\ 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
3901Pfizer/BioNtech BNT162b2: adverse events and insights from an Australian mass vaccination clinic for COVID-19  

N/A

Intern Med J2022       LitCov and CORD-19
3902Factors affecting the serologic response to SARS-CoV-2 vaccination in patients with solid tumors: A prospective study  

N/A

J Infect Chemother2022       LitCov
3903Perceptions of medical students towards and effectiveness of online surgical curriculum: a systematic review  

BACKGROUND: Online education has been used as an adjunct modality for teaching and it attracts attention in recent years as many medical students can not accomplish their clerkship in the hospital due to COVID-19 pandemic. This study aims to collect the articles related to online surgical education for medical students, and to analyze the effectiveness of online education and the perceptions of the medical students. METHOD: We performed a systemic literature search in PubMed, MEDLINE, EMBASE, ERIC and Cochrane library. Keywords used for searching included “medical student”, “online education”, “online teaching”, “online learning”, “distance learning”, “electronic learning”, “virtual learning” and “surgical”. Medical education research study quality instrument (MERSQI) was used for the evaluation of the quality of the searched articles. RESULTS: From 1240 studies retrieved from the databases, 13 articles were included in this study after screening. The publication year was from 2007 to 2021. The mean MERSQI score of the 13 searched articles was 12.5 +/− 1.7 (range 10.0-14.5). There were totally 2023 medical students who attended online surgical curriculum. By online course, improvement of understanding and knowledge on the studied topics could be reached. The confidence in patient encounters could be improved by online curriculum with sharing experiences, discussing, and role playing. However, students felt concentration was poor during online course. Medical students studying through video platform could get better test scores than those studying with textbooks. Regarding basic surgical skills, online teaching of suturing and knot-tying could be possible and was appreciated by the students who could practice away from the hospital and get feedbacks by instructors through online environment. The scores for the clinical competence assessment for incision, suturing and knot-tying were found to be no significant difference between the online teaching group and face-to-face teaching group. CONCLUSION: Online surgical curriculum for medical students is not easy but inevitable in the era of COVID-19 pandemic. Although online course is not the same as physical course, there are some efforts which could be tried to increase the effectiveness. Basic surgical skills could also be taught effectively through online platform. Even if the COVID-19 pandemic is over in the future, online curriculum could still be a helpful adjunct for surgical education.

BMC Med Educ2021       LitCov and CORD-19
3904A large-scale meta-analytic atlas of mental health problems prevalence during the COVID-19 early pandemic  

The COVID‐19 pandemic and related restrictions can impact mental health. To quantify the mental health burden of COVID‐19 pandemic, we conducted a systematic review and meta‐analysis, searching World Health Organization COVID‐19/PsycInfo/PubMed databases (09/29/2020), including observational studies reporting on mental health outcomes in any population affected by COVID‐19. Primary outcomes were the prevalence of anxiety, depression, stress, sleep problems, posttraumatic symptoms. Sensitivity analyses were conducted on severe mental health problems, in high‐quality studies, and in representative samples. Subgroup analyses were conducted stratified by age, sex, country income level, and COVID‐19 infection status. One‐hundred‐seventy‐three studies from February to July 2020 were included (n = 502,261, median sample = 948, age = 34.4 years, females = 63%). Ninety‐one percent were cross‐sectional studies, and 18.5%/57.2% were of high/moderate quality. The highest prevalence emerged for posttraumatic symptoms in COVID‐19 infected people (94%), followed by behavioral problems in those with prior mental disorders (77%), fear in healthcare workers (71%), anxiety in caregivers/family members of people with COVID‐19 (42%), general health/social contact/passive coping style in the general population (38%), depression in those with prior somatic disorders (37%), and fear in other‐than‐healthcare workers (29%). Females and people with COVID‐19 infection had higher rates of almost all outcomes; college students/young adults of anxiety, depression, sleep problems, suicidal ideation; adults of fear and posttraumatic symptoms. Anxiety, depression, and posttraumatic symptoms were more prevalent in low‐/middle‐income countries, sleep problems in high‐income countries. The COVID‐19 pandemic adversely impacts mental health in a unique manner across population subgroups. Our results inform tailored preventive strategies and interventions to mitigate current, future, and transgenerational adverse mental health of the COVID‐19 pandemic.

J Med Virol2022       LitCov and CORD-19
3905Intensive care admissions of children with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicenter observational study  

BACKGROUND: In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). METHODS: We did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome). FINDINGS: 78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0·85–1·22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8–14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4), D-dimer (4030 μg/L to 1659 μg/L), and ferritin (1042 μg/L to 757 μg/L), whereas the lymphocyte count increased to more than 1·0 × 10(9) cells per L by day 3 and troponin increased over the 4 days (from a median of 157 ng/mL to 358 ng/mL). 36 (46%) of 78 patients were invasively ventilated and 65 (83%) needed vasoactive infusions; 57 (73%) received steroids, 59 (76%) received intravenous immunoglobulin, and 17 (22%) received biologic therapies. 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed extracorporeal membrane oxygenation, and two children died. INTERPRETATION: During the study period, the rate of PICU admissions for PIMS-TS was at least 11-fold higher than historical trends for similar inflammatory conditions. Clinical presentations and treatments varied. Coronary artery aneurysms appear to be an important complication. Although immediate survival is high, the long-term outcomes of children with PIMS-TS are unknown. FUNDING: None.

Lancet Child Adolesc Health2020       LitCov and CORD-19
3906Deep Convolutional Neural Network-Based Computer-Aided Detection System for COVID-19 Using Multiple Lung Scans: Design and Implementation Study  

BACKGROUND: Owing to the COVID-19 pandemic and the imminent collapse of health care systems following the exhaustion of financial, hospital, and medicinal resources, the World Health Organization changed the alert level of the COVID-19 pandemic from high to very high. Meanwhile, more cost-effective and precise COVID-19 detection methods are being preferred worldwide. OBJECTIVE: Machine vision–based COVID-19 detection methods, especially deep learning as a diagnostic method in the early stages of the pandemic, have been assigned great importance during the pandemic. This study aimed to design a highly efficient computer-aided detection (CAD) system for COVID-19 by using a neural search architecture network (NASNet)–based algorithm. METHODS: NASNet, a state-of-the-art pretrained convolutional neural network for image feature extraction, was adopted to identify patients with COVID-19 in their early stages of the disease. A local data set, comprising 10,153 computed tomography scans of 190 patients with and 59 without COVID-19 was used. RESULTS: After fitting on the training data set, hyperparameter tuning, and topological alterations of the classifier block, the proposed NASNet-based model was evaluated on the test data set and yielded remarkable results. The proposed model's performance achieved a detection sensitivity, specificity, and accuracy of 0.999, 0.986, and 0.996, respectively. CONCLUSIONS: The proposed model achieved acceptable results in the categorization of 2 data classes. Therefore, a CAD system was designed on the basis of this model for COVID-19 detection using multiple lung computed tomography scans. The system differentiated all COVID-19 cases from non–COVID-19 ones without any error in the application phase. Overall, the proposed deep learning–based CAD system can greatly help radiologists detect COVID-19 in its early stages. During the COVID-19 pandemic, the use of a CAD system as a screening tool would accelerate disease detection and prevent the loss of health care resources.

J Med Internet Res2021       LitCov and CORD-19
3907SARS-CoV-2 Mpro: A Potential Target for Peptidomimetics and Small-Molecule Inhibitors  

The uncontrolled spread of the COVID-19 pandemic caused by the new coronavirus SARS-CoV-2 during 2020–2021 is one of the most devastating events in the history, with remarkable impacts on the health, economic systems, and habits of the entire world population. While some effective vaccines are nowadays approved and extensively administered, the long-term efficacy and safety of this line of intervention is constantly under debate as coronaviruses rapidly mutate and several SARS-CoV-2 variants have been already identified worldwide. Then, the WHO’s main recommendations to prevent severe clinical complications by COVID-19 are still essentially based on social distancing and limitation of human interactions, therefore the identification of new target-based drugs became a priority. Several strategies have been proposed to counteract such viral infection, including the repurposing of FDA already approved for the treatment of HIV, HCV, and EBOLA, inter alia. Among the evaluated compounds, inhibitors of the main protease of the coronavirus (M(pro)) are becoming more and more promising candidates. M(pro) holds a pivotal role during the onset of the infection and its function is intimately related with the beginning of viral replication. The interruption of its catalytic activity could represent a relevant strategy for the development of anti-coronavirus drugs. SARS-CoV-2 M(pro) is a peculiar cysteine protease of the coronavirus family, responsible for the replication and infectivity of the parasite. This review offers a detailed analysis of the repurposed drugs and the newly synthesized molecules developed to date for the treatment of COVID-19 which share the common feature of targeting SARS-CoV-2 M(pro), as well as a brief overview of the main enzymatic and cell-based assays to efficaciously screen such compounds.

