\ 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
4901Iterated Virtual Screening-Assisted Antiviral and Enzyme Inhibition Assays Reveal the Discovery of Novel Promising Anti-SARS-CoV-2 with Dual Activity  

Unfortunately, COVID-19 is still a threat to humankind and has a dramatic impact on human health, social life, the world economy, and food security. With the limited number of suggested therapies under clinical trials, the discovery of novel therapeutic agents is essential. Here, a previously identified anti-SARS-CoV-2 compound named Compound 13 (1,2,5-Oxadiazole-3-carboximidic acid, 4,4′-(methylenediimino) bis,bis[[(2-hydroxyphenyl)methylene]hydrazide) was subjected to an iterated virtual screening against SARS-CoV-2 M(pro) using a combination of Ligand Designer and PathFinder. PathFinder, a computational reaction enumeration tool, was used for the rapid generation of enumerated structures via default reaction library. Ligand designer was employed for the computerized lead optimization and selection of the best structural modification that resulted in a favorable ligand–protein complex. The obtained compounds that showed the best binding to M(pro) were re-screened against TMPRSS2, leading to the identification of 20 shared compounds. The compounds were further visually inspected, which resulted in the identification of five shared compounds M1–5 with dual binding affinity. In vitro evaluation and enzyme inhibition assay indicated that M3, an analogue of Compound 13 afforded by replacing the phenolic moiety with pyridinyl, possesses an improved antiviral activity and safety. M3 displayed in vitro antiviral activity with IC(50) 0.016 µM and M(pro) inhibition activity with IC(50) 0.013 µM, 7-fold more potent than the parent Compound 13 and potent than the antivirals drugs that are currently under clinical trials. Moreover, M3 showed potent activity against human TMPRSS2 and furin enzymes with IC(50) 0.05, and 0.08 µM, respectively. Molecular docking, WaterMap analysis, molecular dynamics simulation, and R-group analysis confirmed the superiority of the binding fit to M3 with the target enzymes. WaterMap analysis calculated the thermodynamic properties of the hydration site in the binding pocket that significantly affects the biological activity. Loading M3 on zinc oxide nanoparticles (ZnO NPs) increased the antiviral activity of the compound 1.5-fold, while maintaining a higher safety profile. In conclusion, lead optimized discovery following an iterated virtual screening in association with molecular docking and biological evaluation revealed a novel compound named M3 with promising dual activity against SARS-CoV-2. The compound deserves further investigation for potential clinical-based studies.

Int J Mol Sci2021       LitCov and CORD-19
4902Singapore COVID-19 Pandemic Response as a Successful Model Framework for Low-Resource Healthcare Settings in Africa?  

N/A

OMICS2020       LitCov and CORD-19
4903Neurological autoimmune diseases following vaccinations against SARS-CoV-2: a case series  

BACKGROUND AND PURPOSE: Population‐based studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines may trigger immune‐mediated thrombotic thrombocytopenia (VITT) raising concerns for other autoimmune responses. The aim was to characterize neurological autoimmunity after SARS‐CoV‐2 vaccinations. METHODS: In this single‐centre prospective case study patients with neurological autoimmunity in temporal association (≤6 weeks) with SARS‐CoV‐2 vaccinations and without other triggers are reported. Clinical, laboratory and imaging data were collected with a median follow‐up of 49 days. RESULTS: In the study period 232,603 inhabitants from the main catchment area of our hospital (Rhein‐Neckar‐Kreis, county) received SARS‐CoV‐2 vaccinations. Twenty‐one cases (new onset n = 17, flares n = 4) diagnosed a median of 11 days (range 3–23) following SARS‐CoV‐2 vaccinations (BNT162b2 n = 12, ChAdOx1 n = 8, mRNA‐1273 n = 1) were identified. Cases included VITT with cerebral venous sinus thrombosis (n = 3), central nervous system demyelinating diseases (n = 8), inflammatory peripheral neuropathies (n = 4), myositis (n = 3), myasthenia (n = 1), limbic encephalitis (n = 1) and giant cell arteritis (n = 1). Patients were predominantly female (ratio 3.2:1) and the median age at diagnosis was 50 years (range 22–86). Therapy included administration of steroids (n = 15), intravenous immunoglobulins in patients with Guillain–Barré syndrome or VITT (n = 4), plasma exchange in cases unresponsive to steroids (n = 3) and anticoagulation in VITT. Outcomes were favourable with partial and complete remissions achieved in 71% and 24%, respectively. Two patients received their second vaccination without further aggravation of autoimmune symptoms under low‐dose immunosuppressants. CONCLUSIONS: In this study various neurological autoimmune disorders encountered following SARS‐CoV‐2 vaccinations are characterized. Given the assumed low incidence and mostly favourable outcome of autoimmune responses, the benefits of vaccinations outweigh the comparatively small risks.

Eur J Neurol2021       LitCov and CORD-19
4904N/A  

N/A

N/A2021       LitCov
4905Adverse events following third dose of mRNA COVID-19 vaccination among nursing home residents who received the primary series  

BACKGROUND: We sought to compare rates of adverse events among nursing home residents who received an mRNA COVID‐19 vaccine booster dose with those who had not yet received their booster. METHODS: We assessed a prospective cohort of 11,200 nursing home residents who received a primary COVID‐19 mRNA vaccine series at least 6 months prior to September 22, 2021 and received a third “booster dose” between September 22, 2021 and February 2, 2022. Residents lived in 239 nursing homes operated by Genesis HealthCare, spanning 21 U.S. states. We screened electronic health records for 20 serious vaccine‐related adverse events that are monitored following receipt of COVID‐19 vaccination by the CDC's Vaccine Safety Datalink. We matched boosted and yet‐to‐be boosted residents during the same time period, comparing rates of events occurring 14 days after booster administration with those occurring 14 days prior to booster administration. To supplement previously reported background rates of adverse events, we report background rates of medical conditions among nursing home residents during 2020, before COVID‐19 vaccines were administered in nursing homes. Events occurring in 2021–2022 were confirmed by physician chart review. We report unadjusted rates of adverse events and used a false discovery rate procedure to adjust for multiplicity of events tested. RESULTS: No adverse events were reported during the 14 days post‐booster. A few adverse events occurred prior to booster (ischemic stroke: 49.4 per 100,000 residents, 95% CI: 21.2, 115.7; venous thromboembolism: 9.9 per 100,000 residents, 95% CI: 1.7, 56.0), though differences in event rates pre‐ versus post‐booster were not statistically significant (p < 0.05) after adjusting for multiple comparisons. No significant differences were detected between post‐booster vaccination rates and prior year 14‐day background rates of medical conditions. CONCLUSIONS: No safety signals were detected following a COVID‐19 mRNA vaccine booster dose in this large multi‐state sample of nursing home residents.

J Am Geriatr Soc2022       LitCov and CORD-19
4906Single domain antibodies derived from ancient animals as broadly neutralizing agents for SARS-CoV-2 and other coronaviruses  

N/A

Biomed Eng Adv2022       LitCov
4907How COVID-19 drives connectedness among commodity and financial markets: Evidence from TVP-VAR and causality-in-quantiles techniques  

With many commodity and financial markets reportedly experiencing poor performances during this COVID-19 pandemic, this study intends to examine the effect of the pandemic on the connectedness among the markets. There are several reasons that suggest that apart from the pandemic affecting the performances of the markets, it can also be a driver of their connectedness, coming from the perspective of the global financial cycle channel. Therefore, we first employ the recently developed time-varying parameter vector autoregressions (TVP-VAR) technique to examine the volatility spillover among the commodity and financial assets. We find evidence of strong volatility across the markets, with gold and USD being net receivers of shocks, and others, net transmitters. With this evidence, we proceed to the evaluation of the influence of the COVID-19 pandemic on the connectedness across the markets using both the linear and non-linear (causality-in-quantiles) causality tests. The causality-in-quantiles test outperforms the linear Granger-causality test, and the results show significant causal impacts of the two measures of COVID-19 pandemic (infectious diseases-based equity market volatility and the growth rate of the U.S. COVID-19 reported cases) on the connectedness across the markets, especially at the lower and middle-level quantiles. Overall, these findings prove that the pandemic has been largely responsible for risks transmission across various commodity and financial markets. This is because it has significantly raised investors’ and policy uncertainties and immensely altered global financial cycle which in turn results in global flows of capital, and movements in the prices of assets across different financial markets.

