\ 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
1901Internet Use, Risk Awareness and Demographic Characteristics Associated With Engagement in Preventive Behaviors and Testing: Cross-Sectional Survey on COVID-19 in the United States  

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, engagement in preventive behaviors and getting tested for the virus play a crucial role in protecting people from contracting the new coronavirus. OBJECTIVE: This study aims to examine how internet use, risk awareness, and demographic characteristics are associated with engagement in preventative behaviors and testing during the COVID-19 pandemic in the United States. METHODS: A cross-sectional survey was conducted on Amazon Mechanical Turk from April 10, 2020, to April 14, 2020. Participants’ internet use (in terms of the extent of receiving information pertaining to COVID-19), risk awareness (whether any immediate family members, close friends or relatives, or people in local communities tested positive for COVID-19), demographics (sex, age, ethnicity, income, education level, marital status, and employment status), as well as their engagement in preventative behaviors and testing were assessed. RESULTS: Our data included 979 valid responses from the United States. Participants who received more COVID-19–related health information online reported more frequent effort to engage in all types of preventive behaviors: wearing a facemask in public (odds ratio [OR] 1.55, 95% CI 1.34-1.79, P<.001), washing hands (OR 1.58, 95% CI 1.35-1.85, P<.001), covering nose and mouth when sneezing and coughing (OR 1.78, 95% CI 1.52-2.10, P<.001), keeping social distance with others (OR 1.41, 95% CI 1.21-1.65, P<.001), staying home (OR 1.40, 95% CI 1.20-1.62, P<.001), avoiding using public transportation (OR 1.57, 95% CI 1.32-1.88, P<.001), and cleaning frequently used surfaces (OR 1.55, 95% CI 1.34-1.79, P<.001). Compared with participants who did not have positive cases in their social circles, those who had immediate family members (OR 1.48, 95% CI 8.28-26.44, P<.001) or close friends and relatives (OR 2.52, 95% CI 1.58-4.03, P<.001) who tested positive were more likely to get tested. Participants’ sex, age, ethnicity, marital status, and employment status were also associated with preventive behaviors and testing. CONCLUSIONS: Our findings revealed that the extent of receiving COVID-19–related information online, risk awareness, and demographic characteristics including sex, ethnicity, age, marital status, and employment status are key factors associated with US residents’ engagement in various preventive behaviors and testing for COVID-19.

J Med Internet Res2020       LitCov and CORD-19
1902Mental Health Status of Healthcare Professionals and Students of Health Sciences Faculties in Kuwait during the COVID-19 Pandemic  

Objectives: This study aimed to assess the impact of the COVID-19 pandemic on the mental health status of healthcare professionals (HCPs) and undergraduate students in the health sciences center (HSCUs). In addition, it explored the factors associated with the increased levels of mental health burden among the study population. Methods: A cross-sectional study was performed using two online-administered questionnaires: the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder 7-item (GAD-7), which were distributed in parallel to HCPs and HSCUs in Kuwait. These instruments are validated assessment scales to assess mental health status: depression (PHQ-9) and anxiety (GAD-7). Statistical analyses were carried out using SPSS- version 25. Results: A total of 857 individuals (559 HCPs and 298 HSCUs) participated in this study. The prevalence of moderately severe depression or severe depression (PHQ-9 total score of ≥15) among respondents was 66.6%. The median (interquartile range, IQR) PHQ-9 score was significantly higher among HSCUs (20 {11.5}) compared to HCPs (17 {8}). The prevalence of severe anxiety (GAD-7 total score of ≥15) among respondents was 36.7%. There were no significant differences between the median (IQR) GAD-7 scores among the HCPs (14 {7}) and HSCUs (13 {8}). Binary logistic regression analysis revealed that three variables were significantly and independently associated with severe depression among HCPs. The prevalence of severe depression was found to be greater among females compared to males. In addition, it was significantly lower among those who were aged ≥50 years, and those who reported that they were not in direct contact with COVID-19 patients. Among HSCUs, females showed greater depression than males. In contrast, those aged >29 years and who had no history of chronic disease showed lower depression compared to their counterparts in the 18–29 years age group and who had a chronic disease history. Conclusions: The COVID-19 pandemic had a significant negative impact on the mental health of HCPs and HSCUs in Kuwait. This highlights the need for proactive efforts to support their mental health and well-being through educational campaigns and psychological support programs.

Int J Environ Res Public Healt2021       LitCov and CORD-19
1903ACE2, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19  

At the end of 2019, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Currently, it is breaking out globally and posing a serious threat to public health. The typically clinical characteristics of COVID-19 patients were fever and respiratory symptoms, and a proportion of patients were accompanied by extrapulmonary symptoms including cardiac injury, kidney injury, liver injury, digestive tract injury, and neurological symptoms. Angiotensin converting enzyme 2 (ACE2) has been proven to be a major receptor for SARS-CoV-2 and could mediate virus entry into cells. And transmembrane protease serine 2 (TMPRSS2) could cleave the spike (S) protein of SARS-CoV-2, which facilitates the fusion of SARS-CoV-2 and cellular membranes. The mRNA expressions of both ACE2 and TMPRSS2 were observed in the heart, digestive tract, liver, kidney, brain and other organs. SARS-CoV-2 may have a capacity to infect extrapulmonary organs due to the expressions of ACE2 and TMPRSS2 in the cells and tissues of these organs. It seems that there is a potential involvement of ACE2 and TMPRSS2 expressions in the virus infection of extrapulmonary organs and the manifestation of symptoms related to these organs in patients with COVID-19. Here, we revealed the expressions of ACE2 and TMPRSS2 in extrapulmonary organs, and we also summarized the clinical manifestation and the management of extrapulmonary complications in patients with COVID-19.

Biomed Pharmacother2020       LitCov and CORD-19
1904Rapid Serological Assays and SARS-CoV-2 Real-Time PCR Assays for the Detection of SARS-CoV-2: Comparative Study  

BACKGROUND: Real-time polymerase chain reaction (RT-PCR) testing for the identification of viral nucleic acid is the current standard for the diagnosis of SARS-CoV-2 infection, but technical issues limit its utilization for large-scale screening. Serological immunoglobulin M (IgM)/IgG testing has been proposed as a useful tool for detecting SARS-CoV-2 exposure. OBJECTIVE: The objective of our study was to compare the results of the rapid serological VivaDiag test for SARS-CoV-2–related IgM/IgG detection with those of the standard RT-PCR laboratory test for identifying SARS-CoV-2 nucleic acid. METHODS: We simultaneously performed both serological and molecular tests with a consecutive series of 191 symptomatic patients. The results provided by a new rapid serological colorimetric test for analyzing IgM/IgG expression were compared with those of RT-PCR testing for SARS-CoV-2 detection. RESULTS: Of the 191 subjects, 70 (36.6%) tested positive for SARS-CoV-2 based on RT-PCR results, while 34 (17.3%) tested positive based on serological IgM/IgG expression. Additionally, 13 (6.8%) subjects tested positive based on serological test results, but also tested negative based on RT-PCR results. The rapid serological test had a sensitivity of 30% and a specificity of 89% compared to the standard RT-PCR assay. Interestingly, the performance of both assays improved 8 days after symptom appearance. After 10 days had passed since symptom appearance, the predictive value of the rapid serological test was higher than that of the standard molecular assay (proportion of positive results: 40% vs 20%). Multivariate analysis showed that age >58 years (P<.01) and period of >15 days after symptom onset (P<.02) were significant and independent factors associated with serological test positivity. CONCLUSIONS: The rapid serological test analyzed in this study seems limited in terms of usefulness when diagnosing SARS-CoV-2 infection. However, it may be useful for providing relevant information on people’s immunoreaction to COVID-19 exposure.

J Med Internet Res2020       LitCov and CORD-19
1905Perception of medical education by learners and teachers during the COVID-19 pandemic: a cross-sectional survey of online teaching  

COVID-19 lockdowns have deeply impacted teaching programs. Online teaching has suddenly become the main form of medical education, a form that may be used as long as the pandemic continues. We aimed at analyzing how online teaching was perceived by both teachers and learners to help determine how to adapt curricula in the next few years. An anonymous cross-sectional survey of medical students, pediatric residents, neonatal fellows, and their respective teachers was conducted between June and August 2020 to assess feelings about quality, attendance, equivalence, and sustainability of online teaching programs. 146 Students and 26 teachers completed the survey. 89% of students agreed that the offered online teaching was an appropriate way of teaching during the pandemic. Less than half of learners and teachers felt they have received or provided a training of an equivalent level and quality as in usual courses. About one-third thought that this online teaching should continue after the crisis ends. Medical school students had significantly more mixed opinions on online teaching than residents and fellows did. Attendance of learners significantly improved with synchronous online classes (p < 0.001), and among more advanced learners (p < 0.002). Our study is the first of this kind to assess simultaneously the feelings of learners at different levels (medical students, residents, and fellows) and their respective teachers of pediatric on programs taught online. It showed that online programs were perceived as appropriate ways of teaching during the COVID pandemic. Further studies are, however, needed to assess the efficacy of such teaching methods on medical skills and communication capabilities.