Biomolecules2021       LitCov and CORD-19
3908Immune response to SARS-CoV-2 Omicron variant in patients and vaccinees following homologous and heterologous vaccinations  

N/A

Commun Biol2022       LitCov
3909Changes of symptoms of eating disorders (ED) and their related psychological health issues during the COVID-19 pandemic: a systematic review and meta-analysis  

BACKGROUND: The COVID-19 pandemic and its related social restrictions have profoundly affected people’s mental health. It can be assumed that symptomatic behaviors and mental health of individuals with eating disorders (ED) deteriorated during this time. To get a thorough overview, we conducted a systematic review and meta-analysis with the following aims: First, to provide a comprehensive overview of symptoms of ED during the COVID-19-related confinement; second, to identify psychological mechanisms which impacted the emergence and maintenance of ED symptoms; third, to describe changes of daily routine and changes of access to healthcare in individuals with ED during confinement. METHODS: We searched Embase, PubMed, and Scopus databases for observational studies published between January 1st, 2020, to July 1st, 2021, which investigated the symptomatology of ED during the COVID-19 pandemic. RESULTS: After the screening, 13 studies with 7848 participants were included in the present systematic review and meta-analysis. The overall pooled prevalence of exacerbation of binge eating, food restriction, purging behaviors, and concerns about food intake in the pooled sample of 7848 was 59.65% (95% CI: 49.30%; 69.60%), and the overall prevalence of improved symptoms of ED in the pooled sample of 741 individuals was 9.37% (95% CI: 3.92%; 16.57%). Furthermore, COVID-19-related social restrictions negatively impacted the psychological health, daily routines, and physical activity of individuals with ED. More specifically, symptoms of anxiety and depression related to ED were increased significantly over time. However, there were also positive aspects to the COVID-19 pandemic. The main positive consequences included more emotional support from the family, less pressure to engage in social activities, and more flexible meal planning. Individuals with ED reported having difficulties getting access to healthcare centers and using telemedicine. They also found a hard time communicating via online sessions. CONCLUSIONS: According to our interpretation, based on the data included in the systematic review and meta-analysis, the COVID-19 pandemic and its related social restrictions detrimentally impacted the mental health of majority of individuals with ED. Limited and impaired access to healthcare interventions appeared to have further exacerbated mental health issues of individuals with ED. Given this background, it seems that individuals with ED demand more attention during the COVID-19 crisis, and it is necessary to ensure that their course of treatment remains uninterrupted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40337-022-00550-9.

J Eat Disord2022       LitCov and CORD-19
3910Meta-Analysis of Risk of Myocarditis After Messenger RNA COVID-19 Vaccine  

Am J Cardiol2022       LitCov and CORD-19
3911Neutralizing Activity and SARS-CoV-2 Vaccine mRNA Persistence in Serum and Breastmilk After BNT162b2 Vaccination in Lactating Women  

BACKGROUND: There is limited information on the functional neutralizing capabilities of breastmilk SARS-CoV-2-specific antibodies and the potential adulteration of breastmilk with vaccine mRNA after SARS-CoV-2 mRNA vaccination. METHODS: We conducted a prospective cohort study of lactating healthcare workers who received the BNT162b2 vaccine and their infants. The presence of SARS-CoV-2 neutralizing antibodies, antibody isotypes (IgG, IgA, IgM) and intact mRNA in serum and breastmilk was evaluated at multiple time points using a surrogate neutralizing assay, ELISA, and PCR, over a 6 week period of the two-dose vaccination given 21 days apart. RESULTS: Thirty-five lactating mothers, median age 34 years (IQR 32-36), were included. All had detectable neutralizing antibodies in the serum immediately before dose 2, with significant increase in neutralizing antibody levels 7 days after this dose [median 168.4 IU/ml (IQR 100.7-288.5) compared to 2753.0 IU/ml (IQR 1627.0-4712.0), p <0.001]. Through the two vaccine doses, all mothers had detectable IgG1, IgA and IgM isotypes in their serum, with a notable increase in all three antibody isotypes after dose 2, especially IgG1 levels. Neutralizing antibodies were detected in majority of breastmilk samples a week after dose 2 [median 13.4 IU/ml (IQR 7.0-28.7)], with persistence of these antibodies up to 3 weeks after. Post the second vaccine dose, all (35/35, 100%) mothers had detectable breastmilk SARS-CoV-2 spike RBD-specific IgG1 and IgA antibody and 32/35 (88.6%) mothers with IgM. Transient, low intact vaccine mRNA levels was detected in 20/74 (27%) serum samples from 21 mothers, and 5/309 (2%) breastmilk samples from 4 mothers within 1 weeks of vaccine dose. Five infants, median age 8 months (IQR 7-16), were also recruited - none had detectable neutralizing antibodies or vaccine mRNA in their serum. CONCLUSION: Majority of lactating mothers had detectable SARS-CoV-2 antibody isotypes and neutralizing antibodies in serum and breastmilk, especially after dose 2 of BNT162b2 vaccination. Transient, low levels of vaccine mRNA were detected in the serum of vaccinated mothers with occasional transfer to their breastmilk, but we did not detect evidence of infant sensitization. Importantly, the presence of breastmilk neutralising antibodies likely provides a foundation for passive immunisation of the breastmilk-fed infant.

Front Immunol2021       LitCov and CORD-19
3912Vaccine Breakthrough Infections with SARS-CoV-2 Variants  

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of clinical concern. In a cohort of 417 persons who had received the second dose of BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) vaccine at least 2 weeks previously, we identified 2 women with vaccine breakthrough infection. Despite evidence of vaccine efficacy in both women, symptoms of coronavirus disease 2019 developed, and they tested positive for SARS-CoV-2 by polymerase-chain-reaction testing. Viral sequencing revealed variants of likely clinical importance, including E484K in 1 woman and three mutations (T95I, del142–144, and D614G) in both. These observations indicate a potential risk of illness after successful vaccination and subsequent infection with variant virus, and they provide support for continued efforts to prevent and diagnose infection and to characterize variants in vaccinated persons. (Funded by the National Institutes of Health and others.)

N Engl J Med2021       LitCov and CORD-19
3913COVID-19-Related Web Search Behaviors and Infodemic Attitudes in Italy: Infodemiological Study  

BACKGROUND: Since the beginning of the novel coronavirus disease (COVID-19) outbreak, fake news and misleading information have circulated worldwide, which can profoundly affect public health communication. OBJECTIVE: We investigated online search behavior related to the COVID-19 outbreak and the attitudes of “infodemic monikers” (ie, erroneous information that gives rise to interpretative mistakes, fake news, episodes of racism, etc) circulating in Italy. METHODS: By using Google Trends to explore the internet search activity related to COVID-19 from January to March 2020, article titles from the most read newspapers and government websites were mined to investigate the attitudes of infodemic monikers circulating across various regions and cities in Italy. Search volume values and average peak comparison (APC) values were used to analyze the results. RESULTS: Keywords such as “novel coronavirus,” “China coronavirus,” “COVID-19,” “2019-nCOV,” and “SARS-COV-2” were the top infodemic and scientific COVID-19 terms trending in Italy. The top five searches related to health were “face masks,” “amuchina” (disinfectant), “symptoms of the novel coronavirus,” “health bulletin,” and “vaccines for coronavirus.” The regions of Umbria and Basilicata recorded a high number of infodemic monikers (APC weighted total >140). Misinformation was widely circulated in the Campania region, and racism-related information was widespread in Umbria and Basilicata. These monikers were frequently searched (APC weighted total >100) in more than 10 major cities in Italy, including Rome. CONCLUSIONS: We identified a growing regional and population-level interest in COVID-19 in Italy. The majority of searches were related to amuchina, face masks, health bulletins, and COVID-19 symptoms. Since a large number of infodemic monikers were observed across Italy, we recommend that health agencies use Google Trends to predict human behavior as well as to manage misinformation circulation in Italy.

JMIR Public Health Surveill2020       LitCov and CORD-19
3914SARS-CoV-2 seroprevalence in South-Central Uganda, during 2019-2021  

BACKGROUND: Globally, key subpopulations such as healthcare workers (HCW) may have a higher risk of contracting SARS-CoV-2. In Uganda, limited access to Personal Protective Equipment and lack of clarity on the extent/pattern of community spread may exacerbate this situation. The country established infection prevention/control measures such as lockdowns and proper hand hygiene. However, due to resource limitations and fatigue, compliance is low, posing continued onward transmission risk. This study aimed to describe extent of SARS-CoV-2 seroprevalence in selected populations within the Rakai region of Uganda. METHODS: From 30th November 2020 to 8th January 2021, we collected venous blood from 753 HCW at twenty-six health facilities in South-Central Uganda and from 227 population-cohort participants who reported specific COVID-19 like symptoms (fever, cough, loss of taste and appetite) in a prior phone-based survey conducted (between May and August 2020) during the first national lockdown. 636 plasma specimens collected from individuals considered high risk for SARS-CoV-2 infection, prior to the first confirmed COVID-19 case in Uganda were also retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek™ rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (CMIA) (Architect AdviseDx SARS-CoV-2 IgM) which targets the spike protein. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity. Overall seroprevalence in each participant group was estimated, adjusting for test performance. RESULTS: The seroprevalence of antibodies to SARS-CoV-2 in HCW was 26.7% [95%CI: 23.5, 29.8] with no difference by sex, age, or cadre. We observed no association between PPE use and seropositivity among exposed healthcare workers. Of the phone-based survey participants, 15.6% [95%CI: 10.9, 20.3] had antibodies to SARS-CoV-2, with no difference by HIV status, sex, age, or occupation. Among 636 plasma specimens collected prior to the first confirmed COVID-19 case, 2.3% [95%CI: 1.2, 3.5] were reactive. CONCLUSIONS: Findings suggest high seroprevalence of antibodies to SARS-CoV-2 among HCW and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-Central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether seroprevalence among plasma specimens collected prior to confirmation of the first COVID-19 case implies prior SARS-CoV-2 exposure in Uganda.

