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)
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.
Exceptional score (in top 0.01%).
Substantial score (in top 1%).
Average score (in bottom 99%).
Score not available.
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)
| Title | Venue | Year | Impact | Source | |
|---|---|---|---|---|---|
| 1801 | The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19 Hyperinflammation in MIS-C differs from that of acute COVID-19. T-cell subsets discriminate Kawasaki disease patients from MIS-C. IL-17A drives Kawasaki, but not MIS-C hyperinflammation. Global profiling reveals candidate autoantibodies with pathogenic potential. | Cell | 2020 | LitCov and CORD-19 | |
| 1802 | Safety and immunogenicity of heterologous vs homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial BACKGROUND: Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer–BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines. METHODS: Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139. FINDINGS: Between Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation. INTERPRETATION: Despite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines. FUNDING: UK Vaccine Task Force and National Institute for Health Research. | Lancet | 2021 | LitCov and CORD-19 | |
| 1803 | SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses. | Cell | 2022 | LitCov and CORD-19 | |
| 1804 | Augmented neutralization of SARS-CoV-2 Omicron variant by boost vaccination and monoclonal antibodies Effective vaccines and monoclonal antibodies have been developed against coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, the appearance of virus variants with higher transmissibility and pathogenicity is a major concern because of their potential to escape vaccines and clinically approved SARS‐CoV‐2‐ antibodies. Here, we use flow cytometry‐based binding and pseudotyped SARS‐CoV‐2 neutralization assays to determine the efficacy of boost immunization and therapeutic antibodies to neutralize the dominant Omicron variant. We provide compelling evidence that the third vaccination with BNT162b2 increases the amount of neutralizing serum antibodies against Delta and Omicron variants, albeit to a lower degree when compared to the parental Wuhan strain. Therefore, a third vaccination is warranted to increase titers of protective serum antibodies, especially in the case of the Omicron variant. We also found that most clinically approved and otherwise potent therapeutic antibodies against the Delta variant failed to recognize and neutralize the Omicron variant. In contrast, some antibodies under preclinical development potentially neutralized the Omicron variant. Our studies also support using a flow cytometry‐based antibody binding assay to rapidly monitor therapeutic candidates and serum titers against emerging SARS‐CoV‐2 variants. | Eur J Immunol | 2022 | LitCov and CORD-19 | |
| 1805 | Automated SARS-COV-2 RNA extraction from patient nasopharyngeal samples using a modified DNA extraction kit for high throughput testing BACKGROUND: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has prompted a need for mass testing to identify patients with viral infection. The high demand has created a global bottleneck in testing capacity, which prompted us to modify available resources to extract viral RNA and perform reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to detect SARS-COV-2. OBJECTIVES: Report on the use of a DNA extraction kit, after modifications, to extract viral RNA that could then be detected using an FDA-approved SARS-COV-2 RT-qPCR assay. MATERIALS AND METHODS: Initially, automated RNA extraction was performed using a modified DNA kit on samples from control subjects, a bacteriophage, and an RNA virus. We then verified the automated extraction using the modified kit to detect in-lab propagated SARSCOV-2 titrations using an FDA approved commercial kit (S, N, and ORF1b genes) and an in-house primer-probe based assay (E, RdRp2 and RdRp4 genes). RESULTS: Automated RNA extraction on serial dilutions SARS-COV-2 achieved successful one-step RT-qPCR detection down to 60 copies using the commercial kit assay and less than 30 copies using the in-house primer-probe assay. Moreover, RT-qPCR detection was successful after automated RNA extraction using this modified protocol on 12 patient samples of SARS-COV-2 collected by nasopharyngeal swabs and stored in viral transport media. CONCLUSIONS: We demonstrated the capacity of a modified DNA extraction kit for automated viral RNA extraction and detection using a platform that is suitable for mass testing. LIMITATIONS: Small patient sample size. CONFLICT OF INTEREST: None. | Ann Saudi Med | 2020 | LitCov and CORD-19 | |
| 1806 | Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 Summary We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000–5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections. | Cell | 2020 | LitCov and CORD-19 | |
| 1807 | Multinational dietary changes and anxiety during the coronavirus pandemic-findings from Israel BACKGROUND: Increased anxiety was frequently reported during the 2020 global COVID-19 pandemic. An association between anxiety and increased body weight has been documented. Identifying associations between diet quality and anxiety may facilitate the development of preventive dietary policy, particularly relevant since obesity appears to increase the risk of adverse COVID-19 outcomes. In this study we aim to examine associations between changes in diet pattern and body weight and anxiety levels during the COVID-19 pandemic among Israeli respondents to an international online survey. METHODS: Conducted between March 30–April 252,020, this was cross-sectional, international and online study. The questionnaire was developed and tested in Hebrew and translated into six other languages: English, Arabic, Spanish, French, Italian, and Russian. The survey was conducted on a Google Survey platform, the link to which was posted on several social media platforms. Adults aged 18 or older who saw and responded to the link on a social media site comprised the study population. RESULTS: Of the 3979 eligible respondents, 1895 indicated their current location as Israel. Most Israeli respondents completed the survey in Hebrew (83.2%) followed by Arabic (9.4%), though responses were recorded in all seven of the survey languages. The median age was 33 (IQ = 22) years, and 75.7% were female. Almost 60% indicated that their pre-pandemic diet was healthier than their current diet, and 25.2% indicated they had gained weight during the pandemic. The median Mediterranean diet score was 9 (IQ = 3). While the median General Anxiety Disorder (GAD-7) score was 5 (IQ = 8), only 37.3% of participants reported at least mild anxiety (a GAD-7 score of 5 or more), while 10.7% reported moderate anxiety or greater (a GAD-7 score of 10 or more). In a multivariate logistic regression model of at least mild anxiety, being male and completing the survey in Hebrew significantly reduced odds of at least mild anxiety, while a worsening of diet quality during the pandemic, weight gain, and isolation significantly increased odds of at least mild anxiety. CONCLUSIONS: During the COVID pandemic, changes in nutrition quality and habits were associated with greater anxiety. These findings suggest the need for routine and continuous surveillance of the nutritional and psychological consequences of outbreaks as part of healthcare preparedness efforts. Organizations responsible for community-based health services (such as Israeli health plans) should adopt specific interventions to improve case finding and support individuals at increased risk of anxiety and declining nutrition status within primary healthcare settings. These interventions should include the provision of appropriate diagnostic instruments, training of medical staff, feedback to physicians and nurses, and raising awareness among the relevant patient population and their caregivers. Primary care physicians should refer people with high anxiety or substantial weight gain during the pandemic to appropriate mental health and dietetic treatment, as needed. TRIAL REGISTRATION: NCT04353934. | Isr J Health Policy Res | 2021 | LitCov and CORD-19 | |
| 1808 | Multisystem inflammatory syndrome in neonates (MIS-N) associated with SARS-CoV-2 infection: a case series Multisystem inflammatory syndrome in neonates (MIS-N) is hypothesised to be caused either following transplacental transfer of SARS-CoV2 antibodies or antibodies developed in the neonate after infection with SARS-CoV-2. In this paper, we aim to discuss the clinical manifestations, laboratory features, and management of neonates diagnosed with MIS-N. We collated information from five participating hospitals in western India. A cohort of newborn infants presenting with multi-system involvement, along with the presence of SARS-CoV2 antibodies, was identified. Current proposed international diagnostic criteria for MIS-N were used to group the cases into three categories of Most likely, Possible, and Unlikely MIS-N. A total of 20 cases were reported with a diagnosis of MIS-N, all having high titres of SARS CoV2 IgG antibodies and negative for SARS CoV2 antigens. Most likely MIS (n = 5) cases presented with respiratory distress (4/5), hypotension and shock (4/5), and encephalopathy (2/5). Inflammatory markers like CRP (1/5), Procalcitonin (1/5), Ferritin (3/5), D-dimer (4/5), and LDH (2/5) were found to be elevated, and four of them had significantly high levels of proBNP. The majority of them (4/5) responded to immunomodulators, three neonates were discharged home, and two died. Possible MIS infants (n = 9) presented with fever (7/9), respiratory distress (4/9), refusal to feed (6/9), lethargy (5/9), and tachycardia (3/9). ProBNP as a marker of cardiac dysfunction was noted to be elevated in four (4/9) infants, correlating with abnormal echocardiography findings in two. In the Unlikely MIS (n = 6) category, three (3/6) infants presented with respiratory distress, one (1/6) with shock and cardiac dysfunction, and only one (1/6) with fever. All of them had elevated inflammatory markers. However, there were other potential diagnoses that could have been responsible for the clinical scenarios in these six cases. Conclusion: MIS-N requires a high index of suspicion and should be considered in a neonate presenting with two or more systems involvement, in the presence of SARS-CoV2 antibodies, along with elevated inflammatory markers, once other common neonatal conditions have been ruled out. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00431-022-04377-z. | Eur J Pediatr | 2022 | LitCov and CORD-19 | |
