\ 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
8851Greatly increased Victorian outpatient private psychiatric care during the COVID-19 pandemic: new MBS-telehealth-item and face-to-face psychiatrist office-based services from April-September 2020  

N/A

Australas Psychiatry2021       LitCov and CORD-19
8852Ultrasensitive and visual detection of SARS-CoV-2 using all-in-one dual CRISPR-Cas12a assay  

The recent outbreak of novel coronavirus (SARS-CoV-2) causing COVID-19 disease spreads rapidly in the world. Rapid and early detection of SARS-CoV-2 facilitates early intervention and prevents the disease spread. Here, we present an All-In-One Dual CRISPR-Cas12a (AIOD-CRISPR) assay for one-pot, ultrasensitive, and visual SARS-CoV-2 detection. By targeting SARS-CoV-2’s nucleoprotein gene, two CRISPR RNAs without protospacer adjacent motif (PAM) site limitation are introduced to develop the AIOD-CRISPR assay and detect the nucleic acids with a sensitivity of few copies. We validate the assay by using COVID-19 clinical swab samples and obtain consistent results with RT-PCR assay. Furthermore, a low-cost hand warmer (~$0.3) is used as an incubator of the AIOD-CRISPR assay to detect clinical samples within 20 min, enabling an instrument-free, visual SARS-CoV-2 detection at the point of care. Thus, our method has the significant potential to provide a rapid, sensitive, one-pot point-of-care assay for SARS-CoV-2.

Nat Commun2020       LitCov and CORD-19
8853Biomarkers and Immune Repertoire Metrics Identified by Peripheral Blood Transcriptomic Sequencing Reveal the Pathogenesis of COVID-19  

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global crisis; however, our current understanding of the host immune response to SARS-CoV-2 infection remains limited. Herein, we performed RNA sequencing using peripheral blood from acute and convalescent patients and interrogated the dynamic changes of adaptive immune response to SARS-CoV-2 infection over time. Our results revealed numerous alterations in these cohorts in terms of gene expression profiles and the features of immune repertoire. Moreover, a machine learning method was developed and resulted in the identification of five independent biomarkers and a collection of biomarkers that could accurately differentiate and predict the development of COVID-19. Interestingly, the increased expression of one of these biomarkers, UCHL1, a molecule related to nervous system damage, was associated with the clustering of severe symptoms. Importantly, analyses on immune repertoire metrics revealed the distinct kinetics of T-cell and B-cell responses to SARS-CoV-2 infection, with B-cell response plateaued in the acute phase and declined thereafter, whereas T-cell response can be maintained for up to 6 months post-infection onset and T-cell clonality was positively correlated with the serum level of anti-SARS-CoV-2 IgG. Together, the significantly altered genes or biomarkers, as well as the abnormally high levels of B-cell response in acute infection, may contribute to the pathogenesis of COVID-19 through mediating inflammation and immune responses, whereas prolonged T-cell response in the convalescents might help these patients in preventing reinfection. Thus, our findings could provide insight into the underlying molecular mechanism of host immune response to COVID-19 and facilitate the development of novel therapeutic strategies and effective vaccines.

Front Immunol2021       LitCov and CORD-19
8854Neutralizing Antibodies and Cytokines in Breast Milk After COVID-19 mRNA Vaccination  

OBJECTIVE: To evaluate immune responses to coronavirus disease 2019 (COVID-19) mRNA-based vaccines present in breast milk and transfer of the immune responses to breastfeeding infants. METHODS: We enrolled 30 lactating women who received mRNA-based COVID-19 vaccines from January through April 2021 in this cohort study. Women provided serial milk samples, including milk expressed before vaccination, across 2–3 weeks after the first dose, and across 3 weeks after the second dose. Women provided their blood, spotted on cards (dried blood spots), 19 days after the first dose and 21 days after the second dose. Stool samples from the breastfed infants were collected 21 days after mothers' second vaccination. Prepandemic samples of milk, dried blood spots, and infant stool were used as controls. Milk, dried blood spots, and infant stool were tested by enzyme-linked immunosorbent assay for receptor-binding domain (RBD)–specific immunoglobulin (Ig)A and IgG. Milk samples were tested for the presence of neutralizing antibodies against the spike and four variants of concern: D614G, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1). Levels of 10 cytokines were measured in milk samples. RESULTS: Milk from COVID-19-immunized women neutralized the spike and four variants of concern, primarily driven by anti-RBD IgG. The immune response in milk also included significant elevation of interferon-γ. The immune response to maternal vaccination was reflected in breastfed infants: anti-RBD IgG and anti-RBD IgA were detected in 33% and 30% of infant stool samples, respectively. Levels of anti-RBD antibodies in infant stool correlated with maternal vaccine side effects. Median antibody levels against RBD were below the positive cutoffs in prepandemic milk and infant stool samples. CONCLUSION: Humoral and cellular immune responses to mRNA-based COVID-19 vaccination are present in most women’s breast milk. The milk anti-RBD antibodies can neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike and variants of concern. Anti-RBD antibodies are transferred to breastfed infants, with the potential to confer passive immunity against SARS-CoV-2.

Obstet Gynecol2021       LitCov and CORD-19
8855Changes in Mental Health among Psychiatric Patients during the COVID-19 Pandemic in Hong Kong-A Cross-Sectional Study  

Background: The COVID-19 pandemic has had substantial impacts on citizens’ daily living. Concerns over mental health issues are rising. Recent studies assessing the psychosocial impact of COVID-19 on the general public revealed alarming results. Meanwhile, the impact of the COVID-19 pandemic on mental health among patients with pre-existing psychiatric disorders remained unclear. Methods: Patients diagnosed with anxiety disorders, depressive disorders, bipolar disorders, or schizophrenia were invited to complete a survey between July and October 2020. The survey collected information on subjects’ demographics, accommodation status, changes in mental health status during the COVID-19 outbreak, and the factors that affect subjects’ mental health during COVID-19. The primary outcome of this study was the change in mental health, defined by psychiatric symptom change and patient satisfaction on symptom control. The secondary outcomes were patients’ emotional status—measured by the Depression, Anxiety and Stress Scale (DASS-21)—during the COVID-19 pandemic and factors that impacted patients’ mental health during the COVID-19 pandemic. Results: Out of the 294 patients recruited, 65.0% were living in hostel while 35.0% were living in the community. The proportion of patients with ‘unsatisfied’ or ‘very unsatisfied’ mental disease control increased from 10.2% to 17.1% after the COVID-19 outbreak (p < 0.001). Under the DASS-21 questionnaire, 24.2% subjects, 32.6% subjects, and 18.9% subjects were classified as severe or extremely severe in terms of the level of depression, anxiety, and stress they experienced, respectively. Patients living in the community, patients with mood disorders, and female patients reported significantly worse control over anxiety and mood symptoms. The three major factors that affected patients’ mental health during COVID-19 were ‘reduced social activities’, ‘worries over people around getting infected’, and ‘reduced exercise’. Conclusion: Psychiatric patients in general have poorer disease control after the COVID-19 outbreak. Patients in the community appeared to be more affected than patients residing in hostels. More efforts should be directed to screening patients with pre-existing mental health disorders to enable timely interventions.

Int J Environ Res Public Healt2022       LitCov and CORD-19
8856Covid-19 and development of heart failure: mystery and truth  

Coronavirus disease 2019 (Covid-19) is a novel worldwide pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During Covid-19 pandemic, socioeconomic deprivation, social isolation, and reduced physical activities may induce heart failure (HF), destabilization, and cause more complications. HF appears as a potential hazard due to SARS-CoV-2 infection, chiefly in elderly patients with underlying comorbidities. In reality, the expression of cardiac ACE2 is implicated as a target point for SARS-CoV-2-induced acute cardiac injury. In SARS-CoV-2 infection, like other febrile illnesses, high blood viscosity, exaggerated pro-inflammatory response, multisystem inflammatory syndrome, and endothelial dysfunction-induced coagulation disorders may increase risk of HF development. Hypoxic respiratory failure, as in pulmonary edema, severe acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) may affect heart hemodynamic stability due to the development of pulmonary hypertension. Indeed, Covid-19-induced HF could be through the development of cytokine storm, characterized by high proliferation pro-inflammatory cytokines. In cytokine storm-mediated cardiac dysfunction, there is a positive correlation between levels of pro-inflammatory cytokine and myocarditis-induced acute cardiac injury biomarkers. Therefore, Covid-19-induced HF is more complex and related from a molecular background in releasing pro-inflammatory cytokines to the neuro-metabolic derangements that together affect cardiomyocyte functions and development of HF. Anti-heart failure medications, mainly digoxin and carvedilol, have potent anti-SARS-CoV-2 and anti-inflammatory properties that may mitigate Covid-19 severity and development of HF. In conclusion, SARS-CoV-2 infection may lead to the development of HF due to direct acute cardiac injury or through the development of cytokine storms, which depress cardiomyocyte function and cardiac contractility. Anti-heart failure drugs, mainly digoxin and carvedilol, may attenuate severity of HF by reducing the infectivity of SARS-CoV-2 and prevent the development of cytokine storms in severely affected Covid-19 patients.