BMC Infect Dis2022       LitCov and CORD-19
3915BNT162b2 Vaccination Elicits Strong Serological Immune Responses Against SARS-CoV-2 Including Variants of Concern in Elderly Convalescents  

Elderly residents of long-term care facilities (LTCFs) have long been underrepresented in studies on vaccine efficacy, particularly in light of currently emerging variants of concern (VOCs). In this prospective observational cohort study, we analyzed serological immune responses in 190 individuals before, 3 weeks after 1(st) and 3 weeks after 2(nd) vaccination with BNT162b2. Unvaccinated COVID-19-convalescent subjects served as reference. End points comprised serum anti-spike IgG and IgA titers as well as neutralization capacities against unmutated and mutated SARS-CoV-2 receptor binding domains including B.1.1.7, B.1.351 and P.1. We found that antibody titers and neutralization capacities up to 3 weeks after 2(nd) vaccination with BNT162b2 were significantly higher in COVID-19-convalescent as compared to COVID-19-naive vaccinees. Moreover, pre-vaccination anti-NCP IgG titers, but not age or gender, had a high impact on the strength and kinetics of post-vaccination neutralization capacity development. Most importantly, BNT162b2-induced neutralization capacity was cross-reactive with VOCs. In contrast to unvaccinated convalescents, vaccinated convalescent individuals of all ages acquired strong neutralizing capacities against current VOCs. The present study suggests that COVID-19-convalescent individuals with a broad age range between 18 and 98 years benefit from BNT162b2 vaccination by developing strong and broad neutralizing immune responses against SARS-CoV-2 including current VOCs.

Front Immunol2021       LitCov and CORD-19
3916Diagnostic Performance Assessment of Saliva RT-PCR and Nasopharyngeal Antigen for the Detection of SARS-CoV-2 in Peru  

N/A

Microbiol Spectr2022       LitCov
3917SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best  

BACKGROUND: Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization. METHODS: Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine. RESULTS: The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only. CONCLUSION: In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10875-021-01133-0.

J Clin Immunol2021       LitCov and CORD-19
3918Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis  

BACKGROUND: Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for Coronavirus Disease 2019 (COVID-19), but the results are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective. METHODS AND FINDINGS: We carried out a systematic review and network meta-analysis (NMA) to systematically evaluate the comparative efficacy and safety of pharmacological interventions and the level of evidence behind each treatment regimen in different clinical settings. Both published and unpublished randomized controlled trials (RCTs) and confounding-adjusted observational studies which met our predefined eligibility criteria were collected. We included studies investigating the effect of pharmacological management of patients hospitalized for COVID-19 management. Mild patients who do not require hospitalization or have self-limiting disease courses were not eligible for our NMA. A total of 110 studies (40 RCTs and 70 observational studies) were included. PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from the beginning of 2020 to August 24, 2020. Studies from Asia (41 countries, 37.2%), Europe (28 countries, 25.4%), North America (24 countries, 21.8%), South America (5 countries, 4.5%), and Middle East (6 countries, 5.4%), and additional 6 multinational studies (5.4%) were included in our analyses. The outcomes of interest were mortality, progression to severe disease (severe pneumonia, admission to intensive care unit (ICU), and/or mechanical ventilation), viral clearance rate, QT prolongation, fatal cardiac complications, and noncardiac serious adverse events. Based on RCTs, the risk of progression to severe course and mortality was significantly reduced with corticosteroids (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.06 to 0.86, p = 0.032, and OR 0.78, 95% CI 0.66 to 0.91, p = 0.002, respectively) and remdesivir (OR 0.29, 95% CI 0.17 to 0.50, p < 0.001, and OR 0.62, 95% CI 0.39 to 0.98, p = 0.041, respectively) compared to standard care for moderate to severe COVID-19 patients in non-ICU; corticosteroids were also shown to reduce mortality rate (OR 0.54, 95% CI 0.40 to 0.73, p < 0.001) for critically ill patients in ICU. In analyses including observational studies, interferon-alpha (OR 0.05, 95% CI 0.01 to 0.39, p = 0.004), itolizumab (OR 0.10, 95% CI 0.01 to 0.92, p = 0.042), sofosbuvir plus daclatasvir (OR 0.26, 95% CI 0.07 to 0.88, p = 0.030), anakinra (OR 0.30, 95% CI 0.11 to 0.82, p = 0.019), tocilizumab (OR 0.43, 95% CI 0.30 to 0.60, p < 0.001), and convalescent plasma (OR 0.48, 95% CI 0.24 to 0.96, p = 0.038) were associated with reduced mortality rate in non-ICU setting, while high-dose intravenous immunoglobulin (IVIG) (OR 0.13, 95% CI 0.03 to 0.49, p = 0.003), ivermectin (OR 0.15, 95% CI 0.04 to 0.57, p = 0.005), and tocilizumab (OR 0.62, 95% CI 0.42 to 0.90, p = 0.012) were associated with reduced mortality rate in critically ill patients. Convalescent plasma was the only treatment option that was associated with improved viral clearance rate at 2 weeks compared to standard care (OR 11.39, 95% CI 3.91 to 33.18, p < 0.001). The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 2.01, 95% CI 1.26 to 3.20, p = 0.003) and fatal cardiac complications in cardiac-impaired populations (OR 2.23, 95% CI 1.24 to 4.00, p = 0.007). No drug was significantly associated with increased noncardiac serious adverse events compared to standard care. The quality of evidence of collective outcomes were estimated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The major limitation of the present study is the overall low level of evidence that reduces the certainty of recommendations. Besides, the risk of bias (RoB) measured by RoB2 and ROBINS-I framework for individual studies was generally low to moderate. The outcomes deducted from observational studies could not infer causality and can only imply associations. The study protocol is publicly available on PROSPERO (CRD42020186527). CONCLUSIONS: In this NMA, we found that anti-inflammatory agents (corticosteroids, tocilizumab, anakinra, and IVIG), convalescent plasma, and remdesivir were associated with improved outcomes of hospitalized COVID-19 patients. Hydroxychloroquine did not provide clinical benefits while posing cardiac safety risks when combined with azithromycin, especially in the vulnerable population. Only 29% of current evidence on pharmacological management of COVID-19 is supported by moderate or high certainty and can be translated to practice and policy; the remaining 71% are of low or very low certainty and warrant further studies to establish firm conclusions.

PLoS Med2020       LitCov and CORD-19
3919Prevalence of anxiety and depression symptoms and association with epidemic-related factors during the epidemic period of COVID-19 among 123,768 workers in China: A large cross-sectional study  

BACKGROUND: : COVID-19 has gained intense attention globally. However, little is known about the COVID-19-ralated mental health status among workers. METHODS: : The cross-sectional online survey with 123,768 workers was conducted from February 2, 2020 to February 7, 2020 on a mega-size labor-intensive factory in Shenzhen, China. Oral consent was obtained prior to the questionnaire survey. The information collected in the survey included demographic characteristics, psychological symptoms, COVID-19-related information, and demands for psychological education and interventions. Symptoms of anxiety and depression were measured by the Zung's Self-Rating Anxiety Scale and Self-Rating Depression Scale. Logistic regression models were performed to determine the association between related factors and mental health status. RESULTS: : The prevalence of anxiety and depression symptoms was 3.4% and 22.8%, respectively. The dominant epidemic-related factors were having confirmed cases in the community (odds ratio [OR], 2.75, 95% CI, 2.37–3.19) and having confirmed friends (OR, 2.44; 95% CI, 1.69–3.52) for the increased risk of anxiety and depression symptoms, respectively. Nevertheless, major traditional risk factors such as general or poor health status and always drinking alcohol were still the dominant factors associated with the increased risk of anxiety and depression symptoms. Overall, 67.3% and 26.8% workers reported desire for psychological education and interventions, respectively. LIMITATIONS: : All assessments were self-reported, resulting in a risk of method bias. CONCLUSIONS: : Our findings show a relatively low prevalence of anxiety symptoms, a relatively high prevalence of depression symptoms, and urgent demand for psychological education and interventions among workers during the COVID-19 outbreak.

J Affect Disord2020       LitCov and CORD-19
3920Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity  

Global dispersal and increasing frequency of the SARS-CoV-2 Spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of Spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large data set, well represented by both Spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the Spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.

Cell2021       LitCov and CORD-19
3921Canadian children's and youth's adherence to the 24-h movement guidelines during the COVID-19 pandemic: A decision tree analysis  

PURPOSE: The purpose of this study was to use decision tree modeling to generate profiles of children and youth who were more or less likely to meet the Canadian 24-h movement guidelines during the COVID-19 outbreak. METHODS: Data for this study were from a nationally representative sample of 1472 Canadian parents (Mean(age) = 45.12, SD = 7.55) of children (5–11 years old) or youth (12–17 years old). Data were collected in April 2020 via an online survey. Survey items assessed demographic, behavioral, social, micro-environmental, and macro-environmental characteristics. Four decision trees of adherence and non-adherence to all movement recommendations combined and each individual movement recommendation (physical activity, screen time, and sleep) were generated. RESULTS: Results revealed specific combinations of adherence and non-adherence characteristics. Characteristics associated with adherence to the recommendation(s) included high parental perceived capability to restrict screen time, being a boy, increases in children's and youth's outdoor physical activity/sport since the COVID-19 outbreak began, having parents younger than 43 years old (for adherence to screen time recommendation), having no to little change in sleep duration since the COVID-19 outbreak began, and having parents older than 35 years old (for adherence to the sleep recommendation). Characteristics associated with non-adherence to the recommendation(s) included low parental perceived capability to restrict screen time, decreases in children's and youth's outdoor physical activity/sport since the COVID-19 outbreak began, primary residences located in all provinces except Quebec, low parental perceived capability to support children's sleep, and increases in sleep duration since the COVID-19 outbreak began. CONCLUSION: Our results show that specific characteristics interact to contribute to (non)adherence to the movement behavior recommendations. Results highlight the importance of targeting parents’ perceived capability for the promotion of children's and youth's movement behaviors during challenging times of the COVID-19 pandemic, paying particular attention to enhancing parental perceived capability to restrict screen time.

