\ BIP! Finder for COVID-19 - Impact-based ranking

BIP! Finder for COVID-19

This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.

Last Update: 18 - 01 - 2023 (628506 entries)

Provided impact measures:
Popularity: Citation-based measure reflecting the current impact.
Influence: Citation-based measure reflecting the total impact.
Reader Attention: The current number of Mendeley readers.
Social Media Attention: The number of recent tweets related to this article.
*More details on these impact measures can be found here.
Score interpretations:
Exceptional score (in top 0.01%).
Substantial score (in top 1%).
Average score (in bottom 99%).
Score not available.
Main data sources:
CORD-19 dataset(1) (list of papers)
LitCovid hub(2) (list of papers)
PMC & PubMed (citations)
Mendeley (number of readers)
COVID-19-TweetIDs(3) (tweets)

Use:  Impact  Relevance & Impact
TitleVenueYearImpactSource
2901Avian infectious bronchitis  

N/A

Adv Vet Sci Comp Med1970       CORD-19
2902Epitope Classification and RBD Binding Properties of Neutralizing Antibodies Against SARS-CoV-2 Variants of Concern  

Severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) causes coronavirus disease 2019 (COVID19) that is responsible for short and long-term disease, as well as death, in susceptible hosts. The receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) protein binds to cell surface angiotensin converting enzyme type-II (ACE2) to initiate viral attachment and ultimately viral pathogenesis. The SARS-CoV-2 S RBD is a major target of neutralizing antibodies (NAbs) that block RBD - ACE2 interactions. In this report, NAb-RBD binding epitopes in the protein databank were classified as C1, C1D, C2, C3, or C4, using a RBD binding profile (BP), based on NAb-specific RBD buried surface area and used to predict the binding epitopes of a series of uncharacterized NAbs. Naturally occurring SARS-CoV-2 RBD sequence variation was also quantified to predict NAb binding sensitivities to the RBD-variants. NAb and ACE2 binding studies confirmed the NAb classifications and determined whether the RBD variants enhanced ACE2 binding to promote viral infectivity, and/or disrupted NAb binding to evade the host immune response. Of 9 single RBD mutants evaluated, K417T, E484K, and N501Y disrupted binding of 65% of the NAbs evaluated, consistent with the assignment of the SARS-CoV-2 P.1 Japan/Brazil strain as a variant of concern (VoC). RBD variants E484K and N501Y exhibited ACE2 binding equivalent to a Wuhan-1 reference SARS-CoV-2 RBD. While slightly less disruptive to NAb binding, L452R enhanced ACE2 binding affinity. Thus, the L452R mutant, associated with the SARS-CoV-2 California VoC (B.1.427/B.1.429-California), has evolved to enhance ACE2 binding, while simultaneously disrupting C1 and C2 NAb classes. The analysis also identified a non-overlapping antibody pair (1213H7 and 1215D1) that bound to all SARS-CoV-2 RBD variants evaluated, representing an excellent therapeutic option for treatment of SARS-CoV-2 WT and VoC strains.

Front Immunol2021       LitCov and CORD-19
2903Rationally Designed ACE2-Derived Peptides Inhibit SARS-CoV-2  

[Image: see text] Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is a novel and highly pathogenic coronavirus and is the causative agent of the coronavirus disease 2019 (COVID-19). The high morbidity and mortality associated with COVID-19 and the lack of an approved drug or vaccine for SARS-CoV-2 underscores the urgent need for developing effective antiviral therapies. Therapeutics that target essential viral proteins are effective at controlling virus replication and spread. Coronavirus Spike glycoproteins mediate viral entry and fusion with the host cell, and thus are essential for viral replication. To enter host cells, the Spike proteins of SARS-CoV-2 and related coronavirus, SARS-CoV, bind the host angiotensin-converting enzyme 2 (ACE2) receptor through their receptor binding domains (RBDs). Here, we rationally designed a panel of ACE2-derived peptides based on the RBD-ACE2 binding interfaces of SARS-CoV-2 and SARS-CoV. Using SARS-CoV-2 and SARS-CoV Spike-pseudotyped viruses, we found that a subset of peptides inhibits Spike-mediated infection with IC(50) values in the low millimolar range. We identified two peptides that bound Spike RBD in affinity precipitation assays and inhibited infection with genuine SARS-CoV-2. Moreover, these peptides inhibited the replication of a common cold causing coronavirus, which also uses ACE2 as its entry receptor. Results from the infection experiments and modeling of the peptides with Spike RBD identified a 6-amino-acid (Glu37-Gln42) ACE2 motif that is important for SARS-CoV-2 inhibition. Our work demonstrates the feasibility of inhibiting SARS-CoV-2 with peptide-based inhibitors. These findings will allow for the successful development of engineered peptides and peptidomimetic-based compounds for the treatment of COVID-19.

Bioconjug Chem2020       LitCov and CORD-19
2904Willingness to Use Home Collection Methods to Provide Specimens for SARS-CoV-2/COVID-19 Research: Survey Study  

BACKGROUND: Innovative laboratory testing approaches for SARS-CoV-2 infection and immune response are needed to conduct research to establish estimates of prevalence and incidence. Self-specimen collection methods have been successfully used in HIV and sexually transmitted infection research and can provide a feasible opportunity to scale up SARS-CoV-2 testing for research purposes. OBJECTIVE: The aim of this study was to assess the willingness of adults to use different specimen collection modalities for themselves and children as part of a COVID-19 research study. METHODS: Between March 27 and April 1, 2020, we recruited 1435 adults aged 18 years or older though social media advertisements. Participants completed a survey that included 5-point Likert scale items stating how willing they were to use the following specimen collection testing modalities as part of a research study: home collection of a saliva sample, home collection of a throat swab, home finger-prick blood collection, drive-through site throat swab, clinic throat swab, and clinic blood collection. Additionally, participants indicated how the availability of home-based collection methods would impact their willingness to participate compared to drive-through and clinic-based specimen collection. We used Kruskal-Wallis tests and Spearman rank correlations to assess if willingness to use each testing modality differed by demographic variables and characteristics of interest. We compared the overall willingness to use each testing modality and estimated effect sizes with Cohen d. RESULTS: We analyzed responses from 1435 participants with a median age of 40.0 (SD=18.2) years and over half of which were female (761/1435, 53.0%). Most participants agreed or strongly agreed that they would be willing to use specimens self-collected at home to participate in research, including willingness to collect a saliva sample (1259/1435, 87.7%) or a throat swab (1191/1435, 83.1%). Willingness to collect a throat swab sample was lower in both a drive-through setting (64%) and clinic setting (53%). Overall, 69.0% (990/1435) of participants said they would be more likely to participate in a research study if they could provide a saliva sample or throat swab at home compared to going to a drive-through site; only 4.4% (63/1435) of participants said they would be less likely to participate using self-collected samples. For each specimen collection modality, willingness to collect specimens from children for research was lower than willingness to use on oneself, but the ranked order of modalities was similar. CONCLUSIONS: Most participants were willing to participate in a COVID-19 research study that involves laboratory testing; however, there was a strong preference for home specimen collection procedures over drive-through or clinic-based testing. To increase participation and minimize bias, epidemiologic research studies of SARS-CoV-2 infection and immune response should consider home specimen collection methods.