Naunyn Schmiedebergs Arch Phar2021       LitCov and CORD-19
8857Evaluating the impact of stay-at-home and quarantine measures on COVID-19 spread  

N/A

BMC Infect Dis2022       LitCov
8858Discovery of New Hydroxyethylamine Analogs against 3CLpro Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies  

[Image: see text] The novel coronavirus, SARS-CoV-2, has caused a recent pandemic called COVID-19 and a severe health threat around the world. In the current situation, the virus is rapidly spreading worldwide, and the discovery of a vaccine and potential therapeutics are critically essential. The crystal structure for the main protease (M(pro)) of SARS-CoV-2, 3-chymotrypsin-like cysteine protease (3CL(pro)), was recently made available and is considerably similar to the previously reported SARS-CoV. Due to its essentiality in viral replication, it represents a potential drug target. Herein, a computer-aided drug design (CADD) approach was implemented for the initial screening of 13 approved antiviral drugs. Molecular docking of 13 antivirals against the 3-chymotrypsin-like cysteine protease (3CL(pro)) enzyme was accomplished, and indinavir was described as a lead drug with a docking score of −8.824 and a XP Gscore of −9.466 kcal/mol. Indinavir possesses an important pharmacophore, hydroxyethylamine (HEA), and thus, a new library of HEA compounds (>2500) was subjected to virtual screening that led to 25 hits with a docking score more than indinavir. Exclusively, compound 16 with a docking score of −8.955 adhered to drug-like parameters, and the structure–activity relationship (SAR) analysis was demonstrated to highlight the importance of chemical scaffolds therein. Molecular dynamics (MD) simulation analysis performed at 100 ns supported the stability of 16 within the binding pocket. Largely, our results supported that this novel compound 16 binds with domains I and II, and the domain II–III linker of the 3CL(pro) protein, suggesting its suitability as a strong candidate for therapeutic discovery against COVID-19.

J Chem Inf Model2020       LitCov and CORD-19
8859COVID-19: Role of Chest CT in Diagnosis and Management  

N/A

AJR Am J Roentgenol2020       LitCov and CORD-19
8860Temperature, Humidity and Latitude Analysis to Estimate Potential Spread and Seasonality of COVID-19  

IMPORTANCE: Coronavirus disease 2019 (COVID-19) infection has resulted in a global crisis. Investigating the potential association of climate and seasonality with the spread of this infection could aid in preventive and surveillance strategies. OBJECTIVE: To examine the association of climate with the spread of COVID-19 infection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined climate data from 50 cities worldwide with and without substantial community spread of COVID-19. Eight cities with substantial spread of COVID-19 (Wuhan, China; Tokyo, Japan; Daegu, South Korea; Qom, Iran; Milan, Italy; Paris, France; Seattle, US; and Madrid, Spain) were compared with 42 cities that have not been affected or did not have substantial community spread. Data were collected from January to March 10, 2020. MAIN OUTCOMES AND MEASURES: Substantial community transmission was defined as at least 10 reported deaths in a country as of March 10, 2020. Climate data (latitude, mean 2-m temperature, mean specific humidity, and mean relative humidity) were obtained from ERA-5 reanalysis. RESULTS: The 8 cities with substantial community spread as of March 10, 2020, were located on a narrow band, roughly on the 30° N to 50° N corridor. They had consistently similar weather patterns, consisting of mean temperatures of between 5 and 11 °C, combined with low specific humidity (3-6 g/kg) and low absolute humidity (4-7 g/m(3)). There was a lack of substantial community establishment in expected locations based on proximity. For example, while Wuhan, China (30.8° N) had 3136 deaths and 80 757 cases, Moscow, Russia (56.0° N), had 0 deaths and 10 cases and Hanoi, Vietnam (21.2° N), had 0 deaths and 31 cases. CONCLUSIONS AND RELEVANCE: In this study, the distribution of substantial community outbreaks of COVID-19 along restricted latitude, temperature, and humidity measurements was consistent with the behavior of a seasonal respiratory virus. Using weather modeling, it may be possible to estimate the regions most likely to be at a higher risk of substantial community spread of COVID-19 in the upcoming weeks, allowing for concentration of public health efforts on surveillance and containment.

JAMA Netw Open2020       LitCov and CORD-19
8861The effectiveness of the TWO-DOSE BNT162b2 vaccine: analysis of real-world data  

BACKGROUND: COVID-19 mRNA vaccines were shown to be highly efficacious in preventing the disease in randomized controlled trials; nonetheless, evidence on the real-world effectiveness of this vaccine is limited. Study objective was to evaluate the effectiveness of BNT162b2 vaccine in preventing SARS-CoV-2 infection and COVID-19-related hospitalization and mortality. METHODS: This historical cohort study included members of a large health provider in Israel that were vaccinated with at least one dose of BNT162b2. The primary outcome was incidence rate of a SARS-CoV-2 infection confirmed with rt-PCR, between 7 to 27 days after second dose (protection-period), as compared to days 1 to 7 after the first dose, where no protection by the vaccine is assumed (reference-period). RESULTS: Data of 1,178,597 individuals vaccinated with BNT162b2 were analyzed (mean age 47.7 years [SD=18.1], 48.4% males) of whom 872,454 (74.0%) reached the protection period. Overall, 4514 infections occurred during the reference period compared to 728 during the protection period, yielding a weighted mean daily incidence of 54.8 per 100,000 (95%CI: 26.1-115.0 per 100,000) and 5.4 per 100,000 (95%CI: 3.5-8.4 per 100,000), respectively. The vaccine effectiveness in preventing infection was 90% (95%CI:79%- 95%) and 94% (95%CI:88%-97%) against COVID-19. Among immunosuppressed patients, vaccine effectiveness against infection was 71% (95%CI:37%-87%). The adjusted hazard ratios for hospitalization in those infected were 0.82 (95%CI:0.36-1.88), 0.45 (95%CI:0.23-0.90), and 0.56 (95%CI:0.36-0.89) in the age groups 16-44, 45-64 and 75 and above, respectively. CONCLUSIONS: The effectiveness of the BNT162b2 vaccine is comparable to the one reported in the phase III clinical trial.

Clin Infect Dis2021       LitCov and CORD-19
8862Higher entropy observed in SARS-CoV-2 genomes from the first COVID-19 wave in Pakistan  

BACKGROUND: We investigated the genome diversity of SARS-CoV-2 associated with the early COVID-19 period to investigate evolution of the virus in Pakistan. MATERIALS AND METHODS: We studied ninety SARS-CoV-2 strains isolated between March and October 2020. Whole genome sequences from our laboratory and available genomes were used to investigate phylogeny, genetic variantion and mutation rates of SARS-CoV-2 strains in Pakistan. Site specific entropy analysis compared mutation rates between strains isolated before and after June 2020. RESULTS: In March, strains belonging to L, S, V and GH clades were observed but by October, only L and GH strains were present. The highest diversity of clades was present in Sindh and Islamabad Capital Territory and the least in Punjab province. Initial introductions of SARS-CoV-2 GH (B.1.255, B.1) and S (A) clades were associated with overseas travelers. Additionally, GH (B.1.255, B.1, B.1.160, B.1.36), L (B, B.6, B.4), V (B.4) and S (A) clades were transmitted locally. SARS-CoV-2 genomes clustered with global strains except for ten which matched Pakistani isolates. RNA substitution rates were estimated at 5.86 x10(−4). The most frequent mutations were 5’ UTR 241C > T, Spike glycoprotein D614G, RNA dependent RNA polymerase (RdRp) P4715L and Orf3a Q57H. Strains up until June 2020 exhibited an overall higher mean and site-specific entropy as compared with sequences after June. Relative entropy was higher across GH as compared with GR and L clades. More sites were under selection pressure in GH strains but this was not significant for any particular site. CONCLUSIONS: The higher entropy and diversity observed in early pandemic as compared with later strains suggests increasing stability of the genomes in subsequent COVID-19 waves. This would likely lead to the selection of site-specific changes that are advantageous to the virus, as has been currently observed through the pandemic.

PLoS One2021       LitCov and CORD-19
8863Do people with mental health problems have lower adherence to precautionary measures in COVID-19 pandemic? A cross-sectional observational study in Hong Kong  

OBJECTIVES: Mental health problems are prevalent during the COVID-19 pandemic, but their effect on adherence to precautionary measures is not well understood. Given that psychological morbidities are associated with lower treatment adherence, and that precautionary measures are important in containing the spread of COVID-19, this study aims to determine if people with mental health problems have lower adherence to precautionary measures against COVID-19. DESIGN: We conducted a cross-sectional territory-wide online survey between 17 June and 31 July 2020 during the COVID-19 pandemic. Clinically significant mental health problems, adherence to precautionary behaviours, and confounding factors such as sociodemographic factors and self-reported physical health were assessed. SETTING: The link to the questionnaire was disseminated to the general population in all 18 districts of Hong Kong using various social media platforms. PARTICIPANTS: 1036 individuals completed the survey. Of them, 1030 met the inclusion criteria of being adult Hong Kong residents. PRIMARY OUTCOME: Adherence to precautionary measures against COVID-19, including wearing face mask, frequent handwashing, household disinfection, social distancing, minimising unnecessary travel, and stocking up on food and daily essentials. RESULTS: Of the 1030 participants, 166 (16.1%) had clinically significant mental health problems. Interestingly, they were more likely to stock up on food and daily essentials during the pandemic (7 (4.2%) vs 15 (1.7%), p=0.04; unadjusted OR=2.49, 95% CI=1.00 to 6.21, p<0.05) and had a lesser tendency to stop social distancing even if the pandemic subsides (86 (51.8%) vs 513 (59.4%), p=0.07; unadjusted OR=0.74, 95% CI=0.53 to 1.03, p=0.07). The latter association remained significant after adjusting for the confounding factors (adjusted OR=0.68, 95% CI=0.48 to 0.96, p=0.03). CONCLUSIONS: Contrary to our hypothesis, people who are mentally unwell might go beyond the recommended precautionary measures. Our findings highlight the need to identify mental health problems and provide care and support for those who might go too far with precautionary measures. TRIAL REGISTRATION NUMBER: ChiCTR 2000033936.