| 1809 | Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients N/A | JAMA | 2021 | LitCov and CORD-19 | |
| 1810 | Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome COVID-19 patients can present with pulmonary edema early in disease. We propose that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the B1R. Without ACE2 acting as a guardian to inactivate the ligands of B1R, the lung environment is prone for local vascular leakage leading to angioedema. Here, we hypothesize that a kinin-dependent local lung angioedema via B1R and eventually B2R is an important feature of COVID-19. We propose that blocking the B2R and inhibiting plasma kallikrein activity might have an ameliorating effect on early disease caused by COVID-19 and might prevent acute respiratory distress syndrome (ARDS). In addition, this pathway might indirectly be responsive to anti-inflammatory agents. | Elife | 2020 | LitCov and CORD-19 | |
| 1811 | Prevalence of anxiety and depression during COVID-19 pandemic among healthcare students in Jordan and its effect on their learning process: A national survey RATIONAL: During pandemics, including the most recent COVID-19 pandemic, the mental health of university healthcare students’ is expected to be affected negatively, impacting the students’ learning process. OBJECTIVES: The aim of this study was to assess the level of anxiety and depression of healthcare students living in Jordan, and the effect on their learning process during the COVID-19 pandemic. METHODS: This descriptive cross-sectional study was conducted via an online survey completed by students studying a healthcare-oriented degree in a university in Jordan. Participants were recruited through social media (Facebook and WhatsApp). The validated previously published Hospital Anxiety and Depression Scale (HADS) questionnaire was used as a part of the online survey to assess students’ anxiety/depression scores. Students’ responses regarding their learning process during the COVID-19 was also assessed. RESULTS: The mean age of participants was 21.62 (SD = 4.90), with the majority being females (67.1%). The HADs’ assessment revealed that 43.8% and 40.0% of participants had normal anxiety and depression scores, while 22.4% showed borderline abnormal anxiety/depression scores (33.8%). Many students (33.8%) were classified to have abnormal anxiety scores, while a smaller proportion (26.2%) was classified to have abnormal depression scores. Smoking (p = 0.022), lower family income (p = 0.039), and use of medications (p = 0.032) were positively associated with higher (worse) anxiety scores. Ranking the learning process during COVID-19 showed that 45.8% of the participants believed it was a ‘good/very good/excellent’ process. CONCLUSIONS: Anxiety and depression levels amongst university healthcare students in Jordan were found to be high when assessed during the COVID-19 pandemic. In addition, the learning process during the pandemic was not accepted by more than half of the students. Implementing psychological interventions for healthcare students during pandemics is strongly recommended in order to optimize students’ mental health and their learning process alike. | PLoS One | 2021 | LitCov and CORD-19 | |
| 1812 | Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients the infection results in moderate to severe acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. High serum levels of IL-6, IL-10 and an immune hyperresponsiveness referred to as a ‘cytokine storm’ have been associated with poor clinical outcome. Despite the large numbers of COVID-19 cases and deaths, information on the phenotype and kinetics of SARS-CoV-2-specific T cells is limited. Here, we studied 10 COVID-19 patients who required admission to an intensive care unit and detected SARS-CoV-2-specific CD4(+) and CD8(+) T cells in 10 out of 10 and 8 out of 10 patients, respectively. We also detected low levels of SARS-CoV-2-reactive T cells in 2 out of 10 healthy controls not previously exposed to SARS-CoV-2, which is indicative of cross-reactivity due to past infection with ‘common cold’ coronaviruses. The strongest T-cell responses were directed to the spike (S) surface glycoprotein, and SARS-CoV-2-specific T cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected. Furthermore, we studied T-cell kinetics and showed that SARS-CoV-2-specific T cells are present relatively early and increase over time. Collectively, these data shed light on the potential variations in T-cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in the disease, and also inform vaccine design and evaluation. | Sci Immunol | 2020 | LitCov and CORD-19 | |
| 1813 | Public Concerns and Mental Health Changes Related to the COVID-19 Pandemic Lockdown in Saudi Arabia N/A | Clin Lab | 2020 | LitCov and CORD-19 | |
| 1814 | Detection of SARS-CoV-2-specific antibodies via rapid diagnostic immunoassays in COVID-19 patients BACKGROUND: Efficient monitoring and control of coronavirus disease 2019 (COVID-19) require access to diagnostic tests, and serological diagnostic testing is desirable. In the current study, antibodies were investigated in patients recently diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Cross-sectional data were obtained from 245 patients in whom SARS-CoV-2 infection had been confirmed via real-time reverse transcriptase-polymerase chain reaction between March and October 2020. Serum samples were acquired between 2 and 60 days following the onset of COVID-19 symptoms or the first detection of SARS-CoV-2 in asymptomatic patients. All specimens were tested simultaneously using an IgM/IgG rapid diagnostic test (RDT), IgG nucleocapsid protein-based chemiluminescent microparticle immunoassay (CMIA), IgG, and IgA spike protein-based enzyme-linked immunosorbent assays (ELISAs). Blood donor samples obtained in 2018 were used as negative controls. RESULTS: The sensitivity and specificity of the RDT IgG were compared with the IgG immunoassays as standards. The RDT IgG exhibited 97.5% sensitivity and 89.4% specificity compared with a CMIA IgG, 98.4% sensitivity, and 78.8% specificity compared with an ELISA IgG. IgM, IgG, and IgA seropositivity rates were low between 1 and 2 weeks after COVID-19 symptom onset or the detection of SARS-CoV-2 RNA. IgM seropositivity rate began decreasing after 4 weeks, whereas IgG and IgA seropositivity rate remained at appreciable levels over the 8-week study period. No cross-reactivity with seasonal coronaviruses was detected. CONCLUSIONS: IgG RDT alone or combined with molecular diagnostic tests may be useful for identifying recent SARS-CoV-2 infection. | Virol J | 2021 | LitCov and CORD-19 | |
| 1815 | Covid-19 Outbreak Progression in Italian Regions: Approaching the Peak by the End of March in Northern Italy and First Week of April in Southern Italy Epidemiological figures of the SARS-CoV-2 epidemic in Italy are higher than those observed in China. Our objective was to model the SARS-CoV-2 outbreak progression in Italian regions vs. Lombardy to assess the epidemic’s progression. Our setting was Italy, and especially Lombardy, which is experiencing a heavy burden of SARS-CoV-2 infections. The peak of new daily cases of the epidemic has been reached on the 29th, while was delayed in Central and Southern Italian regions compared to Northern ones. In our models, we estimated the basic reproduction number (R(0)), which represents the average number of people that can be infected by a person who has already acquired the infection, both by fitting the exponential growth rate of the infection across a 1-month period and also by using day-by-day assessments based on single observations. We used the susceptible–exposed–infected–removed (SEIR) compartment model to predict the spreading of the pandemic in Italy. The two methods provide an agreement of values, although the first method based on exponential fit should provide a better estimation, being computed on the entire time series. Taking into account the growth rate of the infection across a 1-month period, each infected person in Lombardy has involved 4 other people (3.6 based on data of April 23rd) compared to a value of [Formula: see text] , as reported in the Chinese city of Wuhan. According to our model, Piedmont, Veneto, Emilia Romagna, Tuscany and Marche will reach an R(0) value of up to 3.5. The R(0) was 3.11 for Lazio and 3.14 for the Campania region, where the latter showed the highest value among the Southern Italian regions, followed by Apulia (3.11), Sicily (2.99), Abruzzo (3.0), Calabria (2.84), Basilicata (2.66), and Molise (2.6). The R(0) value is decreased in Lombardy and the Northern regions, while it is increased in Central and Southern regions. The expected peak of the SEIR model is set at the end of March, at a national level, with Southern Italian regions reaching the peak in the first days of April. Regarding the strengths and limitations of this study, our model is based on assumptions that might not exactly correspond to the evolution of the epidemic. What we know about the SARS-CoV-2 epidemic is based on Chinese data that seems to be different than those from Italy; Lombardy is experiencing an evolution of the epidemic that seems unique inside Italy and Europe, probably due to demographic and environmental factors. | Int J Environ Res Public Healt | 2020 | LitCov and CORD-19 | |
