\ 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
2451Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon  

This study demonstrates a unique and crucial role of plasmacytoid dendritic cells (pDCs) and pDC-derived type I interferons (IFNs) in the pathogenesis of mouse coronavirus infection. pDCs controlled the fast replicating mouse hepatitis virus (MHV) through the immediate production of type I IFNs. Recognition of MHV by pDCs was mediated via TLR7 ensuring a swift IFN-α production following encounter with this cytopathic RNA virus. Furthermore, the particular type I IFN response pattern was not restricted to the murine coronavirus, but was also found in infection with the highly cytopathic human severe acute respiratory syndrome (SARS) coronavirus. Taken together, our results suggest that rapid production of type I IFNs by pDCs is essential for the control of potentially lethal coronavirus infections.

Blood2007       CORD-19
2452Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly across the USA, causing extensive morbidity and mortality, particularly in the African American community. Autopsy can considerably contribute to our understanding of many disease processes and could provide crucial information to guide management of patients with coronavirus disease 2019 (COVID-19). We report on the relevant cardiopulmonary findings in, to our knowledge, the first autopsy series of ten African American decedents, with the cause of death attributed to COVID-19. METHODS: Autopsies were performed on ten African American decedents aged 44–78 years with cause of death attributed to COVID-19, reflective of the dominant demographic of deaths following COVID-19 diagnosis in New Orleans. Autopsies were done with consent of the decedents' next of kin. Pulmonary and cardiac features were examined, with relevant immunostains to characterise the inflammatory response, and RNA labelling and electron microscopy on representative sections. FINDINGS: Important findings include the presence of thrombosis and microangiopathy in the small vessels and capillaries of the lungs, with associated haemorrhage, that significantly contributed to death. Features of diffuse alveolar damage, including hyaline membranes, were present, even in patients who had not been ventilated. Cardiac findings included individual cell necrosis without lymphocytic myocarditis. There was no evidence of secondary pulmonary infection by microorganisms. INTERPRETATION: We identify key pathological states, including thrombotic and microangiopathic pathology in the lungs, that contributed to death in patients with severe COVID-19 and decompensation in this demographic. Management of these patients should include treatment to target these pathological mechanisms. FUNDING: None.

Lancet Respir Med2020       LitCov and CORD-19
2453Planning for epidemics-the lessons of SARS  

N/A

N Engl J Med2004       CORD-19
2454Myocarditis After BNT162b2 and mRNA-1273 Vaccination  

Supplemental Digital Content is available in the text.

Circulation2021       LitCov and CORD-19
2455The Coronavirus Pandemic: Public Health and American Values  

N/A

J Law Med Ethics2020       LitCov and CORD-19
2456Disproportionate Impact of COVID-19 Pandemic on Racial and Ethnic Minorities  

BACKGROUND: Health disparities are prevalent in many areas of medicine. We aimed to investigate the impact of the COVID-19 pandemic on racial/ethnic groups in the United States (US) and to assess the effects of social distancing, social vulnerability metrics, and medical disparities. METHODS: A cross-sectional study was conducted utilizing data from the COVID-19 Tracking Project and the Centers for Disease Control and Prevention (CDC). Demographic data were obtained from the US Census Bureau, social vulnerability data were obtained from the CDC, social distancing data were obtained from Unacast, and medical disparities data from the Center for Medicare and Medicaid Services. A comparison of proportions by Fisher’s exact test was used to evaluate differences between death rates stratified by age. Negative binomial regression analysis was used to predict COVID-19 deaths based on social distancing scores, social vulnerability metrics, and medical disparities. RESULTS: COVID-19 cumulative infection and death rates were higher among minority racial/ethnic groups than whites across many states. Older age was also associated with increased cumulative death rates across all racial/ethnic groups on a national level, and many minority racial/ethnic groups experienced significantly greater cumulative death rates than whites within age groups ≥ 35 years. All studied racial/ethnic groups experienced higher hospitalization rates than whites. Older persons (≥ 65 years) also experienced more COVID-19 deaths associated with comorbidities than younger individuals. Social distancing factors, several measures of social vulnerability, and select medical disparities were identified as being predictive of county-level COVID-19 deaths. CONCLUSION: COVID-19 has disproportionately impacted many racial/ethnic minority communities across the country, warranting further research and intervention.

Am Surg2020       LitCov and CORD-19
2457Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration  

N/A

Cochrane Database Syst Rev2017       CORD-19
2458Forecasting spatial, socioeconomic and demographic variation in COVID-19 Healthcare demand in England and Wales  

BACKGROUND: COVID-19 poses one of the most profound public health crises for a hundred years. As of mid-May 2020, across the world, almost 300,000 deaths and over 4 million confirmed cases were registered. Reaching over 30,000 deaths by early May, the UK had the highest number of recorded deaths in Europe, second in the world only to the USA. Hospitalization and death from COVID-19 have been linked to demographic and socioeconomic variation. Since this varies strongly by location, there is an urgent need to analyse the mismatch between health care demand and supply at the local level. As lockdown measures ease, reinfection may vary by area, necessitating a real-time tool for local and regional authorities to anticipate demand. METHODS: Combining census estimates and hospital capacity data from ONS and NHS at the Administrative Region, Ceremonial County (CC), Clinical Commissioning Group (CCG) and Lower Layer Super Output Area (LSOA) level from England and Wales, we calculate the number of individuals at risk of COVID-19 hospitalization. Combining multiple sources, we produce geospatial risk maps on an online dashboard that dynamically illustrate how the pre-crisis health system capacity matches local variations in hospitalization risk related to age, social deprivation, population density and ethnicity, also adjusting for the overall infection rate and hospital capacity. RESULTS: By providing fine-grained estimates of expected hospitalization, we identify areas that face higher disproportionate health care burdens due to COVID-19, with respect to pre-crisis levels of hospital bed capacity. Including additional risks beyond age-composition of the area such as social deprivation, race/ethnic composition and population density offers a further nuanced identification of areas with disproportionate health care demands. CONCLUSIONS: Areas face disproportionate risks for COVID-19 hospitalization pressures due to their socioeconomic differences and the demographic composition of their populations. Our flexible online dashboard allows policy-makers and health officials to monitor and evaluate potential health care demand at a granular level as the infection rate and hospital capacity changes throughout the course of this pandemic. This agile knowledge is invaluable to tackle the enormous logistical challenges to re-allocate resources and target susceptible areas for aggressive testing and tracing to mitigate transmission.

BMC Med2020       LitCov and CORD-19
2459Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from SARS-CoV-2 with high potency  

Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed to control this current pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Replication of SARS-CoV-2 depends on the viral RNA-dependent RNA polymerase (RdRp), which is the likely target of the investigational nucleotide analogue remdesivir (RDV). RDV shows broad-spectrum antiviral activity against RNA viruses, and previous studies with RdRps from Ebola virus and Middle East respiratory syndrome coronavirus (MERS-CoV) have revealed that delayed chain termination is RDV's plausible mechanism of action. Here, we expressed and purified active SARS-CoV-2 RdRp composed of the nonstructural proteins nsp8 and nsp12. Enzyme kinetics indicated that this RdRp efficiently incorporates the active triphosphate form of RDV (RDV-TP) into RNA. Incorporation of RDV-TP at position i caused termination of RNA synthesis at position i+3. We obtained almost identical results with SARS-CoV, MERS-CoV, and SARS-CoV-2 RdRps. A unique property of RDV-TP is its high selectivity over incorporation of its natural nucleotide counterpart ATP. In this regard, the triphosphate forms of 2′-C-methylated compounds, including sofosbuvir, approved for the management of hepatitis C virus infection, and the broad-acting antivirals favipiravir and ribavirin, exhibited significant deficits. Furthermore, we provide evidence for the target specificity of RDV, as RDV-TP was less efficiently incorporated by the distantly related Lassa virus RdRp, and termination of RNA synthesis was not observed. These results collectively provide a unifying, refined mechanism of RDV-mediated RNA synthesis inhibition in coronaviruses and define this nucleotide analogue as a direct-acting antiviral.