BMJ Open2021       LitCov and CORD-19
8864Update: COVID-19 Pandemic-Associated Changes in Emergency Department Visits-United States, December 2020-January 2021  

During March 29-April 25, 2020, emergency department (ED) visits in the United States declined by 42% after the declaration of a national emergency for COVID-19 on March 13, 2020. Among children aged ≤10 years, ED visits declined by 72% compared with prepandemic levels (1). To assess the continued impact of the COVID-19 pandemic on EDs, CDC examined trends in visits since December 30, 2018, and compared the numbers and types of ED visits by patient demographic and geographic factors during a COVID-19 pandemic period (December 20, 2020-January 16, 2021) with a prepandemic period 1 year earlier (December 15, 2019-January 11, 2020). After an initial decline during March-April 2020 (1), ED visits increased through July 2020, but at levels below those during the previous year, until December 2020-January 2021 when visits again fell to 25% of prepandemic levels. During this time, among patients aged 0-4, 5-11, 12-17, and ≥18 years, ED visits were lower by 66%, 63%, 38%, and 17%, respectively, compared with ED visits for each age group during the same period before the pandemic. Differences were also observed by region and reasons for ED visits during December 2020-January 2021; more visits during this period were for infectious diseases or mental and behavioral health-related concerns and fewer visits were for gastrointestinal and upper-respiratory-related illnesses compared with ED visits during December 2019-January 2020. Although the numbers of ED visits associated with socioeconomic factors and mental or behavioral health conditions are low, the increased visits by both adults and children for these concerns suggest that health care providers should maintain heightened vigilance in screening for factors that might warrant further treatment, guidance, or intervention during the COVID-19 pandemic.

MMWR Morb Mortal Wkly Rep2021       LitCov and CORD-19
8865Effectiveness of Monovalent mRNA Vaccines Against COVID-19 Associated Hospitalization Among Immunocompetent Adults During BA.1/BA.2 and BA.4/BA.5 Predominant Periods of SARS-CoV-2 Omicron Variant in the United States-IVY Network, 18 States, December 26, 2021-August 31, 2022  

N/A

MMWR Morb Mortal Wkly Rep2022       LitCov
8866Clinical characteristics and outcomes of pregnant women with COVID-19 and comparison with control patients: A systematic review and meta-analysis  

In a large‐scale study, 128176 non‐pregnant patients (228 studies) and 10000 pregnant patients (121 studies) confirmed COVID‐19 cases included in this Meta‐Analysis. The mean (confidence interval [CI]) of age and gestational age of admission (GA) in pregnant women was 33 (28–37) years old and 36 (34–37) weeks, respectively. Pregnant women show the same manifestations of COVID‐19 as non‐pregnant adult patients. Fever (pregnant: 75.5%; non‐pregnant: 74%) and cough (pregnant: 48.5%; non‐pregnant: 53.5%) are the most common symptoms in both groups followed by myalgia (26.5%) and chill (25%) in pregnant and dysgeusia (27%) and fatigue (26.5%) in non‐pregnant patients. Pregnant women are less probable to show cough (odds ratio [OR] 0.7; 95% CI 0.67–0.75), fatigue (OR: 0.58; CI: 0.54–0.61), sore throat (OR: 0.66; CI: 0.61–0.7), headache (OR: 0.55; CI: 0.55–0.58) and diarrhea (OR: 0.46; CI: 0.4–0.51) than non‐pregnant adult patients. The most common imaging found in pregnant women is ground‐glass opacity (57%) and in non‐pregnant patients is consolidation (76%). Pregnant women have higher proportion of leukocytosis (27% vs. 14%), thrombocytopenia (18% vs. 12.5%) and have lower proportion of raised C‐reactive protein (52% vs. 81%) compared with non‐pregnant patients. Leucopenia and lymphopenia are almost the same in both groups. The most common comorbidity in pregnant patients is diabetes (18%) and in non‐pregnant patients is hypertension (21%). Case fatality rate (CFR) of non‐pregnant hospitalized patients is 6.4% (4.4–8.5), and mortality due to all‐cause for pregnant patients is 11.3% (9.6–13.3). Regarding the complications of pregnancy, postpartum hemorrhage (54.5% [7–94]), caesarean delivery (48% [42–54]), preterm labor (25% [4–74]) and preterm birth (21% [12–34]) are in turn the most prevalent complications. Comparing the pregnancy outcomes show that caesarean delivery (OR: 3; CI: 2–5), low birth weight (LBW) (OR: 9; CI: 2.4–30) and preterm birth (OR: 2.5; CI: 1.5–3.5) are more probable in pregnant woman with COVID‐19 than pregnant women without COVID‐19. The most prevalent neonatal complications are neonatal intensive care unit admission (43% [2–96]), fetal distress (30% [12–58]) and LBW (25% [16–37]). The rate of vertical transmission is 5.3% (1.3–16), and the rate of positive SARS‐CoV‐2 test for neonates born to mothers with COVID‐19 is 8% (4–16). Overall, pregnant patients present with the similar clinical characteristics of COVID‐19 when compared with the general population, but they may be more asymptomatic. Higher odds of caesarean delivery, LBW and preterm birth among pregnant patients with COVID‐19 suggest a possible association between COVID‐19 infection and pregnancy complications. Low risk of vertical transmission is present, and SARS‐CoV‐2 can be detected in all conception products, particularly placenta and breast milk. Interpretations of these results should be done cautiously due to the heterogeneity between studies; however, we believe our findings can guide the prenatal and postnatal considerations for COVID‐19 pregnant patients.

Rev Med Virol2021       LitCov and CORD-19
8867Characteristics and Outcomes Among US Patients Hospitalized for Ischemic Stroke Before vs During the COVID-19 Pandemic  

IMPORTANCE: After the emergence of COVID-19, studies reported a decrease in hospitalizations of patients with ischemic stroke (IS), but there are little to no data regarding hospitalizations for the remainder of 2020, including outcome data from a large cohort of patients with IS and comorbid COVID-19. OBJECTIVE: To assess hospital discharge rates, demographic factors, and outcomes of hospitalization associated with the COVID-19 pandemic among US patients with IS before vs during the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the Vizient Clinical Data Base on 324 013 patients with IS at 478 nonfederal hospitals in 43 US states between January 1, 2019, and December 31, 2020. Patients were eligible if they were admitted to the hospital on a nonelective basis and were not receiving hospice care at the time of admission. A total of 41 166 discharged between January and March 2020 were excluded from the analysis because they had unreliable data on COVID-19 status, leaving 282 847 patients for the study. EXPOSURE: Ischemic stroke and laboratory-confirmed COVID-19. MAIN OUTCOMES AND MEASURES: Monthly counts of discharges among patients with IS in 2020. Demographic characteristics and outcomes, including in-hospital death, among patients with IS who were discharged in 2019 (control group) were compared with those of patients with IS with or without comorbid COVID-19 (COVID-19 and non–COVID-19 groups, respectively) who were discharged between April and December 2020. RESULTS: Of the 282 847 patients included in the study, 165 912 (50.7% male; 63.4% White; 26.3% aged ≥80 years) were allocated to the control group; 111 418 of 116 935 patients (95.3%; 51.9% male; 62.8% White; 24.6% aged ≥80 years) were allocated to the non–COVID-19 group and 5517 of 116 935 patients (4.7%; 58.0% male; 42.5% White; 21.3% aged ≥80 years) to the COVID-19 group. A mean (SD) of 13 846 (553) discharges per month among patients with IS was reported in 2019. Discharges began decreasing in February 2020, reaching a low of 10 846 patients in April 2020 before returning to a prepandemic level of 13 639 patients by July 2020. A mean (SD) of 13 492 (554) discharges per month was recorded for the remainder of 2020. Black and Hispanic patients accounted for 21.4% and 7.0% of IS discharges in 2019, respectively, but accounted for 27.5% and 16.0% of those discharged with IS and comorbid COVID-19 in 2020. Compared with patients in the control and non–COVID-19 groups, those in the COVID-19 group were less likely to smoke (16.0% vs 17.2% vs 6.4%, respectively) and to have hypertension (73.0% vs 73.1% vs 68.2%) or dyslipidemia (61.2% vs 63.2% vs 56.6%) but were more likely to have diabetes (39.8% vs 40.5% vs 53.0%), obesity (16.2% vs 18.4% vs 24.5%), acute coronary syndrome (8.0% vs 9.2% vs 15.8%), or pulmonary embolus (1.9% vs 2.4% vs 6.8%) and to require intubation (11.3% vs 12.3% vs 37.6%). After adjusting for baseline factors, patients with IS and COVID-19 were more likely to die in the hospital than were patients with IS in 2019 (adjusted odds ratio, 5.17; 95% CI, 4.83-5.53; National Institutes of Health Stroke Scale adjusted odds ratio, 3.57; 95% CI, 3.15-4.05). CONCLUSIONS AND RELEVANCE: In this cohort study, after the emergence of COVID-19, hospital discharges of patients with IS decreased in the US but returned to prepandemic levels by July 2020. Among patients with IS between April and December 2020, comorbid COVID-19 was relatively common, particularly among Black and Hispanic populations, and morbidity was high.

