\ 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
3101Mobile Health Apps on COVID-19 Launched in the Early Days of the Pandemic: Content Analysis and Review  

BACKGROUND: Mobile health (mHealth) app use is a major concern because of the possible dissemination of misinformation that could harm the users. Particularly, it can be difficult for health care professionals to recommend a suitable app for coronavirus disease (COVID-19) education and self-monitoring purposes. OBJECTIVE: This study aims to analyze and evaluate the contents as well as features of COVID-19 mobile apps. The findings are instrumental in helping health care professionals to identify suitable mobile apps for COVID-19 self-monitoring and education. The results of the mobile apps’ assessment could potentially help mobile app developers improve or modify their existing mobile app designs to achieve optimal outcomes. METHODS: The search for the mHealth apps available in the android-based Play Store and the iOS-based App Store was conducted between April 18 and May 5, 2020. The region of the App Store where we performed the search was the United States, and a virtual private network app was used to locate and access COVID-19 mobile apps from all countries on the Google Play Store. The inclusion criteria were apps that are related to COVID-19 with no restriction in language type. The basic features assessment criteria used for comparison were the requirement for free subscription, internet connection, education or advisory content, size of the app, ability to export data, and automated data entry. The functionality of the apps was assessed according to knowledge (information on COVID-19), tracing or mapping of COVID-19 cases, home monitoring surveillance, online consultation with a health authority, and official apps run by health authorities. RESULTS: Of the 223 COVID-19–related mobile apps, only 30 (19.9%) found in the App Store and 28 (44.4%) in the Play Store matched the inclusion criteria. In the basic features assessment, most App Store (10/30, 33.3%) and Play Store (10/28, 35.7%) apps scored 4 out of 7 points. Meanwhile, the outcome of the functionality assessment for most App Store apps (13/30, 43.3%) was a score of 3 compared to android-based apps (10/28, 35.7%), which scored 2 (out of the maximum 5 points). Evaluation of the basic functions showed that 75.0% (n=36) of the 48 included mobile apps do not require a subscription, 56.3% (n=27) provide symptom advice, and 41.7% (n=20) have educational content. In terms of the specific functions, more than half of the included mobile apps are official mobile apps maintained by a health authority for COVID-19 information provision. Around 37.5% (n=18) and 31.3% (n=15) of the mobile apps have tracing or mapping and home monitoring surveillance functions, respectively, with only 17% (n=8) of the mobile apps equipped with an online consultation function. CONCLUSIONS: Most iOS-based apps incorporate infographic mapping of COVID-19 cases, while most android-based apps incorporate home monitoring surveillance features instead of providing focused educational content on COVID-19. It is important to evaluate the contents and features of COVID-19 mobile apps to guide users in choosing a suitable mobile app based on their requirements.

JMIR Mhealth Uhealth2020       LitCov and CORD-19
3102Neurological complications of coronavirus infection; a comparative review and lessons learned during the COVID-19 pandemic  

INTRODUCTION: Coronavirus disease-19 (COVID-19) pandemic continues to grow all over the world. Several studies have been performed, focusing on understanding the acute respiratory syndrome and treatment strategies. However, there is growing evidence indicating neurological manifestations occur in patients with COVID-19. Similarly, the other coronaviruses (CoV) epidemics; severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) have been associated with neurological complications. METHODS: This systematic review serves to summarize available information regarding the potential effects of different types of CoV on the nervous system and describes the range of clinical neurological complications that have been reported thus far in COVID-19. RESULTS: Two hundred and twenty-five studies on CoV infections associated neurological manifestations in human were reviewed. Of those, 208 articles were pertinent to COVID-19. The most common neurological complaints in COVID-19 were anosmia, ageusia, and headache, but more serious complications, such as stroke, impairment of consciousness, seizures, and encephalopathy, have also been reported. CONCLUSION: There are several similarities between neurological complications after SARS-CoV-1, MERS-CoV and COVID-19, however, the scope of the epidemics and number of patients are very different. Reports on the neurological complications after and during COVID-19 are growing on a daily basis. Accordingly, comprehensive knowledge of these complications will help health care providers to be attentive to these complications and diagnose and treat them timely.

J Neurol Sci2020       LitCov and CORD-19
3103Myopericarditis After the Pfizer Messenger Ribonucleic Acid Coronavirus Disease Vaccine in Adolescents  

Reports have emerged of myocarditis and pericarditis predominantly after the second dose of the coronavirus disease messenger ribonucleic acid vaccine. We describe 13 patients aged 12-17 years who presented with chest pain within 1 week after their second dose of the Pfizer vaccine and were found to have elevated serum troponin levels and evidence of myopericarditis.

J Pediatr2021       LitCov and CORD-19
3104Geographical tracking and mapping of coronavirus disease COVID-19/SARS-CoV-2 epidemic and associated events around the world: how 21st century GIS technologies are supporting the global fight against outbreaks and epidemics  

In December 2019, a new virus (initially called ‘Novel Coronavirus 2019-nCoV’ and later renamed to SARS-CoV-2) causing severe acute respiratory syndrome (coronavirus disease COVID-19) emerged in Wuhan, Hubei Province, China, and rapidly spread to other parts of China and other countries around the world, despite China’s massive efforts to contain the disease within Hubei. As with the original SARS-CoV epidemic of 2002/2003 and with seasonal influenza, geographic information systems and methods, including, among other application possibilities, online real-or near-real-time mapping of disease cases and of social media reactions to disease spread, predictive risk mapping using population travel data, and tracing and mapping super-spreader trajectories and contacts across space and time, are proving indispensable for timely and effective epidemic monitoring and response. This paper offers pointers to, and describes, a range of practical online/mobile GIS and mapping dashboards and applications for tracking the 2019/2020 coronavirus epidemic and associated events as they unfold around the world. Some of these dashboards and applications are receiving data updates in near-real-time (at the time of writing), and one of them is meant for individual users (in China) to check if the app user has had any close contact with a person confirmed or suspected to have been infected with SARS-CoV-2 in the recent past. We also discuss additional ways GIS can support the fight against infectious disease outbreaks and epidemics.

Int J Health Geogr2020       LitCov and CORD-19
3105Estimation of US SARS-CoV-2 Infections, Symptomatic Infections, Hospitalizations and Deaths Using Seroprevalence Surveys  

IMPORTANCE: Estimates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease burden are needed to help guide interventions. OBJECTIVE: To estimate the number of SARS-CoV-2 infections, symptomatic infections, hospitalizations, and deaths in the US as of November 15, 2020. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study of respondents of all ages, data from 4 regional and 1 nationwide Centers for Disease Control and Prevention (CDC) seroprevalence surveys (April [n = 16 596], May, June, and July [n = 40 817], and August [n = 38 355]) were used to estimate infection underreporting multipliers and symptomatic underreporting multipliers. Community serosurvey data from randomly selected members of the general population were also used to validate the underreporting multipliers. MAIN OUTCOMES AND MEASURES: SARS-CoV-2 infections, symptomatic infections, hospitalizations, and deaths. The median of underreporting multipliers derived from the 5 CDC seroprevalence surveys in the 10 states that participated in 2 or more surveys were applied to surveillance data of reported coronavirus disease 2019 (COVID-19) cases for 5 respective time periods to derive estimates of SARS-CoV-2 infections and symptomatic infections, which were summed to estimate SARS-CoV-2 infections and symptomatic infections in the US. Estimates of infections and symptomatic infections were combined with estimates of the hospitalization ratio and fatality ratio to derive estimates of SARS-CoV-2 hospitalizations and deaths. External validity of the surveys was evaluated with the April CDC survey by comparing results to 5 serosurveys (n = 22 118) that used random sampling of the general population. Internal validity of the multipliers from the 10 specific states was assessed in the August CDC survey by comparing multipliers from the 10 states to all states. A sensitivity analysis was conducted using the interquartile range of the multipliers to derive a high and low estimate of SARS-CoV-2 infections and symptomatic infections. The underreporting multipliers were then used to adjust the reported COVID-19 infections to estimate the full SARS-COV-2 disease burden. RESULTS: Adjusting reported COVID-19 infections using underreporting multipliers derived from CDC seroprevalence studies in April (n = 16 596), May (n = 14 291), June (n = 14 159), July (n = 12 367), and August (n = 38 355), there were estimated medians of 46 910 006 (interquartile range [IQR], 38 192 705-60 814 748) SARS-CoV-2 infections, 28 122 752 (IQR, 23 014 957–36 438 592) symptomatic infections, 956 174 (IQR, 782 509–1 238 912) hospitalizations, and 304 915 (IQR, 248 253–395 296) deaths in the US through November 15, 2020. An estimated 14.3% (IQR, 11.6%-18.5%) of the US population were infected by SARS-CoV-2 as of mid-November 2020. CONCLUSIONS AND RELEVANCE: The SARS-CoV-2 disease burden may be much larger than reported COVID-19 cases owing to underreporting. Even after adjusting for underreporting, a substantial gap remains between the estimated proportion of the population infected and the proportion infected required to reach herd immunity. Additional seroprevalence surveys are needed to monitor the pandemic, including after the introduction of safe and efficacious vaccines.