Resour Policy2020       LitCov and CORD-19
4908Teaching clinical practical and communication skills of the clinical skills lab of the University of Veterinary Medicine Hannover, Foundation, Germany during the COVID-19 pandemic  

Objective: The aim of the project is to teach clinical practical and communication skills in the Clinical Skills Lab (CSL) of the University of Veterinary Medicine Hannover, Foundation (TiHo) during the COVID-19 pandemic. Methodology: As a measure to limit potential SARS-CoV2 infections, the CSL learning stations were digitised and made available on the Moodle learning platform of the TiHo. Online quiz stations were also developed, as well as improvisations that allowed students to practise practical skills at home using everyday materials. Courses for Practical Year (PY) students were digitised and again combined with classroom exercises throughout the year. The teaching formats could be evaluated by the students by means of a questionnaire using a Likert scale (1=agree; 4=disagree). Results: A total of 24.92% of students (n=1272) completed the learning stations with improvisations. The quiz stations were completed with a percentage of 75.08%. Students indicated that the improvisations were easily implementable from home (M=1.33) and assisted in learning the practical skills in question (M=1.89). The quiz stations were considered helpful (M=1.40) and complementary to previous CSL offers (M=1.13). The PY students found the amount of teaching materials adequate (M=1.76) and described communication with the lecturers as problem-free (compulsory electives=1.24). Conclusions: Digital teaching is suitable as a supplement to existing face-to-face courses at the CSL, but cannot replace on-site training under the guidance of trained personnel. The CSL will continue to strive for a combination of online and face-to-face courses for some learning stations in the future.

GMS J Med Educ2021       LitCov and CORD-19
4909Cross-reactive antibody against human coronavirus OC43 spike protein correlates with disease severity in COVID-19 patients: a retrospective study  

Seasonal human coronaviruses (HCoVs) including HCoV-229E, -OC43, -NL63, and -HKU1 widely spread in global human populations. However, the relevance of humoral response against seasonal HCoVs to COVID-19 pathogenesis is elusive. In this study, we profiled the temporal changes of IgG antibody against spike proteins (S-IgG) of SARS-CoV-2 and seasonal HCoVs in 838 plasma samples collected from 344 COVID-19 patients. We tested the antigenic cross-reactivities of S protein between SARS-CoV-2 and seasonal HCoVs and evaluated the correlations between the levels of HCoV-OC43 S-IgG and the disease severity in COVID-19 patients. We found that SARS-CoV-2 S-IgG titres mounted until days 22–28, whereas HCoV-OC43 antibody titres increased until days 15–21 and then plateaued until day 46. However, IgG titres against HCoV-NL63, −229E, and -HKU1 showed no significant increase. A two-way cross-reactivity was identified between SARS-CoV-2 and HCoV-OC43. Neutralizing antibodies against SARS-CoV-2 were not detectable in healthy controls who were positive for HCoV-OC43 S-IgG. HCoV-OC43 S-IgG titres were significantly higher in patients with severe disease than those in mild patients at days 1–21 post symptom onset (PSO). Higher levels of HCoV-OC43 S-IgG were also observed in patients requiring mechanical ventilation. At days 1–10 PSO, HCoV-OC43 S-IgG titres correlated to disease severity in the age group over 60. Our data indicate that there is a correlation between cross-reactive antibody against HCoV-OC43 spike protein and disease severity in COVID-19 patients.

Emerg Microbes Infect2021       LitCov and CORD-19
4910Improved immunologic response to COVID-19 vaccine with prolonged dosing interval in haemodialysis patients  

Vaccination against 2019 coronavirus disease (COVID‐19) can reduce disease incidence and severity. Dialysis patients demonstrate a delayed immunologic response to vaccines. We determined factors affecting the immunologic response to COVID‐19 vaccines in haemodialysis patients. All patients within a Swedish haemodialysis network, vaccinated with two doses of COVID‐19 vaccine 2‐8 weeks before inclusion, were eligible for this cross‐sectional study. Severe adult respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike protein antibody levels were determined by EliA SARS‐CoV‐2‐Sp1 IgG test (Thermo Fisher Scientific, Phadia AB) and related to clinical and demographic parameters. Eighty‐nine patients were included. Patients were vaccinated with two doses of Comirnaty (BNT162b2, 73%) or Spikevax (mRNA‐1273, 23,6%). Three patients received combinations of different vaccines. Response rate (antibody titres >7 U/mL) was 89.9%, while 39.3% developed high antibody titres (>204 U/mL), 47 (43‐50) days after the second dose. A previous COVID‐19 infection associated with higher antibody titres (median (25th‐75th percentile) 1558.5 (814.5‐3,763.8) U/mL vs 87 (26‐268) U/mL, P = .002), while time between vaccine doses did not differ between groups (P = .7). Increasing SARS‐CoV‐2 antibody titres were independently associated with increasing time between vaccine doses (B 0.241, P = .02), decreasing serum calcium levels (B −0.233, P = .007) and previous COVID‐19 (B 1.078, P < .001). In conclusion, a longer interval between COVID‐19 mRNA vaccine doses, lower calcium and a previous COVID‐19 infection were independently associated with a stronger immunologic vaccination response in haemodialysis patients. While the response rate was good, only a minority developed high antibody titres, 47 (43‐50) days after the second vaccine dose.

Scand J Immunol2022       LitCov and CORD-19
4911Synergism of TNF-alpha and IFN-gamma Triggers Inflammatory Cell Death, Tissue Damage and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes  

COVID-19 is characterized by excessive production of pro-inflammatory cytokines and acute lung damage associated with patient mortality. While multiple inflammatory cytokines are produced by innate immune cells during SARS-CoV-2 infection, we found that only the combination of TNF-α and IFN-γ induced inflammatory cell death characterized by pyroptosis, apoptosis, and necroptosis (PANoptosis). Mechanistically, TNF-α and IFN-γ co-treatment activated the JAK/STAT1/IRF1 axis, inducing nitric oxide production and driving caspase-8/FADD–mediated PANoptosis. TNF-α and IFN-γ caused a lethal cytokine shock in mice that mirrors the tissue damage and inflammation of COVID-19, and inhibiting PANoptosis protected mice from this pathology and death. Furthermore, treating with neutralizing antibodies against TNF-α and IFN-γ protected mice from mortality during SARS-CoV-2 infection, sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock. Collectively, our findings suggest that blocking the cytokine-mediated inflammatory cell death signaling pathway identified here may benefit patients with COVID-19 or other infectious and autoinflammatory diseases by limiting tissue damage/inflammation.

Cell2020       LitCov and CORD-19
4912Assessment of COVID-19 vaccine hesitancy among Zimbabweans: A rapid national survey  

BACKGROUND: As a way of minimising the devastating effects of the coronavirus disease 2019 (COVID-19) pandemic, scientists hastily developed a vaccine. However, the scale-up of the vaccine is likely to be hindered by the widespread social media misinformation. We therefore conducted a study to assess the COVID-19 vaccine hesitancy among Zimbabweans. METHODS: We conducted a descriptive online cross-sectional survey using a self-administered questionnaire among adults. The questionnaire assessed willingness to be vaccinated; socio-demographic characteristics, individual attitudes and perceptions, effectiveness and safety of the vaccine. Multivariable logistic regression analysis was utilized to examine the independent factors associated with vaccine uptake. RESULTS: We analysed data for 1168 participants, age range of 19–89 years with the majority being females (57.5%). Half (49.9%) of the participants reported that they would accept the COVID-19 vaccine. Majority were uncertain about the effectiveness of the vaccine (76.0%) and its safety (55.0%). About half lacked trust in the government’s ability to ensure availability of an effective vaccine and 61.0% mentioned that they would seek advice from a healthcare worker to vaccinate. Chronic disease [vs no chronic disease—Adjusted Odds Ratio (AOR): 1.50, 95% Confidence Interval (CI)I: 1.10–2.03], males [vs females—AOR: 1.83, 95%CI: 1.37–2.44] and being a healthcare worker [vs not being a health worker—AOR: 1.59, 95%CI: 1.18–2.14] were associated with increased likelihood to vaccinate. CONCLUSION: We found half of the participants willing to vaccinate against COVID-19. The majority lacked trust in the government and were uncertain about vaccine effectiveness and safety. The policy makers should consider targeting geographical and demographic groups which were unlikely to vaccinate with vaccine information, education and communication to improve uptake.