Med Educ Online2021       LitCov and CORD-19
1906Risk of adverse events after covid-19 in Danish children and adolescents and effectiveness of BNT162b2 in adolescents: cohort study  

OBJECTIVES: To assess the risk of acute and post-acute adverse events after SARS-CoV-2 infection in children and adolescents in Denmark and to evaluate the real world effectiveness of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) among adolescents. DESIGN: Cohort study. SETTING: Nationwide Danish healthcare registers. PARTICIPANTS: All Danish people younger than 18 years who were either tested for SARS-CoV-2 using reverse transcriptase polymerase chain reaction (RT-PCR) or vaccinated with BNT162b2 to 1 October 2021. MAIN OUTCOME MEASURES: Risk of hospital admissions (any hospital contact of ≥12 hours); intensive care unit (ICU) admissions; serious complications, including multisystem inflammatory syndrome in children (MIS-C), myocarditis, and neuroimmune disorders; and initiating drug treatment and health service use up to six months after being tested. Vaccine effectiveness in vaccine recipients compared with unvaccinated peers was evaluated as one minus the risk ratio at 20 days after the first dose and 60 days after the second dose. RESULTS: Of 991 682 children and adolescents tested for SARS-CoV-2 using RT-PCR in Denmark, 74 611 (7.5%) were positive. The risk of hospital admission with any variant for ≥12 hours was 0.49% (95% confidence interval 0.44% to 0.54%; 361/74 350), and 0.01% (0.01% to 0.03%; 10/73 187) of participants were admitted to an ICU within 30 days of testing positive. The risk of MIS-C within two months of SARS-CoV-2 infection was 0.05% (0.03% to 0.06%; 32/70 666), whereas no participants had myocarditis outside of MIS-C or encephalitis and fewer than five had Guillain-Barré syndrome. In the post-acute phase (1-6 months after infection), participants who tested positive for SARS-CoV-2 showed a 1.08-fold (95% confidence interval 1.06-fold to 1.10-fold) increase in rate of contacts with general practitioners compared with a reference cohort sampled among all children tested for SARS-CoV-2 during the study period. Overall, 278 649 adolescents received BNT162b2. Compared with unvaccinated adolescents, the estimated vaccine effectiveness among 229 799 adolescents vaccinated with one dose was 62% (95% confidence interval 59% to 65%) after 20 days, and among 175 176 vaccinated with two doses was 93% (92% to 94%) after 60 days during a period when delta was the dominant variant. CONCLUSIONS: The absolute risks of adverse events after SARS-CoV-2 infection were generally low in Danish children and adolescents, although MIS-C occurred in 0.05% (32/70 666) of participants with RT-PCR confirmed SARS-CoV-2 infection. In adjusted analyses, rates of general practitioner visits were slightly increased in SARS-CoV-2 positive children and adolescents, which could indicate persisting symptoms. BNT162b2 appeared to be effective in reducing the risk of SARS-CoV-2 infection with the delta variant in adolescents.

BMJ2022       LitCov and CORD-19
1907Chest X-ray image phase features for improved diagnosis of COVID-19 using convolutional neural network  

PURPOSE: Recently, the outbreak of the novel coronavirus disease 2019 (COVID-19) pandemic has seriously endangered human health and life. In fighting against COVID-19, effective diagnosis of infected patient is critical for preventing the spread of diseases. Due to limited availability of test kits, the need for auxiliary diagnostic approach has increased. Recent research has shown radiography of COVID-19 patient, such as CT and X-ray, contains salient information about the COVID-19 virus and could be used as an alternative diagnosis method. Chest X-ray (CXR) due to its faster imaging time, wide availability, low cost, and portability gains much attention and becomes very promising. In order to reduce intra- and inter-observer variability, during radiological assessment, computer-aided diagnostic tools have been used in order to supplement medical decision making and subsequent management. Computational methods with high accuracy and robustness are required for rapid triaging of patients and aiding radiologist in the interpretation of the collected data. METHOD: In this study, we design a novel multi-feature convolutional neural network (CNN) architecture for multi-class improved classification of COVID-19 from CXR images. CXR images are enhanced using a local phase-based image enhancement method. The enhanced images, together with the original CXR data, are used as an input to our proposed CNN architecture. Using ablation studies, we show the effectiveness of the enhanced images in improving the diagnostic accuracy. We provide quantitative evaluation on two datasets and qualitative results for visual inspection. Quantitative evaluation is performed on data consisting of 8851 normal (healthy), 6045 pneumonia, and 3323 COVID-19 CXR scans. RESULTS: In Dataset-1, our model achieves 95.57% average accuracy for a three classes classification, 99% precision, recall, and F1-scores for COVID-19 cases. For Dataset-2, we have obtained 94.44% average accuracy, and 95% precision, recall, and F1-scores for detection of COVID-19. CONCLUSIONS: Our proposed multi-feature-guided CNN achieves improved results compared to single-feature CNN proving the importance of the local phase-based CXR image enhancement. Future work will involve further evaluation of the proposed method on a larger-size COVID-19 dataset as they become available.

Int J Comput Assist Radiol Sur2021       LitCov and CORD-19
1908SARS-Coronavirus-2 cases in healthcare workers may not regularly originate from patient care: lessons from a university hospital on the underestimated risk of healthcare worker to healthcare worker transmission  

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents an unprecedented healthcare challenge. Various SARS-CoV-2 outbreaks in healthcare facilities have been reported. Healthcare workers (HCWs) may play a critical role in the spread of the virus, particularly when asymptomatic. We examined four healthcare-associated outbreaks of SARS-CoV-2 infections that occurred at a university hospital in Berlin, Germany. We aimed to describe and analyze the spread of the virus in order to draw conclusions for effective containment of SARS-CoV-2 in healthcare facilities. METHODS: Healthcare-associated outbreaks of SARS-CoV-2 infections were defined as two or more laboratory confirmed infections with SARS-CoV-2 where an epidemiological link within the healthcare setting appeared likely. We focused our analysis on one of three sites of the Charité-University Medicine hospital within a 2 month period (March and April 2020). RESULTS: We observed four healthcare-associated outbreaks of SARS-CoV-2 infections, with a total of 24 infected persons (23 HCWs and one patient). The outbreaks were detected in the departments of nephrology and dialysis (n = 9), anesthesiology (n = 8), surgical pediatrics (n = 4), and neurology (n = 3). Each outbreak showed multiple unprotected contacts between infected HCWs. A combination of contact tracing, testing, physical distancing and mandatory continuous wearing of face masks by all HCWs was able to contain all four outbreaks. CONCLUSIONS: HCW to HCW transmission represented the likely source of the four outbreaks. Ensuring proper physical distancing measures and wearing of protective equipment, also when interacting with colleagues, must be a key aspect of fighting COVID-19 in healthcare facilities.

Antimicrob Resist Infect Contr2020       LitCov and CORD-19
1909A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells  

Summary The pandemic coronavirus SARS-CoV-2 threatens public health worldwide. The viral spike protein mediates SARS-CoV-2 entry into host cells and harbors a S1/S2 cleavage site containing multiple arginine residues (multibasic) not found in closely related animal coronaviruses. However, the role of this multibasic cleavage site in SARS-CoV-2 infection is unknown. Here, we report that the cellular protease furin cleaves the spike protein at the S1/S2 site and that cleavage is essential for S-protein-mediated cell-cell fusion and entry into human lung cells. Moreover, optimizing the S1/S2 site increased cell-cell, but not virus-cell, fusion, suggesting that the corresponding viral variants might exhibit increased cell-cell spread and potentially altered virulence. Our results suggest that acquisition of a S1/S2 multibasic cleavage site was essential for SARS-CoV-2 infection of humans and identify furin as a potential target for therapeutic intervention.

Mol Cell2020       LitCov and CORD-19
1910A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward  

BACKGROUND: The COVID-19 pandemic, caused by SARS-CoV-2 virus, has resulted in over 100,000 deaths in the USA. Our institution has treated over 2000 COVID-19 patients during the pandemic in New York City. The pandemic directly impacted cancer patients and the organization of cancer care. Mount Sinai Hospital has a large and diverse multiple myeloma (MM) population. Herein, we report the characteristics of COVID-19 infection and serological response in MM patients in a large tertiary care institution in New York. METHODS: We performed a retrospective study on a cohort of 58 patients with a plasma-cell disorder (54 MM, 4 smoldering MM) who developed COVID-19 between March 1, 2020, and April 30, 2020. We report epidemiological, clinical, and laboratory characteristics including the persistence of viral detection by polymerase chain reaction (PCR) and anti-SARS-CoV-2 antibody testing, treatments initiated, and outcomes. RESULTS: Of the 58 patients diagnosed with COVID-19, 36 were hospitalized and 22 were managed at home. The median age was 67 years; 52% of patients were male and 63% were non-White. Hypertension (64%), hyperlipidemia (62%), obesity (37%), diabetes mellitus (28%), chronic kidney disease (24%), and lung disease (21%) were the most common comorbidities. In the total cohort, 14 patients (24%) died. Older age (> 70 years), male sex, cardiovascular risk, and patients not in complete remission (CR) or stringent CR were significantly (p < 0.05) associated with hospitalization. Among hospitalized patients, laboratory findings demonstrated elevation of traditional inflammatory markers (CRP, ferritin, D-dimer) and a significant (p < 0.05) association between elevated inflammatory markers, severe hypogammaglobulinemia, non-White race, and mortality. Ninety-six percent (22/23) of patients developed antibodies to SARS-CoV-2 at a median of 32 days after initial diagnosis. The median time to PCR negativity was 43 (range 19–68) days from initial positive PCR. CONCLUSIONS: Drug exposure and MM disease status at the time of contracting COVID-19 had no bearing on mortality. Mounting a severe inflammatory response to SARS-CoV-2 and severe hypogammaglobulinemia was associated with higher mortality. The majority of patients mounted an antibody response to SARS-CoV-2. These findings pave a path to the identification of vulnerable MM patients who need early intervention to improve outcomes in future outbreaks of COVID-19.