JAMA Netw Open2021       LitCov and CORD-19
3106Virtual screening and molecular dynamics study of approved drugs as inhibitors of spike protein S1 domain and ACE2 interaction in SARS-CoV-2  

BACKGROUND: The receptor binding domain (RBD) of spike protein S1 domain SARS-CoV-2 plays a key role in the interaction with ACE2, which leads to subsequent S2 domain mediated membrane fusion and incorporation of viral RNA into host cells. In this study we tend to repurpose already approved drugs as inhibitors of the interaction between S1-RBD and the ACE2 receptor. METHODS: 2456 approved drugs were screened against the RBD of S1 protein of SARS-CoV-2 (target PDB ID: 6M17). As the interacting surface between S1-RBD and ACE2 comprises of bigger region, the interacting surface was divided into 3 sites on the basis of interactions (site 1, 2 and 3) and a total of 5 grids were generated (site 1, site 2, site 3, site 1+site 2 and site 2+site 3). A virtual screening was performed using GLIDE implementing HTVS, SP and XP screening. The top hits (on the basis of docking score) were further screened for MM-GBSA. All the top hits were further evaluated in molecular dynamics studies. Performance of the virtual screening protocol was evaluated using enrichment studies. RESULT: and discussion: We performed 5 virtual screening against 5 grids generated. A total of 42 compounds were identified after virtual screening. These drugs were further assessed for their interaction dynamics in molecular dynamics simulation. On the basis of molecular dynamics studies, we come up with 10 molecules with favorable interaction profile, which also interacted with physiologically important residues (residues taking part in the interaction between S1-RBD and ACE2. These are antidiabetic (acarbose), vitamins (riboflavin and levomefolic acid), anti-platelet agents (cangrelor), aminoglycoside antibiotics (Kanamycin, amikacin) bronchodilator (fenoterol), immunomodulator (lamivudine), and anti-neoplastic agents (mitoxantrone and vidarabine). However, while considering the relative side chain fluctuations when compared to the S1-RBD: ACE2 complex riboflavin, fenoterol, cangrelor and vidarabine emerged out as molecules with prolonged relative stability. CONCLUSION: We identified 4 already approved drugs (riboflavin, fenoterol, cangrelor and vidarabine) as possible agents for repurposing as inhibitors of S1:ACE2 interaction. In-vitro validation of these findings are necessary for identification of a safe and effective inhibitor of S1: ACE2 mediated entry of SARS-CoV-2 into the host cell.

J Mol Graph Model2020       LitCov and CORD-19
3107Poor Antibody Response to BioNTech/Pfizer COVID-19 Vaccination in SARS-CoV-2-Naive Residents of Nursing Homes  

BACKGROUND: Residents of nursing homes (NH) are at high risk of COVID-19 related morbidity and death and may respond poorly to vaccination because of old age and frequent comorbidities. METHODS: Seventy-eight residents and 106 staff members, naïve or previously infected with SARS-CoV-2, were recruited in NH in Belgium before immunization with two doses of 30µg BNT162b2 mRNA vaccine at day 0 and day 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD), spike domains S1 and S2, RBD Ab avidity, and neutralizing Ab against SARS-CoV-2 wild type and B.1.351 were assessed at days 0, 21, 28, and 49. RESULTS: SARS-CoV-2 naïve residents had lower Ab responses to BNT162b2 mRNA vaccination than naïve staff. These poor responses involved lower levels of IgG to all spike domains, lower avidity of RBD IgG, and lower levels of Ab neutralizing the vaccine strain. No naïve resident had detectable neutralizing Ab to the B.1.351 variant. In contrast, SARS-CoV-2 infected residents had high responses to mRNA vaccination, with Ab levels comparable to infected staff. Cluster analysis revealed that poor vaccine responders not only included naïve residents but also naïve staff, emphasizing the heterogeneity of responses to mRNA vaccination in the general population. CONCLUSIONS: The poor Ab responses to mRNA vaccination observed in infection naïve residents and in some naïve staff members of NH suggest suboptimal protection against breakthrough infection, especially with variants of concern. These data support the administration of a third dose of mRNA vaccine to further improve protection of NH residents against COVID-19.

Clin Infect Dis2021       LitCov and CORD-19
3108Symptomatic Acute Myocarditis in 7 Adolescents After Pfizer-BioNTech COVID-19 Vaccination  

N/A

Pediatrics2021       LitCov and CORD-19
3109A Case of Myocarditis Presenting With a Hyperechoic Nodule After the First Dose of COVID-19 mRNA Vaccine  

Myocarditis and/or pericarditis have been reported as adverse events following coronavirus disease 2019 (COVID-19) messenger RNA vaccination, with most cases occurring within 1 week after the second dose. We report a rare case of myocarditis after the first dose of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in a 17-year-old boy. Here, we describe the laboratory, electrocardiographic, and imaging findings of myocarditis.

J Korean Med Sci2022       LitCov and CORD-19
3110Associations between body-mass index and COVID-19 severity in 6·9 million people in England: a prospective, community-based, cohort study  

BACKGROUND: Obesity is a major risk factor for adverse outcomes after infection with SARS-CoV-2. We aimed to examine this association, including interactions with demographic and behavioural characteristics, type 2 diabetes, and other health conditions. METHODS: In this prospective, community-based, cohort study, we used de-identified patient-level data from the QResearch database of general practices in England, UK. We extracted data for patients aged 20 years and older who were registered at a practice eligible for inclusion in the QResearch database between Jan 24, 2020 (date of the first recorded infection in the UK) and April 30, 2020, and with available data on BMI. Data extracted included demographic, clinical, clinical values linked with Public Health England's database of positive SARS-CoV-2 test results, and death certificates from the Office of National Statistics. Outcomes, as a proxy measure of severe COVID-19, were admission to hospital, admission to an intensive care unit (ICU), and death due to COVID-19. We used Cox proportional hazard models to estimate the risk of severe COVID-19, sequentially adjusting for demographic characteristics, behavioural factors, and comorbidities. FINDINGS: Among 6 910 695 eligible individuals (mean BMI 26·78 kg/m(2) [SD 5·59]), 13 503 (0·20%) were admitted to hospital, 1601 (0·02%) to an ICU, and 5479 (0·08%) died after a positive test for SARS-CoV-2. We found J-shaped associations between BMI and admission to hospital due to COVID-19 (adjusted hazard ratio [HR] per kg/m(2) from the nadir at BMI of 23 kg/m(2) of 1·05 [95% CI 1·05–1·05]) and death (1·04 [1·04–1·05]), and a linear association across the whole BMI range with ICU admission (1·10 [1·09–1·10]). We found a significant interaction between BMI and age and ethnicity, with higher HR per kg/m(2) above BMI 23 kg/m(2) for younger people (adjusted HR per kg/m(2) above BMI 23 kg/m(2) for hospital admission 1·09 [95% CI 1·08–1·10] in 20–39 years age group vs 80–100 years group 1·01 [1·00–1·02]) and Black people than White people (1·07 [1·06–1·08] vs 1·04 [1·04–1·05]). The risk of admission to hospital and ICU due to COVID-19 associated with unit increase in BMI was slightly lower in people with type 2 diabetes, hypertension, and cardiovascular disease than in those without these morbidities. INTERPRETATION: At a BMI of more than 23 kg/m(2), we found a linear increase in risk of severe COVID-19 leading to admission to hospital and death, and a linear increase in admission to an ICU across the whole BMI range, which is not attributable to excess risks of related diseases. The relative risk due to increasing BMI is particularly notable people younger than 40 years and of Black ethnicity. FUNDING: NIHR Oxford Biomedical Research Centre.