| 1816 | Tweet Topics and Sentiments Relating to COVID-19 Vaccination Among Australian Twitter Users: Machine Learning Analysis BACKGROUND: COVID-19 is one of the greatest threats to human beings in terms of health care, economy, and society in recent history. Up to this moment, there have been no signs of remission, and there is no proven effective cure. Vaccination is the primary biomedical preventive measure against the novel coronavirus. However, public bias or sentiments, as reflected on social media, may have a significant impact on the progression toward achieving herd immunity. OBJECTIVE: This study aimed to use machine learning methods to extract topics and sentiments relating to COVID-19 vaccination on Twitter. METHODS: We collected 31,100 English tweets containing COVID-19 vaccine–related keywords between January and October 2020 from Australian Twitter users. Specifically, we analyzed tweets by visualizing high-frequency word clouds and correlations between word tokens. We built a latent Dirichlet allocation (LDA) topic model to identify commonly discussed topics in a large sample of tweets. We also performed sentiment analysis to understand the overall sentiments and emotions related to COVID-19 vaccination in Australia. RESULTS: Our analysis identified 3 LDA topics: (1) attitudes toward COVID-19 and its vaccination, (2) advocating infection control measures against COVID-19, and (3) misconceptions and complaints about COVID-19 control. Nearly two-thirds of the sentiments of all tweets expressed a positive public opinion about the COVID-19 vaccine; around one-third were negative. Among the 8 basic emotions, trust and anticipation were the two prominent positive emotions observed in the tweets, while fear was the top negative emotion. CONCLUSIONS: Our findings indicate that some Twitter users in Australia supported infection control measures against COVID-19 and refuted misinformation. However, those who underestimated the risks and severity of COVID-19 may have rationalized their position on COVID-19 vaccination with conspiracy theories. We also noticed that the level of positive sentiment among the public may not be sufficient to increase vaccination coverage to a level high enough to achieve vaccination-induced herd immunity. Governments should explore public opinion and sentiments toward COVID-19 and COVID-19 vaccination, and implement an effective vaccination promotion scheme in addition to supporting the development and clinical administration of COVID-19 vaccines. | J Med Internet Res | 2021 | LitCov and CORD-19 | |
| 1817 | Initial chest radiographs and artificial intelligence (AI) predict clinical outcomes in COVID-19 patients: analysis of 697 Italian patients OBJECTIVE: To evaluate whether the initial chest X-ray (CXR) severity assessed by an AI system may have prognostic utility in patients with COVID-19. METHODS: This retrospective single-center study included adult patients presenting to the emergency department (ED) between February 25 and April 9, 2020, with SARS-CoV-2 infection confirmed on real-time reverse transcriptase polymerase chain reaction (RT-PCR). Initial CXRs obtained on ED presentation were evaluated by a deep learning artificial intelligence (AI) system and compared with the Radiographic Assessment of Lung Edema (RALE) score, calculated by two experienced radiologists. Death and critical COVID-19 (admission to intensive care unit (ICU) or deaths occurring before ICU admission) were identified as clinical outcomes. Independent predictors of adverse outcomes were evaluated by multivariate analyses. RESULTS: Six hundred ninety-seven 697 patients were included in the study: 465 males (66.7%), median age of 62 years (IQR 52–75). Multivariate analyses adjusting for demographics and comorbidities showed that an AI system-based score ≥ 30 on the initial CXR was an independent predictor both for mortality (HR 2.60 (95% CI 1.69 − 3.99; p < 0.001)) and critical COVID-19 (HR 3.40 (95% CI 2.35–4.94; p < 0.001)). Other independent predictors were RALE score, older age, male sex, coronary artery disease, COPD, and neurodegenerative disease. CONCLUSION: AI- and radiologist-assessed disease severity scores on CXRs obtained on ED presentation were independent and comparable predictors of adverse outcomes in patients with COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04318366 (https://clinicaltrials.gov/ct2/show/NCT04318366). KEY POINTS: • AI system–based score ≥ 30 and a RALE score ≥ 12 at CXRs performed at ED presentation are independent and comparable predictors of death and/or ICU admission in COVID-19 patients. • Other independent predictors are older age, male sex, coronary artery disease, COPD, and neurodegenerative disease. • The comparable performance of the AI system in relation to a radiologist-assessed score in predicting adverse outcomes may represent a game-changer in resource-constrained settings. | Eur Radiol | 2020 | LitCov and CORD-19 | |
| 1818 | Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention. | Science | 2020 | LitCov and CORD-19 | |
| 1819 | Rates of Maternal and Perinatal Mortality and Vertical Transmission in Pregnancies Complicated by SARS-CoV-2 (SARS-Co-V-2) Infection: A Systematic Review N/A | Obstet Gynecol | 2020 | LitCov and CORD-19 | |
| 1820 | Incidence of Nosocomial COVID-19 in Patients Hospitalized at a Large US Academic Medical Center IMPORTANCE: Some patients are avoiding essential care for fear of contracting coronavirus disease 2019 (COVID-19) in hospitals. There are few data, however, on the risk of acquiring COVID-19 in US hospitals. OBJECTIVE: To assess the incidence of COVID-19 among patients hospitalized at a large US academic medical center in the 12 weeks after the first inpatient case was identified. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all patients admitted to Brigham and Women’s Hospital (Boston, Massachusetts) between March 7 and May 30, 2020. Follow-up occurred through June 17, 2020. Medical records for all patients who first tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse-transcription polymerase chain reaction (RT-PCR) on hospital day 3 or later or within 14 days of discharge were reviewed. EXPOSURES: A comprehensive infection control program was implemented that included dedicated COVID-19 units with airborne infection isolation rooms, personal protective equipment in accordance with US Centers for Disease Control and Prevention recommendations, personal protective equipment donning and doffing monitors, universal masking, restriction of visitors, and liberal RT-PCR testing of symptomatic and asymptomatic patients. MAIN OUTCOMES AND MEASURES: Whether infection was community or hospital acquired based on timing of tests, clinical course, and exposures. RESULTS: Over the 12-week period, 9149 patients (mean [SD] age, 46.1 [26.4] years; median [IQR] age, 51 years [30-67 years]; 5243 female [57.3%]) were admitted to the hospital, for whom 7394 SARS-CoV-2 RT-PCR tests were performed; 697 COVID-19 cases were confirmed, translating into 8656 days of COVID-19–related care. Twelve of the 697 hospitalized patients with COVID-19 (1.7%) first tested positive on hospital day 3 or later (median, 4 days; range, 3-15 days). Of these, only 1 case was deemed to be hospital acquired, most likely from a presymptomatic spouse who was visiting daily and diagnosed with COVID-19 before visitor restrictions and masking were implemented. Among 8370 patients with non–COVID-19–related hospitalizations discharged through June 17, 11 (0.1%) tested positive within 14 days (median time to diagnosis, 6 days; range, 1-14 days). Only 1 case was deemed likely to be hospital acquired, albeit with no known exposures. CONCLUSIONS AND RELEVANCE: In this cohort study of patients in a large academic medical center with rigorous infection control measures, nosocomial COVID-19 was rare during the height of the pandemic in the region. These findings may inform practices in other institutions and provide reassurance to patients concerned about contracting COVID-19 in hospitals. | JAMA Netw Open | 2020 | LitCov and CORD-19 | |
| 1821 | Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2 ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes mellitus. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of Ace2, Ang 1–7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases. | Circ Res | 2020 | LitCov and CORD-19 | |
| 1822 | Evidence for retained spike-binding and neutralizing activity against emerging SARS-CoV-2 variants in serum of COVID-19 mRNA vaccine recipients BACKGROUND: Highly efficacious vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed. However, the emergence of viral variants that are more infectious than the earlier SARS-CoV-2 strains is concerning. Several of these viral variants have the potential to partially escape neutralizing antibody responses, warranting continued immune-monitoring. METHODS: We used a panel of 30 post-mRNA vaccination sera to determine neutralization and RBD and spike binding activity against a number of emerging viral variants. The virus neutralization was determined using authentic SARS-CoV-2 clinical isolates in an assay format that mimics physiological conditions. FINDINGS: We tested seven currently circulating viral variants of concern/interest, including the three Iota sublineages, Alpha (E484K), Beta, Delta and Lambda in neutralization assays. We found only small decreases in neutralization against Iota and Delta. The reduction was stronger against a sub-variant of Lambda, followed by Beta and Alpha (E484K). Lambda is currently circulating in parts of Latin America and was detected in Germany, the US and Israel. Of note, reduction in a receptor binding domain and spike binding assay that also included Gamma, Kappa and A.23.1 was negligible. INTERPRETATION: Taken together, these findings suggest that mRNA SARS-CoV-2 vaccines may remain effective against these viral variants of concern/interest and that spike binding antibody tests likely retain specificity in the face of evolving SARS-CoV-2 diversity. FUNDING: This work is part of the PARIS/SPARTA studies funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. In addition, this work was also partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384), by anonymous donors and by the Serological Sciences Network (SeroNet) in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024, Task Order No. 75N91020F00003. | EBioMedicine | 2021 | LitCov and CORD-19 | |
| 1823 | Neutralizing Monoclonal Antibodies That Target the Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection against SARS-CoV-2 Infection in Syrian Hamsters The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main target for neutralizing antibodies. These antibodies can be elicited through immunization or passively transferred as therapeutics in the form of convalescent-phase sera or monoclonal antibodies (MAbs). Potently neutralizing antibodies are expected to confer protection; however, it is unclear whether weakly neutralizing antibodies contribute to protection. Also, their mechanism of action in vivo is incompletely understood. Here, we demonstrate that 2B04, an antibody with an ultrapotent neutralizing activity (50% inhibitory concentration [IC(50)] of 0.04 μg/ml), protects hamsters against SARS-CoV-2 in a prophylactic and therapeutic infection model. Protection is associated with reduced weight loss and viral loads in nasal turbinates and lungs after challenge. MAb 2B04 also blocked aerosol transmission of the virus to naive contacts. We next examined three additional MAbs (2C02, 2C03, and 2E06), recognizing distinct epitopes within the receptor binding domain of spike protein that possess either minimal (2C02 and 2E06, IC(50) > 20 μg/ml) or weak (2C03, IC(50) of 5 μg/ml) virus neutralization capacity in vitro. Only 2C03 protected Syrian hamsters from weight loss and reduced lung viral load after SARS-CoV-2 infection. Finally, we demonstrated that Fc-Fc receptor interactions were not required for protection when 2B04 and 2C03 were administered prophylactically. These findings inform the mechanism of protection and support the rational development of antibody-mediated protection against SARS-CoV-2 infections. | mBio | 2021 | LitCov and CORD-19 | |