J Biol Chem2020       LitCov and CORD-19
2460Coronavirus infections and immune responses  

Coronaviruses (CoVs) are by far the largest group of known positive‐sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV‐induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.

J Med Virol2020       LitCov and CORD-19
2461Rapid identification of SARS-CoV-2-infected patients at the emergency department using routine testing  

N/A

Clin Chem Lab Med2020       LitCov and CORD-19
2462Health risks at the Hajj  

Annually, millions of Muslims embark on a religious pilgrimage called the “Hajj” to Mecca in Saudi Arabia. The mass migration during the Hajj is unparalleled in scale, and pilgrims face numerous health hazards. The extreme congestion of people and vehicles during this time amplifies health risks, such as those from infectious diseases, that vary each year. Since the Hajj is dictated by the lunar calendar, which is shorter than the Gregorian calendar, it presents public-health policy planners with a moving target, demanding constant preparedness. We review the communicable and non-communicable hazards that pilgrims face. With the rise in global travel, preventing disease transmission has become paramount to avoid the spread of infectious diseases, including SARS (severe acute respiratory syndrome), avian influenza, and haemorrhagic fever. We examine the response of clinicians, the Saudi Ministry of Health, and Hajj authorities to these unique problems, and list health recommendations for prospective pilgrims.

Lancet2006       CORD-19
2463Seroprevalence of Unidentified SARS-CoV-2 Infection in Hong Kong During 3 Pandemic Waves  

IMPORTANCE: Seroprevalence studies inform the extent of infection and assist evaluation of mitigation strategies for the COVID-19 pandemic. OBJECTIVE: To estimate the prevalence of unidentified SARS-CoV-2 infection in the general population of Hong Kong. DESIGN, SETTING, AND PARTICIPANTS: A prospective cross-sectional study was conducted in Hong Kong after each major wave of the COVID-19 pandemic (April 21 to July 7, 2020; September 29 to November 23, 2020; and January 15 to April 18, 2021). Adults (age ≥18 years) who had not been diagnosed with COVID-19 were recruited during each period, and their sociodemographic information, symptoms, travel, contact, quarantine, and COVID-19 testing history were collected. MAIN OUTCOMES AND MEASURES: The main outcome was prevalence of SARS-CoV-2 infection. SARS-CoV-2 IgG antibodies were detected by an enzyme-linked immunosorbent assay based on spike (S1/S2) protein, followed by confirmation with a commercial electrochemiluminescence immunoassay based on the receptor binding domain of spike protein. RESULTS: The study enrolled 4198 participants (2539 [60%] female; median age, 50 years [IQR, 25 years]), including 903 (22%), 1046 (25%), and 2249 (53%) during April 21 to July 7, 2020; during September 29 to November 23, 2020; and during January 15 to April 18, 2021, respectively. The numbers of participants aged 18 to 39 years, 40 to 59 years, and 60 years or older were 1328 (32%), 1645 (39%), and 1225 (29%), respectively. Among the participants, 2444 (58%) stayed in Hong Kong since November 2019 and 2094 (50%) had negative SARS-CoV-2 RNA test results. Only 170 (4%) reported ever having contact with individuals with confirmed cases, and 5% had been isolated or quarantined. Most (2803 [67%]) did not recall any illnesses, whereas 737 (18%), 212 (5%), and 385 (9%) had experienced respiratory symptoms, gastrointestinal symptoms, or both, respectively, before testing. Six participants were confirmed to be positive for anti-SARS-CoV-2 IgG; the adjusted prevalence of unidentified infection was 0.15% (95% CI, 0.06%-0.32%). Extrapolating these findings to the whole population, there were fewer than 1.9 unidentified infections for every recorded confirmed case. The overall prevalence of SARS-CoV-2 infection in Hong Kong before the roll out of vaccination was less than 0.45%. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of participants from the general public in Hong Kong, the prevalence of unidentified SARS-CoV-2 infection was low after 3 major waves of the pandemic, suggesting the success of the pandemic mitigation by stringent isolation and quarantine policies even without complete city lockdown. More than 99.5% of the general population of Hong Kong remain naive to SARS-CoV-2, highlighting the urgent need to achieve high vaccine coverage.

JAMA Netw Open2021       LitCov and CORD-19
2464Characteristics of SARS-CoV-2 positive cases beyond health-care professionals or social and health-care facilities  

BACKGROUND: During the outbreak of SARS-CoV-2 in Italy, infection among health-care professionals and in the context of welfare and health-care facilities was a significant concern. It is known that the elderly or those with concomitant pathologies are at greater risk of a serious evolution of the disease if affected by COVID-19 and that health workers are a category with greater exposure to SARS-CoV-2 infection. Until now, there has been little information on the epidemiological features and transmission dynamics of the COVID-19 outbreak which did not involve health-care professionals or social and health-care facilities. For this reason, this paper aims to describe the epidemiological characteristics of SARS-CoV-2 infection in the general population outside these semi-closed communities. METHODS: The study was designed by analyzing the data of the 1371 SARS-CoV-2 positive subjects observed in Sardinia up to 9 July, 2020 and whose data were available in the public health department. Statistical analysis and graphic representation were performed using STATA and Adobe Illustrator, respectively. RESULTS: Of the positive cases analyzed, 323 (23.5%) are health-care workers and 563 (41.1%) reside in social or health-care facilities. The number of positive cases among the general population (subjects who do not belong to these semi-closed communities), is 399 (29.1%), 208 females and 191 males. The estimated Case Fatality Rate stands at 5.0%, which is almost half the rate reported for all the SARS-CoV-2 positive cases (9.8%). The geographical distribution of positive cases differs considerably from the distribution of the totality of cases in Sardinia. CONCLUSIONS: This review provides an insight into the COVID-19 situation in the general community, ie not involving health-care professionals or social and health-care facilities. Understanding the evolving epidemiology and transmission dynamics of the outbreak outside of these semi-closed communities would provide appropriate information to guide intervention policy. The COVID-19 pandemic has exacerbated the vulnerability of our health-care system. Severe disruptions in care, medicine shortages and unequal access to health-care are but a few examples of the challenges faced by people living in Italy and Europe, highlighting the importance of evidence-based approaches in supporting the development of prevention and response strategies for future pandemics.

BMC Public Health2021       LitCov and CORD-19
2465Longitudinal analyses reveal immunological misfiring in severe COVID-19  

Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)(1–4). However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.

Nature2020       LitCov and CORD-19
2466Middle East Respiratory Syndrome Coronavirus in Bats, Saudi Arabia  

The source of human infection with Middle East respiratory syndrome coronavirus remains unknown. Molecular investigation indicated that bats in Saudi Arabia are infected with several alphacoronaviruses and betacoronaviruses. Virus from 1 bat showed 100% nucleotide identity to virus from the human index case-patient. Bats might play a role in human infection.