J Med Internet Res2020       LitCov and CORD-19
2905Single-port laparoscopic right hemicolectomy: a safe alternative to conventional laparoscopy  

N/A

Dis Colon Rectum2010       CORD-19
2906Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset  

Importance The dynamics of coronavirus disease 2019 (COVID-19) transmissibility are yet to be fully understood. Better understanding of the transmission dynamics is important for the development and evaluation of effective control policies. Objective To delineate the transmission dynamics of COVID-19 and evaluate the transmission risk at different exposure window periods before and after symptom onset. Design, Setting, and Participants This prospective case-ascertained study in Taiwan included laboratory-confirmed cases of COVID-19 and their contacts. The study period was from January 15 to March 18, 2020. All close contacts were quarantined at home for 14 days after their last exposure to the index case. During the quarantine period, any relevant symptoms (fever, cough, or other respiratory symptoms) of contacts triggered a COVID-19 test. The final follow-up date was April 2, 2020. Main Outcomes and Measures Secondary clinical attack rate (considering symptomatic cases only) for different exposure time windows of the index cases and for different exposure settings (such as household, family, and health care). Results We enrolled 100 confirmed patients, with a median age of 44 years (range, 11-88 years), including 56 men and 44 women. Among their 2761 close contacts, there were 22 paired index-secondary cases. The overall secondary clinical attack rate was 0.7% (95% CI, 0.4%-1.0%). The attack rate was higher among the 1818 contacts whose exposure to index cases started within 5 days of symptom onset (1.0% [95% CI, 0.6%-1.6%]) compared with those who were exposed later (0 cases from 852 contacts; 95% CI, 0%-0.4%). The 299 contacts with exclusive presymptomatic exposures were also at risk (attack rate, 0.7% [95% CI, 0.2%-2.4%]). The attack rate was higher among household (4.6% [95% CI, 2.3%-9.3%]) and nonhousehold (5.3% [95% CI, 2.1%-12.8%]) family contacts than that in health care or other settings. The attack rates were higher among those aged 40 to 59 years (1.1% [95% CI, 0.6%-2.1%]) and those aged 60 years and older (0.9% [95% CI, 0.3%-2.6%]). Conclusions and Relevance In this study, high transmissibility of COVID-19 before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized measures may be required, such as social distancing.

JAMA Intern Med2020       LitCov and CORD-19
2907Renin-Angiotensin-Aldosterone System Blockers and the Risk of Covid-19  

BACKGROUND: A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting–enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. METHODS: We carried out a population-based case–control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression. RESULTS: Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. CONCLUSIONS: In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.

N Engl J Med2020       LitCov and CORD-19
2908How generation intervals shape the relationship between growth rates and reproductive numbers  

N/A

Proc Biol Sci2007       CORD-19
2909Hand-assisted laparoscopic colectomy: benefits of laparoscopic colectomy at no extra cost  

N/A

J Am Coll Surg2009       CORD-19
2910Evidence of SARS-CoV-2 Replication and Tropism in the Lungs, Airways and Vascular Endothelium of Patients With Fatal COVID-19: An Autopsy Case Series  

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and replication in various tissues. METHODS: We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case patients (age range, 1 month to 84 years; 21 COVID-19 confirmed, 43 suspected COVID-19) by SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR). For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in situ hybridization (ISH), subgenomic RNA RT-PCR, and whole-genome sequencing. RESULTS: SARS-CoV-2 was identified by RT-PCR in 32 case patients (21 COVID-19 confirmed, 11 suspected). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR–positive case patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes, and macrophages of lungs; epithelial cells of airways; and endothelial cells and vessel walls of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. The D614G variant was detected in 9 RT-PCR–positive case patients. CONCLUSIONS: We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes.

J Infect Dis2021       LitCov and CORD-19
2911Clinical features, laboratory characteristics and outcomes of patients hospitalized with COVID-19: Early report from the United States  

N/A

Diagnosis (Berl)2020       LitCov and CORD-19
2912Endovascular thrombectomy after large-vessel ischemic stroke: a meta-analysis of individual patient data from five randomised trials  

N/A

Lancet2016       CORD-19
2913How Africa has tackled covid-19  

N/A

BMJ2020       LitCov and CORD-19
2914Potential effects of vaccinations on the prevention of COVID-19: rationale, clinical evidence, risks and public health considerations  

N/A

Expert Rev Vaccines2020       LitCov and CORD-19
2915Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study  

OBJECTIVE: To estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death). DESIGN: Test negative design study. SETTING: Ontario, Canada between 14 December 2020 and 19 April 2021. PARTICIPANTS: 324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2. INTERVENTIONS: BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. MAIN OUTCOME MEASURES: Laboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes. RESULTS: Of 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation. CONCLUSIONS: Two doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.

BMJ2021       LitCov and CORD-19
2916The potential impact of COVID-19 in refugee camps in Bangladesh and beyond: A modeling study  

BACKGROUND: COVID-19 could have even more dire consequences in refugees camps than in general populations. Bangladesh has confirmed COVID-19 cases and hosts almost 1 million Rohingya refugees from Myanmar, with 600,000 concentrated in the Kutupalong-Balukhali Expansion Site (mean age, 21 years; standard deviation [SD], 18 years; 52% female). Projections of the potential COVID-19 burden, epidemic speed, and healthcare needs in such settings are critical for preparedness planning. METHODS AND FINDINGS: To explore the potential impact of the introduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Kutupalong-Balukhali Expansion Site, we used a stochastic Susceptible Exposed Infectious Recovered (SEIR) transmission model with parameters derived from emerging literature and age as the primary determinant of infection severity. We considered three scenarios with different assumptions about the transmission potential of SARS-CoV-2. From the simulated infections, we estimated hospitalizations, deaths, and healthcare needs expected, age-adjusted for the Kutupalong-Balukhali Expansion Site age distribution. Our findings suggest that a large-scale outbreak is likely after a single introduction of the virus into the camp, with 61%–92% of simulations leading to at least 1,000 people infected across scenarios. On average, in the first 30 days of the outbreak, we expect 18 (95% prediction interval [PI], 2–65), 54 (95% PI, 3–223), and 370 (95% PI, 4–1,850) people infected in the low, moderate, and high transmission scenarios, respectively. These reach 421,500 (95% PI, 376,300–463,500), 546,800 (95% PI, 499,300–567,000), and 589,800 (95% PI, 578,800–595,600) people infected in 12 months, respectively. Hospitalization needs exceeded the existing hospitalization capacity of 340 beds after 55–136 days, between the low and high transmission scenarios. We estimate 2,040 (95% PI, 1,660–2,500), 2,650 (95% PI, 2,030–3,380), and 2,880 (95% PI, 2,090–3,830) deaths in the low, moderate, and high transmission scenarios, respectively. Due to limited data at the time of analyses, we assumed that age was the primary determinant of infection severity and hospitalization. We expect that comorbidities, limited hospitalization, and intensive care capacity may increase this risk; thus, we may be underestimating the potential burden. CONCLUSIONS: Our findings suggest that a COVID-19 epidemic in a refugee settlement may have profound consequences, requiring large increases in healthcare capacity and infrastructure that may exceed what is currently feasible in these settings. Detailed and realistic planning for the worst case in Kutupalong-Balukhali and all refugee camps worldwide must begin now. Plans should consider novel and radical strategies to reduce infectious contacts and fill health worker gaps while recognizing that refugees may not have access to national health systems.