J Sport Health Sci2020       LitCov and CORD-19
3922Sensitive detection and quantification of SARS-CoV-2 by multiplex droplet digital RT-PCR  

The purpose of this study is to develop a one-step droplet digital RT-PCR (RT-ddPCR) multiplex assay that allows for sensitive quantification of SARS-CoV-2 RNA with respect to human-derived RNA and could be used for screening and monitoring of Covid-19 patients. A one-step RT-ddPCR multiplex assay was developed for simultaneous detection of SARS-CoV-2 E, RdRp and N viral RNA, and human Rpp30 DNA and GUSB mRNA, for internal nucleic acid (NA) extraction and RT-PCR control. Dilution series of viral RNA transcripts were prepared in water and total NA extract of Covid-19-negative patients. As reference assay, an E-GUSB duplex RT-PCR was used. GUSB mRNA detection was used to set validity criteria to assure viral RNA and RT-PCR assay quality and to enable quantification of SARS-CoV-2 RNA. In a background of at least 100 GUSB mRNA copies, 5 copies of viral RNA are reliably detectable and 10 copies viral RNA copies are reliably quantifiable. It was found that assay sensitivity of the RT-ddPCR was not affected by the total NA background while assay sensitivity of the gold standard RT-PCR assay is drastically decreased when SARS-CoV-2 copies were detected in a background of total NA extract compared with water. The present study describes a robust and sensitive one-step ddRT-PCR multiplex assay for reliable quantification of SARS-CoV-2 RNA. By determining the fractional abundance of viral RNA with respect to a human housekeeping gene, viral loads from different samples can be compared, what could be used to investigate the infectiveness and to monitor Covid-19 patients.

Eur J Clin Microbiol Infect Di2020       LitCov and CORD-19
3923Association of Sleep-Related Hypoxia With Risk of COVID-19 Hospitalizations and Mortality in a Large Integrated Health System  

IMPORTANCE: The influence of sleep-disordered breathing (SDB) and sleep-related hypoxemia in SARS-CoV-2 viral infection and COVID-19 outcomes remains unknown. Controversy exists regarding whether to continue treatment for SDB with positive airway pressure given concern for aerosolization with limited data to inform professional society recommendations. OBJECTIVE: To investigate the association of SDB (identified via polysomnogram) and sleep-related hypoxia with (1) SARS-CoV-2 positivity and (2) World Health Organization (WHO)-designated COVID-19 clinical outcomes while accounting for confounding including obesity, underlying cardiopulmonary disease, cancer, and smoking history. DESIGN, SETTING, AND PARTICIPANTS: This case-control study was conducted within the Cleveland Clinic Health System (Ohio and Florida) and included all patients who were tested for COVID-19 between March 8 and November 30, 2020, and who had an available sleep study record. Sleep indices and SARS-CoV-2 positivity were assessed with overlap propensity score weighting, and COVID-19 clinical outcomes were assessed using the institutional registry. EXPOSURES: Sleep study–identified SDB (defined by frequency of apneas and hypopneas using the Apnea-Hypopnea Index [AHI]) and sleep-related hypoxemia (percentage of total sleep time at <90% oxygen saturation [TST <90]). MAIN OUTCOMES AND MEASURES: Outcomes were SARS-CoV-2 infection and WHO-designated COVID-19 clinical outcomes (hospitalization, use of supplemental oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation, and death). RESULTS: Of 350 710 individuals tested for SARS-CoV-2, 5402 (mean [SD] age, 56.4 [14.5] years; 3005 women [55.6%]) had a prior sleep study, of whom 1935 (35.8%) tested positive for SARS-CoV-2. Of the 5402 participants, 1696 were Black (31.4%), 3259 were White (60.3%), and 822 were of other race or ethnicity (15.2%). Patients who were positive vs negative for SARS-CoV-2 had a higher AHI score (median, 16.2 events/h [IQR, 6.1-39.5 events/h] vs 13.6 events/h [IQR, 5.5-33.6 events/h]; P < .001) and increased TST <90 (median, 1.8% sleep time [IQR, 0.10%-12.8% sleep time] vs 1.4% sleep time [IQR, 0.10%-10.8% sleep time]; P = .02). After overlap propensity score–weighted logistic regression, no SDB measures were associated with SARS-CoV-2 positivity. Median TST <90 was associated with the WHO-designated COVID-19 ordinal clinical outcome scale (adjusted odds ratio, 1.39; 95% CI, 1.10-1.74; P = .005). Time-to-event analyses showed sleep-related hypoxia associated with a 31% higher rate of hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005). CONCLUSIONS AND RELEVANCE: In this case-control study, SDB and sleep-related hypoxia were not associated with increased SARS-CoV-2 positivity; however, once patients were infected with SARS-CoV-2, sleep-related hypoxia was an associated risk factor for detrimental COVID-19 outcomes.

JAMA Netw Open2021       LitCov and CORD-19
3924Anthocyanin derivatives as potent inhibitors of SARS-CoV-2 main protease: An in-silico perspective of therapeutic targets against COVID-19 pandemic  

N/A

J Biomol Struct Dyn2021       LitCov and CORD-19
3925The effect of gestational age at BNT162b2 mRNA vaccination on maternal and neonatal SARS-CoV-2 antibody levels  

BACKGROUND: COVID-19 during pregnancy and early infancy can result in severe disease. Evaluating the effect of gestational age at the time of SARS-CoV-2 vaccination on maternal antibody levels and transplacental antibody transfer has important implications for maternal care and vaccination strategies. METHODS: Maternal and cord blood sera were collected from mother/newborn dyads (n=402), following term delivery after antenatal two-dose SARS-CoV-2 BNT162b2 mRNA vaccination. SARS-CoV-2 spike protein (S) and receptor binding domain (RBD)-specific IgG levels were evaluated in the samples collected. RESULTS: Median anti-S and anti-RBD-specific IgG levels in maternal sera at the time of delivery were lowest following 1 (st) trimester vaccination (n=90) (anti-S IgG: 76 AU/mL, anti-RBD-specific IgG: 478 AU/mL), intermediate in those vaccinated in the 2 (nd) trimester (n=124) (anti-S IgG: 126 AU/mL, anti-RBD-specific IgG: 1263 AU/mL), and highest after 3 (rd) trimester vaccination (n=188) (anti-S IgG: 240 AU/mL, anti-RBD-specific IgG: 5855 AU/mL). Antibody levels in neonatal sera followed a similar pattern and were lowest following antenatal vaccination in the 1 (st) trimester (anti-S IgG: 126 AU/mL, anti-RBD-specific IgG: 1140 AU/mL). In a subgroup of parturients vaccinated in the 1 (st) trimester (n=30), a third booster dose was associated with significantly higher maternal and neonatal antibody levels. CONCLUSIONS: These results suggest a considerable antibody waning throughout pregnancy in those vaccinated at early gestation. The observed boosting effect of a third vaccine dose, hints to its potential benefit in those who completed the two-dose vaccine series at early pregnancy or prior to conception. The impact of antenatal immunization timing on SARS-CoV-2 transplacental antibody transfer may influence neonatal seroprotection.

Clin Infect Dis2022       LitCov and CORD-19
3926The inhibitory effect of some natural bioactive compounds against SARS-CoV-2 main protease: insights from molecular docking analysis and molecular dynamic simulation  

This work aimed at evaluating the inhibitory effect of ten natural bioactive compounds (1–10) as potential inhibitors of SARS-CoV-2-3CL main protease (PDB ID: 6LU7) and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT) by molecular docking analysis. The inhibitory effect of all studied compounds was studied with compared to some proposed antiviral drugs which currently used in COVID-19 treatment such as chloroquine, hydroxychloroquine, azithromycin, remdesivir, baloxvir, lopinavir, and favipiravir. Homology modeling and sequence alignment was computed to evaluate the similarity between the SARS-CoV-2-3CL main protease and other SARS-CoV receptors. ADMET properties of all studied compounds were computed and reported. Also, molecular dynamic (MD) simulation was performed on the compound which has the highest binding affinity inside 6LU7 obtained from molecular docking analysis to study it is stability inside receptor in explicit water solvent. Based on molecular docking analysis, we found that caulerpin has the highest binding affinity inside all studied receptors compared to other bioactive compounds and studied drugs. Our homology modeling and sequence alignment showed that SARS-CoV main protease (PDB ID: 3TNT) shares high similarity with 3CLpro (96.00%). Also, ADMET properties confirmed that caulerpin obeys Lipinski’s rule and passes ADMET property, which make it a promising compound to act as a new safe natural drug against SARS-CoV-2-3CL main protease. Finally, MD simulation confirmed that the complex formed between caulerpin and 3CLpro is stable in water explicit and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. Also, binding free energy between caulerpin and 6LU7 confirmed the efficacy of the caulerpin molecule against SARS-CoV-2 main protease. So, this study suggested that caulerpin could be used as a potential candidate in COVID-19 treatment.

J Environ Sci Health A Tox Haz2020       LitCov and CORD-19
3927A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model  

The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50 of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 Å revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.