| 1824 | CCR2 Signaling Restricts SARS-CoV-2 Infection Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a historic pandemic of respiratory disease (coronavirus disease 2019 [COVID-19]), and current evidence suggests that severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here, we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2 signaling restricts the viral burden in the lung. We find that a recently developed mouse-adapted SARS-CoV-2 (MA-SARS-CoV-2) strain as well as the emerging B.1.351 variant trigger an inflammatory response in the lung characterized by the expression of proinflammatory cytokines and interferon-stimulated genes. Using intravital antibody labeling, we demonstrate that MA-SARS-CoV-2 infection leads to increases in circulating monocytes and an influx of CD45(+) cells into the lung parenchyma that is dominated by monocyte-derived cells. Single-cell RNA sequencing (scRNA-Seq) analysis of lung homogenates identified a hyperinflammatory monocyte profile. We utilize this model to demonstrate that mechanistically, CCR2 signaling promotes the infiltration of classical monocytes into the lung and the expansion of monocyte-derived cells. Parenchymal monocyte-derived cells appear to play a protective role against MA-SARS-CoV-2, as mice lacking CCR2 showed higher viral loads in the lungs, increased lung viral dissemination, and elevated inflammatory cytokine responses. These studies have identified a potential CCR2-monocyte axis that is critical for promoting viral control and restricting inflammation within the respiratory tract during SARS-CoV-2 infection. | mBio | 2021 | LitCov and CORD-19 | |
| 1825 | Improved Molecular Diagnosis of COVID-19 by the Novel, Highly Sensitive and Specific COVID-19-RdRp/Hel Real-Time Reverse Transcription-PCR Assay Validated In Vitro and with Clinical Specimens On 31 December 2019, the World Health Organization was informed of a cluster of cases of pneumonia of unknown etiology in Wuhan, China. Subsequent investigations identified a novel coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the affected patients. Highly sensitive and specific laboratory diagnostics are important for controlling the rapidly evolving SARS-CoV-2-associated coronavirus disease 2019 (COVID-19) epidemic. In this study, we developed and compared the performance of three novel real-time reverse transcription-PCR (RT-PCR) assays targeting the RNA-dependent RNA polymerase (RdRp)/helicase (Hel), spike (S), and nucleocapsid (N) genes of SARS-CoV-2 with that of the reported RdRp-P2 assay, which is used in >30 European laboratories. Among the three novel assays, the COVID-19-RdRp/Hel assay had the lowest limit of detection in vitro (1.8 50% tissue culture infective doses [TCID(50)]/ml with genomic RNA and 11.2 RNA copies/reaction with in vitro RNA transcripts). Among 273 specimens from 15 patients with laboratory-confirmed COVID-19 in Hong Kong, 77 (28.2%) were positive by both the COVID-19-RdRp/Hel and RdRp-P2 assays. The COVID-19-RdRp/Hel assay was positive for an additional 42 RdRp-P2-negative specimens (119/273 [43.6%] versus 77/273 [28.2%]; P < 0.001), including 29/120 (24.2%) respiratory tract specimens and 13/153 (8.5%) non-respiratory tract specimens. The mean viral load of these specimens was 3.21 × 10(4) RNA copies/ml (range, 2.21 × 10(2) to 4.71 × 10(5) RNA copies/ml). The COVID-19-RdRp/Hel assay did not cross-react with other human-pathogenic coronaviruses and respiratory pathogens in cell culture and clinical specimens, whereas the RdRp-P2 assay cross-reacted with SARS-CoV in cell culture. The highly sensitive and specific COVID-19-RdRp/Hel assay may help to improve the laboratory diagnosis of COVID-19. | J Clin Microbiol | 2020 | LitCov and CORD-19 | |
| 1826 | The experiences of health-care providers during the COVID-19 crisis in China: a qualitative study Summary Background In the early stages of the outbreak of coronavirus disease 2019 (COVID-19) in Hubei, China, the local health-care system was overwhelmed. Physicians and nurses who had no infectious disease expertise were recruited to provide care to patients with COVID-19. To our knowledge, no studies on their experiences of combating COVID-19 have been published. We aimed to describe the experiences of these health-care providers in the early stages of the outbreak. Methods We did a qualitative study using an empirical phenomenological approach. Nurses and physicians were recruited from five COVID-19-designated hospitals in Hubei province using purposive and snowball sampling. They participated in semi-structured, in-depth interviews by telephone from Feb 10 to Feb 15, 2020. Interviews were transcribed verbatim and analysed using Haase's adaptation of Colaizzi's phenomenological method. Findings We recruited nine nurses and four physicians. Three theme categories emerged from data analysis. The first was “being fully responsible for patients' wellbeing—‘this is my duty’”. Health-care providers volunteered and tried their best to provide care for patients. Nurses had a crucial role in providing intensive care and assisting with activities of daily living. The second category was “challenges of working on COVID-19 wards”. Health-care providers were challenged by working in a totally new context, exhaustion due to heavy workloads and protective gear, the fear of becoming infected and infecting others, feeling powerless to handle patients' conditions, and managing relationships in this stressful situation. The third category was “resilience amid challenges”. Health-care providers identified many sources of social support and used self-management strategies to cope with the situation. They also achieved transcendence from this unique experience. Interpretation The intensive work drained health-care providers physically and emotionally. Health-care providers showed their resilience and the spirit of professional dedication to overcome difficulties. Comprehensive support should be provided to safeguard the wellbeing of health-care providers. Regular and intensive training for all health-care providers is necessary to promote preparedness and efficacy in crisis management. Funding National Key R&D Program of China, Project of Humanities and Social Sciences of the Ministry of Education in China. | Lancet Glob Health | 2020 | LitCov and CORD-19 | |
| 1827 | SARS-CoV-2 Omicron Variant: Exploring Healthcare Workers' Awareness and Perception of Vaccine Effectiveness: A National Survey During the First Week of WHO Variant Alert BACKGROUND: As the SARS-CoV-2 Omicron variant spreads in several countries, healthcare workers' (HCWs) perceptions and worries regarding vaccine effectiveness and boosters warrant reassessment. METHODS: An online questionnaire among HCWs in Saudi Arabia (KSA) was distributed from Dec 1st−6th 2021 to assess their perceptions, vaccine advocacy to the Omicron variant, and their perception of the effectiveness of infection prevention measures and vaccination to prevent its spread, their Omicron variant related worries in comparison to the other variants, and their agreement with mandatory vaccination in general for adults. RESULTS: Among the 1,285 HCW participants, two-thirds were female, 49.8 % were nurses, 46.4% were physicians, and 50.0% worked in tertiary care hospitals. 66.9% considered vaccination to be the most effective way to prevent the spread of the Omicron variant and future variants. The respondents however perceived social distancing (78.0%), universal masking (77.8%), and avoiding unnecessary travel (71.4%) as slightly superior to vaccination to prevent the spread of SARS-CoV-2 variants. HCWs aging 55 or older agreed significantly with vaccine ineffectiveness to control Omicron spread, while those who believed in non-pharmacological infection prevention measures agreed significantly with vaccination for that purpose. Male HCWs had a significant agreement with mandatory vaccination of all eligible adult populations. On the other hand, unwilling HCWs to receive the vaccine had strong disagreements with mandatory vaccination. CONCLUSIONS: The current study in the first week of Omicron showed that only two-thirds of HCWs felt that vaccination was the best option to prevent the spread of the Omicron variant, indicating the need for further motivation campaigns for vaccination and booster dose. HCWs had a strong belief in infection prevention measures to contain the spread of SARS-CoV-2 variants that should be encouraged and augmented. | Front Public Health | 2022 | LitCov and CORD-19 | |