PLoS Med2020       LitCov and CORD-19
2917COVID-19 vaccines: concerns beyond protective efficacy and safety  

N/A

Expert Rev Vaccines2021       LitCov and CORD-19
2918A tug-of-war between SARS-CoV-2 and host antiviral defence: lessons from other pathogenic viruses  

World Health Organization has declared the ongoing outbreak of coronavirus disease 2019 (COVID-19) a Public Health Emergency of International Concern. The virus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. Human infection with SARS-CoV-2 leads to a wide range of clinical manifestations ranging from asymptomatic, mild, moderate to severe. The severe cases present with pneumonia, which can progress to acute respiratory distress syndrome. The outbreak provides an opportunity for real-time tracking of an animal coronavirus that has just crossed species barrier to infect humans. The outcome of SARS-CoV-2 infection is largely determined by virus-host interaction. Here, we review the discovery, zoonotic origin, animal hosts, transmissibility and pathogenicity of SARS-CoV-2 in relation to its interplay with host antiviral defense. A comparison with SARS-CoV, Middle East respiratory syndrome coronavirus, community-acquired human coronaviruses and other pathogenic viruses including human immunodeficiency viruses is made. We summarize current understanding of the induction of a proinflammatory cytokine storm by other highly pathogenic human coronaviruses, their adaptation to humans and their usurpation of the cell death programmes. Important questions concerning the interaction between SARS-CoV-2 and host antiviral defence, including asymptomatic and presymptomatic virus shedding, are also discussed.

Emerg Microbes Infect2020       LitCov and CORD-19
2919Relevance of SARS-CoV-2 related factors ACE2 and TMPRSS2 expressions in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality and disease recurrence in COVID-19 patients  

COVID-19 is caused by a new strain of coronavirus called SARS-coronavirus-2 (SARS-CoV-2), which is a positive sense single strand RNA virus. In humans, it binds to angiotensin converting enzyme 2 (ACE2) with the help a structural protein on its surface called the S-spike. Further, cleavage of the viral spike protein (S) by the proteases like transmembrane serine protease 2 (TMPRSS2) or Cathepsin L (CTSL) is essential to effectuate host cell membrane fusion and virus infectivity. COVID-19 poses intriguing issues with imperative relevance to clinicians. The pathogenesis of GI symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 are of particular relevance because they cannot be sufficiently explained from the existing knowledge of the viral diseases. Tissue specific variations of SARS-CoV-2 cell entry related receptors expression in healthy individuals can help in understanding the pathophysiological basis the aforementioned collection of symptoms. ACE2 mediated dysregulation of sodium dependent glucose transporter (SGLT1 or SLC5A1) in the intestinal epithelium also links it to the pathogenesis of diabetes mellitus which can be a possible reason for the associated mortality in COVID-19 patients with diabetes. High expression of ACE2 in mucosal cells of the intestine and GB make these organs potential sites for the virus entry and replication. Continued replication of the virus at these ACE2 enriched sites may be a basis for the disease recurrence reported in some, thought to be cured, patients. Based on the human tissue specific distribution of SARS-CoV-2 cell entry factors ACE2 and TMPRSS2 and other supportive evidence from the literature, we hypothesize that SARS-CoV-2 host cell entry receptor—ACE2 based mechanism in GI tissue may be involved in COVID-19 (i) in the pathogenesis of digestive symptoms, (ii) in increased diabetic complications, (iii) in disease recurrence.

Med Hypotheses2020       LitCov and CORD-19
2920Venous thromboembolism and COVID-19  

Respir Med Res2020       LitCov and CORD-19
2921SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract  

Summary The mode of acquisition and causes for the variable clinical spectrum of COVID-19 remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore SARS-CoV-2 pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest ACE2 expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) vs distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.

Cell2020       LitCov and CORD-19
2922Comparison of final infarct volumes in patients who received endovascular therapy or intravenous thrombolysis for acute intracranial large-vessel occlusions  

N/A

JAMA Neurol2013       CORD-19
2923Longer Duration of SARS-CoV-2 Infection in a Case of Mild COVID-19 With Weak Production of the Specific IgM and IgG Antibodies  

Background: The relationship between SARS-CoV-2-carrying time and specific antibody production has not yet been reported in re-admitted COVID-19 patients. We reported a case of mild COVID-19 with long virus-carrying time, weak production of virus-specific IgG and IgM antibodies, and recurrence of positive SARS-CoV-2 RNA in stool specimens after discharge. Case Presentation: A 27-year-old male was diagnosed as COVID-19 after returning to Meizhou from Wuhan. Despite extremely mild symptoms, the patient was hospitalized for 24 days because of persistent positive SARS-CoV-2 RNA detection. Three days after recovery discharge, he was hospitalized again for 7 days due to a recurrence of the positive SARS-CoV-2 RNA result, while in a good physical condition. Serological assay, using a fluorescent immunochromatography detection kit specific to SARS-CoV-2, showed that SARS-CoV-2-specific IgM antibodies were undetectable and IgG antibodies were very low on day 8 after onset; both of the antibodies seemingly reached top concentrations on day 15 (just a 6-fold increase of the IgG titer), and then decreased, remaining relatively stable from day 25 after onset until discharge. The production of the IgM and IgG targeting SARS-CoV-2 in this very mild case was much lower than that in a severe case of COVID-19 during the same hospitalizing period, and the latter was used as a control. Conclusion: Mild COVID-19 patients could carry SARS-CoV-2 for a long time, which may be related to the weak production of the virus-specific IgG and IgM. Recurrence of positive SARS-CoV-2 RNA could occur in mild COVID-19 possibly due to intermittent virus shedding, so strict quarantine and health surveillance should be taken for all discharged COVID-19 patients to prevent a potential virus spread.