PLoS One2022       LitCov and CORD-19
4913Development and evaluation of a machine learning-based in-hospital COVID-19 disease outcome predictor (CODOP): A multicontinental retrospective study  

New SARS-CoV-2 variants, breakthrough infections, waning immunity, and sub-optimal vaccination rates account for surges of hospitalizations and deaths. There is an urgent need for clinically valuable and generalizable triage tools assisting the allocation of hospital resources, particularly in resource-limited countries. We developed and validate CODOP, a machine learning-based tool for predicting the clinical outcome of hospitalized COVID-19 patients. CODOP was trained, tested and validated with six cohorts encompassing 29223 COVID-19 patients from more than 150 hospitals in Spain, the USA and Latin America during 2020–22. CODOP uses 12 clinical parameters commonly measured at hospital admission for reaching high discriminative ability up to 9 days before clinical resolution (AUROC: 0·90–0·96), it is well calibrated, and it enables an effective dynamic risk stratification during hospitalization. Furthermore, CODOP maintains its predictive ability independently of the virus variant and the vaccination status. To reckon with the fluctuating pressure levels in hospitals during the pandemic, we offer two online CODOP calculators, suited for undertriage or overtriage scenarios, validated with a cohort of patients from 42 hospitals in three Latin American countries (78–100% sensitivity and 89–97% specificity). The performance of CODOP in heterogeneous and geographically disperse patient cohorts and the easiness of use strongly suggest its clinical utility, particularly in resource-limited countries.

Elife2022       LitCov and CORD-19
4914Epidemiology of mental health problems in COVID-19: a review  

The novel coronavirus disease 2019 (COVID-19) has become a pandemic affecting health and wellbeing globally. In addition to the physical health, economic, and social implications, the psychological impacts of this pandemic are increasingly being reported in the scientific literature. This narrative review reflected on scholarly articles on the epidemiology of mental health problems in COVID-19. The current literature suggests that people affected by COVID-19 may have a high burden of mental health problems, including depression, anxiety disorders, stress, panic attack, irrational anger, impulsivity, somatization disorder, sleep disorders, emotional disturbance, posttraumatic stress symptoms, and suicidal behavior. Moreover, several factors associated with mental health problems in COVID-19 are found, which include age, gender, marital status, education, occupation, income, place of living, close contact with people with COVID-19, comorbid physical and mental health problems, exposure to COVID-19 related news and social media, coping styles, stigma, psychosocial support, health communication, confidence in health services, personal protective measures, risk of contracting COVID-19, and perceived likelihood of survival. Furthermore, the epidemiological distribution of mental health problems and associated factors were heterogeneous among the general public, COVID-19 patients, and healthcare providers. The current evidence suggests that a psychiatric epidemic is cooccurring with the COVID-19 pandemic, which necessitates the attention of the global health community. Future epidemiological studies should emphasize on psychopathological variations and temporality of mental health problems in different populations. Nonetheless, multipronged interventions should be developed and adopted to address the existing psychosocial challenges and promote mental health amid the COVID-19 pandemic.

F1000Res2020       LitCov and CORD-19
4915Depression, anxiety and stress and socio-demographic correlates among general Indian public during COVID-19  

N/A

Int J Soc Psychiatry2020       LitCov and CORD-19
4916Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar  

N/A

Nat Commun2022       LitCov
4917Evaluation of the effects of chlorhexidine and several flavonoids as antiviral purposes on SARS-CoV-2 main protease: molecular docking, molecular dynamics simulation studies  

N/A

J Biomol Struct Dyn2022       LitCov and CORD-19
4918Socioeconomic Disparities in Social Distancing During the COVID-19 Pandemic in the United States: Observational Study  

BACKGROUND: Eliminating disparities in the burden of COVID-19 requires equitable access to control measures across socio-economic groups. Limited research on socio-economic differences in mobility hampers our ability to understand whether inequalities in social distancing are occurring during the SARS-CoV-2 pandemic. OBJECTIVE: We aimed to assess how mobility patterns have varied across the United States during the COVID-19 pandemic and to identify associations with socioeconomic factors of populations. METHODS: We used anonymized mobility data from tens of millions of devices to measure the speed and depth of social distancing at the county level in the United States between February and May 2020, the period during which social distancing was widespread in this country. Using linear mixed models, we assessed the associations between social distancing and socioeconomic variables, including the proportion of people in the population below the poverty level, the proportion of Black people, the proportion of essential workers, and the population density. RESULTS: We found that the speed, depth, and duration of social distancing in the United States are heterogeneous. We particularly show that social distancing is slower and less intense in counties with higher proportions of people below the poverty level and essential workers; in contrast, we show that social distancing is intensely adopted in counties with higher population densities and larger Black populations. CONCLUSIONS: Socioeconomic inequalities appear to be associated with the levels of adoption of social distancing, potentially resulting in wide-ranging differences in the impact of the COVID-19 pandemic in communities across the United States. These inequalities are likely to amplify existing health disparities and must be addressed to ensure the success of ongoing pandemic mitigation efforts.

J Med Internet Res2021       LitCov and CORD-19
4919Characteristics and outcomes of vaccinated and nonvaccinated patients hospitalized in a single Italian hub for COVID-19 during the Delta and Omicron waves in Northern Italy  

N/A

Int J Infect Dis2022       LitCov
4920County-Level Social Distancing and Policy Impact in the United States: A Dynamical Systems Model  

BACKGROUND: Social distancing and public policy have been crucial for minimizing the spread of SARS-CoV-2 in the United States. Publicly available, county-level time series data on mobility are derived from individual devices with global positioning systems, providing a variety of indices of social distancing behavior per day. Such indices allow a fine-grained approach to modeling public behavior during the pandemic. Previous studies of social distancing and policy have not accounted for the occurrence of pre-policy social distancing and other dynamics reflected in the long-term trajectories of public mobility data. OBJECTIVE: We propose a differential equation state-space model of county-level social distancing that accounts for distancing behavior leading up to the first official policies, equilibrium dynamics reflected in the long-term trajectories of mobility, and the specific impacts of four kinds of policy. The model is fit to each US county individually, producing a nationwide data set of novel estimated mobility indices. METHODS: A differential equation model was fit to three indicators of mobility for each of 3054 counties, with T=100 occasions per county of the following: distance traveled, visitations to key sites, and the log number of interpersonal encounters. The indicators were highly correlated and assumed to share common underlying latent trajectory, dynamics, and responses to policy. Maximum likelihood estimation with the Kalman-Bucy filter was used to estimate the model parameters. Bivariate distributional plots and descriptive statistics were used to examine the resulting county-level parameter estimates. The association of chronology with policy impact was also considered. RESULTS: Mobility dynamics show moderate correlations with two census covariates: population density (Spearman r ranging from 0.11 to 0.31) and median household income (Spearman r ranging from –0.03 to 0.39). Stay-at-home order effects were negatively correlated with both (r=–0.37 and r=–0.38, respectively), while the effects of the ban on all gatherings were positively correlated with both (r=0.51, r=0.39). Chronological ordering of policies was a moderate to strong determinant of their effect per county (Spearman r ranging from –0.12 to –0.56), with earlier policies accounting for most of the change in mobility, and later policies having little or no additional effect. CONCLUSIONS: Chronological ordering, population density, and median household income were all associated with policy impact. The stay-at-home order and the ban on gatherings had the largest impacts on mobility on average. The model is implemented in a graphical online app for exploring county-level statistics and running counterfactual simulations. Future studies can incorporate the model-derived indices of social distancing and policy impacts as important social determinants of COVID-19 health outcomes.