Lancet Diabetes Endocrinol2021       LitCov and CORD-19
3111A new hybrid ensemble machine-learning model for severity risk assessment and post-COVID prediction system  

N/A

Math Biosci Eng2022       LitCov and CORD-19
3112Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score  

OBJECTIVE: To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19). DESIGN: Prospective observational cohort study. SETTING: International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium—ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020. PARTICIPANTS: Adults (age ≥18 years) admitted to hospital with covid-19 at least four weeks before final data extraction. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: 35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73). CONCLUSIONS: An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations. STUDY REGISTRATION: ISRCTN66726260

BMJ2020       LitCov and CORD-19
3113COVID-Related Victimization, Racial Bias and Employment and Housing Disruption Increase Mental Health Risk Among US Asian, Black and Latinx Adults  

Background: The mental health of racial/ethnic minorities in the U.S. has been disproportionately impacted by the COVID-19 pandemic. This study examined the extent to which disruptions in employment and housing, coronavirus-specific forms of victimization and racial bias independently and conjointly contributed to mental health risk among Asian, Black, and Latinx adults in the United States during the pandemic. Methods: This study reports on data from 401 Asian, Black, and Latinx adults (age 18–72) who participated in a larger national online survey conducted from October 2020–June 2021, Measures included financial and health information, housing disruptions and distress in response to employment changes, coronavirus related victimization distress and perceived increases in racial bias, depression and anxiety. Results: Asian participants had significantly higher levels of COVID-related victimization distress and perceived increases in racial bias than Black and Latinx. Young adults (<26 years old) were more vulnerable to depression, anxiety, and coronavirus victimization distress than older respondents. Having at least one COVID-related health risk, distress in response to changes in employment and housing disruptions, pandemic related victimization distress and perceived increases in racial bias were positively and significantly related to depression and anxiety. Structural equation modeling indicated COVID-related increases in racial bias mediated the effect of COVID-19 related victimization distress on depression and anxiety. Conclusions: COVID-19 has created new pathways to mental health disparities among racial/ethnic minorities in the U.S. by exacerbating existing structural and societal inequities linked to race. Findings highlight the necessity of mental health services sensitive to specific challenges in employment and housing and social bias experienced by people of color during the current and future health crises.

Front Public Health2021       LitCov and CORD-19
3114Neuropathology of patients with COVID-19 in Germany: a post-mortem case series  

BACKGROUND: Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. METHODS: In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions. FINDINGS: 43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70–86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes. INTERPRETATION: In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included. FUNDING: German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).

Lancet Neurol2020       LitCov and CORD-19
3115Head-to-head performance comparison of self-collected nasal vs professional-collected nasopharyngeal swab for a WHO-listed SARS-CoV-2 antigen-detecting rapid diagnostic test  

In 2020, the World Health Organization (WHO) recommended two SARS-CoV-2 lateral flow antigen-detecting rapid diagnostics tests (Ag-RDTs), both initially with nasopharyngeal (NP) sample collection. Independent head-to-head studies are necessary for SARS-CoV-2 Ag-RDT nasal sampling to demonstrate comparability of performance with nasopharyngeal (NP) sampling. We conducted a head-to-head comparison study of a supervised, self-collected nasal mid-turbinate (NMT) swab and a professional-collected NP swab, using the Panbio™ Ag-RDT (distributed by Abbott). We calculated positive and negative percent agreement between the sampling methods as well as sensitivity and specificity for both sampling techniques compared to the reference standard reverse transcription polymerase chain reaction (RT-PCR). A SARS-CoV-2 infection could be diagnosed by RT-PCR in 45 of 290 participants (15.5%). Comparing the NMT and NP sampling the positive percent agreement of the Ag-RDT was 88.1% (37/42 PCR positives detected; CI 75.0–94.8%). The negative percent agreement was 98.8% (245/248; CI 96.5–99.6%). The overall sensitivity of Panbio with NMT sampling was 84.4% (38/45; CI 71.2–92.3%) and 88.9% (40/45; CI 76.5–95.5%) with NP sampling. Specificity was 99.2% (243/245; CI 97.1–99.8%) for both, NP and NMT sampling. The sensitivity of the Panbio test in participants with high viral load (> 7 log(10) SARS-CoV-2 RNA copies/mL) was 96.3% (CI 81.7–99.8%) for both, NMT and NP sampling. For the Panbio supervised NMT self-sampling yields comparable results to NP sampling. This suggests that nasal self-sampling could be used for to enable scaled-up population testing. Clinical Trial DRKS00021220. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00430-021-00710-9.

Med Microbiol Immunol2021       LitCov and CORD-19
3116The impacts of the COVID-19 outbreak on emergency department visits of surgical patients  

N/A

Ulus Travma Acil Cerrahi Derg2020       LitCov and CORD-19
3117One Year of COVID-19 in Brazil: A Political and Social Overview  

BACKGROUND: Coronavirus Disease 2019 (COVID-19) became the deadliest pandemic of the new millennium. One year after it became a pandemic, the current COVID-19 situation in Brazil is an example of how the impacts of a pandemic are beyond health outcomes and how health, social, and political actions are intertwined. OBJECTIVES: We aimed to provide an overview of the first year of the COVID-19 pandemic in Brazil, from a social and political point of view, and to discuss the perspectives from now on. METHODS: This is a narrative review using official, scientific (PubMed, Medline, and SciELO databases) and publicly available data. Press articles were also used that contain important information not found in these databases. FINDINGS: We address the impacts of COVID-19 in different regions of Brazil, on indigenous populations, health care workers, and how internal social contrasts impacted the pandemics advance across the country. We also discuss key points that culminated in the countrys failed management of the COVID-19 spread, such as poor management of the public health care system, disparities between public and private health care infrastructure, lack of mass testing and viral spread tracking, lack of preparedness and planning to implement strict isolation and social distancing measures, and, most importantly, political instability, a deteriorating Health Ministry and sabotaging attitudes of the countrys president, including anti-scientific actions, underplaying COVID-19 severity, spreading and powering fake news about the pandemic, promoting knowingly inefficient medications for COVID-19 treatment, and interference in collective health policies, including the countrys vaccination plan. CONCLUSIONS: After one year of COVID-19 and a disastrous management of the disease, Brazil has more than 11 million cases, 270,000 deaths, and the highest number of daily deaths due to COVID-19 in the world, most of which could have been avoided and can be credited to negligence of municipal, state, and federal authorities, especially President Jair Messias Bolsonaro. Unfortunately, the country is an example of what not to do in a pandemic setting. KEY POINTS: One year after COVID-19 was declared a pandemic, Brazil had the second higher number of cases and deaths, and the highest number of daily deaths due to the disease. Lack of massive testing, non-stringent and ineffective collective health policies, poor management of the public health care system, and political instability were the main drivers of the countrys flawed management of the COVID-19 advancement. Anti-science and sabotaging actions by government had a pivotal role in the countrys current situation. Brazil has a large territory and is marked by social contrasts among different regions and states, which showed contrasting data regarding the impact caused by COVID-19. COVID-19 databases and data sharing are important to provide an overview of epidemiological aspects of the disease; however, Brazil lacks standardization in these datasets.

Ann Glob Health2021       LitCov and CORD-19
3118Household Transmission of SARS-CoV-2: A Systematic Review and Meta-analysis  

IMPORTANCE: Crowded indoor environments, such as households, are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVES: To examine evidence for household transmission of SARS-CoV-2, disaggregated by several covariates, and to compare it with other coronaviruses. DATA SOURCE: PubMed, searched through October 19, 2020. Search terms included SARS-CoV-2 or COVID-19 with secondary attack rate, household, close contacts, contact transmission, contact attack rate, or family transmission. STUDY SELECTION: All articles with original data for estimating household secondary attack rate were included. Case reports focusing on individual households and studies of close contacts that did not report secondary attack rates for household members were excluded. DATA EXTRACTION AND SYNTHESIS: Meta-analyses were done using a restricted maximum-likelihood estimator model to yield a point estimate and 95% CI for secondary attack rate for each subgroup analyzed, with a random effect for each study. To make comparisons across exposure types, study was treated as a random effect, and exposure type was a fixed moderator. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. MAIN OUTCOMES AND MEASURES: Secondary attack rate for SARS-CoV-2, disaggregated by covariates (ie, household or family contact, index case symptom status, adult or child contacts, contact sex, relationship to index case, adult or child index cases, index case sex, number of contacts in household) and for other coronaviruses. RESULTS: A total of 54 relevant studies with 77 758 participants reporting household secondary transmission were identified. Estimated household secondary attack rate was 16.6% (95% CI, 14.0%-19.3%), higher than secondary attack rates for SARS-CoV (7.5%; 95% CI, 4.8%-10.7%) and MERS-CoV (4.7%; 95% CI, 0.9%-10.7%). Household secondary attack rates were increased from symptomatic index cases (18.0%; 95% CI, 14.2%-22.1%) than from asymptomatic index cases (0.7%; 95% CI, 0%-4.9%), to adult contacts (28.3%; 95% CI, 20.2%-37.1%) than to child contacts (16.8%; 95% CI, 12.3%-21.7%), to spouses (37.8%; 95% CI, 25.8%-50.5%) than to other family contacts (17.8%; 95% CI, 11.7%-24.8%), and in households with 1 contact (41.5%; 95% CI, 31.7%-51.7%) than in households with 3 or more contacts (22.8%; 95% CI, 13.6%-33.5%). CONCLUSIONS AND RELEVANCE: The findings of this study suggest that given that individuals with suspected or confirmed infections are being referred to isolate at home, households will continue to be a significant venue for transmission of SARS-CoV-2.