JAMA Netw Open2021       LitCov and CORD-19
8868Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2  

BACKGROUND: Antibodies raised against human seasonal coronaviruses (sCoVs), which are responsible for the common cold, are known to cross-react with SARS-CoV-2 antigens. This prompts questions about their protective role against SARS-CoV-2 infections and COVID-19 severity. However, the relationship between sCoVs exposure and SARS-CoV-2 correlates of protection are not clearly identified. METHODS: We performed a cross-sectional analysis of cross-reactivity and cross-neutralization to SARS-CoV-2 antigens (S-RBD, S-trimer, N) using pre-pandemic sera from four different groups: pediatrics and adolescents, individuals 21 to 70 years of age, older than 70 years of age, and individuals living with HCV or HIV. Data was then further analysed using machine learning to identify predictive patterns of neutralization based on sCoVs serology. FINDINGS: Antibody cross-reactivity to SARS-CoV-2 antigens varied between 1.6% and 15.3% depending on the cohort and the isotype-antigen pair analyzed. We also show a range of neutralizing activity (0-45%) with median inhibition ranging from 17.6 % to 23.3 % in serum that interferes with SARS-CoV-2 spike attachment to ACE2 independently of age group. While the abundance of sCoV antibodies did not directly correlate with neutralization, we show that neutralizing activity is rather dependent on relative ratios of IgGs in sera directed to all four sCoV spike proteins. More specifically, we identified antibodies to NL63 and OC43 as being the most important predictors of neutralization. INTERPRETATION: Our data support the concept that exposure to sCoVs triggers antibody responses that influence the efficiency of SARS-CoV-2 spike binding to ACE2, which may potentially impact COVID-19 disease severity through other latent variables. FUNDING: This study was supported by a grant by the CIHR (VR2 -172722) and by a grant supplement by the CITF, and by a NRC Collaborative R&D Initiative Grant (PR031-1).

EBioMedicine2021       LitCov and CORD-19
8869Silico analysis of interaction between full-length SARS-CoV-2 S protein with human Ace2 receptor: Modelling, docking, MD simulation  

Many key residues, which mediate the interaction between SARS-CoV2 spike glycoprotein (S protein) and human ACE2 receptor, have been reviewed using the SARS-CoV2 S spike protein with human ACE2 complex. The initial SARS-CoV2 S protein and ACE2 protein complex structure is formed by RBD structure of SARS-CoV2 S protein and ACE2 protein. However, the cryo-EM structure study targeting SARS-Cov S protein with human ACE2 complex has shown that there exist different binding conformations during the binding process facing ACE2 protein. It suggests the interaction between SARS-CoV2 S spike protein complex might have different binding conformations, which request full-length of SARS-CoV2 S protein complex in the structure-functional analysis. In this study, we built a full-length SARS-CoV2 S protein with human ACE2 complex by computational methods. Residues K31, H34, E35 in ACE2 protein were showed both in our full-length model and RBD structure model, which recognized as critical residues in previous studies. Surprisingly, ACE2 residues E564, R559, N556 were only found participating in the interaction of our full-length model, which suggested the full-length model has bigger binding interface. This finding was further supported by the interaction network of full-length model and RBD model. Meanwhile, the method bias was taken into consideration. Eventually, the MM-PBSA results showed the full-length model had a stronger binding free energy (almost 5-fold) than the RBD structure model of SARS-CoV2 S spike protein complex. In computational level, we present a stronger binding model containing a full-length structure of SARS-CoV2 S protein with ACE2 complex.

Biophys Chem2020       LitCov and CORD-19
8870Increasing SARS-CoV-2 RT-qPCR testing capacity by sample pooling  

OBJECTIVES: Limited testing capacity has characterized the ongoing COVID-19 pandemic in Spain, hampering a timely control of outbreaks and the possibilities to reduce the escalation of community transmissions. Here we investigated the potential of using pooling of samples followed by one-step retrotranscription and quantitative PCR (RT-qPCR) to increase SARS-CoV-2 testing capacity. METHODS: We first evaluated different sample pooling (1:5, 1:10 and 1:15) prior to RNA extractions followed by standard RT-qPCR for SARS-CoV-2/COVID-19 diagnosis. The pool size achieving reproducible results in independent tests was then used for assessing nasopharyngeal samples in a tertiary hospital during August 2020. RESULTS: We found that pool size of five samples achieved the highest sensitivity compared to pool sizes of 10 and 15, showing a mean (± SD) Ct shift of 3.5 ± 2.2 between the pooled test and positive samples in the pool. We then used a pool size of five to test a total of 895 pools (4,475 prospective samples) using two different RT-qPCR kits available at that time. The Real Accurate Quadruplex corona-plus PCR Kit (PathoFinder) reported the lowest mean Ct (± SD) shift (2.2 ± 2.4) among the pool and the individual samples. The strategy allows detecting individual samples in the positive pools with Cts in the range of 16.7-39.4. CONCLUSIONS: We found that pools of five samples combined with RT-qPCR solutions helped to increase SARS-CoV-2 testing capacity with minimal loss of sensitivity compared to that resulting from testing the samples independently.

Int J Infect Dis2020       LitCov and CORD-19
8871Workplace Factors, Burnout Signs and Clinical Mental Health Symptoms among Mental Health Workers in Lombardy and Quebec during the First Wave of COVID-19  

Several research contributions have depicted the impact of the pandemic environment on healthcare and social care personnel. Even though the high prevalence of burnout depression and anxiety in healthcare settings before COVID-19 has been well documented in the research, the recent increase in psychological distress and mental health issues in healthcare and mental health workers should be attributed to the effect of the COVID-19 pandemic. The aim of the present study is to develop, evaluate, and compare a model of COVID-19 workplace stressors between two different territories, the Italian region of Lombardy and the Canadian province of Quebec. Within this model, burnout is depicted as the strongest determinant of mental health symptoms for mental health workers. In turn, the main workplace determinants of burnout are the perception of a lack of support from the organization and the fear of contracting COVID-19 at work. Findings also provide insights for designing interventions to promote and protect mental health workers in the context of the pandemic. In conclusion, it is necessary to monitor burnout and carefully analyze elements of organizational culture, in addition to offering clinical and psychological care for those in need.

Int J Environ Res Public Healt2022       LitCov and CORD-19
8872Clinical Characteristics and Risk Factors for Mortality in Very Old Patients Hospitalized With COVID-19 in Spain  

BACKGROUND: Advanced age is a well-known risk factor for poor prognosis in COVID-19. However, few studies have specifically focused on very old inpatients with COVID-19. This study aims to describe the clinical characteristics of very old inpatients with COVID-19 and identify risk factors for in-hospital mortality at admission. METHODS: We conducted a nationwide, multicenter, retrospective, observational study in patients ≥ 80 years hospitalized with COVID-19 in 150 Spanish hospitals (SEMI-COVID-19) Registry (March 1–May 29, 2020). The primary outcome was in-hospital mortality. A uni- and multivariate logistic regression was performed to assess predictors of mortality at admission. RESULTS: A total of 2772 consecutive patients (49.4% men, median age 86.3 years) were analyzed. Rates of atherosclerotic cardiovascular disease, diabetes mellitus, dementia, and Barthel Index < 60 were 30.8%, 25.6%, 30.5%, and 21.0%, respectively. The overall case-fatality rate was 46.9% (n: 1301) and increased with age (80–84 years: 41.6%; 85–90 years: 47.3%; 90–94 years: 52.7%; ≥95 years: 54.2%). After analysis, male sex and moderate-to-severe dependence were independently associated with in-hospital mortality; comorbidities were not predictive. At admission, independent risk factors for death were: oxygen saturation < 90%; temperature ≥ 37.8°C; quick sequential organ failure assessment (qSOFA) score ≥ 2; and unilateral–bilateral infiltrates on chest x-rays. Some analytical findings were independent risk factors for death, including estimated glomerular filtration rate < 45 mL/min/1.73 m(2); lactate dehydrogenase ≥ 500 U/L; C-reactive protein ≥ 80 mg/L; neutrophils ≥ 7.5 × 10(3)/μL; lymphocytes < 0.8 × 10(3)/μL; and monocytes < 0.5 × 10(3)/μL. CONCLUSIONS: This first large, multicenter cohort of very old inpatients with COVID-19 shows that age, male sex, and poor preadmission functional status—not comorbidities—are independently associated with in-hospital mortality. Severe COVID-19 at admission is related to poor prognosis.

J Gerontol A Biol Sci Med Sci2020       LitCov and CORD-19
8873Levels of SARS-CoV-2 antibodies among fully vaccinated individuals with Delta or Omicron variant breakthrough infections  

N/A

Nat Commun2022       LitCov
8874Multi-Institutional Collaborative Surgery Education Didactics: Virtual Adaptations during a Global Pandemic  

OBJECTIVE: The COVID-19 pandemic has disrupted graduate medical education, impacting Accreditation Council for Graduate Medical Education (ACGME)-mandated didactics. We aimed to study the utility of 2 methods of virtual learning: the daily National Surgery Resident Lecture Series (NSRLS), and weekly “SCORE School” educational webinars designed around the Surgical Council on Resident Education (SCORE) curriculum. DESIGN AND SETTING: NSRLS: The National Surgery Resident Lecture Series was a daily virtual educational session initially led by faculty at an individual surgical residency program. Thirty-eight lectures were assessed for number of live viewings (March 23, 2020-May 15, 2020). SCORE SCHOOL: Attendance at eleven weekly SCORE educational webinars was characterized into live and asynchronous viewings (May 13, 2020-August 5, 2020). Each 1-hour live webinar was produced by SCORE on a Wednesday evening and featured nationally recognized surgeon educators using an online platform that allowed for audience interaction. RESULTS: NSRLS: There were a mean of 71 live viewers per NSRLS session (range 19-118). Participation began to decline in the final 2 weeks as elective case volumes increased, but sessions remained well-attended. SCORE SCHOOL: There were a range of 164-3889 live viewers per SCORE School session. Sessions have most commonly been viewed asynchronously (89.8% of viewings). Live viewership decreased as the academic year ended and then rebounded with the start of the new academic year (range 4.9%-27%). Overall, the eight webinars were viewed 11,135 times. Each webinar continues to be viewed a mean of 43 times a day (range 0-102). Overall, the eleven webinars have been viewed a total of 22,722 times. CONCLUSIONS: Virtual didactics aimed at surgical residents are feasible, well-attended (both live and recorded), and have high levels of viewer engagement. We have observed that careful coordination of timing and topics is ideal. The ability for asynchronous viewing is particularly important for attendance. As the COVID-19 pandemic continues to disrupt healthcare systems, training programs must continue to adapt to education via virtual platforms.