JMIR Public Health Surveill2020       LitCov and CORD-19
4921Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomised ascending dose phase I trial  

N/A

EBioMedicine2022       LitCov
4922Previous SARS-CoV-2 Infection, Age and Frailty Are Associated With 6-Month Vaccine induced Anti-Spike Antibody Titer in Nursing Home Residents  

OBJECTIVES: Older nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: Residents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine. METHODS: Comprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity. RESULTS: Of 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [β: 3.00; 95% confidence interval (CI): 2.32–3.70; P < .001] and 6 months (β: 3.59; 95% CI: 2.89–4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (β: −0.05; 95% CI: −0.08 to −0.02; P < .001) and frailty (β: −0.22; 95% CI: −0.33 to −0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity. CONCLUSIONS AND IMPLICATIONS: In older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population.

J Am Med Dir Assoc2022       LitCov and CORD-19
4923Myocarditis and Pericarditis in Adolescents after First and Second doses of mRNA COVID-19 Vaccines  

Eur Heart J Qual Care Clin Out2021       LitCov and CORD-19
4924Impact of COVID-19 pandemic on dental education: online experience and practice expectations among dental students at the University of Jordan  

BACKGROUND: The quarantine associated with the COVID-19 pandemic forced dental schools to suspend their clinical training and to shift to distant learning methods. The aim of this study is to investigate the impact of quarantine on the self-perceived preparedness of dental graduates and to explore the efficacy of online education from students’ perspectives. METHODS: The questionnaire distributed to dental students comprised of two main sections. The first part covered the online education experience, and the second part measured the level of self-perceived preparedness for a range of cognitive, communication and professional skills. RESULTS: The survey yielded a response rate of 72%. The majority of students (77%) agreed that they missed educational experiences as a result of the lockdown. More than half of them felt less motivated to follow-up with distant e-learning and believed that online assessment is not a good method for evaluation. A high percentage of the students (66%) thought that online group discussions had a positive value while 67% preferred online lectures compared to theatre lectures. Majority of students particularly 5th year (78.7%) (p < 0.001) stated that the quarantine increased their collaboration with their colleagues. According to 87% of students, the experience most negatively affected was their clinical training. In general, students showed satisfactory self-perceived preparedness related to a range of attributes and professional skills. CONCLUSIONS: The data showed that students partially appreciated the online system, whereas they did not consider it a substitute for face to face clinical practice. The overall self-perceived preparedness level was promising; however students had reservations regarding independent practice following graduation.

BMC Med Educ2021       LitCov and CORD-19
4925Activation and evasion of type I interferon responses by SARS-CoV-2  

The pandemic of COVID-19 has posed an unprecedented threat to global public health. However, the interplay between the viral pathogen of COVID-19, SARS-CoV-2, and host innate immunity is poorly understood. Here we show that SARS-CoV-2 induces overt but delayed type-I interferon (IFN) responses. By screening 23 viral proteins, we find that SARS-CoV-2 NSP1, NSP3, NSP12, NSP13, NSP14, ORF3, ORF6 and M protein inhibit Sendai virus-induced IFN-β promoter activation, whereas NSP2 and S protein exert opposite effects. Further analyses suggest that ORF6 inhibits both type I IFN production and downstream signaling, and that the C-terminus region of ORF6 is critical for its antagonistic effect. Finally, we find that IFN-β treatment effectively blocks SARS-CoV-2 replication. In summary, our study shows that SARS-CoV-2 perturbs host innate immune response via both its structural and nonstructural proteins, and thus provides insights into the pathogenesis of SARS-CoV-2.

Nat Commun2020       LitCov and CORD-19
4926Advances in the Omicron variant development  

Severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2 has spread worldwide, leading the World Health Organization (WHO) to declare a pandemic, on 11 March 2020. Variants of concern have appeared at regular intervals—Alpha, Beta, Gamma, Delta, and now Omicron. Omicron variant, first identified in Botswana in November 2021, is rapidly becoming the dominant circulating variant. In this review, we provide an overview regarding the molecular profile of the Omicron variant, epidemiology, transmissibility, the impact on vaccines, as well as vaccine escape, and finally, we report the pharmacological agents able to block the endocellular entry of SARS‐CoV‐2 or to inhibit its viral replication. The Omicron has more than 50 mutations, of which the spike protein has 26–35 amino acids different from the original SARS‐CoV‐2 virus or the Delta, some of which are associated with humoral immune escape potential and greater transmissibility. Omicron has a significant growth advantage over Delta, leading to rapid spread with higher incidence levels. The disease so far has been mild compared to the Delta. The two vaccination doses offer little or no protection against Omicron infection while the booster doses provide significant protection against mild illness and likely offer even greater levels of protection against serious illness. Recently, new oral antiviral agents such as molnupiravir and paxlovid have been approved and represent important therapeutic alternatives to antiviral remdesivir. In addition, monoclonal antibodies such as casirivimab/imdevimab bind different epitopes of the spike protein receptor; is this class of drugs effective against the Omicron variant? However, more research is needed to define whether Omicron is indeed more infectious and whether the vaccines, monoclonal antibodies, and antivirals currently available are effective.

J Intern Med2022       LitCov and CORD-19
4927SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants  

Coronavirus 19 Disease (COVID-19) originating in the province of Wuhan, China in 2019, is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), whose infection in humans causes mild or severe clinical manifestations that mainly affect the respiratory system. So far, the COVID-19 has caused more than 2 million deaths worldwide. SARS-CoV-2 contains the Spike (S) glycoprotein on its surface, which is the main target for current vaccine development because antibodies directed against this protein can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. However, the emergence of new SARS-CoV-2 variants could affect the effectiveness of vaccines. Here, we review the different types of vaccines designed and developed against SARS-CoV-2, placing emphasis on whether they are based on the complete S glycoprotein, its antigenic domains such as the receptor-binding domain (RBD) or short epitopes within the S glycoprotein. We also review and discuss the possible effectiveness of these vaccines against emerging SARS-CoV-2 variants.

Front Immunol2021       LitCov and CORD-19
4928Emergence of SARS-CoV-2 B.1.1.7 Lineage-United States, December 29, 2020-January 12, 2021  

On December 14, 2020, the United Kingdom reported a SARS-CoV-2 variant of concern (VOC), lineage B.1.1.7, also referred to as VOC 202012/01 or 20I/501Y.V1.* The B.1.1.7 variant is estimated to have emerged in September 2020 and has quickly become the dominant circulating SARS-CoV-2 variant in England (1). B.1.1.7 has been detected in over 30 countries, including the United States. As of January 13, 2021, approximately 76 cases of B.1.1.7 have been detected in 12 U.S. states.† Multiple lines of evidence indicate that B.1.1.7 is more efficiently transmitted than are other SARS-CoV-2 variants (1-3). The modeled trajectory of this variant in the U.S. exhibits rapid growth in early 2021, becoming the predominant variant in March. Increased SARS-CoV-2 transmission might threaten strained health care resources, require extended and more rigorous implementation of public health strategies (4), and increase the percentage of population immunity required for pandemic control. Taking measures to reduce transmission now can lessen the potential impact of B.1.1.7 and allow critical time to increase vaccination coverage. Collectively, enhanced genomic surveillance combined with continued compliance with effective public health measures, including vaccination, physical distancing, use of masks, hand hygiene, and isolation and quarantine, will be essential to limiting the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Strategic testing of persons without symptoms but at higher risk of infection, such as those exposed to SARS-CoV-2 or who have frequent unavoidable contact with the public, provides another opportunity to limit ongoing spread.

