 Patients Treated with Lactoferrin as a Supplementary Antiviral Agent: A Preliminary Study  

SARS-CoV-2, an enveloped, single-stranded RNA virus causing COVID-19, exerts morbidity and mortality especially in elderly, obese individuals and those suffering from chronic conditions. In addition to the availability of vaccines and the limited efficacy of the first dose of vaccine against SARS-CoV-2 variants, there is an urgent requirement for the discovery and development of supplementary antiviral agents. Lactoferrin (Lf), a pleiotropic cationic glycoprotein of innate immunity, has been proposed as a safe treatment combined with other therapies in COVID-19 patients. Here, we present a small retrospective study on asymptomatic, paucisymptomatic, and moderate symptomatic COVID-19 Lf-treated versus Lf-untreated patients. The time required to achieve SARS-CoV-2 RNA negativization in Lf-treated patients (n = 82) was significantly lower (p < 0.001) compared to that observed in Lf-untreated ones (n = 39) (15 versus 24 days). A link among reduction in symptoms, age, and Lf treatment was found. The Lf antiviral activity could be explained through the interaction with SARS-CoV-2 spike, the binding with heparan sulfate proteoglycans of cells, and the anti-inflammatory activity associated with the restoration of iron homeostasis disorders, which favor viral infection/replication. Lf could be an important supplementary treatment in counteracting SARS-CoV-2 infection, as it is also safe and well-tolerated by all treated patients.

J Clin Med2021       LitCov and CORD-19
543Immune-Mediated Platelet Activation in COVID-19 and Vaccine induced Immune Thrombotic Thrombocytopenia  

Both qualitative and quantitative platelet abnormalities are common in patients with coronavirus disease 2019 (COVID-19) and they correlate with clinical severity and mortality. Activated platelets contribute to the prothrombotic state in COVID-19 patients. Several groups have shown immune-mediated activation of platelets in critically ill COVID-19 patients. Vaccine-induced immune thrombotic thrombocytopenia is an autoimmune condition characterized by thrombocytopenia and life-threatening thrombotic events in the arterial and venous circulation. Although the initial trigger has yet to be determined, activation of platelets by immune complexes through Fc gamma RIIA results in platelet consumption and thrombosis. A better understanding of platelet activation in COVID-19 as well as in vaccine-induced thrombotic complications will have therapeutic implications. In this review, we focused on the role of immune-mediated platelet activation in thrombotic complications during COVID-19 infection and vaccine-induced immune thrombotic thrombocytopenia.

Front Immunol2022       LitCov and CORD-19
544The SARS CoV-2 spike directed non-neutralizing polyclonal antibodies cross-react with Human immunodeficiency virus (HIV-1) gp41  

Cross-reactivity among the two diverse viruses is believed to originate from the concept of antibodies recognizing similar epitopes on the two viral surfaces. Cross-reactive antibody responses have been seen in previous variants of SARS and SARS-CoV-2, but little is known about the cross reactivity with other similar RNA viruses like HIV-1. In the present study, we examined the reactivity the SARS-CoV-2 directed antibodies, via spike, immunized mice sera and demonstrated whether they conferred any cross-reactive neutralization against HIV-1. Our findings show that SARS-CoV-2 spike immunized mice antibodies cross-react with the HIV-1 Env protein. Cross-neutralization among the two viruses is uncommon, suggesting the presence of a non-neutralizing antibody response to conserved epitopes amongst the two viruses. Our results indicate, that SARS-CoV-2 spike antibody cross reactivity is targeted towards the gp41 region of the HIV-1 Env (gp160) protein. Overall, our investigation not only answers a crucial question about the understanding of cross-reactive epitopes of antibodies generated in different viral infections, but also provides critical evidence for developing vaccine immunogens and novel treatment strategies with enhanced efficacy capable of recognising diverse pathogens with similar antigenic features.

Int Immunopharmacol2021       LitCov and CORD-19
545Examining COVID-19 vaccine uptake and attitudes among 2SLGBTQ+ youth experiencing homelessness  

OBJECTIVES: The COVID-19 pandemic has disproportionately impacted 2SLGBTQ+ youth experiencing homelessness. Little is known about vaccine attitudes and uptake among this population. To address this, the objectives of this study were to explore this group’s COVID-19 vaccine attitudes, and facilitators and barriers impacting vaccine uptake. METHODS: 2SLGBTQ+ youth experiencing homelessness in the Greater Toronto Area were recruited to participate in online surveys assessing demographic characteristics, mental health, health service use, and COVID-19 vaccine attitudes. Descriptive statistics and statistical tests were used to analyze survey data to explore variables associated with vaccine confidence. Additionally, a select group of youth and frontline workers from youth serving organizations were invited to participate in online one-on-one interviews. An iterative thematic content approach was used to analyze interview data. Quantitative and qualitative data were merged for interpretation by use of a convergent parallel analytical design. RESULTS: Ninety-two youth completed surveys and 32 youth and 15 key informants participated in one-on-one interviews. Quantitative and qualitative data showed that the majority of 2SLGBTQ+ youth experiencing homelessness were confident in the COVID-19 vaccine; however, numerous youth were non-vaccine confident due to mistrust in the healthcare system, lack of targeted vaccine-related public health information, concerns about safety and side effects, and accessibility issues. Solutions to increase vaccine confidence were provided, including fostering trust, targeted public health messaging, and addressing accessibility needs. CONCLUSION: Our study highlights the need for the vaccine strategy and rollouts to prioritize 2SLGBTQ+ youth experiencing homelessness and to address the pervasive health disparities that have been exacerbated by the pandemic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-12537-x.