JAMA Netw Open2020       LitCov and CORD-19
3119Resistance of SARS-CoV-2 Omicron BA.1 and BA.2 Variants to Vaccine-Elicited Sera and Therapeutic Monoclonal Antibodies  

N/A

Viruses2022       LitCov
3120Mental health and well-being during the COVID-19 pandemic: longitudinal analyses of adults in the UK COVID-19 Mental Health & Wellbeing study  

BACKGROUND: The effects of coronavirus disease 2019 (COVID-19) on the population's mental health and well-being are likely to be profound and long lasting. AIMS: To investigate the trajectory of mental health and well-being during the first 6 weeks of lockdown in adults in the UK. METHOD: A quota survey design and a sampling frame that permitted recruitment of a national sample was employed. Findings for waves 1 (31 March to 9 April 2020), 2 (10 April to 27 April 2020) and 3 (28 April to 11 May 2020) are reported here. A range of mental health factors was assessed: pre-existing mental health problems, suicide attempts and self-harm, suicidal ideation, depression, anxiety, defeat, entrapment, mental well-being and loneliness. RESULTS: A total of 3077 adults in the UK completed the survey at wave 1. Suicidal ideation increased over time. Symptoms of anxiety, and levels of defeat and entrapment decreased across waves whereas levels of depressive symptoms did not change significantly. Positive well-being also increased. Levels of loneliness did not change significantly over waves. Subgroup analyses showed that women, young people (18–29 years), those from more socially disadvantaged backgrounds and those with pre-existing mental health problems have worse mental health outcomes during the pandemic across most factors. CONCLUSIONS: The mental health and well-being of the UK adult population appears to have been affected in the initial phase of the COVID-19 pandemic. The increasing rates of suicidal thoughts across waves, especially among young adults, are concerning.

Br J Psychiatry2020       LitCov and CORD-19
3121Exploration of the impact of the COVID-19 pandemic on the mental health of home Healthcare workers in Japan: a multicenter cross-sectional web-based survey  

BACKGROUND: The COVID-19 pandemic has caused home health care workers (home-HCWs) to experience anxiety. The mental health of home-HCWs and related factors during the COVID-19 pandemic have not been clarified; therefore, we aimed to investigate the status and associated factors of fear of COVID-19 infection, anxiety, and depression among home-HCWs in Japan. METHODS: We conducted a multicenter cross-sectional web-based anonymous survey of home-HCWs in August 2021, during the fifth wave of the pandemic in Japan. We surveyed members of facilities that provided home visit services during the COVID-19 pandemic. We measured the Japanese version of the Fear of COVID-19 scale (FCV-19S-J) and the Hospital Anxiety and Depression scale (HADS) as objective variables, and the Japanese version of the Assessment of Interprofessional Team Collaboration Scale-II (J-AITCS-II) as an explanatory variable. RESULTS: A total of 328 members of 37 facilities responded to the survey, and we ultimately analyzed 311 participants. The most frequent occupation was nurse (32.8%), followed by doctor (24.8%) and medical office staff (18.0%). The mean score of the FCV-19S-J was 16.5 ± 5.0 (7.0 – 31.0), and the prevalences of definitive anxiety and depression were 7.4% and 15.7%, respectively. Multivariate regression analysis revealed that the J-AITCS-II teamwork subscale was significantly negatively associated with FCV-19S-J, HADS-anxiety, and HADS-depression (β = -0.171, p = 0.004; β = -0.151, p = 0.012; β = -0.225, p < 0.001, respectively). Medical office staff showed significant positive associations with FCV-19S-J and HADS-depression (β = 0.219, p = 0.005; β = 0.201, p = 0.009, respectively), and medical social workers with HADS-anxiety and HADS-depression (β = -0.166, p = 0.011; β = -0.214, p < 0.001, respectively) compared with doctors. The unmet support need for expert lectures on COVID-19 was significantly positively associated with FCV-19S-J (β = 0.131, p = 0.048), and the unmet support need for support systems for psychological stress and emotional exhaustion was significantly positively associated with HADS-anxiety (β = 0.141, p = 0.022). CONCLUSIONS: Fear of COVID-19 infection and depression of nurses, medical office staff, and other occupations was significantly higher than those of doctors. These findings suggest that non-physicians were more likely to be fearful and depressed during the COVID-19 pandemic; thus, it is necessary to tailor mental health support based on occupation in the home care setting.

BMC Prim Care2022       LitCov and CORD-19
3122Assessment of air pollution status during COVID-19 lockdown (March-May 2020) over Bangalore City in India  

The coronavirus disease 2019 (COVID-19), which became a global pandemic by March 2020, forced almost all countries over the world to impose the lockdown as a measure of social distancing to control the spread of infection. India also strictly implemented a countrywide lockdown, starting from 24 March to 12 May 2020. This measure resulted in the reduction of the sources of air pollution in general: industrial, commercial, and vehicular pollution in particular, with visible improvement in ambient air quality. In this study, the impact of COVID-19 lockdown on the ambient concentration of air pollutants over the city of Bangalore (India) is assessed using Continuous Ambient Air Quality Measurement (CAAQM) data from 10 monitoring stations spread across the city. The data was obtained from Central Pollution Control Board (CPCB) and Karnataka State Pollution Control Board (KSPCB). The analysis of the relative changes in the ambient concentration of six major air pollutants (NO, NO(2), NO(X), PM(2.5), O(3), and SO(2)) has been carried out for two periods: March–May 2020 (COVID-19 lockdown) and the corresponding period of 2019 during when there was no lockdown. The analysis revealed significant reduction in the concentration of ambient air pollutants at both daily and monthly intervals. This can be attributed to the reduction in sources of emission; vehicular traffic, industrial, and other activities. The average reduction in the concentration of NO, NO(2), NO(X), PM(2.5), and O(3) between 01 March and 12 May 2020 was found to be 63%, 48%, 48%, 18%, and 23% respectively when compared to the same period in 2019. Similarly, the comparative analysis of pollutant concentrations between pre-lockdown (01–23 March 2020) and lockdown (24 March–12 May 2020) periods has shown a huge reduction in the ambient concentration of air pollutants, 47.3% (NO), 49% (NO(2)), 49% (NO(X)), 10% (SO(2)), 37.7% (PM(2.5)), and 15.6% (O(3)), resulting in improved air quality over Bangalore during the COVID-19 lockdown period. It is shown that the strict lockdown resulted in a significant reduction in the pollution levels. Such lockdowns may be useful as emergency intervention strategies to control air pollution in megacities when ambient air quality deteriorates dangerously.

Environ Monit Assess2021       LitCov and CORD-19
3123Characteristics of Ocular Findings of Patients With COVID-19 in Hubei Province, China  

IMPORTANCE: While the outbreak of coronavirus disease 2019 (COVID-19) has resulted in more than 100 000 infected individuals in China and worldwide, there are few reports on the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with ocular abnormalities. Understanding ocular manifestations of patients with COVID-19 by ophthalmologists and others may facilitate the diagnosis and prevention of transmission of the disease. OBJECTIVE: To investigate ocular manifestations and viral prevalence in the conjunctiva of patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In this case series, patients with COVID-19 treated from February 9 to 15, 2020, at a hospital center in Hubei province, China, were retrospectively reviewed for ocular manifestations. During the period of treatment, the ocular signs and symptoms as well as results of blood tests and reverse transcriptase–polymerase chain reaction (RT-PCR) from nasopharyngeal and conjunctival swabs for SARS-CoV-2 were noted and analyzed. MAIN OUTCOMES AND MEASURES: Ocular signs and symptoms as well as results of blood tests and RT-PCR for SARS-CoV-2. RESULTS: Of the 38 included patients with clinically confirmed COVID-19, 25 (65.8%) were male, and the mean (SD) age was 65.8 (16.6) years. Among them, 28 patients (73.7%) had positive findings for COVID-19 on RT-PCR from nasopharyngeal swabs, and of these, 2 patients (5.2%) yielded positive findings for SARS-CoV-2 in their conjunctival as well as nasopharyngeal specimens. A total of 12 of 38 patients (31.6%; 95% CI, 17.5-48.7) had ocular manifestations consistent with conjunctivitis, including conjunctival hyperemia, chemosis, epiphora, or increased secretions. By univariate analysis, patients with ocular symptoms were more likely to have higher white blood cell and neutrophil counts and higher levels of procalcitonin, C-reactive protein, and lactate dehydrogenase than patients without ocular symptoms. In addition, 11 of 12 patients with ocular abnormalities (91.7%; 95% CI, 61.5-99.8) had positive results for SARS-CoV-2 on RT-PCR from nasopharyngeal swabs. Of these, 2 (16.7%) had positive results for SARS-CoV-2 on RT-PCR from both conjunctival and nasopharyngeal swabs. CONCLUSIONS AND RELEVANCE: In this study, one-third of patients with COVID-19 had ocular abnormalities, which frequently occurred in patients with more severe COVID-19. Although there is a low prevalence of SARS-CoV-2 in tears, it is possible to transmit via the eyes.