J Hematol Oncol2020       LitCov and CORD-19
1911Prophylactic anticoagulants for people hospitalised with COVID-19  

N/A

Cochrane Database Syst Rev2020       LitCov and CORD-19
1912Evaluation of SARS-CoV-2 PCR Positive Cases in the Pediatric Emergency Department  

N/A

Mikrobiyol Bul2020       LitCov and CORD-19
1913Covid-19: automatic detection from X-ray images utilizing transfer learning with convolutional neural networks  

In this study, a dataset of X-ray images from patients with common bacterial pneumonia, confirmed Covid-19 disease, and normal incidents, was utilized for the automatic detection of the Coronavirus disease. The aim of the study is to evaluate the performance of state-of-the-art convolutional neural network architectures proposed over the recent years for medical image classification. Specifically, the procedure called Transfer Learning was adopted. With transfer learning, the detection of various abnormalities in small medical image datasets is an achievable target, often yielding remarkable results. The datasets utilized in this experiment are two. Firstly, a collection of 1427 X-ray images including 224 images with confirmed Covid-19 disease, 700 images with confirmed common bacterial pneumonia, and 504 images of normal conditions. Secondly, a dataset including 224 images with confirmed Covid-19 disease, 714 images with confirmed bacterial and viral pneumonia, and 504 images of normal conditions. The data was collected from the available X-ray images on public medical repositories. The results suggest that Deep Learning with X-ray imaging may extract significant biomarkers related to the Covid-19 disease, while the best accuracy, sensitivity, and specificity obtained is 96.78%, 98.66%, and 96.46% respectively. Since by now, all diagnostic tests show failure rates such as to raise concerns, the probability of incorporating X-rays into the diagnosis of the disease could be assessed by the medical community, based on the findings, while more research to evaluate the X-ray approach from different aspects may be conducted.

Phys Eng Sci Med2020       LitCov and CORD-19
1914SARS-CoV-2 Reinfection Rate and Estimated Effectiveness of the Inactivated Whole Virion Vaccine BBV152 Against Reinfection Among Healthcare Workers in New Delhi, India  

IMPORTANCE: A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021. OBJECTIVE: To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India. EXPOSURES: Vaccination with 0, 1, or 2 doses of BBV152. MAIN OUTCOMES AND MEASURES: The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 − adjusted HR) was reported. RESULTS: Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection. CONCLUSIONS AND RELEVANCE: These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.

JAMA Netw Open2022       LitCov and CORD-19
1915Modelling direct and herd protection effects of vaccination against the SARS-CoV-2 Delta variant in Australia  

OBJECTIVES: To analyse the outcomes of COVID‐19 vaccination by vaccine type, age group eligibility, vaccination strategy, and population coverage. DESIGN: Epidemiologic modelling to assess the final size of a COVID‐19 epidemic in Australia, with vaccination program (Pfizer, AstraZeneca, mixed), vaccination strategy (vulnerable first, transmitters first, untargeted), age group eligibility threshold (5 or 15 years), population coverage, and pre‐vaccination effective reproduction number ([Formula: see text]) for the SARS‐CoV‐2 Delta variant as factors. MAIN OUTCOME MEASURES: Numbers of SARS‐CoV‐2 infections; cumulative hospitalisations, deaths, and years of life lost. RESULTS: Assuming [Formula: see text] = 5, the current mixed vaccination program (vaccinating people aged 60 or more with the AstraZeneca vaccine and people under 60 with the Pfizer vaccine) will not achieve herd protection unless population vaccination coverage reaches 85% by lowering the vaccination eligibility age to 5 years. At [Formula: see text] = 3, the mixed program could achieve herd protection at 60‒70% population coverage and without vaccinating 5‒15‐year‐old children. At [Formula: see text] = 7, herd protection is unlikely to be achieved with currently available vaccines, but they would still reduce the number of COVID‐19‐related deaths by 85%. CONCLUSION: Vaccinating vulnerable people first is the optimal policy when population vaccination coverage is low, but vaccinating more socially active people becomes more important as the [Formula: see text] declines and vaccination coverage increases. Assuming the most plausible [Formula: see text] of 5, vaccinating more than 85% of the population, including children, would be needed to achieve herd protection. Even without herd protection, vaccines are highly effective in reducing the number of deaths.

Med J Aust2021       LitCov and CORD-19
1916Predictors of academic performance during the covid-19 outbreak: impact of distance education on mental health, social cognition and memory abilities in an Italian university student sample  

BACKGROUND: This study aimed to investigate the impact of distance education (DE) on mental health, social cognition, and memory abilities in a sample of university students during the national COVID-19 lockdown in Italy and to identify the predictors of academic performance. METHODS: Two hundred and three students (76.4% women, mean age 24.3, SD ± 4.9) responded to an anonymous online cross-sectional survey between July 15 and September 30, 2020, on DE experience and cognitive and social-cognitive variables. A short version of the Beck Depression Inventory-II, ten images from the Eyes Task, and five memory vignette stimuli were included in the survey. Descriptive, one-way ANOVA, correlation, and logistic regression analyses were conducted. RESULTS: Half of the student sample reported significant impairment in concentration and learning abilities during DE. Regarding psychological health, 19.7%, 27.1%, and 23.6% of the sample reported mild, moderate, and severe depressive symptoms, respectively. Correlation analyses showed a statistically significant negative association between depression and the overall subjective evaluation of DE (r = − 0.359; p < 0.000). Changes in one’s study context and habits, i.e., studying alone at one’s parents’ home instead of studying with colleagues or alone in a university “social place” (e.g., the university library), seemed to increase the likelihood of poor academic performance by almost 3 times (O.R. 3.918; p = 0.032). This predictor was no longer statistically significant in the subsequent step when the individual impairment predictors were entered. Learning concentration impairment during DE (O.R. 8.350; p = 0.014), anxiety about COVID-19 contagion for oneself or others (O.R. 3.363; p = 0.022), female gender (O.R. 3.141; p = 0.045), and depressive symptomatology (O.R. 1.093; p = 0.047) were ultimately determined to be the strongest predictors of poor academic performance, whereas the appreciation of DE represented a protective variable (O.R. 0.610; p < 0.000). CONCLUSIONS: The study showed a negative impact of DE on the mental health of students presenting depressive symptoms and impairment in concentration and learning, the latter identified as the strongest predictors of poor academic performances. The study confirms the emerging need to monitor the impact of DE, which occurred during the 2019/2020 academic year and will continue in the coming months, to refine educational offerings and meet students' psychological needs by implementing psychological interventions based on the modifiable variables that seem to compromise students’ psychological well-being and academic outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40359-021-00649-9.

BMC Psychol2021       LitCov and CORD-19
1917The prevalence and influencing factors in anxiety in medical workers fighting COVID-19 in China: a cross-sectional survey  

The coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2 virus) has been sustained in China since December 2019, and has become a pandemic. The mental health of frontline medical staff is a concern. In this study, we aimed to identify the factors influencing medical worker anxiety in China during the COVID-19 outbreak. We conducted a cross-sectional study to estimate the prevalence of anxiety among medical staff in China from 10 February 2020 to 20 February 2020 using the Zung Self-rating Anxiety Scale (SAS) to assess anxiety, with the criteria of normal (⩽49), mild (50–59), moderate (60–70) and severe anxiety (⩾70). We used multivariable linear regression to determine the factors (e.g. having direct contact when treating infected patients, being a medical staff worker from Hubei province, being a suspect case) for anxiety. We also used adjusted models to confirm independent factors for anxiety after adjusting for gender, age, education and marital status. Of 512 medical staff in China, 164 (32.03%) had had direct contact treating infected patients. The prevalence of anxiety was 12.5%, with 53 workers suffering from mild (10.35%), seven workers suffering from moderate (1.36%) and four workers suffering from severe anxiety (0.78%). After adjusting for sociodemographic characteristics (gender, age, education and marital status), medical staff who had had direct contact treating infected patients experienced higher anxiety scores than those who had not had direct contact (β value = 2.33, confidence interval (CI) 0.65–4.00; P = 0.0068). A similar trend was observed in medical staff from Hubei province, compared with those from other parts of China (β value = 3.67, CI 1.44–5.89; P = 0.0013). The most important variable was suspect cases with high anxiety scores, compared to non-suspect cases (β value = 4.44, CI 1.55–7.33; P = 0.0028). In this survey of hospital medical workers during the COVID-19 outbreak in China, we found that study participants experienced anxiety symptoms, especially those who had direct clinical contact with infected patients; as did those in the worst affected areas, including Hubei province; and those who were suspect cases. Governments and healthcare authorities should proactively implement appropriate psychological intervention programmes, to prevent, alleviate or treat increased anxiety.

Epidemiol Infect2020       LitCov and CORD-19
1918Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study  

BACKGROUND: The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting. METHODS: In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/m(2)vs ≥30 kg/m(2)), and comorbidities (binary variable, with or without comorbidities). FINDINGS: Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49–68) for ChAdOx1 nCoV-19 and 69% (66–72) for BNT162b2 at 21–44 days and 72% (63–79) for BNT162b2 after 45–59 days. INTERPRETATION: Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days. FUNDING: ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.