J Surg Educ2020       LitCov and CORD-19
8875Knowledge, attitudes and practices of the Chinese public with respect to coronavirus disease: an online cross-sectional survey  

BACKGROUND: Coronavirus disease (COVID-19) has become a pandemic. The knowledge, attitudes, and practices (KAP) of the public play a major role in the prevention and control of infectious diseases. The objective of the present study was to evaluate the KAP of the Chinese public and to assess potential influencing factors related to practices. METHODS: A cross-sectional online survey was conducted in China in February 2020 via a self-designed questionnaire comprising 33 questions assessing KAP. RESULTS: For the 2136 respondents from 30 provinces or municipalities in China, the accurate response rate for the knowledge section ranged from 72.7 to 99.5%, and the average was 91.2%. Regarding attitude section, the percentage of positive attitudes (“strongly agree” and “agree”) ranged from 94.7 to 99.7%, and the average value was 98.0%. The good practices (“always” and “often”) results ranged from 76.1 to 99.5%, and the average value was 96.8%. The independent samples t-test revealed that gender and ethnic differences had no effect on knowledge, attitude or behaviour (P > 0.05). However, knowledge was associated with age (t = 4.842, p < 0.001), marital status (t = − 5.323, p < 0.001), education level (t = 8.441, p < 0.001), occupation (t = − 10.858, p < 0.001), and place of residence (t = 7.929, p < 0.001). Similarly, attitude was associated with marital status (t = − 2.383, p = 0.017), education level (t = 2.106, p = 0.035), occupation (t = − 4.834, p < 0.001), and place of residence (t = 4.242, p < 0.001). The multiple linear regression analysis results showed that the factors influencing practices were knowledge (t = − 3.281, p = 0.001), attitude (t = 18.756, p < 0.001), occupation (t = − 3.860, p < 0.001), education level (t = 3.136, p = 0.002), and place of residence (t = 3.257, p = 0.001). CONCLUSIONS: The Chinese public exhibited a good level of knowledge of COVID-19, a positive attitude, and high adherence to good practices. COVID-19-related knowledge, attitudes and practices were affected by age, marital status, education level, occupation, and place of residence to varying degrees. In addition, practices were affected by knowledge and attitudes towards COVID-19. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-020-09961-2.

BMC Public Health2020       LitCov and CORD-19
8876Fatal vaccine induced immune thrombotic thrombocytopenia (VITT) post Ad26.COV2.S: first documented case outside US  

PURPOSE: We reported the first described post Ad26.COV2.S (Janssen, Johnson & Johnson) vaccine-induced immune thrombocytopenia (VITT) case outside US. CASE DESCRIPTION: CA young woman without any medical history presented association of deep vein thrombosis and thrombocytopenia at day 10 after vaccine injection. The patient was treated with low-molecular weight heparin at a first medical institution. Twelve days post Ad26.COV2.S vaccination, the patient was admitted at our hospital for neurological deterioration and right hemiplegia. Medical imaging using MRI showed thrombosis of the major anterior part of the sagittal superior sinus with bilateral intraparenchymal hemorrhagic complications. Screening tests for antibodies against platelet factor 4 (PF4)–heparin by rapid lateral flow immunoassay and chemiluminescence techniques were negative. Platelet activation test using heparin-induced multiple electrode aggregometry confirmed the initial clinical hypothesis. Despite immediate treatment with intravenous immunoglobulin, dexamethasone, danaparoid and attempted neurosurgery the patient evolved toward brain death. CONCLUSION: Even though it is an extremely rare complication of vaccination physicians should maintain a high index of suspicion of VITT in patients who received an adenovirus-vector-based SARS-CoV-2 vaccine within the last 30 days with persistent complains compatible with VITT or thromboembolic event associated with thrombocytopenia. The diagnosis should not be excluded if the rapid anti-PF4 immunological nor chemiluminescence techniques yield negative results. An adapted functional assay should be performed to confirm the diagnosis. Early treatment with intravenous immunoglobulin and non-heparin anticoagulants is essential as delayed diagnosis and administration of appropriate treatment is associated with poor prognosis.

Infection2021       LitCov and CORD-19
8877Saliva as a Noninvasive Specimen for Detection of SARS-CoV-2  

Diagnostic testing for COVID-19 is central to controlling the global pandemic. ….

J Clin Microbiol2020       LitCov and CORD-19
8878Flipped teaching eased the transition from face-to-face teaching to online instruction during the COVID-19 pandemic  

Due to the COVID-19 pandemic, Rice University canceled classes for the week of March 9–13, 2020 and shifted all instruction to online only following spring break. For the second half of the semester, animal physiology was taught exclusively over Zoom. Here we describe how a flipped teaching format that was used before the pandemic eased the transition from face-to-face teaching to online instruction. The preclass preparation resources and the active learning materials that were already in place for flipped teaching were helpful in the transition to solely online teaching. Therefore, the focus during the transition was to reconfigure active learning and examinations from the face-to-face format to the online platform. Instead of small group discussions in the classroom, teams interacted in Zoom Breakout Rooms. Rather than taking exams in-person during scheduled class time, students submitted exams online. Additionally, students prerecorded their project presentations instead of presenting them “live” during the last week of classes. Overall, students felt that the class smoothly transitioned to a remote only format. These and other changes to the instructional methods will be implemented during the Spring 2021 semester when the course is taught fully online.

Adv Physiol Educ2021       LitCov and CORD-19
8879Mental health and quality of life among healthcare professionals during the COVID-19 pandemic in India  

BACKGROUND: The COVID‐19 pandemic has placed healthcare professionals (HCP) in stressful circumstances with increased patient loads and a high risk of exposure. We sought to assess the mental health and quality of life (QoL) of Indian HCPs, the fourth highest‐burden country for COVID‐19. METHOD: Using snowball sampling, we conducted an online survey in May 2020 among HCPs. Data were collected on demographics, depression, and anxiety using validated tools, quality of life, and perceived stressors. Multivariable logistic regression and principal component analysis were performed to assess risk factors associated with mental health symptoms. FINDINGS: Of 197 HCPs assessed, 157 (80%) were from Maharashtra, 130 (66%) from public hospitals, 47 (24%) nurses, 66 (34%) physicians, 101 (52%) females, and 81 (41%) ≤30 years. Eighty‐seven percent provided direct COVID‐19 care with 43% caring for >10 patients/day. A large proportion reported symptoms of depression (92, 47%), anxiety (98, 50%), and low QoL (89, 45%). Odds of combined depression and anxiety were 2.37 times higher among single HCPs compared to married (95% CI: 1.03–4.96). Work environment stressors were associated with 46% increased risk of combined depression and anxiety (95% CI: 1.15–1.85). Moderate to severe depression and anxiety were independently associated with increased risk of low QoL [OR: 3.19 (95% CI: 1.30–7.84), OR: 2.84 (95% CI: 1.29–6.29)]. CONCLUSION: Our study demonstrated a high prevalence of symptoms of depression and anxiety and low QoL among Indian HCPs during the COVID‐19 pandemic. There is an urgent need to prevent and treat mental health symptoms among frontline HCPs.

Brain Behav2020       LitCov and CORD-19
8880SARS-CoV-2 seroprevalence among 7950 healthcare workers in the Region of Southern Denmark  

Objective Health-care workers (HCWs) carry a pronounced risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to determine the seroprevalence and potential risk factors of SARS-CoV-2 infection among HCWs in the Region of Southern Denmark after the first pandemic wave in the spring of 2020. Methods Observational study conducted May-June 2020. SARS-CoV-2 IgG and IgM antibodies were measured in plasma. Participants were asked to complete a questionnaire consisting of demographic information, risk factors and COVID-19-related symptoms. Results A total of 7,950 participated. The seroprevalence of SARS-CoV-2 antibodies was 2.1% (95% CI 1.8-2.4). Seropositive participants were significantly older (mean age 48.9 years vs. 46.7 years in seronegative, P=0.022) and a higher percentage had experienced at least one symptom of COVID-19 (P<0.001). The seroprevalence was significantly higher among HCW working on dedicated COVID-19 wards (3.5%, OR 2.02 (95% CI 1.44-2.84). Seroprevalence was significantly related to 11-50 close physical contacts per day outside work (OR 1.54, 95% CI 1.07-2.22). Conclusion The prevalence of SARS-CoV-2 antibodies was low in HCWs. However, the occupational risk for contracting the infection is higher for those working on dedicated COVID-19 wards. Further, our results imply that attention should be paid to occupational risk factors in planning pandemic preparedness.

Int J Infect Dis2021       LitCov and CORD-19
8881ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection  

PURPOSE: Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection. METHODS: We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. RESULTS: Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, Western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2. CONCLUSIONS: Together, these results suggest that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.