JAMA Ophthalmol2020       LitCov and CORD-19
3124Depression, anxiety and stress among Australian nursing and midwifery undergraduate students during the COVID-19 pandemic: a cross-sectional study  

N/A

Int J Nurs Educ Scholarsh2021       LitCov and CORD-19
3125Twin combination of Omicron and Delta variants triggering a tsunami wave of ever high surges in COVID-19 cases: A challenging global threat with a special focus on the Indian subcontinent  

The emergence of Omicron (B.1.1.529) variant of SARS‐CoV‐2 has resulted into a very massive surge in COVID‐19 cases worldwide. Due to continuous emergence of multiple variants of SARS‐CoV‐2, the ongoing pandemic has caused severe morbidity and mortality in last two years. The rate of infectivity of Omicron variant is much higher than Delta variant and in a very quick time Omicron has displaced the Delta variant and now become a dominant variant across the globe. The twin combination of Omicron and Delta variant is triggering a Tsunami wave of ever high surges in COVID‐19 cases worldwide. This article highlights the global threats and challenges posed by Omicron, and strategies to counter it with a particular focus on Indian sub‐continent.

J Med Virol2022       LitCov and CORD-19
3126Viral loads of Delta-variant SARS-CoV-2 breakthrough infections after vaccination and booster with BNT162b2  

N/A

Nat Med2021       LitCov and CORD-19
3127Acute Clinical Syndromes and Suspicion of SARS-CoV-2 Infection: The Experience of a Single Romanian Center in the Early Pandemic Period  

Background and Objectives: During the coronavirus disease 2019 (COVID-19) pandemic, patients with chronic diseases suffering exacerbations have required acute medical care. The purpose of our study was to determine useful criteria for the differentiation of patients with acute clinical syndromes and suspicion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Materials and Methods: This was an observational retrospective study, conducted in an internal medicine clinic from April to May 2020. We collected clinical, biological, and computed tomography (CT) data on patients with exacerbations of chronic diseases and clinical suspicion of SARS-CoV-2 infection. Patients with an already-positive real-time reverse-transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 on presentation at the emergency department were excluded from our study. Results: Of 253 suspected cases, 20 were laboratory-confirmed as having SARS-CoV-2 infection by RT-PCR, whereas COVID-19 diagnosis was ruled out in the remaining 233. Venous thromboembolism (VTE) correlated significantly with COVID-19 diagnosis in suspected patients, while laboratory markers were not significantly different between the two groups. Of the suspected patients, significantly higher percentages of dry cough, fever, myalgias, sore throat, loss of smell and appetite, and ground-glass opacities (GGOs) on CT were found in SARS-CoV-2-positive individuals. Conclusions: The study demonstrated that, until receiving the result of an RT-PCR test for SARS-CoV-2 (usually 12–24 h), association with VTE as a comorbidity, fever, dry cough, and myalgia as clinical features, and GGO on CT are the main markers for the identification of COVID-19 patients among those suspected with acute clinical syndromes. Our results also provide evidence for doctors not to rely solely on biological markers in the case of suspected SARS-CoV-2 infection in patients with exacerbations of chronic diseases. These data are useful for faster decision-making with regard to suspected COVID-19 patients before receiving RT-PCR test results, thus avoiding keeping patients in crowded emergency departments.

Medicina (Kaunas)2021       LitCov and CORD-19
3128SARS-CoV-2: vaccines in the pandemic era  

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused millions of infections and deaths worldwide since its emergence in December 2019. As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs, researchers from the government, academia and industry are developing vaccines at an unprecedented speed to halt the pandemic. In this review, the results of animal experiments and clinical trials on several vaccine technical platforms are summarized, and several challenges are also discussed to further promote the development, evaluation and application of vaccines during the challenging situation of the global pandemic.

Mil Med Res2021       LitCov and CORD-19
3129A Multiplex One-Step RT-qPCR Protocol to Detect SARS-CoV-2 in NP/OP Swabs and Saliva  

Since December 2019, SARS‐CoV‐2 has spread extensively throughout the world, with more than 117 million reported cases and 2.6 million deaths (Johns Hopkins coronavirus resource center, https://coronavirus.jhu.edu/map.html). Detecting the virus is the first step in diagnosing the infection, followed by quarantine to prevent transmission. Nasopharyngeal/oropharyngeal swabs (NP/OP) and saliva are two specimen types that are most often analyzed to detect SARS‐CoV‐2 by molecular tests that detect viral RNA or by antigen/antibody tests that detect viral proteins and/or the host immune response against the virus. Compared to antigen/antibody tests, molecular tests are highly sensitive and specific for detecting the virus. A significant drawback is that specimen collection requirements are specific to each test and cannot be interchanged with another test. Some tests are qualified to be used on NP swabs or saliva, but not both specimen types. Even with NP swabs, a test may be qualified to detect the virus only with swabs collected in viral transport medium (VTM) but not in other media. These restrictive pre‐analytic steps are disadvantageous in that a lab would have to develop and validate different tests for SARS‐CoV‐2 depending on the specimen type and collection media, with added setup cost, infrastructure, and training requirements. To overcome these problems, we developed and validated a cost‐effective multiplex reverse‐transcription real‐time PCR assay that can be used to detect SARS‐CoV‐2 in different specimen types. The assay is highly sensitive and specific, can be used to detect the virus in saliva as well as NP swabs collected in different media such as VTM, saline, and commercial preservative fluid, and serves as one test for all applications. The protocol also describes an optimal laboratory setup and unidirectional workflow for detecting SARS‐CoV‐2 by RT‐qPCR. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Manual viral nucleic acid extraction from NP/OP swabs collected in different media, and from saliva Alternate Protocol 1: Low‐throughput automated extraction on the Qiagen EZ1 Advanced XL machine (1‐14 samples) Alternate Protocol 2: High‐throughput automated extraction on the Kingfisher Flex machine (1‐96 samples) Basic Protocol 2: Multiplex RT‐qPCR protocol to detect SARS‐CoV‐2 Alternate Protocol 3: Multiplex one‐step RT‐qPCR protocol to detect SARS‐CoV‐2 with S and E gene probes labeled with the same fluorochrome

Curr Protoc2021       LitCov and CORD-19
3130Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19  

BACKGROUND: Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (M(pro)) inhibitor with potent pan–human-coronavirus activity in vitro. METHODS: We conducted a phase 2–3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19–related hospitalization or death from any cause through day 28, viral load, and safety were evaluated. RESULTS: A total of 2246 patients underwent randomization; 1120 patients received nirmatrelvir plus ritonavir (nirmatrelvir group) and 1126 received placebo (placebo group). In the planned interim analysis of patients treated within 3 days after symptom onset (modified intention-to treat population, comprising 774 of the 1361 patients in the full analysis population), the incidence of Covid-19–related hospitalization or death by day 28 was lower in the nirmatrelvir group than in the placebo group by 6.32 percentage points (95% confidence interval [CI], −9.04 to −3.59; P<0.001; relative risk reduction, 89.1%); the incidence was 0.77% (3 of 389 patients) in the nirmatrelvir group, with 0 deaths, as compared with 7.01% (27 of 385 patients) in the placebo group, with 7 deaths. Efficacy was maintained in the final analysis involving the 1379 patients in the modified intention-to-treat population, with a difference of −5.81 percentage points (95% CI, −7.78 to −3.84; P<0.001; relative risk reduction, 88.9%). All 13 deaths occurred in the placebo group. The viral load was lower with nirmaltrelvir plus ritonavir than with placebo at day 5 of treatment, with an adjusted mean difference of −0.868 log(10) copies per milliliter when treatment was initiated within 3 days after the onset of symptoms. The incidence of adverse events that emerged during the treatment period was similar in the two groups (any adverse event, 22.6% with nirmatrelvir plus ritonavir vs. 23.9% with placebo; serious adverse events, 1.6% vs. 6.6%; and adverse events leading to discontinuation of the drugs or placebo, 2.1% vs. 4.2%). Dysgeusia (5.6% vs. 0.3%) and diarrhea (3.1% vs. 1.6%) occurred more frequently with nirmatrelvir plus ritonavir than with placebo. CONCLUSIONS: Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns. (Supported by Pfizer; ClinicalTrials.gov number, NCT04960202.)