Lancet Infect Dis2021       LitCov and CORD-19
1919Immunogenicity and safety of SARS-CoV-2 vaccines in clinical trials  

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Front Biosci (Landmark Ed)2021       LitCov and CORD-19
1920SARS-CoV-2 Seroprevalence Among Healthcare Workers by Workplace Exposure Risk in Kashmir, India  

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J Hosp Med2021       LitCov and CORD-19
1921The COVID-19 pandemic and health inequalities  

This essay examines the implications of the COVID-19 pandemic for health inequalities. It outlines historical and contemporary evidence of inequalities in pandemics—drawing on international research into the Spanish influenza pandemic of 1918, the H1N1 outbreak of 2009 and the emerging international estimates of socio-economic, ethnic and geographical inequalities in COVID-19 infection and mortality rates. It then examines how these inequalities in COVID-19 are related to existing inequalities in chronic diseases and the social determinants of health, arguing that we are experiencing a syndemic pandemic. It then explores the potential consequences for health inequalities of the lockdown measures implemented internationally as a response to the COVID-19 pandemic, focusing on the likely unequal impacts of the economic crisis. The essay concludes by reflecting on the longer-term public health policy responses needed to ensure that the COVID-19 pandemic does not increase health inequalities for future generations.

J Epidemiol Community Health2020       LitCov and CORD-19
1922Cytokine Storm  

N Engl J Med2020       LitCov and CORD-19
1923Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants  

BACKGROUND: The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed. METHODS: Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed. Furthermore, we assessed the impact of single natural mutation or co-mutations of concern at key positions of RBD on the neutralization escape and ACE2 binding function by recombinant proteins and pseudoviruses. RESULTS: Thirty-three amino acid positions within four independent antigenic sites (1 to 4) of RBD were identified as valuable indicators of antigenic changes in the RBD. The comprehensive escape mutation map not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the discovery of new immune escape-enabling mutations such as F486L, N450K, F490S, and R346S. Of note, these escape mutations could not affect the ACE2 binding affinity of RBD, among which L452R even enhanced binding. Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect. Conversely, double mutations E484Q and L452R present in B.1.617.1 variant show partial antibody evasion with no evidence for an additive effect. CONCLUSIONS: Our study provides a global view of the determinants for neutralizing antibody recognition, antigenic conservation, and RBD conformation. The in-depth escape maps may have value for prospective surveillance of SARS-CoV-2 immune escape variants. Special attention should be paid to the accumulation of co-mutations at distinct major antigenic sites. Finally, the new broadly reactive NAbs described here represent new potential opportunities for the prevention and treatment of COVID-19. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-021-00985-w.

Genome Med2021       LitCov and CORD-19
1924An internet-based self-help intervention for people with psychological distress due to COVID-19: study protocol for a randomized controlled trial  

BACKGROUND: The coronavirus-19 (COVID-19) has reached pandemic status and is affecting countries all over the world. The COVID-19 pandemic is accompanied by various stressors that require adjustment in everyday life and possibly changes in personal future prospects. While some individuals cope well with these challenges, some develop psychological distress including depressive symptoms, anxiety, or stress. Internet-based self-help interventions have proven to be effective in the treatment of various mental disorders such as depression and anxiety. Based on that, we developed an internet-based self-help program for individuals with psychological distress due to the situation surrounding the COVID-19 pandemic. The 3-week self-help program consists of 6 modules comprising texts, videos, figures, and exercises. Participants can request guidance within the self-help program (guidance on demand). The primary aim of this study is to evaluate the efficacy and feasibility of the self-help program compared to a waiting control condition. METHODS: The design is a parallel group randomized controlled trial. Participants are allocated to a 3-week self-help intervention plus care as usual or a 3-week waiting period with only care as usual. There are follow-ups after 6 weeks and 18 weeks. At least 80 participants with COVID-19 pandemic related psychological distress will be recruited. Primary outcome are depressive symptoms. Secondary outcomes include anxiety and chronic stress, suicidal experiences and behavior, health-related quality of life, generalized optimism and pessimism, embitterment, optimistic self-beliefs, emotion regulation skills, loneliness, resilience, and the satisfaction with and usability of the self-help program. DISCUSSION: To the best of our knowledge, this is one of the first studies investigating the efficacy of an internet-based self-help program for psychological distress due to the situation surrounding the COVID-19 pandemic. Thus, the results of this study may give further insight into the use of internet-based self-help programs in pandemic-related psychological distress. TRIAL REGISTRATION: ClinicalTrials.gov NCT04380909. Retrospectively registered on 8 May 2020.

Trials2021       LitCov and CORD-19
1925Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study  

OBJECTIVES: We aimed to evaluate rates of antibody response to mRNA SARS-CoV-2 vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity. METHODS: A prospective cohort study including consecutive kidney transplant recipients in a single referral transplant center. Participants were tested for anti-spike (anti-S) antibodies 2-4 weeks following second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity. RESULTS: Of 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2-4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titer was 15.5 AU/mL (interquartile range [IQR] 3.5-163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio [OR] 1.025 per ml/min/1.73m(2), 95% confidence interval [CI] 1.014 - 1.037, p<0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95% CI 1.782 - 3.089, p<0.001), younger age (OR 1.032 per year decrease, 95% CI 1.015 - 1.05, p<0.001) and lower calcineurin inhibitors (CNI) blood level (OR 1.987, 95% CI 1.146 - 3.443, p=0.014). No serious adverse events to the vaccine were reported. CONCLUSIONS: Kidney transplant recipients demonstrated inadequate antibody response to mRNA SARS-CoV-2 vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.

Clin Microbiol Infect2021       LitCov and CORD-19
1926Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19 Vaccine  

BACKGROUND: Efficacious vaccines are urgently needed to contain the ongoing coronavirus disease 2019 (Covid-19) pandemic of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A candidate vaccine, Ad26.COV2.S, is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein. METHODS: In this multicenter, placebo-controlled, phase 1–2a trial, we randomly assigned healthy adults between the ages of 18 and 55 years (cohort 1) and those 65 years of age or older (cohort 3) to receive the Ad26.COV2.S vaccine at a dose of 5×10(10) viral particles (low dose) or 1×10(11) viral particles (high dose) per milliliter or placebo in a single-dose or two-dose schedule. Longer-term data comparing a single-dose regimen with a two-dose regimen are being collected in cohort 2; those results are not reported here. The primary end points were the safety and reactogenicity of each dose schedule. RESULTS: After the administration of the first vaccine dose in 805 participants in cohorts 1 and 3 and after the second dose in cohort 1, the most frequent solicited adverse events were fatigue, headache, myalgia, and injection-site pain. The most frequent systemic adverse event was fever. Systemic adverse events were less common in cohort 3 than in cohort 1 and in those who received the low vaccine dose than in those who received the high dose. Reactogenicity was lower after the second dose. Neutralizing-antibody titers against wild-type virus were detected in 90% or more of all participants on day 29 after the first vaccine dose (geometric mean titer [GMT], 224 to 354), regardless of vaccine dose or age group, and reached 100% by day 57 with a further increase in titers (GMT, 288 to 488) in cohort 1a. Titers remained stable until at least day 71. A second dose provided an increase in the titer by a factor of 2.6 to 2.9 (GMT, 827 to 1266). Spike-binding antibody responses were similar to neutralizing-antibody responses. On day 14, CD4+ T-cell responses were detected in 76 to 83% of the participants in cohort 1 and in 60 to 67% of those in cohort 3, with a clear skewing toward type 1 helper T cells. CD8+ T-cell responses were robust overall but lower in cohort 3. CONCLUSIONS: The safety and immunogenicity profiles of Ad26.COV2.S support further development of this vaccine candidate. (Funded by Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services; COV1001 ClinicalTrials.gov number, NCT04436276.)

N Engl J Med2021       LitCov and CORD-19
1927Determinants of COVID-19 vaccine acceptance in the US  

BACKGROUND: The COVID-19 pandemic continues to adversely affect the U.S., which leads globally in total cases and deaths. As COVID-19 vaccines are under development, public health officials and policymakers need to create strategic vaccine-acceptance messaging to effectively control the pandemic and prevent thousands of additional deaths. METHODS: Using an online platform, we surveyed the U.S. adult population in May 2020 to understand risk perceptions about the COVID-19 pandemic, acceptance of a COVID-19 vaccine, and trust in sources of information. These factors were compared across basic demographics. FINDINGS: Of the 672 participants surveyed, 450 (67%) said they would accept a COVID-19 vaccine if it is recommended for them. Males (72%) compared to females, older adults (≥55 years; 78%) compared to younger adults, Asians (81%) compared to other racial and ethnic groups, and college and/or graduate degree holders (75%) compared to people with less than a college degree were more likely to accept the vaccine. When comparing reported influenza vaccine uptake to reported acceptance of the COVID-19 vaccine: 1) participants who did not complete high school had a very low influenza vaccine uptake (10%), while 60% of the same group said they would accept the COVID-19 vaccine; 2) unemployed participants reported lower influenza uptake and lower COVID-19 vaccine acceptance when compared to those employed or retired; and, 3) Black Americans reported lower influenza vaccine uptake and lower COVID-19 vaccine acceptance than all other racial groups reported in our study. Lastly, we identified geographic differences with Department of Health and Human Services (DHHS) regions 2 (New York) and 5 (Chicago) reporting less than 50 percent COVID-19 vaccine acceptance. INTERPRETATION: Although our study found a 67% acceptance of a COVID-19 vaccine, there were noticeable demographic and geographical disparities in vaccine acceptance. Before a COVID-19 vaccine is introduced to the U.S., public health officials and policymakers must prioritize effective COVID-19 vaccine-acceptance messaging for all Americans, especially those who are most vulnerable.