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
4929Exploring overcrowding trends in an inner city emergence department in the UK before and during COVID-19 epidemic  

BACKGROUND: The COVID-19 pandemic and the associated lockdowns have caused significant disruptions across society, including changes in the number of emergency department (ED) visits. This study aims to investigate the impact of three pre-COVID-19 interventions and of the COVID-19 UK-epidemic and the first UK national lockdown on overcrowding within University College London Hospital Emergency Department (UCLH ED). The three interventions: target the influx of patients at ED (A), reduce the pressure on in-patients’ beds (B) and improve ED processes to improve the flow of patents out from ED (C). METHODS: We collected overcrowding metrics (daily attendances, the proportion of people leaving within 4 h of arrival (four-hours target) and the reduction in overall waiting time) during 01/04/2017–31/05/2020. We then performed three different analyses, considering three different timeframes. The first analysis used data 01/04/2017–31/12–2019 to calculate changes over a period of 6 months before and after the start of interventions A-C. The second and third analyses focused on evaluating the impact of the COVID-19 epidemic, comparing the first 10 months in 2020 and 2019, and of the first national lockdown (23/03/2020–31/05/2020). RESULTS: Pre-COVID-19 all interventions led to small reductions in waiting time (17%, p < 0.001 for A and C; an 9%, p = 0.322 for B) but also to a small decrease in the number of patients leaving within 4 h of arrival (6.6,7.4,6.2% respectively A-C,p < 0.001). In presence of the COVID-19 pandemic, attendance and waiting time were reduced (40% and 8%; p < 0.001), and the number of people leaving within 4 h of arrival was increased (6%,p < 0.001). During the first lockdown, there was 65% reduction in attendance, 22% reduction in waiting time and 8% increase in number of people leaving within 4 h of arrival (p < 0.001). Crucially, when the lockdown was lifted, there was an increase (6.5%,p < 0.001) in the percentage of people leaving within 4 h, together with a larger (12.5%,p < 0.001) decrease in waiting time. This occurred despite the increase of 49.6%(p < 0.001) in attendance after lockdown ended. CONCLUSIONS: The mixed results pre-COVID-19 (significant improvements in waiting time with some interventions but not improvement in the four-hours target), may be due to indirect impacts of these interventions, where increasing pressure on one part of the ED system affected other parts. This underlines the need for multifaceted interventions and a system-wide approach to improve the pathway of flow through the ED system is necessary. During 2020 and in presence of the COVID-19 epidemic, a shift in public behaviour with anxiety over attending hospitals and higher use of virtual consultations, led to notable drop in UCLH ED attendance and consequential curbing of overcrowding. Importantly, once the lockdown was lifted, although there was an increase in arrivals at UCLH ED, overcrowding metrics were reduced. Thus, the combination of shifted public behaviour and the restructuring changes during COVID-19 epidemic, maybe be able to curb future ED overcrowding, but longer timeframe analysis is required to confirm this.

BMC Emerg Med2021       LitCov and CORD-19
4930Emerging COVID-19 Neurological Manifestations: Present Outlook and Potential Neurological Challenges in COVID-19 Pandemic  

The unremitting coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) marked a year-long phase of public health adversaries and has severely compromised healthcare globally. Early evidence of COVID-19 noted its impact on the pulmonary and cardiovascular functions, while multiple studies in recent time shed light on its substantial neurological complications, though a comprehensive understanding of the cause(s), the mechanism(s), and their neuropathological outcomes is scarce. In the present review, we conferred evidence of neurological complications in COVID-19 patients and shed light on the SARS-CoV-2 infection routes including the hematogenous, direct/neuronal, lymphatic tissue or cerebrospinal fluid, or infiltration through infected immune cells, while the underlying mechanism of SARS-CoV-2 invasion to the central nervous system (CNS) was also discussed. In an up-to-date manner, we further reviewed the impact of COVID-19 in developing diverse neurologic manifestations associated with CNS, peripheral nervous system (PNS), skeletal muscle, and also pre-existing neurological diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, and myasthenia gravis. Furthermore, we discussed the involvement of key factors including age, sex, comorbidity, and disease severity in exacerbating the neurologic manifestations in COVID-19 patients. An outlook of present therapeutic strategies and state of existing challenges in COVID-19 management was also accessed. Conclusively, the present report provides a comprehensive review of COVID-19-related neurological complications and emphasizes the need for their early clinical management in the ongoing COVID-19 pandemic. [Image: see text]

Mol Neurobiol2021       LitCov and CORD-19
4931The Psychological Burden of COVID-19 Stigma: Evaluation of the Mental Health of Isolated Mild Condition COVID-19 Patients  

BACKGROUND: The objective of this article is to assess the mental health issues of the mild condition coronavirus disease 2019 (COVID-19) patients admitted to a community treatment center (CTC) in Korea. METHODS: A total of 107 patients admitted to a CTC were included as the study population, and their mental health problems including depression (patient health questionnaire-9), anxiety (generalized anxiety disorder scale-7), post-traumatic stress disorder (PTSD) (PTSD checklist-5) and somatic symptoms (by patient health questionnaire-15) were evaluated every week during their stay. The stigma related to COVID-19 infection was evaluated with an adjusted version of the Middle East respiratory syndrome (MERS) stigma scale. RESULTS: During the first week of isolation, the prevalence of more-than-moderate depression was 24.3%, more-than-moderate anxiety was 14.9%, more-than-moderate somatic symptoms was 36.5% and possible PTSD was 5.6% of total population. For depression and anxiety, previous psychiatric history and stigma of COVID-19 infection were significant risk factors. For PTSD, previous psychiatric history and stigma of COVID-19 infection as well as total duration of isolation were found to be significant risk factors. Prevalence of depression, anxiety and possible PTSD remained similar across the four weeks of observations, though the prevalence of severe depression, increased after four weeks of stay. Somatic symptoms seemed to decrease during their stay. CONCLUSION: The results suggest that social mitigation of COVID-19 related stigma, as well as care of patients with pre-existing mental health problems are important mental health measures during this crisis period. It is also important that clinical guidelines and public health policies be well balanced over the protection of the public and those quarantined to minimize the negative psychosocial consequences from isolation of the patients.

J Korean Med Sci2021       LitCov and CORD-19
4932A versatile web app for identifying the drivers of COVID-19 epidemics  

BACKGROUND: No versatile web app exists that allows epidemiologists and managers around the world to comprehensively analyze the impacts of COVID-19 mitigation. The http://covid-webapp.numerusinc.com/ web app presented here fills this gap. METHODS: Our web app uses a model that explicitly identifies susceptible, contact, latent, asymptomatic, symptomatic and recovered classes of individuals, and a parallel set of response classes, subject to lower pathogen-contact rates. The user inputs a CSV file of incidence and, if of interest, mortality rate data. A default set of parameters is available that can be overwritten through input or online entry, and a user-selected subset of these can be fitted to the model using maximum-likelihood estimation (MLE). Model fitting and forecasting intervals are specifiable and changes to parameters allow counterfactual and forecasting scenarios. Confidence or credible intervals can be generated using stochastic simulations, based on MLE values, or on an inputted CSV file containing Markov chain Monte Carlo (MCMC) estimates of one or more parameters. RESULTS: We illustrate the use of our web app in extracting social distancing, social relaxation, surveillance or virulence switching functions (i.e., time varying drivers) from the incidence and mortality rates of COVID-19 epidemics in Israel, South Africa, and England. The Israeli outbreak exhibits four distinct phases: initial outbreak, social distancing, social relaxation, and a second wave mitigation phase. An MCMC projection of this latter phase suggests the Israeli epidemic will continue to produce into late November an average of around 1500 new case per day, unless the population practices social-relaxation measures at least 5-fold below the level in August, which itself is 4-fold below the level at the start of July. Our analysis of the relatively late South African outbreak that became the world’s fifth largest COVID-19 epidemic in July revealed that the decline through late July and early August was characterised by a social distancing driver operating at more than twice the per-capita applicable-disease-class (pc-adc) rate of the social relaxation driver. Our analysis of the relatively early English outbreak, identified a more than 2-fold improvement in surveillance over the course of the epidemic. It also identified a pc-adc social distancing rate in early August that, though nearly four times the pc-adc social relaxation rate, appeared to barely contain a second wave that would break out if social distancing was further relaxed. CONCLUSION: Our web app provides policy makers and health officers who have no epidemiological modelling or computer coding expertise with an invaluable tool for assessing the impacts of different outbreak mitigation policies and measures. This includes an ability to generate an epidemic-suppression or curve-flattening index that measures the intensity with which behavioural responses suppress or flatten the epidemic curve in the region under consideration.