Emerg Infect Dis2013       CORD-19
2467Comparative evaluation of nasopharyngeal swab and saliva specimens for the molecular detection of SARS-CoV-2 RNA in Japanese patients with COVID-19  

Considering the issues of shortage of medical resources and the invasiveness and infection risk involved in the collection of nasopharyngeal swab specimens, there is a need for an effective alternative test specimen for SARS-CoV-2 RNA detection. Here, we investigated suitability of saliva as a non-invasively obtained specimen for molecular detection of SARS-CoV-2 RNA in Japanese patients with COVID-19. In total, 28 paired clinical specimens of saliva and nasopharyngeal swabs were collected from 12 patients at various time points after symptom onset. Each specimen was assayed using reverse transcription real-time polymerase chain reaction (rRT-PCR) on the BD MAX open system using primers and probes targeting the N-gene. The saliva and nasopharyngeal swab specimens showed 19 and 15 positive results, respectively. No invalid (PCR inhibition) result was observed for any specimen. The qualitative results of each specimen obtained in the period immediately after symptom onset were similar. Three convalescent patients presented saliva-positive results, whereas their nasopharyngeal swabs were negative at four different time points, suggesting that saliva may be superior to nasopharyngeal swabs in terms of obtaining stable assay result of SARS-CoV-2. In conclusion, our results suggest that saliva can potentially serve as an alternative to nasopharyngeal swabs as a specimen for SARS-CoV-2 rRT-PCR. As saliva can be collected by patients themselves, it may be an effective way to overcome the shortage of personal protective equipment and specimen sampling tools.

J Infect Chemother2020       LitCov and CORD-19
2468Lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections  

N/A

J Virol2010       CORD-19
2469Single-port laparoscopic totally extraperitoneal inguinal hernia repair with the TriPort system: initial experience  

N/A

Surg Endosc2010       CORD-19
2470Novel coronavirus, poor quarantine and the risk of pandemic  

J Hosp Infect2020       LitCov and CORD-19
2471Longitudinal Monitoring of SARS-CoV-2 IgM and IgG Seropositivity to Detect COVID-19  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel beta-coronavirus that has recently emerged as the cause of the 2019 coronavirus pandemic (COVID-19). Polymerase chain reaction (PCR) based tests are optimal and recommended for the diagnosis of an acute SARS-CoV-2 infection. Serology tests for viral antibodies provide an important tool to diagnose previous exposure to the virus. Here we evaluate the analytical performance parameters of the Diazyme SARS-CoV-2 IgM/IgG serology assays and describe the kinetics of IgM and IgG seroconversion observed in patients with PCR confirmed COVID-19 who were admitted to our hospital. METHODS: We validated the performance of the Diazyme assay in 235 subjects to determine specificity. Subsequently, we evaluated the SARS-CoV-2 IgM and IgG seroconversion of 54 PCR confirmed COVID-19 patients and determined sensitivity of the assay at three different timeframes. RESULT: Sensitivity and specificity for detecting seropositivity at ≥ 15 days following a positive SARS-CoV-2 PCR result, was 100.0% and 98.7% when assaying for the panel of IgM and IgG. The median time to seropositivity observed for a reactive IgM and IgG result from the date of a positive PCR was 5 days (IQR: 2.75-9 days) and 4 days (IQR: 2.75-6.75 days), respectively. CONCLUSIONS: Our data demonstrates that the Diazyme IgM/IgG assays are suited for the purpose of detecting SARS-CoV-2 IgG and IgM in patients with suspected SARS-CoV-2 infections. For the first time, we report longitudinal data showing the evolution of seroconversion for both IgG and IgM in a cohort of acutely ill patients in the United States. We also demonstrate a low false positive rate in patients who were presumed to be disease free.

J Appl Lab Med2020       LitCov and CORD-19
2472Preventing transmission among operating room staff during COVID-19 pandemic: the role of the Aerosol Box and other personal protective equipment  

The COVID-19 pandemic is highly challenging for the operating room staff and healthcare workers in emergency departments. SARS-CoV-2 is a positive-sense single-stranded RNA beta-coronavirus that primarily targets the human respiratory system, with fever, cough, myalgia, and pneumonia as the most common manifestations. However, since SARS-CoV-2 RNA was detected in stool specimens much more attention has been paid to gastrointestinal symptoms such as loss of appetite, nausea, and diarrhea. Furthermore, the expression of ACE-2 receptors in absorptive enterocytes from ileum and colon suggests that these organs should also be considered as a potential high risk for SARS-CoV-2 infection. During aerosol-generating medical procedures (AGMP; e.g. intubating and extubating patients or any surgical procedures), the production of both airborne particles and droplets may increase the risk of infection. In this situation, the surgical staff is strongly recommended to wear personal protective equipment (PPE). A transparent plastic cube, the so-called “Aerosol Box” (AB), has been recently designed to lend further protection against droplets and aerosol exposure during the AGMP.

Updates Surg2020       LitCov and CORD-19
2473A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV  

The outbreak of COVID-19 caused by SARS-CoV-2 virus has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein to 3.1 Å. CR3022 targets a highly conserved epitope, distal from the receptor-binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBD on the trimeric S protein are in the “up” conformation and slightly rotated. Overall, this study provides molecular insights into antibody recognition of SARS-CoV-2.

Science2020       LitCov and CORD-19
2474Severe acute respiratory syndrome diagnostics using a coronavirus protein microarray  

N/A

Proc Natl Acad Sci U S A2006       CORD-19
2475Impact of household quarantine on SARS-Cov-2 infection in mainland China: A mean-field modelling approach  

N/A

Math Biosci Eng2020       LitCov and CORD-19
2476Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design  

The causative agent of severe acute respiratory syndrome (SARS) is a previously unidentified coronavirus, SARS-CoV. The RNA-dependent RNA polymerase (RdRp) of SARS-CoV plays a pivotal role in viral replication and is a potential target for anti-SARS therapy. There is a lack of structural or biochemical data on any coronavirus polymerase. To provide insights into the structure and function of SARS-CoV RdRp, we have located its conserved motifs that are shared by all RdRps, and built a three-dimensional model of the catalytic domain. The structural model permits us to discuss the potential functional roles of the conserved motifs and residues in replication and their potential interactions with inhibitors of related enzymes. We predict important structural attributes of potential anti-SARS-CoV RdRp nucleotide analog inhibitors: hydrogen-bonding capability for the 2′ and 3′ groups of the sugar ring and C3′ endo sugar puckering, and the absence of a hydrophobic binding pocket for non-nucleoside analog inhibitors similar to those observed in hepatitis C virus RdRp and human immunodeficiency virus type 1 reverse transcriptase. We propose that the clinically observed resistance of SARS to ribavirin is probably due to perturbation of the conserved motif A that controls rNTP binding and fidelity of polymerization. Our results suggest that designing anti-SARS therapies can benefit from successful experiences in design of other antiviral drugs. This work should also provide guidance for future biochemical experiments.