| 1828 | Mental Health Problems during the COVID-19 Pandemics and the Mitigation Effects of Exercise: A Longitudinal Study of College Students in China (1) Background: The novel coronavirus disease 2019 (COVID-19) is a global public health emergency that has caused worldwide concern. Vast resources have been allocated to control the pandemic and treat patients. However, little attention has been paid to the adverse impact on mental health or effective mitigation strategies to improve mental health. (2) Purpose: The aim of this study was to assess the adverse impact of the COVID-19 outbreak on Chinese college students’ mental health, understand the underlying mechanisms, and explore feasible mitigation strategies. (3) Methods: During the peak time of the COVID-19 outbreak in China, we conducted longitudinal surveys of sixty-six college students. Structured questionnaires collected information on demographics, physical activity, negative emotions, sleep quality, and aggressiveness level. A mixed-effect model was used to evaluate associations between variables, and the mediating effect of sleep quality was further explored. A generalized additive model was used to determine the dose-response relationships between the COVID-19 death count, physical activity, and negative emotions. (4) Results: The COVID-19 death count showed a direct negative impact on general sleep quality (β = 1.37, 95% confidence interval [95% CI]: 0.55, 2.19) and reduced aggressiveness (β = −6.57, 95% CI: −12.78, −0.36). In contrast, the COVID-19 death count imposed not a direct but an indirect impact on general negative emotions (indirect effect (IE) = 0.81, p = 0.012), stress (IE = 0.40, p < 0.001), and anxiety (IE = 0.27, p = 0.004) with sleep quality as a mediator. Moreover, physical activity directly alleviated general negative emotions (β = −0.12, 95% CI: −0.22, −0.01), and the maximal mitigation effect occurred when weekly physical activity was about 2500 METs. (5) Conclusions: (a) The severity of the COVID-19 outbreak has an indirect effect on negative emotions by affecting sleep quality. (b) A possible mitigation strategy for improving mental health includes taking suitable amounts of daily physical activity and sleeping well. (c) The COVID-19 outbreak has reduced people’s aggressiveness, probably by making people realize the fragility and preciousness of life. | Int J Environ Res Public Healt | 2020 | LitCov and CORD-19 | |
| 1829 | Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread. | J Hosp Infect | 2020 | LitCov and CORD-19 | |
| 1830 | Association of Prior BNT162b2 COVID-19 Vaccination With Symptomatic SARS-CoV-2 Infection in Children and Adolescents During Omicron Predominance N/A | JAMA | 2022 | LitCov and CORD-19 | |
| 1831 | The psychological impact of anxiety and depression on Chinese medical staff during the outbreak of the COVID-19 pandemic: a cross-sectional study N/A | Ann Palliat Med | 2021 | LitCov and CORD-19 | |
| 1832 | Distinctive Roles of Furin and TMPRSS2 in SARS-CoV-2 Infectivity The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directs infection of the lungs and other tissues following its binding to the angiotensin-converting enzyme 2 (ACE2) receptor. For effective infection, the S protein is cleaved at two sites: S1/S2 and S2′. The “priming” of the surface S protein at S1/S2 (PRRAR(685)↓) [the underlined basic amino acids refer to critical residues needed for the furin recognition] by furin has been shown to be important for SARS-CoV-2 infectivity in cells and small-animal models. In this study, for the first time we unambiguously identified by proteomics the fusion activation site S2′ as KPSKR(815)↓ (the underlined basic amino acids refer to critical residues needed for the furin recognition) and demonstrated that this cleavage was strongly enhanced by ACE2 engagement with the S protein. Novel pharmacological furin inhibitors (BOS inhibitors) effectively blocked endogenous S protein processing at both sites in HeLa cells, and SARS-CoV-2 infection of lung-derived Calu-3 cells was completely prevented by combined inhibitors of furin (BOS) and type II transmembrane serine protease 2 (TMPRSS2) (camostat). Quantitative analyses of cell-to-cell fusion and S protein processing revealed that ACE2 shedding by TMPRSS2 was required for TMPRSS2-mediated enhancement of fusion in the absence of S1/S2 priming. We further demonstrated that the collectrin dimerization domain of ACE2 was essential for the effect of TMPRSS2 on cell-to-cell fusion. Overall, our results indicate that furin and TMPRSS2 act synergistically in viral entry and infectivity, supporting the combination of furin and TMPRSS2 inhibitors as potent antivirals against SARS-CoV-2. IMPORTANCE SARS-CoV-2, the etiological agent of COVID-19, has so far resulted in >6.1 million deaths worldwide. The spike protein (S) of the virus directs infection of the lungs and other tissues by binding the angiotensin-converting enzyme 2 (ACE2) receptor. For effective infection, the S protein is cleaved at two sites: S1/S2 and S2′. Cleavage at S1/S2 induces a conformational change favoring the S protein recognition by ACE2. The S2′ cleavage is critical for triggering membrane fusion and virus entry into host cells. Our study highlights the complex dynamics of interaction between the S protein, ACE2, and the host proteases furin and TMPRSS2 during SARS-CoV-2 entry and suggests that the combination of a nontoxic furin inhibitor with a TMPRSS2 inhibitor significantly reduces viral entry in lung cells, as evidenced by an average synergistic ∼95% reduction of viral infection. This represents a powerful novel antiviral approach to reduce viral spread in individuals infected by SARS-CoV-2 or future related coronaviruses. | J Virol | 2022 | LitCov and CORD-19 | |
| 1833 | Cardiovascular impact of COVID-19 with a focus on children: A systematic review BACKGROUND: Since the beginning of the pandemic, coronavirus disease-2019 (COVID-19) in children has shown milder cases and a better prognosis than adults. Although the respiratory tract is the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cardiovascular involvement is emerging as one of the most significant and life-threatening complications of SARS-CoV-2 infection in adults. AIM: To summarize the current knowledge about the potential cardiovascular involvement in pediatric COVID-19 in order to give a perspective on how to take care of them during the current pandemic emergency. METHODS: Multiple searches in MEDLINE, PubMed were performed using the search terms “COVID-19” or “SARS-CoV-2 were used in combination with “myocardial injury” or arrhythmia or “cardiovascular involvement” or heart disease or congenital heart disease or “pulmonary hypertension” or long QT or “cardiomyopathies” or “channelopathies” or Multisystem inflammatory system or PMIS or “MIS-C” or ”Pediatric multisystem inflammatory syndrome or myocarditis or thromboembolism to identify articles published in English language from January 1st, 2020 until July 31st, 2020. The websites of World Health Organization, Centers for Disease control and Prevention, and the Johns Hopkins Coronavirus Resource Center were reviewed to provide up to date numbers and infection control recommendations. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts concerning the subject were reviewed by the authors, and the data were extracted using a standardized collection tool. Data were subsequently analyzed with descriptive statistics. For Pediatric multisystemic inflammatory syndrome temporally associated with COVID-19 (PMIS), multiple meta-analyses were conducted to summarize the pooled mean proportion of different cardiovascular variables in this population in pseudo-cohorts of observed patients. RESULTS: A total of 193 articles were included. Most publications used in this review were single case reports, small case series, and observational small-sized studies or literature reviews. The meta-analysis of 16 studies with size > 10 patients and with complete data about cardiovascular involvement in children with PMIS showed that PMIS affects mostly previously healthy school-aged children and adolescents presenting with Kawasaki disease-like features and multiple organ failure with a focus on the heart, accounting for most cases of pediatric COVID-19 mortality. They frequently presented cardiogenic shock (53%), ECG alterations (27%), myocardial dysfunction (52%), and coronary artery dilation (15%). Most cases required PICU admission (75%) and inotropic support (57%), with the rare need for extracorporeal membrane oxygenation (4%). Almost all of these children wholly recovered in a few days, although rare deaths have been reported (2%). Out of PMIS cases we identified 10 articles reporting sporadic cases of myocarditis, pulmonary hypertension and cardiac arrythmias in previously healthy children. We also found another 10 studies reporting patients with pre-existing heart diseases. Most cases consisted in children with severe COVID-19 infection with full recovery after intensive care support, but cases of death were also identified. The management of different cardiac conditions are provided based on current guidelines and expert panel recommendations. CONCLUSION: There is still scarce data about the role of cardiovascular involvement in COVID-19 in children. Based on our review, children (previously healthy or with pre-existing heart disease) with acute COVID-19 requiring hospital admission should undergo a cardiac workup and close cardiovascular monitoring to identify and treat timely life-threatening cardiac complications. | World J Clin Cases | 2020 | LitCov and CORD-19 | |
| 1834 | Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19 BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support–free days, on an ordinal scale combining in-hospital death (assigned a value of −1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support–free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support–free days was 10 (interquartile range, −1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, −1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.) | N Engl J Med | 2021 | LitCov and CORD-19 | |
| 1835 | A Combination of N and S Antigens With IgA and IgG Measurement Strengthens the Accuracy of SARS-CoV-2 Serodiagnostics BACKGROUND: The primary diagnosis of SARS-CoV-2 infection is based on the detection of virus RNA in nasopharyngeal swab samples. In addition, analysis of humoral immunity against SARS-CoV-2 has an important role in viral diagnostics and seroprevalence estimates. METHODS: We developed and optimized an enzyme immunoassays (EIA) using SARS-CoV-2 nucleoprotein (N), S1 and receptor binding domain (RBD) of the viral spike protein, and N proteins from SARS, MERS, and four low-pathogenic human CoVs. Neutralizing antibody activity was compared with SARS-CoV-2 IgG, IgA and IgM EIA results. RESULTS: The sensitivity of EIA for detecting immune response in COVID-19 patients (n=101) was 77 % in the acute phase and 100 % in the convalescent phase of SARS-CoV-2 infection when N and RBD were used as antigens in IgG and IgA specific EIAs. SARS-CoV-2 infection significantly increased humoral immune responses against the 229E and NL63 N proteins. S1 and RBD-based EIA results had a strong correlation with microneutralization test (MNT) results. CONCLUSIONS: The data indicate that a combination of SARS-CoV-2 S1 or RBD and N proteins and analysis of sera in IgG and IgA immunoglobulin classes provide an excellent basis for specific and sensitive serological diagnostics of COVID-19. | J Infect Dis | 2021 | LitCov and CORD-19 | |