EClinicalMedicine2020       LitCov and CORD-19
1928Comparative study of lung ultrasound and chest computed tomography scan in the assessment of severity of confirmed COVID-19 pneumonia  

PURPOSE: The relationship between lung ultrasound (LUS) and chest computed tomography (CT) scans in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is not clearly defined. The primary objective of our study was to assess the performance of LUS in determining severity of SARS-CoV-2 pneumonia compared with chest CT scan. Secondary objectives were to test the association between LUS score and location of the patient, use of mechanical ventilation, and the pulse oximetry (SpO(2))/fractional inspired oxygen (FiO(2)) ratio. METHODS: A multicentre observational study was performed between 15 March and 20 April 2020. Patients in the Emergency Department (ED) or Intensive Care Unit (ICU) with acute dyspnoea who were PCR positive for SARS-CoV-2, and who had LUS and chest CT performed within a 24-h period, were included. RESULTS: One hundred patients were included. LUS score was significantly associated with pneumonia severity assessed by chest CT and clinical features. The AUC of the ROC curve of the relationship of LUS versus chest CT for the assessment of severe SARS-CoV-2 pneumonia was 0.78 (CI 95% 0.68–0.87; p < 0.0001). A high LUS score was associated with the use of mechanical ventilation, and with a SpO(2)/FiO(2) ratio below 357. CONCLUSION: In known SARS-CoV-2 pneumonia patients, the LUS score was predictive of pneumonia severity as assessed by a chest CT scan and clinical features. Within the limitations inherent to our study design, LUS can be used to assess SARS-CoV-2 pneumonia severity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06186-0) contains supplementary material, which is available to authorized users.

Intensive Care Med2020       LitCov and CORD-19
1929A Feasible Alternative Strategy Targeting Furin Disrupts SARS-CoV-2 Infection Cycle  

The COVID-19 causing coronavirus (SARS-CoV-2) remains a public health threat worldwide. SARS-CoV-2 enters human lung cells via its spike glycoprotein binding to angiotensin-converting enzyme 2 (ACE2). Notably, the cleavage of the spike by the host cell protease furin in virus-producing cells is critical for subsequent spike-driven entry into lung cells. Thus, effective targeted therapies blocking the spike cleavage and activation in viral producing cells may provide an alternate strategy to break the viral transmission cycle and to overcome disease pathology. Here we engineered and described an antibody-based targeted strategy, which directly competes with the furin mediated proteolytic activation of the spike in virus-producing cells. The described approach involves engineering competitive furin substrate residues in the IgG1 Fc-extended flexible linker domain of SARS-CoV-2 spike targeting antibodies. Considering the site of spike furin cleavage and SARS-CoV-2 egress remains uncertain, the experimental strategy pursued here revealed novel mechanistic insights into proteolytic processing of the spike protein, which suggest that processing does not occur in the constitutive secretory pathway. Furthermore, our results show blockade of furin-mediated cleavage of the spike protein for membrane fusion activation and virus host-cell entry function. These findings provide an alternate insight of targeting applicability to SARS-CoV-2 and the future coronaviridae family members, exploiting the host protease system to gain cellular entry and subsequent chain of infections. IMPORTANCE Since its emergence in December 2019, COVID-19 has remained a global economic and health threat. Although RNA and DNA vector-based vaccines induced antibody response and immunological memory have proven highly effective against hospitalization and mortality, their long-term efficacy remains unknown against continuously evolving SARS-CoV-2 variants. As host cell-enriched furin-mediated cleavage of SARS-CoV-2 spike protein is critical for viral entry and chain of the infection cycle, the solution described here of an antibody Fc-conjugated furin competing peptide is significant. In a scenario where spike mutational drifts do not interfere with the Fc-conjugated antibody's epitope, the proposed furin competing strategy confers a broad-spectrum targeting design to impede the production of efficiently transmissible SARS-CoV-2 viral particles. In addition, the proposed approach is plug-and-play against other potentially deadly viruses that exploit secretory pathway independent host protease machinery to gain cellular entry and subsequent transmissions to host cells.

Microbiol Spectr2022       LitCov and CORD-19
1930Detection and evaluation of SARS-CoV-2 nucleic acid contamination in corona virus disease 19 ward surroundings and the surface of medical staff's protective equipment  

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Beijing Da Xue Xue Bao Yi Xue 2020       LitCov and CORD-19
1931Have the COVID-19 pandemic and lockdown affected children's mental health in the long-term? A repeated cross-sectional study  

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BMJ Open2022       LitCov
1932Neuroinvasion, neurotropic and neuroinflammatory events of SARS-CoV-2: understanding the neurological manifestations in COVID-19 patients  

Respiratory viruses are opportunistic pathogens that infect the upper respiratory tract in humans and cause severe illnesses, especially in vulnerable populations. Some viruses have neuroinvasive properties and activate the immune response in the brain. These immune events may be neuroprotective or they may cause long-term damage similar to what is seen in some neurodegenerative diseases. The new “Severe Acute Respiratory Syndrome Coronavirus 2” (SARS-CoV-2) is one of the Respiratory viruses causing highly acute lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical similarities to those reported in “Severe Acute Respiratory Syndrome Coronavirus”(SARS-CoV) and the “Middle East Respiratory Syndrome Coronavirus”(MERS-CoV) including neurological manifestation. To examine the possible neurological damage induced by SARS-CoV-2, it is necessary to understand the immune reactions to viral infection in the brain, and their short- and long-term consequences. Considering the similarities between SARS-CoV and SARS-CoV-2, which will be discussed, cooperative homological and phylogenetical studies lead us to question if SARS-CoV-2 can have similar neuroinvasive capacities and neuroinflammatiory events that may lead to the same short- and long-term neuropathologies that SARS-CoV had shown in human and animal models. To explain the neurological manifestation caused by SARS-CoV-2, we will present a literature review of 765 COVID-19 patients, in which 18% had neurological symptoms and complications, including encephalopathy, encephalitis and cerebrovascular pathologies, acute myelitis, and Guillain-Barré syndrome. Clinical studies describe anosmia or partial loss of the sense of smell as the most frequent symptom in COVID19 patients, suggesting that olfactory dysfunction and the initial ultrarapid immune responses could be a prognostic factor.

Neurol Sci2020       LitCov and CORD-19
1933Highly conserved binding region of ACE2 as a receptor for SARS-CoV-2 between humans and mammals  

Several cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection transmitted from human owners to their dogs have recently been reported. The first ever case of SARS-CoV-2 transmission from a human owner to a domestic cat was confirmed on March 27, 2020. A tiger from a zoo in New York, USA, was also reportedly infected with SARS-CoV-2. It is believed that SARS-CoV-2 was transmitted to tigers from their caretakers, who were previously infected with this virus. On May 25, 2020, the Dutch Minister of Agriculture, Nature and Food Quality reported that two employees were infected with SARS-CoV-2 transmitted from minks. These reports have influenced us to perform a comparative analysis among angiotensin-converting enzyme 2 (ACE2) homologous proteins for verifying the conservation of specific protein regions. One of the most conserved peptides is represented by the peptide “353-KGDFR-357 (H. sapiens ACE2 residue numbering), which is located on the surface of the ACE2 molecule and participates in the binding of SARS-CoV-2 spike receptor binding domain (RBD). Multiple sequence alignments of the ACE2 proteins by ClustalW, whereas the three-dimensional structure of its binding region for the spike glycoprotein of SARS-CoV-2 was assessed by means of Spanner, a structural homology modeling pipeline method. In addition, evolutionary phylogenetic tree analysis by ETE3 was used. ACE2 works as a receptor for the SARS-CoV-2 spike glycoprotein between humans, dogs, cats, tigers, minks, and other animals, except for snakes. The three-dimensional structure of the KGDFR hosting protein region involved in direct interactions with SARS-CoV-2 spike RBD of the mink ACE2 appears to form a loop structurally related to the human ACE2 corresponding protein loop, despite of the reduced available protein length (401 residues of the mink ACE2 available sequence vs 805 residues of the human ACE2). The multiple sequence alignments of the ACE2 proteins shows high homology and complete conservation of the five amino acid residues: 353-KGDFR-357 with humans, dogs, cats, tigers, minks, and other animals, except for snakes. Where the information revealed from our examinations can support precision vaccine design and the discovery of antiviral therapeutics, which will accelerate the development of medical countermeasures, the World Health Organization recently reported on the possible risks of reciprocal infections regarding SARS-CoV-2 transmission from animals to humans.