Nucleic Acids Res2003       CORD-19
2477Evolution of SARS-CoV-2 RNA test results in a patient with fatal COVID-19: a case report  

A 65 year-old man was hospitalized due to fever (38.6°C) and dry cough since 4 days. He visited Wuhan 8 days ago. At admission, nasopharyngeal swabs sample were taken and PCR analysis confirmed SARS-CoV-2RNA positivity. On day 9 after admission, chest CT scan showed diffuse ground-glass shadows in patient’s bilateral lungs. On day 11, his respiratory symptoms worsened. Subsequently, type 1 respiratory failure was diagnosed, coinciding with kidney injury, and subsequently, type 2 respiratory failure occurred, coupled with multi-organ failure including heart and liver. However, patient constitution worsened although SARS-CoV-2 tests were negative since day 13. He died on day 21. Lung biopsy showed areas of diffuse alveolar damage, characterized by extensive acute alveolitis with numerous intra-alveolar neutrophils, lymphocytes and macrophages infiltrations. Microthrombi were seen in the dilated pulmonary capillaries. Immunohistochemistry stainings for SARS-CoV-2-N protein was negative. Taken together, the patient died of multiorgan failure although the SARS-CoV-2 infection was cleared already, implicating that for disease worsening, no active SARS-CoV-2 infection is required.

Hum Pathol2020       LitCov and CORD-19
2478Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers: A Randomized Controlled Trial  

BACKGROUND: Observational evidence suggests that mask wearing mitigates transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is uncertain if this observed association arises through protection of uninfected wearers (protective effect), via reduced transmission from infected mask wearers (source control), or both. OBJECTIVE: To assess whether recommending surgical mask use outside the home reduces wearers' risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures. DESIGN: Randomized controlled trial (DANMASK-19 [Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection]). (ClinicalTrials.gov: NCT04337541) SETTING: Denmark, April and May 2020. PARTICIPANTS: Adults spending more than 3 hours per day outside the home without occupational mask use. INTERVENTION: Encouragement to follow social distancing measures for coronavirus disease 2019, plus either no mask recommendation or a recommendation to wear a mask when outside the home among other persons together with a supply of 50 surgical masks and instructions for proper use. MEASUREMENTS: The primary outcome was SARS-CoV-2 infection in the mask wearer at 1 month by antibody testing, polymerase chain reaction (PCR), or hospital diagnosis. The secondary outcome was PCR positivity for other respiratory viruses. RESULTS: A total of 3030 participants were randomly assigned to the recommendation to wear masks, and 2994 were assigned to control; 4862 completed the study. Infection with SARS-CoV-2 occurred in 42 participants recommended masks (1.8%) and 53 control participants (2.1%). The between-group difference was −0.3 percentage point (95% CI, −1.2 to 0.4 percentage point; P = 0.38) (odds ratio, 0.82 [CI, 0.54 to 1.23]; P = 0.33). Multiple imputation accounting for loss to follow-up yielded similar results. Although the difference observed was not statistically significant, the 95% CIs are compatible with a 46% reduction to a 23% increase in infection. LIMITATION: Inconclusive results, missing data, variable adherence, patient-reported findings on home tests, no blinding, and no assessment of whether masks could decrease disease transmission from mask wearers to others. CONCLUSION: The recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a community with modest infection rates, some degree of social distancing, and uncommon general mask use. The data were compatible with lesser degrees of self-protection. PRIMARY FUNDING SOURCE: The Salling Foundations.

Ann Intern Med2020       LitCov and CORD-19
2479A COVID-19 vaccine-dare to dream  

N/A

Br J Community Nurs2020       LitCov and CORD-19
2480Characteristics and well-being of urban informal home care providers during COVID-19 pandemic: a population-based study  

OBJECTIVES: Globally, the COVID-19 pandemic has overwhelmed many healthcare systems, which has hampered access to routine clinical care during lockdowns. Informal home care, care provided by non-healthcare professionals, increases the community’s healthcare capacity during pandemics. There is, however, limited research about the characteristics of informal home care providers and the challenges they face during such public health emergencies. DESIGN: A random, cross-sectional, population-based, RDD, telephone survey study was conducted to examine patterns of home care, characteristics of informal home care providers and the challenges experienced by these care providers during this pandemic. SETTING: Data were collected from 22 March to 1 April 2020 in Hong Kong, China. PARTICIPANTS: A population representative study sample of Chinese-speaking adults (n=765) was interviewed. PRIMARY AND SECONDARY OUTCOME MEASURES: The study examined the characteristics of informal home care providers and self-reported health requirements of those who needed care. The study also examined providers’ self-perceived knowledge to provide routine home care as well as COVID-19 risk reduction care. Respondents were asked of their mental health status related to COVID-19. RESULTS: Of the respondents, 25.1% of 765 provided informal home care during the studied COVID-19 pandemic period. Among the informal home care providers, 18.4% of respondents took leave from school/work during the epidemic to provide care for the sick, fragile elderly and small children. Care providers tended to be younger aged, female and housewives. Approximately half of care providers reported additional mental strain and 37.2% reported of challenges in daily living during epidemic. Although most informal home care providers felt competent to provide routine care, 49.5% felt inadequately prepared to cope with the additional health risks of COVID-19. CONCLUSION: During public health emergencies, heavy reliance on informal home healthcare providers necessitates better understanding of their specific needs and increased government services to support informal home care.

BMJ Open2020       LitCov and CORD-19
2481Mismatched Double-Stranded RNA: PolyI:PolyC12U  