Cell2020       LitCov and CORD-19
3928Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation and deployment  

The COVID-19 pandemic is unlikely to end until there is global roll-out of vaccines that protect against severe disease and preferably drive herd immunity. Regulators in numerous countries have authorised or approved COVID-19 vaccines for human use, with more expected to be licensed in 2021. Yet having licensed vaccines is not enough to achieve global control of COVID-19: they also need to be produced at scale, priced affordably, allocated globally so that they are available where needed, and widely deployed in local communities. In this Health Policy paper, we review potential challenges to success in each of these dimensions and discuss policy implications. To guide our review, we developed a dashboard to highlight key characteristics of 26 leading vaccine candidates, including efficacy levels, dosing regimens, storage requirements, prices, production capacities in 2021, and stocks reserved for low-income and middle-income countries. We use a traffic-light system to signal the potential contributions of each candidate to achieving global vaccine immunity, highlighting important trade-offs that policy makers need to consider when developing and implementing vaccination programmes. Although specific datapoints are subject to change as the pandemic response progresses, the dashboard will continue to provide a useful lens through which to analyse the key issues affecting the use of COVID-19 vaccines. We also present original data from a 32-country survey (n=26 758) on potential acceptance of COVID-19 vaccines, conducted from October to December, 2020. Vaccine acceptance was highest in Vietnam (98%), India (91%), China (91%), Denmark (87%), and South Korea (87%), and lowest in Serbia (38%), Croatia (41%), France (44%), Lebanon (44%), and Paraguay (51%).

Lancet2021       LitCov and CORD-19
3929SARS-CoV-2 activates lung epithelial cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients  

BACKGROUND: The outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a global health emergency. We aim to decipher SARS-CoV-2 infected cell types, the consequent host immune response and their interplay in lung of COVID-19 patients. METHODS: We analyzed single-cell RNA sequencing (scRNA-seq) data of bronchoalveolar lavage fluid (BALF) samples from 10 healthy donors, 6 severe COVID-19 patients and 3 mild recovered patients. The expressions of SARS-CoV-2 receptors (ACE2 and TMPRSS2) were examined among different cell types. The immune cells infiltration patterns, their expression profiles, and interplays between immune cells and SARS-CoV-2 target cells were further investigated. FINDINGS: Compared to healthy controls, ACE2 and TMPRSS2 expressions were significantly higher in lung epithelial cells of COVID-19 patients, in particular club and ciliated cells. SARS-CoV-2 activated pro-inflammatory genes and interferon/cytokine signaling in these cells. In severe COVID-19 patients, significantly higher neutrophil, but lower macrophage in lung was observed along with markedly increased cytokines expression compared with healthy controls and mild patients. By contrast, neutrophil and macrophage returned to normal level whilst more T and NK cells accumulation were observed in mild patients. Moreover, SARS-CoV-2 infection altered the community interplays of lung epithelial and immune cells: interactions between the club and immune cells were higher in COVID-19 patients compared to healthy donors; on the other hand, immune-immune cells interactions appeared the strongest in mild patients. INTERPRETATION: SARS-CoV-2 could infect lung epithelium, alter communication patterns between lung epithelial cells and immune system, and drive dysregulated host immune response in COVID-19 patients.

EBioMedicine2021       LitCov and CORD-19
3930Orthodontic Adolescent Patients' Attitudes toward Protective Face Mask Wearing during the COVID-19 Pandemic  

Background and Objectives: The COVID-19 pandemic led to restrictive measures, which aimed to limit the spread of the SARS-CoV-2 virus. These restrictions impacted all areas of life, including the activity of dental offices. For patients with orthodontic appliances, closing the dental offices was a major issue, as most orthodontic treatments last for more than a year and require regular checkups. The aim of this research was to assess the impact that the restrictive measures that were imposed during the COVID-19 pandemic, and, especially, wearing a face mask had on a sample of Romanian teenagers undergoing fixed orthodontic treatment. Material and Methods: The study group consisted of 277 orthodontic patients, with ages between 12 and 17.9 years, from North-Western Romania. They completed a 9-item questionnaire. The control group consisted of 231 participants, with ages between 12 and 17.9 years. They completed an 8-item questionnaire. Results: Most patients from the study group were not worried that wearing a protective face mask would hide their braces (never—49.5%; rarely—26.7%), and their desire to undergo an orthodontic treatment was not affected by the compulsoriness of face mask wearing (never—51.6%; rarely—26%). In contrast to that, in the control group, more than 50% of the participants were worried to some degree that wearing a protective face mask would hide their smile (occasionally—29.9%; frequently—18.2%; very frequently—2.2%). The majority of the participants from the study group did not consider interrupting the orthodontic treatment due to the COVID-19 pandemic (62.5%), and the majority of the participants from the control group did not consider not going to the dentist due to the COVID-19 pandemic (70.6%). Most of the participants from the study group were not happy that they had to wear a face mask, which covered their orthodontic appliances, during the orthodontic treatment (68.6%). The attitude was similar to that of the participants from the control group, who were not happy that they had to wear a face mask, that covered their smile (51.1%). In the study group, most patients did not want face mask wearing to continue to be compulsory, given the fact that their orthodontic appliances were no longer visible (52%). In the control group, the attitude was similar, with 48.1% of the participants not wanting face mask compulsoriness to be maintained. Conclusions: In conclusion, although, most patients would not like to continue wearing a face mask as a mandatory regulation, they were not concerned or negatively affected by wearing a protective face mask, even though face masks hid their braces.

Medicina (Kaunas)2022       LitCov and CORD-19
3931COVID-19 pneumonia: different respiratory treatments for different phenotypes?  

Intensive Care Med2020       LitCov and CORD-19
3932Neutralizing Human Antibodies against SARS-CoV-2 Isolated from a Human Synthetic Fab Phage Display Library  

Since it was first reported in Wuhan, China, in 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic outbreak resulting in a tremendous global threat due to its unprecedented rapid spread and an absence of a prophylactic vaccine or therapeutic drugs treating the virus. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a key player in the viral entry into cells through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor protein, and the RBD has therefore been crucial as a drug target. In this study, we used phage display to develop human monoclonal antibodies (mAbs) that neutralize SARS-CoV-2. A human synthetic Fab phage display library was panned against the RBD of the SARS-CoV-2 spike protein (SARS-2 RBD), yielding ten unique Fabs with moderate apparent affinities (EC(50) = 19–663 nM) for the SARS-2 RBD. All of the Fabs showed no cross-reactivity to the MERS-CoV spike protein, while three Fabs cross-reacted with the SARS-CoV spike protein. Five Fabs showed neutralizing activities in in vitro assays based on the Fabs’ activities antagonizing the interaction between the SARS-2 RBD and ACE2. Reformatting the five Fabs into immunoglobulin Gs (IgGs) greatly increased their apparent affinities (K(D) = 0.08–1.0 nM), presumably due to the effects of avidity, without compromising their non-aggregating properties and thermal stability. Furthermore, two of the mAbs (D12 and C2) significantly showed neutralizing activities on pseudo-typed and authentic SARS-CoV-2. Given their desirable properties and neutralizing activities, we anticipate that these human anti-SARS-CoV-2 mAbs would be suitable reagents to be further developed as antibody therapeutics to treat COVID-19, as well as for diagnostics and research tools.

Int J Mol Sci2021       LitCov and CORD-19
3933Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update  

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly pathogenic novel virus that has caused a massive pandemic called coronavirus disease 2019 (COVID-19) worldwide. Wuhan, a city in China became the epicenter of the outbreak of COVID-19 in December 2019. The disease was declared a pandemic globally by the World Health Organization (WHO) on 11 March 2020. SARS-CoV-2 is a beta CoV of the Coronaviridae family which usually causes respiratory symptoms that resemble common cold. Multiple countries have experienced multiple waves of the disease and scientific experts are consistently working to find answers to several unresolved questions, with the aim to find the most suitable ways to contain the virus. Furthermore, potential therapeutic strategies and vaccine development for COVID-19 management are also considered. Currently, substantial efforts have been made to develop successful and safe treatments and SARS-CoV-2 vaccines. Some vaccines, such as inactivated vaccines, nucleic acid-based, and vector-based vaccines, have entered phase 3 clinical trials. Additionally, diverse small molecule drugs, peptides and antibodies are being developed to treat COVID-19. We present here an overview of the virus interaction with the host and environment and anti-CoV therapeutic strategies; including vaccines and other methodologies, designed for prophylaxis and treatment of SARS-CoV-2 infection with the hope that this integrative analysis could help develop novel therapeutic approaches against COVID-19.

Front Immunol2021       LitCov and CORD-19
3934Detection of COVID-19: A review of the current literature and future perspectives  

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the coronavirus disease 2019 (COVID-19) worldwide pandemic. This unprecedented situation has garnered worldwide attention. An effective strategy for controlling the COVID-19 pandemic is to develop highly accurate methods for the rapid identification and isolation of SARS-CoV-2 infected patients. Many companies and institutes are therefore striving to develop effective methods for the rapid detection of SARS-CoV-2 ribonucleic acid (RNA), antibodies, antigens, and the virus. In this review, we summarize the structure of the SARS-CoV-2 virus, its genome and gene expression characteristics, and the current progression of SARS-CoV-2 RNA, antibodies, antigens, and virus detection. Further, we discuss the reasons for the observed false-negative and false-positive RNA and antibody detection results in practical clinical applications. Finally, we provide a review of the biosensors which hold promising potential for point-of-care detection of COVID-19 patients. This review thereby provides general guidelines for both scientists in the biosensing research community and for those in the biosensor industry to develop a highly sensitive and accurate point-of-care COVID-19 detection system, which would be of enormous benefit for controlling the current COVID-19 pandemic.