Vet Q2020       LitCov and CORD-19
1934COVID-19 mRNA Vaccines Are Generally Safe in the Short Term: A Vaccine Vigilance Real-World Study Says  

BACKGROUND: The prophylactic vaccination of COVID-19 mRNA vaccines is the first large-scale application of this kind in the human world. Over 1.8 million doses of the COVID-19 vaccine had been administered in the US until December 2020, and around 0.2% submitted AE reports to the Vaccine Adverse Event Reporting System (VAERS). This study aimed to evaluate the AEs following immunization (AEFIs) and analyze the potential associations based on the information from the VAERS database. METHODS: We searched the VAERS database recorded AEFIs after COVID-19 vaccines in December 2020. After data mapping, we summarized demographic and clinical features of reported cases. Fisher exact test was used to comparing the clinical characteristics among AE groups with an anaphylactic response, concerning neurological disorders and death. RESULTS: VAERS reported 3,908 AEFIs of COVID-19 vaccines in December 2020. Most (79.68%) were reported after the first dose of the vaccine. Among the reported cases, we found that general disorders (48.80%), nervous system disorders (46.39%), and gastrointestinal disorders (25.54%) were the most common AEFIs. The allergy history was more frequent in vaccine recipients with anaphylactic reactions than those without (64.91% vs. 49.62%, OR = 1.88, P <0.017). History of anxiety or depression was more common in subjects reporting severe neurological AEFIs than those reporting other AEFIs (18.37% vs. 7.85%, OR = 2.64, P <0.017). Cases reporting death were significantly older (79.36 ± 10.41-year-old vs. 42.64 ± 12.55-year-old, P <0.01, 95% CI 29.30–44.15) and more likely experienced hypertension (50.00% vs. 11.42%, OR = 7.76, P <0.01) and neurological disorders (50.00% vs. 5.36%, OR = 17.65, P <0.01) than other vaccine recipients. The outpatient and emergency room visit rates were 11.92 and 22.42% for AEFIs, and 2.53% of cases needed hospitalization. CONCLUSION: AEFIs of COVID-19 mRNA vaccines were generally non-severe local or systemic reactions. A prior allergy history is the risk factor for anaphylaxis, while a history of anxiety may link with severe neurological AEs. Such vaccine recipients need further evaluation and monitor.

Front Immunol2021       LitCov and CORD-19
1935Probing structural basis for enhanced binding of SARS-CoV-2 P.1 variant spike protein with the human ACE2 receptor  

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J Cell Biochem2022       LitCov and CORD-19
1936An Integrated Strategy for the Prevention of SARS-CoV-2 Infection in Healthcare Workers: A Prospective Observational Study  

Background: Since the beginning of SARS-CoV-2 outbreak, a large number of infections have been reported among healthcare workers (HCWs). The aim of this study was to investigate the occurrence of SARS-CoV-2 infection among HCWs involved in the first management of infected patients and to describe the measures adopted to prevent the transmission in the hospital. Methods: This prospective observational study was conducted between February 21 and April 16, 2020, in the Padua University Hospital (north-east Italy). The infection control policy adopted consisted of the following: the creation of the “Advanced Triage” area for the evaluation of SARS-CoV-2 cases, and the implementation of an integrated infection control surveillance system directed to all the healthcare personnel involved in the Advance Triage area. HCWs were regularly tested with nasopharyngeal swabs for SARS-CoV-2; body temperature and suggestive symptoms were evaluated at each duty. Demographic and clinical data of both patients and HCWs were collected and analyzed; HCWs’ personal protective equipment (PPE) consumption was also recorded. The efficiency of the control strategy among HCWs was evaluated identifying symptomatic infection (primary endpoint) and asymptomatic infection (secondary endpoint) with confirmed detection of SARS-CoV-2. Results: 7595 patients were evaluated in the Advanced Triage area: 5.2% resulted positive and 72.4% was symptomatic. The HCW team was composed of 60 members. A total of 361 nasopharyngeal swabs were performed on HCWs. All the swabs resulted negative and none of the HCWs reached the primary or the secondary endpoint. Conclusions: An integrated hospital infection control strategy, consisting of dedicated areas for infected patients, strict measures for PPE use and mass surveillance, is successful to prevent infection among HCWs.

Int J Environ Res Public Healt2020       LitCov and CORD-19
1937Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 through Computational Drug Repurposing Study  

[Image: see text] The recent outbreak of novel coronavirus disease-19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed 3D structures of key viral proteins are resolved. The virus causing COVID-19 is SARS-CoV-2. Taking advantage of a recently released crystal structure of SARS-CoV-2 main protease in complex with a covalently bonded inhibitor, N3 (Liu et al., 10.2210/pdb6LU7/pdb), I conducted virtual docking screening of approved drugs and drug candidates in clinical trials. For the top docking hits, I then performed molecular dynamics simulations followed by binding free energy calculations using an end point method called MM-PBSA-WSAS (molecular mechanics/Poisson–Boltzmann surface area/weighted solvent-accessible surface area; Wang, Chem. Rev.2019, 119, 947831244000; Wang, Curr. Comput.-Aided Drug Des.2006, 2, 287; Wang; HouJ. Chem. Inf. Model., 2012, 52, 119922497310). Several promising known drugs stand out as potential inhibitors of SARS-CoV-2 main protease, including carfilzomib, eravacycline, valrubicin, lopinavir, and elbasvir. Carfilzomib, an approved anticancer drug acting as a proteasome inhibitor, has the best MM-PBSA-WSAS binding free energy, −13.8 kcal/mol. The second-best repurposing drug candidate, eravacycline, is synthetic halogenated tetracycline class antibiotic. Streptomycin, another antibiotic and a charged molecule, also demonstrates some inhibitory effect, even though the predicted binding free energy of the charged form (−3.8 kcal/mol) is not nearly as low as that of the neutral form (−7.9 kcal/mol). One bioactive, PubChem 23727975, has a binding free energy of −12.9 kcal/mol. Detailed receptor–ligand interactions were analyzed and hot spots for the receptor–ligand binding were identified. I found that one hot spot residue, His41, is a conserved residue across many viruses including SARS-CoV, SARS-CoV-2, MERS-CoV, and hepatitis C virus (HCV). The findings of this study can facilitate rational drug design targeting the SARS-CoV-2 main protease.

J Chem Inf Model2020       LitCov and CORD-19
1938Detection of SARS-CoV-2 and the L452R spike mutation using reverse transcription loop-mediated isothermal amplification plus bioluminescent assay in real-time (RT-LAMP-BART)  

The new coronavirus infection (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be fatal, and several variants of SARS-CoV-2 with mutations of the receptor-binding domain (RBD) have increased avidity for human cell receptors. A single missense mutation of U to G at nucleotide position 1355 (U1355G) in the spike (S) gene changes leucine to arginine (L452R) in the spike protein. This mutation has been observed in the India and California strains (B.1.617 and B.1.427/B.1.429, respectively). Control of COVID-19 requires rapid and reliable detection of SARS-CoV-2. Therefore, we established a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay plus a bioluminescent assay in real-time (BART) to detect SARS-CoV-2 and the L452R spike mutation. The specificity and sensitivity of the RT-LAMP-BART assay was evaluated using synthetic RNAs including target sequences and RNA-spiked clinical nasopharyngeal and saliva specimens as well as reference strains representing five viral and four bacterial pathogens. The novel RT-LAMP-BART assay to detect SARS-CoV-2 was highly specific compared to the conventional real-time RT-PCR. Within 25 min, the RT-LAMP-BART assay detected 80 copies of the target gene in a sample, whereas the conventional real-time RT-PCR method detected 5 copies per reaction within 130 min. Using RNA-spiked specimens, the sensitivity of the RT-LAMP-BART assay was slightly attenuated compared to purified RNA as a template. The results were identical to those of the conventional real-time RT-PCR method. Furthermore, using a peptide nucleic acid (PNA) probe, the RT-LAMP-BART method correctly identified the L452R spike mutation. This is the first report describes RT-LAMP-BART as a simple, inexpensive, rapid, and useful assay for detection of SARS-CoV-2, its variants of concern, and for screening of COVID-19.

PLoS One2022       LitCov and CORD-19
1939COVID-19 and Italy: what next?  

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already taken on pandemic proportions, affecting over 100 countries in a matter of weeks. A global response to prepare health systems worldwide is imperative. Although containment measures in China have reduced new cases by more than 90%, this reduction is not the case elsewhere, and Italy has been particularly affected. There is now grave concern regarding the Italian national health system's capacity to effectively respond to the needs of patients who are infected and require intensive care for SARS-CoV-2 pneumonia. The percentage of patients in intensive care reported daily in Italy between March 1 and March 11, 2020, has consistently been between 9% and 11% of patients who are actively infected. The number of patients infected since Feb 21 in Italy closely follows an exponential trend. If this trend continues for 1 more week, there will be 30 000 infected patients. Intensive care units will then be at maximum capacity; up to 4000 hospital beds will be needed by mid-April, 2020. Our analysis might help political leaders and health authorities to allocate enough resources, including personnel, beds, and intensive care facilities, to manage the situation in the next few days and weeks. If the Italian outbreak follows a similar trend as in Hubei province, China, the number of newly infected patients could start to decrease within 3–4 days, departing from the exponential trend. However, this cannot currently be predicted because of differences between social distancing measures and the capacity to quickly build dedicated facilities in China.

Lancet2020       LitCov and CORD-19
1940Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe  

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Circulation2021       LitCov and CORD-19
1941SARS-CoV-2 Infection in Healthcare Professionals and General Population During "First Wave" of COVID-19 Pandemic: A Cross-Sectional Study Conducted in Sicily, Italy  

On December 31, 2019, an outbreak of lower respiratory infections was documented in Wuhan caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the beginning, SARS-CoV-2 has caused many infections among healthcare workers (HCWs) worldwide. Aims of this study were: a. to compare the distribution among the HCWs and the general population of SARS-CoV-2 infections in Western Sicily and Italy; b. to describe the characteristics of HCWs infected with SARS-CoV-2 in the western Sicilian healthcare context during the first wave of the epidemic diffusion in Italy. Incidence and mean age of HCWs infected with SARS-CoV-2 were comparable in Western Sicily and in the whole Italian country. The 97.6% of infections occurred in HCWs operating in non-coronavirus disease 2019 (COVID-19) working environments, while an equal distribution of cases between hospital and primary care services context was documented. Nurses and healthcare assistants, followed by physicians, were the categories more frequently infected by SARS-CoV-2. The present study suggests that healthcare workers are easily infected compared to the general population but that often infection could equally occur in hospital and non-hospital settings. Safety of HCWs in counteracting the COVID-19 pandemic must be strengthened in hospital [adequate provision of personal protective equipment (PPE), optimization of human resources, implementation of closed and independent groups of HCWs, creation of traffic control building and dedicated areas in every healthcare context] and non-hospital settings (influenza vaccination, adequate psychophysical support, including refreshments during working shifts, adequate rest, and family support).