BMC Public Health2022       LitCov and CORD-19
546Early Intubation and Increased COVID-19 Mortality: A Propensity Score-Matched Retrospective Cohort Study  

OBJECTIVES: There has been controversy about the timing and indications for intubation and mechanical ventilation in novel coronavirus disease 2019. This study assessed the effect of early intubation and mechanical ventilation on all-cause, inhospital mortality for coronavirus disease 2019 patients. DESIGN: Multicenter retrospective cohort study. SETTING: Eleven municipal hospitals in New York City from March 1, 2020, to December 1, 2020. PATIENTS: Adult patients who tested positive for coronavirus disease 2019 in the emergency department were subsequently admitted. Patients with do-not-intubate orders at admission were excluded. INTERVENTIONS: Intubation within 48 hours of triage and intubation at any point during hospital stay. MEASUREMENTS AND MAIN RESULTS: Data from 7,597 coronavirus disease 2019 patients were included; of these, 1,628 (21%) were intubated overall and 807 (11%) were intubated within 48 hours of triage. After controlling for available confounders, intubation rates for coronavirus disease 2019 patients varied significantly across hospitals and decreased steadily as the pandemic progressed. After nearest neighbor propensity score matching, intubation within 48 hours of triage was associated with higher all-cause mortality (hazard ratio, 1.30 [1.15–1.48]; p < 0.0001), as was intubation at any time point (hazard ratio, 1.62 [1.45–1.80]; p < 0.0001). Among intubated patients, intubation within 48 hours of triage was not significantly associated with differences in mortality (hazard ratio, 1.09 [0.94–1.26]; p = 0.26). These results remained robust to multiple sensitivity analyses. CONCLUSIONS: Intubation within 48 hours of triage, as well as at any time point in the hospital course, was associated with increased mortality in coronavirus disease 2019 patients in this observational study.

Crit Care Explor2021       LitCov and CORD-19
547Detection of SARS-CoV-2 RNA in Medical Wastewater in Wuhan During the COVID-19 Outbreak  

Virol Sin2021       LitCov and CORD-19
548Omicron's message on vaccines: Boosting begets breadth  

In this issue of Cell, three studies confirm that SARS-CoV-2 Omicron strongly evades a key immune defense—neutralizing antibodies. However, while one- or two-dose vaccine regimens fail to induce anti-Omicron neutralizing antibodies, a homologous 3rd-dose booster rescues neutralization function in a way that highlights the adaptability of immune memory, where recalled immune memory extends antibody reach across-SARS-CoV-2 variants.

Cell2022       LitCov and CORD-19
549Medical sequels of COVID-19  

COVID-19 pandemic has impacted the world population, with a high rate of morbidity and mortality. While the evidence to date has attempted to describe clinical feature of acute illness, recent reports have also begun to describe persistent symptoms that extend beyond the initial period of illness. Adverse outcomes, in addition to respiratory, have been found to occur at different levels: cardiovascular, neurological, or immunological; skin, gastrointestinal or renal manifestations. The detrimental effect on mental health has also been described, not only in COVID-19 patients. The burden of disease secondary to this pandemic is likely to be enormous and not limited to acute disease alone, thus epidemiological studies are needed to further investigate the long-term impact of this disease. This review summarizes the current evidence on short-term effects and describes the possible long-term sequelae of COVID-19.

Med Clin (Barc)2021       LitCov and CORD-19
550Maoto, a Traditional Japanese Herbal Medicine, Inhibits Uncoating of Influenza Virus  

We previously reported in randomized controlled trials that maoto, a traditional herbal medicine, showed clinical and virological efficacy for seasonal influenza. In this study, a culturing system for influenza was used to test the effect of maoto. A549 cells in the culture were infected with influenza virus A (PR8) and followed after treatment with maoto; the virus titers in the culture supernatant, intracellular viral proteins, and viral RNA were determined. When infected cells were cultured with maoto for 24 hr, the virus titer and protein were significantly reduced compared with medium only. Other subtypes, A/H3N2, H1N1pdm, and B, were also inhibited by maoto. Proliferation of viral RNA in a 6 hr culture was inhibited by maoto in the early phase, especially in the first 30 min. Focusing on the entry step of the influenza virus, we found that endosomal pH, regulated by vacuolar-type H(+) ATPase (V-ATPase) located in the membrane, was increased when treated with maoto. We also found that uncoating of influenza viruses was also inhibited by maoto, resulting in the increase of the number of virus particles in endosomes. These results strongly suggest that the inhibition of endosomal acidification by maoto results in blocking influenza virus entry to cytoplasm, probably through the inhibition of V-ATPase. The present study provides evidence that supports the clinical use of maoto for the treatment of influenza.

Evid Based Complement Alternat2017       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
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(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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