Front Immunol2020       LitCov and CORD-19
2924Reconsidering the technical aspects and quality management background of faecal microbiota transplantation due to the novel coronavirus pandemic  

N/A

Orv Hetil2020       LitCov and CORD-19
2925Engaging adolescents in changing behaviour (EACH-B): a study protocol for a cluster randomised controlled trial to improve dietary quality and physical activity  

BACKGROUND: Poor diet and lack of physical activity are strongly linked to non-communicable disease risk, but modifying them is challenging. There is increasing recognition that adolescence is an important time to intervene; habits formed during this period tend to last, and physical and psychological changes during adolescence make it an important time to help individuals form healthier habits. Improving adolescents’ health behaviours is important not only for their own health now and in adulthood, but also for the health of any future children. Building on LifeLab—an existing, purpose-built educational facility at the University of Southampton—we have developed a multi-component intervention for secondary school students called Engaging Adolescents in Changing Behaviour (EACH-B) that aims to motivate and support adolescents to eat better and be more physically active. METHODS: A cluster randomised controlled trial is being conducted to evaluate the effectiveness of the EACH-B intervention. The primary outcomes of the intervention are self-reported dietary quality and objectively measured physical activity (PA) levels, both assessed at baseline and at 12-month follow-up. The EACH-B intervention consists of three linked elements: professional development for teachers including training in communication skills to support health behaviour change; the LifeLab educational module comprising in-school teaching of nine science lessons linked to the English National Curriculum and a practical day visit to the LifeLab facility; and a personalised digital intervention that involves social support and game features that promote eating better and being more active. Both the taught module and the LifeLab day are designed with a focus on the science behind the messages about positive health behaviours, such as diet and PA, for the adolescents now, in adulthood and their future offspring, with the aim of promoting personal plans for change. The EACH-B research trial aims to recruit approximately 2300 secondary school students aged 12–13 years from 50 schools (the clusters) from Hampshire and neighbouring counties. Participating schools will be randomised to either the control or intervention arm. The intervention will be run during two academic years, with continual recruitment of schools throughout the school year until the sample size is reached. The schools allocated to the control arm will receive normal schooling but will be offered the intervention after data collection for the trial is complete. An economic model will be developed to assess the cost-effectiveness of the EACH-B intervention compared with usual schooling. DISCUSSION: Adolescents’ health needs are often ignored and they can be difficult to engage in behaviour change. Building a cheap, sustainable way of engaging them in making healthier choices will benefit their long-term health and that of their future children. TRIAL REGISTRATION: ISRCTN 74109264. Registered on 30 August 2019. EACH-B is a cluster randomised controlled trial, funded by the National Institute for Health Research (RP-PG-0216-20004).

Trials2020       CORD-19
2926Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients  

BACKGROUND: Due to the general susceptibility of new coronaviruses, the clinical characteristics and outcomes of elderly and young patients may be different. OBJECTIVE: To analyze the clinical characteristics of elderly patients with 2019 new-type coronavirus pneumonia (COVID-19). METHODS: This is a retrospective study of patients with new coronavirus pneumonia (COVID-19) who were hospitalized in Hainan Provincial People's Hospital from January 15, 2020 to February 18, 2020. Compare the clinical characteristics of elderly with Young and Middle-aged patients. RESULTS: A total of 56 patients were enrolled 18 elderly patients (32.14%), and 38 young and middle-aged patients (67.86%). The most common symptoms in both groups were fever, followed by cough and sputum. Four patients in the elderly group received negative pressure ICU for mechanical ventilation, and five patients in the young and middle-aged group. One patient died in the elderly group (5.56%), and two patients died in the young and middle-aged group (5.26%). The PSI score of the elderly group was higher than that of the young and middle-aged group (P < 0.001). The proportion of patients with PSI grades IV and V was significantly higher in the elderly group than in the young and middle-aged group (P < 0.05). The proportion of multiple lobe involvement in the elderly group was higher than that in the young and middle-aged group (P < 0.001), and there was no difference in single lobe lesions between the two groups. The proportion of lymphocytes in the elderly group was significantly lower than that in the young and middle-aged group (P < 0.001), and the C-reactive protein was significantly higher in the young group (P < 0.001). The Lopinavir and Ritonavir Tablets, Chinese medicine, oxygen therapy, and mechanical ventilation were statistically different in the elderly group and the young and middle-aged group, and the P values were all <0.05. INTERPRETATION: The mortality of elderly patients with COVID-19 is higher than that of young and middle-aged patients, and the proportion of patients with PSI grade IV and V is significantly higher than that of young and middle-aged patients. Elderly patients with COVID-19 are more likely to progress to severe disease.

J Infect2020       LitCov and CORD-19
2927Seroprevalence of and Risk Factors Associated With SARS-CoV-2 Infection in Healthcare Workers During the Early COVID-19 Pandemic in Italy  

IMPORTANCE: Identifying health care settings and professionals at increased risk of SARS-CoV-2 infection is crucial to defining appropriate strategies, resource allocation, and protocols to protect health care workers (HCWs) and patients. Moreover, such information is crucial to decrease the risk that HCWs and health care facilities become amplifiers for SARS-CoV-2 transmission in the community. OBJECTIVE: To assess the association of different health care professional categories and operational units, including in-hospital wards, outpatient facilities, and territorial care departments, with seroprevalence and odds of SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted using IgG serological tests collected from April 1 through May 26, 2020, in the Lombardy region in Italy. Voluntary serological screening was offered to all clinical and nonclinical staff providing any health care services or support to health care services in the region. Data were analyzed from June 2020 through April 2021. EXPOSURES: Employment in the health care sector. MAIN OUTCOMES AND MEASURES: Seroprevalence of positive IgG antibody tests for SARS-CoV-2 was collected, and odds ratios of experiencing infection were calculated. RESULTS: A total of 140 782 professionals employed in the health sector were invited to participate in IgG serological screening, among whom 82 961 individuals (59.0% response rate) were tested for SARS-CoV-2 antibodies, with median (interquartile range [IQR]; range) age, 50 (40-56; 19-83) years and 59 839 (72.1%) women. Among these individuals, 10 115 HCWs (12.2%; 95% CI, 12.0%-12.4%) had positive results (median [IQR; range] age, 50 [39-55; 20-80] years; 7298 [72.2%] women). Statistically significantly higher odds of infection were found among health assistants (adjusted odds ratio [aOR], 1.48; 95% CI, 1.33-1.65) and nurses (aOR, 1.28; 95% CI, 1.17-1.41) compared with administrative staff and among workers employed in internal medicine (aOR, 2.24; 95% CI, 1.87-2.68), palliative care (aOR, 1.84; 95% CI, 1.38-2.44), rehabilitation (aOR, 1.59; 95% CI, 1.33-1.91), and emergency departments (aOR, 1.56; 95% CI, 1.29-1.89) compared with those working as telephone operators. Statistically significantly lower odds of infection were found among individuals working in forensic medicine (aOR, 0.40; 95% CI, 0.19-0.88), histology and anatomical pathology (aOR, 0.71; 95% CI, 0.52-0.97), and medical device sterilization (aOR, 0.54; 95% CI, 0.35-0.84) compared with those working as telephone operators. The odds of infection for physicians and laboratory personnel were not statistically significantly different from those found among administrative staff. The odds of infection for workers employed in intensive care units and infectious disease wards were not statistically significantly different from those of telephone operators. CONCLUSIONS AND RELEVANCE: These findings suggest that professionals partially accustomed to managing infectious diseases had higher odds of SARS-CoV-2 infection. The findings further suggest that adequate organization of clinical wards and personnel, appropriate personal protective equipment supply, and training of all workers directly and repeatedly exposed to patients with clinical or subclinical COVID-19 should be prioritized to decrease the risk of infection in health care settings.