Ampligen® [polyI:polyC12U] is a mismatched double-stranded RNA that acts by inducing interferon production (immunomodulator) and by activating an intracellular enzyme (RNase-L) against viral RNA transcripts (antiviral). Ampligen®, currently under development by Hemispherx Biopharma in the US, acts on the immunological system through T-lymphocyte stimulation and is indicated for the treatment of chronic fatigue syndrome and acquired immunodeficiency deficiency syndrome (AIDS), as part of the combined therapy. Ampligen® is available for licensing worldwide. In February 2004, Fujisawa Deutschland GmbH, a subsidiary of Fujisawa Pharmaceutical Co., entered into an option agreement with Hemispherx Biopharma with the intent of becoming a distributor for Ampligen® for the potential treatment of chronic fatigue syndrome in Germany, Switzerland and Austria. An option fee of €400 000 was paid pursuant to the terms of the option agreement and upon execution of the Distribution Agreement, Fujisawa will pay Hemispherx fees and milestone payments with a potential worth of several millions of dollars.[1] In September 2003, Hemispherx Biopharma Inc. entered into an agreement with Guangdong Medicine Group Corporation to organise clinical trials, marketing, sales and distribution for both of its lead compounds, Ampligen® and Alferon N® in the People’s Republic of China. The agreement stipulates that the Guangdong Medicine Group Corporation (GMC) will conduct clinical trials with Ampligen® for the treatment of HIV. All costs related to the trials are to be covered by GMC. Additionally, GMC has to develop and implement marketing and promotional programmes.[2] In May 2003, Hemispherx Biopharma and the Center for Cell and Gene Therapy entered into a research project agreement that will see Ampligen® implemented in a protocol used in patients with relapsed EBV-positive Hodgkin’s Lymphoma.[3] In March 2002, Esteve and Hemispherx Biopharma entered into a collaborative agreement under which Esteve will be the sole distributor of Ampligen® in Spain, Portugal and Andorra for the treatment of chronic fatigue syndrome. Under this agreement, in addition to other terms, Esteve will also collaborate in the drug product development by conducting clinical studies in Spain in patients coinfected with HIV/HCV. In July 2001 Hemispherx Biopharma announced that it had formed a strategic alliance with Empire Health Resources for clinical trials of Ampligen® in the treatment of HIV and hepatitis C virus infections. Empire Health Resources, a healthcare management firm, will be responsible for accrual and retention of patients for HIV trials, and protocols for trials in patients with hepatitis C or both HIV and hepatitis C infections. Hemispherx has entered into a collaboration with RED Laboratories, and RED Laboratories NV expects that this will facilitate the continued development of Ampligen®. Hemispherx has also entered into an agreement with Schering Plough to use a Schering facility as its principal manufacturing platform in the US. This agreement may be expanded to include other territories. Hemispherx and AOP Orphan Pharmaceuticals have signed a marketing agreement for Ampligen® for the treatment of chronic fatigue syndrome for Austria, the Czech Republic, Poland and Hungary. In an arrangement between Hemispherx and Bioclones, Bioclones has certain marketing rights for Ampligen® in the Southern Hemisphere, UK and Ireland. In the US, Ampligen® has been granted orphan drug status for the treatment of AIDS, renal cell carcinoma (phase II, completed), chronic fatigue syndrome (phase III) and invasive/metastatic malignant melanoma (phase II). In August 2004, Hemispherx announced that it intends to use the proceeds from the private placement of company stock to complete the clinical work for its immunotherapeutics/ antivirals Ampligen® and Oragens™. Previously, Hemispherx submitted an application to the EMEA for the approval of Ampligen® for the treatment of chronic fatigue syndrome; the first stage of the regulatory review has been cleared. In 2000, Hemispherx Europe (Hemispherx) obtained orphan drug status for Ampligen® for the treatment of chronic fatigue syndrome in the EU, providing Hemispherx with 10 years of marketing exclusivity following the launch of the drug, as well as potential financial research benefits for the agent. In February 2000, Crystaal Corporation (now Biovail Pharmaceuticals Canada) acquired exclusive marketing rights to Ampligen® in Canada, where it submitted an NDA for the agent for the treatment of chronic fatigue syndrome. In the meantime, Ampligen® has been available since May 1996 under the Canadian Emergency Drug Release Programme for the treatment of chronic fatigue syndrome and immune dysfunction syndrome by Rivex Pharma (Helix BioPharma). Bioclones has initiated clinical studies with Ampligen® for the treatment of chronic fatigue syndrome in Australia. The active substance for Ampligen® is manufactured by F.H. Faulding Ltd. Clinical treatment programmes for chronic fatigue syndrome in other Pacific Rim countries are planned. Ampligen® is available for severe chronic fatigue syndrome on a named patient, cost-recovery basis in South Africa. Hemispherx has developed a ‘ready-to-use’ liquid formulation of the drug and has begun treating patients with chronic fatigue syndrome in ongoing clinical trials. Hemispherx has also developed an oral version of the drug (Oragen®), which is undergoing preclinical evaluation. In February 2001, Hemispherx Biopharma announced that it was initiating phase II/III trials of Ampligen® in the treatment of late-stage, multidrug-resistant strains of HIV in the European Union. Patients treated in these studies will have exhausted all other treatment options. In July 2001, Hemispherx stated that Ampligen® was being evaluated in a phase IIb trial in patients with HIV in the US. The trial, comprising two studies, REARMI and REARMII (Research/Evaluation of Ampligen® for Retroviral Mutations I and II), will evaluate the ability of Ampligen® to prevent the emergence of mutated, drug-resistant strains of the virus. ‘Several hundred’ patients currently on antiretroviral therapy and at risk of viral relapse will be enrolled at centres in Connecticut, New York, Florida and California. A second phase IIb study evaluating the effect of Ampligen® on structured treatment interruptions (STI) is also underway. Final results from this study were reported in December 2002. NIH sponsored studies of potential therapies for SARS have identified Ampligen® as having unusually high and consistent antiviral activity against human coronavirus, the pathogen implicated as the causative agent of the disease. Ampligen® demonstrated very high potency at very low concentrations (0.4 μg/mL) and had a favourable safety profile.[4] In October 2003, Hemispherx announced that, based on these promsing new results, the company will stockpile injectible and/or oral formats of Ampligen® and Alferon N®.[5] Independent researchers have demonstrated the antiviral activity of Ampligen® against flaviviruses (West Nile virus, Equine Encephalitis virus, Dengue fever virus and Japanese Encephalitis virus) as well as virus classes associated with bioterrorism. In an animal study, Ampligen® was shown to prevent destruction of nerve cells, reduce virus concentrations in the brain and blood stream and increase survival rates.[6] Researchers at the Rega Institute in Belgium have published results from an animal study demonstrating that Ampligen® was superior at protecting mice against coxsackie B3 virus-induced myocarditis compared with pegylated interferon.[7] In May 2004 Hemispherx announced that it had filed an expanded US patent application covering the use of Ampligen® for the potential treatment and prevention of severe acute respiratory syndrome (SARS) and dreaded emerging viruses.

Drugs R D2004       CORD-19
2482Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6 and nucleocapsid proteins function as interferon antagonists  

N/A

J Virol2007       CORD-19
2483Transmission of infectious diseases during commercial air travel  

Because of the increasing ease and affordability of air travel and mobility of people, airborne, food-borne, vector-borne, and zoonotic infectious diseases transmitted during commercial air travel are an important public health issue. Heightened fear of bioterrorism agents has caused health officials to re-examine the potential of these agents to be spread by air travel. The severe acute respiratory syndrome outbreak of 2002 showed how air travel can have an important role in the rapid spread of newly emerging infections and could potentially even start pandemics. In addition to the flight crew, public health officials and health care professionals have an important role in the management of infectious diseases transmitted on airlines and should be familiar with guidelines provided by local and international authorities.

Lancet2005       CORD-19
2484Deep vein thrombosis and pulmonary embolism among hospitalized COVID-19-positive patients predicted for higher mortality and prolonged intensive care unit and hospital stays in a multisite healthcare system  

OBJECTIVE: We assessed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients with coronavirus disease 2019 (COVID-19) compared with that in a matched cohort with similar cardiovascular risk factors and the effects of DVT and PE on the hospital course. METHODS: We performed a retrospective review of prospectively collected data from COVID-19 patients who had been hospitalized from March 11, 2020 to September 4, 2020. The patients were randomly matched in a 1:1 ratio by age, sex, hospital of admission, smoking history, diabetes mellitus, and coronary artery disease with a cohort of patients without COVID-19. The primary endpoint was the incidence of DVT/PE and the odds of developing DVT/PE using a conditional logistic regression model. The secondary endpoint was the hospitalization outcomes for COVID-19 patients with and without DVT/PE, including mortality, intensive care unit (ICU) admission, ICU stay, and length of hospitalization (LOH). Multivariable regression analysis was performed to identify the variables associated with mortality, ICU admission, discharge disposition, ICU duration, and LOH. RESULTS: A total of 13,310 patients had tested positive for COVID-19, 915 of whom (6.9%) had been hospitalized across our multisite health care system. The mean age of the hospitalized patients was 60.8 ± 17.0 years, and 396 (43.3%) were women. Of the 915 patients, 82 (9.0%) had had a diagnosis of DVT/PE confirmed by ultrasound examination of the extremities and/or computed tomography angiography of the chest. The odds of presenting with DVT/PE in the setting of COVID-19 infection was greater than that without COVID-19 infection (0.6% [5 of 915] vs 9.0% [82 of 915]; odds ratio [OR], 18; 95% confidence interval [CI], 8.0-51.2; P < .001). The vascular risk factors were not different between the COVID-19 patients with and without DVT/PE. Mortality (P = .02), the need for ICU stay (P < .001), duration of ICU stay (P < .001), and LOH (P < .001) were greater in the DVT/PE cohort than in the cohort without DVT/PE. On multivariable logistic regression analysis, the hemoglobin (OR, 0.71; 95% CI, 0.46-0.95; P = .04) and D-dimer (OR, 1.0; 95% CI, 0.33-1.56; P = .03) levels were associated with higher mortality. Higher activated partial thromboplastin times (OR, 1.1; 95% CI, 1.00-1.12; P = .03) and higher interleukin-6 (IL-6) levels (OR, 1.0; 95% CI, 1.01-1.07; P = .05) were associated with a greater risk of ICU admission. IL-6 (OR, 1.0; 95% CI, 1.00-1.02; P = .05) was associated with a greater risk of rehabilitation placement after discharge. On multivariable gamma regression analysis, hemoglobin (coefficient, −3.0; 95% CI, 0.03-0.08; P = .005) was associated with a prolonged ICU stay, and the activated partial thromboplastin time (coefficient, 2.0; 95% CI, 0.003-0.006; P = .05), international normalized ratio (coefficient, −3.2; 95% CI, 0.06-0.19; P = .002) and IL-6 (coefficient, 2.4; 95% CI, 0.0011-0.0027; P = .02) were associated with a prolonged LOH. CONCLUSIONS: A significantly greater incidence of DVT/PE occurred in hospitalized COVID-19–positive patients compared with a non–COVID-19 cohort matched for cardiovascular risk factors. Patients affected by DVT/PE were more likely to experience greater mortality, to require ICU admission, and experience prolonged ICU stays and LOH compared with COVID-19–positive patients without DVT/PE. Advancements in DVT/PE prevention are needed for patients hospitalized for COVID-19 infection.