Ocul Surf2020       LitCov and CORD-19
8882Delineating phenotypes of Kawasaki disease and SARS-CoV-2 Related inflammatory multisystem syndrome: a French study and literature review  

OBJECTIVE: To better define the clinical distinctions between the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related paediatric inflammatory multisystem syndrome (PIMS) and Kawasaki disease (KD). METHODS: We compared three groups of patients: group 1, cases from our national historic KD database (KD-HIS), before the SARS-CoV-2 pandemic; group 2, patients with KD admitted to an intensive care unit (KD-ICU) from both our original cohort and the literature, before the SARS-CoV-2 pandemic; and group 3, patients with PIMS from the literature. RESULTS: KD-HIS included 425 patients [male:female ratio 1.3, mean age 2.8 years (s.d. 2.4)], KD-ICU 176 patients [male:female ratio 1.3, mean age 3.5 years (s.d. 3.1)] and PIMS 404 patients [male:female ratio 1.4, mean age 8.8 years (s.d. 3.7)]. As compared with KD-HIS patients, KD-ICU and PIMS patients had a higher proportion of cardiac failure, digestive and neurological signs. KD-ICU and PIMS patients also had a lower frequency of typical KD-mucocutaneous signs, lower platelet count, higher CRP and lower sodium level. As compared with KD-HIS and KD-ICU patients, PIMS patients were older and more frequently had myocarditis; they also had fewer coronary abnormalities and lower sodium levels. Unresponsiveness to IVIG was more frequent in KD-ICU than KD-HIS and PIMS patients. CONCLUSION: On clinical grounds, KD-HIS, KD-ICU and PIMS might belong to a common spectrum of non-specific pathogen-triggered hyperinflammatory states. The causes of increasing inflammation severity within the three entities and the different effects on the heart remain to be determined.

Rheumatology (Oxford)2021       LitCov and CORD-19
8883Utility of lateral flow tests in SARS-CoV-2 infection monitorization  

INTRODUCTION: The diagnosis of SARS-CoV-2 infection is crucial for medical and public health reasons, to allow the best treatment of cases and the best control of the pandemic. Serology testing allows for the detection of asymptomatic infections and 19-COVID cases once the virus has been cleared. We analyzed the usefulness of the SARS-CoV-2 rapid test of Autobio and tried to correlate its pattern with the severity of COVID19 infection. MATERIAL AND METHODS: We analyzed the accuracy and clinical usefulness of a point-of-care IgM and/or IgG test for SARS-CoV-2 in 35 COVID-19 patients [12 (34.3%) mild-moderate and 23 (65.7%) severe-critical] admitted to a field hospital in Madrid, as well as in 5 controls. RESULTS: The mean time from the first day of symptoms to the antibody test was 28 days (SD: 8.7), similar according to the severity of the disease. All patients with SARS-CoV-2 PCR+ showed the corresponding IgG positivity, while these results were negative in all control individuals. A total of 26 (74%) cases also presented with positive IgM, 19 (83%) were severe-critical cases and 7 (58%) were mild-moderate cases. The IgM response lasted longer in the severe critical cases (mean: 29.7 days; SD: 8.4) compared to the moderate cases (mean: 21.2 days; SD: 2.0). CONCLUSIONS: Rapid serology tests are useful for the diagnosis of patients with COVID-19 (mainly IgG detection) and may also be correlated with the severity of the infection (based on IgM detection).

Rev Esp Quimioter2020       LitCov and CORD-19
8884Prescribing of Opioid Analgesics and Buprenorphine for Opioid Use Disorder During the COVID-19 Pandemic  

IMPORTANCE: The COVID-19 pandemic disrupted medical care, impacting prescribing of opioid analgesics and buprenorphine for opioid use disorder. Understanding these patterns can help address barriers to care. OBJECTIVE: To evaluate how prescribing of opioid analgesics and buprenorphine for opioid use disorder changed throughout the COVID-19 pandemic among both new and existing patients. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, use of opioid analgesics and buprenorphine for opioid use disorder from March 18 to September 1, 2020, was projected using a national database of retail prescriptions from January 1, 2018, to March 3, 2020. Actual prescribing was compared with projected levels for all, existing, and new patients. EXPOSURES: The data include prescriptions to patients independent of insurance status or type and cover 90% of retail prescriptions, 70% of mail-order prescriptions, and 70% of nursing home prescriptions. MAIN OUTCOMES AND MEASURES: Prescriptions for opioid analgesics and buprenorphine for opioid use disorder. Outcomes included total number of prescriptions, total morphine milligram equivalents, mean morphine milligram equivalents per prescription, mean dispensed units per prescription, and number of patients filling prescriptions. RESULTS: A total of 452 691 261 prescriptions for opioid analgesics and buprenorphine for opioid use disorder were analyzed for 90 420 353 patients (50 921 535 female patients [56%]; mean [SD] age, 49 [20] years). From March 18 to May 19, 2020, 1877 million total morphine milligram equivalents of opioid analgesics were prescribed weekly vs 1843 million projected, a ratio of 102% (95% prediction interval [PI], 94%-111%; P = .71). The weekly number of opioid-naive patients receiving opioids was 370 051 vs 564 929 projected, or 66% of projected (95% PI, 63%-68%; P < .001). Prescribing of buprenorphine was as projected for existing patients, while the number of new patients receiving buprenorphine weekly was 9865 vs 12 008 projected, or 82% (95% PI, 76%-88%; P < .001). From May 20 to September 1, 2020, opioid prescribing for new patients returned to 100% of projected (95% PI, 96%-104%; P = .95), while the number of new patients receiving buprenorphine weekly was 10 436 vs 11 613 projected, or 90% (95% PI, 83%-97%; P = .009). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, existing patients receiving opioid analgesics and buprenorphine for opioid use disorder generally maintained access to these medications during the COVID-19 pandemic. Opioid prescriptions for opioid-naive patients decreased briefly and then rebounded, while initiation of buprenorphine remained at a low rate through August 2020. Reductions in treatment entry may be associated with increased overdose deaths.

JAMA Netw Open2021       LitCov and CORD-19
8885SARS-CoV-2 spike D614G change enhances replication and transmission  

N/A

Nature2021       LitCov and CORD-19
8886A prospective observational study for justification, safety and efficacy of a third dose of mRNA vaccine in patients receiving maintenance hemodialysis  

The level of protection achieved by the standard two doses of COVID-19 mRNA vaccines in patients receiving maintenance hemodialysis (MHD) remains unclear. To study this we used the French Renal Epidemiology and Information Network (REIN) Registry to compare the incidence and severity of 1474 cases of COVID-19 diagnosed in patients receiving MHD after none, one or two doses of vaccine. Vaccination significantly reduce COVID-19 incidence and severity but 11% of patients infected after two doses still died. Lack of vaccinal protection in patients naïve for SARS-CoV-2 could be due to defective Tfh response [38% patients with negative spike-specific CD4(+) T cell interferon gamma release assay] and failure to generate viral neutralizing titers of anti-spike receptor binding domain (RBD) IgGs (63% patients with titer at or under 997 BAU/ml, defining low/no responders) after two doses of vaccine. To improve protection, a third dose of vaccine was administered to 75 patients [57 low/no responders, 18 high responders after two doses] from the ROMANOV cohort that prospectively enrolled patients receiving MHD vaccinated with BNT162b2 (Pfizer). Tolerance to the third dose was excellent. High responders to two doses did not generate more anti-RBD IgGs after three doses but had more side effects. Importantly, 31 (54%) of low/no responders to two doses reached neutralizing titers of anti-RBD IgGs after three doses. A positive interferon gamma release assay and/or suboptimal titer of anti-RBD IgGs after two doses were the only predictive variables for response to three doses in multivariate analysis. Thus, the standard scheme of vaccination insufficiently protects patients receiving MHD. Anti-RBD IgG and specific CD4(+) T cell response after two doses can guide personalized administration of the third dose, which improves the humoral response of SARS-CoV-2 naïve patients receiving MHD.

Kidney Int2021       LitCov and CORD-19
8887A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations  

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their differing antibody response profiles. Here, we performed a pilot study of four serological assays to assess the amounts of anti–SARS-CoV-2 antibodies in serum samples obtained from 491 healthy individuals before the SARS-CoV-2 pandemic, 51 individuals hospitalized with COVID-19, 209 suspected cases of COVID-19 with mild symptoms, and 200 healthy blood donors. We used two ELISA assays that recognized the full-length nucleoprotein (N) or trimeric spike (S) protein ectodomain of SARS-CoV-2. In addition, we developed the S-Flow assay that recognized the S protein expressed at the cell surface using flow cytometry, and the luciferase immunoprecipitation system (LIPS) assay that recognized diverse SARS-CoV-2 antigens including the S1 domain and the carboxyl-terminal domain of N by immunoprecipitation. We obtained similar results with the four serological assays. Differences in sensitivity were attributed to the technique and the antigen used. High anti–SARS-CoV-2 antibody titers were associated with neutralization activity, which was assessed using infectious SARS-CoV-2 or lentiviral-S pseudotype virus. In hospitalized patients with COVID-19, seroconversion and virus neutralization occurred between 5 and 14 days after symptom onset, confirming previous studies. Seropositivity was detected in 32% of mildly symptomatic individuals within 15 days of symptom onset and in 3% of healthy blood donors. The four antibody assays that we used enabled a broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in different subpopulations within one region.

Sci Transl Med2020       LitCov and CORD-19
8888Willingness of Greek general population to get a COVID-19 vaccine  

BACKGROUND: Epidemiological data indicate that a large part of population needs to be vaccinated to achieve herd immunity. Hence, it is of high importance for public health officials to know whether people are going to get vaccinated for COVID-19. The objective of the present study was to examine the willingness of adult residents in Greece to receive a COVID-19 vaccine. METHODS: A cross-sectional was survey conducted among the adult general population of Greece between April 28, 2020 to May 03, 2020 (last week of lockdown), using a mixed methodology for data collection: Computer Assisted Telephone Interviewing (CATI) and Computer Assisted web Interviewing (CAWI). Using a sample size calculator, the target sample size was found to be around 1000 respondents. To ensure a nationally representative sample of the urban/rural population according to the Greek census 2011, a proportionate stratified by region systematic sampling procedure was used to recruit particpants. Data collection was guided through a structured questionnaire. Regarding willingness to COVID-19 vaccination, participants were asked to answer the following question: “If there was a vaccine available for the novel coronavirus, would you do it?” RESULTS: Of 1004 respondents only 57.7% stated that they are going to get vaccinated for COVID-19. Respondents aged > 65 years old, those who either themselves or a member of their household belonged to a vulnerable group, those believing that the COVID-19 virus was not developed in laboratories by humans, those believing that coronavirus is far more contagious and lethal compared to the H1N1 virus, and those believing that next waves are coming were statistically significantly more likely to be willing to get a COVID-19 vaccine. Higher knowledge score regarding symptoms, transmission routes and prevention and control measures against COVID-19 was significantly associated with higher willingness of respondents to get vaccinated. CONCLUSION: A significant proportion of individuals in the general population are unwilling to receive a COVID-19 vaccine, stressing the need for public health officials to take immediate awareness-raising measures. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41256-021-00188-1.