Biosens Bioelectron2020       LitCov and CORD-19
3935Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China  

BACKGROUND: Cancer patients are regarded as a highly vulnerable group in the current Coronavirus Disease 2019 (COVID-19) pandemic. To date, the clinical characteristics of COVID-19-infected cancer patients remain largely unknown. PATIENTS AND METHODS: In this retrospective cohort study, we included cancer patients with laboratory-confirmed COVID-19 from three designated hospitals in Wuhan, China. Clinical data were collected from medical records from 13 January 2020 to 26 February 2020. Univariate and multivariate analyses were carried out to assess the risk factors associated with severe events defined as a condition requiring admission to an intensive care unit, the use of mechanical ventilation, or death. RESULTS: A total of 28 COVID-19-infected cancer patients were included; 17 (60.7%) patients were male. Median (interquartile range) age was 65.0 (56.0–70.0) years. Lung cancer was the most frequent cancer type (n = 7; 25.0%). Eight (28.6%) patients were suspected to have hospital-associated transmission. The following clinical features were shown in our cohort: fever (n = 23, 82.1%), dry cough (n = 22, 81%), and dyspnoea (n = 14, 50.0%), along with lymphopaenia (n = 23, 82.1%), high level of high-sensitivity C-reactive protein (n = 23, 82.1%), anaemia (n = 21, 75.0%), and hypoproteinaemia (n = 25, 89.3%). The common chest computed tomography (CT) findings were ground-glass opacity (n = 21, 75.0%) and patchy consolidation (n = 13, 46.3%). A total of 15 (53.6%) patients had severe events and the mortality rate was 28.6%. If the last antitumour treatment was within 14 days, it significantly increased the risk of developing severe events [hazard ratio (HR) = 4.079, 95% confidence interval (CI) 1.086–15.322, P = 0.037]. Furthermore, patchy consolidation on CT on admission was associated with a higher risk of developing severe events (HR = 5.438, 95% CI 1.498–19.748, P = 0.010). CONCLUSIONS: Cancer patients show deteriorating conditions and poor outcomes from the COVID-19 infection. It is recommended that cancer patients receiving antitumour treatments should have vigorous screening for COVID-19 infection and should avoid treatments causing immunosuppression or have their dosages decreased in case of COVID-19 coinfection.

Ann Oncol2020       LitCov and CORD-19
3936ACE2 and TMPRSS2 expression by clinical, HLA, immune and microbial correlates across 34 human cancers and matched normal tissues: implications for SARS-CoV-2 COVID-19  

BACKGROUND: Pandemic COVID-19 by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) infection is facilitated by the ACE2 receptor and protease TMPRSS2. Modestly sized case series have described clinical factors associated with COVID-19, while ACE2 and TMPRSS2 expression analyses have been described in some cell types. Patients with cancer may have worse outcomes to COVID-19. METHODS: We performed an integrated study of ACE2 and TMPRSS2 gene expression across and within organ systems, by normal versus tumor, across several existing databases (The Cancer Genome Atlas, Census of Immune Single Cell Expression Atlas, The Human Cell Landscape, and more). We correlated gene expression with clinical factors (including but not limited to age, gender, race, body mass index, and smoking history), HLA genotype, immune gene expression patterns, cell subsets, and single-cell sequencing as well as commensal microbiome. RESULTS: Matched normal tissues generally display higher ACE2 and TMPRSS2 expression compared with cancer, with normal and tumor from digestive organs expressing the highest levels. No clinical factors were consistently identified to be significantly associated with gene expression levels though outlier organ systems were observed for some factors. Similarly, no HLA genotypes were consistently associated with gene expression levels. Strong correlations were observed between ACE2 expression levels and multiple immune gene signatures including interferon-stimulated genes and the T cell-inflamed phenotype as well as inverse associations with angiogenesis and transforming growth factor-β signatures. ACE2 positively correlated with macrophage subsets across tumor types. TMPRSS2 was less associated with immune gene expression but was strongly associated with epithelial cell abundance. Single-cell sequencing analysis across nine independent studies demonstrated little to no ACE2 or TMPRSS2 expression in lymphocytes or macrophages. ACE2 and TMPRSS2 gene expression associated with commensal microbiota in matched normal tissues particularly from colorectal cancers, with distinct bacterial populations showing strong associations. CONCLUSIONS: We performed a large-scale integration of ACE2 and TMPRSS2 gene expression across clinical, genetic, and microbiome domains. We identify novel associations with the microbiota and confirm host immunity associations with gene expression. We suggest caution in interpretation regarding genetic associations with ACE2 expression suggested from smaller case series.

J Immunother Cancer2020       LitCov and CORD-19
3937Impact of a prolonged COVID-19 lockdown on patterns of admission, mortality and performance indicators in a cardiovascular intensive care unit  

BACKGROUND: The effects of an early and prolonged lockdown during the COVID-19 pandemic on cardiovascular intensive care units is not well established. This study analyses patterns of admission, mortality and performance Indicators in a cardiovascular intensive care unit before and during the Argentine lockdown in the COVID-19 pandemic. METHODS: This is a retrospective observational cross-sectional study of all consecutive patients aged 18 years or more admitted to the Cardiac Intensive Care Unit at a high-volume reference hospital in Buenos Aires, Argentina comparing hospitalization rates, primary causes of admission, inpatient utilisation indicators, pharmacy supplies expenditures, and in-hospital mortality between March 5 and July 31, 2020 with two corresponding control periods in 2019 and 2018. RESULTS: We included 722 patients [mean age of 61.6 (SD 15.5) years; 237 (32.8%)] were females. Overall hospitalisations dropped 53.2% (95%CI: 45.3, 61.0%) from 295.5 patients/year over the periods 2018/2019 to 137 patients in 2020. Cardiovascular disease-related admissions dropped 59.9%, while admission for noncardiac causes doubled its prevalence from 9.6% over the periods 2018/2019 to 22.6% in the study period (P<0.001). In the period 2020, the bed occupancy rate fell from 82.2% to 77.4%, and the bed turnover rate dropped 50% from 7.88 to 3.91 monthly discharges/bed. The average length of stay doubled from 3.26 to 6.75 days, and the turnover interval increased from 3.8 to 8.39 days in 2020. Pharmacy supplies expenditures per discharge increased 134% along with a rise in antibiotics usage from 6.5 to 11.4 vials/ampoules per discharge (P<0.02). Overall mortality increased from 7% (n=41) to 13.9% (n=19) (P=0.008) at the expense of noncardiac related admissions (3.6% to 19.4%, P=0.01). CONCLUSIONS: This study found a significant reduction in overall and cardiovascular disease-related causes of admission to the cardiac intensive care unit, worse performance indicators and increased in-hospital mortality along the first five months of the early and long-lasting COVID-19 lockdown in Argentina. These results highlight the need to foster public awareness concerning the risks of avoiding hospital attendance. Moreover, health systems should follow strict screening protocols to prevent potential biases in the admission of patients with critical conditions unrelated to the COVID-19 pandemic.

Int J Qual Healthcare2021       LitCov and CORD-19
3938Comparing News Articles and Tweets About COVID-19 in Brazil: Sentiment Analysis and Topic Modeling Approach  

BACKGROUND: The COVID-19 pandemic is severely affecting people worldwide. Currently, an important approach to understand this phenomenon and its impact on the lives of people consists of monitoring social networks and news on the internet. OBJECTIVE: The purpose of this study is to present a methodology to capture the main subjects and themes under discussion in news media and social media and to apply this methodology to analyze the impact of the COVID-19 pandemic in Brazil. METHODS: This work proposes a methodology based on topic modeling, namely entity recognition, and sentiment analysis of texts to compare Twitter posts and news, followed by visualization of the evolution and impact of the COVID-19 pandemic. We focused our analysis on Brazil, an important epicenter of the pandemic; therefore, we faced the challenge of addressing Brazilian Portuguese texts. RESULTS: In this work, we collected and analyzed 18,413 articles from news media and 1,597,934 tweets posted by 1,299,084 users in Brazil. The results show that the proposed methodology improved the topic sentiment analysis over time, enabling better monitoring of internet media. Additionally, with this tool, we extracted some interesting insights about the evolution of the COVID-19 pandemic in Brazil. For instance, we found that Twitter presented similar topic coverage to news media; the main entities were similar, but they differed in theme distribution and entity diversity. Moreover, some aspects represented negative sentiment toward political themes in both media, and a high incidence of mentions of a specific drug denoted high political polarization during the pandemic. CONCLUSIONS: This study identified the main themes under discussion in both news and social media and how their sentiments evolved over time. It is possible to understand the major concerns of the public during the pandemic, and all the obtained information is thus useful for decision-making by authorities.