J Transl Med2021       LitCov and CORD-19
4933Racial Disparities in COVID-19 Testing and Outcomes: Retrospective Cohort Study in an Integrated Health System  

BACKGROUND: Racial disparities exist in outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. OBJECTIVE: To evaluate the contribution of race/ethnicity in SARS-CoV-2 testing, infection, and outcomes. DESIGN: Retrospective cohort study (1 February 2020 to 31 May 2020). SETTING: Integrated health care delivery system in Northern California. PARTICIPANTS: Adult health plan members. MEASUREMENTS: Age, sex, neighborhood deprivation index, comorbid conditions, acute physiology indices, and race/ethnicity; SARS-CoV-2 testing and incidence of positive test results; and hospitalization, illness severity, and mortality. RESULTS: Among 3 481 716 eligible members, 42.0% were White, 6.4% African American, 19.9% Hispanic, and 18.6% Asian; 13.0% were of other or unknown race. Of eligible members, 91 212 (2.6%) were tested for SARS-CoV-2 infection and 3686 had positive results (overall incidence, 105.9 per 100 000 persons; by racial group, White, 55.1; African American, 123.1; Hispanic, 219.6; Asian, 111.7; other/unknown, 79.3). African American persons had the highest unadjusted testing and mortality rates, White persons had the lowest testing rates, and those with other or unknown race had the lowest mortality rates. Compared with White persons, adjusted testing rates among non-White persons were marginally higher, but infection rates were significantly higher; adjusted odds ratios [aORs] for African American persons, Hispanic persons, Asian persons, and persons of other/unknown race were 2.01 (95% CI, 1.75 to 2.31), 3.93 (CI, 3.59 to 4.30), 2.19 (CI, 1.98 to 2.42), and 1.57 (CI, 1.38 to 1.78), respectively. Geographic analyses showed that infections clustered in areas with higher proportions of non-White persons. Compared with White persons, adjusted hospitalization rates for African American persons, Hispanic persons, Asian persons, and persons of other/unknown race were 1.47 (CI, 1.03 to 2.09), 1.42 (CI, 1.11 to 1.82), 1.47 (CI, 1.13 to 1.92), and 1.03 (CI, 0.72 to 1.46), respectively. Adjusted analyses showed no racial differences in inpatient mortality or total mortality during the study period. For testing, comorbid conditions made the greatest relative contribution to model explanatory power (77.9%); race only accounted for 8.1%. Likelihood of infection was largely due to race (80.3%). For other outcomes, age was most important; race only contributed 4.5% for hospitalization, 12.8% for admission illness severity, 2.3% for in-hospital death, and 0.4% for any death. LIMITATION: The study involved an insured population in a highly integrated health system. CONCLUSION: Race was the most important predictor of SARS-CoV-2 infection. After infection, race was associated with increased hospitalization risk but not mortality. PRIMARY FUNDING SOURCE: The Permanente Medical Group, Inc.

Ann Intern Med2021       LitCov and CORD-19
4934SARS-CoV-2 infection of hACE2 transgenic mice causes severe lung inflammation and impaired function  

Although animal models have been evaluated for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, none have fully recapitulated the severe lung disease phenotypes seen in hospitalized human cases. Here, we evaluate transgenic mice expressing the human ACE2 receptor driven by the cytokeratin-18 gene promoter (K18-hACE2) as a model of SARS-CoV-2 infection. Intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice results in high levels of viral infection in lungs with spread to other organs. A decline in pulmonary function occurs 4 days after peak viral titer and correlates with infiltration of monocytes, neutrophils, and activated T cells. SARS-CoV-2-infected lung tissues show a massively upregulated innate immune response with signatures of NF-kB-dependent, type I and II interferon signaling, and leukocyte activation pathways. Thus, the K18-hACE2 model of SARS-CoV-2 infection shares many features of severe COVID-19 infection and can be used to define the basis of lung disease and test immune and antiviral-based countermeasures.

Nat Immunol2020       LitCov and CORD-19
4935A case of acute demyelinating polyradiculoneuropathy with bilateral facial palsy after ChAdOx1 nCoV-19 vaccine  

BACKGROUND: The coronavirus disease 2019 (COVID-19) global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in late 2019. Researchers around the world are aggressively working to develop a vaccine. One of the vaccines approved against COVID-19 is Oxford–AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19. CASE REPORT: We described a patient who developed four limb distal paraesthesia, postural instability, and facial diplegia, ten days after vaccination with ChAdOx1 nCoV-19 (ABW1277). The electrophysiological findings were compatible with acute demyelinating motor polyneuropathy (Guillain-Barrè syndrome). DISCUSSION: We therefore want to describe a temporal correlation between administration of ChAdOx1 nCoV-19 (ABW1277) vaccine and GBS without evidence of other predisposing infectious or autoimmune factors. This paper aims to highlight the importance of pharmacovigilance and subsequent reports will be needed to evaluate the possible correlation between these two events.

Neurol Sci2021       LitCov and CORD-19
4936Active Surveillance of Adverse Events in Healthcare Workers Recipients After Vaccination with COVID-19 BNT162b2 Vaccine (Pfizer-BioNTech, Comirnaty): A Cross-Sectional Study  

In this cross-sectional study, adverse events after the first and second dose of BNT162b2 mRNA (Pfizer-BioNTech, Comirnaty) vaccine against coronavirus disease 2019 were investigated among employees of clinics in central Italy. A 42-items questionnaire was administrated to vaccine recipients. Adverse events were classified based on severity and occurrence as reported in the literature. A descriptive/univariate analysis using Chi-square or Fisher’s Exact tests was performed. Odds ratio (OR) and 95% confidence intervals were calculated to assess risk factors. 340 individuals (61.5% females; median age 49 years) participated. Adverse events were reported by 279 (82%) and 281 (82.6%) individuals as induced by the first and second dose, respectively. Mild reactions were mainly reported (80.9% and 80.3%), followed by moderate (11.8% and 37.1%) and severe (3.8% and 4.7%). Adverse events were identical to those already described as very common (81.8% and 80.6%), although vaccine-coincidental events not cited in the literature were reported by 6% and 15.6% following each dose. Age ≤ 55 years was a risk factor for any adverse event after each injection (ORs: 2.942 and 2.818), as well as female sex for those mild (ORs: 1.856 and 2.818) and common (ORs: 3.452 and 2.145). Findings were consistent with national reports as most of the adverse events were mild and associated with female sex and young age, while investigations are needed for reactions not described elsewhere. Data are useful to support the vaccine safety profile, also because largely targeted healthcare personnel more skilled than general population in self-diagnosis of health-related issues.

J Community Health2021       LitCov and CORD-19
4937Blended and e-learning in pediatric education: harnessing lessons learned from the COVID-19 pandemic  

Face-to-face education as the traditional basis for medical education was disrupted by the COVID-19 pandemic as learners and educators were moved online with little time for preparation. Fortunately, as online learning has grown, together with medical education shifting to problem-based and team-centered learning over the last three decades, existing resources have been adapted and improved upon to meet the challenges. Effective blended learning has resulted in innovative synchronous and asynchronous learning platforms. Clearly, to do this well requires time, effort, and adjustment from clinicians, educators, and learners, but it should result in an engaging change in teaching practice. Its success will rely on an evaluation of learning outcomes, educator and learner satisfaction, and long-term retention of knowledge. It will be important to maintain ongoing assessment of all aspects of the medical education process, including how to best teach and assess theory, physiology, pathology, history-taking, physical examination, and clinical management. Conclusion: The COVID-19 pandemic triggered emergency transitional processes for teaching and assessment in medical education which built upon existing innovations in teaching medicine with the use of technology. These strategies will continue to evolve so as to provide the basis for an enduring hybrid teaching model involving blended and e-learning in medical education..