J Vasc Surg Venous Lymphat Dis2021       LitCov and CORD-19
2485Open reading frame 1a-encoded subunits of the arterivirus replicase induce endoplasmic reticulum-derived double-membrane vesicles which carry the viral replication complex  

N/A

J Virol1999       CORD-19
2486Evaluation of reverse transcription-PCR assays for rapid diagnosis of severe acute respiratory syndrome associated with a novel coronavirus  

N/A

J Clin Microbiol2003       CORD-19
2487Reference gene selection for quantitative real-time PCR analysis in virus infected cells: SARS corona virus, Yellow fever virus, Human Herpesvirus-6, Camelpox virus and Cytomegalovirus infections  

Ten potential reference genes were compared for their use in experiments investigating cellular mRNA expression of virus infected cells. Human cell lines were infected with Cytomegalovirus, Human Herpesvirus-6, Camelpox virus, SARS coronavirus or Yellow fever virus. The expression levels of these genes and the viral replication were determined by real-time PCR. Genes were ranked by the BestKeeper tool, the GeNorm tool and by criteria we reported previously. Ranking lists of the genes tested were tool dependent. However, over all, β-actin is an unsuitable as reference gene, whereas TATA-Box binding protein and peptidyl-prolyl-isomerase A are stable reference genes for expression studies in virus infected cells.

Virol J2005       CORD-19
2488pediatric patients seen in 18 emergency departments during the COVID-19 pandemic  

BACKGROUND: Public health mitigation strategies in British Columbia during the pandemic included stay-at-home orders and closure of non-essential services. While most primary physicians’ offices were closed, hospitals prepared for a pandemic surge and emergency departments (EDs) stayed open to provide care for urgent needs. We sought to determine whether ED paediatric presentations prior and during the COVID-19 pandemic changed and review acuity compared with seasonal adjusted prior year. METHODS: We analysed records from 18 EDs in British Columbia, Canada, serving 60% of the population. We included children 0–16 years old and excluded those with no recorded acuity or discharge disposition and those left without being seen by a physician. We compared prepandemic (before the first COVID-19 case), early pandemic (after first COVID-19 case) and peak pandemic (during public health emergency) periods as well as a similar time from the previous year. RESULTS: A reduction of 57% and 70% in overall visits was recorded in the children’s hospital ED and the general hospitals EDs, respectively. Average daily visits declined significantly during the peak-pandemic period (167.44±40.72) compared with prepandemic period (543.53±58.8). Admission rates increased mainly due to the decrease in the rate of visits with lower acuity. Children with complaints of ‘fever’ and ‘gastrointestinal’ symptoms had both the largest overall volume and per cent reduction in visits between peak-pandemic and prior year (79% and 74%, respectively). CONCLUSION: Paediatric emergency medicine attendances were reduced to one-third of normal numbers during the 2020 COVID-19 lockdown in British Columbia, Canada, with the reduction mainly seen in minor illnesses that do not usually require admission.

Emerg Med J2020       LitCov and CORD-19
2489Psychological impact of mass quarantine on population during pandemics-The COVID-19 Lock-Down (COLD) study  

BACKGROUND: Quarantine often is an unpleasant experience. The aim of this study is to explore the degree of psychological distress in terms of–Depression, Anxiety and Stress among the adult population in India during the strict 21 days mandatory lockdown. We hypothesize that quantification of psychological impact of current situation will help us to modify the policies and implementation strategies. This assessment might also help in future to keep targeted services in place, to cope up with the psychological distress of the quarantined population. METHOD: A cross sectional survey design was adopted to assess the psychological state of general population in India, during the COVID-19 mandatory lockdown period, with the help of a validated questionnaire. FINDINGS: The reported prevalence of depression was around 30.5%, which was the highest among the variables of psychological health. Anxiety was reported by 22.4%, followed by stress which was seen in 10.8% of respondents. In the third week the incidence of depression (37.8% versus 23.4%; p<0.001), anxiety (26.6% versus 18.2%; p<0.001) and stress (12.2% versus 9.3%; p<0.045) was reported to be significantly higher as compared to second week. INTERPRETATION: Our results suggest a progressively detrimental impact of lockdown on various aspects of psychological health. We noticed around eight to ten fold increase in the prevalence of depression (30.5%) and anxiety (22.4%) during lockdown, as compared to baseline statistics in Indian population (3·1–3·6% for depressive disorders and 3·0–3·5% for anxiety disorders).

PLoS One2020       LitCov and CORD-19
2490Metagenomic Next-Generation Sequencing of Nasopharyngeal Specimens Collected from Confirmed and Suspect COVID-19 Patients  

Metagenomic next-generation sequencing (mNGS) offers an agnostic approach for emerging pathogen detection directly from clinical specimens. In contrast to targeted methods, mNGS also provides valuable information on the composition of the microbiome and might uncover coinfections that may associate with disease progression and impact prognosis. To evaluate the use of mNGS for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and/or other infecting pathogens, we applied direct Oxford Nanopore long-read third-generation metatranscriptomic and metagenomic sequencing. Nasopharyngeal (NP) swab specimens from 50 patients under investigation for CoV disease 2019 (COVID-19) were sequenced, and the data were analyzed by the CosmosID bioinformatics platform. Further, we characterized coinfections and the microbiome associated with a four-point severity index. SARS-CoV-2 was identified in 77.5% (31/40) of samples positive by RT-PCR, correlating with lower cycle threshold (Ct) values and fewer days from symptom onset. At the time of sampling, possible bacterial or viral coinfections were detected in 12.5% of SARS-CoV-2-positive specimens. A decrease in microbial diversity was observed among COVID-19-confirmed patients (Shannon diversity index, P = 0.0082; Chao richness estimate, P = 0.0097; Simpson diversity index, P = 0.018), and differences in microbial communities were linked to disease severity (P = 0.022). Furthermore, statistically significant shifts in the microbiome were identified among SARS-CoV-2-positive and -negative patients, in the latter of whom a higher abundance of Propionibacteriaceae (P = 0.028) and a reduction in the abundance of Corynebacterium accolens (P = 0.025) were observed. Our study corroborates the growing evidence that increased SARS-CoV-2 RNA detection from NP swabs is associated with the early stages rather than the severity of COVID-19. Further, we demonstrate that SARS-CoV-2 causes a significant change in the respiratory microbiome. This work illustrates the utility of mNGS for the detection of SARS-CoV-2, for diagnosing coinfections without viral target enrichment or amplification, and for the analysis of the respiratory microbiome.