N Engl J Med2022       LitCov and CORD-19
3131SARS-CoV-2 deregulates the vascular and immune functions of brain pericytes via Spike protein  

Coronavirus disease 19 (COVID-19) is a respiratory illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 pathogenesis causes vascular-mediated neurological disorders via elusive mechanisms. SARS-CoV-2 infects host cells via the binding of viral Spike (S) protein to transmembrane receptor, angiotensin-converting enzyme 2 (ACE2). Although brain pericytes were recently shown to abundantly express ACE2 at the neurovascular interface, their response to SARS-CoV-2 S protein is still to be elucidated. Using cell-based assays, we found that ACE2 expression in human brain vascular pericytes was increased upon S protein exposure. Pericytes exposed to S protein underwent profound phenotypic changes associated with an elongated and contracted morphology accompanied with an enhanced expression of contractile and myofibrogenic proteins, such as α-smooth muscle actin (α-SMA), fibronectin, collagen I, and neurogenic locus notch homolog protein-3 (NOTCH3). On the functional level, S protein exposure promoted the acquisition of calcium (Ca(2+)) signature of contractile ensheathing pericytes characterized by highly regular oscillatory Ca(2+) fluctuations. Furthermore, S protein induced lipid peroxidation, oxidative and nitrosative stress in pericytes as well as triggered an immune reaction translated by activation of nuclear factor-kappa-B (NF-κB) signaling pathway, which was potentiated by hypoxia, a condition associated with vascular comorbidities that exacerbate COVID-19 pathogenesis. S protein exposure combined to hypoxia enhanced the production of pro-inflammatory cytokines involved in immune cell activation and trafficking, namely macrophage migration inhibitory factor (MIF). Using transgenic mice expressing the human ACE2 that recognizes S protein, we observed that the intranasal infection with SARS-CoV-2 rapidly induced hypoxic/ischemic-like pericyte reactivity in the brain of transgenic mice, accompanied with an increased vascular expression of ACE2. Moreover, we found that SARS-CoV-2 S protein accumulated in the intranasal cavity reached the brain of mice in which the nasal mucosa is deregulated. Collectively, these findings suggest that SARS-CoV-2 S protein impairs the vascular and immune regulatory functions of brain pericytes, which may account for vascular-mediated brain damage. Our study provides a better understanding for the mechanisms underlying cerebrovascular disorders in COVID-19, paving the way to develop new therapeutic interventions.

Neurobiol Dis2021       LitCov and CORD-19
3132Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis  

Abstract Introduction We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals. In answering questions raised regarding our study, we updated our database and repeated all analyses. Methods We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first. Results We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%). The median follow-up duration increased from 7 to 14 days. All patients received pharmacological thromboprophylaxis. The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41–57%). The majority of thrombotic events were PE (65/75; 87%). In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091–0.92). Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4–12). Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35–1.8). Conclusion In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

Thromb Res2020       LitCov and CORD-19
3133Determinants of Spike infectivity, processing and neutralization in SARS-CoV-2 Omicron subvariants BA.1 and BA.2  

N/A

Cell Host Microbe2022       LitCov
3134Hematological findings and complications of COVID-19  

COVID‐19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL‐6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID‐19 patients. Elevated D‐Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life‐threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID‐19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.

Am J Hematol2020       LitCov and CORD-19
3135Site-specific glycan analysis of the SARS-CoV-2 spike  

The emergence of the betacoronavirus, SARS-CoV-2, the causative agent of COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.

Science2020       LitCov and CORD-19
3136A Case Report of Immune Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination  

Immune thrombocytopenia (ITP) is an autoimmune condition characterized by platelet destruction through antibody-mediated mechanism. ITP is one of the manifestations of a coronavirus disease, as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several cases of ITP have been described after vaccination with two mRNA-based vaccines—BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)—against SARS-CoV-2. Herein, we report a case of ITP occurring after vaccination with ChAdOx1 adenovirus vector nCoV-19 (AstraZeneca) vaccine in Korea. A 66-year-old woman presented with multiple ecchymoses on both upper and lower extremities and gingival bleeding, appearing 3 days after receiving the first dose of ChAdOx1 nCoV-19. Her laboratory results showed isolated severe thrombocytopenia without evidence of combined coagulopathy. She was diagnosed with ITP and successfully treated with high-dose dexamethasone and intravenous immunoglobulin. Clinical suspicion to identify vaccine-related ITP is important to promptly initiate appropriate treatment.

J Korean Med Sci2021       LitCov and CORD-19
3137SARS-CoV-2-Specific T Cell Responses Are Stronger in Children With Multisystem Inflammatory Syndrome Compared to Children With Uncomplicated SARS-CoV-2 Infection  

BACKGROUND: Despite similar rates of infection, adults and children have markedly different morbidity and mortality related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Compared to adults, children have infrequent severe manifestations of acute infection but are uniquely at risk for the rare and often severe Multisystem Inflammatory Syndrome in Children (MIS-C) following infection. We hypothesized that these differences in presentation are related to differences in the magnitude and/or antigen specificity of SARS-CoV-2-specific T cell (CST) responses between adults and children. We therefore set out to measure the CST response in convalescent adults versus children with and without MIS-C following SARS-CoV-2 infection. METHODS: CSTs were expanded from blood collected from convalescent children and adults post SARS-CoV-2 infection and evaluated by intracellular flow cytometry, surface markers, and cytokine production following stimulation with SARS-CoV-2-specific peptides. Presence of serum/plasma antibody to spike and nucleocapsid was measured using the luciferase immunoprecipitation systems (LIPS) assay. FINDINGS: Twenty-six of 27 MIS-C patients, 7 of 8 non-MIS-C convalescent children, and 13 of 14 adults were seropositive for spike and nucleocapsid antibody. CST responses in MIS-C patients were significantly higher than children with uncomplicated SARS-CoV-2 infection, but weaker than CST responses in convalescent adults. INTERPRETATION: Age-related differences in the magnitude of CST responses suggest differing post-infectious immunity to SARS-CoV-2 in children compared to adults post uncomplicated infection. Children with MIS-C have CST responses that are stronger than children with uncomplicated SARS-CoV-2 infection and weaker than convalescent adults, despite near uniform seropositivity.

Front Immunol2021       LitCov and CORD-19
3138Influence of Health Beliefs on Adherence to COVID-19 Preventative Practices: International, Social Media-Based Survey Study  

BACKGROUND: Health behavior is influenced by culture and social context. However, there are limited data evaluating the scope of these influences on COVID-19 response. OBJECTIVE: This study aimed to compare handwashing and social distancing practices in different countries and evaluate practice predictors using the health belief model (HBM). METHODS: From April 11 to May 1, 2020, we conducted an online, cross-sectional survey disseminated internationally via social media. Participants were adults aged 18 years or older from four different countries: the United States, Mexico, Hong Kong (China), and Taiwan. Primary outcomes were self-reported handwashing and social distancing practices during COVID-19. Predictors included constructs of the HBM: perceived susceptibility, perceived severity, perceived benefits, perceived barriers, self-efficacy, and cues to action. Associations of these constructs with behavioral outcomes were assessed by multivariable logistic regression. RESULTS: We analyzed a total of 71,851 participants, with 3070 from the United States, 3946 from Mexico, 1201 from Hong Kong (China), and 63,634 from Taiwan. Of these countries, respondents from the United States adhered to the most social distancing practices (χ(2)(3)=2169.7, P<.001), while respondents from Taiwan performed the most handwashing (χ(2)(3)=309.8, P<.001). Multivariable logistic regression analyses indicated that self-efficacy was a positive predictor for handwashing (odds ratio [OR](United States) 1.58, 95% CI 1.21-2.07; OR(Mexico) 1.5, 95% CI 1.21-1.96; OR(Hong Kong) 2.48, 95% CI 1.80-3.44; OR(Taiwan) 2.30, 95% CI 2.21-2.39) and social distancing practices (OR(United States) 1.77, 95% CI 1.24-2.49; OR(Mexico) 1.77, 95% CI 1.40-2.25; OR(Hong Kong) 3.25, 95% CI 2.32-4.62; OR(Taiwan) 2.58, 95% CI 2.47-2.68) in all countries. Handwashing was positively associated with perceived susceptibility in Mexico, Hong Kong, and Taiwan, while social distancing was positively associated with perceived severity in the United States, Mexico, and Taiwan. CONCLUSIONS: Social media recruitment strategies can be used to reach a large audience during a pandemic. Self-efficacy was the strongest predictor for handwashing and social distancing. Policies that address relevant health beliefs can facilitate adoption of necessary actions for preventing COVID-19. Our findings may be explained by the timing of government policies, the number of cases reported in each country, individual beliefs, and cultural context.

J Med Internet Res2021       LitCov and CORD-19
3139Effects of Covid-19 Lockdown on Mental Health and Sleep Disturbances in Italy  

Italy was the first European country that entered a nationwide lockdown during the COVID-19 pandemic. Since quarantine can impact on mental health, this study aimed to estimate the prevalence of depressive symptoms, anxiety symptoms and sleeping disturbances in the Italian population during lockdown. The factors that might influence such outcomes were explored. A national cross-sectional survey was performed during the last 14 days of the Italian lockdown. Questionnaires assessed socio-demographics characteristic, behaviors and healthcare access. The outcomes were assessed using Patient Health Questionnaire-2 and Generalized Anxiety Disorder-2. Participants with sleep disturbances completed the Insomnia Severity Index. The sample size was 1515. Depression and anxiety symptom prevalence was 24.7% and 23.2%; 42.2% had sleep disturbances and, among them, 17.4% reported moderate/severe insomnia. Being female, an increased time spent on the internet and an avoidance of activities through peer pressure increased the likelihood of at least one mental health outcome. Increasing age, an absence of work-related troubles and being married or being a cohabitant reduced such a probability. Females and participants with chronic conditions were associated with a higher prevalence of sleep disturbances. It is crucial to study effective interventions, specifically planning strategies, for more vulnerable groups and to consider the role of the internet.