Eur J Pediatr2021       LitCov and CORD-19
4938Telehealth for delivery of haemophilia comprehensive care during the COVID-19 pandemic  

INTRODUCTION: The COVID‐19 pandemic caused an unprecedented impact to haemophilia healthcare delivery. In particular, rapid implementation of telehealth solutions was required to ensure continued access to comprehensive care. AIMS: To explore patient and healthcare provider (HCP) experience of telehealth in a European Haemophilia Comprehensive Care Centre. METHOD: A systematic evaluation was performed to survey patient and HCP experience and compare clinical activity levels with telehealth to in‐person attendances. RESULTS: Public health measures implemented in March 2020 to reduce COVID‐19 spread resulted in a 63% decrease in medical/nursing clinic consultation activity compared to the same period in 2019. Implementation of digital care pathways resulted in marked increase in activity (52% greater than 2019). Importantly, enhanced patient engagement was noted, with a 60% reduction in non‐attendance rates. Survey of patients who had participated in medical/nursing teleconsultations demonstrated that teleconsultations improved access (79%), reduced inconvenience (82%), was easy to use (94%) and facilitated good communication with the HCP (97%). A survey exploring the telemedicine experience of HCPs, illustrated that HCPs were satisfied with teleconsultation and the majority (79%) would like to continue to offer teleconsultation as part of routine patient care. In addition to medical/nursing reviews, continued access to physiotherapy with virtual exercise classes for people with haemophilia and teleconsultation for acute dental issues was equally successful. CONCLUSION: During an unprecedented public health emergency, telehealth has enabled continued access to specialized haemophilia comprehensive care. Our novel findings show that this alternative is acceptable to both patients and HCPs and offers future novel opportunities.

Haemophilia2020       LitCov and CORD-19
4939A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2  

Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. B38 and H4 block the binding between virus S-protein RBD and cellular receptor ACE2. A competition assay indicates their different epitopes on the RBD, making them a potential virus-targeting MAb-pair to avoid immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide a structural basis for rational vaccine design.

Science2020       LitCov and CORD-19
4940Psychological distress, coping behaviors and preferences for support among New York healthcare workers during the COVID-19 pandemic  

OBJECTIVE: The mental health toll of COVID-19 on healthcare workers (HCW) is not yet fully described. We characterized distress, coping, and preferences for support among NYC HCWs during the COVID-19 pandemic. METHODS: This was a cross-sectional web survey of physicians, advanced practice providers, residents/fellows, and nurses, conducted during a peak of inpatient admissions for COVID-19 in NYC (April 9th–April 24th 2020) at a large medical center in NYC (n = 657). RESULTS: Positive screens for psychological symptoms were common; 57% for acute stress, 48% for depressive, and 33% for anxiety symptoms. For each, a higher percent of nurses/advanced practice providers screened positive vs. attending physicians, though housestaff's rates for acute stress and depression did not differ from either. Sixty-one percent of participants reported increased sense of meaning/purpose since the COVID-19 outbreak. Physical activity/exercise was the most common coping behavior (59%), and access to an individual therapist with online self-guided counseling (33%) garnered the most interest. CONCLUSIONS: NYC HCWs, especially nurses and advanced practice providers, are experiencing COVID-19-related psychological distress. Participants reported using empirically-supported coping behaviors, and endorsed indicators of resilience, but they also reported interest in additional wellness resources. Programs developed to mitigate stress among HCWs during the COVID-19 pandemic should integrate HCW preferences.

Gen Hosp Psychiatry2020       LitCov and CORD-19
4941The Impact of COVID-19 on Admissions and Management of Patients with Atrial Fibrillation Episodes in the Emergency Department  

Background: During the COVID-19 pandemic, the number of admissions to the emergency department (ED) due to a primary diagnosis of atrial fibrillation (AF) has decreased when compared to pre-pandemic times. The principal aim of the study was to assess the frequency of SARS-CoV-2 infections and sinus rhythm restoration among patients who arrived at the ED with AF. Secondary aims included determining whether patients arriving at the ED principally due to AF delayed their presentations and whether the frequency of successful cardioversion for AF was decreased during the pandemic period. Materials and Methods: A retrospective analysis of medical records of patients admitted to two hospital EDs due to AF during July–December 2019 (pre-pandemic period) versus July–December 2020 (pandemic period) was performed. Results: During the study periods, 601 ED visits by 497 patients were made due to the primary diagnosis of AF. The patients were aged 71.2+/−13.5 years and 51.3% were male. The duration of an AF episode before the ED admission was 10 h (4.5–30 h) during the pandemic period vs. 5 h (3–24 h) during the non-pandemic period (p = 0.001). A shorter duration of the AF episode before ED admission was associated with the successful restoration of the sinus rhythm. During the pandemic period, among patients with short-lasting AF who were not treated with Phenazolinum, the restoration of the sinus rhythm was more frequent in the Copernicus Memorial Hospital than in the University Hospital (p = 0.026). A positive SARS-CoV-2 test was found in 5 (1%) patients, while 2 other patients (0.5%) had a prior diagnosis of COVID-19 disease noted in their medical history. Conclusions: 1. The number of AF episodes treated in these two EDs was lower during the pandemic than non-pandemic period. 2. The patients with AF appeared at the ED later after AF onset in the pandemic period. 3. Successful cardioversion of atrial fibrillation was more frequent during the pre-pandemic period in one of the two hospitals. 4. A difference of approaches to the treatment of short-lasting AF episodes between EDs during the pandemic period may exist between these two EDs. 5. The patients with SARS-CoV-2 infection during the second wave of the COVID-19 pandemic constituted a small percentage of the patients admitted to EDs due to an AF episode.

Int J Environ Res Public Healt2021       LitCov and CORD-19
4942Telemedicine as a component of forward triage in a pandemic  

OBJECTIVE(S): Coronavirus disease 2019 (COVID-19) presents an enormous challenge to healthcare systems globally. Optimizing access to healthcare while minimizing face-to-face patient encounters is critical to limiting exposures, conserving resources, and preserving health. We aimed to evaluate the utility of a COVID-focused telehealth program in avoiding potential in-person visits while maintaining high patient satisfaction. METHODS: All patients with COVID-related virtual visits at our center between March and May 2020 were included. Demographic, satisfaction, and clinical information were gathered using a modified, validated telehealth satisfaction questionnaire disseminated via email or telephone. Data were analyzed using Stata. RESULTS: Of 581 eligible patients, 180 (31%) responded to the survey. Symptoms (73%) and possible exposure (22%) were the main reasons cited for pursuing a virtual visit; cough (44%) and fever (36%) were the most common presenting symptoms. Regarding patient satisfaction, most patients rated the experience as “very good” or “excellent”, and 94% of respondents said they would recommend COVID-focused triage through telehealth to others. Over 81% of patients indicated that, if telehealth was not an option, they would have sought an in-person encounter. Ultimately, only 27% of patients reported pursuing a face-to-face encounter after participating in the virtual visit. CONCLUSION: Based on patient self-reporting, telemedicine potentially prevented face-to-face COVID-related encounters. Patients expressed satisfaction with the virtual process and were less likely to pursue in-person consultation. Leveraging a telehealth strategy for forward triage has the potential to reduce exposures while conserving healthcare resources.

Healthc (Amst)2021       LitCov and CORD-19
4943Reverse Transcription Recombinase-Aided Amplification Assay With Lateral Flow Dipstick Assay for Rapid Detection of 2019 Novel Coronavirus  

BACKGROUND: The emerging Coronavirus Disease-2019 (COVID-19) has challenged the public health globally. With the increasing requirement of detection for SARS-CoV-2 outside of the laboratory setting, a rapid and precise Point of Care Test (POCT) is urgently needed. METHODS: Targeting the nucleocapsid (N) gene of SARS-CoV-2, specific primers, and probes for reverse transcription recombinase-aided amplification coupled with lateral flow dipstick (RT-RAA/LFD) platform were designed. For specificity evaluation, it was tested with human coronaviruses, human influenza A virus, influenza B viruses, respiratory syncytial virus, and hepatitis B virus, respectively. For sensitivity assay, it was estimated by templates of recombinant plasmid and pseudovirus of SARS-CoV-2 RNA. For clinical assessment, 100 clinical samples (13 positive and 87 negatives for SARS-CoV-2) were tested via quantitative reverse transcription PCR (RT-qPCR) and RT-RAA/LFD, respectively. RESULTS: The limit of detection was 1 copies/μl in RT-RAA/LFD assay, which could be conducted within 30 min at 39°C, without any cross-reaction with other human coronaviruses and clinical respiratory pathogens. Compared with RT-qPCR, the established POCT assay offered 100% specificity and 100% sensitivity in the detection of clinical samples. CONCLUSION: This work provides a convenient POCT tool for rapid screening, diagnosis, and monitoring of suspected patients in SARS-CoV-2 endemic areas.