JAMA Netw Open2021       LitCov and CORD-19
2928Human serum from SARS-CoV-2-vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant  

BACKGROUND: The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and immediately classified as a variant of concern (VOC), since it shows substantially more mutations in the spike protein than any previous variant, especially in the receptor-binding domain (RBD). We analyzed the binding of the Omicron RBD to the human angiotensin-converting enzyme-2 receptor (ACE2) and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta, or Delta RBD variants. METHODS: All RBDs were produced in insect cells. RBD binding to ACE2 was analyzed by ELISA and microscale thermophoresis (MST). Similarly, sera from 27 COVID-19 patients, 81 vaccinated individuals, and 34 booster recipients were titrated by ELISA on RBDs from the original Wuhan strain, Beta, Delta, and Omicron VOCs. In addition, the neutralization efficacy of authentic SARS-CoV-2 wild type (D614G), Delta, and Omicron by sera from 2× or 3× BNT162b2-vaccinated persons was analyzed. RESULTS: Surprisingly, the Omicron RBD showed a somewhat weaker binding to ACE2 compared to Beta and Delta, arguing that improved ACE2 binding is not a likely driver of Omicron evolution. Serum antibody titers were significantly lower against Omicron RBD compared to the original Wuhan strain. A 2.6× reduction in Omicron RBD binding was observed for serum of 2× BNT162b2-vaccinated persons. Neutralization of Omicron SARS-CoV-2 was completely diminished in our setup. CONCLUSION: These results indicate an immune escape focused on neutralizing antibodies. Nevertheless, a boost vaccination increased the level of anti-RBD antibodies against Omicron, and neutralization of authentic Omicron SARS-CoV-2 was at least partially restored. This study adds evidence that current vaccination protocols may be less efficient against the Omicron variant. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02312-5.

BMC Med2022       LitCov and CORD-19
2929ZCURVE_CoV: a new system to recognize protein coding genes in coronavirus genomes and its applications in analyzing SARS-CoV genomes  

A new system to recognize protein coding genes in the coronavirus genomes, specially suitable for the SARS-CoV genomes, has been proposed in this paper. Compared with some existing systems, the new program package has the merits of simplicity, high accuracy, reliability, and quickness. The system ZCURVE_CoV has been run for each of the 11 newly sequenced SARS-CoV genomes. Consequently, six genomes not annotated previously have been annotated, and some problems of previous annotations in the remaining five genomes have been pointed out and discussed. In addition to the polyprotein chain ORFs 1a and 1b and the four genes coding for the major structural proteins, spike (S), small envelop (E), membrane (M), and nuleocaspid (N), respectively, ZCURVE_CoV also predicts 5–6 putative proteins in length between 39 and 274 amino acids with unknown functions. Some single nucleotide mutations within these putative coding sequences have been detected and their biological implications are discussed. A web service is provided, by which a user can obtain the annotated result immediately by pasting the SARS-CoV genome sequences into the input window on the web site (http://tubic.tju.edu.cn/sars/). The software ZCURVE_CoV can also be downloaded freely from the web address mentioned above and run in computers under the platforms of Windows or Linux.

Biochem Biophys Res Commun2003       CORD-19
2930Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy  

A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24–72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0–2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.

Autoimmun Rev2020       LitCov and CORD-19
2931Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China  

As of 29 February 2020 there were 79,394 confirmed cases and 2,838 deaths from COVID-19 in mainland China. Of these, 48,557 cases and 2,169 deaths occurred in the epicenter, Wuhan. A key public health priority during the emergence of a novel pathogen is estimating clinical severity, which requires properly adjusting for the case ascertainment rate and the delay between symptoms onset and death. Using public and published information, we estimate that the overall symptomatic case fatality risk (the probability of dying after developing symptoms) of COVID-19 in Wuhan was 1.4% (0.9–2.1%), which is substantially lower than both the corresponding crude or naïve confirmed case fatality risk (2,169/48,557 = 4.5%) and the approximator(1) of deaths/deaths + recoveries (2,169/2,169 + 17,572 = 11%) as of 29 February 2020. Compared to those aged 30–59 years, those aged below 30 and above 59 years were 0.6 (0.3–1.1) and 5.1 (4.2–6.1) times more likely to die after developing symptoms. The risk of symptomatic infection increased with age (for example, at ~4% per year among adults aged 30–60 years).

Nat Med2020       LitCov and CORD-19
2932The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity  

N/A

J Virol2005       CORD-19
2933The impact of SARS-CoV-2 on the mental health of healthcare workers in a hospital setting-A Systematic Review  

OBJECTIVES: The SARS‐CoV‐2 global pandemic has subjected healthcare workers (HCWs) to high risk of infection through direct workplace exposure, coupled with increased workload and psychological stress. This review aims to determine the impact of SARS‐CoV‐2 on mental health outcomes of hospital‐based HCWs and formulate recommendations for future action. METHODS: A systematic review was performed between 31st December 2019 and 17th June 2020 through Ovid Medline and Embase databases (PROSPERO ID CRD42020181204). Studies were included for review if they investigated the impact of SARS‐CoV‐2 on mental health outcomes of hospital‐based HCWs and used validated psychiatric scoring tools. Prevalence of ICD‐10 classified psychiatric disorders was the primary outcome measure. RESULTS: The initial search returned 436 articles. Forty‐four studies were included in final analysis, with a total of 69,499 subjects. Prevalence ranges of six mental health outcomes were identified: depression 13.5%‐44.7%; anxiety 12.3%‐35.6%; acute stress reaction 5.2%‐32.9%; post‐traumatic stress disorder 7.4%‐37.4%; insomnia 33.8%‐36.1%; and occupational burnout 3.1%‐43.0%. Direct exposure to SARS‐CoV‐2 patients was the most common risk factor identified for all mental health outcomes except occupational burnout. Nurses, frontline HCWs, and HCWs with low social support and fewer years of working experience reported the worst outcomes. CONCLUSION: The SARS‐CoV‐2 pandemic has significantly impacted the mental health of HCWs. Frontline staff demonstrate worse mental health outcomes. Hospitals should be staffed to meet service provision requirements and to mitigate the impact onmental health. This can be improved with access to rapid‐response psychiatric teams and should be continually monitored throughout the pandemic and beyond its conclusion.

J Occup Health2020       LitCov and CORD-19
2934Survey of stress reactions among Healthcare workers involved with the SARS outbreak  

N/A

Psychiatr Serv2004       CORD-19
2935Regulation of IRF-3-dependent Innate Immunity by the Papain-like Protease Domain of the Severe Acute Respiratory Syndrome Coronavirus  

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a novel coronavirus that causes a highly contagious respiratory disease, SARS, with significant mortality. Although factors contributing to the highly pathogenic nature of SARS-CoV remain poorly understood, it has been reported that SARS-CoV infection does not induce type I interferons (IFNs) in cell culture. However, it is uncertain whether SARS-CoV evades host detection or has evolved mechanisms to counteract innate host defenses. We show here that infection of SARS-CoV triggers a weak IFN response in cultured human lung/bronchial epithelial cells without inducing the phosphorylation of IFN-regulatory factor 3 (IRF-3), a latent cellular transcription factor that is pivotal for type I IFN synthesis. Furthermore, SARS-CoV infection blocked the induction of IFN antiviral activity and the up-regulation of protein expression of a subset of IFN-stimulated genes triggered by double-stranded RNA or an unrelated paramyxovirus. In searching for a SARS-CoV protein capable of counteracting innate immunity, we identified the papain-like protease (PLpro) domain as a potent IFN antagonist. The inhibition of the IFN response does not require the protease activity of PLpro. Rather, PLpro interacts with IRF-3 and inhibits the phosphorylation and nuclear translocation of IRF-3, thereby disrupting the activation of type I IFN responses through either Toll-like receptor 3 or retinoic acid-inducible gene I/melanoma differentiation-associated gene 5 pathways. Our data suggest that regulation of IRF-3-dependent innate antiviral defenses by PLpro may contribute to the establishment of SARS-CoV infection.