| 1836 | Youth Mask-Wearing and Social-Distancing Behavior at In-Person High School Graduations During the COVID-19 Pandemic N/A | J Adolesc Health | 2021 | LitCov and CORD-19 | |
| 1837 | Dynamic profile of RT-PCR findings from 301 COVID-19 patients in Wuhan, China: A descriptive study BACKGROUND: With the spread of Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, its effect on society is amplified. We aimed to describe the viral detection results across different timepoints throughout the disease course. METHODS: A retrospective study of 301 confirmed COVID-19 patients hospitalized at Tongji Hospital in Wuhan, China, were included. Demographic characteristics of the patients were collected. Upper respiratory specimens (throat and/or nasal swabs) were obtained and analyzed by real-time RT-PCR for SARS-CoV-2 infection. Period of viral infection and the contagious stage were analyzed. RESULTS: Of 301 hospitalized COVID-19 patients, the median age was 58 years and 51.2% were male. The median period between symptoms presence and positive SARS-CoV-2 RT-PCR results was 16 days (IQR, 10-23, N = 301). The median period between symptoms presence and an effective negative SARS-CoV-2 RT-PCR result was 20 days (IQR, 17-24; N = 216). Infected patient ≥65 years old stayed contagious longer (22 days vs 19 days, p = 0.015). Although two consecutive negative results were confirmed in 70 patients, 30% of them had positive viral test results for the third time. Using specimens from nasal swabs to run the RT-PCR test showed a higher positive rate than using specimens from throat swabs. CONCLUSIONS: This large-scale investigation with 1113 RT-PCR test results from 301 COVID-19 patients showed that the average contagious period of SARS-CoV-2 infected patients was 20 days. Longer observation period and more than 2 series of negative viral test are necessary for patients ≥65 years. | J Clin Virol | 2020 | LitCov and CORD-19 | |
| 1838 | SARS-CoV-2 infection in pregnancy during the first wave of COVID-19 in the Netherlands: a prospective nationwide population-based cohort study (NethOSS) OBJECTIVE: To describe characteristics, risk factors and maternal, obstetric and neonatal outcomes of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). DESIGN: Multi‐centre prospective population‐based cohort study. SETTING: Nationwide study in the Netherlands. POPULATION: Pregnant women with confirmed SARS‐CoV‐2 infection admitted to hospital or in home‐isolation: 1 March 2020 to 31 August 2020. METHODS: Pregnant women with positive polymerase chain reaction or antibody tests were registered using the Netherlands Obstetrics Surveillance System (NethOSS). (Selective) testing occurred according to national guidelines. Data from the national birth registry (pregnant pre‐coronavirus disease 2019 [COVID‐19] cohort) and an age‐matched cohort of COVID‐19‐positive women (National Institute for Public Health and the Environment; fertile age COVID‐19 cohort) were used as reference. MAIN OUTCOME MEASURES: Incidence of SARS‐CoV‐2 infection in pregnant women. Maternal, obstetric and neonatal outcomes including hospital and intensive care admission. RESULTS: Of 376 registered pregnant women with confirmed SARS‐CoV‐2 infection, 20% (74/376) were admitted to hospital, of whom 84% (62/74) were due to SARS‐CoV‐2; 10% (6/62) were admitted to intensive care and 15% (9/62) to obstetric high‐care units. Risk factors for admission were non‐European country of origin (odds ratio [OR] 1.73, 95% CI 1.01–2.96) and being overweight/obese (OR 1.86, 95% CI 1.51–3.20). No maternal or perinatal deaths occurred. Caesarean section after labour‐onset was increased (OR 1.58, 95% CI 1.09–2.28). Hospital and intensive care admission were higher compared with the fertile age COVID‐19 cohort (OR 6.75, 95% CI 5.18–8.81 and OR 2.52, 95% CI 1.11–5.77, respectively). CONCLUSIONS: Non‐European country of origin and being overweight/obese are risk factors for severe course of SARS‐CoV‐2 infection in pregnancy, risk of caesarean section and hospital and intensive care unit admission are increased. TWEETABLE ABSTRACT: Pregnant women with SARS‐CoV‐2 in the Netherlands show increased hospital/ICU admission and caesarean section. | BJOG | 2021 | LitCov and CORD-19 | |
| 1839 | Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer IMPORTANCE: Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear. OBJECTIVE: To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment. The controls were taken from a convenience sample of the patients’ family/caregivers who accompanied them to treatment. The study was conducted between February 22, 2021, and March 15, 2021 at Davidoff Cancer Center at Beilinson Hospital (Petah Tikva, Israel). INTERVENTIONS: Blood samples were drawn from the study participants. Serum samples were analyzed and the titers of the IgG antibodies against SARS-CoV-2 spike receptor–binding domain were determined using a commercially available immunoassay. Seropositivity was defined as 50 or greater AU/mL. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of seropositivity. Secondary outcomes included comparisons of IgG titers and identifying factors that were associated with seropositivity using univariate/multivariable analyses. RESULTS: The analysis included 180 participants, which comprised 102 patients with cancer (median [interquartile range (IQR)] age, 66 [56-72] years; 58 men [57%]) and 78 healthy controls (median [IQR] age, 62 [49-70] years; 25 men [32%]). The most common tumor type was gastrointestinal (29 [28%]). In the patient group, 92 (90%) were seropositive for SARS-CoV 2 antispike IgG antibodies after the second vaccine dose, whereas in the control group, all were seropositive. The median IgG titer in the patients with cancer was significantly lower than that in the controls (1931 [IQR, 509-4386] AU/mL vs 7160 [IQR, 3129-11 241] AU/mL; P < .001). In a multivariable analysis, the only variable that was significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy (β, −3.5; 95% CI, −5.6 to −1.5). CONCLUSIONS AND RELEVANCE: In this cohort study of patients with cancer who were receiving active systemic therapy, 90% of patients exhibited adequate antibody response to the BNT162b2 vaccine, although their antibody titers were significantly lower than those of healthy controls. Further research into the clinical relevance of lower titers and their durability is required. Nonetheless, the data support vaccinating patients with cancer as a high priority, even during therapy. | JAMA Oncol | 2021 | LitCov and CORD-19 | |
| 1840 | Association of tiered restrictions and a second lockdown with COVID-19 deaths and hospital admissions in England: a modelling study BACKGROUND: A second wave of COVID-19 cases in autumn, 2020, in England led to localised, tiered restrictions (so-called alert levels) and, subsequently, a second national lockdown. We examined the impact of these tiered restrictions, and alternatives for lockdown stringency, timing, and duration, on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and hospital admissions and deaths from COVID-19. METHODS: We fit an age-structured mathematical model of SARS-CoV-2 transmission to data on hospital admissions and hospital bed occupancy (ISARIC4C/COVID-19 Clinical Information Network, National Health Service [NHS] England), seroprevalence (Office for National Statistics, UK Biobank, REACT-2 study), virology (REACT-1 study), and deaths (Public Health England) across the seven NHS England regions from March 1, to Oct 13, 2020. We analysed mobility (Google Community Mobility) and social contact (CoMix study) data to estimate the effect of tiered restrictions implemented in England, and of lockdowns implemented in Northern Ireland and Wales, in October, 2020, and projected epidemiological scenarios for England up to March 31, 2021. FINDINGS: We estimated a reduction in the effective reproduction number (R(t)) of 2% (95% credible interval [CrI] 0–4) for tier 2, 10% (6–14) for tier 3, 35% (30–41) for a Northern Ireland-stringency lockdown with schools closed, and 44% (37–49) for a Wales-stringency lockdown with schools closed. From Oct 1, 2020, to March 31, 2021, a projected COVID-19 epidemic without tiered restrictions or lockdown results in 280 000 (95% projection interval 274 000–287 000) hospital admissions and 58 500 (55 800–61 100) deaths. Tiered restrictions would reduce hospital admissions to 238 000 (231 000–245 000) and deaths to 48 600 (46 400–50 700). From Nov 5, 2020, a 4-week Wales-type lockdown with schools remaining open—similar to the lockdown measures announced in England in November, 2020—was projected to further reduce hospital admissions to 186 000 (179 000–193 000) and deaths to 36 800 (34 900–38 800). Closing schools was projected to further reduce hospital admissions to 157 000 (152 000–163 000) and deaths to 30 300 (29 000–31 900). A projected lockdown of greater than 4 weeks would reduce deaths but would bring diminishing returns in reducing peak pressure on hospital services. An earlier lockdown would have reduced deaths and hospitalisations in the short term, but would lead to a faster resurgence in cases after January, 2021. In a post-hoc analysis, we estimated that the second lockdown in England (Nov 5–Dec 2) reduced R(t) by 22% (95% CrI 15–29), rather than the 32% (25–39) reduction estimated for a Wales-stringency lockdown with schools open. INTERPRETATION: Lockdown measures outperform less stringent restrictions in reducing cumulative deaths. We projected that the lockdown policy announced to commence in England on Nov 5, with a similar stringency to the lockdown adopted in Wales, would reduce pressure on the health service and would be well timed to suppress deaths over the winter period, while allowing schools to remain open. Following completion of the analysis, we analysed new data from November, 2020, and found that despite similarities in policy, the second lockdown in England had a smaller impact on behaviour than did the second lockdown in Wales, resulting in more deaths and hospitalisations than we originally projected when focusing on a Wales-stringency scenario for the lockdown. FUNDING: Horizon 2020, UK Medical Research Council, and the National Institute for Health Research. | Lancet Infect Dis | 2021 | LitCov and CORD-19 | |