JMIR Public Health Surveill2021       LitCov and CORD-19
3939The Spread of COVID-19 Crisis Communication by German Public Authorities and Experts on Twitter: Quantitative Content Analysis  

BACKGROUND: The COVID-19 pandemic led to the necessity of immediate crisis communication by public health authorities. In Germany, as in many other countries, people choose social media, including Twitter, to obtain real-time information and understanding of the pandemic and its consequences. Next to authorities, experts such as virologists and science communicators were very prominent at the beginning of German Twitter COVID-19 crisis communication. OBJECTIVE: The aim of this study was to detect similarities and differences between public authorities and individual experts in COVID-19 crisis communication on Twitter during the first year of the pandemic. METHODS: Descriptive analysis and quantitative content analysis were carried out on 8251 original tweets posted from January 1, 2020, to January 15, 2021. COVID-19–related tweets of 21 authorities and 18 experts were categorized into structural, content, and style components. Negative binomial regressions were performed to evaluate tweet spread measured by the retweet and like counts of COVID-19–related tweets. RESULTS: Descriptive statistics revealed that authorities and experts increasingly tweeted about COVID-19 over the period under study. Two experts and one authority were responsible for 70.26% (544,418/774,865) of all retweets, thus representing COVID-19 influencers. Altogether, COVID-19 tweets by experts reached a 7-fold higher rate of retweeting (t(8,249)=26.94, P<.001) and 13.9 times the like rate (t(8,249)=31.27, P<.001) compared with those of authorities. Tweets by authorities were much more designed than those by experts, with more structural and content components; for example, 91.99% (4997/5432) of tweets by authorities used hashtags in contrast to only 19.01% (536/2819) of experts’ COVID-19 tweets. Multivariate analysis revealed that such structural elements reduce the spread of the tweets, and the incidence rate of retweets for authorities’ tweets using hashtags was approximately 0.64 that of tweets without hashtags (Z=–6.92, P<.001). For experts, the effect of hashtags on retweets was insignificant (Z=1.56, P=.12). CONCLUSIONS: Twitter data are a powerful information source and suitable for crisis communication in Germany. COVID-19 tweet activity mirrors the development of COVID-19 cases in Germany. Twitter users retweet and like communications regarding COVID-19 by experts more than those delivered by authorities. Tweets have higher coverage for both authorities and experts when they are plain and for authorities when they directly address people. For authorities, it appears that it was difficult to win recognition during COVID-19. For all stakeholders studied, the association between number of followers and number of retweets was highly significantly positive (authorities Z=28.74, P<.001; experts Z=25.99, P<.001). Updated standards might be required for successful crisis communication by authorities.

JMIR Public Health Surveill2021       LitCov and CORD-19
3940Inference of SARS-CoV-2 spike-binding neutralizing antibody titers in sera from hospitalized COVID-19 patients by using commercial enzyme and chemiluminescent immunoassays  

Whether antibody levels measured by commercially available enzyme or chemiluminescent immunoassays targeting the SARS-CoV-2 spike (S) protein can act as a proxy for serum neutralizing activity remains to be established for many of these assays. We evaluated the degree of correlation between neutralizing antibodies (NtAb) binding the SARS-CoV-2 spike (S) protein and SARS-CoV-2-S-IgG levels measured by four commercial immunoassays in sera drawn from hospitalized COVID-19 patients. Ninety sera from 51 hospitalized COVID-19 patients were tested by a pseudotyped virus neutralization assay, the LIAISON SARS-CoV-2 S1/S2 IgG, the Euroimmun SARS-CoV-2 IgG ELISA, the MAGLUMI 2019-nCoV IgG, and the COVID-19 ELISA IgG assays. Overall, the results obtained with the COVID-19 ELISA IgG test showed the highest agreement with the NtAb assay (κ, 0.85; 95% CI, 0.63–1). The most sensitive tests were the pseudotyped virus NtAb assay and the COVID-19 ELISA IgG assay (92.2% for both). Overall, the degree correlation between antibody titers resulting in 50% virus neutralization (NtAb(50)) in the pseudotyped virus assay and SARS-CoV-2 IgG levels was strong for the Euroimmun SARS-CoV-2 IgG ELISA (rho = 0.73) and moderate for the remaining assays (rho = 0.48 to 0.59). The kinetic profile of serum NtAb(50) titers could not be reliably predicted by any of the SARS-CoV-2 IgG immunoassays. The suitability of SARS-CoV-2-S-IgG commercial immunoassays for inferring neutralizing activity of sera from hospitalized COVID-19 patients varies widely across tests and is influenced by the time of sera collection after the onset of symptoms.

Eur J Clin Microbiol Infect Di2021       LitCov and CORD-19
3941Effectiveness of CoronaVac, ChAdOx1 nCoV-19, BNT162b2 and Ad26.COV2.S among individuals with previous SARS-CoV-2 infection in Brazil: a test-negative, case-control study  

BACKGROUND: COVID-19 vaccines have proven highly effective among individuals without a previous SARS-CoV-2 infection, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with previous infection is less clear. We aimed to estimate the effectiveness of four COVID-19 vaccines against symptomatic infection, hospitalisation, and death for individuals with laboratory-confirmed previous SARS-CoV-2 infection. METHODS: Using national COVID-19 notification, hospitalisation, and vaccination datasets from Brazil, we did a test-negative, case-control study to assess the effectiveness of four vaccines (CoronaVac [Sinovac], ChAdOx1 nCoV-19 [AstraZeneca], Ad26.COV2.S [Janssen], and BNT162b2 [Pfizer-BioNtech]) for individuals with laboratory-confirmed previous SARS-CoV-2 infection. We matched cases with RT-PCR positive, symptomatic COVID-19 with up to ten controls with negative RT-PCR tests who presented with symptomatic illnesses, restricting both groups to tests done at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity and the odds of hospitalisation or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. FINDINGS: Between Feb 24, 2020, and Nov 11, 2021, we identified 213 457 individuals who had a subsequent, symptomatic illness with RT-PCR testing done at least 90 days after their initial SARS-CoV-2 infection and after the vaccination programme started. Among these, 30 910 (14·5%) had a positive RT-PCR test consistent with reinfection, and we matched 22 566 of these cases with 145 055 negative RT-PCR tests from 68 426 individuals as controls. Among individuals with previous SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection 14 or more days from vaccine series completion was 39·4% (95% CI 36·1–42·6) for CoronaVac, 56·0% (51·4–60·2) for ChAdOx1 nCoV-19, 44·0% (31·5–54·2) for Ad26.COV2.S, and 64·8% (54·9–72·4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1 nCoV-19, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose than after the first dose. Effectiveness against hospitalisation or death 14 or more days from vaccine series completion was 81·3% (75·3–85·8) for CoronaVac, 89·9% (83·5–93·8) for ChAdOx1 nCoV-19, 57·7% (−2·6 to 82·5) for Ad26.COV2.S, and 89·7% (54·3–97·7) for BNT162b2. INTERPRETATION: All four vaccines conferred additional protection against symptomatic infections and severe outcomes among individuals with previous SARS-CoV-2 infection. The provision of a full vaccine series to individuals after recovery from COVID-19 might reduce morbidity and mortality. FUNDING: Brazilian National Research Council, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Oswaldo Cruz Foundation, JBS, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Generalitat de Catalunya.

Lancet Infect Dis2022       LitCov and CORD-19
3942Classifying chest CT images as COVID-19 positive/negative using a convolutional neural network ensemble model and uniform experimental design method  

BACKGROUND: To classify chest computed tomography (CT) images as positive or negative for coronavirus disease 2019 (COVID-19) quickly and accurately, researchers attempted to develop effective models by using medical images. RESULTS: A convolutional neural network (CNN) ensemble model was developed for classifying chest CT images as positive or negative for COVID-19. To classify chest CT images acquired from COVID-19 patients, the proposed COVID19-CNN ensemble model combines the use of multiple trained CNN models with a majority voting strategy. The CNN models were trained to classify chest CT images by transfer learning from well-known pre-trained CNN models and by applying their algorithm hyperparameters as appropriate. The combination of algorithm hyperparameters for a pre-trained CNN model was determined by uniform experimental design. The chest CT images (405 from COVID-19 patients and 397 from healthy patients) used for training and performance testing of the COVID19-CNN ensemble model were obtained from an earlier study by Hu in 2020. Experiments showed that, the COVID19-CNN ensemble model achieved 96.7% accuracy in classifying CT images as COVID-19 positive or negative, which was superior to the accuracies obtained by the individual trained CNN models. Other performance measures (i.e., precision, recall, specificity, and F(1)-score) obtained bythe COVID19-CNN ensemble model were higher than those obtained by individual trained CNN models. CONCLUSIONS: The COVID19-CNN ensemble model had superior accuracy and excellent capability in classifying chest CT images as COVID-19 positive or negative.

BMC Bioinformatics2021       LitCov and CORD-19
3943COVID-19 and mucormycosis superinfection: the perfect storm  

BACKGROUND: The recent emergence of the Coronavirus Disease (COVID-19) disease had been associated with reports of fungal infections such as aspergillosis and mucormycosis especially among critically ill patients treated with steroids. The recent surge in cases of COVID-19 in India during the second wave of the pandemic had been associated with increased reporting of invasive mucormycosis post COVID-19. There are multiple case reports and case series describing mucormycosis in COVID-19. PURPOSE: In this review, we included most recent reported case reports and case-series of mucormycosis among patients with COVID-19 and describe the clinical features and outcome. RESULTS: Many of the mucormycosis reports were eported from India, especially in COVID-19 patients who were treated and recovered patients. The most commonly reported infection sites were rhino-orbital/rhino-cerebral mucormycosis. Those patients were diabetic and had corticosteroids therapy for controlling the severity of COVID-19, leading to a higher fatality in such cases and complicating the pandemic scenario. The triad of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), corticosteroid use and uncontrolled diabetes mellitus have been evident for significant increase in the incidence of angioinvasive maxillofacial mucormycosis. In addition, the presence of spores and other factors might play a role as well. CONCLUSION: With the ongoing COVID-19 pandemic and increasing number of critically ill patients infected with SARS-CoV-2, it is important to develop a risk-based approach for patients at risk of mucormycosis based on the epidemiological burden of mucormycosis, prevalence of diabetes mellitus, COVID-19 disease severity and use of immune modulating agents including the combined use of corticosteroids and immunosuppressive agents in patients with cancer and transplants.