mBio2020       LitCov and CORD-19
2491Characteristics of Newborns Born to SARS-CoV-2-Positive Mothers: A Retrospective Cohort Study  

N/A

Am J Perinatol2020       LitCov and CORD-19
2492COVID-19 among Health Workers in Germany and Malaysia  

We report on the suspected case reports filed for SARS-CoV-2 infections and COVID-19 illnesses among health and social welfare workers in Germany. In addition, we report about COVID-19 in health workers in Malaysia. Claims for occupational diseases caused by SARS-CoV-2 are recorded separately in a database of the Statutory Accident Insurance and Prevention in the Health and Welfare Services (BGW). This database is analyzed according to its content as of May 22, 2020. In addition, the notifiable cases of SARS-CoV-2 infections from personnel in medical institutions (e.g., clinics and doctor’s office) and social welfare institutions (e.g., nursing homes, shelters and refugee camps) following the German Infection Protection Act are analyzed. The report from Malaysia is based on personal experience and publications of the government. In Germany at present, 4398 suspected case reports for the diagnosis of SARS-CoV-2 infections among health and social workers have been filed. This figure is four times the number of all reported infections normally received per year. The majority of claims, regardless of being a confirmed infection, concerned nurses (n = 6927, 63.9%). The mortality rate for workers infected with SARS-CoV-2 is 0.2% to 0.5%. Doctors are affected by severe illness more frequently than other occupational groups (8.1% vs. 4.1%). In Malaysia, work-related infection of health workers (HW) occurred mainly when COVID-19 was not suspected in patients and no adequate personal protective equipment (PPE) was worn. Although knowledge on the spread of SARS-CoV-2 infections among workers remains limited, the impact appears to be substantial. This is supported by the mortality rate among infected workers. Occupational health check-ups carried out at the present time should be systematically analyzed in order to gain more information on the epidemiology of COVID-19 among HW. Since the supply and use of PPE improved, the infection risk of HW in Malaysia seems to have decreased.

Int J Environ Res Public Healt2020       LitCov and CORD-19
2493Diagnosing COVID-19: The Disease and Tools for Detection  

[Image: see text] COVID-19 has spread globally since its discovery in Hubei province, China in December 2019. A combination of computed tomography imaging, whole genome sequencing, and electron microscopy were initially used to screen and identify SARS-CoV-2, the viral etiology of COVID-19. The aim of this review article is to inform the audience of diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics. We describe point-of-care diagnostics that are on the horizon and encourage academics to advance their technologies beyond conception. Developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics.

ACS Nano2020       LitCov and CORD-19
2494Characteristics Associated With Racial/Ethnic Disparities in COVID-19 Outcomes in an Academic Healthcare System  

IMPORTANCE: Black patients are overrepresented in the number of COVID-19 infections, hospitalizations, and deaths in the US. Reasons for this disparity may be due to underlying comorbidities or sociodemographic factors that require further exploration. OBJECTIVE: To systematically determine patient characteristics associated with racial/ethnic disparities in COVID-19 outcomes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used comparative groups of patients tested or treated for COVID-19 at the University of Michigan from March 10, 2020, to April 22, 2020, with an outcome update through July 28, 2020. A group of randomly selected untested individuals were included for comparison. Examined factors included race/ethnicity, age, smoking, alcohol consumption, comorbidities, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and residential-level socioeconomic characteristics. EXPOSURE: In-house polymerase chain reaction (PCR) tests, commercial antibody tests, nasopharynx or oropharynx PCR deployed by the Michigan Department of Health and Human Services and reverse transcription–PCR tests performed in external labs. MAIN OUTCOMES AND MEASURES: The main outcomes were being tested for COVID-19, having test results positive for COVID-19 or being diagnosed with COVID-19, being hospitalized for COVID-19, requiring intensive care unit (ICU) admission for COVID-19, and COVID-19–related mortality (including inpatient and outpatient). Medical comorbidities were defined from the International Classification of Diseases, Ninth Revision, and International Classification of Diseases, Tenth Revision, codes and were aggregated into a comorbidity score. Associations with COVID-19 outcomes were examined using odds ratios (ORs). RESULTS: Of 5698 patients tested for COVID-19 (mean [SD] age, 47.4 [20.9] years; 2167 [38.0%] men; mean [SD] BMI, 30.0 [8.0]), most were non-Hispanic White (3740 patients [65.6%]) or non-Hispanic Black (1058 patients [18.6%]). The comparison group included 7168 individuals who were not tested (mean [SD] age, 43.1 [24.1] years; 3257 [45.4%] men; mean [SD] BMI, 28.5 [7.1]). Among 1139 patients diagnosed with COVID-19, 492 (43.2%) were White and 442 (38.8%) were Black; 523 (45.9%) were hospitalized, 283 (24.7%) were admitted to the ICU, and 88 (7.7%) died. Adjusting for age, sex, socioeconomic status, and comorbidity score, Black patients were more likely to be hospitalized compared with White patients (OR, 1.72 [95% CI, 1.15-2.58]; P = .009). In addition to older age, male sex, and obesity, living in densely populated areas was associated with increased risk of hospitalization (OR, 1.10 [95% CI, 1.01-1.19]; P = .02). In the overall population, higher risk of hospitalization was also observed in patients with preexisting type 2 diabetes (OR, 1.82 [95% CI, 1.25-2.64]; P = .02) and kidney disease (OR, 2.87 [95% CI, 1.87-4.42]; P < .001). Compared with White patients, obesity was associated with higher risk of having test results positive for COVID-19 among Black patients (White: OR, 1.37 [95% CI, 1.01-1.84]; P = .04. Black: OR, 3.11 [95% CI, 1.64-5.90]; P < .001; P for interaction = .02). Having any cancer was associated with higher risk of positive COVID-19 test results for Black patients (OR, 1.82 [95% CI, 1.19-2.78]; P = .005) but not White patients (OR, 1.08 [95% CI, 0.84-1.40]; P = .53; P for interaction = .04). Overall comorbidity burden was associated with higher risk of hospitalization in White patients (OR, 1.30 [95% CI, 1.11-1.53]; P = .001) but not in Black patients (OR, 0.99 [95% CI, 0.83-1.17]; P = .88; P for interaction = .02), as was type 2 diabetes (White: OR, 2.59 [95% CI, 1.49-4.48]; P < .001; Black: OR, 1.17 [95% CI, 0.66-2.06]; P = .59; P for interaction = .046). No statistically significant racial differences were found in ICU admission and mortality based on adjusted analysis. CONCLUSIONS AND RELEVANCE: These findings suggest that preexisting type 2 diabetes or kidney diseases and living in high–population density areas were associated with higher risk for COVID-19 hospitalization. Associations of risk factors with COVID-19 outcomes differed by race.