| 1841 | Deep-COVID: Predicting COVID-19 from chest X-ray images using deep transfer learning The COVID-19 pandemic is causing a major outbreak in more than 150 countries around the world, having a severe impact on the health and life of many people globally. One of the crucial step in fighting COVID-19 is the ability to detect the infected patients early enough, and put them under special care. Detecting this disease from radiography and radiology images is perhaps one of the fastest ways to diagnose the patients. Some of the early studies showed specific abnormalities in the chest radiograms of patients infected with COVID-19. Inspired by earlier works, we study the application of deep learning models to detect COVID-19 patients from their chest radiography images. We first prepare a dataset of 5,000 Chest X-rays from the publicly available datasets. Images exhibiting COVID-19 disease presence were identified by board-certified radiologist. Transfer learning on a subset of 2,000 radiograms was used to train four popular convolutional neural networks, including ResNet18, ResNet50, SqueezeNet, and DenseNet-121, to identify COVID-19 disease in the analyzed chest X-ray images. We evaluated these models on the remaining 3,000 images, and most of these networks achieved a sensitivity rate of 98% ( ± 3%), while having a specificity rate of around 90%. Besides sensitivity and specificity rates, we also present the receiver operating characteristic (ROC) curve, precision-recall curve, average prediction, and confusion matrix of each model. We also used a technique to generate heatmaps of lung regions potentially infected by COVID-19 and show that the generated heatmaps contain most of the infected areas annotated by our board certified radiologist. While the achieved performance is very encouraging, further analysis is required on a larger set of COVID-19 images, to have a more reliable estimation of accuracy rates. The dataset, model implementations (in PyTorch), and evaluations, are all made publicly available for research community at https://github.com/shervinmin/DeepCovid.git | Med Image Anal | 2020 | LitCov and CORD-19 | |
| 1842 | Inactivating Three Interferon Antagonists Attenuates Pathogenesis of an Enteric Coronavirus N/A | J Virol | 2020 | LitCov and CORD-19 | |
| 1843 | Battle Buddies: Rapid Deployment of a Psychological Resilience Intervention for Healthcare Workers During the COVID-19 Pandemic The outbreak of the coronavirus disease 2019 (COVID-19) and its rapid global spread have created unprecedented challenges to health care systems. Significant and sustained efforts have focused on mobilization of personal protective equipment, intensive care beds, and medical equipment, while substantially less attention has focused on preserving the psychological health of the medical workforce tasked with addressing the challenges of the pandemic. And yet, similar to battlefield conditions, health care workers are being confronted with ongoing uncertainty about resources, capacities, and risks; as well as exposure to suffering, death, and threats to their own safety. These conditions are engendering high levels of fear and anxiety in the shortterm, and place individuals at risk for persistent stressexposure syndromes, subclinical mental health symptoms, and professional burnout in the longterm. Given the potentially wide-ranging mental health impact of COVID-19, protecting health care workers from adverse psychological effects of the pandemic is critical. Therefore, we present an overview of the potential psychological stress responses to the COVID-19 crisis in medical providers and describe preemptive resilience-promoting strategies at the organizational and personal level. We then describe a rapidly deployable Psychological Resilience Intervention founded on a peersupport model (Battle Buddies) developed by the United States Army. This intervention—the product of a multidisciplinary collaboration between the Departments of Anesthesiology and Psychiatry & Behavioral Sciences at the University of Minnesota Medical Center—also incorporates evidence-informed “stress inoculation” methods developed for managing psychological stress exposure in providers deployed to disasters. Our multilevel, resource-efficient, and scalable approach places 2 key tools directly in the hands of providers: (1) apeersupport Battle Buddy; and (2) adesignated mental health consultant who can facilitate training in stress inoculation methods, provide additional support, or coordinate referral for external professional consultation. In parallel, we have instituted a voluntary research data-collection component that will enable us to evaluate the intervention’s effectiveness while also identifying the most salient resilience factors for future iterations. It is our hope that these elements will provide guidance to other organizations seeking to protect the well-being of their medical workforce during the pandemic. Given the remarkable adaptability of human beings, we believe that, by promoting resilience, our diverse health care workforce can emerge from this monumental challenge with new skills, closer relationships, and greater confidence in the power of community. | Anesth Analg | 2020 | LitCov and CORD-19 | |
| 1844 | SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2 We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain (RBD). Docking studies suggest a heparin/heparan sulfate-binding site adjacent to the ACE2 binding site. Both ACE2 and heparin can bind independently to spike protein in vitro and a ternary complex can be generated using heparin as a scaffold. Electron micrographs of spike protein suggests that heparin enhances the open conformation of the RBD that binds ACE2. On cells, spike protein binding depends on both heparan sulfate and ACE2. Unfractionated heparin, non-anticoagulant heparin, heparin lyases, and lung heparan sulfate potently block spike protein binding and/or infection by pseudotyped virus and authentic SARS-CoV-2 virus. We suggest a model in which viral attachment and infection involves heparan sulfate-dependent enhancement of binding to ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin presents new therapeutic opportunities. | Cell | 2020 | LitCov and CORD-19 | |
| 1845 | Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study BACKGROUND: The COVID-19 pandemic is challenging advanced health systems, which are dealing with an overwhelming number of patients in need of intensive care for respiratory failure, often requiring intubation. Prone positioning in intubated patients is known to reduce mortality in moderate-to-severe acute respiratory distress syndrome. We aimed to investigate feasibility and effect on gas exchange of prone positioning in awake, non-intubated patients with COVID-19-related pneumonia. METHODS: In this prospective, feasibility, cohort study, patients aged 18–75 years with a confirmed diagnosis of COVID-19-related pneumonia receiving supplemental oxygen or non-invasive continuous positive airway pressure were recruited from San Gerardo Hospital, Monza, Italy. We collected baseline data on demographics, anthropometrics, arterial blood gas, and ventilation parameters. After baseline data collection, patients were helped into the prone position, which was maintained for a minimum duration of 3 h. Clinical data were re-collected 10 min after prone positioning and 1 h after returning to the supine position. The main study outcome was the variation in oxygenation (partial pressure of oxygen [PaO(2)]/fractional concentration of oxygen in inspired air [FiO(2)]) between baseline and resupination, as an index of pulmonary recruitment. This study is registered on ClinicalTrials.gov, NCT04365959, and is now complete. FINDINGS: Between March 20 and April 9, 2020, we enrolled 56 patients, of whom 44 (79%) were male; the mean age was 57·4 years (SD 7·4) and the mean BMI was 27·5 kg/m(2) (3·7). Prone positioning was feasible (ie, maintained for at least 3 h) in 47 patients (83·9% [95% CI 71·7 to 92·4]). Oxygenation substantially improved from supine to prone positioning (PaO(2)/FiO(2) ratio 180·5 mm Hg [SD 76·6] in supine position vs 285·5 mm Hg [112·9] in prone position; p<0·0001). After resupination, improved oxygenation was maintained in 23 patients (50·0% [95% CI 34·9–65·1]; ie, responders); however, this improvement was on average not significant compared with before prone positioning (PaO(2)/FiO(2) ratio 192·9 mm Hg [100·9] 1 h after resupination; p=0·29). Patients who maintained increased oxygenation had increased levels of inflammatory markers (C-reactive protein: 12·7 mg/L [SD 6·9] in responders vs 8·4 mg/L [6·2] in non-responders; and platelets: 241·1 × 10(3)/μL [101·9] vs 319·8 × 10(3)/μL [120·6]) and shorter time between admission to hospital and prone positioning (2·7 days [SD 2·1] in responders vs 4·6 days [3·7] in non-responders) than did those for whom improved oxygenation was not maintained. 13 (28%) of 46 patients were eventually intubated, seven (30%) of 23 responders and six (26%) of 23 non-responders (p=0·74). Five patients died during follow-up due to underlying disease, unrelated to study procedure. INTERPRETATION: Prone positioning was feasible and effective in rapidly ameliorating blood oxygenation in awake patients with COVID-19-related pneumonia requiring oxygen supplementation. The effect was maintained after resupination in half of the patients. Further studies are warranted to ascertain the potential benefit of this technique in improving final respiratory and global outcomes. FUNDING: University of Milan-Bicocca. | Lancet Respir Med | 2020 | LitCov and CORD-19 | |
| 1846 | Burnout in Intensive Care Unit Workers during the Second Wave of the COVID-19 Pandemic: A Single Center Cross-Sectional Italian Study The COVID-19 pandemic had a massive impact on the Italian healthcare systems, which became overwhelmed, leading to an increased risk of psychological pressure on ICU workers. The present study aimed to investigate the prevalence of distress (anxiety, depression and insomnia symptoms), burnout syndrome and resilience in healthcare workers during the COVID-19 pandemic and to detect potential factors associated with their psychological response. This cross-sectional, survey-based study enrolled 136 healthcare workers assisting COVID-19 patients in the new COVID-19 ward (Intensive Care Unit), at Milano Fiera, Lombardy. Participants completed an online survey that comprised different validated and standardized questionnaires: Maslach Burnout Inventory (MBI), Resilience Scale for adults (RSA), Hospital Anxiety and Depression scale (HADS) and Insomnia Severity Index (ISI). Socio-demographic and work characteristics were also collected. Out of 136 ICU specialists, there were 84 nurses (62%) and 52 physicians (38%). Over half (60%) met the criteria for burnout, with nearly the same percentages among nurses and physicians. Nurses reported significantly higher scores of anxiety and insomnia levels. Forty-five percent of participants reported symptoms of depression (of whom 13.9% in the clinical range) and most of the staff showed moderate to high levels (82.4%) of resilience. The COVID-19 pandemic can have a significant impact on ICU staff. Effective interventions are needed to maintain healthcare professionals’ mental health and relieve burnout. Follow-up and tailored procedures should be provided to alleviate the psychological burden in the frontline staff at highest risk. | Int J Environ Res Public Healt | 2021 | LitCov and CORD-19 | |