Infection2021       LitCov and CORD-19
3944Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset  

Importance The dynamics of coronavirus disease 2019 (COVID-19) transmissibility are yet to be fully understood. Better understanding of the transmission dynamics is important for the development and evaluation of effective control policies. Objective To delineate the transmission dynamics of COVID-19 and evaluate the transmission risk at different exposure window periods before and after symptom onset. Design, Setting, and Participants This prospective case-ascertained study in Taiwan included laboratory-confirmed cases of COVID-19 and their contacts. The study period was from January 15 to March 18, 2020. All close contacts were quarantined at home for 14 days after their last exposure to the index case. During the quarantine period, any relevant symptoms (fever, cough, or other respiratory symptoms) of contacts triggered a COVID-19 test. The final follow-up date was April 2, 2020. Main Outcomes and Measures Secondary clinical attack rate (considering symptomatic cases only) for different exposure time windows of the index cases and for different exposure settings (such as household, family, and health care). Results We enrolled 100 confirmed patients, with a median age of 44 years (range, 11-88 years), including 56 men and 44 women. Among their 2761 close contacts, there were 22 paired index-secondary cases. The overall secondary clinical attack rate was 0.7% (95% CI, 0.4%-1.0%). The attack rate was higher among the 1818 contacts whose exposure to index cases started within 5 days of symptom onset (1.0% [95% CI, 0.6%-1.6%]) compared with those who were exposed later (0 cases from 852 contacts; 95% CI, 0%-0.4%). The 299 contacts with exclusive presymptomatic exposures were also at risk (attack rate, 0.7% [95% CI, 0.2%-2.4%]). The attack rate was higher among household (4.6% [95% CI, 2.3%-9.3%]) and nonhousehold (5.3% [95% CI, 2.1%-12.8%]) family contacts than that in health care or other settings. The attack rates were higher among those aged 40 to 59 years (1.1% [95% CI, 0.6%-2.1%]) and those aged 60 years and older (0.9% [95% CI, 0.3%-2.6%]). Conclusions and Relevance In this study, high transmissibility of COVID-19 before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized measures may be required, such as social distancing.

JAMA Intern Med2020       LitCov and CORD-19
3945Impact of the COVID-19 pandemic on quality of life and mental health in children and adolescents in Germany  

The COVID-19 pandemic has caused unprecedented changes in the lives of 1.6 billion children and adolescents. First non-representative studies from China, India, Brazil, the US, Spain, Italy, and Germany pointed to a negative mental health impact. The current study is the first nationwide representative study to investigate the impact of the COVID-19 pandemic on health-related quality of life (HRQoL) and mental health of children and adolescents in Germany from the perspective of children themselves. A representative online survey was conducted among n = 1586 families with 7- to 17-year-old children and adolescents between May 26 and June 10. The survey included internationally established and validated instruments for measuring HRQoL (KIDSCREEN-10), mental health problems (SDQ), anxiety (SCARED), and depression (CES-DC). Results were compared with data from the nationwide, longitudinal, representative BELLA cohort study (n = 1556) conducted in Germany before the pandemic. Two-thirds of the children and adolescents reported being highly burdened by the COVID-19 pandemic. They experienced significantly lower HRQoL (40.2% vs. 15.3%), more mental health problems (17.8% vs. 9.9%) and higher anxiety levels (24.1% vs. 14.9%) than before the pandemic. Children with low socioeconomic status, migration background and limited living space were affected significantly more. Health promotion and prevention strategies need to be implemented to maintain children’s and adolescents’ mental health, improve their HRQoL, and mitigate the burden caused by COVID-19, particularly for children who are most at risk. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00787-021-01726-5.

Eur Child Adolesc Psychiatry2021       LitCov and CORD-19
3946Neutralising antibody responses to SARS-CoV-2 omicron among elderly nursing home residents following a booster dose of BNT162b2 vaccine: A community-based, prospective, longitudinal cohort study  

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EClinicalMedicine2022       LitCov
3947The Influence of the COVID-19 Epidemic on Prevention and Vaccination Behaviors Among Chinese Children and Adolescents: Cross-sectional Online Survey Study  

BACKGROUND: The COVID-19 epidemic and the related containment strategies may affect parental and pediatric health behaviors. OBJECTIVE: The goal of this study was to assess the change in children’s and adolescents’ prevention and vaccination behaviors amid China’s COVID-19 epidemic. METHODS: We conducted a cross-sectional online survey in mid-March 2020 using proportional quota sampling in Wuhan (the epidemic epicenter) and Shanghai (a nonepicenter). Data were collected from 1655 parents with children aged 3 to 17 years. Children’s and adolescents’ prevention behaviors and regular vaccination behaviors before and during the epidemic were assessed. Descriptive analyses were used to investigate respondents’ characteristics, public health prevention behaviors, unproven protection behaviors, and vaccination behaviors before and during the COVID-19 epidemic. Univariate analyses were performed to compare differences in outcome measures between cities and family characteristics, using chi-square tests or Fisher exact tests (if expected frequency was <5) and analyses of variance. Multivariate logistic regressions were used to identify the factors and disparities associated with prevention and vaccination behaviors. RESULTS: Parent-reported prevention behaviors increased among children and adolescents during the COVID-19 epidemic compared with those before the epidemic. During the epidemic, 82.2% (638/776) of children or adolescents always wore masks when going out compared with 31.5% (521/1655) before the epidemic; in addition, 25.0% (414/1655) and 79.8% (1321/1655) had increased their frequency and duration of handwashing, respectively, although only 46.9% (776/1655) went out during the epidemic. Meanwhile, 56.1% (928/1655) of the families took unproven remedies against COVID-19. Parent-reported vaccination behaviors showed mixed results, with 74.8% (468/626) delaying scheduled vaccinations and 80.9% (1339/1655) planning to have their children get the influenza vaccination after the epidemic. Regarding socioeconomic status, children and adolescents from larger families and whose parents had lower education levels were less likely to improve prevention behaviors but more likely to take unproven remedies. Girls were less likely than boys to always wear a mask when going out and wash their hands. CONCLUSIONS: Prevention behaviors and attitudes toward influenza vaccination have improved during the COVID-19 epidemic. Public health prevention measures should be continuously promoted, particularly among girls, parents with lower education levels, and larger families. Meanwhile, misinformation about COVID-19 remains a serious challenge and needs to be addressed by public health stakeholders.

JMIR Public Health Surveill2021       LitCov and CORD-19
3948Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease  

SARS-CoV-2 is the etiological agent responsible for the global COVID-19 outbreak. The main protease (M(pro)) of SARS-CoV-2 is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting M(pro). Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The X-ray crystal structures of SARS-CoV-2 M(pro) in complex with 11a or 11b, both determined at 1.5 Å resolution, showed that the aldehyde groups of 11a and 11b are covalently bound to Cys145 of M(pro). Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity, suggesting that these compounds are promising drug candidates.

Science2020       LitCov and CORD-19
3949Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant  

The emergence of the Omicron variant of SARS-CoV-2 is an urgent global health concern(1). In this study, our statistical modelling suggests that Omicron has spread more rapidly than the Delta variant in several countries including South Africa. Cell culture experiments showed Omicron to be less fusogenic than Delta and than an ancestral strain of SARS-CoV-2. Although the spike (S) protein of Delta is efficiently cleaved into two subunits, which facilitates cell–cell fusion(2,3), the Omicron S protein was less efficiently cleaved compared to the S proteins of Delta and ancestral SARS-CoV-2. Furthermore, in a hamster model, Omicron showed decreased lung infectivity and was less pathogenic compared to Delta and ancestral SARS-CoV-2. Our multiscale investigations reveal the virological characteristics of Omicron, including rapid growth in the human population, lower fusogenicity and attenuated pathogenicity.

Nature2022       LitCov and CORD-19
3950COVID-19-associated rhino-orbital-cerebral mucormycosis: A systematic review, meta-analysis and meta-regression analysis  

BACKGROUND: Till now, no meta-analysis is available to address the clinical profile, risk factors, different interventions, and outcomes among COVID-19–associated rhino-orbito-cerebral mucormycosis (C-ROCM) cases. MATERIALS AND METHODS: Eight literature databases were screened using appropriate keywords from November 1, 2019, to June 30, 2021. The objectives were to analyze the clinical and microbiological profile, risk factor/comorbidity, intervention, and outcome. “R-metafor package” was used for analysis. RESULTS: A total of 23 studies were included. The mean age of presentation of C-ROCM was 54.6 years. The most common presentation was ptosis (72.7%), lid edema (60.6%), proptosis (60.6%), ophthalmoplegia (57.3%), loss of vision (53.7%), facial edema (34.7%), and nasal-blockage (11.8%). Evidence of intracranial spread was seen in 42.8% of cases. Rhizopus was the most common fungus (57.1%) isolated in fungal culture. Among C-ROCM patients, diabetes was the commonest comorbid condition, and the use of corticosteroids related to COVID-19 treatment was the most common risk factor (85.75%). Compared to controlled diabetics, C-ROCM was significantly higher among uncontrolled diabetics (odds ratio [OR] 0.15, 95% confidence interval [C.I.] 0.041–0.544, P = 0.0010). However, no significant association was seen between C-ROCM and COVID-19 severity (OR 0.930, 95% C.I. 0.212–4.087, P = 0.923). For treatment, amphotericin-B was the most common antifungal drug used which was followed by surgical options. However, mortality was high (prevalence 0.344, 95% C.I. 0.205–0.403) despite treatment. CONCLUSION: Although local rhino-orbito symptoms were the first to appear, rapid intracranial extension was seen in a significant number of C-ROCM cases. Uncontrolled diabetes and excessive use of corticosteroid were the most common risk factors present among the C-ROCM cases. High index clinical suspicion is imperative (specifically among COVID-19 patients with diabetes), and routine screening may be helpful.

Indian J Pharmacol2021       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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