J Biol Chem2007       CORD-19
2936'Vaccine hesitancy' among university students in Italy during the COVID-19 pandemic  

The debate around vaccines has been in the spotlight over the last few years in Europe, both within the scientific community and the general public debate. In this regard, the case of the Italian vaccination debate is particularly worrying given that Italy has been one of the European countries with the highest number of measles cases in the recent past. According to this scenario, we conducted a cross-sectional study on a convenience sample of Italian university students aimed at: (1) exploring their attitudes towards a future vaccine to prevent COVID-19 and; (2) evaluating the impact of the university curricula (healthcare vs. non-healthcare curricula) on the intention to vaccinate. Descriptive analysis on the 735 students that answered to the question on the intention to vaccinate showed that 633 (86.1%) students reported that they would choose to have a vaccination for the COVID-19 coronavirus; on the other side, 102 (13.9%) students reported that they would not or be not sure to vaccine (low intention to vaccinate). This means that in our sample more than one student out of 10 shows low intention to vaccinate (vaccine hesitancy). Furthermore, when running analysis comparing healthcare students versus non-healthcare students we found no significant differences in responses’ percentage distribution (p = .097). Understanding the student’s perspective about the future COVID-19 vaccine and supporting their health engagement and consciousness may be useful in planning adequate response and multidisciplinary educational strategies—including the psychological perspective on vaccine hesitancy underlying factors - in the post-pandemic period.

Eur J Epidemiol2020       LitCov and CORD-19
2937COVID-19 vaccination intention in the UK: results from the COVID-19 vaccination acceptability study (CoVAccS), a nationally representative cross-sectional survey  

To investigate factors associated with intention to be vaccinated against COVID-19 we conducted a cross-sectional survey of 1,500 UK adults, recruited from an existing online research panel. Data were collected between 14th and 17th July 2020. We used linear regression analyses to investigate associations between intention to be vaccinated for COVID-19 “when a vaccine becomes available to you” and sociodemographic factors, previous influenza vaccination, general vaccine attitudes and beliefs, attitudes and beliefs about COVID-19, and attitudes and beliefs about a COVID-19 vaccination. 64% of participants reported being very likely to be vaccinated against COVID-19, 27% were unsure, and 9% reported being very unlikely to be vaccinated. Personal and clinical characteristics, previous influenza vaccination, general vaccination beliefs, and beliefs and attitudes about COVID-19 and a COVID-19 vaccination explained 76% of the variance in vaccination intention. Intention to be vaccinated was associated with more positive general COVID-19 vaccination beliefs and attitudes, weaker beliefs that the vaccination would cause side effects or be unsafe, greater perceived information sufficiency to make an informed decision about COVID-19 vaccination, greater perceived risk of COVID-19 to others (but not risk to oneself), older age, and having been vaccinated for influenza last winter (2019/20). Despite uncertainty around the details of a COVID-19 vaccination, most participants reported intending to be vaccinated for COVID-19. Actual uptake may be lower. Vaccination intention reflects general vaccine beliefs and attitudes. Campaigns and messaging about a COVID-19 vaccination could consider emphasizing the risk of COVID-19 to others and necessity for everyone to be vaccinated.

Hum Vaccin Immunother2020       LitCov and CORD-19
2938Estimation of SARS-CoV-2 mortality during the early stages of an epidemic: A modeling study in Hubei, China and six regions in Europe  

BACKGROUND: As of 16 May 2020, more than 4.5 million cases and more than 300,000 deaths from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. Reliable estimates of mortality from SARS-CoV-2 infection are essential for understanding clinical prognosis, planning healthcare capacity, and epidemic forecasting. The case–fatality ratio (CFR), calculated from total numbers of reported cases and reported deaths, is the most commonly reported metric, but it can be a misleading measure of overall mortality. The objectives of this study were to (1) simulate the transmission dynamics of SARS-CoV-2 using publicly available surveillance data and (2) infer estimates of SARS-CoV-2 mortality adjusted for biases and examine the CFR, the symptomatic case–fatality ratio (sCFR), and the infection–fatality ratio (IFR) in different geographic locations. METHOD AND FINDINGS: We developed an age-stratified susceptible-exposed-infected-removed (SEIR) compartmental model describing the dynamics of transmission and mortality during the SARS-CoV-2 epidemic. Our model accounts for two biases: preferential ascertainment of severe cases and right-censoring of mortality. We fitted the transmission model to surveillance data from Hubei Province, China, and applied the same model to six regions in Europe: Austria, Bavaria (Germany), Baden-Württemberg (Germany), Lombardy (Italy), Spain, and Switzerland. In Hubei, the baseline estimates were as follows: CFR 2.4% (95% credible interval [CrI] 2.1%–2.8%), sCFR 3.7% (3.2%–4.2%), and IFR 2.9% (2.4%–3.5%). Estimated measures of mortality changed over time. Across the six locations in Europe, estimates of CFR varied widely. Estimates of sCFR and IFR, adjusted for bias, were more similar to each other but still showed some degree of heterogeneity. Estimates of IFR ranged from 0.5% (95% CrI 0.4%–0.6%) in Switzerland to 1.4% (1.1%–1.6%) in Lombardy, Italy. In all locations, mortality increased with age. Among individuals 80 years or older, estimates of the IFR suggest that the proportion of all those infected with SARS-CoV-2 who will die ranges from 20% (95% CrI 16%–26%) in Switzerland to 34% (95% CrI 28%–40%) in Spain. A limitation of the model is that count data by date of onset are required, and these are not available in all countries. CONCLUSIONS: We propose a comprehensive solution to the estimation of SARS-Cov-2 mortality from surveillance data during outbreaks. The CFR is not a good predictor of overall mortality from SARS-CoV-2 and should not be used for evaluation of policy or comparison across settings. Geographic differences in IFR suggest that a single IFR should not be applied to all settings to estimate the total size of the SARS-CoV-2 epidemic in different countries. The sCFR and IFR, adjusted for right-censoring and preferential ascertainment of severe cases, are measures that can be used to improve and monitor clinical and public health strategies to reduce the deaths from SARS-CoV-2 infection.