Front Cell Infect Microbiol2021       LitCov and CORD-19
4944Mental Health Impacts of the COVID-19 Pandemic on International University Students, Related Stressors and Coping Strategies  

Background: The coronavirus disease 2019 (COVID-19) pandemic has disrupted university teaching globally. The mental health impacts on international university students have been overlooked. Aims: This study examined the differences in COVID-19-related stressors and mental health impacts between international university students studying in the UK or USA who returned to their home country or region (returnees) and those who stayed in their institution country (stayers), and identified COVID-19-related stressors and coping strategies that were predictors of mental health. Method: An online questionnaire survey was conducted from April 28 through May 12, 2020 using an exponential, non-discriminative snowball sampling strategy (registered at the National Institutes of Health: NCT04365361). Results: A total of 124 full-time international university students (36.3% male) were included: 75.8% had returned to their home country or region for reasons related to COVID-19; 77.4% were pursuing a bachelor's program, and 53.2% were in programs with practicum component. 84.7% of all students had moderate-to-high perceived stress, 12.1% had moderate-to-severe symptoms of anxiety and depression, and 17.7% had moderate-to-severe symptoms of insomnia. Compared with returnees, stayers had significantly higher stress from COVID-19-related stressors such as personal health and lack of social support (Cohen's d: 0.57–1.11), higher perceived stress [10-item Perceived Stress Scale (PSS-10)] {22.6 ± 6.2 vs. 19.1 ± 6.1, β [95% confidence interval (CI)]: 4.039 (0.816, 7.261), Cohen's d: 0.52}, and more severe insomnia symptoms [Insomnia Severity Index (ISI)] [11.8 ± 6.1 vs. 7.6 ± 5.2, β (95% CI): 3.087 (0.262, 5.912), Cohen's d: 0.45], with moderate-to-large effect sizes. Compared with males, females reported significantly higher stress from uncertainties about academic program (Cohen's d: 0.45) with a small effect size. In the total sample, stress related to academics (e.g., personal attainment, uncertainties about academic program, and changes in teaching/learning format), health (including personal health and health of family and friends), availability of reliable COVID-19-related information, and lack of social support predicted more negative mental health impacts. Resilience, positive thinking, and exercise were predictors of less severe mental health impacts. Conclusions: Stayers experienced more adverse mental health impacts than returnees. We call on educators and mental health professionals to provide appropriate support for international students, particularly the stayers, during the pandemic.

Front Psychiatry2020       LitCov and CORD-19
4945The coagulopathy, endotheliopathy and vasculitis of COVID-19  

BACKGROUND: COVID-19-associated coagulopathy (CAC) characterized by the elevated D-dimer without remarkable changes of other global coagulation markers is associated with various thrombotic complications and disease severity. The purpose of this review is to elucidate the pathophysiology of this unique coagulopathy. METHODS: The authors performed online search of published medical literature through PubMed using the MeSH (Medical Subject Headings) term COVID-19, SARS-CoV-2, coronavirus, coagulopathy, and thrombus. Then, selected 51 articles that closely relevant to coagulopathy in COVID-19. RESULTS: The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the pneumocytes, immune cells, and vascular endothelial cells. The alveolar damage and the pulmonary microvascular thrombosis are the major causes of acute lung injury in COVID-19. The endotheliopathy that occurs is due to direct SARS-CoV-2 infection and activation of other pathways that include the immune system and thromboinflammatory responses leading to what is termed CAC. As a result, both microvascular and macrovascular thrombotic events occur in arterial, capillary, venule, and large vein vascular beds to produce multiorgan dysfunction and thrombotic complications. In addition to the endothelial damage, SARS-CoV-2 also can cause vasculitis and presents as a systemic inflammatory vascular disease. Clinical management of COVID-19 includes anticoagulation but novel therapies for endotheliopathy, hypercoagulability, and vasculitis are needed. CONCLUSION: The endotheliopathy due to direct endothelial infection with SARS-COV-2 and the indirect damage caused by inflammation play the predominant role in the development of CAC. The intensive control of thromboinflammation is necessary to improve the outcome of this highly detrimental contagious disease.

Inflamm Res2020       LitCov and CORD-19
4946Consistent localization of SARS-CoV-2 spike glycoprotein and ACE2 over TMPRSS2 predominance in placental villi of 15 COVID-19 positive maternal-fetal dyads  

INTRODUCTION: While the COVID-19 pandemic continues to have a significant global health impact, rates of maternal to infant vertical transmission remain low (<5%). Parenchymal changes of placentas from COVID-19 infected mothers have been reported by several groups, but the localization and relative abundance of SARS-CoV-2 viral proteins and cellular entry machinery has not been fully characterized within larger placental tissue cohorts. METHODS: An extended placental tissue cohort including samples from 15 COVID-19 positive maternal-fetal dyads (with n = 5 cases with evidence of fetal transmission) in comparison with 10 contemporary COVID-19 negative controls. Using comparative immunofluorescence, we examined the localization and relative tissue abundance of SARS-CoV2 spike glycoprotein (CoV2 SP) along with the co-localization of two SARS-CoV2 viral entry proteins angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). RESULTS/CONCLUSIONS: CoV2 SP was present within the villous placenta in COVID-19 positive pregnancies with and without evidence of fetal transmission. We further identified the predominance of ACE2 expression in comparison with TMPRSS2. Importantly, both CoV2 SP and ACE2 expression consistently localized primarily within the outer syncytiotrophoblast layer placental villi, a key physiologic interface between mother and fetus. Overall this study provides an important basis for the ongoing evaluation of SARS-CoV-2 physiology in pregnancy and highlights the importance of the placenta as a key source of primary human tissue for ongoing diagnostic and therapeutic research efforts to reduce the global burden of COVID-19.

Placenta2020       LitCov and CORD-19
4947Risk Factors of Mortality for Patients Receiving Venovenous ECMO for COVID-19 Acute Respiratory Distress Syndrome  

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Surg Infect (Larchmt)2021       LitCov and CORD-19
4948Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C  

Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (<5, 5–11, 12–21 years) in 177 pediatric patients hospitalized with severe acute COVID-19, acute MIS-C, and in convalescent samples of outpatients with mild COVID-19 during 2020 and early 2021. Across all patients, less than 10% show neutralizing antibody titers against Omicron. Children <5 years of age hospitalized with severe acute COVID-19 have lower neutralizing antibodies to SARS-CoV-2 variants compared with patients >5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection and the clinical disease outcome from emerging SARS-CoV-2 variants and supports the need for vaccination in children.

Nat Commun2022       LitCov and CORD-19
4949Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase  

BACKGROUND: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported. METHODS: We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021. RESULTS: The trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified. CONCLUSIONS: The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)

N Engl J Med2021       LitCov and CORD-19
4950Implementing education: Personal communication with a healthcare professional is a critical step to address vaccine hesitancy for people with multiple sclerosis  

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Mult Scler Relat Disord2022       LitCov

(1) COVID-19 Open Research Dataset (CORD-19). 2020. Version 2022-06-02. Retrieved from https://ai2-semanticscholar-cord-19.s3-us-west-2.amazonaws.com/historical_releases.html. Accessed 2022-06-05. doi:10.5281/zenodo.3715506
(2) Chen Q, Allot A, & Lu Z. (2020) Keep up with the latest coronavirus research, Nature 579:193 and Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Research. 2020. (version 2023-01-10)
(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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