Int J Environ Res Public Healt2020       LitCov and CORD-19
3140Safety, tolerability and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial  

BACKGROUND: A vaccine against COVID-19 is urgently needed for older adults, in whom morbidity and mortality due to the disease are increased. We aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in adults aged 60 years and older. METHODS: We did a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial of CoronaVac in healthy adults aged 60 years and older in Renqiu (Hebei, China). Vaccine or placebo was given by intramuscular injection in two doses (days 0 and 28). Phase 1 comprised a dose-escalation study, in which participants were allocated to two blocks: block 1 (3 μg inactivated virus in 0·5 mL of aluminium hydroxide solution per injection) and block 2 (6 μg per injection). Within each block, participants were randomly assigned (2:1) using block randomisation to receive CoronaVac or placebo (aluminium hydroxide solution only). In phase 2, participants were randomly assigned (2:2:2:1) using block randomisation to receive either CoronaVac at 1·5 μg, 3 μg, or 6 μg per dose, or placebo. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint was seroconversion rate at 28 days after the second injection (which was assessed in all participants who had received the two doses of vaccine according to their random assignment, had antibody results available, and did not violate the trial protocol). Seroconversion was defined as a change from seronegative at baseline to seropositive for neutralising antibodies to live SARS-CoV-2 (positive cutoff titre 1/8), or a four-fold titre increase if the participant was seropositive at baseline. This study is ongoing and is registered with ClinicalTrials.gov (NCT04383574). FINDINGS: Between May 22 and June 1, 2020, 72 participants (24 in each intervention group and 24 in the placebo group; mean age 65·8 years [SD 4·8]) were enrolled in phase 1, and between June 12 and June 15, 2020, 350 participants were enrolled in phase 2 (100 in each intervention group and 50 in the placebo group; mean age 66·6 years [SD 4·7] in 349 participants). In the safety populations from both phases, any adverse reaction within 28 days after injection occurred in 20 (20%) of 100 participants in the 1·5 μg group, 25 (20%) of 125 in the 3 μg group, 27 (22%) of 123 in the 6 μg group, and 15 (21%) of 73 in the placebo group. All adverse reactions were mild or moderate in severity and injection site pain (39 [9%] of 421 participants) was the most frequently reported event. As of Aug 28, 2020, eight serious adverse events, considered unrelated to vaccination, have been reported by seven (2%) participants. In phase 1, seroconversion after the second dose was observed in 24 of 24 participants (100·0% [95% CI 85·8–100·0]) in the 3 μg group and 22 of 23 (95·7% [78·1–99·9]) in the 6 μg group. In phase 2, seroconversion was seen in 88 of 97 participants in the 1·5 μg group (90·7% [83·1–95·7]), 96 of 98 in the 3 μg group (98·0% [92·8–99·8]), and 97 of 98 (99·0% [94·5–100·0]) in the 6 μg group. There were no detectable antibody responses in the placebo groups. INTERPRETATION: CoronaVac is safe and well tolerated in older adults. Neutralising antibody titres induced by the 3 μg dose were similar to those of the 6 μg dose, and higher than those of the 1·5 μg dose, supporting the use of the 3 μg dose CoronaVac in phase 3 trials to assess protection against COVID-19. FUNDING: Chinese National Key Research and Development Program and Beijing Science and Technology Program.

Lancet Infect Dis2021       LitCov and CORD-19
3141Severity of respiratory failure at admission and in-hospital mortality in patients with COVID-19: a prospective observational multicenter study  

OBJECTIVES: COVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF). The influence of hARF severity on patients’ outcomes is still poorly understood. DESIGN: Observational, prospective, multicentre study. SETTING: Three academic hospitals in Milan (Italy) involving three respiratory high dependency units and three general wards. PARTICIPANTS: Consecutive adult hospitalised patients with a virologically confirmed diagnosis of COVID-19. Patients aged <18 years or unable to provide informed consent were excluded. INTERVENTIONS: Anthropometrical, clinical characteristics and blood biomarkers were assessed within the first 24 hours from admission. hARF was graded as follows: severe (partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <100 mm Hg); moderate (PaO2/FiO2 101–200 mm Hg); mild (PaO2/FiO2 201–300 mm Hg) and normal (PaO2/FiO2 >300 mm Hg). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the assessment of clinical characteristics and in-hospital mortality based on the severity of respiratory failure. Secondary outcomes were intubation rate and application of continuous positive airway pressure during hospital stay. RESULTS: 412 patients were enrolled (280 males, 68%). Median (IQR) age was 66 (55–76) years with a PaO2/FiO2 at admission of 262 (140–343) mm Hg. 50.2% had a cardiovascular disease. Prevalence of mild, moderate and severe hARF was 24.4%, 21.9% and 15.5%, respectively. In-hospital mortality proportionally increased with increasing impairment of gas exchange (p<0.001). The only independent risk factors for mortality were age ≥65 years (HR 3.41; 95% CI 2.00 to 5.78, p<0.0001), PaO2/FiO2 ratio ≤200 mm Hg (HR 3.57; 95% CI 2.20 to 5.77, p<0.0001) and respiratory failure at admission (HR 3.58; 95% CI 1.05 to 12.18, p=0.04). CONCLUSIONS: A moderate-to-severe impairment in PaO2/FiO2 was independently associated with a threefold increase in risk of in-hospital mortality. Severity of respiratory failure is useful to identify patients at higher risk of mortality. TRIAL REGISTRATION NUMBER: NCT04307459

BMJ Open2020       LitCov and CORD-19
3142In-silico screening of plant-derived antivirals against main protease, 3CLpro and endoribonuclease, NSP15 proteins of SARS-CoV-2  

Novel Coronavirus or SARS-CoV-2 outbreak has developed a pandemic condition all over the world. The virus is highly infectious and spreads by human to human local transmission mode. Till date, there is no vaccination or drugs been approved for the treatment by the World Health Organisation. Henceforth, the discovery of the potential drugs is an urgent and utmost requirement for the medical fraternity. Since, the side effects of plant-derived compounds will be lower compared to synthetic/chemical drugs. The Main protease (3CL(pro) or NSP5) and endoribonuclease (NSP15) proteins are necessity for viral replication and its survival in the host cell. In the present study, in-silico approach of drug development was used to search for potential antiviral plant-derived compounds as inhibitors against SARS-CoV-2 replication proteins. Eight plant-derived compounds of which the antiviral activity was known and available, and two reported drugs against SARS-CoV-2 selected for the molecular docking analysis. The docking results suggested that bisdemethoxycurcumin, demethoxycurcumin, scutellarin, quercetin and myricetin showed least binding energy, i.e., greater than −6.5 Kcal/mol against 3CL(pro) and endoribonuclease of SARS-CoV-2. Further studies of ADME-Tox and bioavailability of drugs were also performed that exhibited efficient parameters of drug likeness. Molecular dynamics simulation calculations were performed for the most negative binding affinity of the compound to evaluate the dynamic behavior,and stability of protein-ligand complex. Our findings suggest that these compounds could be potential inhibitors of SARS‐CoV-2 main protease and endoribonuclease. However, further in-vitro and pre-clinical experiments would validate the potential inhibitors of SARS‐CoV‐2 proteins.

J Biomol Struct Dyn2020       LitCov and CORD-19
3143Assessment of the Acceptability and Feasibility of Using Mobile Robotic Systems for Patient Evaluation  

N/A

JAMA Netw Open2021       LitCov and CORD-19
3144Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor  

The 2002–3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history(1). An ongoing outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV)(2) suggests that this group of viruses remains a major threat and that their distribution is wider than previously recognized. Although bats have been suggested as the natural reservoirs of both viruses(3–5), attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa(5–8), but none are considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins (S) to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2)(9,10). Here, we report whole genome sequences of two novel bat CoVs from Chinese horseshoe bats (Family: Rhinolophidae) in Yunnan, China; RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat CoVs, particularly in the receptor binding domain (RDB) of the S protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat fecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses the ACE2s from human, civet and Chinese horseshoe bat for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.