PLoS Med2020       LitCov and CORD-19
2939Epidemiology of viral respiratory infections  

N/A

Am J Med2002       CORD-19
2940Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping and analysis of spike variants  

N/A

J Virol2005       CORD-19
2941The Effect of the COVID-19 Pandemic on Physicians' Use and Perception of Telehealth: The Case of Lebanon  

The COVID-19 pandemic forced physicians to quickly adapt and find ways to provide their usual offline services by using online tools. We aimed to understand how physicians adapted to the sudden need for telehealth and if their perception of telehealth changed due to their experience during the COVID-19 pandemic. We conducted an exploratory sequential mixed-methods study. We interviewed five Lebanese physicians and thematically analyzed the interviews. We developed a questionnaire based on the analysis results and administered it online to physicians in Lebanon. In total, 140 responses were collected. We found that, during the COVID-19 pandemic, physicians engaged in more telehealth activities in the realms of telemedicine, public awareness, continuing medical education, research, administration, and teaching. They also expanded their repertoire of information-technology tools. Our results also show that there was a significant shift in the physicians’ perceptions, indicating greater openness and willingness to adopt telehealth services. However, a significant amount of skepticism and uncertainty regarding telemedicine remains, especially concerning its efficiency, safety, and the adequacy of existing regulations. Based on our findings, we offer recommendations for health IT policy makers, developers, and researchers, to sustain the continuity of telehealth activities beyond the COVID-19 pandemic.

Int J Environ Res Public Healt2020       LitCov and CORD-19
2942Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on haemodialysis  

BACKGROUND: Patients with chronic renal insufficiency on maintenance haemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only a few studies have addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population. METHODS: We assessed immunogenicity of the mRNA vaccine BNT162b2 in at-risk dialysis patients and characterised systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements. We further compared binding capacity and neutralization efficacy of vaccination-induced immunoglobulins against emerging SARS-CoV-2 variants Alpha, Beta, Epsilon and Cluster 5 by ACE2-RBD competition assay. FINDINGS: Patients on maintenance haemodialysis exhibit detectable but variable cellular and humoral immune responses against SARS-CoV-2 and variants of concern after a two-dose regimen of BNT162b2. Although vaccination-induced immunoglobulins were detectable in saliva and plasma, both anti-SARS-CoV-2 IgG and neutralization efficacy was reduced compared to a vaccinated non-dialysed control population. Similarly, T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides was significantly diminished. INTERPRETATION: Quantifiable humoral and cellular immune responses after BNT162b2 vaccination in individuals on maintenance haemodialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in the face of emerging variants of concern may favour this at-risk population for re-vaccination using modified vaccines at the earliest opportunity. FUNDING: Initiative and Networking Fund of the Helmholtz Association of German Research Centres, EU Horizon 2020 research and innovation program, State Ministry of Baden-Württemberg for Economic Affairs, Labour and Tourism.

EBioMedicine2021       LitCov and CORD-19
2943Perception and attitudes of medical students on clinical clerkship in the era of the COVID-19 pandemic  

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) has been placing severe strain on global healthcare systems and medical education programs, leading to growing demands for medical students to assume the role of preliminary healthcare providers. OBJECTIVES: To assess the perception and attitudes of medical students about clinical clerkship training during the COVID-19 pandemic. DESIGN: A cross-sectional survey with web-based 3-fields/14-items questionnaire was conducted, from April 7 to 14, 2020, to evaluate their self-assessed perception and attitudes on clerkship training of hospital practice under the COVID-19 outbreak and spread among 161 (78 on pre-clerkship course, 83 on clinical clerkship course) medical students at Dankook University College of Medicine, Cheonan, Republic of Korea. RESULTS: Of the 151 medical students who completed the survey, 81 students (53.7%) considered themselves familiar with COVID-19. Although the students were concerned about the spread of the virus during clinical clerkship training, 118 (78.1%) students preferred the clerkship training in a hospital practice. The students in the clinical clerkship program preferred this over those in the pre-clerkship program (85.7% vs. 70.2%, P = 0.03), primarily because a clinical clerkship could not be replaced by an online class during the COVID-19 pandemic. In addition, their responses indicated, in order of significance, fear of not completing the clerkship course on time, willingness to participate as a preliminary healthcare provider in pandemic, the potential waste of tuition, and belief that a hospital is rather safe. The change in the academic calendar had not a positive impact on the lifestyles of many students. CONCLUSIONS: In circumstances such as the COVID-19 pandemic, educational strategies to clinical clerkship training for medical students should be developed to provide them with the opportunity to be actively involved in hospital practice under strict safety guidance focused on preventing virus infection and transmission.

Med Educ Online2020       LitCov and CORD-19
2944"I Have a Cough": An Interactive Virtual Respiratory Case-Based Module  

INTRODUCTION: The COVID-19 pandemic has radically disrupted traditional models of medical education, forcing rapid evolution in the delivery of clinical training. As a result, clinical educators must quickly transition away from in-person sessions and develop effective virtual learning opportunities instead. This virtual resource was designed to replace a clinical simulation session for the physical examination course for medical students in the preclinical years. METHODS: We designed an online interactive module in three sections for preclinical (first- or second-year) medical students who had not yet learned the respiratory physical exam. The first section incorporated demonstration and practice of the components of the respiratory physical exam that could be effectively taught via videoconferencing software. Following this, students conducted a telemedicine encounter with a standardized patient and received patient-centered feedback evaluating their communication skills. The final segment involved a case discussion and clinical reasoning component. RESULTS: These sessions were implemented for 122 first-year medical students. The module was well received by the students. A majority felt that it helped improve their telemedicine communication skills (93%), interpretation of physical exam findings (84%), development of differential diagnosis (95%), and correlation of clinical and basic science content (93%). DISCUSSION: Our pilot educational session demonstrates that this virtual instruction method is an effective tool for teaching basic clinical skills during medical school. Virtual learning resources allow remote instruction to take place and can be a supplement when face-to-face clinical teaching is not possible.

MedEdPORTAL2020       LitCov and CORD-19
2945A review of the literature on sexual and reproductive health of African migrant and refugee children  

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Reprod Health2021       CORD-19
2946Underage Youth and Young Adult e-Cigarette Use and Access Before and During the COVID-19 Pandemic  