JAMA Netw Open2020       LitCov and CORD-19
2495Single-port access in laparoscopic cholecystectomy  

N/A

Surg Endosc2009       CORD-19
2496Empirical Evidence for the Effect of Airline Travel on Inter-Regional Influenza Spread in the United States  

BACKGROUND: The influence of air travel on influenza spread has been the subject of numerous investigations using simulation, but very little empirical evidence has been provided. Understanding the role of airline travel in large-scale influenza spread is especially important given the mounting threat of an influenza pandemic. Several recent simulation studies have concluded that air travel restrictions may not have a significant impact on the course of a pandemic. Here, we assess, with empirical data, the role of airline volume on the yearly inter-regional spread of influenza in the United States. METHODS AND FINDINGS: We measured rate of inter-regional spread and timing of influenza in the United States for nine seasons, from 1996 to 2005 using weekly influenza and pneumonia mortality from the Centers for Disease Control and Prevention. Seasonality was characterized by band-pass filtering. We found that domestic airline travel volume in November (mostly surrounding the Thanksgiving holiday) predicts the rate of influenza spread (r (2) = 0.60; p = 0.014). We also found that international airline travel influences the timing of influenza mortality (r (2) = 0.59; p = 0.016). The flight ban in the US after the terrorist attack on September 11, 2001, and the subsequent depression of the air travel market, provided a natural experiment for the evaluation of flight restrictions; the decrease in air travel was associated with a delayed and prolonged influenza season. CONCLUSIONS: We provide the first empirical evidence for the role of airline travel in long-range dissemination of influenza. Our results suggest an important influence of international air travel on the timing of influenza introduction, as well as an influence of domestic air travel on the rate of inter-regional influenza spread in the US. Pandemic preparedness strategies should account for a possible benefit of airline travel restrictions on influenza spread.

PLoS Med2006       CORD-19
2497COVID-19: The first documented coronavirus pandemic in history  

Abstract The novel human coronavirus disease COVID-19 has become the fifth documented pandemic since the 1918 flu pandemic. COVID-19 was first reported in Wuhan, China, and subsequently spread worldwide. The coronavirus was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses based on phylogenetic analysis. SARS-CoV-2 is believed to be a spillover of an animal coronavirus and later adapted the ability of human-to-human transmission. Because the virus is highly contagious, it rapidly spreads and continuously evolves in the human population. In this review article, we discuss the basic properties, potential origin, and evolution of the novel human coronavirus. These factors may be critical for studies of pathogenicity, antiviral designs, and vaccine development against the virus.

Biomed J2020       LitCov and CORD-19
2498Prognostic Value of Right Ventricular Longitudinal Strain in Patients With COVID-19  

Abstract Objectives We aimed to investigate whether right ventricular longitudinal strain (RVLS) was independently predictive of higher mortality in coronavirus disease 2019 (COVID-19) patients. Background RVLS obtained from two-dimensional speckle-tracking echocardiography (2D-STE) has been recently demonstrated to be a more accurate and sensitive tool to estimate RV function. The prognostic value of RVLS in patients with COVID-19 remains unknown. Methods 120 consecutive patients with COVID-19 who underwent echocardiography examination were enrolled in our study. Conventional right ventricular (RV) function parameters, including RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) and tricuspid tissue Doppler annular velocities (S’), were obtained. RVLS was determined by 2D-STE. RV function was categorized by tertiles of RVLS. Results Compared with patients in the highest RVLS tertile, those in the lowest tertile were more likely to have a higher heart rate, D-dimer and C-reactive protein, high-flow oxygen and invasive mechanical ventilation therapy, higher incidence of acute heart injury, acute respiratory distress syndrome (ARDS) and deep vein thrombosis, and higher mortality. After a median follow-up of 51 days, 18 patients died. Compared with survivors, non-survivors displayed enlarged right-heart chamber, diminished RV function, and elevated pulmonary artery systolic pressure. Male, ARDS, RVLS, RVFAC and TAPSE were significant univariate predictors of higher risk of mortality (P < 0.05 for all). The Cox model using RVLS (hazard ratio [HR]: 1.33, 95% confidence intervals [CI]: 1.15~1.53; P < 0.001; Akaike Information Criterion [AIC] =129; C-index = 0.89) was found to predict higher mortality more accurately than that with RVFAC (AIC =142; C-index = 0.84) and TAPSE (AIC = 144; C-index = 0.83). The best cutoff value of RVLS for prediction of outcome was −23% (area under the curve, 0.87; P < 0.001; sensitivity, 94.4%; specificity, 64.7%). Conclusions RVLS is a powerful predictor of higher mortality in patients with COVID-19. Our study supports the application of RVLS to identify higher risk COVID-19 patients.

JACC Cardiovasc Imaging2020       LitCov and CORD-19
2499The mechanism of RNA recombination in poliovirus  

Abstract We have investigated RNA recombination among poliovirus genomes by analyzing both intratypic and intertypic recombinant crosses involving the same defined genetic markers. Sequence analysis of the recombinant junctions of 13 nonsibling intertypic recombinants showed that intertypic RNA recombination is not site-specific, nor does it require extensive homology between the recombining parents at the crossover site. To discriminate between breaking-rejoining and copy choice mechanisms of RNA recombination, we have inhibited the replication of the recombining parents independently and found opposite effects on the frequency of genetic recombination in intratypic crosses. The results strongly support a copy choice mechanism for RNA recombination, in which the viral RNA polymerase switches templates during negative strand synthesis.

Cell1986       CORD-19
2500Managing patient flows in radiation oncology during the COVID-19 pandemic: Reworking existing treatment designs to prevent infections at a German hot spot area University Hospital  

PURPOSE: The described work aimed to avoid cancellations of indispensable treatments by implementing active patient flow management practices and optimizing infrastructure utilization in the radiation oncology department of a large university hospital and regional COVID-19 treatment center close to the first German SARS-CoV‑2 hotspot region Heinsberg in order to prevent nosocomial infections in patients and personnel during the pandemic. PATIENTS AND METHODS: The study comprised year-to-date intervention analyses of in- and outpatient key procedures, machine occupancy, and no-show rates in calendar weeks 12 to 19 of 2019 and 2020 to evaluate effects of active patient flow management while monitoring nosocomial COVID-19 infections. RESULTS: Active patient flow management helped to maintain first-visit appointment compliance above 85.5%. A slight appointment reduction of 10.3% daily (p = 0.004) could still significantly increase downstream planning CT scheduling (p = 0.00001) and performance (p = 0.0001), resulting in an absolute 20.1% (p = 0.009) increment of CT performance while avoiding overbooking practices. Daily treatment start was significantly increased by an absolute value of 18.5% (p = 0.026). Hypofractionation and acceleration were significantly increased (p = 0.0043). Integrating strict testing guidelines, a distancing regimen for staff and patients, hygiene regulations, and precise appointment scheduling, no SARS-CoV‑2 infection in 164 tested radiation oncology service inpatients was observed. CONCLUSION: In times of reduced medical infrastructure capacities and resources, controlling infrastructural time per patient as well as optimizing facility utilization and personnel workload during treatment evaluation, planning, and irradiation can help to improve appointment compliance and quality management. Avoiding recurrent and preventable exposure to healthcare infrastructure has potential health benefits and might avert cross infections during the pandemic. Active patient flow management in high-risk COVID-19 regions can help Radiation Oncologists to continue and initiate treatments safely, instead of cancelling and deferring indicated therapies.

Strahlenther Onkol2020       LitCov and CORD-19

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

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