Nature2013       CORD-19
3145Beliefs and practices among primary care physicians during the first wave of the COVID-19 pandemic in Baden-Wuerttemberg (Germany): an observational study  

BACKGROUND: During the first wave of the COVID-19 pandemic various ambulatory health care models (SARS-CoV-2 contact points: Subspecialised Primary Care Practices, Fever Clinics, and Special Places for Corona-Testing) were organised in a short period in Baden-Wuerttemberg, a region in Southern Germany. The aim of these SARS-CoV-2 contact points was to ensure medical treatment for patients with (suspected) and without SARS-CoV-2 infection. The present study aimed to assess the beliefs and practices of primary care physicians who either led a Subspecialised Primary Care Practice or a Primary Care Practice providing care as usual in Baden-Wuerttemberg during the first wave of the COVID-19 pandemic. METHODS: This cross-sectional study was based on a paper-based questionnaire in primary care physicians during the first wave of the pandemic. Participants were identified via the web page of the Association of Statutory Health Insurance Physicians Baden-Wuerttemberg. The questionnaire was distributed in June and July 2020. It measured knowledge, practices, self-efficacy and fears towards SARS-CoV-2, using newly developed questions. Data was descriptively analysed. RESULTS: One hundred fifty-five participants (92 leads of SARS-CoV-2 contact points/ 63 leads of primary care practices) completed the questionnaire. Out of 92 leads of SARS-CoV-2 contact points 74 stated to lead n Subspecialised Primary Care Practices. About half participants of both groups did not fear an own infection with the novel virus (between 50.8% and 62.2%), however about 75% feared financial loss. Knowledge was gained using various sources; main sources were the Association of Statutory Health Insurance Physicians (between 82.5% and 83.8%) and the German Society for Hygiene and Microbiology (RKI) (between 88.9% and 95.9%). Leads of Subspecialised Primary Care Practice felt more confident to perform anamnestic/diagnostic procedures (p < 0.001). The same was found for the confidence level regarding decision-making concerning the further treatment (p < 0.001). Several prevention measures to contain the spread of SARS-CoV-2 were adopted. Subspecialised Primary Care Practice had treated on average more patients with (suspected) COVID-19 (mean 408.12) than primary care practices (mean 83.8) (p < 0.001). CONCLUSION: The results of this study suggest that the Subspecialised Primary Care Practice that were implemented during the first wave of the SARS-CoV-2 pandemic contributed containment of the pandemic. Leads of Subspecialised Primary Care Practice indicated that physical separation of patients with potential SARS-CoV-2 infection was easier compared to those who continued working in their own practice. Additionally, leads of Subspecialised Primary Care Practice felt more confident in dealing with patients with SARS-CoV-2 infection. TRIAL REGISTRATION: The study has been prospectively registered at the German Clinical Trial Register (DRKS00022224). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12875-021-01433-9.

BMC Fam Pract2021       LitCov and CORD-19
3146Multiple Sclerosis Disease-Modifying Therapy and the COVID-19 Pandemic: Implications on the Risk of Infection and Future Vaccination  

The coronavirus 2019 (COVID-19) pandemic is expected to linger. Decisions regarding initiation or continuation of disease-modifying therapy for multiple sclerosis have to consider the potential relevance to the pandemic. Understanding the mechanism of action and the possible idiosyncratic effects of each therapeutic agent on the immune system is imperative during this special time. The infectious side-effect profile as well as the route and frequency of administration of each therapeutic agent should be carefully considered when selecting a new treatment or deciding on risk mitigation strategies for existing therapy. More importantly, the impact of each agent on the future severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) vaccine should be carefully considered in treatment decisions. Moreover, some multiple sclerosis therapies may have beneficial antiviral effects against SARS-CoV-2 while others may have beneficial immune-modulating effects against the cytokine storm and hyperinflammatory phase of the disease. Conventional injectables have a favorable immune profile without an increased exposure risk and therefore may be suitable for mild multiple sclerosis during the pandemic. However, moderate and highly active multiple sclerosis will continue to require treatment with oral or intravenous high-potency agents but a number of risk mitigation strategies may have to be implemented. Immune-modulating therapies such as the fumerates, sphinogosine-1P modulators, and natalizumab may be anecdotally preferred over cell-depleting immunosuppressants during the pandemic from the immune profile standpoint. Within the cell-depleting agents, selective (ocrelizumab) or preferential (cladribine) depletion of B cells may be relatively safer than non-selective depletion of lymphocytes and innate immune cells (alemtuzumab). Patients who develop severe iatrogenic or idiosyncratic lymphopenia should be advised to maintain social distancing even in areas where lockdown has been removed or ameliorated. Patients with iatrogenic hypogammaglobulinemia may require prophylactic intravenous immunoglobulin therapy in certain situations. When the future SARS-CoV-2 vaccine becomes available, patients with multiple sclerosis should be advised that certain therapies may interfere with mounting a protective immune response to the vaccine and that serological confirmation of a response may be required after vaccination. They should also be aware that most multiple sclerosis therapies are incompatible with live vaccines if a live SARS-CoV-2 vaccine is developed. In this article, we review and compare disease-modifying therapies in terms of their effect on the immune system, published infection rates, potential impact on SARS-CoV-2 susceptibility, and vaccine-related implications. We propose risk mitigation strategies and practical approaches to disease-modifying therapy during the COVID-19 pandemic.

CNS Drugs2020       LitCov and CORD-19
3147Effect of priming interval on reactogenicity, peak immunological response and waning after homologous and heterologous COVID-19 vaccine schedules: exploratory analyses of Com-COV, a randomised control trial  

N/A

Lancet Respir Med2022       LitCov
3148SARS-CoV-2-specific humoral and cell-mediated immune responses after immunization with inactivated COVID-19 vaccine in kidney transplant recipients (CVIM 1 study)  

Immunogenicity following inactivated SARS‐CoV‐2 vaccination among solid organ transplant recipients has not been assessed. Seventy‐five patients (37 kidney transplant [KT] recipients and 38 healthy controls) received two doses, at 4‐week intervals, of an inactivated whole‐virus SARS‐CoV‐2 vaccine. SARS‐CoV‐2‐specific humoral (HMI) and cell‐mediated immunity (CMI) were measured before, 4 weeks post‐first dose, and 2 weeks post‐second dose. The median (IQR) age of KT recipients was 50 (42–54) years and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median (IQR) time since transplant was 4.5 (2–9.5) years. Among 35 KT patients, the median (IQR) of anti‐RBD IgG level measured by CLIA after vaccination was not different from baseline, but was significantly lower than in controls (2.4 [1.1–3.7] vs. 1742.0 [747.7–3783.0] AU/ml, p < .01) as well as percentages of neutralizing antibody inhibition measured by surrogate viral neutralization test (0 [0–0] vs. 71.2 [56.8–92.2]%, p < .01). However, the median (IQR) of SARS‐CoV‐2 mixed peptides‐specific T cell responses measured by ELISpot was significantly increased compared with baseline (30 [4–120] vs. 12 [0–56] T cells/10(6) PBMCs, p = .02) and not different from the controls. Our findings revealed weak HMI but comparable CMI responses in fully vaccinated KT recipients receiving inactivated SARS‐CoV‐2 vaccination compared to immunocompetent individuals (Thai Clinical Trials Registry, TCTR20210226002).

Am J Transplant2021       LitCov and CORD-19
3149Prevalence and predictors of in-hospital mortality of patients hospitalized with COVID-19 infection  

BACKGROUND: The severity and mortality from COVID-19 infection vary among populations. The aim of this study was to determine the prevalence and predictors of mortality among patients hospitalized with COVID-19 infection in a tertiary care hospital in Oman. METHODS: We conducted a retrospective study using database that included: demographic, clinical characteristics, laboratory parameters, medications and clinical outcomes of all patients hospitalized in Royal Hospital, Muscat, Oman, between March 12, 2020 and December 1(st) 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 infected patients. RESULTS: In total,1,002 patients with COVID-19 infection with mean age of the cohort was 54 ± 16 years (65% (n = 650) male) were included, with an overall and intensive care unit (ICU) mortalities of 26% (n = 257) and 42% (n = 199/473), respectively. The prevalence of ICU admission was 47% (n = 473) and the need for mechanical ventilation was 41% (n = 413). The overall length of stay in the ICU was 13 (9 - 21) days. Adjusting for other factors in the model, the multivariable logistic regression demonstrated that in-hospital mortality in admitted COVID-19 patients was associated with old age (p < 0.001), heart diseases (adjusted odds ratio (aOR), 1.84; 95% confidence interval (CI): 1.11-3.03; p = 0.018), liver diseases (aOR, 4.48; 95% CI: 1.04-19.3; p = 0.044), those with higher ferritin levels (aOR, 1.00; 95% CI: 1.00-1.00; p = 0.006), acute respiratory distress syndrome (ARDS) (aOR, 3.20; 95% CI: 1.65-6.18; p = 0.001), sepsis (aOR, 1.77; 95% CI: 1.12-2.80; p = 0.022), and those that had ICU admission (aOR, 2.22; 95% CI: 1.12-4.38; p = 0.022). CONCLUSION: In this cohort, mortality in hospitalized COVID-19 patients was high and was associated with advanced age, heart diseases, liver disease, high ferritin, ARDS, sepsis and ICU admission. These high-risk groups should be prioritized for COVID-19 vaccinations.

J Infect Public Health2021       LitCov and CORD-19
3150Estimated BNT162b2 Vaccine Effectiveness Against Infection With Delta and Omicron Variants Among US Children 5 to 11 Years of Age  

N/A

JAMA Netw Open2022       LitCov

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(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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