Glob Health Res Policy2021       LitCov and CORD-19
8889Stigmatization and psychological impact of COVID-19 pandemic on frontline healthcare Workers in Nigeria: a qualitative study  

INTRODUCTION: The COVID-19 pandemic has had a great toll on global health. Frontline healthcare workers (FHCW) directly involved in the treatment of COVID-19 patients have faced some physical and psychological challenges. This study explored the stigma and traumatic experiences of the FHCW during the COVID-19 pandemic in Nigeria. METHODS: We recruited twenty FHCW directly involved in the treatment of COVID-19 patients through purposive and snowball sampling techniques. Face-to-face in-depth interviews were conducted for all participants, and qualitative analysis of data was done using Colaizzi’s phenomenological method. RESULTS: Five themes identified were: Early stage of the pandemic (fear, anxiety, public fright, other countries repatriating their citizens, the socio-economic impact of the pandemic and a call to duty for the FHCW); working with COVID-19 patients (excitement on patients recovery and duty stress); psychological, mental and emotional trauma; stigmatization (stigmatized by colleagues, family, friends or their residential communities, reasons for stigmatization which were fear of infection, limited knowledge of the virus and working at the isolation centre and the effect of stigma); and recommendations (education and awareness creation, government showing more care towards the FHCW and provision of health insurance for FHCW to take care of those that get infected in the line of duty). CONCLUSION: Stigmatization has proven to be a major challenge for FHCW in conducting their duties. The psychological impact experienced by FHCW may affect the quality of the services rendered by these workers. The study reveals the need of education and awareness creation in the ongoing pandemic. There is a need for the government and society to acknowledge and appreciate the efforts of FHCW.

BMC Psychiatry2021       LitCov and CORD-19
8890The deep impact of the COVID-19 pandemic on medical students: An online cross-sectional study evaluating Turkish students' anxiety  

AIM: Coronavirus Disease 2019 (COVID‐19) changed the delivery of medical education in Turkey by moving to an emergency remote teaching system and led to many challenges for future doctors. In this study, we aimed to explore the impact of the COVID‐19 pandemic on medical students, to assess their anxiety level and their main anxiety sources related to this pandemic. METHODS: A Google Form was distributed to medical students using the virtual snowball sampling method. The form included the Beck Anxiety Inventory and additional 19 questions on sociodemographic characteristics, perceived level of knowledge about the epidemic, self‐risk perceptions of COVID‐19 and their anxiety levels about some other topics related to COVID‐19. RESULTS: Overall, 3105 medical students with a mean age of 22.37 ± 2.46, took the survey. Amongst the participants, only 32% of the students defined their knowledge about the precautions that should be taken during an epidemic disease as acceptable. Students reported highest anxiety level for the continuing spread of COVID‐19 in Turkey and transmitting coronavirus to another person. Clinically significant anxiety prevalence was 23.2%. Regression analysis revealed that factors that increased the risk of being anxious included being female, being other than a 5th‐year student, thinking that being a medical student would increase the risk of coronavirus transmission or being uncertain about it, being exposed to a patient with COVID‐19 or being uncertain about it, being anxious about the continuing spread of COVID‐19 in Turkey, being anxious about acquiring COVID‐19, being anxious for graduating and being on active duty, being anxious about a medical training interruption. CONCLUSION: Our results suggest that anxiety is prevalent amongst Turkish medical students during the COVID‐19 pandemic and they have a weak preparedness for a pandemic such as COVID‐19. Based on our results, new strategies should be implemented for medical education and for alleviating students’ anxiety levels.

Int J Clin Pract2021       LitCov and CORD-19
8891The effect of maternal SARS-CoV-2 infection timing on birth outcomes: a retrospective multicenter cohort study  

BACKGROUND: The impact of maternal SARS-CoV-2 infection remains unclear. In this study, we evaluated the risk of maternal SARS-CoV-2 infection on birth outcomes and how this is modulated by the pregnancy trimester in which the infection occurs. We also developed models to predict gestational age at delivery for people following a SARS-CoV-2 infection during pregnancy. METHODS: We did a retrospective cohort study of the impact of maternal SARS-CoV-2 infection on birth outcomes. We used clinical data from Providence St Joseph Health electronic health records for pregnant people who delivered in the USA at the Providence, Swedish, or Kadlec sites in Alaska, California, Montana, Oregon, or Washington. The SARS-CoV-2 positive cohort included people who had a positive SARS-CoV-2 PCR-based test during pregnancy, subdivided by trimester of infection. No one in this cohort had been vaccinated for COVID-19 at time of infection. The SARS-CoV-2 negative cohort were people with at least one negative SARS-CoV-2 PCR-based test and no positive tests during pregnancy. Cohorts were matched on common covariates impacting birth outcomes, and univariate and multivariate analysis were done to investigate risk factors and predict outcomes. The primary outcome was gestational age at delivery with annotation of preterm birth classification. We trained multiple supervised learning models on 24 features of the SARS-CoV-2 positive cohort to evaluate performance and feature importance for each model and discuss the impact of SARS-CoV-2 infection on gestational age at delivery. FINDINGS: Between March 5, 2020, and July 4, 2021, 73 666 pregnant people delivered, 18 335 of whom had at least one SARS-CoV-2 test during pregnancy before Feb 14, 2021. We observed 882 people infected with SARS-CoV-2 during their pregnancy (first trimester n=85; second trimester n=226; and third trimester n=571) and 19 769 people who have never tested positive for SARS-CoV-2 and received at least one negative SARS-CoV-2 test during their pregnancy. SARS-CoV-2 infection indicated an increased risk of preterm delivery (p<0·05) and stillbirth (p<0·05), accounted for primarily by first and second trimester SARS-CoV-2 infections. Gestational age at SARS-CoV-2 infection was correlated with gestational age at delivery (p<0·01) and had the greatest impact on predicting gestational age at delivery. The people in this study had mild or moderate SARS-CoV-2 infections and acute COVID-19 severity was not correlated with gestational age at delivery (p=0·31). INTERPRETATION: These results suggest that pregnant people would benefit from increased monitoring and enhanced prenatal care after first or second trimester SARS-CoV-2 infection, regardless of acute COVID-19 severity. FUNDING: US National Institutes of Health.

Lancet Digit Health2022       LitCov and CORD-19
8892Environmental Issues and Neurological Manifestations Associated with COVID-19 Pandemic: New Aspects of the Disease?  

Coronavirus (SARS-CoV-2) emerged in China in December 2019 and rapidly caused a global health pandemic. Current evidence seems to suggest a possible link with ecosystem disequilibrium and even air pollution. The primary manifestations affect respiratory and circulatory systems, but neurological features are also being reported through case reports and case series. We summarize neurological symptoms and complications associated with COVID-19. We have searched for original articles published in PubMed/Medline, PubMed Central and Google Scholar using the following keywords: “COVID-19”, “Coronavirus”, “pandemic”, “SARS-COV-2”, “neurology”, “neurological”, “complications” and “manifestations”. We found around 1000 publications addressing the issue of neurological conditions associated with COVID-19 infection. Amongst those, headache and dizziness are the most common reported symptoms followed by encephalopathy and delirium, while the most frequent complications are cerebrovascular accidents, Guillain–Barré syndrome, acute transverse myelitis, and acute encephalitis. Specific symptoms affecting the peripheral nervous system such as hyposmia and dysgeusia are the most common manifestations recorded in the selected studies. Interestingly, it was noted that these kinds of neurological symptoms might precede the typical features, such as fever and cough, in COVID patients. Neurological symptoms and complications associated with COVID-19 should be considered as a part of the clinical features of this novel global pandemic.

Int J Environ Res Public Healt2020       LitCov and CORD-19
8893Humoral and Cellular Immune Response After Third and Fourth SARS-CoV-2 mRNA Vaccination in Liver Transplant Recipients  

N/A

Clin Gastroenterol Hepatol2022       LitCov
8894Mapping cross-variant neutralizing sites on the SARS-CoV-2 spike protein  

The emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of currently approved vaccines and authorized therapeutic monoclonal antibodies (MAbs). It is hence important to continue searching for SARS-CoV-2 broadly neutralizing MAbs and defining their epitopes. Here, we isolate 9 neutralizing mouse MAbs raised against the spike protein of a SARS-CoV-2 prototype strain and evaluate their neutralizing potency towards a panel of variants, including B.1.1.7, B.1.351, B.1.617.1, and B.1.617.2. By using a combination of biochemical, virological, and cryo-EM structural analyses, we identify three types of cross-variant neutralizing MAbs, represented by S5D2, S5G2, and S3H3, respectively, and further define their epitopes. S5D2 binds the top lateral edge of the receptor-binding motif within the receptor-binding domain (RBD) with a binding footprint centred around the loop(477–489), and efficiently neutralizes all variant pseudoviruses, but the potency against B.1.617.2 was observed to decrease significantly. S5G2 targets the highly conserved RBD core region and exhibits comparable neutralization towards the variant panel. S3H3 binds a previously unreported epitope located within the evolutionarily stable SD1 region and is able to near equally neutralize all of the variants tested. Our work thus defines three distinct cross-variant neutralizing sites on the SARS-CoV-2 spike protein, providing guidance for design and development of broadly effective vaccines and MAb-based therapies.