IMPORTANCE: Understanding patterns of e-cigarette use and access during the coronavirus disease 2019 (COVID-19) pandemic is important because e-cigarettes may put users at risk for more severe respiratory effects and other health problems. OBJECTIVE: To examine whether underage youth and young adults who ever used e-cigarettes self-reported changes in access and use of e-cigarettes since the COVID-19 pandemic began. DESIGN, SETTING, AND PARTICIPANTS: A national, cross-sectional online survey study was conducted from May 6 to May 14, 2020. This sample of 4351 participants aged 13 to 24 years across the US included 2167 e-cigarette ever-users. Quota sampling was used to balance for age, sex, race/ethnicity, and 50% having ever used e-cigarettes. MAIN OUTCOMES AND MEASURES: Change in e-cigarette use (increase, decrease, quit, no change, and switch to another product) and access to e-cigarettes (easier or harder, and change in point-of-purchase) before and after the COVID-19 pandemic began, reasons for change, number of times e-cigarettes were used, nicotine dependence, and sociodemographic data. RESULTS: This study focused on 2167 e-cigarette ever-users among 4351 participants who completed the survey. Among 2167 e-cigarette users, a total of 1442 were younger than 21 years and 725 were aged 21 years or older; 1397 were female (64.5%) and 438 identified as lesbian, gay, bisexual, transgender, queer (20.2%). The survey completion rate was 40%. Since the COVID-19 pandemic began, 1198 of 2125 e-cigarette users (56.4%) changed their use: 388 individuals (32.4%) quit, 422 individuals (35.3%) reduced the amount of nicotine, 211 individuals (17.6%) increased nicotine use, 94 individuals (7.8%) increased cannabis use, and 82 individuals (6.9%) switched to other products. Participants reported that not being able to go to vape shops and product unavailability were the reasons accessing e-cigarettes was difficult after the pandemic began. Since the COVID-19 pandemic began, individuals reported purchasing from alternative retail stores (disposables, 150 of 632 [23.7%]; pod-based, 144 of 797 [18.1%]; and other e-cigarette, 125 of 560 [22.3%], ie, between 18.1% and 23.7%), purchasing online instead of retail (disposables, 115 of 632 [18.2%]; pod-based, 156 of 797 [19.6%]; and other e-cigarette, 111 of 560 [19.8%], ie, between 18.2% to 19.8%), and shifted to retail instead of online (disposables, 11 of 632 [1.7%]; pod-based, 17 of 797 [2.0%]; and other e-cigarette, 13 of 560 [2.3%], ie, between 1.7%-2.3%). Other individuals reported no change: from retail stores (disposables 262 of 632 [41.5%]; pod-based 344 of 797 [43.2%]; and other e-cigarette, 223 of 560 [39.8%], ie, between 39.8% and 43.2%) and online (disposables 94 of 632 [14.9%]; pod-based 136 of 797 [17.1%]; and other e-cigarette, 88 of 560 [15.8%], ie, between 14.9% and 17.1%). Underage youth reported e-cigarette deliveries from vape shops and/or dealers or friends who received such deliveries, and 63 of 229 (27.5%) self-reported accessing e-cigarettes without age verification. e-Cigarette users were 52% less likely to quit or reduce their use if they previously used e-cigarettes between 11 and 99 times (adjusted odds ratio, 0.48; 95% CI, 0.30-0.78), 68% less likely to quit if they previously used e-cigarettes more than 100 times (adjusted odds ratio, 0.32; 95% CI, 0.20-0.51), and 51% were less likely to quit if they were nicotine dependent (adjusted odds ratio, 0.49; 95% CI, 0.35-0.70). CONCLUSIONS AND RELEVANCE: During the COVID-19 pandemic, youth e-cigarette users reported changes in e-cigarette use, point-of-purchase, and ability to purchase e-cigarettes without age verification. The US Food and Drug Administration and local policy makers may find these data useful to inform policies to prevent e-cigarette sales to underage youth.

JAMA Netw Open2020       LitCov and CORD-19
2947The COVID-19 pandemic: The 'black swan' for mental Healthcare and a turning point for e-health  

Internet Interv2020       LitCov and CORD-19
2948SARS-CoV-2/COVID-19: a primer for cardiologists  

In the late autumn of 2019, a new potentially lethal human coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The pandemic spread of this zoonotic virus has created a global health emergency and an unprecedented socioeconomic crisis. The severity of coronavirus disease 2019 (COVID-19), the illness caused by SARS-CoV‑2, is highly variable. Most patients (~85%) develop no or mild symptoms, while others become seriously ill, some succumbing to disease-related complications. In this review, the SARS-CoV‑2 life cycle, its transmission and the clinical and immunological features of COVID-19 are described. In addition, an overview is presented of the virological assays for detecting ongoing SARS-CoV‑2 infections and the serological tests for SARS-CoV-2-specific antibody detection. Also discussed are the different approaches to developing a COVID-19 vaccine and the perspectives of treating COVID-19 with antiviral drugs, immunomodulatory agents and anticoagulants/antithrombotics. Finally, the cardiovascular manifestations of COVID-19 are briefly touched upon. While there is still much to learn about SARS-CoV‑2, the tremendous recent advances in biomedical technology and knowledge and the huge amount of research into COVID-19 raise the hope that a remedy for this disease will soon be found. COVID-19 will nonetheless have a lasting impact on human society. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12471-020-01475-1) contains supplementary material, which is available to authorized users.

Neth Heart J2020       LitCov and CORD-19
2949Synthesis and evaluation of isatin derivatives as effective SARS coronavirus 3CL protease inhibitors  

N-Substituted isatin derivatives were prepared from the reaction of isatin and various bromides via two steps. Bioactivity assay results (in vitro tests) demonstrated that some of these compounds are potent and selective inhibitors against SARS coronavirus 3CL protease with IC(50) values ranging from 0.95 to 17.50 μM. Additionally, isatin 4o exhibited more potent inhibition for SARS coronavirus protease than for other proteases including papain, chymotrypsin, and trypsin.

Bioorg Med Chem Lett2005       CORD-19
2950Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020  

BACKGROUND: Cancer is one of the leading causes of death globally, but its burden is not uniform. GLOBOCAN 2020 has newly updated the estimates of cancer burden. This study summarizes the most recent changing profiles of cancer burden worldwide and in China and compares the cancer data of China with those of other regions. METHODS: We conducted a descriptive secondary analysis of the GLOBOCAN 2020 data. To depict the changing global profile of the leading cancer types in 2020 compared with 2018, we extracted the numbers of cases and deaths in 2018 from GLOBOCAN 2018. We also obtained cancer incidence and mortality from the 2015 National Cancer Registry Report in China when sorting the leading cancer types by new cases and deaths. For the leading cancer types according to sex in China, we summarized the estimated numbers of incidence and mortality, and calculated China's percentage of the global new cases and deaths. RESULTS: Breast cancer displaced lung cancer to become the most leading diagnosed cancer worldwide in 2020. Lung, liver, stomach, breast, and colon cancers were the top five leading causes of cancer-related death, among which liver cancer changed from the third-highest cancer mortality in 2018 to the second-highest in 2020. China accounted for 24% of newly diagnosed cases and 30% of the cancer-related deaths worldwide in 2020. Among the 185 countries included in the database, China's age-standardized incidence rate (204.8 per 100,000) ranked 65th and the age-standardized mortality rate (129.4 per 100,000) ranked 13th. The two rates were above the global average. Lung cancer remained the most common cancer type and the leading cause of cancer death in China. However, breast cancer became the most frequent cancer type among women if the incidence was stratified by sex. Incidences of colorectal cancer and breast cancer increased rapidly. The leading causes of cancer death varied minimally in ranking from 2015 to 2020 in China. Gastrointestinal cancers, including stomach, colorectal, liver, and esophageal cancers, contributed to a massive burden of cancer for both sexes. CONCLUSIONS: The burden of breast cancer is increasing globally. China is undergoing cancer transition with an increasing burden of lung cancer, gastrointestinal cancer, and breast cancers. The mortality rate of cancer in China is high. Comprehensive strategies are urgently needed to target China's changing profiles of the cancer burden.

Chin Med J (Engl)2021       CORD-19

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

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