| 1847 | Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review N/A | Cochrane Database Syst Rev | 2020 | LitCov and CORD-19 | |
| 1848 | Infection or a third dose of mRNA vaccine elicits neutralizing antibody responses against SARS-CoV-2 in kidney transplant recipients Transplant recipients, who receive therapeutic immunosuppression to prevent graft rejection, are characterized by high coronavirus disease 2019 (COVID-19)-related mortality and defective response to vaccines. We observed that previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but not the standard two-dose regimen of vaccination, provided protection against symptomatic COVID-19 in kidney transplant recipients. We therefore compared the cellular and humoral immune responses of these two groups of patients. Neutralizing anti-Receptor Binding Domain (RBD) IgG antibodies were identified as the primary correlate of protection for transplant recipients. Analysis of virus-specific B and T cell responses suggested that the generation of neutralizing anti-RBD IgG may have depended upon cognate T-B cell interactions that took place in germinal center, potentially acting as a limiting checkpoint. High dose mycophenolate mofetil, an immunosuppressive drug, was associated with fewer antigen-specific B and T follicular helper (Tfh) cells after vaccination; this was not observed in patients recently infected with SARS-CoV-2. Finally, we observed that, in two independent prospective cohorts, administration of a third dose of SARS-CoV-2 mRNA vaccine restored neutralizing titers of anti-RBD IgG in about 40% of individuals who had not previously responded to two doses of vaccine. Together, these findings suggest that a third dose of SARS-CoV-2 mRNA vaccine improves the RBD-specific responses of transplant patients treated with immunosuppressive drugs. | Sci Transl Med | 2022 | LitCov and CORD-19 | |
| 1849 | SARS-CoV-2 spike produced in insect cells elicits high neutralization titres in non-human primates The current coronavirus disease 2019 (COVID-19) pandemic was the result of the rapid transmission of a highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is no efficacious vaccine or therapeutic. Toward the development of a vaccine, here we expressed and evaluated as potential candidates four versions of the spike (S) protein using an insect cell expression system: receptor binding domain (RBD), S1 subunit, the wild-type S ectodomain (S-WT), and the prefusion trimer-stabilized form (S-2P). We showed that RBD appears as a monomer in solution, whereas S1, S-WT, and S-2P associate as homotrimers with substantial glycosylation. Cryo-electron microscopy analyses suggested that S-2P assumes an identical trimer conformation as the similarly engineered S protein expressed in 293 mammalian cells but with reduced glycosylation. Overall, the four proteins confer excellent antigenicity with convalescent COVID-19 patient sera in enzyme-linked immunosorbent assay (ELISA), yet show distinct reactivities in immunoblotting. RBD, S-WT and S-2P, but not S1, induce high neutralization titres (>3-log) in mice after a three-round immunization regimen. The high immunogenicity of S-2P could be maintained at the lowest dose (1 μg) with the inclusion of an aluminium adjuvant. Higher doses (20 μg) of S-2P can elicit high neutralization titres in non-human primates that exceed 40-times the mean titres measured in convalescent COVID-19 subjects. Our results suggest that the prefusion trimer-stabilized SARS-CoV-2 S-protein from insect cells may offer a potential candidate strategy for the development of a recombinant COVID-19 vaccine. | Emerg Microbes Infect | 2020 | LitCov and CORD-19 | |
| 1850 | Intensive care for seriously ill patients affected by novel coronavirus sars-CoV-2: Experience of the Crema Hospital, Italy AIMS: In this work, the survival and mortality data of 54 consecutive patients admitted to the Intensive Care Unit (ICU) and suffering from severe respiratory insufficiency imputable to viral SARS - CoV - 2 infection were analyzed and shared, after a critical review of the evidence in order to optimize the most dedicated clinical and treatment strategy, for a future ‘targeted’ management in the care of the possible return flu outbreak. METHODS: At our Emergency Department of the Crema Hospital, from the beginning of the pandemic until the end of June 2020, 54 consecutive patients admitted to ICU suffering from severe acute respiratory infection (SARI) and severe respiratory distress (ARDS) attributable to viral SARS - CoV - 2 infection were recruited. The recruitment criterion was based on refractory hypoxia, general condition and clinical impairment, comorbidities and CT images. The incoming parameters of the blood chemistry and radiology investigations and the timing of the gold - tracheal intubation were compared. Medical therapy was based on the application of shared protocols. RESULTS: The onset of symptoms was varyng, i.e. within the range of 1–14 days. The average time from the admission to the emergency room to the admission to intensive care was approximately 120 h. The average number of days of hospitalization in the ICU was 28 days. With a majority of male patients, the most significant age group was between 60 and 69 years. There were 21 deaths and, compared to the survivors, the deceased ones were older at an average age of about 67 years (vs an average age of the survivors of about 59 years). From the available data entering the ICU, the surviving patients presented average better values of oximetry and blood gas analysis, with a lower average dosage of D-Dimer than the deceased. Ones with a presence of bilateral pneumonia in all patients, the worsening of the ARDS occurred in 31 patients. 9 out of 25 patients early intubated died, while 12 out of 23 patients died when intubation was performed after 24 h of non-invasive ventilation. The presence of multiple comorbidities was shown in 17 of 28 patients and revealed an additional adverse prognostic factor. Also, more than one complication in the same patient were detected; after respiratory worsening, renal failure was more frequently found in 16 patients. Some particular complications such as lesions induced by ventilation with barotrauma mechanism (VILI), ischemic heart disease and the appearance of central and peripheral neurological events were detected too. CONSIDERATIONS: SARS - CoV - 2 disease is caused by a new coronavirus that has its main route of transmission through respiratory droplets and close contact, resulting in a sudden onset of the clinical syndrome with acute respiratory infection (SARI) and severe respiratory distress (ARDS). But it can also appear with other symptoms such as gastrointestinal or neurological events, as to be considered as a disease with multisystem phenotype. This pathology evolves towards a serious form of systemic disease from an acute lung damage to venous and arterial thromboembolic complications and multi-organ failure, mostly associated with high mortality. All patients received empirical or targeted antibiotic therapy for prevention and control of infections of potential pathogens, together with low molecular weight heparin therapy. The majority of patients was subjected to the off - label protocol with antivirals and hydroxychloroquine therapy, we used cortisone support therapy under surveillance and in 3 cases the protocol with anti - IL6 monoclonal antibody (Tolicizumab). In a simplified classification of the tomographic examination of the chest, mostly 3D and 2C lesions were found in the deceased patients with a prevalence of severe and moderate forms, whilst in the survivors the distribution appears with a prevalence of medium and moderate forms. Among the intubated patients, 21 patients, all suffering from worsening ARDS, died whilst there was no mortality in patients subjected to non-invasive ventilation it so. The heterogeneity of the respiratory syndromes and the presence of multiple comorbidities represent an unfortunate prognostic factor. Among the complications, besides the respiratory worsening, renal failure, liver failure and the state of sepsis were most frequently found; less frequent complications were lesions induced by ventilation with a barotrauma mechanism, ischemic heart disease, the appearance of central neurological events of sensory alterations, meningo - encephalitis and cerebral hemorrhage, and peripheral neurological events with polyneuro - myopathies. Mechanical ventilation can adversely affect the prognosis due to lung damage induced, protective ventilation remains the necessary treatment during severe hypoxia in patients with SARS - CoV - 2. The essential prerequisite remains the search for optimal ‘customized’ values since conditions can vary from patient to patient and, in the same patient, during different times of ventilation. CONCLUSIONS: In these extraordinary circumstances, our reality was among the most affected and was able to hold the impact thanks to the immediate great response set in place by the operators, although it costed us an effort especially the one to try to guarantee a high quality level of assistance and care compared to the huge wave of patients in seriously bad conditions. Further research on this heterogeneous pathology and data sharing could help identify a more dedicated clinical decision-making and treatment pathway that, together with a resource planning, would allow us to better face any new disease outbreak. | Am J Emerg Med | 2020 | LitCov and CORD-19 |
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(3) Currently tweets of June 23rd to June 29th 2022 have been considered.