Emerg Microbes Infect2022       LitCov and CORD-19
8895COVID-19 vaccination beliefs, attitudes and behaviours among health and social care workers in the UK: A mixed-methods study  

BACKGROUND: The UK began delivering its COVID-19 vaccination programme on 8 December 2020, with health and social care workers (H&SCWs) given high priority for vaccination. Despite well-documented occupational exposure risks, however, there is evidence of lower uptake among some H&SCW groups. METHODS: We used a mixed-methods approach—involving an online cross-sectional survey and semi-structured interviews–to gain insight into COVID-19 vaccination beliefs, attitudes, and behaviours amongst H&SCWs in the UK by socio-demographic and employment variables. 1917 people were surveyed– 1656 healthcare workers (HCWs) and 261 social care workers (SCWs). Twenty participants were interviewed. FINDINGS: Workplace factors contributed to vaccination access and uptake. SCWs were more likely to not be offered COVID-19 vaccination than HCWs (OR:1.453, 95%CI: 1.244–1.696). SCWs specifically reported uncertainties around how to access COVID-19 vaccination. Participants who indicated stronger agreement with the statement ‘I would recommend my organisation as a place to work’ were more likely to have been offered COVID-19 vaccination (OR:1.285, 95%CI: 1.056–1.563). Those who agreed more strongly with the statement ‘I feel/felt under pressure from my employer to get a COVID-19 vaccine’ were more likely to have declined vaccination (OR:1.751, 95%CI: 1.271–2.413). Interviewees that experienced employer pressure to get vaccinated felt this exacerbated their vaccine concerns and increased distrust. In comparison to White British and White Irish participants, Black African and Mixed Black African participants were more likely to not be offered (OR:2.011, 95%CI: 1.026–3.943) and more likely to have declined COVID-19 vaccination (OR:5.550, 95%CI: 2.294–13.428). Reasons for declining vaccination among Black African participants included distrust in COVID-19 vaccination, healthcare providers, and policymakers. CONCLUSION: H&SCW employers are in a pivotal position to facilitate COVID-19 vaccination access, by ensuring staff are aware of how to get vaccinated and promoting a workplace environment in which vaccination decisions are informed and voluntary.

PLoS One2022       LitCov and CORD-19
8896A new insight into sex-specific non-coding RNAs and networks in response to SARS-CoV-2  

SARS-CoV-2 is the RNA virus responsible for COVID-19, the prognosis of which has been found to be slightly worse in men. The present study aimed to analyze the expression of different mRNAs and their regulatory molecules (miRNAs and lncRNAs) to consider the potential existence of sex-specific expression patterns and COVID-19 susceptibility using bioinformatics analysis. The binding sites of all human mature miRNA sequences on the SARS-CoV-2 genome nucleotide sequence were predicted by the miRanda tool. Sequencing data was excavated using the Galaxy web server from GSE157103, and the output of feature counts was analyzed using DEseq2 packages to obtain differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) and DEG annotation analyses were performed using the ToppGene and Metascape tools. Using the RNA Interactome Database, we predicted interactions between differentially expressed lncRNAs and differentially expressed mRNAs. Finally, their networks were constructed with top miRNAs. We identified 11 miRNAs with three to five binding sites on the SARS-COVID-2 genome reference. MiR-29c-3p, miR-21-3p, and miR-6838-5p occupied four binding sites, and miR-29a-3p had five binding sites on the SARS-CoV-2 genome. Moreover, miR-29a-3p, and miR-29c-3p were the top miRNAs targeting DEGs. The expression levels of miRNAs (125, 181b, 130a, 29a, b, c, 212, 181a, 133a) changed in males with COVID-19, in whom they regulated ACE2 expression and affected the immune response by affecting phagosomes, complement activation, and cell-matrix adhesion. Our results indicated that XIST lncRNA was up-regulated, and TTTY14, TTTY10, and ZFY-AS1 lncRN as were down-regulated in both ICU and non-ICU men with COVID-19. Dysregulation of noncoding-RNAs has critical effects on the pathophysiology of men with COVID-19, which is why they may be used as biomarkers and therapeutic agents. Overall, our results indicated that the miR-29 family target regulation patterns and might become promising biomarkers for severity and survival outcome in men with COVID-19.

Infect Genet Evol2021       LitCov and CORD-19
8897The COVID-19 pandemic-related psychological distress and job burnout among Serbian pharmacy practitioners: a cross-sectional online study  

N/A

Eur Rev Med Pharmacol Sci2022       LitCov and CORD-19
8898Burnout and secondary traumatic stress in health-system pharmacists during the COVID-19 pandemic  

PURPOSE: To describe the prevalence of burnout and secondary traumatic stress (STS) in health-system pharmacists during the coronavirus disease 2019 (COVID-19) pandemic. Methods. A cross-sectional, professional pharmacy organization listserver–based online survey of a target group of health-system pharmacists across the United States was conducted. The survey was sent out through professional organization listservers and was anonymous and voluntary. The survey questionnaire included items regarding demographics and employment characteristics, COVID-19–related questions, a survey of respondents’ perceptions of the prevalence and severity of burnout, and the Professional Quality of Life Scale (ProQOL). The ProQOL assessed respondents for compassion satisfaction (subcategorized as burnout and STS) and compassion fatigue. Descriptive statistics was used to assess the prevalence of burnout and STS. RESULTS: Four hundred eighty-four health-system pharmacists completed the survey. Based on respondents’ self-ratings of burnout, 47% were identified as having current burnout and 81% as having a history of burnout. Based on ProQOL scoring, 65.3% of respondents were identified as having a moderate or high likelihood of burnout, which was a prevalence higher than that indicated by respondents’ self-ratings. Additionally, 51.4% of respondents were identified as having a moderate or high probability of STS and 99.4% as having a moderate or high probability of compassion satisfaction. CONCLUSION: The survey found that over half of health-system pharmacists were affected with burnout, half with STS, and three-fourths with compassion satisfaction during the COVID-19 pandemic. Unfortunately, the development of burnout and STS in these health-system pharmacists may lead to several work-related consequences (eg, increase risk of medical errors, depression); therefore, addressing burnout and STS is crucial. Further studies of the consequences of burnout and STS during the COVID-19 pandemic are needed.

Am J Health Syst Pharm2021       LitCov and CORD-19
8899Is the COVID-19 Pandemic a High-Risk Period for College Student Alcohol Use? A Comparison of Three Spring Semesters  

BACKGROUND: There has been widespread concern that the COVID‐19 pandemic may be a high‐risk time for alcohol use among heavy drinking populations such as college students. Initial efforts to evaluate changes in college drinking have not yet accounted for typical drinking patterns within a semester. METHODS: To fill this gap, we evaluated how college student drinking patterns changed with the onset of restrictions related to the COVID‐19 pandemic during spring 2020 relative to spring 2018 and 2019. Participants were 1,365 college students aged 19 and older, including 895 students who reported past‐month alcohol use. Daily drinking data were extracted from an online Timeline Followback survey. RESULTS: Negative binomial hurdle models revealed that, with the onset of the COVID‐19 pandemic in spring 2020, college student drinkers did not increase their drinking frequency as was typical in late spring semester, and the number of drinks per occasion declined substantially (28% reduction), greater than the change observed from early to late spring 2018 (3% reduction) or spring 2019 (8% increase). This reduction in drinking quantity in spring 2020 was larger for college student drinkers who moved residences because of the pandemic (49% reduction) than students who did not move (21% reduction). Perceptions in pandemic‐related changes in drinking also revealed that 83.5% of college student drinkers self‐reported that their drinking stayed the same or decreased. CONCLUSIONS: Findings suggest that, on average, college students drank less—not more—during the onset of the COVID‐19 pandemic and highlight the importance of living situation in college student drinking behavior. More research is needed to assess alcohol use in other universities, as this information could be utilized in norms‐based interventions to further reduce drinking in students who remain at risk.

Alcohol Clin Exp Res2021       LitCov and CORD-19
8900Therapeutically Administered Ribonucleoside Analogue MK-4482/EIDD-2801 Blocks SARS-CoV-2 Transmission in Ferrets  

The coronavirus disease 2019 (COVID-19) pandemic is having a catastrophic impact on human health1. Widespread community transmission has triggered stringent distancing measures with severe socio-economic consequences. Gaining control of the pandemic will depend on the interruption of transmission chains until vaccine-induced or naturally acquired protective herd immunity arises. However, approved antiviral treatments such as remdesivir and reconvalescent serum cannot be delivered orally2,3, making them poorly suitable for transmission control. We previously reported the development of an orally efficacious ribonucleoside analogue inhibitor of influenza viruses, MK-4482/EIDD-2801 (refs. 4,5), that was repurposed for use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently in phase II/III clinical trials (NCT04405570 and NCT04405739). Here, we explored the efficacy of therapeutically administered MK-4482/EIDD-2801 to mitigate SARS-CoV-2 infection and block transmission in the ferret model, given that ferrets and related members of the weasel genus transmit the virus efficiently with minimal clinical signs6-9, which resembles the spread in the human young-adult population. We demonstrate high SARS-CoV-2 burden in nasal tissues and secretions, which coincided with efficient transmission through direct contact. Therapeutic treatment of infected animals with MK-4482/EIDD-2801 twice a day significantly reduced the SARS-CoV-2 load in the upper respiratory tract and completely suppressed spread to untreated contact animals. This study identified oral MK-4482/EIDD-2801 as a promising antiviral countermeasure to break SARS-CoV-2 community transmission chains.

Nat Microbiol2020       LitCov and CORD-19

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

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