Front Public Health2021       LitCov and CORD-19
1942Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19  

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JAMA Intern Med2020       LitCov and CORD-19
1943Outpatient treatment of COVID-19 with steroids in the phase of mild pneumonia without the need for admission as an opportunity to modify the course of the disease: A structured summary of a randomised controlled trial  

OBJECTIVES: The aim of this study is to explore the effectiveness and safety of oral corticosteroids (prednisone) in the treatment of early stage SARS-Cov-2 pneumonia in patients who do not yet meet hospital admission criteria. TRIAL DESIGN: Randomized clinical trial, controlled, open, parallel group, to evaluate the effectiveness of steroids in adult patients with confirmed COVID-19, with incipient pulmonary involvement, without hospital admission criteria. Patients will be stratified by the presence or not of radiological data on pneumonia. PARTICIPANTS: We will include patients with early stage SARS-Cov-2 pneumonia who do not meet hospital admission criteria from the reference hospital, the Hospital Universitario de Burgos, in the region of Castilla y León, Spain. Patients will be followed-up by specialist physicians and Primary Health Care professionals. Inclusion criteria: - Men and women. - Age between 18 and 75 years old. - Diagnosed SARS-CoV-2 infection, by PCR and/or IgM+ antibody test and/or antigen test. - Clinical diagnosis of lung involvement: (respiratory symptoms +/- pathological auscultation +/- O2 desaturation) - Chest X-ray with mild-moderate alterations or normal. - Patients who give their verbal informed consent in front of witnesses, which will be reflected in the patients’ medical records. Exclusion criteria: - Oxygen desaturation below 93% or P0(2) < 62. - Moderate-severe dyspnea or significant respiratory or general deterioration that makes admission advisable. - Chest X-ray with multifocal infiltrates. - Insulin-dependent diabetes with poor control or glycaemia in the emergency room test greater than 300 mg/ml (fasting or not). - Other significant comorbidities: Severe renal failure (creatinine clearance < 30 mL/min); cirrhosis or chronic liver disease, poorly controlled hypertension. - Heart rhythm disturbances (including prolonged QT). - Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents); cancer. - Pregnant or breast-feeding women. - Patients under use of glucocorticoids for other diseases. - History of allergy or intolerance to any of the drugs in the study (prednisone, azithromycin or hydroxychloroquine). - Patients who took one or more of the study drugs in the 7 days prior to study inclusion. - Patients taking non-suppressible drugs with risk of QT prolongation or significant interactions. - Patients unwilling or unable to participate until study completion. - Participation in another study. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard outpatient treatment only (group 1) or standard outpatient treatment plus prednisone (group 2). - Group 1: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days. - Group 2: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days + prednisone 60 mg / 24 h for 3 days, 30 mg / 24 h for 3 days and 15 mg / 24 h for 3 days. MAIN OUTCOMES: If the patient requires ambulatory observation, according to the protocol established in this respect in the Emergency Department, meets all the criteria for inclusion and none for exclusion, data will be taken by the person responsible on the data collection sheet. The main result is admission after 30 days. Secondary outcomes are 30-day ICU admission and hospital stay. The safety variable will be the occurrence of clinical symptoms or delirium related to the steroids. Also, the possible decompensations of diabetes will be measured. All tests will be on an intention-to-treat basis. RANDOMISATION: Treatment will be assigned according to stratified randomization by the presence or absence of radiological data of lung involvement (previously performed by random sequence 1:1 generated with Epidat and kept hidden by opaque, sealed envelopes, which will only be opened after inclusion and basal measurement). BLINDING (MASKING): Participants, caregivers and personnel responsible for outcomes measurement will not be blinded to group assignment, once the patient is included and the basal measurement performed, as per protocol design. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The percentage of patients with incipient lung involvement is unknown, but given that pulmonary involvement already exists it is estimated to be around 20%. We consider that the intervention could reduce this percentage to 5%, so the necessary sample size would be 200 subjects (100 per group), with a power of 80% and an estimated loss percentage of 10%. TRIAL STATUS: The protocol with code TAC-COVID-19, version 2.0 on date: April 16, 2020 is approved by the Spanish Drug Agency (AEMPS) and the local Ethics Committee. The trial is in the recruitment phase. Recruitment began 19 April, 2020 and is anticipated to be complete by April 2021. TRIAL REGISTRATION: The trial was registered under the title “OUTPATIENT TREATMENT OF EARLY PULMONARY COVID19 WITH CORTICOSTEROIDS AS AN OPPORTUNITY TO MODIFY THE COURSE OF THE DISEASE” with EudraCT number 2020-001622-64, registered on 3 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
1944SARS-CoV-2 Variants, Vaccines and Host Immunity  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new beta coronavirus that emerged at the end of 2019 in the Hubei province of China. SARS-CoV-2 causes coronavirus disease 2019 (COVID-19) and was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. Herd or community immunity has been proposed as a strategy to protect the vulnerable, and can be established through immunity from past infection or vaccination. Whether SARS-CoV-2 infection results in the development of a reservoir of resilient memory cells is under investigation. Vaccines have been developed at an unprecedented rate and 7 408 870 760 vaccine doses have been administered worldwide. Recently emerged SARS-CoV-2 variants are more transmissible with a reduced sensitivity to immune mechanisms. This is due to the presence of amino acid substitutions in the spike protein, which confer a selective advantage. The emergence of variants therefore poses a risk for vaccine effectiveness and long-term immunity, and it is crucial therefore to determine the effectiveness of vaccines against currently circulating variants. Here we review both SARS-CoV-2-induced host immune activation and vaccine-induced immune responses, highlighting the responses of immune memory cells that are key indicators of host immunity. We further discuss how variants emerge and the currently circulating variants of concern (VOC), with particular focus on implications for vaccine effectiveness. Finally, we describe new antibody treatments and future vaccine approaches that will be important as we navigate through the COVID-19 pandemic.

Front Immunol2021       LitCov and CORD-19
1945Rapid and High-Throughput Reverse Transcriptase Quantitative PCR (RT-qPCR) Assay for Identification and Differentiation between SARS-CoV-2 Variants B.1.1.7 and B.1.351  

Emerging SARS-CoV-2 (SC-2) variants with increased infectivity and vaccine resistance are of major concern. Rapid identification of such variants is important for the public health decision making and to provide valuable data for epidemiological and policy decision making. We developed a multiplex reverse transcriptase quantitative PCR (RT-qPCR) assay that can specifically identify and differentiate between the emerging B.1.1.7 and B.1.351 SC-2 variants. In a single assay, we combined four reactions—one that detects SC-2 RNA independently of the strain, one that detects the D3L mutation, which is specific to variant B.1.1.7, one that detects the 242 to 244 deletion, which is specific to variant B.1.351, and the fourth reaction, which identifies the human RNAseP gene, serving as an endogenous control for RNA extraction integrity. We show that the strain-specific reactions target mutations that are strongly associated with the target variants and not with other major known variants. The assay’s specificity was tested against a panel of respiratory pathogens (n = 16), showing high specificity toward SC-2 RNA. The assay’s sensitivity was assessed using both in vitro transcribed RNA and clinical samples and was determined to be between 20 and 40 viral RNA copies per reaction. The assay performance was corroborated with Sanger and whole-genome sequencing, showing complete agreement with the sequencing results. The new assay is currently implemented in the routine diagnostic work at the Central Virology Laboratory, and may be used in other laboratories to facilitate the diagnosis of these major worldwide-circulating SC-2 variants. IMPORTANCE This study describes the design and utilization of a multiplex reverse transcriptase quantitative PCR (RT-qPCR) to identify SARS-COV-2 (SC2) RNA in general and, specifically, to detect whether it is of lineage B.1.1.7 or B.1.351. Implementation of this method in diagnostic and research laboratories worldwide may help the efforts to contain the COVID-19 pandemic. The method can be easily scaled up and be used in high-throughput laboratories, as well as small ones. In addition to immediate help in diagnostic efforts, this method may also help in epidemiological studies focused on the spread of emerging SC-2 lineages.

Microbiol Spectr2021       LitCov and CORD-19
1946Perspectives on Telehealth for older adults during the COVID-19 pandemic using the quadruple aim: interviews with 48 physicians  

BACKGROUND: Telehealth delivery expanded quickly during the COVID-19 pandemic after the reduction of payment and regulatory barriers, but older adults are the least likely to benefit from this expansion. Little is known about physician experiences initiating telehealth and factors that fostered or discouraged adoption during the COVID-19 pandemic with older adult patients. Therefore, our objective was to understand experiences of frontline physicians caring for older adults via telehealth during the COVID-19 pandemic. METHODS: We conducted semi-structured interviews from September 2020 to November 2020 with 48 physicians. We recruited a diverse sample of geriatricians (n = 18), primary care (n = 15), and emergency (n = 15) physicians from all United Stated (US) regions, rural-urban settings, and academic-community practices who cared for older adult patients during the pandemic using purposive sampling methods. We completed framework analysis of the transcribed interviews to identify emerging themes and used the Quadruple Aim to organize themes. RESULTS: Frontline physicians described telehealth as a more flexible, value-based, and patient-centered mode of health care delivery. Benefits of using telehealth to treat older adults included reducing deferred care and increasing timely care, improving efficiency for physicians, enhancing communication with caregivers and patients, reducing patient travel burdens, and facilitating health outreach and education. Challenges included unequal access for rural, older, or cognitively impaired patients. Physicians noted that payment parity with in-person visits, between video and telephone visits, and relaxation of restrictive regulations would enhance their ability to continue to offer telehealth. CONCLUSIONS: Frontline physicians who treated older adults during the COVID-19 pandemic were largely in favor of continuing telehealth use beyond the pandemic; however, they noted that sustainability would depend on enacting policies that address access inequities and reimbursement concerns. Our data provide policy insights that if placed into action could facilitate the long-term success of telehealth and encourage a more flexible healthcare delivery system in the US. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-022-02860-8.

BMC Geriatr2022       LitCov and CORD-19
1947Estimating the potential impact of COVID-19-related disruptions on HIV incidence and mortality among men who have sex with men in the United States: a modelling study  

BACKGROUND: During the COVID-19 pandemic, gay and other men who have sex with men (MSM) in the United States (US) report similar or fewer sexual partners and reduced HIV testing and care access. Pre-exposure prophylaxis (PrEP) use has declined. We estimated the potential impact of COVID-19 on HIV incidence and mortality among US MSM. METHODS: We used a calibrated HIV transmission model for MSM in Baltimore, Maryland, and available data on COVID-19-related disruptions to predict impacts of data-driven reductions in sexual partners(0%,25%,50%), condom use(5%), HIV testing(20%), viral suppression(10%), PrEP initiations(72%), PrEP use(9%) and ART initiations(50%), exploring different disruption durations and magnitudes. We estimated the median (95% credible interval) change in cumulative new HIV infections and deaths among MSM over one and five years, compared with a scenario without COVID-19-related disruptions. FINDINGS: A six-month 25% reduction in sexual partners among Baltimore MSM, without HIV service changes, could reduce new HIV infections by 12·2%(11·7,12·8%) and 3·0%(2·6,3·4%) over one and five years, respectively. In the absence of changes in sexual behaviour, the six-month data-driven disruptions to condom use, testing, viral suppression, PrEP initiations, PrEP use and ART initiations combined were predicted to increase new HIV infections by 10·5%(5·8,16·5%) over one year, and by 3·5%(2·1,5·4%) over five years. A 25% reduction in partnerships offsets the negative impact of these combined service disruptions on new HIV infections (overall reduction 3·9%(−1·0,7·4%), 0·0%(−1·4,0·9%) over one, five years, respectively), but not on HIV deaths (corresponding increases 11·0%(6·2,17·7%), 2·6%(1·5,4·3%)). The predicted impacts of reductions in partnerships or viral suppression doubled if they lasted 12 months or if disruptions were twice as large. INTERPRETATION: Maintaining access to ART and adherence support is of the utmost importance to minimise excess HIV-related mortality due to COVID-19 restrictions in the US, even if accompanied by reductions in sexual partnerships. FUNDING: NIH

medRxiv2020       CORD-19
1948The 5% of the Population at High Risk for Severe COVID-19 Infection Is Identifiable and Needs to Be Taken Into Account When Reopening the Economy  

The goal of this column is to help mental health care professionals understand coronavirus disease 2019 (COVID-19) so that they can better explain the complexities of the current crisis to their patients. The bottom-line of this column is that, while COVID-19 can infect virtually everyone in the human population, only about 5% are susceptible to severe infection requiring admission to an intensive care unit and/or causing a fatal outcome and this population can be identified on the basis of comorbid medical illness and/or age. These numbers are based on experience in China, the United States, and Europe. Table 1 presents an analysis conducted by the US Centers for Disease Control and Prevention (CDC), which is further supported by several other sources reviewed in the article. The population at risk for severe infection are individuals with comorbid medical illness and those 85 years of age and older. The comorbid medical illnesses identified as risk factors are preexisting respiratory and cardiovascular disease, immunocompromised status, morbid obesity (ie, body mass index ≥40), diabetes mellitus, and possibly significant kidney or liver impairment. Parenthetically, news reports and the literature sometimes cite age 60 years and older as a risk factor but age between 60 and 85 years is likely a surrogate for having 1 or more of these comorbid medical conditions. While 5% may initially seem like a small number, it nevertheless potentially represents 16.5 million people, given the United States population of 330 million. That is a tremendous number of people requiring intensive care unit admission and/or potentially dying, and individuals in this population have overwhelmed the US health care system in some hotspots. For this reason, this column suggests taking this at-risk population into account in mitigation strategies when attempting to open the US economy. The column addresses the following questions: (1) What are the 3 aspects of the race to minimize the damage caused by COVID-19? (2) What data are currently available to help guide decisions to be made? (3) What strategies have been employed to date and how successful have they been? and (4) Might risk stratification of exposure be a viable strategy to minimize the damage caused by the virus? The race to minimize the damage caused by COVID-19 requires that we obtain knowledge about the disease and its treatment or prevention, how to best safeguard public health and avoid overwhelming the health care system, and how to minimize the societal damage caused by substantial disruption of the economy. Data gathered over the past 4 months since the COVID-19 virus emerged as a human pathogen have provided guidance for our decisions going forward. The most widely adopted strategies for dealing with the COVID-19 pandemic to date have involved the epidemiological approach of encouraging good hygiene practices and social distancing, including orders to “shelter in place,” quarantine of high-risk individuals, and isolation of infected individuals. The goal of this epidemiological approach has been to “flatten the curve” by reducing the height of the peak of the infection to avoid overwhelming the health care system and society in general, while buying time to learn more about the disease and find more effective ways to deal with it. However, now that more is known about COVID-19 and the portion of the population that is most at risk for serious adverse outcomes including death, it may be possible to move from a shelter-in-place approach for the entire population to focus on those at most risk and thus facilitate a gradual and rational phased reduction of social restrictions to reopen the economy. Such a graduated opening would be based on regions of countries meeting specific criteria in terms of being able to contain the virus, coupled with vigorous monitoring to look for outbreaks, followed by case monitoring, isolation of infected individuals and quarantine of exposed individuals, and increased use of testing for active disease as well as for immunity. Taking the data on high-risk individuals into account would allow for a gradual lifting of restrictions on the majority of the population while maintaining more stringent safeguards to protect the vulnerable portion of the population. Nevertheless, the entire population would need to continue to practice good hygiene and social distancing while simultaneously—and perhaps even more vigorously—focusing on sheltering the vulnerable population until adequate community immunity has been achieved to prevent the spread of the virus, whether that is accomplished through natural exposure alone or with the addition of safe and effective vaccine(s) which may not be available for a year. Continued widespread testing for antibodies will help determine how far or close this country is—and other countries are—from developing effective community immunity.

J Psychiatr Pract2020       LitCov and CORD-19
1949Characteristics of SARS-CoV-2 positive cases beyond health-care professionals or social and health-care facilities  

BACKGROUND: During the outbreak of SARS-CoV-2 in Italy, infection among health-care professionals and in the context of welfare and health-care facilities was a significant concern. It is known that the elderly or those with concomitant pathologies are at greater risk of a serious evolution of the disease if affected by COVID-19 and that health workers are a category with greater exposure to SARS-CoV-2 infection. Until now, there has been little information on the epidemiological features and transmission dynamics of the COVID-19 outbreak which did not involve health-care professionals or social and health-care facilities. For this reason, this paper aims to describe the epidemiological characteristics of SARS-CoV-2 infection in the general population outside these semi-closed communities. METHODS: The study was designed by analyzing the data of the 1371 SARS-CoV-2 positive subjects observed in Sardinia up to 9 July, 2020 and whose data were available in the public health department. Statistical analysis and graphic representation were performed using STATA and Adobe Illustrator, respectively. RESULTS: Of the positive cases analyzed, 323 (23.5%) are health-care workers and 563 (41.1%) reside in social or health-care facilities. The number of positive cases among the general population (subjects who do not belong to these semi-closed communities), is 399 (29.1%), 208 females and 191 males. The estimated Case Fatality Rate stands at 5.0%, which is almost half the rate reported for all the SARS-CoV-2 positive cases (9.8%). The geographical distribution of positive cases differs considerably from the distribution of the totality of cases in Sardinia. CONCLUSIONS: This review provides an insight into the COVID-19 situation in the general community, ie not involving health-care professionals or social and health-care facilities. Understanding the evolving epidemiology and transmission dynamics of the outbreak outside of these semi-closed communities would provide appropriate information to guide intervention policy. The COVID-19 pandemic has exacerbated the vulnerability of our health-care system. Severe disruptions in care, medicine shortages and unequal access to health-care are but a few examples of the challenges faced by people living in Italy and Europe, highlighting the importance of evidence-based approaches in supporting the development of prevention and response strategies for future pandemics.

BMC Public Health2021       LitCov and CORD-19
1950More than 50 long-term effects of COVID-19: a systematic review and meta-analysis  

COVID-19 can involve persistence, sequelae, and other medical complications that last weeks to months after initial recovery. This systematic review and meta-analysis aims to identify studies assessing the long-term effects of COVID-19. LitCOVID and Embase were searched to identify articles with original data published before the 1st of January 2021, with a minimum of 100 patients. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. PRISMA guidelines were followed. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included (age 17–87 years). The included studies defined long-COVID as ranging from 14 to 110 days post-viral infection. It was estimated that 80% of the infected patients with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). Multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.

Sci Rep2021       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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